FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Karageorgiadis, A
Gourgari, E
Lyssikatos, C
Stratakis, CA
Lodish, MB
AF Karageorgiadis, Alexander
Gourgari, Evgenia
Lyssikatos, Charalampos
Stratakis, Constantine A.
Lodish, Maya Beth
TI Growth Hormone and Prolactin Secretion in Patients with Carney Complex
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Karageorgiadis, Alexander] NICHD, NIH, Bethesda, MD USA.
[Gourgari, Evgenia] Georgetown Univ Hosp, Washington, DC 20007 USA.
[Lyssikatos, Charalampos; Stratakis, Constantine A.; Lodish, Maya Beth] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0603
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100331
ER
PT J
AU Katz, LS
Geras-Raaka, E
Gershengorn, MC
AF Katz, Liora S.
Geras-Raaka, Elizabeth
Gershengorn, Marvin C.
TI Heritability of Fat Accumulation in White Adipocytes
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Katz, Liora S.; Geras-Raaka, Elizabeth; Gershengorn, Marvin C.] NIDDK, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR46-1
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103190
ER
PT J
AU Kavarthapu, R
Morris, CHT
Dufau, ML
AF Kavarthapu, Raghuveer
Morris, Chon-Hwa Tsai
Dufau, Maria L.
TI Androgen Modulation of Germ Cell Nuclear Factor (GCNF) Regulates
GRTH/DDX25 Specific Expression in Germ Cells
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Kavarthapu, Raghuveer; Morris, Chon-Hwa Tsai] NIH, Bethesda, MD 20892 USA.
[Dufau, Maria L.] NICHD, NIH, Bethesda, MD USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP36-4
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805107184
ER
PT J
AU Kavarthapu, R
Morris, CHT
Dufau, ML
AF Kavarthapu, Raghuveer
Morris, Chon-Hwa Tsai
Dufau, Maria L.
TI Androgen Modulation of Germ Cell Nuclear Factor (GCNF) Regulates
GRTH/DDX25 Specific Expression in Germ Cells
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Kavarthapu, Raghuveer; Morris, Chon-Hwa Tsai] NIH, Bethesda, MD 20892 USA.
[Dufau, Maria L.] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0003
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104155
ER
PT J
AU Kissell, KA
Schisterman, E
Hwang, BS
Chen, ZS
Perkins, N
Wactawski-Wende, J
Mumford, S
AF Kissell, Kerri Ann
Schisterman, Enrique
Hwang, Beom Seuk
Chen, Zhen Seuk
Perkins, Neil
Wactawski-Wende, Jean
Mumford, Sunni
TI History of Adverse Pregnancy Outcomes and Maternal Serum Anti-Mullerian
Hormone Levels
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Kissell, Kerri Ann; Schisterman, Enrique; Perkins, Neil; Mumford, Sunni] NICHD, NIH, Bethesda, MD USA.
[Hwang, Beom Seuk; Chen, Zhen Seuk] NICHD, Bethesda, MD USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Buffalo, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0015
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104284
ER
PT J
AU Latrofa, F
Ricci, D
Sisti, E
Montanelli, L
Piaggi, P
Rago, T
Fiore, E
Marino, M
Vitti, P
AF Latrofa, Francesco
Ricci, Debora
Sisti, Eleonora
Montanelli, Lucia
Piaggi, Paolo
Rago, Teresa
Fiore, Emilio
Marino, Michele
Vitti, Paolo
TI Evaluation of the Level of Thyroglobulin Autoantibodies Interfering with
Thyroglobulin Measurement in Patients with Differentiated Thyroid
Carcinoma
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Latrofa, Francesco; Ricci, Debora; Sisti, Eleonora; Montanelli, Lucia; Rago, Teresa; Fiore, Emilio; Marino, Michele; Vitti, Paolo] Univ Pisa, I-56100 Pisa, Italy.
[Piaggi, Paolo] NIDDK, NIH, Phoenix, AZ USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0565
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109206
ER
PT J
AU Latrofa, F
Ricci, D
Montanelli, L
Piaggi, P
Mazzi, B
Bianchi, F
Brozzi, F
Santini, P
Fiore, E
Marino, M
Tonacchera, M
Vitti, P
AF Latrofa, Francesco
Ricci, Debora
Montanelli, Lucia
Piaggi, Paolo
Mazzi, Barbara
Bianchi, Francesca
Brozzi, Federica
Santini, Pierina
Fiore, Emilio
Marino, Michele
Tonacchera, Massimo
Vitti, Paolo
TI Thyroglobulin Autoantibodies Switch to IgG1 and IgG3 Subclasses after
131I Treatment for Graves' Hyperthyroidism: Autoantibodies Subclasses
Are Related to the Activity of Autoimmune Thyroid Disease
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Latrofa, Francesco; Ricci, Debora; Montanelli, Lucia; Mazzi, Barbara; Bianchi, Francesca; Brozzi, Federica; Santini, Pierina; Fiore, Emilio; Marino, Michele; Tonacchera, Massimo; Vitti, Paolo] Univ Pisa, I-56100 Pisa, Italy.
[Piaggi, Paolo] NIDDKD, NIH, Phoenix, AZ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0538
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109073
ER
PT J
AU Lee, P
Smith, S
Linderman, JD
Courville, AB
Brychta, RJ
Dieckmann, W
Werner, CD
Chen, K
Celi, FS
AF Lee, Paul
Smith, Sheila
Linderman, Joyce D.
Courville, Amber B.
Brychta, Robert J.
Dieckmann, William
Werner, Charlotte D.
Chen, Kong
Celi, Francesco S.
TI Impact of Chronic Cold Exposure in Humans (ICEMAN) Study: Evidence for
Brown Adipose Tissue Plasticity Modulating Glucose Metabolism in Humans
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Lee, Paul; Smith, Sheila; Linderman, Joyce D.; Brychta, Robert J.; Werner, Charlotte D.; Chen, Kong] NIDDK, Diabet Endocrinol Obes Branch, NIH, Bethesda, MD 20892 USA.
[Courville, Amber B.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Dieckmann, William] NIH, PET Dept, Bethesda, MD 20892 USA.
[Celi, Francesco S.] Virginia Commonwealth Univ, Richmond, VA USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0887
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103035
ER
PT J
AU Li, YQ
Chen, M
Gavrilova, O
Weinstein, LS
AF Li, Yong-Qi
Chen, Min
Gavrilova, Oksana
Weinstein, Lee S.
TI G(s)alpha Deficiency in Fat Tissues Leads to Improved Glucose Metabolism
and Insulin Sensitivity without Effects on Body Weight
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Li, Yong-Qi; Chen, Min; Gavrilova, Oksana; Weinstein, Lee S.] NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0901
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103042
ER
PT J
AU Liu, J
Cinar, R
Xiong, K
Ntambi, JM
Kunos, G
AF Liu, Jie
Cinar, Resat
Xiong, Keming
Ntambi, James M.
Kunos, George
TI Identification of Endogenous Inhibitors of Fatty Acid Amide Hydrolase in
the Liver
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Liu, Jie; Cinar, Resat] NIH, Rockville, MD USA.
[Xiong, Keming; Kunos, George] NIAAA, NIH, Rockville, MD 20852 USA.
[Ntambi, James M.] Univ Wisconsin, Madison, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR15-3
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805106049
ER
PT J
AU Liu, SS
Emmanouil, S
Mertz, E
Salpea, P
Shapiro, J
Leikin, S
Stratakis, CA
AF Liu, Sisi
Emmanouil, Saloustros
Mertz, Edward
Salpea, Paraskevi
Shapiro, Jenna
Leikin, Sergey
Stratakis, Constantine A.
TI Abnormal cAMP-Dependent Protein Kinase Activity Leads to Bone Tumors in
Adult Mice but This Depends on the PKA Subunit Expressions
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Liu, Sisi; Emmanouil, Saloustros; Salpea, Paraskevi; Shapiro, Jenna] NICHD, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
[Mertz, Edward; Leikin, Sergey] NICHD, Sect Phys Biochem, NIH, Bethesda, MD USA.
[Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR31-2
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105212
ER
PT J
AU Liu, SS
Berthon, AS
Szarek, E
Emmanouil, S
Salpea, P
Stratakis, CA
AF Liu, Sisi
Berthon, Annabel Sophie
Szarek, Eva
Emmanouil, Saloustros
Salpea, Paraskevi
Stratakis, Constantine A.
TI Can COX-II Inhibitor be Used for Treatment of Cushing Syndrome Due to
cAMP-Dependent Protein Kinase Defects? a Mouse Study
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Liu, Sisi; Emmanouil, Saloustros; Salpea, Paraskevi] NICHD, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
[Berthon, Annabel Sophie; Szarek, Eva; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0795
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101296
ER
PT J
AU Liu, SS
Berthon, AS
Szarek, E
Emmanouil, S
Salpea, P
Stratakis, CA
AF Liu, Sisi
Berthon, Annabel Sophie
Szarek, Eva
Emmanouil, Saloustros
Salpea, Paraskevi
Stratakis, Constantine A.
TI Can COX-II Inhibitor be Used for Treatment of Cushing Syndrome Due to
cAMP-Dependent Protein Kinase Defects? a Mouse Study
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Liu, Sisi; Emmanouil, Saloustros; Salpea, Paraskevi] NICHD, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
[Berthon, Annabel Sophie; Szarek, Eva; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP14-2
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100192
ER
PT J
AU Lodish, MB
Ardeshirpour, Y
Afshari, A
Gourgari, E
Keil, M
Belyayskaya, E
Lyssikatos, C
Chernomordik, V
Gandjbakhche, A
Stratakis, CA
AF Lodish, Maya Beth
Ardeshirpour, Yasaman
Afshari, Ali
Gourgari, Evgenia
Keil, Margaret
Belyayskaya, Elena
Lyssikatos, Charalampos
Chernomordik, Victor
Gandjbakhche, Amir
Stratakis, Constantine A.
TI Non-Invasive Multi-Spectral Imaging for Pre and Post-Operative
Assessment of Patients with Cushing's Syndrome
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Lodish, Maya Beth; Ardeshirpour, Yasaman; Afshari, Ali; Keil, Margaret; Belyayskaya, Elena; Lyssikatos, Charalampos; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
[Gourgari, Evgenia] Georgetown Univ Hosp, Washington, DC 20007 USA.
[Chernomordik, Victor; Gandjbakhche, Amir] NICHD, Bethesda, MD USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0830
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105034
ER
PT J
AU London, E
Nesterova, MV
Huang, V
Stratakis, CA
AF London, Edra
Nesterova, Maria V.
Huang, Vincent
Stratakis, Constantine A.
TI Protein Kinase a (PKA) Subunit R2alpha Knockout Mice Are Leaner Than WT
Mice, but Also Eat Less When Given High-Fat Diet: Is Central or
Peripheral PKA Regulation the Cause of Diet-Induced Obesity (DIO)
Resistance?
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [London, Edra] NICHD, Bethesda, MD USA.
[Nesterova, Maria V.] NICHD, NIH, Bethesda, MD USA.
[Huang, Vincent] NICHD, Intramural Summer Student Program NSSP, Bethesda, MD USA.
[Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0879
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103066
ER
PT J
AU Lui, JL
Cheung, C
Zhu, ZY
Dimitrov, D
Baron, J
AF Lui, Julian
Cheung, Crystal
Zhu, Zhongyu
Dimitrov, Dimiter
Baron, Jeffrey
TI Human Monoclonal Antibody Fragments for Targeting Therapeutics to Growth
Plate Cartilage
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Lui, Julian] NICHD, Bethesda, MD USA.
[Cheung, Crystal] NIH, Bethesda, MD 20892 USA.
[Zhu, Zhongyu; Dimitrov, Dimiter] NCI, Frederick, MD 21701 USA.
[Baron, Jeffrey] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR24-4
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104119
ER
PT J
AU Madan, R
Goyal, RM
Jonklaas, J
Burman, K
AF Madan, Ritu
Goyal, Rachna Manju
Jonklaas, Jacqueline
Burman, Kenneth
TI Methimazole Induced Fulminant Hepatic Failure
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Madan, Ritu] NIH, Bethesda, MD 20892 USA.
[Goyal, Rachna Manju] Georgetown Univ Hosp, Arlington, VA USA.
[Jonklaas, Jacqueline] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
[Burman, Kenneth] Washington Hosp Ctr, Kensington, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0468
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805108206
ER
PT J
AU Mallappa, A
Daley, LA
Van Ryzin, C
Merke, DP
AF Mallappa, Ashwini
Daley, Loh-Ann
Van Ryzin, Carol
Merke, Deborah P.
TI Quality of Life in Adults with Classic Congenital Adrenal Hyperplasia:
Females Have Reduced Quality of Life Compared to Males
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Mallappa, Ashwini; Daley, Loh-Ann; Van Ryzin, Carol; Merke, Deborah P.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0820
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105023
ER
PT J
AU Mallappa, A
Daley, LA
Sinaii, N
Van Ryzin, C
Huatan, H
Digweed, D
Eckland, D
Whitaker, M
Nieman, LK
Ross, RJ
Merke, DP
AF Mallappa, Ashwini
Daley, Lori-Ann
Sinaii, Ninet
Van Ryzin, Carol
Huatan, Hiep
Digweed, Dena
Eckland, David
Whitaker, Martin
Nieman, Lynnette K.
Ross, Richard J.
Merke, Deborah P.
TI A Phase 2 Study of Chronocort (R), a Modified Release Formulation of
Hydrocortisone, in the Treatment of Adults with Classic Congenital
Adrenal Hyperplasia
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Mallappa, Ashwini; Daley, Lori-Ann; Sinaii, Ninet; Van Ryzin, Carol; Nieman, Lynnette K.; Merke, Deborah P.] NIH, Bethesda, MD 20892 USA.
[Huatan, Hiep; Digweed, Dena; Eckland, David; Whitaker, Martin] Diurnal Ltd, Cardiff, S Glam, Wales.
[Ross, Richard J.] Univ Sheffield, Sheffield, S Yorkshire, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR02-5
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102326
ER
PT J
AU Martinez, PE
Schmidt, PJ
Thompson, KD
Nieman, LK
Morrow, AL
Cintron, D
Rubinow, DR
AF Martinez, Pedro E.
Schmidt, Peter John
Thompson, Karla D.
Nieman, Lynnette K.
Morrow, A. Leslie
Cintron, Dahima
Rubinow, David R.
TI Effects of Dutasteride, a 5 Alpha-Reductase Type I Inhibitor, on Pmdd
Symptoms: Results of a Pilot Study
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Martinez, Pedro E.] NIMH, NIH, Bethesda, MD 20892 USA.
[Schmidt, Peter John; Thompson, Karla D.] NIMH, Bethesda, MD 20892 USA.
[Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA.
[Morrow, A. Leslie] UNC Sch Med, Chapel Hill, NC USA.
[Cintron, Dahima] Univ Puerto Rico, San Juan, PR 00936 USA.
[Rubinow, David R.] Univ North Carolina Chaple, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0020
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104251
ER
PT J
AU Martinez, PE
Schmidt, PJ
Thompson, KD
Nieman, LK
Morrow, AL
Cintron, D
Rubinow, DR
AF Martinez, Pedro E.
Schmidt, Peter John
Thompson, Karla D.
Nieman, Lynnette K.
Morrow, A. Leslie
Cintron, Dahima
Rubinow, David R.
TI Effects of Dutasteride, a 5 Alpha-Reductase Type I Inhibitor, on Pmdd
Symptoms: Results of a Pilot Study
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Martinez, Pedro E.] NIMH, NIH, Bethesda, MD 20892 USA.
[Schmidt, Peter John; Thompson, Karla D.] NIMH, Bethesda, MD 20892 USA.
[Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA.
[Morrow, A. Leslie] UNC Sch Med, Chapel Hill, NC USA.
[Cintron, Dahima] Univ Puerto Rico, San Juan, PR 00936 USA.
[Rubinow, David R.] Univ North Carolina Chaple, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP04-3
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104226
ER
PT J
AU Mehta, A
Zhang, LS
Boufraqech, M
Patel, D
Nilubol, N
Kebebew, E
AF Mehta, Amit
Zhang, Lisa
Boufraqech, Myriem
Patel, Dhaval
Nilubol, Naris
Kebebew, Electron
TI Carfilzomib, a Second Generation Proteasome Inhibitor, Has Anticancer
Activity in Anaplastic Thyroid Cancer
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Mehta, Amit; Zhang, Lisa; Boufraqech, Myriem; Patel, Dhaval; Nilubol, Naris; Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0543
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109183
ER
PT J
AU Mehta, A
Zhang, LS
Boufraqech, M
Patel, D
Nilubol, N
Davis, SR
Zhang, YQ
Li, ZY
Shen, M
Kebebew, E
AF Mehta, Amit
Zhang, Lisa
Boufraqech, Myriem
Patel, Dhaval
Nilubol, Naris
Davis, Sean R.
Zhang, Yaqin
Li, Zhuyin
Shen, Min
Kebebew, Electron
TI Integrated Genome-Wide Expression Analysis and High Throughput Drug
Screening in Anaplastic Thyroid Cancer Identifies YM155, a Survivin
Inhibitor, As a Novel Therapeutic Agent
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Mehta, Amit; Zhang, Lisa; Boufraqech, Myriem; Patel, Dhaval; Nilubol, Naris; Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA.
[Davis, Sean R.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Li, Zhuyin; Shen, Min] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR52-5
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109146
ER
PT J
AU Modali, SD
Desai, SS
Parekh, VI
Kebebew, E
Agarwal, SK
AF Modali, Sita D.
Desai, Shruti S.
Parekh, Vaishali I.
Kebebew, Electron
Agarwal, Sunita K.
TI Tumor Suppressor Role of the Long Non-Coding RNA MEG3 in Insulinomas and
in Insulinoma Cell Proliferation
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Modali, Sita D.] NIDDK, NIH, Bethesda, MD USA.
[Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR50-1
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805108102
ER
PT J
AU Morissette, R
Chen, WY
Xu, Z
Dreilling, JL
Quezado, MM
McDonnell, NB
Merke, DP
AF Morissette, Rachel
Chen, Wuyan
Xu, Zhi
Dreilling, Jennifer L.
Quezado, Martha M.
McDonnell, Nazli B.
Merke, Deborah P.
TI A Novel Variant in Tenascin-X May be Associated with an Ehlers Danlos
Phenotype in Patients with Congenital Adrenal Hyperplasia
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Morissette, Rachel; Merke, Deborah P.] NIH, Bethesda, MD 20892 USA.
[Chen, Wuyan] PreventionGenet, Marshfield, WI USA.
[Xu, Zhi] Univ Hong Kong, Pokfulam, Hong Kong, Peoples R China.
[Dreilling, Jennifer L.; Quezado, Martha M.] NCI, Bethesda, MD 20892 USA.
[McDonnell, Nazli B.] Eastern Colorado Hlth Syst, Colorado Springs, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0377
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100291
ER
PT J
AU Muniyappa, R
Chen, K
Brychta, RJ
Abel, BS
Mullins, K
Staker, P
Van der Ploeg, LHT
Connors, H
Gottesdiener, K
Reitman, ML
Skarulis, MC
AF Muniyappa, Ranganath
Chen, Kong
Brychta, Robert J.
Abel, Brent Samuel
Mullins, Katherine
Staker, Pamela
Van der Ploeg, Lex H. T.
Connors, Hillori
Gottesdiener, Keith
Reitman, Marc L.
Skarulis, Monica C.
TI A Randomized, Double-Blind, Placebo-Controlled, Crossover Study to
Evaluate the Effect of a Melanocortin Receptor 4 (MC4R) Agonist, RM-493,
on Resting Energy Expenditure (REE) in Obese Subjects
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Muniyappa, Ranganath; Chen, Kong; Brychta, Robert J.; Abel, Brent Samuel; Mullins, Katherine; Staker, Pamela; Reitman, Marc L.; Skarulis, Monica C.] NIH, Bethesda, MD 20892 USA.
[Van der Ploeg, Lex H. T.; Connors, Hillori; Gottesdiener, Keith] Rhythm Metab Inc, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR16-5
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103140
ER
PT J
AU Narsana, N
Madan, R
Onumah, BM
AF Narsana, Niyati
Madan, Ritu
Onumah, Barbara Mensah
TI Denosumab Induced Hypocalcemia in Multiple Myeloma
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Narsana, Niyati] Medstar Washington Hosp Ctr, Washington, DC USA.
[Madan, Ritu] NIH, Bethesda, MD 20892 USA.
[Onumah, Barbara Mensah] Washington Hosp Ctr, Washington, DC 20010 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0215
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105146
ER
PT J
AU Nella, AA
Mallappa, A
Gounden, V
Daley, LA
Gonzalez, A
Hindmarsh, PC
Soldin, S
Merke, DP
AF Nella, Aikaterini A.
Mallappa, Ashwini
Gounden, Verena
Daley, Lori-Ann
Gonzalez, Adam
Hindmarsh, Peter C.
Soldin, Steven
Merke, Deborah P.
TI A Pilot Study Assessing the Use of Continuous Subcutaneous
Hydrocortisone Infusion in the Treatment of Congenital Adrenal
Hyperplasia: Preliminary Data
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Nella, Aikaterini A.; Mallappa, Ashwini; Gounden, Verena; Daley, Lori-Ann; Gonzalez, Adam; Soldin, Steven; Merke, Deborah P.] NIH, Bethesda, MD 20892 USA.
[Hindmarsh, Peter C.] UCL, London, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0664
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101287
ER
PT J
AU Nilsson, O
Guo, M
Dunbar, NS
Popovic, J
Flynn, DP
Jacobsen, C
Lui, J
Hirschhorn, JN
Baron, J
Dauber, A
AF Nilsson, Ola
Guo, Michael
Dunbar, Nancy S.
Popovic, Jadranka
Flynn, Daniel P.
Jacobsen, Christina
Lui, Julian
Hirschhorn, Joel N.
Baron, Jeffrey
Dauber, Andrew
TI Whole-Exome Sequencing Identifies ACAN Mutations in Autosomal Dominant
Short Stature with Accelerated Skeletal Maturation
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Nilsson, Ola; Baron, Jeffrey] NICHD, NIH, Bethesda, MD USA.
[Guo, Michael] Harvard Med Sch, Boston, MA USA.
[Dunbar, Nancy S.] Connecticut Childrens Med Ctr, Hartford, CT USA.
[Popovic, Jadranka] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA.
[Flynn, Daniel P.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
[Jacobsen, Christina] Chldrns Hosp Boston, Boston, MA USA.
[Lui, Julian] NICHD, Bethesda, MD USA.
[Hirschhorn, Joel N.; Dauber, Andrew] Boston Childrens Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR24-1
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104115
ER
PT J
AU Papadopoulou, A
Siamatras, T
Delgado-Morales, R
Amin, ND
Shukla, V
Pant, HC
Almeida, OFX
Kino, T
AF Papadopoulou, Anna
Siamatras, Thomas
Delgado-Morales, Raul
Amin, Niranjana D.
Shukla, Varsha
Pant, Harish C.
Almeida, Osborne F. X.
Kino, Tomoshige
TI Acute and Chronic Stress Differentially Regulate Enzymatic Activity and
Protein Expression of the Cyclin-Dependent Kinase 5 (CDK5) in Mouse
Brain Partly through Modulation of the Glucocorticoid Signaling Pathway:
Implication to Major Depression
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Papadopoulou, Anna; Siamatras, Thomas] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Delgado-Morales, Raul; Almeida, Osborne F. X.] Max Planck Inst Psychiat, Munich, Germany.
[Amin, Niranjana D.; Shukla, Varsha; Pant, Harish C.] NINDS, Bethesda, MD 20892 USA.
[Kino, Tomoshige] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR48-3
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102039
ER
PT J
AU Park, JW
Zhao, L
Kim, DW
Cheng, SY
AF Park, Jeong Won
Zhao, Li
Kim, Dong Wook
Cheng, Sheue-Yann
TI Src-Dependent Phosphorylation at Tyr406 Confers the Tumor Suppressor
Function of Thyroid Hormone Receptor beta
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Park, Jeong Won; Zhao, Li; Kim, Dong Wook; Cheng, Sheue-Yann] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR25-5
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109128
ER
PT J
AU Polotsky, AJ
Allshouse, AA
Casson, PR
Coutifaris, C
Diamond, MP
Christman, GM
Schlaff, WD
Alvero, R
Trussell, JC
Krawetz, SA
Santoro, N
Eisenberg, E
Zhang, HP
Legro, RS
AF Polotsky, Alex Joel
Allshouse, Amanda Ashleigh
Casson, Peter Raymond
Coutifaris, Christos
Diamond, Michael P.
Christman, Gregory M.
Schlaff, Wlliam D.
Alvero, Ruben
Trussell, J. C.
Krawetz, Stephen A.
Santoro, Nanette
Eisenberg, Esther
Zhang, Heping
Legro, Richard S.
CA RMN
TI Impact of Male Factors and Adiposity on Pregnancy and Live Birth in
Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) Trial
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Polotsky, Alex Joel; Allshouse, Amanda Ashleigh; Alvero, Ruben; Santoro, Nanette] Univ Colorado Denver, Aurora, CO USA.
[Casson, Peter Raymond] Univ Vermont, Burlington, VT USA.
[Coutifaris, Christos] Hosp Univ PA, Philadelphia, PA USA.
[Diamond, Michael P.] Georgia Regents Univ, Augusta, GA USA.
[Christman, Gregory M.] Univ Florida, Shands Hosp, Gainesville, FL USA.
[Schlaff, Wlliam D.] Jefferson Univ, Philadelphia, PA USA.
[Trussell, J. C.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA.
[Krawetz, Stephen A.] Wayne State Univ, Sch Med, Detroit, MI USA.
[Eisenberg, Esther] Vanderbilt Univ, Nashville, TN USA.
[Zhang, Heping] Yale Univ, New Haven, CT USA.
[Legro, Richard S.] Penn State Univ, Hershey, PA USA.
[RMN] NICHD, NIH, Rockville, MD USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0063
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109078
ER
PT J
AU Pooley, JR
Presman, DM
Ganesan, S
Schiltz, RL
Sheshasayee, A
Levi, V
Keskin, O
Lightman, SL
Hager, GL
AF Pooley, John R.
Presman, Diego M.
Ganesan, Sundar
Schiltz, Rodney L.
Sheshasayee, Ashwini
Levi, Valeria
Keskin, Ozlem
Lightman, Stafford L.
Hager, Gordon L.
TI The Interaction of MR and GR in the Nucleus and at DNA: Transcriptional
Implications for the Glucocorticoid Response of Stress-Associated Brain
Regions
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Pooley, John R.; Presman, Diego M.; Schiltz, Rodney L.; Sheshasayee, Ashwini; Hager, Gordon L.] NCI, Bethesda, MD 20892 USA.
[Ganesan, Sundar] NIAID, Bethesda, MD 20892 USA.
[Levi, Valeria] Univ Buenos Aires, Buenos Aires, DF, Argentina.
[Keskin, Ozlem] Koc Univ, Istanbul, Turkey.
[Lightman, Stafford L.] Univ Bristol, Bristol, Avon, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR49-5
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105040
ER
PT J
AU Raghavan, P
Mehta, G
Sharma, ST
Chittiboina, P
Oldfield, EH
Nieman, LK
AF Raghavan, Pooja
Mehta, Gautam
Sharma, Susmeeta T.
Chittiboina, Prashant
Oldfield, Edward Hudson
Nieman, Lynnette K.
TI Multiple Pituitary Adenomas in Cushing's Disease: A Clinical Dilemma
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Raghavan, Pooja] NIH, North Bethesda, MD USA.
[Mehta, Gautam; Chittiboina, Prashant; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA.
[Sharma, Susmeeta T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Oldfield, Edward Hudson] Univ Virginia, Charlottesville, VA USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0601
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101126
ER
PT J
AU Raghavan, P
Kassai, A
Sharma, ST
Peltsverger, M
Nieman, LK
AF Raghavan, Pooja
Kassai, Andrea
Sharma, Susmeeta T.
Peltsverger, Maya
Nieman, Lynnette K.
TI Acute Psychosis As the Initial Manifestation of ACTH-Dependent Cushing's
Syndrome
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Raghavan, Pooja] NIH, North Bethesda, MD USA.
[Kassai, Andrea; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA.
[Sharma, Susmeeta T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Peltsverger, Maya] New Hanover Reg Med Ctr, Wilmington, NC USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0775
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805106078
ER
PT J
AU Raghayan, P
Diker-Cohen, T
Rajan, DP
Sharma, ST
Nieman, LK
AF Raghayan, Pooja
Diker-Cohen, Talia
Rajan, Dhyan P.
Sharma, Susmeeta T.
Nieman, Lynnette K.
TI Colonic Perforation As the Initial Presentation in Cushing's Disease
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Raghayan, Pooja] NIH, North Bethesda, MD USA.
[Diker-Cohen, Talia; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA.
[Rajan, Dhyan P.] Nassau Univ, Med Ctr, E Meadow, NY USA.
[Sharma, Susmeeta T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0774
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805106067
ER
PT J
AU Rago, T
Scutari, M
Latrofa, F
Loiacono, V
Piaggi, P
Marchetti, I
Romani, R
Basolo, F
Miccoli, P
Tonacchera, M
Vitti, P
AF Rago, Teresa
Scutari, Maria
Latrofa, Francesco
Loiacono, Valeria
Piaggi, Paolo
Marchetti, Ivo
Romani, Rossana
Basolo, Fulvio
Miccoli, Paolo
Tonacchera, Massimo
Vitti, Paolo
TI The Large Majority of 1520 Patients with Indeterminate Thyroid Nodule at
Cytology Have a Favourable Outcome and a Clinical Risk Score Has a High
Negative Predictive Value for a More Cumbersome Cancer Disease
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Rago, Teresa; Scutari, Maria; Latrofa, Francesco; Loiacono, Valeria; Marchetti, Ivo; Romani, Rossana; Basolo, Fulvio; Miccoli, Paolo; Tonacchera, Massimo; Vitti, Paolo] Univ Pisa, Pisa, Italy.
[Piaggi, Paolo] NIDDK, NIH, Phoenix, AZ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0544
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109184
ER
PT J
AU Ramamoorthy, S
Oakley, RH
Foley, JF
Cidlowski, JA
AF Ramamoorthy, Sivapriya
Oakley, Robert H.
Foley, Julie F.
Cidlowski, John A.
TI Glucocorticoid Receptor Isoform Knock-in Mice Have Unique Responses to
Glucocorticolds
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Ramamoorthy, Sivapriya; Oakley, Robert H.; Foley, Julie F.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Cidlowski, John A.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR49-4
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105039
ER
PT J
AU Ramirez, AH
Niven, RA
Wood, BJ
Chang, R
Marx, SJ
Collins, MT
AF Ramirez, Andrea Havens
Niven, Ruth A.
Wood, Bradford J.
Chang, Richard
Marx, Stephen J.
Collins, Michael T.
TI Successful Palliation of Metastatic Parathyroid Carcinoma with Denosumab
and Microwave and Radiofrequency Ablation
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Ramirez, Andrea Havens; Wood, Bradford J.] NIH, Bethesda, MD 20892 USA.
[Niven, Ruth A.] Tel Aviv Univ, Tel Aviv, Israel.
[Chang, Richard] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Marx, Stephen J.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Collins, Michael T.] NIDCD, NIH, Bethesda, MD USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0295
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805108023
ER
PT J
AU Ramnitz, MS
Del Rivero, J
Gourh, P
Ovejero, D
Bhattacharyya, N
Guthrie, L
Goldbach-Mansky, R
Wodajo, F
Seo-Mayer, P
Arabshahi, B
Jackson, M
Boskey, A
White, KE
Molinolo, AA
Gafni, RI
Collins, MT
AF Ramnitz, Mary Scott
Del Rivero, Jaydira
Gourh, Pravitt
Ovejero, Diana
Bhattacharyya, Nisan
Guthrie, Lori
Goldbach-Mansky, Raphaela
Wodajo, Felasfa
Seo-Mayer, Patricia
Arabshahi, Bita
Jackson, Malaka
Boskey, Adele
White, Kenneth E.
Molinolo, Alfredo A.
Gafni, Rachel I.
Collins, Michael T.
TI Familial Tumoral Calcinosis: Lessons from a Rare Disorder of Ectopic
Mineralization
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Ramnitz, Mary Scott; Gourh, Pravitt; Ovejero, Diana; Bhattacharyya, Nisan; Guthrie, Lori; Goldbach-Mansky, Raphaela; Molinolo, Alfredo A.; Gafni, Rachel I.; Collins, Michael T.] NIH, Bethesda, MD 20892 USA.
[Del Rivero, Jaydira] NICHHD, NIH, Bethesda, MD 20892 USA.
[Wodajo, Felasfa] Virginia Hosp Ctr, Arlington, VA USA.
[Seo-Mayer, Patricia] Pediat Specialists Virginia, Fairfax, VA USA.
[Arabshahi, Bita] Inova Fairfax Hosp, Falls Church, VA USA.
[Jackson, Malaka] Univ South Carolina, Sch Med, Columbia, SC USA.
[Boskey, Adele] Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA.
[White, Kenneth E.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0222
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105178
ER
PT J
AU Reitman, ML
Lute, B
Jou, W
Lateef, D
Goldgof, M
Xiao, CY
Pinol, RA
Kravitz, A
Huang, YG
Girardet, C
Butler, A
Gavrilova, O
AF Reitman, Marc L.
Lute, Beth
Jou, William
Lateef, Dalya
Goldgof, Margalit
Xiao, Cuiying
Pinol, Ramon A.
Kravitz, Alexxai
Huang, Yuning George
Girardet, Clemence
Butler, Andrew
Gavrilova, Oksana
TI Biphasic Effect of Melanocortin Agonist Mtii on Metabolic Rate and Body
Temperature
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Reitman, Marc L.] Diabet Endocrinol & Obes Branch, Bethesda, MD USA.
[Lute, Beth; Jou, William; Lateef, Dalya; Goldgof, Margalit; Xiao, Cuiying; Pinol, Ramon A.; Kravitz, Alexxai; Huang, Yuning George; Gavrilova, Oksana] NIDDK, NIH, Bethesda, MD USA.
[Girardet, Clemence] Scripps Res Inst, Jupiter, FL USA.
[Butler, Andrew] St Louis Univ, Sch Med, St Louis, MO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR16-4
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103138
ER
PT J
AU Reyes-Capo, DP
Marshal, JD
Naggert, JK
Bryant, JC
Hicks, MD
Kattapurami, MM
Heller, T
Liu, CY
Turkbey, E
Myles, JG
Bernstein, SB
Reynolds, JC
Shamburek, RD
Gahl, WA
Gunay-Aygun, M
Han, JC
AF Reyes-Capo, Daniela P.
Marshal, Jan D.
Naggert, Jurgen K.
Bryant, Joy C.
Hicks, Melanie D.
Kattapurami, Meera M.
Heller, Theo
Liu, Chia-Ying
Turkbey, Evrim
Myles, Jennifer G.
Bernstein, Shanna B.
Reynolds, James C.
Shamburek, Robert D.
Gahl, William A.
Gunay-Aygun, Meral
Han, Joan C.
TI Endocrine and Metabolic Characterization of Alstrom Syndrome
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Reyes-Capo, Daniela P.; Bryant, Joy C.; Hicks, Melanie D.; Kattapurami, Meera M.; Heller, Theo; Liu, Chia-Ying; Turkbey, Evrim; Myles, Jennifer G.; Bernstein, Shanna B.; Reynolds, James C.; Shamburek, Robert D.; Gahl, William A.; Gunay-Aygun, Meral; Han, Joan C.] NIH, Bethesda, MD 20892 USA.
[Marshal, Jan D.; Naggert, Jurgen K.] Jackson Lab, Bar Harbor, ME 04609 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0929
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103255
ER
PT J
AU Roth, MY
Shih, G
Ilani, N
Wang, C
Page, ST
Bremner, WJ
Swerdloff, RS
Sitruk-Ware, R
Blithe, DL
Amory, JK
AF Roth, Mara Yvonne
Shih, Grace
Ilani, Niloufar
Wang, Christina
Page, Stephanie T.
Bremner, William J.
Swerdloff, Ronald S.
Sitruk-Ware, Regine
Blithe, Diana Lynn
Amory, John K.
TI High Acceptability of a Combination of Nestorone (R) and Testosterone
Gels for Male Hormonal Contraception in a Randomized Controlled Trial
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Roth, Mara Yvonne; Shih, Grace; Page, Stephanie T.; Bremner, William J.; Amory, John K.] Univ Washington, Seattle, WA 98195 USA.
[Ilani, Niloufar; Wang, Christina] Harbor UCLA Med Ctr, Torrance, CA 90509 USA.
[Ilani, Niloufar; Wang, Christina; Swerdloff, Ronald S.] Los Angeles Biomed Res Inst, Torrance, CA USA.
[Page, Stephanie T.] Harborview Med Ctr, Seattle, WA USA.
[Swerdloff, Ronald S.] Harbor Univ Calif, Med Ctr, Torrance, CA USA.
[Sitruk-Ware, Regine] Populat Council, New York, NY 10021 USA.
[Blithe, Diana Lynn] NICHHD, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0061
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109055
ER
PT J
AU Sadowski, SM
Millo, CM
Cottle-Delisie, C
Merkel, R
Yang, L
Marx, SJ
Nilubol, N
Herscovitch, P
Kebebew, E
AF Sadowski, Samira Mercedes
Millo, Corina M.
Cottle-Delisie, Candice
Merkel, Roxanne
Yang, Lily
Marx, Stephen J.
Nilubol, Naris
Herscovitch, Peter
Kebebew, Electron
TI Prospective Evaluation of 68Gallium-Dotatate PET/CT in Detecting Unknown
Primary and Metastatic Neuroendocrine Tumors
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Sadowski, Samira Mercedes; Cottle-Delisie, Candice; Merkel, Roxanne; Yang, Lily; Nilubol, Naris; Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA.
[Millo, Corina M.; Herscovitch, Peter] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Marx, Stephen J.] NIDDK, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0302
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805108063
ER
PT J
AU Schernthaner-Reiter, MH
Trivellin, G
Nesterova, MV
Hernandez-Ramirez, LC
Aflorei, ED
Sierra, MD
Stratakis, CA
Korbonits, M
AF Schernthaner-Reiter, Marie Helene
Trivellin, Giampaolo
Nesterova, Maria V.
Hernandez-Ramirez, Laura C.
Aflorei, Elena Daniela
Sierra, Maria De La Luz
Stratakis, Constantine A.
Korbonits, Marta
TI Interaction of AIP with the cAMP-Dependent Protein Kinase (PKA) Pathway
and Its Role in Pituitary Tumor Formation
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Schernthaner-Reiter, Marie Helene; Trivellin, Giampaolo; Nesterova, Maria V.; Sierra, Maria De La Luz; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
[Hernandez-Ramirez, Laura C.; Aflorei, Elena Daniela; Korbonits, Marta] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0640
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109322
ER
PT J
AU Schernthaner-Reiter, MH
Trivellin, G
Nesterova, MV
Hernandez-Ramirez, LC
Aflorei, ED
Sierra, MD
Stratakis, CA
Korbonits, M
AF Schernthaner-Reiter, Marie Helene
Trivellin, Giampaolo
Nesterova, Maria V.
Hernandez-Ramirez, Laura C.
Aflorei, Elena Daniela
Sierra, Maria De La Luz
Stratakis, Constantine A.
Korbonits, Marta
TI Interaction of AIP with the cAMP-Dependent Protein Kinase (PKA) Pathway
and Its Role in Pituitary Tumor Formation
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Schernthaner-Reiter, Marie Helene; Trivellin, Giampaolo; Nesterova, Maria V.; Sierra, Maria De La Luz; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
[Hernandez-Ramirez, Laura C.; Aflorei, Elena Daniela; Korbonits, Marta] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP09-4
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102106
ER
PT J
AU Schlogl, M
Votruba, S
Piaggi, P
Walter, M
Krakoff, J
Thearle, MS
AF Schlogl, Mathias
Votruba, Susi
Piaggi, Paolo
Walter, Mary
Krakoff, Jonathan
Thearle, Marie S.
TI Higher 24h Ad Libitum Food Intake Predicts Lower Fasting Plasma Irisin
Concentrations in Adult Humans
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Schlogl, Mathias] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
[Votruba, Susi; Piaggi, Paolo; Thearle, Marie S.] NIDDK, NIH, Phoenix, AZ USA.
[Walter, Mary] NIDDK, NIH, Bethesda, MD 20892 USA.
[Krakoff, Jonathan] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0875
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103023
ER
PT J
AU Sertedaki, A
Markou, A
Kaltsas, GA
Androulakis, L
Pappa, T
Gouli, A
Papanastasiou, L
Zacharoulis, A
Karavidas, A
Ragkou, D
Vlachakis, D
Kossida, S
Campanac, E
Hoffman, DA
De La Luz, M
Xekouki, P
Stratakis, CA
Charmandari, E
Chrousos, GP
Piaditis, GP
AF Sertedaki, Amalia
Markou, Athina
Kaltsas, Gregory A.
Androulakis, Loannis
Pappa, Theodora
Gouli, Aggeliki
Papanastasiou, Labrini
Zacharoulis, Achilles
Karavidas, Apostolos
Ragkou, Despoina
Vlachakis, Dimitrios
Kossida, Sophia
Campanac, Emilie
Hoffman, Dax A.
De La Luz, Maria
Xekouki, Paraskevi
Stratakis, Constantine A.
Charmandari, Evangelia
Chrousos, George P.
Piaditis, Georgios P.
TI Mutations of the KCNJ5 Gene in Patients with Hypertension and Increased
Aldosterone Response to ACTH
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Sertedaki, Amalia; Kaltsas, Gregory A.; Charmandari, Evangelia; Chrousos, George P.] Univ Athens, Sch Med, Athens, Greece.
[Markou, Athina; Androulakis, Loannis; Pappa, Theodora; Gouli, Aggeliki; Papanastasiou, Labrini; Zacharoulis, Achilles; Karavidas, Apostolos; Ragkou, Despoina; Piaditis, Georgios P.] G Gennimatas Gen Hosp, Athens, Greece.
[Vlachakis, Dimitrios; Kossida, Sophia] Acad Athens, Biomed Res Fdn, Athens, Greece.
[Campanac, Emilie; Hoffman, Dax A.; De La Luz, Maria; Xekouki, Paraskevi; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
RI Charmandari, Evangelia/B-6701-2011
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0837
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805106105
ER
PT J
AU Sertedaki, A
Markou, A
Kaltsas, GA
Androulakis, L
Pappa, T
Gouli, A
Papanastasiou, L
Zacharoulis, A
Karavidas, A
Ragkou, D
Vlachakis, D
Kossida, S
Campanac, E
Hoffman, DA
De La Luz, M
Xekouki, P
Stratakis, CA
Charmandari, E
Chrousos, GP
Piaditis, GP
AF Sertedaki, Amalia
Markou, Athina
Kaltsas, Gregory A.
Androulakis, Loannis
Pappa, Theodora
Gouli, Aggeliki
Papanastasiou, Labrini
Zacharoulis, Achilles
Karavidas, Apostolos
Ragkou, Despoina
Vlachakis, Dimitrios
Kossida, Sophia
Campanac, Emilie
Hoffman, Dax A.
De La Luz, Maria
Xekouki, Paraskevi
Stratakis, Constantine A.
Charmandari, Evangelia
Chrousos, George P.
Piaditis, Georgios P.
TI Mutations of the KCNJ5 Gene in Patients with Hypertension and Increased
Aldosterone Response to ACTH
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Sertedaki, Amalia; Kaltsas, Gregory A.; Charmandari, Evangelia; Chrousos, George P.] Univ Athens, Sch Med, Athens, Greece.
[Markou, Athina; Androulakis, Loannis; Pappa, Theodora; Gouli, Aggeliki; Papanastasiou, Labrini; Zacharoulis, Achilles; Karavidas, Apostolos; Ragkou, Despoina; Piaditis, Georgios P.] G Gennimatas Gen Hosp, Athens, Greece.
[Vlachakis, Dimitrios; Kossida, Sophia] Acad Athens, Biomed Res Fdn, Athens, Greece.
[Campanac, Emilie; Hoffman, Dax A.; De La Luz, Maria; Xekouki, Paraskevi; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP06-4
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805106082
ER
PT J
AU Sfeir, JG
Rother, KI
Popii, VB
AF Sfeir, Jad G.
Rother, Kristina I.
Popii, Violeta Botea
TI Liraglutide: An Alternative to Insulin for New Onset Type 1 Diabetes in
Adults?
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Sfeir, Jad G.] Lankenau Med Ctr, Wynnewood, PA USA.
[Rother, Kristina I.] NIDDK, Bethesda, MD 20892 USA.
[Popii, Violeta Botea] Main Line Hlth, Wynnewood, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0977
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805107046
ER
PT J
AU Shapiro, J
Liu, S
Stratakis, CA
AF Shapiro, Jenna
Liu, Sisi
Stratakis, Constantine A.
TI Alteration of PKA Subunit Expression on the Osteogenic Behavior of MC3T3
Murine Pre-Osteoblasts
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Shapiro, Jenna; Liu, Sisi] NICHD, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
[Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0234
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105205
ER
PT J
AU Sharma, ST
Yanovski, JA
Abraham, SB
Nieman, LK
AF Sharma, Susmeeta T.
Yanovski, Jack A.
Abraham, Smita Baid
Nieman, Lynnette K.
TI Utility of Measurement of Dexamethasone Levels in the Diagnostic Testing
for Cushing's Syndrome
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Sharma, Susmeeta T.; Abraham, Smita Baid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Yanovski, Jack A.; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR02-1
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102281
ER
PT J
AU Sharma, ST
Sinaii, N
Nieman, LK
AF Sharma, Susmeeta T.
Sinaii, Ninet
Nieman, Lynnette K.
TI Factors Predicting the Development of Severe Transanninitis with
Ketoconazole Treatment in Cushing's Syndrome
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Sharma, Susmeeta T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Sinaii, Ninet; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP27-1
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100137
ER
PT J
AU Sharma, ST
Sinaii, N
Nieman, LK
AF Sharma, Susmeeta T.
Sinaii, Ninet
Nieman, Lynnette K.
TI Factors Predicting the Development of Severe Transanninitis with
Ketoconazole Treatment in Cushing's Syndrome
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Sharma, Susmeeta T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Sinaii, Ninet; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0772
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103071
ER
PT J
AU Sharma, ST
Sinaii, N
Nieman, LK
AF Sharma, Susmeeta T.
Sinaii, Ninet
Nieman, Lynnette K.
TI Combination Treatment with Ketoconazole and Metyrapone in Cushing's
Syndrome
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Sharma, Susmeeta T.] Eunice Kennedy Shrivel Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Sinaii, Ninet; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0777
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103128
ER
PT J
AU Shulman, DI
Winer, KK
AF Shulman, Dorothy I.
Winer, Karen K.
TI Results of One Year of Therapy with Recombinant Human Parathyroid
Hormone 1-34 (rhPTH 1-34) Delivered By Insulin Pump in 3 Women with
Activating Mutations of the Calcium Sensing Receptor (CASR)
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Shulman, Dorothy I.] Univ S FL, Morsani Coll Med, Tampa, FL USA.
[Winer, Karen K.] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0193
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105055
ER
PT J
AU Slominski, A
Kim, TK
Takeda, Y
Janjetovic, Z
Brozyna, A
Skobowiat, C
Wang, J
Postlethwaite, A
Li, W
Tuckey, RC
Jetten, AM
AF Slominski, Andrzej
Kim, Tae-Kang
Takeda, Yukimasa
Janjetovic, Zorica
Brozyna, Anna
Skobowiat, Cezary
Wang, Jin
Postlethwaite, Arnold
Li, Wei
Tuckey, Robert C.
Jetten, Anton M.
TI RORa and RORg Are Expressed in Human Skin and Serve As Receptors for
Endogenously Produced Noncalcemic 20-Hydroxy- and
20,23-Dihydroxy-Vitamin D
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Slominski, Andrzej; Kim, Tae-Kang; Janjetovic, Zorica; Skobowiat, Cezary; Wang, Jin; Postlethwaite, Arnold; Li, Wei] Univ Tennessee, HSC, Memphis, TN USA.
[Takeda, Yukimasa; Jetten, Anton M.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Brozyna, Anna] Nicolaus Copernicus Univ, Torun, Poland.
[Tuckey, Robert C.] Univ Western Australia, Crawley, Australia.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0407
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102288
ER
PT J
AU Sumner, AE
Thoreson, CK
O'Connor, MY
Reynolds, JC
Ricks, M
Chung, ST
AF Sumner, Anne E.
Thoreson, Caroline K.
O'Connor, Michelle Y.
Reynolds, James C.
Ricks, Madia
Chung, Stephanie T.
TI Vitamin D Levels Defined As Insufficient By the Institute of Medicine
and the Endocrine Society May be Adequate in Africans
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Sumner, Anne E.; Thoreson, Caroline K.; O'Connor, Michelle Y.; Ricks, Madia; Chung, Stephanie T.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Reynolds, James C.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0248
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105319
ER
PT J
AU Suzuki, S
Kino, T
AF Suzuki, Shigeru
Kino, Tomoshige
TI Sirt1 Enhances the Transcriptional Activity of the Glucocorticoid
Receptor in Its Deacetylase Activity-Independent Fashion
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Suzuki, Shigeru; Kino, Tomoshige] NICHD, NIH, Bethesda, MD USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0433
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102229
ER
PT J
AU Swerdloff, RS
Pak, Y
Wang, C
Liu, PY
Bhasin, S
Gill, TM
Matsumoto, AM
Pahor, M
Surampudi, P
Romashkan, S
Hadley, E
Snyder, PJ
AF Swerdloff, Ronald S.
Pak, Youngju
Wang, Christina
Liu, Peter Y.
Bhasin, Shalender
Gill, Thomas M.
Matsumoto, Alvin M.
Pahor, Marco
Surampudi, Prasanth
Romashkan, Sergei
Hadley, Evan
Snyder, Peter J.
TI Testosterone Pharmacokinetics (PK) in Older Men Participating in the
Testosterone Trials (The T Trials)
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Swerdloff, Ronald S.; Pak, Youngju; Wang, Christina; Surampudi, Prasanth] Harbor UCLA Med Ctr, Torrance, CA 90509 USA.
[Swerdloff, Ronald S.; Pak, Youngju; Wang, Christina; Surampudi, Prasanth] Los Angeles Biomed Res Inst, Torrance, CA USA.
[Liu, Peter Y.] Harbor UCLA Med Ctr, Los Angeles, CA USA.
[Liu, Peter Y.] Los Angeles Biomed Res Inst, Los Angeles, CA USA.
[Bhasin, Shalender] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA.
[Gill, Thomas M.] Yale Sch Med, New Haven, CT USA.
[Matsumoto, Alvin M.] VA Puget Sound Hlth Care Sys, Seattle, WA USA.
[Pahor, Marco] Univ Florida, Gainesville, FL USA.
[Romashkan, Sergei; Hadley, Evan] NIA, Bethesda, MD 20892 USA.
[Snyder, Peter J.] Univ Penn, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0086
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805107202
ER
PT J
AU Szarek, E
Leal, LF
Kotula-Balak, M
Bilinska, B
Stratakis, CA
AF Szarek, Eva
Leal, Leticia Ferro
Kotula-Balak, Malgorzata
Bilinska, Barbara
Stratakis, Constantine A.
TI A cAMP-Specific Phosphodiesterase, Phosphodiesterase 8B (PDE8B), Affects
Sertoli Cell Proliferation in Adult Mice
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Szarek, Eva; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
[Leal, Leticia Ferro] Univ Sao Paulo, Ribeirao Preto, SP, Brazil.
[Kotula-Balak, Malgorzata; Bilinska, Barbara] Jagiellonian Univ, Krakow, Poland.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR36-4
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805107236
ER
PT J
AU Takasawa, K
Pelosi, E
Takagi, M
Morio, T
Asahara, H
Schlessinger, D
Mizutani, S
Koopman, P
Kashimada, K
AF Takasawa, Kei
Pelosi, Emanuele
Takagi, Masatoshi
Morio, Tomohiro
Asahara, Hiroshi
Schlessinger, David
Mizutani, Shuki
Koopman, Peter
Kashimada, Kenichi
TI FOXL2 Transcriptionally Represses Sf1 Expression By Antagonizing WT1
during Ovarian Development in Mice
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Takasawa, Kei; Takagi, Masatoshi; Morio, Tomohiro; Asahara, Hiroshi; Mizutani, Shuki; Kashimada, Kenichi] Tokyo Med & Dent Univ, Tokyo, Japan.
[Pelosi, Emanuele; Schlessinger, David] NIA, NIH, Biomed Res Ctr, Intramural Res Program, Bethesda, MD 20892 USA.
[Koopman, Peter] Univ Queensland, Brisbane, Qld, Australia.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0113
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805107246
ER
PT J
AU Thearle, MS
Schlogl, M
Bonfiglio, SM
Krakoff, J
AF Thearle, Marie S.
Schlogl, Mathias
Bonfiglio, Susan M.
Krakoff, Jonathan
TI Energy Expenditure Response to 24 Hours of Overfeeding and Fasting Are
Related to Adiposity
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Thearle, Marie S.] NIDDK, NIH, Phoenix, AZ USA.
[Schlogl, Mathias; Bonfiglio, Susan M.; Krakoff, Jonathan] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR16-3
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103137
ER
PT J
AU Tiano, JP
Springer, DA
Rane, SG
AF Tiano, Joseph P.
Springer, Danielle A.
Rane, Sushil G.
TI Transforming Growth Factor-Beta Is Negatively Associated with Irisin in
Exercised Obese Mice
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Tiano, Joseph P.; Springer, Danielle A.; Rane, Sushil G.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0349
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100236
ER
PT J
AU Tuna, MM
Karakilic, E
Basaran, MN
Dogan, BA
Imga, NN
Arduc, A
Tutuncu, Y
Unal, T
Berker, D
Guler, S
AF Tuna, Mazhar Muslum
Karakilic, Ersen
Basaran, Mehtap Navdar
Dogan, Bercem Aycicek
Imga, Narin Nasiroglu
Arduc, Ayse
Tutuncu, Yasemin
Unal, Tuba
Berker, Dilek
Guler, Serdar
TI Evaluation of Immunohistochemical Staining Features in Acromegaly
Patients- Comparing with Clinical Findings
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Tuna, Mazhar Muslum; Dogan, Bercem Aycicek; Imga, Narin Nasiroglu; Unal, Tuba; Berker, Dilek] Ankara Numune Training & Res Hosp, Ankara, Turkey.
[Karakilic, Ersen; Basaran, Mehtap Navdar] Ankara Numune Educ & Training Hosp, Ankara, Turkey.
[Arduc, Ayse] NIDDK, Diabet Endocrine & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Tutuncu, Yasemin] Haydarpasa Numune Training & Res Hosp, Istanbul, Turkey.
[Guler, Serdar] Hitit Univ, Fac Med, Corum, Turkey.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0620
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101020
ER
PT J
AU van Berkel, A
Rao, JU
Kusters, B
Demir, T
Visser, E
Mensenkamp, A
van der Laak, JAWM
Oosterwijk, E
Lenders, JW
Sweep, FCGJ
Wevers, RA
Hermus, ARMM
Langenhuijzen, HJF
Kunst, HPM
Pacak, K
Gotthardt, M
Timmers, HJLM
AF van Berkel, Anouk
Rao, Jyotsna U.
Kusters, Benno
Demir, Tuna
Visser, Erik
Mensenkamp, Arjen
van der Laak, Jeroen A. W. M.
Oosterwijk, Egbert
Lenders, Jacques W. M.
Sweep, Fred C. G. J.
Wevers, Ron A.
Hermus, Ad R. M. M.
Langenhuijzen, Hans J. F.
Kunst, Henricus P. M.
Pacak, Karel
Gotthardt, Martin
Timmers, Henri J. L. M.
TI Correlation Between in Vivo 18F-Fluorodeoxyglucose PET and
lmmunohistochemical Markers of Glucose Uptake and Metabolism in
Pheochromocytoma and Paraganglioma
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [van Berkel, Anouk; Rao, Jyotsna U.; Visser, Erik; van der Laak, Jeroen A. W. M.; Hermus, Ad R. M. M.; Timmers, Henri J. L. M.] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands.
[Kusters, Benno; Demir, Tuna; Mensenkamp, Arjen; Oosterwijk, Egbert; Sweep, Fred C. G. J.; Wevers, Ron A.; Langenhuijzen, Hans J. F.; Kunst, Henricus P. M.; Gotthardt, Martin] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands.
[Lenders, Jacques W. M.] Raboud Univ, Med Ctr, Nijmegen, Netherlands.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP14-1
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100181
ER
PT J
AU van Berkel, A
Rao, JU
Kusters, B
Demir, T
Visser, E
Mensenkamp, A
van der Laak, JAWM
Oosterwijk, E
Lenders, JWM
Sweep, FCGJ
Wevers, RA
Hermus, ARMM
Langenhuijzen, HJF
Kunst, HPM
Pacak, K
Gotthardt, M
Timmers, HJLM
AF van Berkel, Anouk
Rao, Jyotsna U.
Kusters, Benno
Demir, Tuna
Visser, Erik
Mensenkamp, Arjen
van der Laak, Jeroen A. W. M.
Oosterwijk, Egbert
Lenders, Jacques W. M.
Sweep, Fred C. G. J.
Wevers, Ron A.
Hermus, Ad R. M. M.
Langenhuijzen, Hans J. F.
Kunst, Henricus P. M.
Pacak, Karel
Gotthardt, Martin
Timmers, Henri J. L. M.
TI Correlation Between in Vivo 18F-Fluorodeoxyglucose PET and
lmmunohistochemical Markers of Glucose Uptake and Metabolism in
Pheochromocytoma and Paraganglioma
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [van Berkel, Anouk; Rao, Jyotsna U.; Visser, Erik; van der Laak, Jeroen A. W. M.; Lenders, Jacques W. M.; Hermus, Ad R. M. M.; Timmers, Henri J. L. M.] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands.
[Kusters, Benno; Demir, Tuna; Mensenkamp, Arjen; Oosterwijk, Egbert; Sweep, Fred C. G. J.; Wevers, Ron A.; Langenhuijzen, Hans J. F.; Kunst, Henricus P. M.; Gotthardt, Martin] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0798
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101329
ER
PT J
AU Venturutti, L
Russo, RIC
Yankilevich, P
Oakley, RH
Huang, THM
Schillaci, R
Cidlowski, JA
Elizalde, PV
AF Venturutti, Leandro
Cordo Russo, Rosalia Inas
Yankilevich, Patricio
Oakley, Robert H.
Huang, Tim H-M
Schillaci, Roxana
Cidlowski, John A.
Virginia Elizalde, Patricia
TI Tumor Suppressor Mir-16 Mediates Trastuzumab Therapeutic Effects in
Breast Cancer Via Its Novel Targets, Cyclin J (CCNJ) and Fuse Binding
Protein 1 (FUBP1)
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Venturutti, Leandro; Cordo Russo, Rosalia Inas; Schillaci, Roxana; Virginia Elizalde, Patricia] Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt, Buenos Aires, DF, Argentina.
[Yankilevich, Patricio] IBIOBA CONICET MPSP, Buenos Aires, DF, Argentina.
[Oakley, Robert H.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Huang, Tim H-M] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
NIEHS NIH, Res Triangle Pk, NC USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0318
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805108126
ER
PT J
AU Xekouki, P
Zilbermint, M
Faucz, FR
Lodish, MB
Berthon, AS
Schernthaner-Reiter, MH
Hodes, A
Sierra, MDLL
Bertherat, JY
Stratakis, CA
AF Xekouki, Paraskevi
Zilbermint, Mihail
Faucz, Fabio Rueda
Lodish, Maya Beth
Berthon, Annabel Sophie
Schernthaner-Reiter, Marie Helene
Hodes, Aaron
Sierra, Maria De La Luz
Bertherat, Jerome Yves
Stratakis, Constantine A.
TI Mutations of ARMC5 Gene May be Implicated in Primary Hyperaldosteronism
(PA)
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Xekouki, Paraskevi; Zilbermint, Mihail; Faucz, Fabio Rueda; Lodish, Maya Beth; Berthon, Annabel Sophie; Schernthaner-Reiter, Marie Helene; Sierra, Maria De La Luz; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
[Hodes, Aaron] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
[Bertherat, Jerome Yves] CNRS, INSERM, Unite 1016, Unite Mixte Rech 8104,Inst Cochin, Paris, France.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0841
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805106109
ER
PT J
AU Yang, RF
Tsai-Morris, CH
Dufau, ML
AF Yang, Ruifeng
Tsai-Morris, Chon-Hwa
Dufau, Maria L.
TI Elucidation of RNA Binding Regions of Gonadotropin Regulated Testicular
RNA Helicase (GRTH/DDX25) Protein to Transcripts of a Chromatin
Remodeling Protein Essential for Spermatogenesis
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Yang, Ruifeng; Tsai-Morris, Chon-Hwa] NIH, Bethesda, MD 20892 USA.
[Dufau, Maria L.] NICHD, NIH, Bethesda, MD USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0100
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805107258
ER
PT J
AU Yanovski, JA
Lee, BG
Koo, J
Gavrilova, O
Taylor-Douglas, D
Roberson, R
Koutzoumis, D
AF Yanovski, Jack A.
Lee, Bong Gi
Koo, JaShin
Gavrilova, Oksana
Taylor-Douglas, Dezmond
Roberson, Robin
Koutzoumis, Dimitri
TI Studies of Mechanisms for Pediatric Obesity Due to Melanocortin 3
Receptor (MC3R) Insufficiency Using Knock-in Mice Expressing Human Wild
Type MC3R or Thr6Lys+Va1811Ie Human Variant MC3R
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Yanovski, Jack A.; Lee, Bong Gi; Koo, JaShin; Taylor-Douglas, Dezmond; Roberson, Robin; Koutzoumis, Dimitri] NIH, Bethesda, MD 20892 USA.
[Gavrilova, Oksana] NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR53-2
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104134
ER
PT J
AU Yuditskaya, S
Gounden, V
Soldin, S
Celi, FS
AF Yuditskaya, Susan
Gounden, Verena
Soldin, Steven
Celi, Francesco S.
TI Low Serum Triiodothyronine Levels Associated with Symptomatic
Hypothyroidism in an Athyreotic Patient on Adequate Levothyroxine
Replacement
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Yuditskaya, Susan; Gounden, Verena; Soldin, Steven] NIH, Bethesda, MD 20892 USA.
[Celi, Francesco S.] NIDDKD, NIH, Bethesda, MD USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0522
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805108264
ER
PT J
AU Yuditskaya, S
Sharma, ST
Nieman, LK
AF Yuditskaya, Susan
Sharma, Susmeeta T.
Nieman, Lynnette K.
TI Ectopic Corticotropinoma or ACTH-Secreting Breast Cancer Metastasis?
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Yuditskaya, Susan; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA.
[Sharma, Susmeeta T.] Eunice Kennedy Shrivel Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0662
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101101
ER
PT J
AU Zilbermint, M
Faucz, FR
Lodish, MB
Szarek, E
Trivellin, G
Sinaii, N
Libe, R
Assie, G
Espiard, S
Drougat, L
Ragazzon, B
Bertherat, JY
Stratakis, CA
AF Zilbermint, Mihail
Faucz, Fabio Rueda
Lodish, Maya Beth
Szarek, Eva
Trivellin, Giampaolo
Sinaii, Ninet
Libe, Rossella
Assie, Guillaume
Espiard, Stephanie
Drougat, Ludivine
Ragazzon, Bruno
Bertherat, Jerome Yves
Stratakis, Constantine A.
TI Macronodular Adrenal Hyperplasia Due to Mutations in an Armadillo Repeat
Containing 5 (ARMC5) Gene: A Clinical and Genetic Investigation
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Zilbermint, Mihail; Faucz, Fabio Rueda; Lodish, Maya Beth; Szarek, Eva; Trivellin, Giampaolo; Sinaii, Ninet; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
[Libe, Rossella; Assie, Guillaume; Espiard, Stephanie; Drougat, Ludivine; Ragazzon, Bruno; Bertherat, Jerome Yves] Inst Cochin, INSERM, Unite 1016, CNRS,UMR 8104, Paris, France.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR14-1
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102217
ER
PT J
AU Zilbermint, M
Hodes, A
Lodish, MB
Sinaii, N
Belyavskaya, E
Lyssikatos, C
Rosenberg, K
Meyer, J
Stratakis, CA
AF Zilbermint, Mihail
Hodes, Aaron
Lodish, Maya Beth
Sinaii, Ninet
Belyavskaya, Elena
Lyssikatos, Charalampos
Rosenberg, Kendra
Meyer, Jerrold
Stratakis, Constantine A.
TI Hair Cortisol Measurement in the Evaluation of Cushing's Syndrome: A
Pilot Study
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Zilbermint, Mihail; Lodish, Maya Beth; Sinaii, Ninet; Belyavskaya, Elena; Lyssikatos, Charalampos; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
[Hodes, Aaron] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
[Rosenberg, Kendra; Meyer, Jerrold] Univ Massachusetts, Amherst, MA 01003 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0658
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101280
ER
PT J
AU Zuber, S
Wesley, R
Eisenhofer, G
Pacak, K
Kantorovich, V
AF Zuber, Samuel
Wesley, Robert
Eisenhofer, Graeme
Pacak, Karel
Kantorovich, Vitaly
TI Clinical Utility of Chromogranin a in Sdhx-Related Paragangliomas
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Zuber, Samuel; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Wesley, Robert] NIH, Bethesda, MD USA.
[Eisenhofer, Graeme] Univ Hosp Carl Gustav Carus, Dresden, Germany.
[Kantorovich, Vitaly] Univ Connecticut, Ctr Hlth, Farmington, CT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR27-1
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100070
ER
PT J
AU Ghosh, G
Grewal, J
Mannisto, T
Mendola, P
Chen, Z
Xie, YL
Laughon, SK
AF Ghosh, Gaurav
Grewal, Jagteshwar
Mannisto, Tuija
Mendola, Pauline
Chen, Zhen
Xie, Yunlong
Laughon, S. Katherine
TI RACIAL/ETHNIC DIFFERENCES IN PREGNANCY-RELATED HYPERTENSIVE DISEASE IN
NULLIPAROUS WOMEN
SO ETHNICITY & DISEASE
LA English
DT Article
DE Ethnic Groups; Hypertension; Pregnancy-induced; Pre-eclampsia
ID RISK-FACTORS; MATERNAL HYPERTENSION; HISPANIC WOMEN; PREECLAMPSIA;
POPULATION; OUTCOMES; COHORT; COMPLICATIONS; DISPARITIES; MANAGEMENT
AB Objective: Hypertension and cardiovascular disease rates vary by race/ethnicity in nonpregnant adults. We aimed to examine racial/ethnic differences in prevalence and severity of hypertensive diseases during pregnancy in nulliparous women.
Design, Setting, Participants: Nulliparous women with singleton deliveries and electronic medical record data on demographics and pregnancy outcomes (n=56,617) were selected from the Consortium on Safe Labor (2002-2008). Multivariable logistic regression was performed to calculate the adjusted odds of gestational hypertension, mild preeclampsia, severe preeclampsia, eclampsia, chronic hypertension, superimposed preeclampsia, and unspecified hypertension for women who were non-Hispanic Black, Hispanic, Asian/Pacific Islander, and multiracial/other race/ethnicity, compared with non-Hispanic White women.
Results: Non-Hispanic Black women had higher odds of entering pregnancy with chronic hypertension (adjusted odds ratio (AOR) =1.43, 95% confidence interval (CI) 1.11-1.84) and had higher odds of developing mild (AOR=1.26, 95% CI 1.10-1.45), severe (AOR=1.31, 95% CI 1.10-1.57) or superimposed preeclampsia (AOR=1.98, 95% CI 1.40-2.80) compared to non-Hispanic White women. Hispanic women and Asian/Pacific Islanders had higher odds of remaining normotensive (AOR=1.22, 95% CI 1.12-1.33 and AOR=1.55, 95% CI 1.31-1.84, respectively).
Conclusions: Odds for specific gestational hypertensive diseases varied by race/ethnicity among women during their first pregnancy. Non-Hispanic Black women experienced more severe disease, while Hispanic women and Asian/Pacific Islanders had an overall decreased risk compared to non-Hispanic Whites. Patterns of racial/ethnic variation associated with hypertensive diseases during pregnancy were similar to racial/ethnic associations reported for adultonset cardiovascular disease, suggesting that there may be common pathways and shared risk factors.
C1 [Ghosh, Gaurav; Grewal, Jagteshwar; Mannisto, Tuija; Mendola, Pauline; Laughon, S. Katherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Rockville, MD 20852 USA.
[Chen, Zhen; Xie, Yunlong] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, NIH, Rockville, MD 20852 USA.
RP Laughon, SK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM laughonsk@mail.nih.gov
OI Grewal, Jagteshwar/0000-0002-0141-4876; Mendola,
Pauline/0000-0001-5330-2844; Grantz, Katherine/0000-0003-0276-8534
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health [HHSN267200603425C]
FX The Consortium on Safe Labor was supported by the Intramural Research
Program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development, National Institutes of Health, through Contract
No. HHSN267200603425C.
NR 30
TC 6
Z9 6
U1 1
U2 3
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
EI 1945-0826
J9 ETHNIC DIS
JI Ethn. Dis.
PD SUM
PY 2014
VL 24
IS 3
BP 283
EP 289
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CU7KT
UT WOS:000363717300003
PM 25065068
ER
PT J
AU Walker, ER
Nelson, CR
Antoine-LaVigne, D
Thigpen, DT
Puggal, MA
Sarpong, DF
Smith, AM
Stewart, AL
Henderson, FC
AF Walker, Evelyn R.
Nelson, Cheryl R.
Antoine-LaVigne, Donna
Thigpen, Darcel T.
Puggal, Mona A.
Sarpong, Daniel F.
Smith, Alice M.
Stewart, Alyce L.
Henderson, Frances C.
TI RESEARCH PARTICIPANTS' OPINIONS ON GENETIC RESEARCH AND REASONS FOR
PARTICIPATION: A JACKSON HEART STUDY FOCUS GROUP ANALYSIS
SO ETHNICITY & DISEASE
LA English
DT Article
DE Community-based Participatory Research; Genetics; Ethics; Community
Education
ID AFRICAN-AMERICANS; RECRUITMENT
AB The Jackson Heart Study (JHS) convened focus groups to engage the community in dialogue on participation in the National, Heart, Lung and Blood Institute's Candidate Gene Resource (CARe) project. CARe, a genome wide association and candidate gene study, required the release of participant phenotypic and genotypic data with storage at NIH for widespread distribution to qualified researchers. The authors wanted to assess the willingness of an African American community to participate in the genetics research, given the past history of bioethical misconduct in ethnic minority communities. The discussion produced the following specific issues of interest: reasons for participants' interest in genetics research; participants' knowledge about the JHS; and participants' knowledge about genetics research and its advantages and disadvantages. Training on genetic issues was also developed for the JHS community and staff.
C1 [Walker, Evelyn R.] Mississippi Dept Hlth, Ridgeland, MS 39157 USA.
[Nelson, Cheryl R.; Puggal, Mona A.] NHLBI, NIH, Bethesda, MD USA.
[Antoine-LaVigne, Donna; Sarpong, Daniel F.; Smith, Alice M.; Stewart, Alyce L.] Jackson State Univ, Jackson, MS 39217 USA.
[Henderson, Frances C.] Univ Mississippi, Med Ctr, University, MS 38677 USA.
RP Walker, ER (reprint author), Mississippi Dept Hlth, Off Hlth Promot & Hlth Equ, Ridgeland, MS 39157 USA.
EM Evelyn.Walker@msdh.ms.gov
FU National Heart, Lung, and Blood Institute [HHSN268201300046C,
HHSN268201300047C, HHSN268201300048C, HHSN268201300049C,
HHSN268201300050C]; National Institute on Minority Health and Health
Disparities
FX The Jackson Heart Study is supported by contracts HHSN268201300046C,
HHSN268201300047C, HHSN268201300048C, HHSN268201300049C,
HHSN268201300050C from the National Heart, Lung, and Blood Institute and
the National Institute on Minority Health and Health Disparities. We
also acknowledge Doris Withers, PhD Medgar Evers College, School of
Science, Health, and Technology (Biology Department) for her guidance
with the focus groups and in completing this manuscript.
NR 19
TC 1
Z9 1
U1 0
U2 0
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
EI 1945-0826
J9 ETHNIC DIS
JI Ethn. Dis.
PD SUM
PY 2014
VL 24
IS 3
BP 290
EP 297
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CU7KT
UT WOS:000363717300004
PM 25065069
ER
PT J
AU McLean, MH
Hanson, ML
Gold, B
Golubeva, Y
Anver, MR
Wu, X
Sun, D
Steidler, L
Durum, SK
AF McLean, M. H.
Hanson, M. L.
Gold, B.
Golubeva, Y.
Anver, M. R.
Wu, X.
Sun, D.
Steidler, L.
Durum, S. K.
TI INTRA-LUMINAL INTERLEUKIN (IL)-27 IS A POTENTIAL FUTURE THERAPEUTIC FOR
INFLAMMATORY BOWEL DISEASE
SO GUT
LA English
DT Meeting Abstract
CT Annual Meeting of the British-Society-of-Gastroenterology (BSG)
CY JUN 16-19, 2014
CL Manchester, ENGLAND
SP British Soc Gastroenterol
C1 [McLean, M. H.; Hanson, M. L.; Durum, S. K.] NCI, Canc & Inflammat Program, Bethesda, MD 20892 USA.
[Gold, B.] NCI, Human Genet Sect, Bethesda, MD 20892 USA.
[Golubeva, Y.; Anver, M. R.] Leidos Biomedical Res Inc, Lab Anim Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Wu, X.; Sun, D.] Leidos Biomedical Res Inc, Lab Mol Technol, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Steidler, L.] ActoGenix NV, Zwijnaarde, Belgium.
NR 0
TC 1
Z9 1
U1 1
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
EI 1468-3288
J9 GUT
JI Gut
PD JUN
PY 2014
VL 63
SU 1
MA PTU-103
BP A84
EP A84
DI 10.1136/gutjnl-2014-307263.177
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CO8OF
UT WOS:000359428500179
ER
PT J
AU Finegold, J
Bordachar, P
Kyriacou, A
Sohaib, SMA
Kanagaratnam, P
Ploux, S
Lim, B
Peters, N
Davies, DW
Lefroy, D
Ritter, P
Francis, D
Whinnett, Z
AF Finegold, Judith
Bordachar, Pierre
Kyriacou, Andreas
Sohaib, S. M. Afzal
Kanagaratnam, Prapa
Ploux, Sylvain
Lim, Boon
Peters, Nicholas
Davies, David Wyn
Lefroy, David
Ritter, Philippe
Francis, Darrel
Whinnett, Zachary
TI CORRELATION AND REPRODUCIBILITY OF INVASIVE AND NON-INVASIVE
HAEMODYNAMIC PARAMETERS FOR IDENTIFYING OPTIMAL AV DELAY IN CARDIAC
RESYNCHRONISATION THERAPY
SO HEART
LA English
DT Meeting Abstract
CT Annual Conference of the British-Cardiovascular-Society
CY JUN 02-04, 2014
CL Manchester, ENGLAND
SP British Cardiovascular Soc
C1 [Finegold, Judith; Kyriacou, Andreas; Sohaib, S. M. Afzal; Francis, Darrel; Whinnett, Zachary] Natl Heart & Lung Inst, Int Ctr Circulatory Hlth, Bethesda, MD USA.
[Bordachar, Pierre; Ploux, Sylvain; Ritter, Philippe] Hop Haut Leveque, Pessac, France.
[Kanagaratnam, Prapa; Lim, Boon; Peters, Nicholas; Davies, David Wyn; Lefroy, David] Imperial Coll, London, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
EI 1468-201X
J9 HEART
JI Heart
PD JUN
PY 2014
VL 100
SU 3
MA 41
BP A22
EP A23
DI 10.1136/heartjnl-2014-306118.41
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP5UR
UT WOS:000359951000042
ER
PT J
AU Finegold, J
Cazeau, S
Sohaib, SMA
Kyriacou, A
Manisty, C
Ritter, P
Bordachar, P
Whinnett, Z
Francis, D
AF Finegold, Judith
Cazeau, Serge
Sohaib, S. M. Afzal
Kyriacou, Andreas
Manisty, Charlotte
Ritter, Philippe
Bordachar, Pierre
Whinnett, Zachary
Francis, Darrel
TI THE EFFECT OF ALTERING AV DELAY ON THE PRE-EJECTION PERIOD IN PATIENTS
WITH BIVENTRICULAR PACEMAKERS
SO HEART
LA English
DT Meeting Abstract
CT Annual Conference of the British-Cardiovascular-Society
CY JUN 02-04, 2014
CL Manchester, ENGLAND
SP British Cardiovascular Soc
C1 [Finegold, Judith; Sohaib, S. M. Afzal; Kyriacou, Andreas; Manisty, Charlotte; Whinnett, Zachary; Francis, Darrel] Natl Heart & Lung Inst, Int Ctr Circulatory Hlth, Bethesda, MD USA.
[Cazeau, Serge] Paris St Joseph, Dept Rythmol, Paris, France.
[Ritter, Philippe; Bordachar, Pierre] Hop Haut Leveque, Pessac, France.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
EI 1468-201X
J9 HEART
JI Heart
PD JUN
PY 2014
VL 100
SU 3
MA 40
BP A22
EP A22
DI 10.1136/heartjnl-2014-306118.40
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP5UR
UT WOS:000359951000041
ER
PT J
AU Crous, PW
Giraldo, A
Hawksworth, DL
Robert, V
Kirk, PM
Guarro, J
Robbertse, B
Schoch, CL
Damm, U
Trakunyingcharoen, T
Groenewald, JZ
AF Crous, Pedro W.
Giraldo, Alejandra
Hawksworth, David L.
Robert, Vincent
Kirk, Paul M.
Guarro, Josep
Robbertse, Barbara
Schoch, Conrad L.
Damm, Ulrike
Trakunyingcharoen, Thippawan
Groenewald, Johannes Z.
TI The Genera of Fungi: fixing the application of type species of generic
names
SO IMA FUNGUS
LA English
DT Article
DE DNA Barcodes; fungal systematic; ITS; LSU; typification;
www.GeneraofFungi.org
AB To ensure a stable platform for fungal taxonomy, it is of paramount importance that the genetic application of generic names be based on their DNA sequence data, and wherever possible, not morphology or ecology alone. To facilitate this process, a new database, accessible at www.GeneraofFungi.org (GoF) was established, which will allow deposition of metadata linked to holo-, lecto-, neo- or epitype specimens, cultures and DNA sequence data of the type species of genera. Although there are presently more than 18 000 fungal genera described, we aim to initially focus on the subset of names that have been placed on the "Without-prejudice List of Protected Generic Names of Fungi" (see IMA Fungus 4(2): 381-443, 2013). To enable the global mycological community to keep track of typification events and avoid duplication, special MycoBank Typification identfiers (MBT) will be issued upon deposit of metadata in MycoBank. MycoBank is linked to GoF, thus deposited metadata of generic type species will be displayed in GoF (and vice versa), but will also be linked to Index Fungorum (IF) and the curated RefSeq Targeted Loci (RTL) database in GenBank at the National Center for Biotechnology Information (NCBI). This initial paper focuses on eight genera of appendaged coelomycetes, the type species of which are neo- or epitypified here: Bartalinia (Bartalinia robillardoides; Amphisphaeriaceae, Xylariales), Chaetospermum (Chaetospermum chaetosporum, incertae sedis, Sebacinales), Coniella (Coniella fragariae, Schizoparmaceae, Diaporthales), Crinitospora (Crinitospora pulchra, Melanconidaceae, Diaporthales), Eleutheromyces (Eleutheromyces subulatus, Helotiales), Kellermania (Kellermania yuccigena, Planistromataceae, Botryosphaeriales), Mastigosporium (Mastigosporium album, Helotiales), and Mycotribulus (Mycotribulus mirabilis, Agaricales). Authors interested in contributing accounts of individual genera to larger multi-authored papers to be published in IMA Fungus, should contact the associate editors listed below for the major groups of fungi on the List of Protected Generic Names for Fungi.
C1 [Crous, Pedro W.; Robert, Vincent; Groenewald, Johannes Z.] CBS KNAW Fungal Biodivers Ctr, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.
[Crous, Pedro W.] Univ Utrecht, Dept Biol, Microbiol, NL-3584 CT Utrecht, Netherlands.
[Crous, Pedro W.] Wageningen Univ & Res Ctr WUR, Lab Phytopathol, NL-6708 PB Wageningen, Netherlands.
[Giraldo, Alejandra; Guarro, Josep] Univ Rovira & Virgili, Fac Med & Ciencies Salut, Unitat Micol, Tarragona, Spain.
[Giraldo, Alejandra; Guarro, Josep] Univ Rovira & Virgili, IISPV, Tarragona, Spain.
[Hawksworth, David L.] Univ Complutense Madrid, Fac Farm, Dept Biol Vegetal 2, E-28040 Madrid, Spain.
[Hawksworth, David L.] Nat Hist Museum, Dept Life Sci, London SW7 5BD, England.
[Hawksworth, David L.; Kirk, Paul M.] Royal Bot Gardens, Mycol Sect, Richmond TW9 3DS, Surrey, England.
[Kirk, Paul M.] Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing 100101, Peoples R China.
[Robbertse, Barbara; Schoch, Conrad L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Damm, Ulrike] Senckenberg Museum Nat Hist Gorlitz, D-02806 Gorlitz, Germany.
[Trakunyingcharoen, Thippawan] Chiang Mai Univ, Fac Agr, Dept Entomol & Plant Pathol, Chiang Mai 50200, Thailand.
RP Crous, PW (reprint author), CBS KNAW Fungal Biodivers Ctr, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.
EM p.crous@cbs.knaw.nl
RI Groenewald, Johannes/F-4667-2011; Crous, Pedro/H-1489-2012;
OI Crous, Pedro/0000-0001-9085-8825; Guarro, Josep/0000-0002-7839-7568
FU Royal Golden Jubilee Ph.D. Programme [PHD/0353/2552]; Spanish Ministerio
de Economia y Competitividad [CGL 2011-27185]; Intramural Research
Program of the NIH, National Library of Medicine
FX We thank the technical staff, Arien van Iperen (cultures), Marjan
Vermaas (photographic plates), and Mieke Starink-Willemse (DNA
isolation, amplification and sequencing) for their invaluable
assistance. Thippawan Trakunyingcharoen acknowledges financial support
from the Royal Golden Jubilee Ph.D. Programme (Grant No. PHD/0353/2552).
Alejandra Giraldo Lopez is grateful for the financial support received
from the Spanish Ministerio de Economia y Competitividad, grant CGL
2011-27185. Conrad L. Schoch and Barbara Robbertse acknowledge support
from the Intramural Research Program of the NIH, National Library of
Medicine.
NR 78
TC 16
Z9 17
U1 1
U2 9
PU INT MYCOLOGICAL ASSOC
PI BERKELEY
PA C/O J TAYLOR, DEPT PLANT & MICROBIAL BIOLOGY, BERKELEY, CA 94720 USA
SN 2210-6340
EI 2210-6359
J9 IMA FUNGUS
JI IMA Fungus
PD JUN
PY 2014
VL 5
IS 1
BP 141
EP 160
DI 10.5598/imafungus.2014.05.01.14
PG 20
WC Mycology
SC Mycology
GA V46UJ
UT WOS:000209908800028
PM 25083414
ER
PT J
AU Moten, A
Schafer, D
Farmer, P
Kim, J
Ferrari, M
AF Moten, Asad
Schafer, Daniel
Farmer, Paul
Kim, Jim
Ferrari, Mauro
TI Redefining global health priorities: Improving cancer care in developing
settings
SO JOURNAL OF GLOBAL HEALTH
LA English
DT Editorial Material
C1 [Moten, Asad; Schafer, Daniel] Healthnovat Int, Inst Translat Med & Novel Therapeut, Houston, TX 77089 USA.
[Moten, Asad] Univ Oxford, Nuffield Dept Clin Med, Dept Primary Care Hlth Sci, Oxford, England.
[Moten, Asad; Ferrari, Mauro] Natl Canc Inst Alliance Nanotechnol Canc, NIH, Bethesda, MD USA.
[Farmer, Paul] Harvard Univ, Sch Med, Harvard Global Hlth Inst, Boston, MA USA.
[Kim, Jim] WHO Int Agcy Res Canc, World Bank, United Nations Dev Grp, New York, NY USA.
[Ferrari, Mauro] Alliance NanoHlth, Dept Nanomed, Houston Methodist Res Inst, Houston, TX USA.
RP Moten, A (reprint author), Healthnovat Int, 12403 Salama Falls, Houston, TX 77089 USA.
EM aimoten@gmail.com
FU World Health Organization [001]
NR 14
TC 3
Z9 3
U1 0
U2 3
PU UNIV EDINBURGH, GLOBAL HEALTH SOC
PI EDINBURGH
PA CENTRE POPULATION HEALTH SCIENCES, TEVIOT PL, EDINBURGH, EH8 9AG,
ENGLAND
SN 2047-2978
EI 2047-2986
J9 J GLOB HEALTH
JI J. Glob. Health
PD JUN
PY 2014
VL 4
IS 1
AR 010304
DI 10.7189/jogh.04.010304
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA V42SJ
UT WOS:000209633200005
PM 24976959
ER
PT J
AU Burch, PT
Gerstenberger, E
Ravishankar, C
Hehir, DA
Davies, RR
Colan, SD
Sleeper, LA
Newburger, JW
Clabby, ML
Williams, IA
Li, JS
Uzark, K
Cooper, DS
Lambert, LM
Pemberton, VL
Pike, NA
Anderson, JB
Dunbar-Masterson, C
Khaikin, S
Zyblewski, SC
Minich, LL
AF Burch, Phillip T.
Gerstenberger, Eric
Ravishankar, Chitra
Hehir, David A.
Davies, Ryan R.
Colan, Steven D.
Sleeper, Lynn A.
Newburger, Jane W.
Clabby, Martha L.
Williams, Ismee A.
Li, Jennifer S.
Uzark, Karen
Cooper, David S.
Lambert, Linda M.
Pemberton, Victoria L.
Pike, Nancy A.
Anderson, Jeffrey B.
Dunbar-Masterson, Carolyn
Khaikin, Svetlana
Zyblewski, Sinai C.
Minich, L. Luann
CA Pediat Heart Network Investigators
TI Longitudinal Assessment of Growth in Hypoplastic Left Heart Syndrome:
Results From the Single Ventricle Reconstruction Trial
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE growth; hypoplastic left heart syndrome; pediatrics; risk factors
AB Background-We sought to characterize growth between birth and age 3 years in infants with hypoplastic left heart syndrome who underwent the Norwood procedure.
Methods and Results-We performed a secondary analysis using the Single Ventricle Reconstruction Trial database after excluding patients <37 weeks gestation (N=498). We determined length-for-age z score (LAZ) and weight-for-age z score (WAZ) at birth and age 3 years and change in WAZ over 4 clinically relevant time periods. We identified correlates of change in WAZ and LAZ using multivariable linear regression with bootstrapping. Mean WAZ and LAZ were below average relative to the general population at birth (P<0.001, P=0.05, respectively) and age 3 years (P<0.001 each). The largest decrease in WAZ occurred between birth and Norwood discharge; the greatest gain occurred between stage II and 14 months. At age 3 years, WAZ and LAZ were <-2 in 6% and 18%, respectively. Factors associated with change in WAZ differed among time periods. Shunt type was associated with change in WAZ only in the Norwood discharge to stage II period; subjects with a Blalock-Taussig shunt had a greater decline in WAZ than those with a right ventricle-pulmonary artery shunt (P=0.002).
Conclusions-WAZ changed over time and the predictors of change in WAZ varied among time periods. By age 3 years, subjects remained small and three times as many children were short as were underweight (>2 SD below normal). Failure to find consistent risk factors supports the strategy of tailoring nutritional therapies to patient-and stage-specific targets.
C1 [Burch, Phillip T.; Lambert, Linda M.] Univ Utah, Dept Surg, Salt Lake City, UT USA.
[Minich, L. Luann] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[Gerstenberger, Eric; Sleeper, Lynn A.] New England Res Inst, Watertown, MA 02172 USA.
[Ravishankar, Chitra] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Hehir, David A.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA.
[Davies, Ryan R.] Nemours AI DuPont Hosp Children, Wilmington, DE USA.
[Colan, Steven D.; Newburger, Jane W.; Dunbar-Masterson, Carolyn] Childrens Hosp Boston, Boston, MA USA.
[Colan, Steven D.; Newburger, Jane W.; Dunbar-Masterson, Carolyn] Harvard Univ, Sch Med, Boston, MA USA.
[Clabby, Martha L.; Khaikin, Svetlana] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Williams, Ismee A.] Columbia Univ, Med Ctr, New York, NY USA.
[Li, Jennifer S.] Duke Univ, Med Ctr, Durham, NC USA.
[Uzark, Karen] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Cooper, David S.; Anderson, Jeffrey B.] Univ Cincinnati, Cincinnati, OH USA.
[Pemberton, Victoria L.] NIH, Bethesda, MD 20892 USA.
[Pike, Nancy A.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Zyblewski, Sinai C.] Med Univ S Carolina, Charleston, SC 29425 USA.
RP Burch, PT (reprint author), Primary Childrens Med Ctr, Div Cardiothorac Surg, 100 North Mario Capecchi Dr, Salt Lake City, UT 84113 USA.
EM Phillip.Burch@hsc.utah.edu
OI Davies, Ryan/0000-0003-4631-9685
FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279,
HL068281, HL068285, HL068292, HL068290, HL068288, HL085057]
FX Supported by U01 grants from the National Heart, Lung, and Blood
Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292,
HL068290, HL068288, HL085057).
NR 31
TC 9
Z9 9
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD JUN
PY 2014
VL 3
IS 3
AR e000079
DI 10.1161/JAHA.114.000079
PG 15
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V41RD
UT WOS:000209562400004
PM 24958780
ER
PT J
AU Hunter, CM
McKinnon, RA
Esposito, L
AF Hunter, C. M.
McKinnon, R. A.
Esposito, L.
TI News from the NIH: research to evaluate "natural experiments" related to
obesity and diabetes
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT News Item
ID BODY-MASS INDEX; UNITED-STATES; PREVALENCE; CHILDREN; TRENDS
C1 [Hunter, C. M.] NIDDKD, Bethesda, MD 20892 USA.
[McKinnon, R. A.] NCI, Bethesda, MD 20892 USA.
[Esposito, L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Hunter, CM (reprint author), NIDDKD, Bethesda, MD 20892 USA.
NR 14
TC 5
Z9 5
U1 1
U2 1
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD JUN
PY 2014
VL 4
IS 2
BP 127
EP 129
DI 10.1007/s13142-013-0250-z
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CL2PL
UT WOS:000356786400001
PM 24904694
ER
PT J
AU Zhu, ZH
Yin, YF
Zheng, K
Li, F
Chen, XY
Zhang, FC
Zhang, X
AF Zhu, Zhaohui
Yin, Yufeng
Zheng, Kun
Li, Fang
Chen, Xiaoyuan
Zhang, Fengchun
Zhang, Xuan
TI Evaluation of synovial angiogenesis in patients with rheumatoid
arthritis using Ga-68-PRGD2 PET/CT: a prospective proof-of-concept
cohort study
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Article
ID DISEASE-ACTIVITY; INTEGRIN; CANCER; EXPRESSION; ADHESION; TARGET
AB Background The study aimed to evaluate the use of positron emission tomography/computed tomography (PET/CT) with Ga-68-PRGD2 as the tracer for imaging of synovial angiogenesis in patients with rheumatoid arthritis (RA).
Methods Twenty untreated active patients with RA underwent Ga-68-PRGD2 PET/CT and F-18-FDG PET/CT before treatment; two patients with osteoarthritis served as controls. Among the 20 patients with RA, 12 repeated the evaluations after 3-month treatment. The image findings were correlated with core variables of disease activity, including the clinical disease activity index (cDAI).
Results Our findings demonstrated that Ga-68-PRGD2 specifically accumulated in the synovia with active inflammation rich in neovasculature with high-level alpha(v)beta(3)-integrin expression, but not in the F-18-FDG-avid inflammatory lymph nodes. In patients with intense F-18-FDG uptake in muscles caused by arthritic pain, we observed that Ga-68-PRGD2 PET/CT was better able to evaluate disease severity than F-18-FDG PET/CT. Both Ga-68-PRGD2 accumulation and F-18-FDG uptake changed in response to therapeutic intervention, whereas the changes of Ga-68-PRGD2, not F-18-FDG, significantly correlated with clinical measures of changes in the form of cDAI.
Conclusions This is the first integrin imaging study conducted in patients with RA that preliminarily indicates the effectiveness of the novel method for evaluating synovial angiogenesis.
C1 [Zhu, Zhaohui; Zheng, Kun; Li, Fang] Chinese Acad Med Sci, Dept Nucl Med, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China.
[Zhu, Zhaohui; Yin, Yufeng; Zheng, Kun; Li, Fang; Zhang, Fengchun; Zhang, Xuan] Peking Union Med Coll, Beijing 100730, Peoples R China.
[Yin, Yufeng; Zhang, Fengchun; Zhang, Xuan] Chinese Acad Med Sci, Dept Rheumatol, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China.
[Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
RP Zhang, X (reprint author), Chinese Acad Med Sci, Dept Rheumatol, Peking Union Med Coll Hosp, 1 Shuaifuyuan,Wangfujing St, Beijing 100730, Peoples R China.
EM zhuzhh@pumch.cn; zxpumch2003@sina.com
FU National Natural Science Foundation of China [81325019, 81171370,
81172859, 81271614, 81273312, 81371596]; National High Technology
Research and Development Project of China [2011AA020111, 2012AA02A513];
National Major Scientific and Technological Special Project
[2012ZX09303006-002]; National Basic Research Program of China (973
program) [2013CB733802, 2014CB744503]; Research Special Fund for Public
Welfare Industry of Health [201202004]; Capital Health Research and
Development of Special Foundation [2011-4001-02]; Capital Special
Project for Featured Clinical Application [Z121107001012119]; National
Laboratory Special Fund [2060204]; Intramural Research Program (IRP);
National Institute of Biomedical Imaging and Bioengineering (NIBIB);
National Institutes of Health (NIH); Beijing Municipal Natural Science
Foundation [7141008]
FX This study was funded in part by the National Natural Science Foundation
of China (81325019, 81171370, 81172859, 81271614, 81273312, 81371596),
the National High Technology Research and Development Project of China
(2011AA020111, 2012AA02A513), the National Major Scientific and
Technological Special Project (2012ZX09303006-002), the National Basic
Research Program of China (973 program 2013CB733802, 2014CB744503), the
Research Special Fund for Public Welfare Industry of Health (201202004),
the Capital Health Research and Development of Special Foundation
(2011-4001-02), the Capital Special Project for Featured Clinical
Application (Z121107001012119), the National Laboratory Special Fund
(2060204), the Intramural Research Program (IRP), National Institute of
Biomedical Imaging and Bioengineering (NIBIB) and National Institutes of
Health (NIH) and Beijing Municipal Natural Science Foundation (7141008).
NR 20
TC 16
Z9 17
U1 2
U2 8
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
EI 1468-2060
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD JUN
PY 2014
VL 73
IS 6
BP 1269
EP 1272
DI 10.1136/annrheumdis-2013-204820
PG 4
WC Rheumatology
SC Rheumatology
GA AG4AW
UT WOS:000335362100056
PM 24532680
ER
PT J
AU Auer, DR
Sysa-Shah, P
Bedja, D
Simmers, JL
Pak, E
Dutra, A
Cohn, R
Gabrielson, KL
Chakravarti, A
Kapoor, A
AF Auer, Dallas R.
Sysa-Shah, Polina
Bedja, Djahida
Simmers, Jessica L.
Pak, Evgenia
Dutra, Amalia
Cohn, Ronald
Gabrielson, Kathleen L.
Chakravarti, Aravinda
Kapoor, Ashish
TI Generation of a cre recombinase-conditional Nos1ap over-expression
transgenic mouse
SO BIOTECHNOLOGY LETTERS
LA English
DT Article
DE Cardiac arrhythmia; Conditional over-expression; GENOME-wide association
studies; NOS1AP; QT interval; Sudden cardiac death; Transgenic mouse
ID NITRIC-OXIDE SYNTHASE; QT INTERVAL DURATION; MODULATES CARDIAC
REPOLARIZATION; COMMON VARIANTS; CAPON; CELLS; PROTEIN; GENE;
CHROMOSOME; DEATH
AB Polymorphic non-coding variants at the NOS1AP locus have been associated with the common cardiac, metabolic and neurological traits and diseases. Although, in vitro gene targeting-based cellular and biochemical studies have shed some light on NOS1AP function in cardiac and neuronal tissue, to enhance our understanding of NOS1AP function in mammalian physiology and disease, we report the generation of cre recombinase-conditional Nos1ap over-expression transgenic mice (Nos1ap (Tg)). Conditional transgenic mice were generated by the pronuclear injection method and three independent, single-site, multiple copies integration event-based founder lines were selected. For heart-restricted over-expression, Nos1ap (Tg) mice were crossed with Mlc2v-cre and Nos1ap transcript over-expression was observed in left ventricles from Nos1ap (Tg); Mlc2v-cre F-1 mice. We believe that with the potential of conditional over-expression, Nos1ap (Tg) mice will be a useful resource in studying NOS1AP function in various tissues under physiological and disease states.
C1 [Auer, Dallas R.; Simmers, Jessica L.; Chakravarti, Aravinda; Kapoor, Ashish] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
[Sysa-Shah, Polina; Bedja, Djahida; Gabrielson, Kathleen L.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA.
[Pak, Evgenia; Dutra, Amalia] NHGRI, NIH, Bethesda, MD 20892 USA.
[Cohn, Ronald] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
RP Chakravarti, A (reprint author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, 733 N Broadway, Baltimore, MD 21205 USA.
EM psysa1@jhmi.edu; dbedja1@jhmi.edu; jlsimmers@gmail.com;
epak@mail.nih.gov; adutra@mail.nih.gov; ronald.cohn@sickkids.ca;
kgabriel@jhmi.edu; aravinda@jhmi.edu; ashish@jhmi.edu
FU Donald R. Reynolds Foundation; National Institutes of Health
FX We are grateful to Dr. Andras Nagy (Mount Sinai Hospital, Toronto) for
providing the pCLIP vector and to Dr. Kenneth Chien (Massachusetts
General Hospital, Boston) for providing the Mlc2v-cre mice. We are
thankful to Dr. Gordon Tomaselli, Dr. David Kass and Gary Steel (Johns
Hopkins University, Baltimore) for critical discussions. This work was
supported in part by funds from the Donald R. Reynolds Foundation and
the National Institutes of Health.
NR 26
TC 1
Z9 1
U1 0
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-5492
EI 1573-6776
J9 BIOTECHNOL LETT
JI Biotechnol. Lett.
PD JUN
PY 2014
VL 36
IS 6
BP 1179
EP 1185
DI 10.1007/s10529-014-1473-x
PG 7
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA AG0ZY
UT WOS:000335145800007
PM 24563304
ER
PT J
AU Hirsch, DS
Shen, Y
Dokmanovic, M
Yu, J
Mohan, N
Elzarrad, MK
Wu, WJ
AF Hirsch, Dianne S.
Shen, Yi
Dokmanovic, Milos
Yu, Joyce
Mohan, Nishant
Elzarrad, Mohammed Khair
Wu, Wen Jin
TI Insulin activation of vacuolar protein sorting 34 mediates localized
phosphatidylinositol 3-phosphate production at lamellipodia and
activation of mTOR/S6K1
SO CELLULAR SIGNALLING
LA English
DT Article
DE Class III phosphatidylinositol 3-kinase/vacuolar protein sorting 34
(VPS34); Insulin; Src; ptdins(3)p; S6 kinase 1 (S6K1); mTOR
ID MAMMALIAN-CELLS; TYROSINE PHOSPHORYLATION; ACTIN CYTOSKELETON; S6
KINASE; 3-KINASE; RESISTANCE; MOTILITY; INSIGHTS; HVPS34; GROWTH
AB The class III phosphatidylinositol 3-kinase, VPS34, phosphorylates the 03 hydroxyl of inositol generating phosphatidylinositol 3-phosphate (ptdins(3)p). Initial studies suggested that ptdins(3)p solely functioned as a component of vesicular and endosomal membranes and that VPS34 did not function in signal transduction. However, VPS34 has recently been shown to be required for insulin-mediated activation of S6 kinase 1 (S6K1). Whether VPS34 activity is directly regulated by insulin is unclear. It is also not known whether VPS34 activity can be spatially restricted in response to extracellular stimuli. Data presented here demonstrate that in response to insulin, VPS34 is activated and translocated to lamellipodia where it produces ptdins(3)p. The localized production of ptdins(3)p is dependent on Src phosphorylation of VPS34.1n cells expressing VPS34 with mutations at Y231 or Y310, which are Src-phosphorylation sites, insulin-stimulated VPS34 translocation to the plasma membrane and lamellipodia formation are blocked. mTOR also colocalizes with VPS34 and ptdins(3)p at lamellipodia following insulin-stimulation. In cells expressing the VPS34-Y231F mutant, which blocks lamellipodia formation, mTOR localization at the plasma membrane and insulin-mediated S6K1 activation are reduced. This suggests that mTOR localization at lamellipodia is important for full activation of S6K1 induced by insulin. These data demonstrate that insulin can spatially regulate VPS34 activity through Src-mediated tyrosine phosphorylation and that this membrane localized activity contributes to lamellipodia formation and activation of mTOR/S6K1signaling. Published by Elsevier Inc.
C1 [Hirsch, Dianne S.; Shen, Yi; Dokmanovic, Milos; Yu, Joyce; Mohan, Nishant; Elzarrad, Mohammed Khair; Wu, Wen Jin] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA.
[Elzarrad, Mohammed Khair] NCI, Interagency Oncol Task Force IOTF Fellowship Prog, NIH, Bethesda, MD 20892 USA.
RP Wu, WJ (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, HFD 123,29B Lincoln Dr,Room 3NN20, Bethesda, MD 20892 USA.
EM wen.wu@fda.hhs.gov
NR 37
TC 3
Z9 4
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
EI 1873-3913
J9 CELL SIGNAL
JI Cell. Signal.
PD JUN
PY 2014
VL 26
IS 6
BP 1258
EP 1268
DI 10.1016/j.cellsig.014.02.009
PG 11
WC Cell Biology
SC Cell Biology
GA AG0OH
UT WOS:000335114300011
PM 24582588
ER
PT J
AU Boularan, C
Kehrl, JH
AF Boularan, Cedric
Kehrl, John H.
TI Implications of non-canonical G-protein signaling for the immune system
SO CELLULAR SIGNALLING
LA English
DT Review
DE G-protein signaling; Immune system; Ric-8A; Non-canonical
ID HETEROTRIMERIC G-PROTEINS; PASTEURELLA-MULTOCIDA TOXIN;
GUANINE-NUCLEOTIDE EXCHANGE; ASYMMETRIC CELL-DIVISION; CONTROLS
AUTOPHAGIC SEQUESTRATION; CYSTEINE-STRING-PROTEIN; T-LYMPHOCYTE
DIVISION; N-TERMINAL KINASE; G-ALPHA-I; C-BETA 1
AB Heterotrimeric guanine nucleotide-binding proteins (G proteins), which consist of three subunits alpha, beta and gamma, function as molecular switches to control downstream effector molecules activated by G protein-coupled receptors (GPCRs). The GTP/GDP binding status of G alpha transmits information about the ligand binding state of the GPCR to intended signal transduction pathways. In immune cells heterotrimeric G proteins impact signal transduction pathways that directly, or indirectly, regulate cell migration, activation, survival, proliferation, and differentiation. The cells of the innate and adaptive immune sykem abundantly express chemoattractant receptors and lesser amounts of many other types of GPCRs. But heterotrimeric G-proteins not only function in classical GPCR signaling, but also in non-canonical signaling. In these pathways the guanine exchange factor (GEF) exerted by a GPCR in the canonical pathway is replaced or supplemented by another protein such as Ric-8A. In addition, other proteins such as AGS3-6 can compete with G beta gamma for binding to GDP bound G alpha. This competition can promote G beta gamma signaling by freeing G beta gamma from rapidly rebinding GDP bound G alpha. The proteins that participate in these non-canonical signaling pathways will be briefly described and their role, or potential one, in cells of the immune system will be highlighted. Published by Elsevier Inc.
C1 [Boularan, Cedric; Kehrl, John H.] NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11B08,10 Ctr Dr MSC 1876, Bethesda, MD 20892 USA.
EM jkehrl@niaid.nih.gov
OI Kehrl, John/0000-0002-6526-159X
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases; National Institutes of Health
FX The authors would like to thank Dr. Anthony Fauci for his continued
support. This work benefitted from data assembled by ImmGen consortium.
This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 171
TC 10
Z9 10
U1 1
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
EI 1873-3913
J9 CELL SIGNAL
JI Cell. Signal.
PD JUN
PY 2014
VL 26
IS 6
BP 1269
EP 1282
DI 10.1016/j.cellsig.014.02.010
PG 14
WC Cell Biology
SC Cell Biology
GA AG0OH
UT WOS:000335114300012
PM 24583286
ER
PT J
AU Aliev, G
Priyadarshini, M
Reddy, VP
Grieg, NH
Kaminsky, Y
Cacabelos, R
Ashraf, GM
Jabir, NR
Kamal, MA
Nikolenko, VN
Zamyatnin, AA
Benberin, VV
Bachurin, SO
AF Aliev, G.
Priyadarshini, M.
Reddy, V. P.
Grieg, N. H.
Kaminsky, Y.
Cacabelos, R.
Ashraf, G. Md
Jabir, N. R.
Kamal, M. A.
Nikolenko, V. N.
Zamyatnin, A. A., Jr.
Benberin, V. V.
Bachurin, S. O.
TI Oxidative Stress Mediated Mitochondrial and Vascular Lesions as Markers
in the Pathogenesis of Alzheimer Disease
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Article
DE Alzheimer disease; antioxidants; cerebrovascular pathology;
mitochondria; neurodegeneration; oxidative stress
ID ACETYL-L-CARNITINE; MILD COGNITIVE IMPAIRMENT; ALPHA-LIPOIC-ACID;
CHRONIC CEREBRAL HYPOPERFUSION; AMYLOID PRECURSOR PROTEIN; TARGETED
ANTIOXIDANT MITOQ; NEURODEGENERATIVE DISEASES; MOUSE MODEL; OLD RATS;
ENDOTHELIAL DYSFUNCTION
AB Mitochondrial dysfunction plausibly underlies the aging-associated brain degeneration. Mitochondria play a pivotal role in cellular bioenergetics and cell-survival. Oxidative stress consequent to chronic hypoperfusion induces mitochondrial damage, which is implicated as the primary cause of cerebrovascular accidents (CVA) mediated Alzheimer's disease (AD). The mitochondrial function deteriorates with aging, and the mitochondrial damage correlates with increased intracellular production of oxidants and pro-oxidants. The prolonged oxidative stress and the resultant hypoperfusion in the brain tissues stimulate the expression of nitric oxide synthase (NOS) enzymes, which further drives the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The ROS and RNS collectively contributes to the dysfunction of the blood-brain barrier (BBB) and damage to the brain parenchymal cells. Delineating the molecular mechanisms of these processes may provide clues for the novel therapeutic targets for CVA and AD patients.
C1 [Aliev, G.] GALLY Int Biomed Res Consulting LLC, San Antonio, TX 78229 USA.
[Aliev, G.] Univ Atlanta, Sch Hlth Sci & Healthcare Adm, Johns Creek, GA 30097 USA.
[Priyadarshini, M.] Aligarh Muslim Univ, Fac Life Sci, Dept Biochem, Aligarh 202002, Uttar Pradesh, India.
[Reddy, V. P.] Missouri Univ Sci & Technol, Dept Chem, Rolla, MO 65409 USA.
[Grieg, N. H.] NIA, Drug Design & Dev Sect, Lab Neurosci, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Kaminsky, Y.] Russian Acad Sci, Inst Theoret & Expt Biophys, Pushchino 142290, Russia.
[Cacabelos, R.] Inst CNS Disorders & Genom Med, EuroEspes Biomed Res Ctr, Bergondo 15165, La Coruna, Spain.
[Cacabelos, R.] Camilo Jose Cela Univ, Bergondo 15165, La Coruna, Spain.
[Ashraf, G. Md; Jabir, N. R.; Kamal, M. A.] King Abdulaziz Univ, King Fahd Med Res Ctr, Jeddah 21589, Saudi Arabia.
[Nikolenko, V. N.] Sechenov First Moscow State Med Univ, Dept Anat, Moscow 119991, Russia.
[Zamyatnin, A. A., Jr.] Sechenov First Moscow State Med Univ, Inst Mol Med, Moscow 119991, Russia.
[Benberin, V. V.] Med Ctr Adm President Republ Kazakhstan, Astana 010000, Kazakhstan.
[Bachurin, S. O.] Russian Acad Sci, Inst Physiol Act Cpds, Chernogolovka 142432, Moscow Region, Russia.
RP Aliev, G (reprint author), GALLY Int Biomed Res Consulting LLC, 7733 Louis Pasteur Dr,330, San Antonio, TX 78229 USA.
EM aliev03@gmail.com
RI Zamyatnin, Andrey/D-6443-2012; Ashraf, Ghulam Md/H-9485-2012;
Rehumathbeevi, Jabir/H-9483-2012;
OI Zamyatnin, Andrey/0000-0002-3046-4565; Ashraf, Ghulam
Md/0000-0002-9820-2078; Rehumathbeevi, Jabir/0000-0001-8548-7986; Kamal,
Mohammad Amjad/0000-0003-0088-0565
FU GALLY International Biomedical Research Consulting LLC, San Antonio,
Texas, USA
FX We thank Ms. Galina Alieva for her editorial work. These studies were
partially supported by the GALLY International Biomedical Research
Consulting LLC, San Antonio, Texas, USA. Dr. Medha Priyadarshini is an
incumbent of DST-INSPIRE Faculty Award, Dept. of Science and Technology,
Govt. of India. Thanks are due to DSR and KFMRC (King Abdulaziz
University, Jeddah, Saudi Arabia) for the facilities.
NR 159
TC 49
Z9 55
U1 5
U2 39
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 0929-8673
EI 1875-533X
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD JUN
PY 2014
VL 21
IS 19
BP 2208
EP 2217
PG 10
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA AG4MF
UT WOS:000335393300010
PM 24372221
ER
PT J
AU Liu, XD
Wang, XL
Bai, X
Liu, XL
Wu, XP
Zhao, Y
Sun, SM
Yu, L
Su, XZ
Wang, ZQ
Wang, F
Liu, MY
AF Liu, X. D.
Wang, X. L.
Bai, X.
Liu, X. L.
Wu, X. P.
Zhao, Y.
Sun, S. M.
Yu, L.
Su, X. Z.
Wang, Z. Q.
Wang, F.
Liu, M. Y.
TI Oral administration with attenuated Salmonella encoding a Trichinella
cystatin-like protein elicited host immunity
SO EXPERIMENTAL PARASITOLOGY
LA English
DT Article
DE Trichinella spiralis; Cystatin-like protein; Attenuated Salmonella;
Th1/Th2; Immunosuppressive; Eukaryotic expression system
ID GUT EPITHELIAL MONOLAYERS; PHOP-VIRULENCE REGULON; PROTECTIVE IMMUNITY;
TYPHIMURIUM VIRULENCE; GENE-THERAPY; DNA VACCINES; T-BET; SPIRALIS;
CELLS; ENTERICA
AB Trichinellosis is a public health problem and is regarded as an emergent/re-emergent disease in various countries. The cDNA encoding a cystatin-like protein (Ts-cystatin) was identified by immunoscreening intestinal muscle larvae cDNA libraries with serum from pigs experimentally infected with 20,000 Trichinella spiralis muscle larvae. To study its impact on host immunity, we chose a eukaryotic expression system based on several comparisons of immunogenicity between the two Salmonella typhimurium administration schemes, which indicated that the eukaryotic expression system was superior. Humoral IgG and mucosal IgA were measured to determine the antibody response. To explore whether Th1 and Th2 responses were responsible for the induced protection, Th1- and Th2-specific cellular transcription factors and the cytokine profile were examined. Changes in the T lymphocyte and macrophage populations were detected by flow cytometry. Lastly, parasitological examination was examined. The results showed that Ts-cystatin induced a Th1/Th2-mixed type of immune response and decreased STAT6 transcription. The intestinal adult recovery increased by 10.9% in the Ts-cystatin group, the Ts-cystatin group fecundity rate was decreased by 91%. Furthermore, the number of muscle larvae did not change compared with the control group. In conclusion, our results suggest that Ts-cystatin plays an important role in Trichinella resistance to rapid expulsion by the host and is worth further study. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Liu, X. D.; Wang, X. L.; Bai, X.; Liu, X. L.; Zhao, Y.; Sun, S. M.; Yu, L.; Wang, F.; Liu, M. Y.] Jilin Univ, Inst Zoonosis, Key Lab Zoonoses Res, Minist Educ, Changchun 130062, Peoples R China.
[Wu, X. P.] Natl Inst Parasit Dis, Chinese Ctr Dis Control & Prevent, Shanghai 200025, Peoples R China.
[Liu, M. Y.] Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225009, Peoples R China.
[Su, X. Z.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Wang, Z. Q.] Zhengzhou Univ, Coll Med, Dept Parasitol, Zhengzhou 450052, Peoples R China.
RP Wu, XP (reprint author), Jilin Univ, Inst Zoonosis, Key Lab Zoonoses Res, Minist Educ, Changchun 130062, Peoples R China.
EM xpwu@jlu.edu.cn; zhaoyingsohu@sohu.com; liumy@jlu.edu.cn
OI Su, Xinzhuan/0000-0003-3246-3248
FU Ministry of Science and Technology of China [MOST 2011AA10A215];
Postdoctoral fund in China [2012M520683]; National Natural Science
Foundation of China [NSFC 31030064, 30972177, 81070311, 31072124]
FX This work was supported by grants from the Ministry of Science and
Technology of China (MOST 2011AA10A215), Postdoctoral fund in China
(2012M520683) and the National Natural Science Foundation of China (NSFC
31030064, 30972177, 81070311, 31072124).
NR 41
TC 9
Z9 9
U1 0
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4894
EI 1090-2449
J9 EXP PARASITOL
JI Exp. Parasitol.
PD JUN
PY 2014
VL 141
BP 1
EP 11
DI 10.1016/j.exppara.2014.03.015
PG 11
WC Parasitology
SC Parasitology
GA AG6QD
UT WOS:000335542600001
PM 24636891
ER
PT J
AU Daye, PM
Optican, LM
Blohm, G
Lefevre, P
AF Daye, Pierre M.
Optican, Lance M.
Blohm, Gunnar
Lefevre, Philippe
TI Hierarchical control of two-dimensional gaze saccades
SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE
LA English
DT Article
DE Gaze saccades; Eye; Head; Feedback control; Superior colliculus; VOR
suppression
ID EYE-HEAD COORDINATION; CAUDAL FASTIGIAL NUCLEUS; MONKEY SUPERIOR
COLLICULUS; VESTIBULOOCULAR REFLEX SUPPRESSION; STEM OMNIPAUSE NEURONS;
MUSCIMOL INACTIVATION; REVERSIBLE INACTIVATION; UNRESTRAINED CAT;
TECTORETICULOSPINAL NEURONS; MOVEMENT KINEMATICS
AB Coordinating the movements of different body parts is a challenging process for the central nervous system because of several problems. Four of these main difficulties are: first, moving one part can move others; second, the parts can have different dynamics; third, some parts can have different motor goals; and fourth, some parts may be perturbed by outside forces. Here, we propose a novel approach for the control of linked systems with feedback loops for each part. The proximal parts have separate goals, but critically the most distal part has only the common goal. We apply this new control policy to eye-head coordination in two-dimensions, specifically head-unrestrained gaze saccades. Paradoxically, the hierarchical structure has controllers for the gaze and the head, but not for the eye (the most distal part). Our simulations demonstrate that the proposed control structure reproduces much of the published empirical data about gaze movements, e.g., it compensates for perturbations, accurately reaches goals for gaze and head from arbitrary initial positions, simulates the nine relationships of the head-unrestrained main sequence, and reproduces observations from lesion and single-unit recording experiments. We conclude by showing how our model can be easily extended to control structures with more linked segments, such as the control of coordinated eye on head on trunk movements.
C1 [Daye, Pierre M.; Optican, Lance M.] NEI, NIH, Sensorimotor Res Lab, Bethesda, MD 20892 USA.
[Blohm, Gunnar] Queens Univ, Ctr Neurosci Studies, Kingston, ON K7L 3N6, Canada.
[Lefevre, Philippe] UCLouvain, ICTeam, IoNS, B-1348 Louvain, Belgium.
RP Daye, PM (reprint author), NEI, NIH, Sensorimotor Res Lab, 49 Convent Dr,Room 2A50, Bethesda, MD 20892 USA.
EM pierre.daye@gmail.com; lanceoptican@nih.gov; gunnar.blohm@queensu.ca;
philippe.lefevre@uclouvain.be
FU Intramural Research Program of the National Eye Institute; National
Science and Engineering Research Council (Canada); Ontario Research Fund
(Canada); Canadian Foundation for Innovation (Canada); Botterell
Foundation (Queens University, Kingston, ON, Canada); Fonds National de
la Recherche Scientifique, Action de Recherche Concertee (Belgium);
Interuniversity Attraction Poles Programmes; Belgian State, Science
Policy Office
FX Drs. Optican and Daye were supported by the Intramural Research Program
of the National Eye Institute.; Dr. Blohm has been supported by the
National Science and Engineering Research Council (Canada), the Ontario
Research Fund (Canada), the Canadian Foundation for Innovation (Canada)
and the Botterell Foundation (Queens University, Kingston, ON, Canada).;
Dr. Lefevre has been supported by Fonds National de la Recherche
Scientifique, Action de Recherche Concertee (Belgium). This paper
presents research results of the Belgian Network Dynamical Systems,
Control and Optimization, funded by the Interuniversity Attraction Poles
Programmes, initiated by the Belgian State, Science Policy Office.
NR 94
TC 8
Z9 8
U1 1
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0929-5313
EI 1573-6873
J9 J COMPUT NEUROSCI
JI J. Comput. Neurosci.
PD JUN
PY 2014
VL 36
IS 3
BP 355
EP 382
DI 10.1007/s10827-013-0477-1
PG 28
WC Mathematical & Computational Biology; Neurosciences
SC Mathematical & Computational Biology; Neurosciences & Neurology
GA AG2JA
UT WOS:000335241100003
PM 24062206
ER
PT J
AU Vogtmann, E
Shu, XO
Li, HL
Chow, WH
Yang, G
Ji, BT
Cai, H
Yu, C
Gao, YT
Zheng, W
Xiang, YB
AF Vogtmann, Emily
Shu, Xiao-Ou
Li, Hong-Lan
Chow, Wong-Ho
Yang, Gong
Ji, Bu-Tian
Cai, Hui
Yu, Chang
Gao, Yu-Tang
Zheng, Wei
Xiang, Yong-Bing
TI Cholelithiasis and the risk of liver cancer: results from cohort studies
of 134 546 Chinese men and women
SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
LA English
DT Article
ID SEVERE GALLSTONE DISEASE; EXTRAHEPATIC CHOLANGIOCARCINOMA;
CHOLECYSTECTOMY; POPULATION; EPIDEMIOLOGY; TAIWAN; HEALTH
AB Background Cholelithiasis and cholecystectomy have been proposed as risk factors for liver cancer, but findings have been inconsistent. We assessed this association using data from the Shanghai Women's and Men's Health Studies.
Methods History of cholelithiasis and cholecystectomy were reported at baseline and follow-up interviews, and liver cancer diagnoses were ascertained from the Shanghai Cancer Registry and Vital Statistics Unit. Adjusted hazard ratios (aHRs) and 95% CIs were calculated after adjustment for potential confounders.
Results A history of cholelithiasis and cholecystectomy was reported by 9.5% and 3.6% of participants at baseline, respectively. After a total of 859 882 person-years of follow-up for women and 391 093 for men, incident liver cancer was detected in 160 women and 252 men. A positive association was observed between a history of cholelithiasis or cholecystectomy and liver cancer in men (aHR 1.46; 95% CI 1.02 to 2.07) and women (aHR 1.55; 95% CI 1.06 to 2.26). Similar results were observed for cholelithiasis only, but cholecystectomy did not reach statistical significance. There was no strong evidence for detection bias of liver cancer due to cholelithiasis or cholecystectomy.
Conclusions Our study suggests that cholelithiasis and possibly cholecystectomy may increase the risk of liver cancer.
C1 [Vogtmann, Emily; Li, Hong-Lan; Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Shanghai Canc Inst, Renji Hosp, State Key Lab Oncogene & Related Genes,Sch Med, Shanghai 200032, Peoples R China.
[Vogtmann, Emily; Li, Hong-Lan; Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Shanghai Canc Inst, Renji Hosp, Dept Epidemiol,Sch Med, Shanghai 200032, Peoples R China.
[Vogtmann, Emily; Shu, Xiao-Ou; Yang, Gong; Cai, Hui; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA.
[Vogtmann, Emily] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Chow, Wong-Ho] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Yu, Chang] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA.
RP Xiang, YB (reprint author), Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst, 25,Lane 2200,Xie Tu Rd, Shanghai 200032, Peoples R China.
EM ybxiang@shsci.org
FU State Key Project Specialized for Infectious Diseases of China
[2008ZX10002-015, 2012ZX10002008-002]; United States National Institutes
of Health [R37 CA070867, R01 CA082729]; Fogarty International Clinical
Research Scholars and Fellows Program at Vanderbilt University [R24
TW007988-5]; Cancer Prevention and Control Training Program at the
University of Alabama at Birmingham - National Institutes of Health
[5R25 CA047888]
FX This work was supported by funds from the State Key Project Specialized
for Infectious Diseases of China (No. 2008ZX10002-015 and
2012ZX10002008-002 to Y-BX); the United States National Institutes of
Health (R37 CA070867 to WZ, and R01 CA082729 to X-OS); the Fogarty
International Clinical Research Scholars and Fellows Program at
Vanderbilt University (R24 TW007988-5 to EV and H-LL); and the Cancer
Prevention and Control Training Program at the University of Alabama at
Birmingham funded through the National Institutes of Health (5R25
CA047888 to EV). The funding organisations had no role in the design and
conduct of the study; the collection, analysis and interpretation of the
data; or the preparation, review or approval of the manuscript.
NR 30
TC 1
Z9 1
U1 1
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0143-005X
EI 1470-2738
J9 J EPIDEMIOL COMMUN H
JI J. Epidemiol. Community Health
PD JUN
PY 2014
VL 68
IS 6
BP 565
EP 570
DI 10.1136/jech-2013-203503
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AG4AV
UT WOS:000335362000013
PM 24574318
ER
PT J
AU Ito, T
Li, XM
Kurima, K
Choi, BY
Wangemann, P
Griffith, AJ
AF Ito, Taku
Li, Xiangming
Kurima, Kiyoto
Choi, Byung Yoon
Wangemann, Philine
Griffith, Andrew J.
TI Slc26a4-insufficiency causes fluctuating hearing loss and stria
vascularis dysfunction
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Conditional; Doxycycline; Endocochlear potential; Fluctuation; Hearing
loss; Hypomorph; Inducible; SLC26A4; Stria vascularis; Transgenic;
Vestibular aqueduct
ID SYNDROME MOUSE MODEL; VESTIBULAR AQUEDUCT SYNDROME; GENOTYPE-PHENOTYPE
CORRELATION; KCNJ10 PROTEIN EXPRESSION; BLOOD-BRAIN-BARRIER; K-CL
COTRANSPORTER; OUTER HAIR-CELLS; PENDRED-SYNDROME; INNER-EAR;
ENDOLYMPHATIC HYDROPS
AB SLC26A4 mutations can cause a distinctive hearing loss phenotype with sudden drops and fluctuation inpatients. Existing Slc26a4 mutant mouse lines have a profound loss of hearing and vestibular function, with severe inner ear malformations that do not model this human phenotype. In this study, we generated.51c26a4-insufficient mice by manipulation of doxycycline administration to a transgenic mouse line in which all S1c26a4 expression was under the control of doxycycline. Doxycycline was administered from conception to embryonic day 17.5, and then it was discontinued. Auditory brainstem response thresholds showed significant fluctuation of hearing loss from 1 through 3 months of age. The endocochlear potential, which is required for inner ear sensory cell function, correlated with auditory brainstem response thresholds. We observed degeneration of stria vascularis intermediate cells, the cells that generate the endocochlear potential, but no other abnormalities within the cochlea. We conclude that fluctuations of hearing result from fluctuations of the endocochlear potential and stria vascularis dysfunction in S1c26a4-insufficient mouse ears. This model can now be used to test potential interventions to reduce or prevent sudden hearing loss or fluctuation in human patients. Our strategy to generate a hypomorphic mouse model utilizing the tet-on system will be applicable to other diseases in which a hypomorphic allele is needed to model the human phenotype. Published by Elsevier Inc.
C1 [Ito, Taku; Kurima, Kiyoto; Griffith, Andrew J.] Natl Inst Deafness & Commun Disorders, Otolaryngol Branch, NIH, Bethesda, MD 20892 USA.
[Li, Xiangming; Wangemann, Philine] Kansas State Univ, Dept Anat & Physiol, Manhattan, KS 66506 USA.
[Choi, Byung Yoon] Natl Inst Deafness & Commun Disorders, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
RP Griffith, AJ (reprint author), Natl Inst Deafness & Commun Disorders, Otolaryngol Branch, NIH, 35A Convent Dr,Room GF-103, Bethesda, MD 20892 USA.
EM griffita@nidcd.nih.gov
FU National Institutes of Health intramural research [DC-Z01-000039-16,
DC-Z01-000060-12, NIH-R01-DC012151]; CVM-SMILE from Kansas State
University; National Institutes of Health extramural fund [P20-RR017686]
FX The authors thank Daniel Marcus and our NIDCD colleagues for helpful
discussions, and Thomas Friedman and Tracy Fitzgerald for critical
review of the manuscript. This work was supported by the National
Institutes of Health intramural research funds DC-Z01-000039-16,
DC-Z01-000060-12, NIH-R01-DC012151 and CVM-SMILE from Kansas State
University, and the National Institutes of Health extramural fund
P20-RR017686. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 70
TC 4
Z9 4
U1 1
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0969-9961
EI 1095-953X
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD JUN
PY 2014
VL 66
BP 53
EP 65
DI 10.1016/j.nbd.2014.02.002
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA AG0IG
UT WOS:000335098600005
PM 24561068
ER
PT J
AU McCrindle, BW
Zak, V
Pemberton, VL
Lambert, LM
Vetter, VL
Lai, WW
Uzark, K
Margossian, R
Atz, AM
Cook, A
Newburger, JW
AF McCrindle, Brian W.
Zak, Victor
Pemberton, Victoria L.
Lambert, Linda M.
Vetter, Victoria L.
Lai, Wyman W.
Uzark, Karen
Margossian, Renee
Atz, Andrew M.
Cook, Amanda
Newburger, Jane W.
CA Pediatric Heart Network Investigat
TI Functional health status in children and adolescents after Fontan:
comparison of generic and disease-specific assessments
SO CARDIOLOGY IN THE YOUNG
LA English
DT Article
DE Fontan procedure; paediatrics; congenital; cardiac defects
ID QUALITY-OF-LIFE; CONGENITAL CARDIAC-DISEASE; ACQUIRED HEART-DISEASE;
PHYSICAL-ACTIVITY; VALIDATION; RESPONSIVENESS; RELIABILITY; INVENTORY;
VALIDITY; PARENTS
AB Purpose: The aim of this study was to compare associations between generic versus disease-specific functional health status assessments and patient and clinical characteristics for patients with severe congenital heart disease. Methods: This was a cross-sectional observational study involving 325 single ventricle patients, aged 10-18 years, after Fontan procedure. Enrolled patients underwent a medical history review, laboratory testing, and assessment of the functional health status by completion of the generic Child Report Child Health Questionnaire and the disease-specific Congenital Heart Adolescent and Teenage questionnaire. Correlated conceptually equivalent domains from both questionnaires were identified and their associations with patient and clinical variables were compared. Results: From the generic assessment, patients perceived marginally lower physical functioning (p = 0.05) but greater freedom from bodily pain compared with a normal population (p < 0.001). The equivalent physical functioning/limitations domain of the generic instrument, compared with the disease-specific instrument, had similar associations (higher multi-variable model R-2) with medical history variables (R-2 = 0.14 versus R-2 = 0.12, respectively) and stronger associations with exercise testing variables (R-2 = 0.22 versus R-2 = 0.06). Similarly, the corresponding freedom from bodily pain/symptoms domains from both questionnaires showed a greater association for the generic instrument with medical history variables (R-2 = 0.15 versus R-2 = 0.09, respectively) and non-cardiac conditions (R-2 = 0.13 versus R-2 = 0.06). The associations of each questionnaire with echocardiographic results, cardiac magnetic resonance imaging results, and serum brain natriuretic peptide levels were uniformly weak (R-2 range <0.01 to 0.04). Conclusions: Assessment of the physical functional health status using generic and disease-specific instruments yields few differences with regard to associations between conceptually similar domains and patient and clinical characteristics for adolescents after Fontan procedure.
C1 [McCrindle, Brian W.] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Zak, Victor] New England Res Inst, Watertown, MA 02172 USA.
[Pemberton, Victoria L.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Lambert, Linda M.] Univ Utah, Primary Childrens Med Ctr, Salt Lake City, UT USA.
[Vetter, Victoria L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Lai, Wyman W.] Columbia Univ, Med Ctr, New York, NY USA.
[Uzark, Karen] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Margossian, Renee; Newburger, Jane W.] Childrens Hosp Boston, Boston, MA USA.
[Atz, Andrew M.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Cook, Amanda] Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA.
RP McCrindle, BW (reprint author), Univ Toronto, Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
EM brian.mccrindle@sickkids.ca
RI Hurwitz Koweek, lynne/N-1351-2015
OI Hurwitz Koweek, lynne/0000-0001-9990-3397
FU National Institutes of Health, National Heart, Lung, and Blood Institute
[HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290,
HL068288]
FX None of the authors have any financial disclosures to make. The study
was supported by U01 grants from the National Institutes of Health,
National Heart, Lung, and Blood Institute (HL068269, HL068270, HL068279,
HL068281, HL068285, HL068292, HL068290, HL068288). The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Heart, Lung and Blood Institute or the
National Institutes of Health.
NR 35
TC 3
Z9 3
U1 0
U2 8
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 1047-9511
EI 1467-1107
J9 CARDIOL YOUNG
JI Cardiol. Young
PD JUN
PY 2014
VL 24
IS 3
BP 469
EP 477
DI 10.1017/S1047951113000632
PG 9
WC Cardiac & Cardiovascular Systems; Pediatrics
SC Cardiovascular System & Cardiology; Pediatrics
GA AF7GX
UT WOS:000334883700014
PM 23746330
ER
PT J
AU Raft, S
Andrade, LR
Shao, DM
Akiyama, H
Henkemeyer, M
Wu, DK
AF Raft, Steven
Andrade, Leonardo R.
Shao, Dongmei
Akiyama, Haruhiko
Henkemeyer, Mark
Wu, Doris K.
TI Ephrin-B2 governs morphogenesis of endolymphatic sac and duct epithelia
in the mouse inner ear
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Ephrin-B2; EphB2; Eph-ephrin; Foxi1; Notch; Pendrin; Slc26a4;
Proton-translocating ATPase; DIx5; Gbx2; Signaling; Morphogenesis;
Proliferation; Growth; Mouse; Embryo; Cre-mediated gene inactivation;
Inner ear; Otocyst; Vestibular; Deafness; Endolymph; Otoconia; Fluid
homeostasis; Endolymphatic sac; Endolymphatic duct
ID RENAL TUBULAR-ACIDOSIS; TRANSCRIPTION FACTOR FOXI1; VESTIBULAR AQUEDUCT;
CELL-PROLIFERATION; PENDRED-SYNDROME; TARGETED DISRUPTION; DEFICIENT
MICE; HEARING-LOSS; DEAFNESS; DEFECTS
AB Control over ionic composition and volume of the inner ear luminal fluid endolymph is essential for normal hearing and balance. Mice deficient in either the EphB2 receptor tyrosine kinase or the cognate transmembrane ligand ephrin-B2 (Efnb2) exhibit background strain-specific vestibular-behavioral dysfunction and signs of abnormal endolymph homeostasis. Using various loss-of-function mouse models, we found that Efnb2 is required for growth and morphogenesis of the embryonic endolymphatic epithelium, a precursor of the endolymphatic sac (ES) and duct (ED), which mediate endolymph homeostasis. Conditional inactivation of Efnb2 in early-stage embryonic ear tissues disrupted cell proliferation, cell survival, and epithelial folding at the origin of the endolymphatic epithelium. This correlated with apparent absence of an ED, mis-localization of ES ion transport cells relative to inner ear sensory organs, dysplasia of the endolymph fluid space, and abnormally formed otoconia (extracellular calcite-protein composites) at later stages of embryonic development. A comparison of Efnb2 and Notch signaling-deficient mutant phenotypes indicated that these two signaling systems have distinct and non-overlapping roles in ES/ED development. Homozygous deletion of the Efnb2 C-terminus caused abnormalities similar to those found in the conditional Efnb2 null homozygote. Analyses of fetal Efnb2 C-terminus deletion heterozygotes found mis-localized ES ion transport cells only in the genetic background exhibiting vestibular dysfunction. We propose that developmental dysplasias described here are a gene dose-sensitive cause of the vestibular dysfunction observed in EphB-Efnb2 signaling-deficient mice. Published by Elsevier Inc.
C1 [Raft, Steven; Wu, Doris K.] Natl Inst Deafness & Other Commun Disorders, Sect Sensory Cell Regenerat & Dev, NIH, Bethesda, MD 20892 USA.
[Andrade, Leonardo R.] Univ Fed Rio de Janeiro, CCS, Inst Biomed Sci, Lab Biomineralizat, BR-21941902 Rio De Janeiro, Brazil.
[Shao, Dongmei] Univ Texas SW Med Ctr Dallas, Dept Otolaryngol, Dallas, TX 75390 USA.
[Akiyama, Haruhiko] Gifu Univ, Dept Orthoped, Gifu 5011194, Japan.
[Henkemeyer, Mark] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA.
RP Raft, S (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Sensory Cell Regenerat & Dev, NIH, Bethesda, MD 20892 USA.
EM rafts@nidcd.nih.gov; wud@nidcd.nih.gov
RI Andrade, Leonardo/C-9554-2011
OI Andrade, Leonardo/0000-0002-0004-5677
FU Intramural NIH HHS [Z99 DC999999, ZIA DC000021-20]; NIMH NIH HHS [R01
MH066332]
NR 79
TC 5
Z9 5
U1 0
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
EI 1095-564X
J9 DEV BIOL
JI Dev. Biol.
PD JUN 1
PY 2014
VL 390
IS 1
BP 51
EP 67
DI 10.1016/j.ydbio.2014.02.019
PG 17
WC Developmental Biology
SC Developmental Biology
GA AF2UO
UT WOS:000334568200005
PM 24583262
ER
PT J
AU Mueller, GA
Ankney, JA
Glesner, J
Khurana, T
Edwards, LL
Pedersen, LC
Perera, L
Slater, JE
Pomes, A
London, RE
AF Mueller, Geoffrey A.
Ankney, John A.
Glesner, Jill
Khurana, Taruna
Edwards, Lori L.
Pedersen, Lars C.
Perera, Lalith
Slater, Jay E.
Pomes, Anna
London, Robert E.
TI Characterization of an anti-Bla g 1 scFv: Epitope mapping and
cross-reactivity
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Allergen; Structure; Bla g 1; scFv; Cockroach; Epitope
ID COCKROACH ALLERGEN BLA-G-2; INNER-CITY CHILDREN; MONOCLONAL-ANTIBODY;
AMERICAN COCKROACH; HYDROGEN-EXCHANGE; MOLECULAR-CLONING;
CRYSTAL-STRUCTURE; EXPOSURE; BINDING; IGE
AB Bla g 1 is a major allergen from Blatella germanica and one of the primary allergens used to assess cockroach allergen exposure. The epitope of an anti-Bla g 1 scEv was mapped in order to better understand cross reactivity with other group 1 cockroach allergens and patient IgE epitopes. X-ray crystallography was used to determine the structure of the scFv. The scEv epitope on Bla g 1 was located by alanine scanning sitedirected mutagenesis and ELISA. Twenty-six rBla g 1-GST alanine mutants were evaluated for variations in binding to the scFv compared to the wild type allergen. Six mutants showed a significant difference in scFv binding affinity. These mutations clustered to form a discontinuous epitope mainly comprising two helices of Bla g 1. The allergen-scFv complex was modeled based on the results, and the epitope region was found to have low sequence similarity with Per a 1, especially among the residues identified as functionally important for the scFy binding to Bla g I. Indeed, the scEv failed to bind Per a 1 in American cockroach extract. The scEv was unable to inhibit the binding of IgE antibodies from a highly cockroach allergic patient to Bla g 1. Based on the surface area of Bla g 1 occluded by the scFv, putative regions of patient IgE-Bla g 1 interactions can be inferred. This scFy could be best utilized as a capture antibody in an IgE detection ELISA, or to differentiate Bla g 1 from Per a 1 in environmental exposure assays. Published by Elsevier Ltd.
C1 [Mueller, Geoffrey A.; Ankney, John A.; Edwards, Lori L.; Pedersen, Lars C.; Perera, Lalith; London, Robert E.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Khurana, Taruna; Slater, Jay E.] US FDA, Bethesda, MD 20892 USA.
[Glesner, Jill; Pomes, Anna] Indoor Biotechnol Inc, Charlottesville, VA 22903 USA.
RP Mueller, GA (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM mueller3@niehs.nih.gov
OI Pomes, Anna/0000-0002-8729-1829
FU Intramural Research Program of the National Institute of Environmental
Health Sciences, National Institutes of Health [Z01-ES102885-01,
ZIA-ES102645]; National Institute of Allergy and Infectious Diseases of
the National Institutes of Health [R01A1077653]; U. S. Department of
Energy, Office of Science, Office of Basic Energy Sciences
[W-31-109-Eng-38]
FX This research was supported in part by Research Project Number
Z01-ES102885-01 to REL, and ZIA-ES102645 to LCP in the Intramural
Research Program of the National Institute of Environmental Health
Sciences, National Institutes of Health. Research reported in this
publication was supported in part by the National Institute of Allergy
and Infectious Diseases of the National Institutes of Health under Award
Number R01A1077653 (PI: AP). The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Institutes of Health. Use of the Advanced Photon Source was
supported by the U. S. Department of Energy, Office of Science, Office
of Basic Energy Sciences, under Contract No. W-31-109-Eng-38. The
authors thank Traci Hall and Andrea Moon for a critical reading of the
manuscript.
NR 37
TC 1
Z9 1
U1 0
U2 17
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD JUN
PY 2014
VL 59
IS 2
BP 200
EP 207
DI 10.1016/j.molimm.2014.02.003
PG 8
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA AF8TP
UT WOS:000334988800011
PM 24667070
ER
PT J
AU Yedjou, CG
Saeed, MA
Hossain, MA
Dorsey, W
Yu, HT
Tchounwou, PB
AF Yedjou, Clement G.
Saeed, Musabbir A.
Hossain, Md. Alamgir
Dorsey, Waneene
Yu, Hongtao
Tchounwou, Paul B.
TI Basic apoptotic and necrotic cell death in human liver carcinoma
(HepG(2)) cells induced by synthetic azamacrocycle
SO ENVIRONMENTAL TOXICOLOGY
LA English
DT Article
DE HepG2 cells; cytotoxicity; azamacrocycle; necrosis; apoptosis
ID TRANSCRIPTIONAL ACTIVATION; STRESS GENES; CANCER CELLS; NECROSIS;
EXPRESSION; RECEPTORS; COMPLEXES; ANALOGS; ANION
AB Treatment of diseases with synthetic materials has been an aspiration of mankind since the dawn of human development. In this research, three complex compounds of azamacrocycle (TD1, TD2, and TD3) were synthesized, and experiments were conducted to determine whether their toxicity to human liver carcinoma (HepG(2)) cells is associated with apoptotic and/or necrotic cell death. Cell survival was determined by MTT assay. Apoptosis and necrosis were measured by annexin V FITC/PI assay using the flow cytometry and by propidium iodide (PI) assay using the cellometer vision. HepG(2) cells were treated with different concentrations of azamacrocycles for 48 h. Results from MTT assay indicated that all the three azamacrocycles significantly (p < 0.05) reduce cell viability in a dose-dependent manner, showing 48 h-LD50 values of about 37.97, 33.60, and 19.29 mu M, for TD3, TD1 and TD2, respectively. Among the three compounds tested, TD2 showed the most pronounced cytotoxic activity against HepG(2) cells, being about twofold more potent than TD3. The order of toxicity was TD2 > TD1 > TD3. Because TD2 exerted the most cytotoxic activity against HepG(2) cells, it was used in the subsequent apoptosis and necrosis-related experiments. The flow cytometry assessment showed a strong dose-response relationship with regard to TD2 exposure and annexin V/PI positive cells. PI assay data indicated that TD2 exposure increased the proportion of fluorescence positive cells. Overall, our results indicate that azamacrocycle toxicity to HepG(2) cells is associated with apoptotic and necrotic cell death resulting from phosphatidylserine externalization and loss of membrane integrity. (c) 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 605-611, 2014.
C1 [Yedjou, Clement G.; Dorsey, Waneene; Tchounwou, Paul B.] Jackson State Univ, NIH RCMI Ctr Environm Hlth, Cell & Toxicogen Res Lab, Jackson, MS 39217 USA.
[Saeed, Musabbir A.; Hossain, Md. Alamgir; Yu, Hongtao] Jackson State Univ, Dept Chem & Biochem, Jackson, MS 39217 USA.
RP Tchounwou, PB (reprint author), Jackson State Univ, NIH RCMI Ctr Environm Hlth, Cell & Toxicogen Res Lab, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA.
EM paul.b.tchounwou@jsums.edu
FU National Institutes of Health (RCMI-Center for Environmental Health at
Jackson State University) [5G12RR013459-14]; National Science Foundation
[CHE-0821357]
FX Contract grant sponsor: National Institutes of Health (RCMI-Center for
Environmental Health at Jackson State University).; Contract grant
number: 5G12RR013459-14.; Contract grant sponsor: National Science
Foundation.; Contract grant number: CHE-0821357.
NR 39
TC 4
Z9 4
U1 0
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1520-4081
EI 1522-7278
J9 ENVIRON TOXICOL
JI Environ. Toxicol.
PD JUN
PY 2014
VL 29
IS 6
BP 605
EP 611
DI 10.1002/tox.21786
PG 7
WC Environmental Sciences; Toxicology; Water Resources
SC Environmental Sciences & Ecology; Toxicology; Water Resources
GA AE9BS
UT WOS:000334299500001
PM 22644747
ER
PT J
AU Kim, GY
Gabrea, A
Demchenko, YN
Bergsagel, L
Roschke, AV
Kuehl, WM
AF Kim, Gina Y.
Gabrea, Ana
Demchenko, Yulia N.
Bergsagel, Leif
Roschke, Anna V.
Kuehl, W. Michael
TI Complex IGH rearrangements in multiple myeloma: Frequent detection
discrepancies among three different probe sets
SO GENES CHROMOSOMES & CANCER
LA English
DT Article
ID TRANSLOCATIONS; ABNORMALITIES; IMMUNOGLOBULIN; PROGRESSION; 14Q32; CELL
AB Primary IGH translocations involving seven recurrent partner loci and oncogenes are present in about 40% of multiple myeloma tumors. Secondary IGH rearrangements, which occur in a smaller fraction of tumors, usually are complex structures, including insertions or translocations that can involve three chromosomes, and often with involvement of MYC. The main approach to detect IGH rearrangements is interphase-but sometimes metaphase-FISH strategies that use a telomeric variable region probe and a centromeric constant region/ E alpha enhancer or 3 ' flanking probe to detect a separation of these two probes, or a fusion of these probes with probes located at nonrandom partner sites in the genome. We analyzed 18 myeloma cell lines for detection discrepancies among Vysis, Cytocell, and in-house IGH probe sets that hybridize with differing sequences in the IGH locus. There were no detection discrepancies for the three telomeric IGH probes, or for unrearranged IGH loci or primary IGH translocations using the centromeric IGH probes. However, the majority of complex IGH rearrangements had detection discrepancies among the three centromeric IGH probes. (c) 2014 Wiley Periodicals, Inc.
C1 [Kim, Gina Y.; Gabrea, Ana; Demchenko, Yulia N.; Roschke, Anna V.; Kuehl, W. Michael] NCI, Genet Branch, Bethesda, MD 20892 USA.
[Bergsagel, Leif] Mayo Clin Arizona, Ctr Comprehens Canc, Scottsdale, AZ USA.
RP Kuehl, WM (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 6002C, Bethesda, MD 20892 USA.
EM kuehlw@helix.nih.gov
FU Intramural Research Program of the National Institute of Health,
National Cancer Institute, Center for Cancer Research
FX Supported by: The Intramural Research Program of the National Institute
of Health, National Cancer Institute, Center for Cancer Research.
NR 18
TC 1
Z9 1
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1045-2257
EI 1098-2264
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD JUN
PY 2014
VL 53
IS 6
BP 467
EP 474
DI 10.1002/gcc.22158
PG 8
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA AE2LE
UT WOS:000333803600003
PM 24585545
ER
PT J
AU Simpson, MS
Demner-Fushman, D
Antani, SK
Thoma, GR
AF Simpson, Matthew S.
Demner-Fushman, Dina
Antani, Sameer K.
Thoma, George R.
TI Multimodal biomedical image indexing and retrieval using descriptive
text and global feature mapping
SO INFORMATION RETRIEVAL
LA English
DT Article
DE Multimodal image retrieval; Image indexing; Clustering
ID BAYES POINT MACHINES; ANNOTATION; SEARCH; QUANTIZATION; DATABASES;
PICTURES; FUSION; SCALE; QUERY
AB The images found within biomedical articles are sources of essential information useful for a variety of tasks. Due to the rapid growth of biomedical knowledge, image retrieval systems are increasingly becoming necessary tools for quickly accessing the most relevant images from the literature for a given information need. Unfortunately, article text can be a poor substitute for image content, limiting the effectiveness of existing text-based retrieval methods. Additionally, the use of visual similarity by content-based retrieval methods as the sole indicator of image relevance is problematic since the importance of an image can depend on its context rather than its appearance. For biomedical image retrieval, multimodal approaches are often desirable. We describe in this work a practical multimodal solution for indexing and retrieving the images contained in biomedical articles. Recognizing the importance of text in determining image relevance, our method combines a predominately text-based image representation with a limited amount of visual information, in the form of quantized content-based visual features, through a process called global feature mapping. The resulting multimodal image surrogates are easily indexed and searched using existing text-based retrieval systems. Our experimental results demonstrate that our multimodal strategy significantly improves upon the retrieval accuracy of existing approaches. In addition, unlike many retrieval methods that utilize content-based visual features, the response time of our approach is negligible, making it suitable for use with large collections.
C1 [Simpson, Matthew S.; Demner-Fushman, Dina; Antani, Sameer K.; Thoma, George R.] NIH, Lister Hill Natl Ctr Biomed Commun, US Natl Lib Med, Bethesda, MD 20892 USA.
RP Simpson, MS (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM simpsonmatt@mail.nih.gov; ddemner@mail.nih.gov; santani@mail.nih.gov;
gthoma@mail.nih.gov
OI Antani, Sameer/0000-0002-0040-1387
FU U.S. National Library of Medicine, National Institutes of Health
FX The authors would like to thank Dr. Md. Mahmudur Rahman and Srinivas
Phadnis for extracting and preparing the content-based and text-based
features of the images used in this work. This work is supported by the
intramural research program of the U.S. National Library of Medicine,
National Institutes of Health, and by an appointment to the NLM Research
Participation Program administered by the Oak Ridge Institute for
Science and Education.
NR 86
TC 2
Z9 2
U1 0
U2 10
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1386-4564
EI 1573-7659
J9 INFORM RETRIEVAL
JI Inf. Retr.
PD JUN
PY 2014
VL 17
IS 3
BP 229
EP 264
DI 10.1007/s10791-013-9235-2
PG 36
WC Computer Science, Information Systems
SC Computer Science
GA AF1SQ
UT WOS:000334494200002
ER
PT J
AU Gattass, R
Galkin, TW
Desimone, R
Ungerleider, LG
AF Gattass, Ricardo
Galkin, Thelma W.
Desimone, Robert
Ungerleider, Leslie G.
TI Subcortical Connections of Area V4 in the Macaque
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE pulvinar; claustrum; caudate; putamen; superior colliculus; amygdala
ID LATERAL GENICULATE-NUCLEUS; MONKEY SUPERIOR COLLICULUS; INFERIOR
PULVINAR COMPLEX; VISUAL-SPATIAL ATTENTION; CALCIUM-BINDING PROTEINS;
SUB-CORTICAL STRUCTURES; BEHAVING RHESUS-MONKEY; NEW-WORLD MONKEY;
STRIATE CORTEX; MACACA-MULATTA
AB Area V4 has numerous, topographically organized connections with multiple cortical areas, some of which are important for spatially organized visual processing, and others which seem important for spatial attention. Although the topographic organization of V4's connections with other cortical areas has been established, the detailed topography of its connections with subcortical areas is unclear. We therefore injected retrograde and anterograde tracers in different topographical regions of V4 in nine macaques to determine the organization of its subcortical connections. The injection sites included representations ranging from the fovea to far peripheral eccentricities in both the upper and lower visual fields. The topographically organized connections of V4 included bidirectional connections with four subdivisions of the pulvinar, two subdivisions of the claustrum, and the interlaminar portions of the lateral geniculate nucleus, and efferent projections to the superficial and intermediate layers of the superior colliculus, the thalamic reticular nucleus, and the caudate nucleus. All of these structures have a possible role in spatial attention. The nontopographic, or converging, connections included bidirectional connections with the lateral nucleus of the amygdala, afferent inputs from the dorsal raphe, median raphe, locus coeruleus, ventral tegmentum and nucleus basalis of Meynert, and efferent projections to the putamen. Any role of these structures in attention may be less spatially specific. J. Comp. Neurol. 522:1941-1965, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Gattass, Ricardo] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Cognit Physiol, BR-21941900 Rio de Janeiro, RJ, Brazil.
[Galkin, Thelma W.; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Desimone, Robert] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Desimone, Robert] MIT, McGovern Inst, Cambridge, MA 02139 USA.
RP Ungerleider, LG (reprint author), Lab Brain & Cognit, NIMH Bldg 10,Room 4C104,10 Ctr Dr, Bethesda, MD 20892 USA.
EM ungerlel@mail.nih.gov
FU NIMH Intramural Research Program; NEI, NIH [RO1EY017292]
FX Grant sponsor: NIMH Intramural Research Program; Grant sponsor: NEI,
NIH; Grant number: RO1EY017292 (to R.D.).
NR 136
TC 10
Z9 10
U1 3
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9967
EI 1096-9861
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD JUN 1
PY 2014
VL 522
IS 8
BP 1941
EP 1965
DI 10.1002/cne.23513
PG 25
WC Neurosciences; Zoology
SC Neurosciences & Neurology; Zoology
GA AD9RW
UT WOS:000333603200015
PM 24288173
ER
PT J
AU Henning, T
Butler, K
Mitchell, J
Ellis, S
Deyounks, F
Farshy, C
Phillips, C
Papp, J
Patton, D
Caldwell, H
Sturdevant, G
McNicholl, J
Kersh, E
AF Henning, Tara
Butler, Katherine
Mitchell, James
Ellis, Shanon
Deyounks, Frank
Farshy, Carol
Phillips, Christi
Papp, John
Patton, Dorothy
Caldwell, Harlan
Sturdevant, Gail
McNicholl, Janet
Kersh, Ellen
TI Development of a rectal sexually transmitted infection - HIV coinfection
model utilizing Chlamydia trachomatis and SHIVSF162p3
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Article
DE men who have sex with men; STD
ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEISSERIA-GONORRHOEAE; NONHUMAN-PRIMATES;
MACAQUE MODEL; GENITAL-TRACT; TRANSMISSION; SEX; MEN; TENOFOVIR; SYSTEM
AB BackgroundRectal sexually transmitted infections (STIs) may increase HIV susceptibility in men who have sex with men (MSM), and Chlamydia trachomatis is prevalent among HIV-positive MSM. To study STIs and HIV infection in MSM, we first evaluated whether cynomolgus macaques can sustain both C.trachomatis and SHIVSF162p3 infections(.)
MethodsFour SHIVSF162p3-positive male cynomolgus macaques were used (n=3 rectally inoculated with 10(6) IFU; n=1 control). Systemic and rectal SHIV RNA levels and cytokines were measured by real-time PCR and Luminex assays, respectively.
ResultsMacaques were successfully Chlamydia infected. Rectal SHIV shedding (P=0.02 (2)) and levels of G-CSF, IL-1ra, IL-6, IL-8, IFN-, and TNF- (P0.01, Mann-Whitney) in rectal secretions increased following infection.
ConclusionsThese pilot data successfully demonstrate rectal C.trachomatis-SHIV coinfection in cynomolgus macaques and suggest the feasibility of a rectal C.trachomatis model for SHIV susceptibility and biomedical prevention studies in the context of rectal STIs.
C1 [Henning, Tara; Butler, Katherine; Mitchell, James; Ellis, Shanon; Deyounks, Frank; McNicholl, Janet; Kersh, Ellen] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA 30333 USA.
[Farshy, Carol; Phillips, Christi; Papp, John] Ctr Dis Control & Prevent, Div STD Prevent, Atlanta, GA 30333 USA.
[Patton, Dorothy] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA.
[Caldwell, Harlan; Sturdevant, Gail] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Kersh, E (reprint author), Ctr Dis Control & Prevent, Div HIV AIDS Prevent, 1600 Clifton Rd NE,MS A-25, Atlanta, GA 30333 USA.
EM ekersh@cdc.gov
FU CDC [Y1-A1-0681-02]; NIH [Y1-A1-0681-02]
FX The authors thank Dr. John Brooks and Dr. Pragna Patel for advisement on
rectal pathogens. The authors thank Patty Guenthner for her assistance
with macaques' SHIV infection data from the previous titration study.
This work was funded by CDC and an interagency agreement (Y1-A1-0681-02)
between CDC and NIH.
NR 27
TC 3
Z9 3
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0047-2565
EI 1600-0684
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD JUN
PY 2014
VL 43
IS 3
BP 135
EP 143
DI 10.1111/jmp.12103
PG 9
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA AF2EF
UT WOS:000334524700001
PM 24460742
ER
PT J
AU Vaughan, KL
Szarowicz, MD
Herbert, RL
Mattison, JA
AF Vaughan, Kelli L.
Szarowicz, Mark D.
Herbert, Richard L.
Mattison, Julie A.
TI Comparison of anesthesia protocols for intravenous glucose tolerance
testing in rhesus monkeys
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Article
DE glucose regulation; IVGTT; non-human primate; pharmacology; rhesus
macaque
ID MACACA-MULATTA; MEDETOMIDINE; MACAQUES; KETAMINE; CATS; RATS
AB BackgroundDrugs commonly used to sedate non-human primates for physiological sample collection can affect the metabolic system and alter rates of glucose metabolism. This study was designed to compare the physiological and metabolic effects of ketamine/diazepam, telazol, and ketamine/dexmedetomidine.
MethodsSeven female rhesus monkeys underwent intravenous glucose tolerance testing under each of three anesthesia conditions. Blood glucose, insulin, physiological parameters, and sedation characteristics were measured and recorded.
ResultsGlucose and insulin values were both significantly impacted by ketamine/dexmedetomidine sedation while remaining consistent during ketamine and telazol sedation. Heart rate was also significantly lowered during ketamine/dexmedetomidine anesthesia. Though, ketamine/dexmedetomidine resulted in a longer time between induction of anesthesia and need for a supplemental dose of anesthesia drug.
ConclusionsTelazol and ketamine have minimal cardiorespiratory and metabolic effects compared to ketamine/dexmedetomidine. Although practicably interchangeable, telazol appears to be the most efficient for intravenous glucose tolerance testings with non-human primates.
C1 [Vaughan, Kelli L.; Szarowicz, Mark D.; Mattison, Julie A.] NIA, Translat Gerontol Branch, Intramural Res Program, NIH, Dickerson, MD 20842 USA.
[Vaughan, Kelli L.; Szarowicz, Mark D.] SoBran Inc, Burtonsville, MD USA.
[Herbert, Richard L.] NIAID, NIH, Anim Ctr, Dickerson, MD USA.
RP Vaughan, KL (reprint author), NIA, Translat Gerontol Branch, Intramural Res Program, NIH, 16701 Elmer Sch Rd,Bldg 103, Dickerson, MD 20842 USA.
EM kelli.vaughan@nih.gov
OI Vaughan, Kelli/0000-0001-5274-582X
FU Intramural Research Program, National Institute on Aging, NIH
FX The authors would like to thank Joe Travis, Rob Young, and Ed Tilmont
for their technical support. This project was supported entirely by the
Intramural Research Program, National Institute on Aging, NIH.
NR 15
TC 3
Z9 3
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0047-2565
EI 1600-0684
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD JUN
PY 2014
VL 43
IS 3
BP 162
EP 168
DI 10.1111/jmp.12104
PG 7
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA AF2EF
UT WOS:000334524700004
PM 24697511
ER
PT J
AU Canugovi, C
Shamanna, RA
Croteau, DL
Bohr, VA
AF Canugovi, Chandrika
Shamanna, Raghavendra A.
Croteau, Deborah L.
Bohr, Vilhelm A.
TI Base excision DNA repair levels in mitochondrial lysates of Alzheimer's
disease
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Base excision repair; 5-Hydroxyuracil; Ligation; Alzheimer's disease;
Mitochondria
ID INCREASED OXIDATIVE DAMAGE; MILD COGNITIVE IMPAIRMENT;
CYTOCHROME-C-OXIDASE; AMYLOID-BETA; LIGASE-III; BRAIN; NUCLEAR;
DELETIONS; DYSFUNCTION; MORPHOLOGY
AB Alzheimer's disease (AD) is a senile dementia with increased incidence in older subjects (age > 65 years). One of the earliest markers of AD is oxidative DNA damage. Recently, it has been reported that preclinical AD patient brains show elevated levels of oxidative damage in both nuclear and mitochondrial nucleic acids. Moreover, different oxidative lesions in mitochondrial DNA are between 5- and 10-fold higher than in nuclear DNA in both control and AD postmortem brains. We previously showed that there is a significant loss of base excision repair (BER) components in whole tissue extracts of AD and mild cognitive impairment subjects relative to matched control subjects. However, comprehensive analysis of specific steps in BER levels in mitochondrial extracts of AD patient brains is not available. In this study, we mainly investigated various components of BER in mitochondrial extracts of AD and matched control postmortem brain samples. We found that the 5-hydroxyuracil incision and ligase activities are significantly lower in AD brains, whereas the uracil incision, abasic site cleavage, and deoxyribonucleotide triphosphate incorporation activities are normal in these samples. Published by Elsevier Inc.
C1 [Canugovi, Chandrika; Shamanna, Raghavendra A.; Croteau, Deborah L.; Bohr, Vilhelm A.] Natl Inst Aging, Lab Mol Gerontol, Baltimore, MD 21224 USA.
RP Bohr, VA (reprint author), Natl Inst Aging, Lab Mol Gerontol, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM vbohr@nih.gov
FU Intramural Research Program of the National Institutes of Health and
National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the National Institutes of Health and National Institute on Aging. We
would like to thank Harvard Brain Bank for the human postmortem brain
samples used in this study. Additionally, we would like to thank Huiming
Lu and Somnath Ghosh for critically reading the manuscript.
NR 35
TC 18
Z9 18
U1 1
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUN
PY 2014
VL 35
IS 6
BP 1293
EP 1300
DI 10.1016/j.neurobiolaging.2014.01.004
PG 8
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA AE4RO
UT WOS:000333970800009
PM 24485507
ER
PT J
AU Benitez, BA
Jin, SC
Guerreiro, R
Graham, R
Lord, J
Harold, D
Sims, R
Lambert, JC
Gibbs, JR
Bras, J
Sassi, C
Harari, O
Bertelsen, S
Lupton, MK
Powell, J
Bellenguez, C
Brown, K
Medway, C
Haddick, PCG
van der Brug, MP
Bhangale, T
Ortmann, W
Behrens, T
Mayeux, R
Pericak-Vance, MA
Farrer, LA
Schellenberg, GD
Haines, JL
Turton, J
Braae, A
Barber, I
Fagan, AM
Holtzman, DM
Morris, JC
Williams, J
Kauwe, JSK
Amouyel, P
Morgan, K
Singleton, A
Hardy, J
Goate, AM
Cruchaga, C
AF Benitez, Bruno A.
Jin, Sheng Chih
Guerreiro, Rita
Graham, Rob
Lord, Jenny
Harold, Denise
Sims, Rebecca
Lambert, Jean-Charles
Gibbs, J. Raphael
Bras, Jose
Sassi, Celeste
Harari, Oscar
Bertelsen, Sarah
Lupton, Michelle K.
Powell, John
Bellenguez, Celine
Brown, Kristelle
Medway, Christopher
Haddick, Patrick C. G.
van der Brug, Marcel P.
Bhangale, Tushar
Ortmann, Ward
Behrens, Tim
Mayeux, Richard
Pericak-Vance, Margaret A.
Farrer, Lindsay A.
Schellenberg, Gerard D.
Haines, Jonathan L.
Turton, Jim
Braae, Anne
Barber, Imelda
Fagan, Anne M.
Holtzman, David M.
Morris, John C.
Williams, Julie
Kauwe, John S. K.
Amouyel, Philippe
Morgan, Kevin
Singleton, Andy
Hardy, John
Goate, Alison M.
Cruchaga, Carlos
CA 3C Study Grp
EADI Consortium
ADGC
ADNI
GERAD Consortium
TI Missense variant in TREML2 protects against Alzheimer's disease
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE TREM2; Genome-wide association studies; Conditional analysis;
Endophenotype; Gene; Alzheimer's disease; Association
ID ASSOCIATION
AB TREM and TREM-like receptors are a structurally similar protein family encoded by genes clustered on chromosome 6p21.11. Recent studies have identified a rare coding variant (p. R47H) in TREM2 that confers a high risk for Alzheimer's disease (AD). In addition, common single nucleotide polymorphisms in this genomic region are associated with cerebrospinal fluid biomarkers for AD and a common intergenic variant found near the TREML2 gene has been identified to be protective for AD. However, little is known about the functional variant underlying the latter association or its relationship with the p. R47H. Here, we report comprehensive analyses using whole-exome sequencing data, cerebrospinal fluid biomarker analyses, meta-analyses (16,254 cases and 20,052 controls) and cell-based functional studies to support the role of the TREML2 coding missense variant p. S144G (rs3747742) as a potential driver of the metaanalysis AD-associated genome-wide association studies signal. Additionally, we demonstrate that the protective role of TREML2 in AD is independent of the role of TREM2 gene as a risk factor for AD. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Benitez, Bruno A.; Jin, Sheng Chih; Harari, Oscar; Bertelsen, Sarah; Goate, Alison M.; Cruchaga, Carlos] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Fagan, Anne M.; Holtzman, David M.; Morris, John C.; Goate, Alison M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Morris, John C.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Goate, Alison M.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Holtzman, David M.; Morris, John C.] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA.
[Fagan, Anne M.; Holtzman, David M.; Morris, John C.; Goate, Alison M.] Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA.
[Fagan, Anne M.; Holtzman, David M.; Morris, John C.; Goate, Alison M.; Cruchaga, Carlos] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA.
[Harold, Denise; Sims, Rebecca] Cardiff Univ, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales.
[Graham, Rob; van der Brug, Marcel P.] Genentech Inc, Diagnost Discovery Dept, San Francisco, CA 94080 USA.
[Bhangale, Tushar] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA.
[Ortmann, Ward; Behrens, Tim; Singleton, Andy; Hardy, John] Genentech Inc, Dept Human Genet, San Francisco, CA 94080 USA.
[Guerreiro, Rita; Sassi, Celeste] UCL Inst Neurol, Dept Mol Neurosci, London, England.
[Guerreiro, Rita; Gibbs, J. Raphael; Sassi, Celeste] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA.
[Kauwe, John S. K.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA.
[Mayeux, Richard] Columbia Univ, Taub Inst Alzheimers Dis & Aging Brain, Dept Neurol, New York, NY USA.
[Mayeux, Richard] Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10027 USA.
[Pericak-Vance, Margaret A.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA.
[Pericak-Vance, Margaret A.] Univ Miami, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Med, Boston, MA USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Biomed Genet, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Biomed Genet, Boston, MA USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Ophthalmol, Boston, MA USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Schellenberg, Gerard D.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Haines, Jonathan L.] Vanderbilt Univ, Vanderbilt Ctr Human Genet Res, Dept Mol Physiol & Biophys, Nashville, TN 37235 USA.
[Lord, Jenny; Brown, Kristelle; Medway, Christopher; Braae, Anne; Barber, Imelda; Morgan, Kevin] Univ Nottingham, Sch Mol Med Sci, Nottingham NG7 2RD, England.
[Lupton, Michelle K.; Powell, John] Kings Coll London, Inst Psychiat, London, England.
[Lambert, Jean-Charles; Bellenguez, Celine; Amouyel, Philippe] INSERM, F-59045 Lille, France.
[Lambert, Jean-Charles; Bellenguez, Celine; Amouyel, Philippe; Cruchaga, Carlos] Univ Lille 2, Lille, France.
[Lambert, Jean-Charles; Bellenguez, Celine; Amouyel, Philippe] Inst Pasteur, F-59019 Lille, France.
RP Cruchaga, C (reprint author), Washington Univ, Sch Med, Dept Psychiat, 660 South Euclid Ave B8134, St Louis, MO 63110 USA.
EM goatea@psychiatry.wustl.edu; cruchagac@psychiatry.wustl.edu
RI Tsuang, Debby/L-7234-2016; Hardy, John/C-2451-2009; Singleton,
Andrew/C-3010-2009; Bras, Jose/A-1428-2011; Powell, John/G-4412-2011;
lambert, jean-charles/F-8787-2013; Lambert, jean-charles/A-9553-2014;
Guerreiro, Rita/A-1327-2011; Benitez, Bruno/E-7116-2014;
OI Tsuang, Debby/0000-0002-4716-1894; Harold, Denise/0000-0001-5195-0143;
Powell, John/0000-0001-6124-439X; Lambert,
jean-charles/0000-0003-0829-7817; Bras, Jose/0000-0001-8186-0333;
Farrer, Lindsay/0000-0001-5533-4225; Benitez, Bruno/0000-0002-2699-3878;
Cruchaga, Carlos/0000-0002-0276-2899
FU French National Foundation on Alzheimer's disease and related disorders;
LABEX (laboratory of excellence program investment for the future)
DISTALZ grant (Development of Innovative Strategies for a
Transdisciplinary approach to ALZheimer's disease); Caisse Nationale
Maladie des Travailleurs Salaries; Direction Generale de la Sante; MGEN;
Institut de la Longevite; Agence Francaise de Securite Sanitaire des
Produits de Sante; Aquitaine and Bourgogne Regional Councils; Fondation
de France; French Ministry of Research and INSERM "Cohortes et
collections de donnees biologiques" programme
FX EADI1 was supported by the French National Foundation on Alzheimer's
disease and related disorders. Data management involved the Centre
National de Genotypage, the Institut Pasteur de Lille, Inserm, FRC
(fondation pour la recherche sur le cerveau), and Rotary. This work has
been developed and supported by the LABEX (laboratory of excellence
program investment for the future) DISTALZ grant (Development of
Innovative Strategies for a Transdisciplinary approach to ALZheimer's
disease). The Three-City Study was performed as part of collaboration
between the Institut National de la Sante et de la Recherche Medicale
(Inserm), the Victor Sega len Bordeaux II University, and
Sanofi-Synthelabo. The Fondation pour la Recherche Medicale funded the
preparation and initiation of the study. The 3C Study was also funded by
the Caisse Nationale Maladie des Travailleurs Salaries, Direction
Generale de la Sante, MGEN, Institut de la Longevite, Agence Francaise
de Securite Sanitaire des Produits de Sante, the Aquitaine and Bourgogne
Regional Councils, Fondation de France, and the joint French Ministry of
Research and INSERM "Cohortes et collections de donnees biologiques"
programme. Lille Genopo le received an unconditional grant from Eisai.
NR 25
TC 18
Z9 18
U1 0
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUN
PY 2014
VL 35
IS 6
AR 1510.e19
DI 10.1016/j.neurobiolaging.2013.12.010
PG 8
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA AE4RO
UT WOS:000333970800035
PM 24439484
ER
PT J
AU Calvo, A
Moglia, C
Canosa, A
Brunetti, M
Barberis, M
Traynor, BJ
Carrara, G
Valentini, C
Restagno, G
Chio, A
AF Calvo, Andrea
Moglia, Cristina
Canosa, Antonio
Brunetti, Maura
Barberis, Marco
Traynor, Bryan J.
Carrara, Giovanna
Valentini, Consuelo
Restagno, Gabriella
Chio, Adriano
TI A de novo nonsense mutation of the FUS gene in an apparently familial
amyotrophic lateral sclerosis case
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Amyotrophic lateral sclerosis; FUS; de novo mutation
ID HEXANUCLEOTIDE REPEAT; ALS; C9ORF72; AUTISM; SCHIZOPHRENIA; PHENOTYPE;
FTD
AB Mutations in C9ORF72, SOD1, TARDBP, and FUS genes account for approximately two-third of familial cases and 5% of sporadic amyotrophic lateral sclerosis (ALS) cases. We present the first case of an ALS patient carrying a de novo nonsense mutation in exon 14 of the FUS gene (c.1483c>t; p.R495X) with an apparently familial ALS. This mutation causes a phenotype characterized by a young age at onset, a rapid course (<24 months), and a bulbar onset with early respiratory involvement with a predominant lower motor neuron disease. De novo mutations could account for a sizable number of apparently sporadic ALS patients carrying mutations of ALS-related genes. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Calvo, Andrea; Moglia, Cristina; Canosa, Antonio; Chio, Adriano] Univ Turin, Rita Levi Montalcini Dept Neurosci, ALS Ctr, I-10126 Turin, Italy.
[Brunetti, Maura; Barberis, Marco; Restagno, Gabriella] Azienda Osped Citta Salute & Sci, Mol Genet Lab, Turin, Italy.
[Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Carrara, Giovanna; Valentini, Consuelo] Dept Neuroradiol, Azienda Osped Citta Salute & Sci, Dept Neuroradiol, Turin, Italy.
[Chio, Adriano] Neurosci Inst Torino, Turin, Italy.
RP Calvo, A (reprint author), Univ Turin, Rita Levi Montalcini Dept Neurosci, ALS Ctr, Via Cherasco 15, I-10126 Turin, Italy.
EM achio@usa.net
RI Calvo, Andrea/K-4141-2016; Moglia, Cristina/K-4142-2016;
OI Calvo, Andrea/0000-0002-5122-7243; Moglia, Cristina/0000-0001-7377-7222;
Chio, Adriano/0000-0001-9579-5341
FU Fondazione Vialli e Mauro for ALS Research Onlus; Federazione Italiana
Giuoco Calcio; Ministero della Salute [RF-PIE-2007-635695,
RF-2010-2309849]; Joint Programmed-Neurodegenerative Disease Research
(Strength Project); European Community [259867]; Intramural Research
Program of the National Institutes of Health and the National Institute
on Aging [Z01 AG000949-02]
FX Adriano Chio had full access to all the data in the study and takes
responsibility for the integrity of the data and the accuracy of the
data analysis. We thank the patient and her family for having
collaborated to this study. This work was funded by grants of Fondazione
Vialli e Mauro for ALS Research Onlus, Federazione Italiana Giuoco
Calcio, Ministero della Salute (Ricerca Sanitaria Finalizzata 2007,
grant RF-PIE-2007-635695, and 2010, grant RF-2010-2309849), and Joint
Programmed-Neurodegenerative Disease Research (Strength Project). The
research leading to these results has received funding from the European
Community's Health Seventh Framework Programme (FP7/2007-2013) (grant
agreement no. 259867). This work was supported in part by the Intramural
Research Program of the National Institutes of Health and the National
Institute on Aging (project Z01 AG000949-02). Funding organizations had
no role in design and conduct of the study; collection, management,
analysis, and interpretation of the data; and preparation, review, or
approval of the manuscript.
NR 31
TC 3
Z9 3
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUN
PY 2014
VL 35
IS 6
AR 1513.e7
DI 10.1016/j.neurobiolaging.2013.12.028
PG 5
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA AE4RO
UT WOS:000333970800042
PM 24439481
ER
PT J
AU Dong, J
Gao, JJ
Nalls, M
Gao, X
Huang, XM
Han, JL
Singleton, AB
Chen, HL
AF Dong, Jing
Gao, Jianjun
Nalls, Michael
Gao, Xiang
Huang, Xuemei
Han, Jiali
Singleton, Andrew B.
Chen, Honglei
CA IPDGC
TI Susceptibility loci for pigmentation and melanoma in relation to
Parkinson's disease
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Pigmentation; Melanoma; Parkinson's disease; Susceptibility
ID GENOME-WIDE ASSOCIATION; GENETIC-DETERMINANTS; RISK; CANCER;
METAANALYSIS; EUROPEANS; VARIANTS; HAIR
AB Growing evidence suggests that Parkinson's disease (PD) patients have a lower risk for most types of cancer except for melanoma, which has a modest positive association with PD. Pigmentation genes have been hypothesized to contribute to this association. We therefore examined whether genetic susceptibility loci for pigmentation or melanoma was associated with PD risk in 2 large independent datasets. In the Parkinson's Genes and Environment (PAGE) study, we examined 11 single-nucleotide polymorphisms (SNPs) identified from previous genome-wide association studies (GWAS) of pigmentation or melanoma in relation to PD among 808 PD cases and 1623 controls; furthermore, we also examined the colors of hair, eye, or skin and melanoma in relation to PD. In the International Parkinson's Disease Genomic Consortium (IPDGC), we examined a broader selection of 360 pigmentation or melanoma GWAS SNPs in relation to PD among 5,333 PD cases and 12,019 controls. All participants were non-Hispanic Whites. As expected, in the PAGE study, most SNPs were associated with 1 or more pigmentation phenotypes. However, neither these SNPs nor pigmentation phenotypes were associated with PD risk after Bonferroni correction with the exception of rs4911414 at the ASIP gene (p.001). A total of 18 PD cases (2.2%) and 26 controls (1.6%) had a diagnosis of melanoma with an odds ratio of 1.3 (95% confidence interval: 0.7-2.4). In the IPDGC analysis, none of the 360 SNPs, including rs4911414, were associated with PD risk after adjusting for multiple comparisons. In conclusion, we did not find significant associations between GWAS SNPs of pigmentation or melanoma and the risk for PD. Published by Elsevier Inc.
C1 [Dong, Jing; Gao, Jianjun; Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Gao, Jianjun] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Nalls, Michael; Singleton, Andrew B.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Gao, Xiang] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Gao, Xiang] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Gao, Xiang; Han, Jiali] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA.
RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA.
EM chenh2@niehs.nih.gov
RI Bloem, B.R./H-8013-2014; Wood, Nicholas/C-2505-2009; van de Warrenburg,
Bart/D-1935-2010; Martinez, Maria/B-3111-2013; Guerreiro,
Rita/A-1327-2011; corvol, jean-christophe/I-6387-2012; Revesz,
Tamas/A-8732-2010; Trabzuni, Daniah/C-4034-2012; Deuschl,
Gunther/A-7986-2010; Lees, Andrew/A-6605-2009; Scheffer,
Hans/E-4644-2012; Hardy, John/C-2451-2009; Cooper, J Mark/D-5826-2013;
Schapira, Anthony/A-1245-2010; Singleton, Andrew/C-3010-2009; Bras,
Jose/A-1428-2011; Deloukas, Panos/B-2922-2013; Morris, Huw/B-8527-2008;
OI Wood, Nicholas/0000-0002-9500-3348; Martinez, Maria/0000-0003-2180-4537;
corvol, jean-christophe/0000-0001-7325-0199; Revesz,
Tamas/0000-0003-2501-0259; Trabzuni, Daniah/0000-0003-4826-9570; Bras,
Jose/0000-0001-8186-0333; Plagnol, Vincent/0000-0002-5597-9215;
Scheffer, Hans/0000-0002-2986-0915; Cooper, J Mark/0000-0002-3007-3054;
Schapira, Anthony/0000-0002-3018-3966; Deloukas,
Panos/0000-0001-9251-070X; Morris, Huw/0000-0002-5473-3774; Bhatia,
Kailash/0000-0001-8185-286X; Chen, Honglei/0000-0003-3446-7779
FU Intramural Research Program of the NIH; National Institute of
Environmental Health Sciences [Z01-ES-101986]; National Cancer Institute
[Z01-CP010196-02]; National Institute on Aging [Z01-AG000949-02]
FX The authors are grateful to the continuous contribution of participants
of the PAGE study and the International PD Genomic Consortium. We also
thank investigators from the NIH-AARP Diet and Health Study for their
continuous support. This study was supported by the Intramural Research
Program of the NIH, the National Institute of Environmental Health
Sciences (Z01-ES-101986), the National Cancer Institute
(Z01-CP010196-02), and the National Institute on Aging
(Z01-AG000949-02).
NR 20
TC 8
Z9 8
U1 1
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUN
PY 2014
VL 35
IS 6
AR 1512.e5
DI 10.1016/j.neurobiolaging.2013.12.020
PG 6
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA AE4RO
UT WOS:000333970800039
PM 24439955
ER
PT J
AU Mondul, AM
Weinstein, SJ
Moy, KA
Mannisto, S
Albanes, D
AF Mondul, Alison M.
Weinstein, Stephanie J.
Moy, Kristin A.
Mannisto, Satu
Albanes, Demetrius
TI Vitamin D- binding protein, circulating vitamin D and risk of renal cell
carcinoma
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE renal cell carcinoma; vitamin D-binding protein; 25-hydroxyvitamin D;
prospective studies
ID 25-HYDROXYVITAMIN D; PANCREATIC-CANCER; PROSTATE-CANCER; KIDNEY CANCER;
ASSOCIATION; COHORT; TRIAL
AB Cell culture experiments suggest that vitamin D may inhibit renal carcinogenesis, but human studies of circulating 25-hydroxyvitamin D [25(OH)D], the accepted measure of vitamin D status, and kidney cancer have been null. Limited research has examined the role of circulating vitamin D-binding protein (DBP) in the association between 25(OH)D and disease risk, and it is unclear whether free 25(OH)D in circulation is a better measure of effective exposure, or if DBP may independently impact outcomes. We conducted a nested case-control analysis within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study to examine whether circulating DBP concentration was prospectively associated with risk of renal cell carcinoma, and whether it modified the association with 25(OH)D. Renal cell carcinoma cases (n = 262) were matched 1:1 to controls on age (1 year) and date of blood collection ( 30 days). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of renal cell carcinoma risk by quartiles of 25(OH)D, DBP and the molar ratio of 25(OH)D:DBP, a proxy for free circulating 25(OH)D. Men with higher DBP concentrations were at significantly decreased risk of kidney cancer (Q4 vs. Q1: OR = 0.17, 95% CI = 0.08-0.33; p-trend < 0.0001), a finding unchanged by adjustment for 25(OH)D. Although we observed no association with total 25(OH)D, we found slightly increased risk with higher levels of estimated free 25(OH)D [Q4 vs. Q1 of the 25(OH)D:DBP ratio, OR = 1.61, 95% CI = 0.95-2.73; p-trend = 0.09]. The strong protective association observed between higher circulating DBP concentration and kidney cancer risk requires replication but suggests a vitamin D-independent influence of DBP.
What's new? Circulating vitamin D binding protein (DBP) has been implicated in the etiology of certain cancers, where it may act directly or by modifying circulating vitamin D concentrations and disease risk. In this examination of the association between DBP and renal cell carcinoma (RCC) specifically, a strong protective association was found between elevated circulating DBP concentrations and kidney cancer. The association was unchanged after adjustment for circulating vitamin D. The results suggest that DBP may influence risk of RCC through a biologic mechanism unrelated to vitamin D status.
C1 [Mondul, Alison M.; Weinstein, Stephanie J.; Moy, Kristin A.; Albanes, Demetrius] NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA.
[Mannisto, Satu] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Mondul, AM (reprint author), NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM mondulam@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015;
OI Mondul, Alison/0000-0002-8843-1416; Mannisto, Satu/0000-0002-8668-3046
FU Intramural NIH HHS [Z99 CA999999]
NR 24
TC 14
Z9 14
U1 0
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD JUN 1
PY 2014
VL 134
IS 11
BP 2699
EP 2706
DI 10.1002/ijc.28596
PG 8
WC Oncology
SC Oncology
GA AC8RO
UT WOS:000332801700019
PM 24214881
ER
PT J
AU Hiram-Bab, S
Katz, LS
Shapira, H
Sandbank, J
Gershengorn, MC
Oron, Y
AF Hiram-Bab, Sahar
Katz, Liora S.
Shapira, Hagit
Sandbank, Judith
Gershengorn, Marvin C.
Oron, Yoram
TI Platelet- Derived Growth Factor BB Mimics Serum- Induced Dispersal of
Pancreatic Epithelial Cell Clusters
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID INSULIN-PRODUCING CELLS; MESENCHYMAL STEM-CELLS; PRECURSOR CELLS;
EMBRYONIC STEM; BETA-CATENIN; IN-VITRO; PROGENITOR CELLS; BONE-MARROW;
MULTIPOTENTIAL NESTIN; SIGNALING PATHWAY
AB We showed previously that proliferating human islet-derived de-differentiated cells (DIDs) exhibit many characteristics of mesenchymal stem cells. Dispersed DIDs can be induced by serum deprivation to undergo mesenchymal-to-epithelial transition and aggregate into epithelial cell clusters (ECCs). Conversely, ECCs can be induced to disperse and undergo epithelial-to-mesenchymal transition (EMT) by re-addition of mammalian sera. In this study, we show that platelet-derived growth factor BB (PDGF-BB) mimics and mediates serum-induced ECCs' dispersal accompanied by accumulation of cytoplasmic -catenin and a decrease in the levels of insulin and glucagon mRNAs. Moreover, we show that PDGF-BB-induced dispersal of ECCs is a more general phenomenon that occurs also with bone marrow mesenchymal stem cells (BM-MSCs) and dermal fibroblasts (DFs). In DIDs, BM-MSCs, and DFs, PDGF decreased the levels of DKK1 mRNA, suggesting involvement of the Wnt signaling pathway. PDGF-BB stimulated a significant increase in S473 phosphorylation of Akt and the PI3K specific inhibitor (PIP828) partially inhibited PDGF-BB-induced ECC dispersal. Lastly, the PDGF-receptor (PDGF-R) antagonist JNJ-10198409 inhibited both PDGF-BBand serum-induced ECC dispersal. Epidermal growth factor (EGF), which shares most of the PDGF signaling pathway, did not induce dispersal and only weakly stimulated Akt phosphorylation. Our data suggest that PDGF-BB mediates serum-induced DIDs dispersal, correlated with the activation of the PI3K-Akt pathway. J. Cell. Physiol. 229: 743-751, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Hiram-Bab, Sahar; Oron, Yoram] Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel.
[Katz, Liora S.; Gershengorn, Marvin C.] NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
[Shapira, Hagit; Sandbank, Judith] Maccabi Hlth Org, Cent Lab, Inst Pathol, Rehovot, Israel.
[Sandbank, Judith] Tel Aviv Univ, Sackler Fac Med, Dept Pathol, IL-69978 Tel Aviv, Israel.
RP Oron, Y (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel.
EM medfair@post.tau.ac.il
FU Intramural Research Program NIDDK; NIH [Z01 DK011007]; SNSF
[PBGEP3-139875]
FX Contract grant sponsor: Intramural Research Program NIDDK.; Contract
grant sponsor: NIH;; Contract grant number: Z01 DK011007.; Contract
grant sponsor: SNSF;; Contract grant number: PBGEP3-139875.
NR 69
TC 1
Z9 1
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9541
EI 1097-4652
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD JUN
PY 2014
VL 229
IS 6
BP 743
EP 751
DI 10.1002/jcp.24493
PG 9
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA AB7YP
UT WOS:000332007600007
PM 24129818
ER
PT J
AU Kang, N
Won, M
Rhee, M
Ro, H
AF Kang, Nami
Won, Minho
Rhee, Myungchull
Ro, Hyunju
TI Siah Ubiquitin Ligases Modulate Nodal Signaling during Zebrafish
Embryonic Development
SO MOLECULES AND CELLS
LA English
DT Article
DE antivin/Lft1; body patterning; FoxH1/Fast1; Nodal; Siah2; zebrafish
ID 7 IN-ABSENTIA; TGF-BETA; TRANSCRIPTIONAL REPRESSOR;
CELL-DIFFERENTIATION; GENE-EXPRESSION; DEGRADATION; ORGANIZER; HOMOLOG;
ACTIVIN; PROTEIN
AB Siah2 is a zebrafish homologue of mammalian Siah family. Siah acts as an E3 ubiquitin ligase that binds proteins destined for degradation. Extensive homology between siah and Drosophila Siah homologue (sina) suggests their important physiological roles during embryonic development. However, detailed functional studies of Siah in vertebrate development have not been carried out. Here we report that Siah2 specifically augments nodal related gene expression in marginal blastomeres at late blastula through early gastrula stages of zebrafish embryos. Siah2 dependent Nodal signaling augmentation is confirmed by cell-based reporter gene assays using 293T cells and 3TPluciferase reporter plasmid. We also established a molecular hierarchy of Siah as a upstream regulator of FoxH1/Fast1 transcriptional factor in Nodal signaling. Elevated expression of nodal related genes by overexpression of Siah2 was enough to override the inhibitory effects of atv and lft2 on the Nodal signaling. In particular, E3 ubiquitin ligase activity of Siah2 is critical to limit the duration and/or magnitude of Nodal signaling. Additionally, since the embryos injected with Siah morpholinos mimicked the atv overexpression phenotype at least in part, our data support a model in which Siah is involved in mesendoderm patterning via modulating Nodal signaling.
C1 [Kang, Nami; Rhee, Myungchull; Ro, Hyunju] Chungnam Natl Univ, Dept Biol Sci, Coll Biosci & Biotechnol, Taejon 305764, South Korea.
[Won, Minho] Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, Program Genom Differentiat, NIH, Bethesda, MD USA.
RP Rhee, M (reprint author), Chungnam Natl Univ, Dept Biol Sci, Coll Biosci & Biotechnol, Taejon 305764, South Korea.
EM mrhee@cnu.ac.kr; rohyunju@cnu.ac.kr
FU Basic Science Research Program through the National Research Foundation
of Korea (NRF) - Ministry of Education, Science and Technology
[NRF-2012R1A1A4A01012264]
FX We thank I. B. Dawid (NIH-NICHD, USA) for the valuable comments for and
thorough reading of our manuscript. This research was supported by Basic
Science Research Program through the National Research Foundation of
Korea (NRF) funded by the Ministry of Education, Science and Technology
(NRF-2012R1A1A4A01012264).
NR 48
TC 3
Z9 3
U1 0
U2 2
PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
PI SEOUL
PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 1016-8478
EI 0219-1032
J9 MOL CELLS
JI Mol. Cells
PD MAY 31
PY 2014
VL 37
IS 5
BP 389
EP 398
DI 10.14348/molcells.2014.0032
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AQ1SF
UT WOS:000342560600005
PM 24823357
ER
PT J
AU Wu, WT
Jin, M
Wang, YJ
Liu, BY
Shen, DF
Chen, P
Hannes, S
Li, ZY
Hirani, SM
Jawad, S
Sen, HN
Chan, CC
Nussenblatt, RB
Wei, L
AF Wu, Wenting
Jin, Ming
Wang, Yujuan
Liu, Baoying
Shen, Defen
Chen, Ping
Hannes, Susan
Li, Zhiyu
Hirani, Sima
Jawad, Shayma
Sen, H. Nida
Chan, Chi-Chao
Nussenblatt, Robert B.
Wei, Lai
CA Unite Human Ocular Inflammat Conso
TI Overexpression of IL-17RC associated with ocular sarcoidosis
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE Ocular sarcoidosis; IL-17RC; CD8
ID GENOME-WIDE ASSOCIATION; CD4(+) T-CELLS; SUSCEPTIBILITY; MYCOBACTERIAL;
DISEASES; UVEITIS; BTNL2; GENE
AB Background: Sarcoidosis is a chronic inflammatory disease with a systemic granulomatous disorder affecting multiple organs including the eye. Both CD4(+) T cell and macrophage have been linked to the pathogenesis of the disease.
Methods: The expression of IL-17RC was measured using FACS, immunohistochemistry and real-time PCR. Serum level of IL-17 was detected using ELISA.
Results: An elevated expression of IL-17RC on CD8(+) T cells in peripheral blood was found in patients with ocular sarcoidosis as compared to healthy controls. Interestingly, we found a significant increase in the serum level of IL-17 in patients with ocular sarcoidosis as compared to healthy controls, which may be responsible for the induction of IL-17RC on CD8(+) cells. In addition, IL-17RC appeared only in the retinal tissue of the patient with clinically active sarcoidosis.
Conclusions: Our results suggested a potential involvement of IL-17RC(+) CD8(+) T cells in pathogenesis of ocular sarcoidosis.
C1 [Wu, Wenting; Wang, Yujuan; Liu, Baoying; Shen, Defen; Chen, Ping; Hannes, Susan; Li, Zhiyu; Hirani, Sima; Jawad, Shayma; Sen, H. Nida; Chan, Chi-Chao; Nussenblatt, Robert B.; Wei, Lai] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Wu, Wenting] Beijing Univ Chinese Med, Beijing, Peoples R China.
[Wu, Wenting; Jin, Ming] China Japan Friendship Hosp, Dept Ophthalmol, Beijing, Peoples R China.
[Wang, Yujuan; Wei, Lai] Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China.
RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM drbob@nei.nih.gov; weil9@mail.sysu.edu.cn
RI wang, yujuan/C-8428-2016
FU intramural research program of NEI; NCCAM
FX This study is supported by the intramural research program of NEI and
NCCAM.
NR 33
TC 7
Z9 7
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD MAY 31
PY 2014
VL 12
AR 152
DI 10.1186/1479-5876-12-152
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AK5NO
UT WOS:000338471800001
PM 24885153
ER
PT J
AU Spottiswoode, N
Duffy, PE
Drakesmith, H
AF Spottiswoode, Natasha
Duffy, Patrick E.
Drakesmith, Hal
TI Iron, anemia and hepcidin in malaria
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Review
DE hepcidin; malaria; iron; anemia; global health
ID PLASMODIUM-FALCIPARUM MALARIA; ANTIMICROBIAL PEPTIDE HEPCIDIN;
CONTROLLED-TRIAL; YOUNG-CHILDREN; SALMONELLA INFECTIONS; HELMINTH
INFECTIONS; PRESCHOOL-CHILDREN; INTRACELLULAR IRON; CHELATION-THERAPY;
DEFICIENCY ANEMIA
AB Malaria and iron have a complex but important relationship. Plasmodium proliferation requires iron, both during the clinically silent liver stage of growth and in the disease-associated phase of erythrocyte infection. Precisely how the protozoan acquires its iron from its mammalian host remains unclear, but iron chelators can inhibit pathogen growth in vitro and in animal models. In humans, iron deficiency appears to protect against severe malaria, while iron supplementation increases risks of infection and disease. Malaria itself causes profound disturbances in physiological iron distribution and utilization, through mechanisms that include hemolysis, release of heme, dyserythropoiesis, anemia, deposition of iron in macrophages, and inhibition of dietary iron absorption. These effects have significant consequences. Malarial anemia is a major global health problem, especially in children, that remains incompletely understood and is not straightforward to treat. Furthermore, the changes in iron metabolism during a malaria infection may modulate susceptibility to co-infections. The release of heme and accumulation of iron in granulocytes may explain increased vulnerability to non-typhoidal Salmonella during malaria. The redistribution of iron away from hepatocytes and into macrophages may confer host resistance to superinfection, whereby blood-stage parasitemia prevents the development of a second liver-stage Plasmodium infection in the same organism. Key to understanding the pathophysiology of iron metabolism in malaria is the activity of the iron regulatory hormone hepcidin. Hepcidin is upregulated during blood-stage parasitemia and likely mediates much of the iron redistribution that accompanies disease. Understanding the regulation and role of hepcidin may offer new opportunities to combat malaria and formulate better approaches to treat anemia in the developing world.
C1 [Spottiswoode, Natasha; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Bethesda, MD 20892 USA.
[Spottiswoode, Natasha; Drakesmith, Hal] Univ Oxford, Weatherall Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England.
RP Drakesmith, H (reprint author), Univ Oxford, Weatherall Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England.
EM hdrakes@hammer.imm.ox.ac.uk
FU Intramural Research Program of NIAID, NIH; NIH Oxford - Cambridge
Scholars Program; Medical Research Council, UK; Bill and Melinda Gates
Foundation
FX Natasha Spottiswoode and Patrick E. Duffy are supported by the
Intramural Research Program of NIAID, NIH. Natasha Spoutswoode was also
supported through the NIH Oxford - Cambridge Scholars Program during the
period of writing. Hal Drakesmith is supported by the Medical Research
Council, UK and by the Bill and Melinda Gates Foundation.
NR 105
TC 22
Z9 23
U1 4
U2 13
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PD MAY 30
PY 2014
VL 5
AR 125
DI 10.3389/fphar.2014.00125
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AX7KE
UT WOS:000347094100001
PM 24910614
ER
PT J
AU Yazawa, I
AF Yazawa, Itaru
TI Reciprocal functional interactions between the brainstem and the lower
spinal cord
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE entrainment; hyperoxic/normocapnic state; locomotion; locomotor pattern
generator; respiration
ID RESPIRATORY RHYTHM ENTRAINMENT; CENTRAL CHEMOSENSITIVITY; IN-VITRO; RAT;
STIMULATION; EXERCISE; VASOPRESSIN; MOUSE; BARORECEPTORS; CONTRACTIONS
AB The interplay of the neuronal discharge patterns regarding respiration and locomotion was investigated using electrophysiological techniques in a decerebrate and arterially perfused in situ mouse preparation. The phrenic, tibial, and/or peroneal nerve discharge became clearly organized into discharge episodes of increasing frequency and duration, punctuated by periods of quiescence as the perfusion flow rate increased at room temperature. The modulated sympathetic tone induced by the hyperoxic/normocapnic state was found to activate the locomotor pattern generator (LPG) via descending pathways and generate a left and right alternating discharge during discharge episodes in the motor nerves. The rhythm coupling of respiration and locomotion occurred at a 1:1 frequency ratio. Although the phrenic discharge synchronized with the tibial discharge at all flow rates tested, the time lag between peaks of the two discharges during locomotion was approximate to 400 ms rather than approximate to 200 ms, suggesting spinal feedback via ascending pathways. The incidence of the phrenic and tibial discharge episodes decreased by approximate to 50% after spinalization at the twelfth thoracic cord and the respiratory rhythm was more regular. These results indicate that: (i) locomotion can be generated in a hyperoxic/normocapnic state induced by specific respiratory conditions, (ii) the central mechanism regarding entrainment of respiratory and locomotor rhythms relies on spinal feedback via ascending pathways, initiated by the activated LPG generating locomotion, and (iii) the increase in respiratory rate seen during locomotion is caused not only by afferent mechanical and nociceptive inputs but also by impulses from the activated spinal cord producing a locomotor-like discharge via ascending pathways.
C1 [Yazawa, Itaru] NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA.
RP Yazawa, I (reprint author), Showa Univ, Sch Dent, Dept Oral Physiol, Shinagawa Ku, 1-5-8 Hatanodai, Tokyo 1428555, Japan.
EM yazawa-ns@umin.ac.jp
FU National Institute of Neurological Disorders and Stroke
FX This work was supported by the intramural program of the National
Institute of Neurological Disorders and Stroke. I thank Dr. A. E.
Pickering for his helpful comments regarding the manuscript.
NR 40
TC 4
Z9 4
U1 1
U2 1
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD MAY 30
PY 2014
VL 8
AR 124
DI 10.3389/fnins.2014.00124
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA AW8BB
UT WOS:000346484500001
PM 24910591
ER
PT J
AU Barroso, M
Florindo, C
Kalwa, H
Silva, Z
Turanov, AA
Carlson, BA
de Almeida, IT
Blom, HJ
Gladyshev, VN
Hatfield, DL
Michel, T
Castro, R
Loscalzo, J
Handy, DE
AF Barroso, Madalena
Florindo, Cristina
Kalwa, Hermann
Silva, Zelia
Turanov, Anton A.
Carlson, Bradley A.
de Almeida, Isabel Tavares
Blom, Henk J.
Gladyshev, Vadim N.
Hatfield, Dolph L.
Michel, Thomas
Castro, Rita
Loscalzo, Joseph
Handy, Diane E.
TI Inhibition of Cellular Methyltransferases Promotes Endothelial Cell
Activation by Suppressing Glutathione Peroxidase 1 Protein Expression
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Cell Adhesion; Endothelial Cell; Glutathione Peroxidase; Oxidative
Stress; Selenoprotein; S-Adenosylhomocysteine; tRNA Methylation
ID S-ADENOSYLHOMOCYSTEINE CONCENTRATIONS; INTERCELLULAR-ADHESION
MOLECULE-1; SELENOCYSTEINE TRANSFER-RNA; THIOREDOXIN REDUCTASE;
HYDROGEN-PEROXIDE; CARDIOVASCULAR EVENTS; ARGININE METHYLATION; DNA
HYPOMETHYLATION; VASCULAR-DISEASE; OXIDATIVE STRESS
AB Background: Methylation of tRNA(Sec) facilitates the incorporation of selenocysteine at a UGA codon during translation. Results: Accumulation of the homocysteine precursor S-adenosylhomocysteine decreases tRNA(Sec) methylation, reducing glutathione peroxidase 1 expression and increasing oxidative stress-induced inflammatory activation of endothelial cells. Conclusion: Methylation modulates the expression of selenoproteins to regulate redox-dependent inflammatory pathways. Significance: Hypomethylation stress promotes a proatherogenic endothelial cell phenotype. S-Adenosylhomocysteine (SAH) is a negative regulator of most methyltransferases and the precursor for the cardiovascular risk factor homocysteine. We have previously identified a link between the homocysteine-induced suppression of the selenoprotein glutathione peroxidase 1 (GPx-1) and endothelial dysfunction. Here we demonstrate a specific mechanism by which hypomethylation, promoted by the accumulation of the homocysteine precursor SAH, suppresses GPx-1 expression and leads to inflammatory activation of endothelial cells. The expression of GPx-1 and a subset of other selenoproteins is dependent on the methylation of the tRNA(Sec) to the Um34 form. The formation of methylated tRNA(Sec) facilitates translational incorporation of selenocysteine at a UGA codon. Our findings demonstrate that SAH accumulation in endothelial cells suppresses the expression of GPx-1 to promote oxidative stress. Hypomethylation stress, caused by SAH accumulation, inhibits the formation of the methylated isoform of the tRNA(Sec) and reduces GPx-1 expression. In contrast, under these conditions, the expression and activity of thioredoxin reductase 1, another selenoprotein, is increased. Furthermore, SAH-induced oxidative stress creates a proinflammatory activation of endothelial cells characterized by up-regulation of adhesion molecules and an augmented capacity to bind leukocytes. Taken together, these data suggest that SAH accumulation in endothelial cells can induce tRNA(Sec) hypomethylation, which alters the expression of selenoproteins such as GPx-1 to contribute to a proatherogenic endothelial phenotype.
C1 [Barroso, Madalena; Kalwa, Hermann; Michel, Thomas; Loscalzo, Joseph; Handy, Diane E.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA.
[Turanov, Anton A.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Barroso, Madalena; Florindo, Cristina; de Almeida, Isabel Tavares; Castro, Rita] Univ Lisbon, Res Inst Med & Pharmaceut Sci iMed UL, Fac Pharm, P-1649004 Lisbon, Portugal.
[de Almeida, Isabel Tavares; Castro, Rita] Univ Lisbon, Fac Pharm, Dept Biochem & Human Biol, P-1649004 Lisbon, Portugal.
[Silva, Zelia] Univ Nova Lisboa, Fac Ciencias Med, Dept Imunol, Chron Dis Res Ctr, P-1099085 Lisbon, Portugal.
[Carlson, Bradley A.; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Mouse Canc Genet Program, NIH, Bethesda, MD 20892 USA.
[Blom, Henk J.] Univ Hosp, Ctr Pediat & Adolescent Med, Dept Gen Pediat, D-79106 Freiburg, Germany.
RP Handy, DE (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM dhandy@rics.bwh.harvard.edu
RI Castro, Rita /G-7731-2011; silva, zelia/O-7243-2015; iMed.ULisboa,
iMed.ULisboa/C-6292-2014; iMed.ULisboa, MetGen /B-5293-2014; Faculdade
de Ciencias Medicas, Nova Medical School/K-6209-2013;
OI Castro, Rita /0000-0002-4585-0741; silva, zelia/0000-0001-6660-426X;
Blom, Henk/0000-0001-5202-9241; Florindo, Cristina/0000-0002-0664-5411
FU National Institutes of Health [HL067195, HL070819, HL048743, HL107192,
HL108630, HL46457, HL48743, GM061603]; American Heart Association;
Portuguese Fundacao para a Ciencia e a Tecnologia
[PTDC/SAU-ORG/112683/2009, SFRH/BD/73021/2010]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants HL067195, HL070819, HL048743, HL107192, and HL108630 (to
J. L.); HL46457 and HL48743 (to T. M.); and GM061603 (to V. N. G.). This
work was also supported by an American Heart Association postdoctoral
fellowship grant (to H. K.) and by Portuguese Fundacao para a Ciencia e
a Tecnologia Grants PTDC/SAU-ORG/112683/2009 (to R. C.) and
SFRH/BD/73021/2010 (M. B.).
NR 65
TC 7
Z9 7
U1 1
U2 12
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 30
PY 2014
VL 289
IS 22
BP 15350
EP 15362
DI 10.1074/jbc.M114.549782
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AJ2DL
UT WOS:000337465400019
PM 24719327
ER
PT J
AU Bollmann, F
Wu, ZX
Oelze, M
Siuda, D
Xia, N
Henke, J
Daiber, A
Li, HG
Stumpo, DJ
Blackshear, PJ
Kleinert, H
Pautz, A
AF Bollmann, Franziska
Wu, Zhixiong
Oelze, Matthias
Siuda, Daniel
Xia, Ning
Henke, Jenny
Daiber, Andreas
Li, Huige
Stumpo, Deborah J.
Blackshear, Perry J.
Kleinert, Hartmut
Pautz, Andrea
TI Endothelial Dysfunction in Tristetraprolin-deficient Mice Is Not Caused
by Enhanced Tumor Necrosis Factor-alpha Expression
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Atherosclerosis; Endothelial Dysfunction; NADPH Oxidase; Reactive
Nitrogen Species; Reactive Oxygen Species (ROS); Tumor Necrosis Factor
(TNF)
ID FINGER PROTEIN TRISTETRAPROLIN; MESSENGER-RNA TURNOVER; NITRIC-OXIDE
SYNTHASE; RHEUMATOID-ARTHRITIS; GENE-EXPRESSION; TNF-ALPHA;
CARDIOVASCULAR MORTALITY; REDUCES ATHEROSCLEROSIS; CHRONIC INFLAMMATION;
VASCULAR-DISEASE
AB Cardiovascular events are important co-morbidities in patients with chronic inflammatory diseases like rheumatoid arthritis. Tristetraprolin (TTP) regulates pro-inflammatory processes through mRNA destabilization and therefore TTP-deficient mice (TTP-/- mice) develop a chronic inflammation resembling human rheumatoid arthritis. We used this mouse model to evaluate molecular signaling pathways contributing to the enhanced atherosclerotic risk in chronic inflammatory diseases. In the aorta of TTP-/- mice we observed elevated mRNA expression of known TTP targets like tumor necrosis factor- (TNF-) and macrophage inflammatory protein-1, as well as of other pro-atherosclerotic mediators, like Calgranulin A, Cathepsin S, and Osteopontin. Independent of cholesterol levels TTP-/- mice showed a significant reduction of acetylcholine-induced, nitric oxide-mediated vasorelaxation. The endothelial dysfunction in TTP-/- mice was associated with increased levels of reactive oxygen and nitrogen species (RONS), indicating an enhanced nitric oxide inactivation by RONS in the TTP-/- animals. The altered RONS generation correlates with increased expression of NADPH oxidase 2 (Nox2) resulting from enhanced Nox2 mRNA stability. Although TNF- is believed to be a central mediator of inflammation-driven atherosclerosis, genetic inactivation of TNF- neither improved endothelial function nor normalized Nox2 expression or RONS production in TTP-/- animals. Systemic inflammation caused by TTP deficiency leads to endothelial dysfunction. This process is independent of cholesterol and not mediated by TNF- solely. Thus, other mediators, which need to be identified, contribute to enhanced cardiovascular risk in chronic inflammatory diseases.
C1 [Bollmann, Franziska; Wu, Zhixiong; Siuda, Daniel; Xia, Ning; Henke, Jenny; Li, Huige; Kleinert, Hartmut; Pautz, Andrea] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Pharmacol, D-55131 Mainz, Germany.
[Bollmann, Franziska; Siuda, Daniel] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Thrombosis & Hemostasis, D-55131 Mainz, Germany.
[Oelze, Matthias] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Med Clin 2, D-55131 Mainz, Germany.
[Stumpo, Deborah J.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
RP Kleinert, H (reprint author), Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Pharmacol, D-55131 Mainz, Germany.
EM kleinert@mail.uni-mainz.de; pautz@uni-mainz.de
RI Xia, Ning/P-3535-2015; Li, Huige/M-2662-2013
OI Li, Huige/0000-0003-3458-7391
FU Federal Ministry of Education and Research [BMBF 01EO1003]; Innovation
Foundation of the State of Rhineland-Palatinate [961-386261/917K];
Deutsche Forschungsgemeinschaft [LI 1759/1-1]
FX This work was supported by Federal Ministry of Education and Research
Grant BMBF 01EO1003, Innovation Foundation of the State of
Rhineland-Palatinate Grant 961-386261/917K, and Deutsche
Forschungsgemeinschaft Grant LI 1759/1-1 (to H. K.).
NR 70
TC 2
Z9 2
U1 0
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 30
PY 2014
VL 289
IS 22
BP 15653
EP 15665
DI 10.1074/jbc.M114.566984
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AJ2DL
UT WOS:000337465400047
PM 24727475
ER
PT J
AU Nakajima, T
Sato, K
Hanaoka, H
Watanabe, R
Harada, T
Choyke, PL
Kobayashi, H
AF Nakajima, Takahito
Sato, Kazuhide
Hanaoka, Hirofumi
Watanabe, Rira
Harada, Toshiko
Choyke, Peter L.
Kobayashi, Hisataka
TI The effects of conjugate and light dose on photo-immunotherapy induced
cytotoxicity
SO BMC CANCER
LA English
DT Article
DE Photoimmunotherapy; Near infrared light; Light dose; Necrosis;
Cytotoxicity
ID NEAR-INFRARED PHOTOIMMUNOTHERAPY; CELLS IN-VITRO; FLUORESCENT PROTEINS;
CELLULAR-DYNAMICS; UVC IRRADIATION; CANCER-CELLS; VIVO; EFFICACY; GFP;
MICE
AB Background: Photoimmunotherapy (PIT) is a highly cell-selective cancer therapy, which employs monoclonal antibodies conjugated to a potent photosensitizer (mAb-IR700). Once the conjugate has bound to the target cell, exposure to near infrared (NIR) light induces necrosis only in targeted cells with minimal damage to adjacent normal cells in vivo. Herein, we report on the effect of altering mAb-IR700 and light power and dose on effectiveness of PIT.
Methods: For evaluating cytotoxicity, we employed ATP-dependent bioluminescence imaging using a luciferase-transfected MDA-MB-468luc cell line, which expresses EGFR and luciferase. In in vitro experiments, panitumumab-IR700 (Pan-IR700) concentration was varied in combination with varying NIR light doses administered by an LED at one of three power settings, 100 mA and 400 mA continuous wave and 1733 mA intermittent wave. For in vivo experiments, the MDA-MB-468luc orthotopic breast cancer was treated with varying doses of Pan-IR700 and light.
Results: The in vitro cell study demonstrated that PIT induced cytotoxicity depended on light dose, when the conjugate concentration was kept constant. Increasing the dose of Pan-IR700 allowed lowering of the light dose to achieve equal effects thus indicating that for a given level of efficacy, the conjugate concentration multiplied by the light dose was a constant. A similar relationship between conjugate and light dose was observed in vivo.
Conclusions: The efficacy of PIT is defined by the product of the number of bound antibody conjugates and the dose of NIR light and can be achieve equally with continuous and pulse wave LED light using different power densities.
C1 [Nakajima, Takahito; Sato, Kazuhide; Hanaoka, Hirofumi; Watanabe, Rira; Harada, Toshiko; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room B3B69,MSC 1088, Bethesda, MD 20892 USA.
EM Kobayash@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 15
TC 6
Z9 6
U1 1
U2 17
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD MAY 30
PY 2014
VL 14
AR 389
DI 10.1186/1471-2407-14-389
PG 7
WC Oncology
SC Oncology
GA AJ2ZF
UT WOS:000337533500001
PM 24885589
ER
PT J
AU Cassetti, MC
Halstead, SB
AF Cassetti, M. Cristina
Halstead, Scott B.
TI Consultation on dengue vaccines: Progress in understanding protection,
26-28 June 2013, Rockville, Maryland
SO VACCINE
LA English
DT Article
DE Dengue; Dengue virus; Dengue hemorrhagic fever; Severe dengue; Vaccine;
Immunopathogenesis; Acquired immunity; T cell immunity; Innate immunity
ID IN-DEPTH ANALYSIS; VIRUS-INFECTION; HEMORRHAGIC-FEVER; ENVELOPE PROTEIN;
THAI VILLAGES; TRANSMISSION; ANTIBODIES; IMMUNIZATION; PATHOGENESIS;
CHILDREN
AB There is an unmet need for a dengue vaccine to further prevent the spread of this disease and contain the growing pandemic. To this end several vaccine companies and academic groups are actively pursuing the development of a tetravalent vaccine to prevent dengue. In the last few years progress has been made in this area, including the first results of a vaccine efficacy trial and improved understanding of the immune responses to the infection. Despite this progress, development of dengue vaccines faces important challenges including the need for a vaccine that induces balanced immune responses against all dengue strains and an incomplete understanding of the mechanism(s) of protection against infection and disease. This is a summary of a Consultation on dengue vaccines held in June 26-28,2013 by the National Institute of Allergy and Infectious Diseases (part of the US National Institutes of Health) and the Dengue Vaccine Initiative (part of the International Vaccine Institute). The primary goal of this consultation was to review the progress in dengue vaccine development, evaluate the known mechanism of protection of dengue vaccines and discuss avenues for future research.
C1 [Cassetti, M. Cristina] NIAID, NIH, Bethesda, MD 20892 USA.
[Halstead, Scott B.] Int Vaccine Inst, Dengue Vaccine Initiat, Seoul, South Korea.
RP Halstead, SB (reprint author), 5824 Edson Lane N, Bethesda, MD 20852 USA.
EM halsteads@erols.com
FU Sanofipasteur, Lyons, France, Takeda Pharmaceuticals, Chicago, Illinois,
the Bill and Melinda Gates Foundation, Seattle, Washington [24050]
FX This meeting received organizational support from the Henry M Jackson
Foundation, Bethesda, Maryland and financial support from Sanofipasteur,
Lyons, France, Takeda Pharmaceuticals, Chicago, Illinois, the Bill and
Melinda Gates Foundation, Seattle, Washington (Contract # 24050) No
grant numbers for sanofi or Takeda grants to the Jackson Foundation and
the NIH Office of Rare Diseases.
NR 39
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD MAY 30
PY 2014
VL 32
IS 26
BP 3115
EP 3121
DI 10.1016/j.vaccine.2014.04.017
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AI4YL
UT WOS:000336872500001
PM 24768502
ER
PT J
AU Maximova, OA
Speicher, JM
Skinner, JR
Murphy, BR
St Claire, MC
Ragland, DR
Herbertd, RL
Pare, DR
Moore, RM
Pletnev, AG
AF Maximova, Olga A.
Speicher, James M.
Skinner, Jeff R.
Murphy, Brian R.
St Claire, Marisa C.
Ragland, Danny R.
Herbertd, Richard L.
Pare, Dan R.
Moore, Rashida M.
Pletnev, Alexander G.
TI Assurance of neuroattenuation of a live vaccine against West Nile virus:
A comprehensive study of neuropathogenesis after infection with chimeric
WN/DEN4 Delta 30 vaccine in comparison to two parental viruses and a
surrogate flavivirus reference vaccine
SO VACCINE
LA English
DT Article
DE West Nile virus (WNV); Live attenuated WNV vaccine; Neuropathogenesis;
Neurovirulence; Nonhuman primates
ID HEALTHY-ADULTS; UNITED-STATES; PRECLINICAL EVALUATION; NEUTRALIZING
ANTIBODY; PROTECTIVE EFFICACY; RHESUS-MONKEYS; CLINICAL-TRIAL; PHASE-II;
IMMUNOGENICITY; DISEASE
AB The upsurge of West Nile virus (WNV) human infections in 2012 suggests that the US can expect periodic WNV outbreaks in the future. Availability of safe and effective vaccines against WNV in endemic areas, particularly for aging populations that are at high risk of West Nile neuroinvasive disease (WNND), could be beneficial. WN/DEN4 Delta 30 is a live, attenuated chimeric vaccine against WNV produced by replacement of the genes encoding the pre-membrane and envelope protein genes of the vaccine virus against dengue virus type 4 (DEN4 Delta 30) with corresponding sequences derived from a wild type WNV. Following intrathalamic inoculation of nonhuman primates (NHPs), a comprehensive neuropathogenesis study was performed and neurovirulence of WN/DEN4 Delta 30 vaccine candidate was compared to that of two parental viruses (i.e., WNV and DEN4 Delta 30), as well as to that of an attenuated flavivirus surrogate reference (i.e., yellow fever YF 17D). Clinical and virological data, as well as results of a semi-quantitative histopathological analysis, demonstrated that WN/DEN4 Delta 30 vaccine is highly attenuated for the central nervous system (CNS) of NHPs in comparison to a wild type WNV. Importantly, based on the virus replicative ability in the CNS of NHPs and the degree of induced histopathological changes, the level of neuroattenuation of WN/DEN4 Delta 30 vaccine was similar to that of YF 17D, and therefore within an acceptable range. In addition, we show that the DEN4 Delta 30 vaccine tested in this study also has a low neurovirulence profile. In summary, our results demonstrate a high level of neuroattenuation of two vaccine candidates, WN/DEN4 Delta 30 and DEN4 Delta 30. We also show here a remarkable sensitivity of our WNV-NY99 NHP model, as well as striking resemblance of the observed neuropathology to that seen in human WNND. These results support the use of this NHP model for translational studies of WNV neuropathogenesis and/or testing the effectiveness of vaccines and therapeutic approaches. Published by Elsevier Ltd.
C1 [Maximova, Olga A.; Speicher, James M.; Murphy, Brian R.; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Skinner, Jeff R.] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA.
[St Claire, Marisa C.; Ragland, Danny R.] NIAID, Off Chief Scientist, Integrated Res Facil, NIH, Frederick, MD 21702 USA.
[Herbertd, Richard L.; Pare, Dan R.; Moore, Rashida M.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Maximova, OA (reprint author), NIAID, Infect Dis Lab, NIH, 33 North Dr, Bethesda, MD 20892 USA.
EM maximovao@niaid.nih.gov; apletnev@niaid.nih.gov
FU NIAID Intramural Research Program
FX We acknowledge Lawrence Faucette, Marina Rahman, Katherine Shea, Marsha
Abramson, Sarah Rovezzi, Dr. Robin Kastenmayer, and Dr. William Elkins
(Comparative Medicine Branch, NIAID, NIH), Russell Byrum (Integrated
Research Facility, NIAID, NIH), Dr. Dzung Thach and Anthony Gresko
(Laboratory of Infectious Diseases, NIAID, NIH), and Dr. Shari
Price-Schiavi and the staff of the Pathology Associates Division of
Charles River Laboratories (Frederick, MD) for their most valuable help
with animal experiments and excellent technical support. We also thank
Dr. Jeffrey Cohen, Dr. Jeffrey Taubenberger, and Dr. Stephen Whitehead
(Laboratory of Infectious Diseases, NIAID, NIH) for their support,
helpful discussions and critical reading of the manuscript. This work
was supported by funds provided by the NIAID Intramural Research
Program.
NR 49
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U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD MAY 30
PY 2014
VL 32
IS 26
BP 3187
EP 3197
DI 10.1016/j.vaccine.2014.04.002
PG 11
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AI4YL
UT WOS:000336872500012
PM 24736001
ER
PT J
AU Donahue, RN
Duncan, BB
Fry, TJ
Jones, B
Bachovchin, WW
Kiritsy, CP
Lai, JH
Wu, WG
Zhao, P
Liu, YX
Tsang, KY
Hodge, JW
AF Donahue, Renee N.
Duncan, Brynn B.
Fry, Terry J.
Jones, Barry
Bachovchin, William W.
Kiritsy, Christopher P.
Lai, Jack H.
Wu, Wengen
Zhao, Peng
Liu, Yuxin
Tsang, Kwong-Yok
Hodge, James W.
TI A pan inhibitor of DASH family enzymes induces immunogenic modulation
and sensitizes murine and human carcinoma cells to antigen-specific
cytotoxic T lymphocyte killing: implications for combination therapy
with cancer vaccines
SO VACCINE
LA English
DT Article
DE Immunogenic modulation; T-cell response; DASH family enzymes;
Immunotherapy; Vaccine
ID DIPEPTIDYL-PEPTIDASE-IV; ANTITUMOR RESPONSES; CHEMOTHERAPY; EXPRESSION;
POTENT; IMMUNOTHERAPY; IRRADIATION; VACCINATION; GENERATION; TALABOSTAT
AB Recent studies have suggested that pan inhibitors of dipeptidyl peptidase-4 activity and/or structure homologs (DASH), including ARI-4175, can mediate tumor regression by immune-mediated mechanisms. This study assessed the potential of combining ARI-4175 with cancer vaccines. We evaluated ARI-4175's effect on immunogenic modulation, ability to sensitize tumor cells to antigen-specific CTL killing, effect on immune-cell subsets and function, and antitumor activity in 2 tumor models, both as a monotherapy and in combination with a recombinant viral or dendritic cell (DC)-based tumor-cell vaccine.
ARI-4175's effects on the growth, surface phenotype, and antigen-specific CTL-mediated lysis of murine and human carcinoma cell lines were assessed in vitro. In vivo, C57BL-6 mice were treated orally with ARI-4175, after which splenocytes were assessed by flow cytometry and functional assays. Antitumor studies were performed in murine models of colon carcinoma (MC38-CEA(+) in CEA-transgenic C57BL6 mice) and rhabdomyosarcoma (M3-9-M in C57BL-6 mice). Mice received oral ARI-4175 alone or in combination with a vaccine consisting of recombinant vaccinia/fowlpox CEA-TRICOM (colon model) or a DC-based tumor-cell vaccine (rhabdomyosarcoma model).
Exposure to ARI-4175 had no effect on the proliferation or viability of carcinoma cells in vitro; however, it did alter tumor phenotype, making murine and human tumor cells more sensitive to antigen-specific CTL killing. Assessment of immune-cell subsets and function indicated that ARI-4175 increased levels of natural killer cells and DCs. Detrimental immune effects, including reduced T effector cells and increased immunosuppressive cells (Tregs, MDSCs), were normalized when treatment stopped, suggesting that scheduling is critical when combining this agent with vaccine. As a monotherapy, ARI-4175 had potent antitumor activity in both tumor models, and had even greater effects when combined with a vaccine (either DC-based or poxviral vector based). These findings provide the rationale for the combined use of cancer immunotherapy with DASH enzyme inhibitors such as ARI-4175. Published by Elsevier Ltd.
C1 [Donahue, Renee N.; Tsang, Kwong-Yok; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Duncan, Brynn B.; Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Jones, Barry; Bachovchin, William W.; Lai, Jack H.; Wu, Wengen; Zhao, Peng; Liu, Yuxin] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA.
[Bachovchin, William W.; Kiritsy, Christopher P.; Lai, Jack H.] Arisaph Pharmaceut, Boston, MA USA.
RP Hodge, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM renee.donahue@nih.gov; bbd6@georgetown.edu; fryt@mail.nih.gov;
Barry.jones@tufts.edu; william.bachoychin@tufts.edu;
ckiritsy@arisaph.com; Jack.Lai@tufts.edu; Wengen.Wu@tufts.edu;
Peng.Zhao@tufts.edu; Yu.Liu@tufts.edu; tsangkwo@mail.nih.gov;
hodgej@mail.nih.gov
RI Hodge, James/D-5518-2015
OI Hodge, James/0000-0001-5282-3154
FU Intramural Research Program of the Center for Cancer Research; National
Cancer Institute; Intramural Program, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, Intramural
Program, National Institutes of Health.
NR 33
TC 3
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U1 0
U2 10
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD MAY 30
PY 2014
VL 32
IS 26
BP 3223
EP 3231
DI 10.1016/j.vaccine.2014.04.008
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AI4YL
UT WOS:000336872500017
PM 24731809
ER
PT J
AU Sagar, D
Masih, S
Schell, T
Jacobson, S
Comber, JD
Philip, R
Wigdahl, B
Jain, P
Khan, ZK
AF Sagar, Divya
Masih, Shet
Schell, Todd
Jacobson, Steven
Comber, Joseph D.
Philip, Ramila
Wigdahl, Brian
Jain, Pooja
Khan, Zafar K.
TI In vivo immunogenicity of Tax(11-19) epitope in HLA-A2/DTR transgenic
mice: Implication for dendritic cell-based anti-HTLV-1 vaccine
SO VACCINE
LA English
DT Article
DE HTLV-1; Tax; Dendritic cells; HLA-A2.1 transgenic mice; CD11c-DTR
transgenic mice
ID VIRUS TYPE-I; CD8(+) T-CELLS; MURINE LEUKEMIA-VIRUS; MYELIN
BASIC-PROTEIN; TOLERANCE INDUCTION; TAX PROTEIN; TYPE-1 TAX; HTLV-I;
AUTOIMMUNE ENCEPHALOMYELITIS; NEUROLOGICAL DISEASE
AB Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR hybrid mouse strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund's adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-beta was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly hybrid mouse strain could be used for investigating DC involvement in human class-I-restricted immune responses. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Sagar, Divya; Masih, Shet; Jain, Pooja; Khan, Zafar K.] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Drexel Inst Biotechnol & Virol Res, Philadelphia, PA 19104 USA.
[Schell, Todd] Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA USA.
[Jacobson, Steven] NIH, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA.
[Comber, Joseph D.; Philip, Ramila] Immunotope Inc, Doylestown, PA USA.
[Wigdahl, Brian] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA.
[Wigdahl, Brian] Drexel Univ, Coll Med, Inst Mol Med & Infect Dis, Ctr Mol Virol & Translat Neurosci, Philadelphia, PA 19104 USA.
RP Jain, P (reprint author), Drexel Univ, Coll Med, Drexel Inst Biotechnol & Virol Res, Dept Microbiol & Immunol, 3805 Old Easton Rd, Doylestown, PA 18902 USA.
EM pooja.jain@drexelmed.edu; zkhan@drexelmed.edu
OI Masih, Shet/0000-0003-1920-476X; Philip, Ramila/0000-0003-1530-7665
FU Public Health Service, National Institutes of Health [NIAID R21
AI093172-01]; NIAID [R01 AI077414]; NCI [R01]
FX This work was supported by the Public Health Service, National
Institutes of Health, grant NIAID R21 AI093172-01 to ZKK. Supports
through NIAID R01 AI077414 to PJ and NCI R01 to BW/PJ are also
acknowledged. We also wish to acknowledge the kind gift of SP2/0
transfectants secreting mouse recombinant Flt-3L from Dr. Robert
Rottapel, Ontario Cancer Institute, Toronto, Canada. Both strains of
mice were purchased from Jackson Laboratories, which helped in obtaining
permission to cross-breed from the original source of these mice and
requested acknowledgment of Dr. Dan Littman for B6.FVB-Tg Itgax-DTR/EGFP
57Lan/J (CD11c-DTR) mice.
NR 65
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U2 3
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PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD MAY 30
PY 2014
VL 32
IS 26
BP 3274
EP 3284
DI 10.1016/j.vaccine.2014.03.087
PG 11
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AI4YL
UT WOS:000336872500024
PM 24739247
ER
PT J
AU Massart, R
Suderman, M
Provencal, N
Yi, C
Bennett, AJ
Suomi, S
Szyf, M
AF Massart, R.
Suderman, M.
Provencal, N.
Yi, C.
Bennett, A. J.
Suomi, S.
Szyf, M.
TI HYDROXYMETHYLATION AND DNA METHYLATION PROFILES IN THE PREFRONTAL CORTEX
OF THE NON-HUMAN PRIMATE RHESUS MACAQUE AND THE IMPACT OF MATERNAL
DEPRIVATION ON HYDROXYMETHYLATION
SO NEUROSCIENCE
LA English
DT Article
DE monkeys; hydroxymethylation; brain; early-adversity; rearing; maternal
deprivation
ID EMBRYONIC STEM-CELLS; EARLY-LIFE STRESS; EPIGENETIC REGULATION; EARLY
EXPERIENCE; BASE-RESOLUTION; GENE-EXPRESSION; THYMINE DNA; HUMAN BRAIN;
5-HYDROXYMETHYLCYTOSINE; ENVIRONMENT
AB 5-Hydroxymethylcytosine (5hmC) is abundant in the brain, suggesting an important role in epigenetic control of neuronal functions. In this paper, we show that 5hmC and 5-methylcytosine (5mC) levels are coordinately distributed in gene promoters of the rhesus macaque prefrontal cortex. Although promoter hydroxymethylation and methylation are overall negatively correlated with expression, a subset of highly expressed genes involved in specific cerebral functions is associated with high levels of 5mC and 5hmC. These relationships were also observed in the mouse cortex. Furthermore, we found that early-life maternal deprivation is associated, in the adult monkey cortex, with DNA hydroxymethylation changes of promoters of genes related to neurological functions and psychological disorders. These results reveal that early social adversity triggers variations in brain DNA hydroxymethylation that could be detected in adulthood. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Massart, R.; Suderman, M.; Provencal, N.; Yi, C.; Szyf, M.] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada.
[Provencal, N.; Szyf, M.] McGill Univ, Sackler Program Epigenet & Dev Psychobiol, Montreal, PQ H3G 1Y6, Canada.
[Provencal, N.] Univ Montreal, Res Unit Childrens Psychosocial Maladjustment, Montreal, PQ H3T 1C5, Canada.
[Provencal, N.] Univ Montreal, St Justine Hosp, Res Ctr, Montreal, PQ H3T 1C5, Canada.
[Bennett, A. J.; Suomi, S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA.
[Bennett, A. J.] Univ Wisconsin, Dept Psychol, Madison, WI 53715 USA.
[Bennett, A. J.] Univ Wisconsin, Harlow Ctr Biol Psychol, Madison, WI 53715 USA.
RP Suomi, S (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, DHHS, Bethesda, MD 20892 USA.
EM suomis@lce.nichd.nih.gov; moshe.szyf@mcgill.ca
FU Canadian Institute of Health Research (CIHR); Sackler Program in
Psychobiology and Epigenetics at McGill University; European Research
Area-Neuron Network (ERA-NET NEURON); Division of Intramural Research,
Eunice Kennedy Shriver National Institutes of Child Health and Human
Development (NICHD), National Institutes of Health (NIH)
FX Supported by a grant from the Canadian Institute of Health Research
(CIHR) to M. S. and the Sackler Program in Psychobiology and Epigenetics
at McGill University to MS and a grant from the European Research
Area-Neuron Network (ERA-NET NEURON) to M. S. and by funds from the
Division of Intramural Research, Eunice Kennedy Shriver National
Institutes of Child Health and Human Development (NICHD), National
Institutes of Health (NIH). S. S. is a fellow of the Canadian Institute
for Advanced Research. We would like to thank Claire Guillemin, Angela
Ruggiero, Dongsha Wang, Peter J. Pierre, David P. Friedman for their
technical assistance and discussions. The authors declare no conflict of
interest.
NR 64
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U1 0
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
EI 1873-7544
J9 NEUROSCIENCE
JI Neuroscience
PD MAY 30
PY 2014
VL 268
BP 139
EP 148
DI 10.1016/j.neuroscience.2014.03.021
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA AG6AX
UT WOS:000335501900013
PM 24657458
ER
PT J
AU Lee, JE
Ge, K
AF Lee, Ji-Eun
Ge, Kai
TI Transcriptional and epigenetic regulation of PPAR gamma expression
during adipogenesis
SO CELL AND BIOSCIENCE
LA English
DT Review
DE PPAR gamma; Adipogenesis; Transcriptional regulation; Enhancer;
Epigenetic regulation; Histone acetylation; Histone methylation;
Chromatin remodeling
ID ACTIVATED-RECEPTOR-GAMMA; FAMILIAL PARTIAL LIPODYSTROPHY; LYSINE-4
METHYLTRANSFERASE COMPLEX; ADIPOCYTE DIFFERENTIATION; HISTONE H3;
C/EBP-ALPHA; BINDING-PROTEINS; GENOME-WIDE; IN-VIVO; CELL
DIFFERENTIATION
AB The nuclear receptor PPAR gamma is a master regulator of adipogenesis. PPAR gamma is highly expressed in adipose tissues and its expression is markedly induced during adipogenesis. In this review, we describe the current knowledge, as well as future directions, on transcriptional and epigenetic regulation of PPAR gamma expression during adipogenesis. Investigating the molecular mechanisms that control PPAR gamma expression during adipogenesis is critical for understanding the development of white and brown adipose tissues, as well as pathological conditions such as obesity and diabetes. The robust induction of PPAR gamma expression during adipogenesis also serves as an excellent model system for studying transcriptional and epigenetic regulation of cell-type-specific gene expression.
C1 [Lee, Ji-Eun; Ge, Kai] NIDDK, Adipocyte Biol & Gene Regulat Sect, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
RP Ge, K (reprint author), NIDDK, Adipocyte Biol & Gene Regulat Sect, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
EM kaig@niddk.nih.gov
RI Lee, Ji-Eun/F-7891-2011
OI Lee, Ji-Eun/0000-0002-3768-7016
NR 104
TC 27
Z9 27
U1 7
U2 32
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD MAY 29
PY 2014
VL 4
AR 29
DI 10.1186/2045-3701-4-29
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AJ0BK
UT WOS:000337313800001
PM 24904744
ER
PT J
AU Robinson, TP
Wint, GRW
Conchedda, G
Van Boeckel, TP
Ercoli, V
Palamara, E
Cinardi, G
D'Aietti, L
Hay, SI
Gilbert, M
AF Robinson, Timothy P.
Wint, G. R. William
Conchedda, Giulia
Van Boeckel, Thomas P.
Ercoli, Valentina
Palamara, Elisa
Cinardi, Giuseppina
D'Aietti, Laura
Hay, Simon I.
Gilbert, Marius
TI Mapping the Global Distribution of Livestock
SO PLOS ONE
LA English
DT Article
ID AVIAN INFLUENZA; DOMESTIC DUCKS; CLIMATE-CHANGE; LAND-COVER; AFRICA;
SYSTEMS; ASIA; TRYPANOSOMOSIS; DYNAMICS; THAILAND
AB Livestock contributes directly to the livelihoods and food security of almost a billion people and affects the diet and health of many more. With estimated standing populations of 1.43 billion cattle, 1.87 billion sheep and goats, 0.98 billion pigs, and 19.60 billion chickens, reliable and accessible information on the distribution and abundance of livestock is needed for a many reasons. These include analyses of the social and economic aspects of the livestock sector; the environmental impacts of livestock such as the production and management of waste, greenhouse gas emissions and livestock-related land-use change; and large-scale public health and epidemiological investigations. The Gridded Livestock of the World (GLW) database, produced in 2007, provided modelled livestock densities of the world, adjusted to match official (FAOSTAT) national estimates for the reference year 2005, at a spatial resolution of 3 minutes of arc (about 5x5 km at the equator). Recent methodological improvements have significantly enhanced these distributions: more up-to date and detailed sub-national livestock statistics have been collected; a new, higher resolution set of predictor variables is used; and the analytical procedure has been revised and extended to include a more systematic assessment of model accuracy and the representation of uncertainties associated with the predictions. This paper describes the current approach in detail and presents new global distribution maps at 1 km resolution for cattle, pigs and chickens, and a partial distribution map for ducks. These digital layers are made publically available via the Livestock Geo-Wiki (http://www.livestock.geo-wiki.org), as will be the maps of other livestock types as they are produced.
C1 [Robinson, Timothy P.] ILRI, Livestock Syst & Environm Res Theme LSE, Nairobi, Kenya.
[Robinson, Timothy P.; Conchedda, Giulia; Ercoli, Valentina; Palamara, Elisa; Cinardi, Giuseppina; D'Aietti, Laura] Food & Agr Org United Nations FAO, Anim Prod & Hlth Div AGA, Rome, Italy.
[Wint, G. R. William] Univ Oxford, Dept Zool, ERGO, Oxford OX1 3PS, England.
[Van Boeckel, Thomas P.; Gilbert, Marius] Univ Libre Brussels, Brussels, Belgium.
[Van Boeckel, Thomas P.; Gilbert, Marius] Fonds Natl Rech Sci, Brussels, Belgium.
[Van Boeckel, Thomas P.] Princeton Univ, Dept Biol, Dept Ecol & Evolutionary, Princeton, NJ 08544 USA.
[Van Boeckel, Thomas P.] Princeton Environm Inst, Princeton, NJ USA.
[Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
[Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Robinson, TP (reprint author), ILRI, Livestock Syst & Environm Res Theme LSE, Nairobi, Kenya.
EM t.robinson@cgiar.org
RI Hay, Simon/F-8967-2015;
OI Hay, Simon/0000-0002-0611-7272; Gilbert, Marius/0000-0003-3708-3359
FU Consultative Group on International Agricultural Research (CGIAR)
Research Programmes: Humidtropics; Climate Change, Agriculture and Food
Security (CCAFS); Agriculture for Nutrition and Health (A4NH); 'Fonds
National de la Recherche Scientifique' (FNRS); Wellcome Trust [095066];
Li Ka Shing Foundation; Research and Policy for Infectious Disease
Dynamics (RAPIDD) program of the Science & Technology Directorate,
Department of Homeland Security; Fogarty International Center (FIC);
Animal Production and Health Division (AGA) of the Food and Agriculture
Organization (FAO) of the United Nations: in particular the UK
Department for International Development (DFID); USAID; United States
NIH FIC grant [3R01TW007869-03, 1R56TW009502-01]; FNRS Projet de
Recherche (PDR) [T.0073.13]; National Institutes of Health (NIH)
FX TPR is funded by the following Consultative Group on International
Agricultural Research (CGIAR) Research Programmes: Humidtropics; Climate
Change, Agriculture and Food Security (CCAFS); and Agriculture for
Nutrition and Health (A4NH). MG & TPVB are funded by the 'Fonds National
de la Recherche Scientifique' (FNRS). SIH is funded by a Senior Research
Fellowship from the Wellcome Trust (#095066) and receives support from
the Li Ka Shing Foundation. SIH also acknowledges funding support from
the Research and Policy for Infectious Disease Dynamics (RAPIDD) program
of the Science & Technology Directorate, Department of Homeland
Security, and the Fogarty International Center (FIC), National
Institutes of Health (NIH). The bulk of this work was funded through
various programmes and projects within the Animal Production and Health
Division (AGA) of the Food and Agriculture Organization (FAO) of the
United Nations: in particular the UK Department for International
Development (DFID)-funded Pro-Poor Livestock Policy Initiative and the
USAID-funded Emerging Pandemic Threats Plus (EPT+) programme. Other
contributors include the United States NIH FIC grants: 3R01TW007869-03
and 1R56TW009502-01 and the FNRS Projet de Recherche (PDR) T.0073.13.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 65
TC 62
Z9 63
U1 13
U2 78
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 29
PY 2014
VL 9
IS 5
AR e96084
DI 10.1371/journal.pone.0096084
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3UR
UT WOS:000336790800001
PM 24875496
ER
PT J
AU Li, MX
Volker, J
Breslauer, KJ
Wilson, DM
AF Li, Mengxia
Voelker, Jens
Breslauer, Kenneth J.
Wilson, David M., III
TI APE1 Incision Activity at Abasic Sites in Tandem Repeat Sequences
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE APEX1; AP or abasic site; tandem repeat; telomere; trinucleotide
expansion
ID BASE EXCISION-REPAIR; HUMAN APURINIC ENDONUCLEASE; EQUILIBRIUM MELTING
CURVES; URACIL-DNA GLYCOSYLASE; REPLICATION PROTEIN-A; CELL NUCLEAR
ANTIGEN; BULGE LOOPS; APURINIC/APYRIMIDINIC ENDONUCLEASE;
NUCLEOTIDE-SEQUENCE; THERMODYNAMIC DATA
AB Repetitive DNA sequences, such as those present in microsatellites and minisatellites, telomeres, and trinucleotide repeats (linked to fragile X syndrome, Huntington disease, etc.), account for nearly 30% of the human genome. These domains exhibit enhanced susceptibility to oxidative attack to yield base modifications, strand breaks, and abasic sites; have a propensity to adopt non-canonical DNA forms modulated by the positions of the lesions; and, when not properly processed, can contribute to genome instability that underlies aging and disease development. Knowledge on the repair efficiencies of DNA damage within such repetitive sequences is therefore crucial for understanding the impact of such domains on genomic integrity. In the present study, using strategically designed oligonucleotide substrates, we determined the ability of human apurinic/apyrimidinic endonuclease 1 (APE1) to cleave at apurinic/apyrimidinic (AP) sites in a collection of tandem DNA repeat landscapes involving telomeric and CAG/CTG repeat sequences. Our studies reveal the differential influence of domain sequence, conformation, and AP site location/relative positioning on the efficiency of APE1 binding and strand incision. Intriguingly, our data demonstrate that APE1 endonuclease efficiency correlates with the thermodynamic stability of the DNA substrate. We discuss how these results have both predictive and mechanistic consequences for understanding the success and failure of repair protein activity associated with such oxidatively sensitive, conformationally plastic/dynamic repetitive DNA domains. Published by Elsevier Ltd.
C1 [Li, Mengxia; Wilson, David M., III] NIA, Lab Mol Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Voelker, Jens; Breslauer, Kenneth J.] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA.
[Breslauer, Kenneth J.] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA.
RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM wilsonda@mail.nih.gov
FU Intramural Research Program at the National Institutes of Health,
National Institute on Aging; National Institutes of Health [GM23509,
GM34469, CA47995]
FX We wish to thank Dr. Yie Liu (National Institute on Aging) and Dr. G.
Eric Plum (IBET Inc., Columbus, OH) for their constructive comments on
the manuscript. This research was supported by the Intramural Research
Program at the National Institutes of Health, National Institute on
Aging, and National Institutes of Health grants GM23509, GM34469, and
CA47995 (to K.J.B.).
NR 62
TC 5
Z9 6
U1 1
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD MAY 29
PY 2014
VL 426
IS 11
BP 2183
EP 2198
DI 10.1016/j.jmb.2014.03.014
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AI2PA
UT WOS:000336699300004
PM 24703901
ER
PT J
AU Volkow, ND
Frieden, TR
Hyde, PS
Cha, SS
AF Volkow, Nora D.
Frieden, Thomas R.
Hyde, Pamela S.
Cha, Stephen S.
TI Medication-Assisted Therapies - Tackling the Opioid-Overdose Epidemic
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID DEATHS
C1 [Volkow, Nora D.] NIDA, NIH, Bethesda, MD 20892 USA.
[Hyde, Pamela S.] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA.
[Cha, Stephen S.] Ctr Medicare Serv, Ctr Medicaid & CHIP Serv, Baltimore, MD USA.
[Cha, Stephen S.] Ctr Medicaid Serv, Ctr Medicaid & CHIP Serv, Baltimore, MD USA.
[Frieden, Thomas R.] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Volkow, ND (reprint author), NIDA, NIH, Bethesda, MD 20892 USA.
NR 5
TC 133
Z9 133
U1 3
U2 14
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAY 29
PY 2014
VL 370
IS 22
BP 2063
EP 2066
DI 10.1056/NEJMp1402780
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA AH9BM
UT WOS:000336434000003
PM 24758595
ER
PT J
AU Padmakumar, VC
Masiuk, KE
Luger, D
Lee, C
Coppola, V
Tessarollo, L
Hoover, SB
Karavanova, I
Buonanno, A
Simpson, RM
Yuspa, SH
AF Padmakumar, V. C.
Masiuk, Katelyn E.
Luger, Dror
Lee, Christina
Coppola, Vincenzo
Tessarollo, Lino
Hoover, Shelley B.
Karavanova, Irina
Buonanno, Andres
Simpson, R. Mark
Yuspa, Stuart H.
TI Detection of differential fetal and adult expression of chloride
intracellular channel 4 (CLIC4) protein by analysis of a green
fluorescent protein knock-in mouse line
SO BMC DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE CLIC4; GFP knockin; Fetal brain; Adult brain; Kidney function
ID DENSE-CORE VESICLES; GENE-EXPRESSION; MOLECULAR-CLONING; NUCLEAR
TRANSLOCATION; ION CHANNEL; CL-CHANNEL; RAT-BRAIN; CELLS; FAMILY; P64H1
AB Background: Chloride Intracellular Channel 4 (CLIC4) is one of seven members in the closely related CLIC protein family. CLIC4 is involved in multiple cellular processes including apoptosis, cellular differentiation, inflammation and endothelial tubulogenesis. Despite over a decade of research, no comprehensive in situ expression analysis of CLIC4 in a living organism has been reported. In order to fulfill this goal, we generated a knock-in mouse to express Green Fluorescent Protein (GFP) from the CLIC4 locus, thus substituting the GFP coding region for CLIC4. We used GFP protein expression to eliminate cross reaction with other CLIC family members.
Results: We analyzed CLIC4 expression during embryonic development and adult organs. During mid and late gestation, CLIC4 expression is modulated particularly in fetal brain, heart, thymus, liver and kidney as well as in developing brown adipose tissue and stratifying epidermis. In the adult mouse, CLIC4 is highly expressed globally in vascular endothelial cells as well as in liver, lung alveolar septae, pancreatic acini, spermatogonia, renal proximal tubules, cardiomyocytes and thymic epithelial cells. Neural expression included axonal tracks, olfactory bulb, Purkinje cell layer and dentate gyrus. Renal CLIC4 expression was most pronounced in proximal tubules, although altered renal function was not detected in the absence of CLIC4. Myeloid cells and B cells of the spleen are rich in CLIC4 expression as are CD4 and CD8 positive T cells.
Conclusions: In a comprehensive study detailing CLIC4 expression in situ in a mouse model that excludes cross reaction with other family members, we were able to document previously unreported expression for CLIC4 in developing fetus, particularly the brain. In addition, compartmentalized expression of CLIC4 in specific adult tissues and cells provides a focus to explore potential functions of this protein not addressed previously.
C1 [Padmakumar, V. C.; Masiuk, Katelyn E.; Luger, Dror; Lee, Christina; Hoover, Shelley B.; Simpson, R. Mark; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Karavanova, Irina; Buonanno, Andres] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurobiol Sect, Bethesda, MD USA.
[Coppola, Vincenzo; Tessarollo, Lino] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA.
[Yuspa, Stuart H.] NCI, NIH, Bethesda, MD 20892 USA.
RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
EM yuspas@mail.nih.gov
OI Coppola, Vincenzo/0000-0001-6163-1779
FU Intramural Research Program of the Center for Cancer Research; National
Cancer Institute; National Institute on Minority Health and Health
Disparities
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute and National Institute on
Minority Health and Health Disparities.
NR 48
TC 6
Z9 6
U1 1
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-213X
J9 BMC DEV BIOL
JI BMC Dev. Biol.
PD MAY 28
PY 2014
VL 14
AR 24
DI 10.1186/1471-213X-14-24
PG 17
WC Developmental Biology
SC Developmental Biology
GA AK7DU
UT WOS:000338587300001
PM 24886590
ER
PT J
AU Cruz, FC
Babin, KR
Leao, RM
Goldart, EM
Bossert, JM
Shaham, Y
Hope, BT
AF Cruz, Fabio C.
Babin, Klil R.
Leao, Rodrigo M.
Goldart, Evan M.
Bossert, Jennifer M.
Shaham, Yavin
Hope, Bruce T.
TI Role of Nucleus Accumbens Shell Neuronal Ensembles in Context-Induced
Reinstatement of Cocaine-Seeking
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE conditioned cues; Daun02 inactivation; drug environment; extinction;
Fos; self-administration
ID MEDIAL PREFRONTAL CORTEX; C-FOS IMMUNOREACTIVITY; INDUCED RELAPSE;
HEROIN SEEKING; DRUG SEEKING; GLUTAMATE RECEPTORS; BASAL GANGLIA; RATS;
STRIATUM; CORE
AB Environmental contexts previously associated with drug use provoke relapse to drug use in humans and reinstatement of drug seeking in animal models of drug relapse. We examined whether context-induced reinstatement of cocaine seeking is mediated by activation of context-selected nucleus accumbens neurons. We trained rats to self-administer cocaine in Context A and extinguished their lever-pressing in a distinct Context B. On test day, reexposure to the cocaine-associated Context A reinstated cocaine seeking and increased expression of the neural activity marker Fos in 3.3% of accumbens shell and 1.6% of accumbens core neurons. To assess a causal role for these activated neurons, we used the Daun02 inactivation procedure to selectively inactivate these neurons. We trained c-fos-lacZ transgenic rats to self-administer cocaine in Context A and extinguished their lever-pressing in Context B. On induction day, we exposed rats to either Context A or a novel Context C for 30 min and injected Daun02 or vehicle into accumbens shell or core 60 min later. On test day, 3 d after induction day, the ability of Context A to reinstate cocaine seeking and increase neuronal activity in accumbens shell was attenuated when Daun02 was previously injected after exposure to Context A. Daun02 injections after exposure to the novel Context C had no effect on context-induced reinstatement of cocaine seeking despite much greater numbers of Fos-expressing neurons induced by Context C. Daun02 injections in accumbens core had no effect. Our data suggest that context-induced reinstatement of cocaine seeking is mediated by activation of context-selected accumbens shell but not core neuronal ensembles.
C1 [Cruz, Fabio C.; Babin, Klil R.; Leao, Rodrigo M.; Goldart, Evan M.; Bossert, Jennifer M.; Shaham, Yavin; Hope, Bruce T.] NIDA, Behav Neurosci Branch, IRP, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
RP Hope, BT (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH, 251 Bayview Dr, Baltimore, MD 21224 USA.
EM bhope@intra.nida.nih.gov
RI Hope, Bruce/A-9223-2010
OI Hope, Bruce/0000-0001-5804-7061
FU National Institute on Drug Abuse, Intramural Research Program, National
Institutes of Health
FX This work was supported by the National Institute on Drug Abuse,
Intramural Research Program, National Institutes of Health.
NR 53
TC 32
Z9 32
U1 1
U2 12
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAY 28
PY 2014
VL 34
IS 22
BP 7437
EP 7446
DI 10.1523/JNEUROSCI.0238-14.2014
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA AI8CE
UT WOS:000337131800005
PM 24872549
ER
PT J
AU Marchant, NJ
Rabei, R
Kaganovsky, K
Caprioli, D
Bossert, JM
Bonci, A
Shaham, Y
AF Marchant, Nathan J.
Rabei, Rana
Kaganovsky, Konstantin
Caprioli, Daniele
Bossert, Jennifer M.
Bonci, Antonello
Shaham, Yavin
TI A Critical Role of Lateral Hypothalamus in Context-Induced Relapse to
Alcohol Seeking after Punishment-Imposed Abstinence
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE alcohol; context; lateral hypothalamus; nucleus accumbens; punishment;
relapse
ID NUCLEUS-ACCUMBENS SHELL; DOPAMINE D-1-FAMILY RECEPTORS; CUE-INDUCED
REINSTATEMENT; MEDIAL PREFRONTAL CORTEX; VENTRAL TEGMENTAL AREA; COCAINE
SEEKING; DRUG-SEEKING; REWARD-SEEKING; FEEDING-BEHAVIOR; HEROIN SEEKING
AB In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABA(A) + GABA(B) receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse.
C1 [Marchant, Nathan J.; Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M.; Shaham, Yavin] NIDA, Behav Neurosci Res Branch, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Bonci, Antonello] NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Marchant, Nathan J.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia.
[Bonci, Antonello] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD 21287 USA.
[Bonci, Antonello] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD 21287 USA.
RP Marchant, NJ (reprint author), Biomed Res Ctr, Room 08A721,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM nathan.marchant@nih.gov
OI Kaganovsky, Konstantin/0000-0002-1577-109X; Marchant,
Nathan/0000-0001-8269-0532
FU National Institute on Drug Abuse, Intramural Research Program; National
Health and Medical Research Council [1053308]
FX This work was supported by the National Institute on Drug Abuse,
Intramural Research Program. N.J.M. received support from Early Career
Fellowship 1053308 by the National Health and Medical Research Council.
NR 65
TC 15
Z9 15
U1 1
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAY 28
PY 2014
VL 34
IS 22
BP 7447
EP 7457
DI 10.1523/JNEUROSCI.0256-14.2014
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA AI8CE
UT WOS:000337131800006
PM 24872550
ER
PT J
AU Chen, GY
Qju, HL
Prasad, PN
Chen, XY
AF Chen, Guanying
Qju, Hailong
Prasad, Paras N.
Chen, Xiaoyuan
TI Upconversion Nanoparticles: Design, Nanochemistry, and Applications in
Theranostics
SO CHEMICAL REVIEWS
LA English
DT Review
ID NEAR-INFRARED LIGHT; RESONANCE ENERGY-TRANSFER; EARTH FLUORIDE
NANOCRYSTALS; PHOTON-UPCONVERTING NANOPARTICLES; SURFACE-PLASMON
RESONANCE; RAY COMPUTED-TOMOGRAPHY; LANTHANIDE-DOPED NANOCRYSTALS;
CORE-SHELL NANOPARTICLES; DENSITY-FUNCTIONAL CALCULATIONS; CONVERTING
PHOSPHOR TECHNOLOGY
C1 [Chen, Guanying; Qju, Hailong] Harbin Inst Technol, Sch Chem Engn & Technol, Harbin 150001, Heilongjiang, Peoples R China.
[Chen, Guanying; Qju, Hailong; Prasad, Paras N.] SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA.
[Chen, Guanying; Qju, Hailong; Prasad, Paras N.] SUNY Buffalo, Inst Lasers Photon & Biophoton, Buffalo, NY 14260 USA.
[Prasad, Paras N.] Korea Univ, Dept Chem, Seoul 136701, South Korea.
[Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Chen, GY (reprint author), Harbin Inst Technol, Sch Chem Engn & Technol, Harbin 150001, Heilongjiang, Peoples R China.
EM guanying@buffalo.edu; pnprasad@buffalo.edu; shawn.chen@nih.gov
RI Chen, Guanying/D-8584-2011
OI Chen, Guanying/0000-0002-4789-1176
FU National Key Basic Research Program (973 Project) [2013CB733802,
2014CB744503]; Natural Science Foundation of China [51102066, 81371596];
Program for Basic Research Excellent Talents in Harbin Institute of
Technology [BRETIII 2012018]; Intramural Research Program (IRP) of the
National Institute of Biomedical Imaging and Bioengineering (NIBIB),
National Institutes of Health (NIH)
FX This work was supported by the National Key Basic Research Program (973
Project) (2013CB733802, 2014CB744503), the Natural Science Foundation of
China (No. 51102066, 81371596), the Program for Basic Research Excellent
Talents in Harbin Institute of Technology (BRETIII 2012018), and the
Intramural Research Program (IRP) of the National Institute of
Biomedical Imaging and Bioengineering (NIBIB), National Institutes of
Health (NIH).
NR 468
TC 467
Z9 475
U1 153
U2 923
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
EI 1520-6890
J9 CHEM REV
JI Chem. Rev.
PD MAY 28
PY 2014
VL 114
IS 10
BP 5161
EP 5214
DI 10.1021/cr400425h
PG 54
WC Chemistry, Multidisciplinary
SC Chemistry
GA AI1SV
UT WOS:000336635900002
PM 24605868
ER
PT J
AU Costa, VD
Averbeck, BB
AF Costa, Vincent D.
Averbeck, Bruno B.
TI Looking into the future
SO ELIFE
LA English
DT Editorial Material
ID PARIETAL CORTEX; POSITION; NEURONS; SYSTEM
C1 [Costa, Vincent D.; Averbeck, Bruno B.] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA.
RP Costa, VD (reprint author), NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA.
EM vincent.costa@nih.gov
RI Costa, Vincent/A-2086-2015
OI Costa, Vincent/0000-0002-5412-8945
NR 9
TC 2
Z9 2
U1 1
U2 4
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD MAY 28
PY 2014
VL 3
AR e03146
DI 10.7554/eLife.03146
PG 3
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AI2CV
UT WOS:000336665600001
PM 24872505
ER
PT J
AU Cummings, SR
Studenski, S
Ferrucci, L
AF Cummings, Steven R.
Studenski, Stephanie
Ferrucci, Luigi
TI A Diagnosis of Dismobility-Giving Mobility Clinical Visibility A
Mobility Working Group Recommendation
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID SUBSEQUENT DISABILITY; PHYSICAL PERFORMANCE; OLDER-ADULTS; GAIT SPEED
C1 [Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, San Francisco, CA 94107 USA.
[Studenski, Stephanie; Ferrucci, Luigi] NIA, Intramural Program, Baltimore, MD 21224 USA.
RP Cummings, SR (reprint author), Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, 185 Berry St,Ste 5700, San Francisco, CA 94107 USA.
EM scummings@sfcc-cpmc.net
FU Intramural NIH HHS [Z01 AG000015-49]
NR 10
TC 41
Z9 41
U1 2
U2 8
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 28
PY 2014
VL 311
IS 20
BP 2061
EP 2062
DI 10.1001/jama.2014.3033
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AH8MQ
UT WOS:000336392400016
PM 24763978
ER
PT J
AU Cotton, PB
Durkalski, V
Romagnuolo, J
Pauls, Q
Fogel, E
Tarnasky, P
Aliperti, G
Freeman, M
Kozarek, R
Jamidar, P
Wilcox, M
Serrano, J
Brawman-Mintzer, O
Elta, G
Mauldin, P
Thornhill, A
Hawes, R
Wood-Williams, A
Orrell, K
Drossman, D
Robuck, P
AF Cotton, Peter B.
Durkalski, Valerie
Romagnuolo, Joseph
Pauls, Qi
Fogel, Evan
Tarnasky, Paul
Aliperti, Giuseppe
Freeman, Martin
Kozarek, Richard
Jamidar, Priya
Wilcox, Mel
Serrano, Jose
Brawman-Mintzer, Olga
Elta, Grace
Mauldin, Patrick
Thornhill, Andre
Hawes, Robert
Wood-Williams, April
Orrell, Kyle
Drossman, Douglas
Robuck, Patricia
TI Effect of Endoscopic Sphincterotomy for Suspected Sphincter of Oddi
Dysfunction on Pain-Related Disability Following Cholecystectomy The
EPISOD Randomized Clinical Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; FUNCTIONAL GASTROINTESTINAL
DISORDERS; FINDINGS TYPE-I; HEALTH-STATUS; RISK-FACTORS; DSM-IV; ERCP;
GALLBLADDER; SYMPTOMS; DISEASE
AB IMPORTANCE Abdominal pain after cholecystectomy is common and may be attributed to sphincter of Oddi dysfunction. Management often involves endoscopic retrograde cholangiopancreatography (ERCP) with manometry and sphincterotomy.
OBJECTIVE To determine whether endoscopic sphincterotomy reduces pain and whether sphincter manometric pressure is predictive of pain relief.
DESIGN, SETTING, AND PATIENTS Multicenter, sham-controlled, randomized trial involving 214 patients with pain after cholecystectomy without significant abnormalities on imaging or laboratory studies, and no prior sphincter treatment or pancreatitis randomly assigned (August 6, 2008-March 23, 2012) to undergo sphincterotomy or sham therapy at 7 referral medical centers. One-year follow-up was blinded. The final follow-up visit was March 21, 2013.
INTERVENTIONS After ERCP, patients were randomized 2: 1 to sphincterotomy (n = 141) or sham (n = 73) irrespective of manometry findings. Those randomized to sphincterotomy with elevated pancreatic sphincter pressures were randomized again (1: 1) to biliary or to both biliary and pancreatic sphincterotomies. Seventy-two were entered into an observational study with conventional ERCP managemeny.
MAIN OUTCOMES AND MEASURES Success of treatment was defined as less than 6 days of disability due to pain in the prior 90 days both at months 9 and 12 after randomization, with no narcotic use and no further sphincter intervention.
RESULTS Twenty-seven patients (37%; 95% CI, 25.9%-48.1%) in the sham treatment group vs 32 (23%; 95% CI, 15.8%-29.6%) in the sphincterotomy group experienced successful treatment (adjusted risk difference, -15.6%; 95% CI, -28.0% to -3.3%; P =.01). Of the patients with pancreatic sphincter hypertension, 14 (30%; 95% CI, 16.7%-42.9%) who underwent dual sphincterotomy and 10 (20%; 95% CI, 8.7%-30.5%) who underwent biliary sphincterotomy alone experienced successful treatment. Thirty-seven treated patients (26%; 95% CI, 19%-34%) and 25 patients (34%; 95% CI, 23%-45%) in the sham group underwent repeat ERCP interventions (P =.22). Manometry results were not associated with the outcome. No clinical subgroups appeared to benefit from sphincterotomy more than others. Pancreatitis occurred in 15 patients (11%) after primary sphincterotomies and in 11 patients (15%) in the sham group. Of the nonrandomized patients in the observational study group, 5 (24%; 95% CI, 6%-42%) who underwent biliary sphincterotomy, 12 (31%; 95% CI, 16%-45%) who underwent dual sphincterotomy, and 2 (17%; 95% CI, 0%-38%) who did not undergo sphincterotomy had successful treatment.
CONCLUSIONS AND RELEVANCE In patients with abdominal pain after cholecystectomy undergoing ERCP with manometry, sphincterotomy vs sham did not reduce disability due to pain. These findings do not support ERCP and sphincterotomy for these patients.
C1 [Cotton, Peter B.; Durkalski, Valerie; Romagnuolo, Joseph; Pauls, Qi; Mauldin, Patrick; Thornhill, Andre; Hawes, Robert; Wood-Williams, April; Orrell, Kyle] Med Univ S Carolina, Charleston, SC 29425 USA.
[Fogel, Evan] Indiana Univ, Indianapolis, IN 46204 USA.
[Tarnasky, Paul] Dallas Med Ctr, Dallas, TX USA.
[Aliperti, Giuseppe] Midwest Therapeut Endoscopy Consultants, St Louis, MO USA.
[Freeman, Martin] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Kozarek, Richard] Virginia Mason Med Ctr, Seattle, WA 98101 USA.
[Jamidar, Priya] Yale Univ, New Haven, CT USA.
[Wilcox, Mel] Univ Alabama Birmingham, Birmingham, AL USA.
[Serrano, Jose; Robuck, Patricia] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA.
[Brawman-Mintzer, Olga] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Elta, Grace] Univ Michigan, Ann Arbor, MI 48109 USA.
[Hawes, Robert] Florida Hosp, Orlando, FL USA.
[Drossman, Douglas] Univ N Carolina, Chapel Hill, NC USA.
[Drossman, Douglas] Drossman Gastroenterol PLLC, Chapel Hill, NC USA.
RP Cotton, PB (reprint author), Med Univ S Carolina, Ctr Digest Dis, ART 7094,MSC 290,25 Courtenay Dr, Charleston, SC 29425 USA.
EM cottonp@musc.edu
FU National Institutes of Diabetes and Digestive and Kidney Diseases [U01
DK074739]
FX This study was funded by grant U01 DK074739 from the National Institutes
of Diabetes and Digestive and Kidney Diseases.
NR 40
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U1 12
U2 16
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 28
PY 2014
VL 311
IS 20
BP 2101
EP 2109
DI 10.1001/jama.2014.5220
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AH8MQ
UT WOS:000336392400026
PM 24867013
ER
PT J
AU Arany, PR
Cho, A
Hunt, TD
Sidhu, G
Shin, K
Hahm, E
Huang, GX
Weaver, J
Chen, ACH
Padwa, BL
Hamblin, MR
Barcellos-Hoff, MH
Kulkarni, AB
Mooney, DJ
AF Arany, Praveen R.
Cho, Andrew
Hunt, Tristan D.
Sidhu, Gursimran
Shin, Kyungsup
Hahm, Eason
Huang, George X.
Weaver, James
Chen, Aaron Chih-Hao
Padwa, Bonnie L.
Hamblin, Michael R.
Barcellos-Hoff, Mary Helen
Kulkarni, Ashok B.
Mooney, David J.
TI Photoactivation of Endogenous Latent Transforming Growth Factor-beta 1
Directs Dental Stem Cell Differentiation for Regeneration
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID GROWTH-FACTOR-BETA; LEVEL LASER IRRADIATION; IN-VITRO; PULP COMPLEX;
BONE-MARROW; ACTIVATION; TGF-BETA-1; AMELOBLASTS; PROTEINS; MATRIX
AB Rapid advancements in the field of stem cell biology have led to many current efforts to exploit stem cells as therapeutic agents in regenerative medicine. However, current ex vivo cell manipulations common to most regenerative approaches create a variety of technical and regulatory hurdles to their clinical translation, and even simpler approaches that use exogenous factors to differentiate tissue-resident stem cells carry significant off-target side effects. We show that non-ionizing, low-power laser (LPL) treatment can instead be used as a minimally invasive tool to activate an endogenous latent growth factor complex, transforming growth factor-beta 1 (TGF-beta 1), that subsequently differentiates host stem cells to promote tissue regeneration. LPL treatment induced reactive oxygen species (ROS) in a dose-dependent manner, which, in turn, activated latent TGF-beta 1 (LTGF-beta 1) via a specific methionine residue (at position 253 on LAP). Laser-activated TGF-beta 1 was capable of differentiating human dental stem cells in vitro. Further, an in vivo pulp capping model in rat teeth demonstrated significant increase in dentin regeneration after LPL treatment. These in vivo effects were abrogated in TGF-LPL-induced receptor II (TGF-beta RII) conditional knockout (DSPP(Cre)TGF-beta RIIfl/fl) mice or when wild-type mice were given a TGF-beta RI inhibitor. These findings indicate a pivotal role for TGF-beta in mediating LPL-induced dental tissue regeneration. More broadly, this work outlines a mechanistic basis for harnessing resident stem cells with a light-activated endogenous cue for clinical regenerative applications.
C1 [Arany, Praveen R.; Hunt, Tristan D.; Sidhu, Gursimran; Shin, Kyungsup; Hahm, Eason; Huang, George X.; Mooney, David J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Arany, Praveen R.; Weaver, James; Mooney, David J.] Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
[Arany, Praveen R.; Shin, Kyungsup] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Arany, Praveen R.] Leder Human Biol & Translat Med, Boston, MA 02115 USA.
[Arany, Praveen R.; Cho, Andrew; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA.
[Chen, Aaron Chih-Hao; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Padwa, Bonnie L.] Childrens Hosp, Boston, MA 02115 USA.
[Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Barcellos-Hoff, Mary Helen] NYU, Sch Med, New York, NY 10016 USA.
RP Mooney, DJ (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM mooneyd@seas.harvard.edu
OI Barcellos-Hoff, Mary Helen/0000-0002-5994-9558
FU Harvard Presidential Scholarship; Wyss institute, Harvard Catalyst;
Harvard Clinical and Translational Science Center [National Center for
Research Resources (NCRR)]; National Center for Advancing Translational
Sciences (NCATS); NIH [1UL1 TR001102-01]; Harvard University;
[R37-DE-013349]; [R01-DE019023-01]; [R01-AI-050875]; [ZIA-DE-000698]
FX R37-DE-013349 (D.J.M.), R01-DE019023-01, R01-AI-050875 (M.R.H.),
ZIA-DE-000698 (A.B.K.), Harvard Presidential Scholarship (P.R.A.), Wyss
institute, Harvard Catalyst, Harvard Clinical and Translational Science
Center [National Center for Research Resources (NCRR) and National
Center for Advancing Translational Sciences (NCATS), NIH, 1UL1
TR001102-01, and financial contributions from Harvard University and its
affiliated academic health care centers], and the intramural research
program, NIDCR, NIH (A.B.K. and P.R.A.). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of Harvard Catalyst, Harvard University and its
affiliated academic health care centers, or the NIH.
NR 45
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U1 0
U2 33
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAY 28
PY 2014
VL 6
IS 238
AR 238ra69
DI 10.1126/scitranslmed.3008234
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AI2DZ
UT WOS:000336668900002
PM 24871130
ER
PT J
AU Zabow, G
Dodd, SJ
Koretsky, AP
AF Zabow, Gary
Dodd, Stephen J.
Koretsky, Alan P.
TI Ellipsoidal Microcavities: Electromagnetic Properties, Fabrication, and
Use as Multispectral MRI Agents
SO SMALL
LA English
DT Article
DE ellipsoidal colloids; magnetic microparticles; MRI contrast agents;
nanofabrication
ID PARTICLES; FIELD
C1 [Zabow, Gary; Dodd, Stephen J.; Koretsky, Alan P.] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Zabow, Gary] NIST, Electromagnet Div, Phys Measurement Lab, Boulder, CO 80305 USA.
RP Zabow, G (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
EM zabowg@ninds.nih.gov
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU NIH NINDS Intramural Research Program
FX This work was supported in part by the NIH NINDS Intramural Research
Program. We thank the NIH Mouse Imaging Facility for use of the 14T MRI,
and Dr. John Moreland for useful discussion and for NIST cleanroom
access.
NR 23
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U1 1
U2 20
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1613-6810
EI 1613-6829
J9 SMALL
JI Small
PD MAY 28
PY 2014
VL 10
IS 10
BP 1902
EP 1907
DI 10.1002/smll.201303045
PG 6
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA AI1KX
UT WOS:000336611000003
PM 24623519
ER
PT J
AU Anderson, LA
Atman, AA
McShane, CM
Titmarsh, GJ
Engels, EA
Koshiol, J
AF Anderson, L. A.
Atman, A. A.
McShane, C. M.
Titmarsh, G. J.
Engels, E. A.
Koshiol, J.
TI Common infection-related conditions and risk of lymphoid malignancies in
older individuals
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
ID NON-HODGKIN-LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; MULTIPLE-MYELOMA;
MEDICAL HISTORY; CELL LYMPHOMA; INFLAMMATORY CONDITIONS; IMMUNE;
POLYMORPHISMS; CELLULITIS; HEPATITIS
AB Background: Chronic antigenic stimulation may initiate non-Hodgkin (NHL) and Hodgkin lymphoma (HL) development. Antecedent, infection-related conditions have been associated, but evidence by lymphoproliferative subtype is limited.
Methods: From the US SEER-Medicare database, 44 191 NHL, 1832 HL and 200 000 population-based controls, frequency matched to all SEER cancer cases, were selected. Logistic regression models, adjusted for potential confounders, compared infection-related conditions in controls with HL and NHL patients and by the NHL subtypes diffuse large B-cell, T-cell, follicular and marginal zone lymphoma (MZL). Stratification by race was undertaken.
Results: Respiratory tract infections were broadly associated with NHL, particularly MZL. Skin infections were associated with a 15-28% increased risk of NHL and with most NHL subtypes, particularly cellulitis with T-cell lymphoma (OR 1.36, 95% CI 1.24-1.49). Only herpes zoster remained associated with HL following Bonferroni correction (OR 1.55, 95% CI 1.28-1.87). Gastrointestinal and urinary tract infections were not strongly associated with NHL or HL. In stratified analyses by race, sinusitis, pharyngitis, bronchitis and cellulitis showed stronger associations with total NHL in blacks than whites (P < 0.001).
Conclusions: Infections may contribute to the aetiologic pathway and/or be markers of underlying immune modulation. Precise elucidation of these mechanisms may provide important clues for understanding how immune disturbance contributes to lymphoma.
C1 [Anderson, L. A.; Atman, A. A.; McShane, C. M.; Titmarsh, G. J.] Queens Univ Belfast, Ctr Publ Hlth, Belfast BT12 6BJ, Antrim, North Ireland.
[Engels, E. A.; Koshiol, J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Anderson, LA (reprint author), Queens Univ Belfast, Ctr Publ Hlth, Belfast BT12 6BJ, Antrim, North Ireland.
EM l.anderson@qub.ac.uk
OI Anderson, Lesley/0000-0002-1000-3649
FU Intramural Research Program of the National Cancer Institute; Queen's
University Belfast
FX This work was supported by the Intramural Research Program of the
National Cancer Institute. GT is a PhD student at the Queen's University
Belfast in receipt of funding from MPD Voice. CMS is a PhD student at
the Queen's University Belfast in receipt of a Department for Employment
and Learning (Northern Ireland) funded scholarship. This study used the
linked SEER-Medicare database. The interpretation and reporting of these
data are the sole responsibility of the authors. We acknowledge the
efforts of the Applied Research Program, NCI; the Office of Research,
Development and Information, Centers for Medicare and Medicaid Services;
Information Management Services, Inc.; and the Surveillance,
Epidemiology, and End Results (SEER) Program tumour registries in the
creation of the SEER-Medicare database. We also thank Dr Winnie Ricker,
Information Management Services, Rockville, MD, USA for constructing and
analysing the data set.
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U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAY 27
PY 2014
VL 110
IS 11
BP 2796
EP 2803
DI 10.1038/bjc.2014.173
PG 8
WC Oncology
SC Oncology
GA AI8HB
UT WOS:000337150600019
PM 24691420
ER
PT J
AU Winkler, CW
Taylor, KG
Peterson, KE
AF Winkler, Clayton W.
Taylor, Katherine G.
Peterson, Karin E.
TI Location Is Everything: let-7b microRNA and TLR7 Signaling Results in a
Painful TRP
SO SCIENCE SIGNALING
LA English
DT Article
ID CAUSES NEURODEGENERATION; NEGATIVE REGULATOR; RECEPTOR 7; AGONISTS;
PROTEIN
AB Extracellular let-7b, a microRNA found in the central nervous system, affects neurons through its interaction with Toll-like receptor 7 (TLR7), but with divergent outcomes in different neurons. Lehmann et al. found that let-7b stimulation of cortical and hippocampal neurons led to neuronal apoptosis, whereas Park et al. report that let-7b activation of TLR7 stimulated the cation channel transient receptor potential A1 (TRPA1) on dorsal root ganglia sensory neurons and induced pain responses. The primary difference that may influence these distinct responses to let-7b is the localization of TLR7 to the endosome in the cortical and hippocampal neurons or the plasma membrane in the sensory neurons. These studies suggest that different types of neurons traffic TLR7 to distinct membrane locations, affecting the functional response of neurons to let-7b stimulation.
C1 [Winkler, Clayton W.; Taylor, Katherine G.; Peterson, Karin E.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Peterson, KE (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM petersonka@niaid.nih.gov
RI Peterson, Karin/D-1492-2016
OI Peterson, Karin/0000-0003-4177-7249
NR 12
TC 6
Z9 6
U1 0
U2 14
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1945-0877
EI 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD MAY 27
PY 2014
VL 7
IS 327
AR pe14
DI 10.1126/scisignal.2005407
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AI8OI
UT WOS:000337178300002
PM 24866018
ER
PT J
AU de Messieres, M
Huang, RK
He, Y
Lee, JC
AF de Messieres, Michel
Huang, Rick K.
He, Yi
Lee, Jennifer C.
TI Amyloid Triangles, Squares, and Loops of Apolipoprotein C-III
SO BIOCHEMISTRY
LA English
DT Article
ID FIBRIL-FORMATION; A-I; CARDIOVASCULAR-SYSTEM; ALPHA-SYNUCLEIN;
ATHEROSCLEROSIS; LIPOPROTEIN; INSIGHTS; MUTATION; DOMAIN; APOC3
AB While a significant component of atherosclerotic plaques has been characterized as amyloid, the specific proteins remain to be fully identified. Probable amyloidogenic proteins are apolipoproteins (Apos), which are vital for the formation and function of lipoproteins. ApoCIII is an abundant protein implicated in atherosclerosis, and we show it forms a ribbonlike looped amyloid, strikingly similar to that previously reported for ApoAI and ApoCII. Triangles and squares with a width of similar to 50 nm were also observed, which may be a novel form of amyloid or related to previously reported amyloid rings.
C1 [de Messieres, Michel; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, Bethesda, MD 20892 USA.
[He, Yi] NHLBI, Prot Express Facil, Biochem & Biophys Ctr, Bethesda, MD 20892 USA.
[Huang, Rick K.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
RP Lee, JC (reprint author), NHLBI, Lab Mol Biophys, Bldg 10, Bethesda, MD 20892 USA.
EM leej4@mail.nih.gov
RI Lee, Jennifer/E-9658-2015
OI Lee, Jennifer/0000-0003-0506-8349
FU National Institutes of Health, National Heart, Lung and Blood Institute;
National Institute of Arthritis and Musculoskeletal and Skin Diseases
FX Supported by the Intramural Research Program at the National Institutes
of Health, the National Heart, Lung and Blood Institute, and the
National Institute of Arthritis and Musculoskeletal and Skin Diseases.
NR 28
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U1 4
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAY 27
PY 2014
VL 53
IS 20
BP 3261
EP 3263
DI 10.1021/bi500502d
PG 3
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AI1SY
UT WOS:000336636300001
PM 24804986
ER
PT J
AU Miranda, KM
Wink, DA
AF Miranda, Katrina M.
Wink, David A.
TI Persulfides and the cellular thiol landscape
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID HYDROGEN-SULFIDE; METABOLISM; BIOLOGY; SULFUR
C1 [Miranda, Katrina M.] Univ Arizona, Dept Chem & Biochem, Tucson, AZ 85721 USA.
[Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Wink, DA (reprint author), NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
EM wink@mail.nih.gov
NR 15
TC 7
Z9 7
U1 0
U2 14
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 27
PY 2014
VL 111
IS 21
BP 7505
EP 7506
DI 10.1073/pnas.1405665111
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH8TO
UT WOS:000336411300015
PM 24828533
ER
PT J
AU Imashimizu, M
Kashlev, M
AF Imashimizu, Masahiko
Kashlev, Mikhail
TI Unveiling translocation intermediates of RNA polymerase
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID 3.3 ANGSTROM RESOLUTION; STRUCTURAL BASIS; TRANSCRIPTION ELONGATION;
TRIGGER LOOP; POL II; DYNAMICS; SITE; DROSOPHILA; MECHANISM; COMPLEX
C1 [Imashimizu, Masahiko; Kashlev, Mikhail] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Kashlev, M (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM kashlevm@mail.nih.gov
NR 27
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Z9 3
U1 1
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 27
PY 2014
VL 111
IS 21
BP 7507
EP 7508
DI 10.1073/pnas.1406413111
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH8TO
UT WOS:000336411300016
PM 24828529
ER
PT J
AU Luque, D
Gomez-Blanco, J
Garriga, D
Brilot, AF
Gonzalez, JM
Havens, WM
Carrascosa, JL
Trus, BL
Verdaguer, N
Ghabrial, SA
Caston, JR
AF Luque, Daniel
Gomez-Blanco, Josue
Garriga, Damia
Brilot, Axel F.
Gonzalez, Jose M.
Havens, Wendy M.
Carrascosa, Jose L.
Trus, Benes L.
Verdaguer, Nuria
Ghabrial, Said A.
Caston, Jose R.
TI Cryo-EM near-atomic structure of a dsRNA fungal virus shows ancient
structural motifs preserved in the dsRNA viral lineage
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE 3D cryo-EM; chrysovirus; structural homology; virus evolution
ID PENICILLIUM-CHRYSOGENUM-VIRUS; MULTIPLE SEQUENCE ALIGNMENT;
ELECTRON-MICROSCOPY; CAPSID PROTEIN; CARBOXYSOME SHELL; RNA VIRUS;
EVOLUTION; IMAGE; CRYOMICROSCOPY; VISUALIZATION
AB Viruses evolve so rapidly that sequence-based comparison is not suitable for detecting relatedness among distant viruses. Structure-based comparisons suggest that evolution led to a small number of viral classes or lineages that can be grouped by capsid protein (CP) folds. Here, we report that the CP structure of the fungal dsRNA Penicillium chrysogenum virus (PcV) shows the progenitor fold of the dsRNA virus lineage and suggests a relationship between lineages. Cryo-EM structure at near-atomic resolution showed that the 982-aa PcV CP is formed by a repeated alpha-helical core, indicative of gene duplication despite lack of sequence similarity between the two halves. Superimposition of secondary structure elements identified a single "hotspot" at which variation is introduced by insertion of peptide segments. Structural comparison of PcV and other distantly related dsRNA viruses detected preferential insertion sites at which the complexity of the conserved alpha-helical core, made up of ancestral structural motifs that have acted as a skeleton, might have increased, leading to evolution of the highly varied current structures. Analyses of structural motifs only apparent after systematic structural comparisons indicated that the hallmark fold preserved in the dsRNA virus lineage shares a long (spinal) alpha-helix tangential to the capsid surface with the head-tailed phage and herpesvirus viral lineage.
C1 [Luque, Daniel; Gomez-Blanco, Josue; Gonzalez, Jose M.; Carrascosa, Jose L.; Caston, Jose R.] CSIC, Ctr Nacl Biotecnol, Dept Struct Macromol, Madrid 28049, Spain.
[Luque, Daniel] Inst Salud Carlos III, Ctr Nacl Microbiol, Madrid 28220, Spain.
[Garriga, Damia; Verdaguer, Nuria] CSIC, Inst Biol Mol Barcelona, E-08028 Barcelona, Spain.
[Brilot, Axel F.] Brandeis Univ, Dept Biochem, Waltham, MA 02454 USA.
[Havens, Wendy M.; Ghabrial, Said A.] Univ Kentucky, Dept Plant Pathol, Lexington, KY 40546 USA.
[Trus, Benes L.] NIH, Imaging Sci Lab, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Caston, JR (reprint author), CSIC, Ctr Nacl Biotecnol, Dept Struct Macromol, Campus Cantoblanco, Madrid 28049, Spain.
EM jrcaston@cnb.csic.es
RI Caston, Jose/L-5896-2014; Luque, Daniel/I-6467-2015;
OI Caston, Jose/0000-0003-2350-9048; Luque, Daniel/0000-0002-0151-6020;
Gonzalez, Jose M/0000-0001-5569-0705; Garriga,
Damia/0000-0003-0410-538X; Brilot, Axel/0000-0001-8548-4224
FU Canadian National Science and Engineering Research Council; National
Institutes of Health [P01 GM62580]; Spanish Ministry of Economy and
Competitivity [BFU 2011-29038, BIO2011-24333, BIO BFU2011-25902];
National Institutes of Health Intramural Research Program; Center for
Information Technology
FX We thank N. Grigorieff for continuous technical and intellectual
support, stimulating discussions, and critical reading of the
manuscript; C. Xu for maintaining the Brandeis EM facility and help with
data collection; and C. Mark for editorial assistance. A. F. B. was
supported by a grant from the Canadian National Science and Engineering
Research Council. The Brandeis EM facility is supported by National
Institutes of Health Grant P01 GM62580. This work was supported by
Spanish Ministry of Economy and Competitivity Grant BFU 2011-29038 (to
J.L.C.), Grant BIO2011-24333 (to N. V.), and Grant BIO BFU2011-25902 (to
J.R.C.), and by a grant from the National Institutes of Health
Intramural Research Program and the Center for Information Technology
(to B.L.T.).
NR 47
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Z9 7
U1 0
U2 16
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 27
PY 2014
VL 111
IS 21
BP 7641
EP 7646
DI 10.1073/pnas.1404330111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH8TO
UT WOS:000336411300040
PM 24821769
ER
PT J
AU Onozawa, M
Zhang, ZH
Kim, YJ
Goldberg, L
Varga, T
Bergsagel, PL
Kuehl, WM
Aplan, PD
AF Onozawa, Masahiro
Zhang, Zhenhua
Kim, Yoo Jung
Goldberg, Liat
Varga, Tamas
Bergsagel, P. Leif
Kuehl, W. Michael
Aplan, Peter D.
TI Repair of DNA double-strand breaks by templated nucleotide sequence
insertions derived from distant regions of the genome
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE polymorphism; TSIP; LINE-1; DNA patch
ID INDEPENDENT LINE-1 RETROTRANSPOSITION; REVERSE-TRANSCRIPTASE INHIBITORS;
CHROMOSOMAL TRANSLOCATIONS; SWITCH RECOMBINATION; STRUCTURAL VARIATION;
REARRANGEMENTS; EVOLUTION; MUTATIONS; REVEALS; CAPTURE
AB We used the I-SceI endonuclease to produce DNA double-strand breaks (DSBs) and observed that a fraction of these DSBs were repaired by insertion of sequences, which we termed "templated sequence insertions" (TSIs), derived from distant regions of the genome. These TSIs were derived from genic, retrotransposon, or telomere sequences and were not deleted from the donor site in the genome, leading to the hypothesis that they were derived from reverse-transcribed RNA. Cotransfection of RNA and an I-SceI expression vector demonstrated insertion of RNA-derived sequences at the DNA-DSB site, and TSIs were suppressed by reverse-transcriptase inhibitors. Both observations support the hypothesis that TSIs were derived from RNA templates. In addition, similar insertions were detected at sites of DNA DSBs induced by transcription activator-like effector nuclease proteins. Whole-genome sequencing of myeloma cell lines revealed additional TSIs, demonstrating that repair of DNA DSBs via insertion was not restricted to experimentally produced DNA DSBs. Analysis of publicly available databases revealed that many of these TSIs are polymorphic in the human genome. Taken together, these results indicate that insertional events should be considered as alternatives to gross chromosomal rearrangements in the interpretation of whole-genome sequence data and that this mutagenic form of DNA repair may play a role in genetic disease, exon shuffling, and mammalian evolution.
C1 [Onozawa, Masahiro; Zhang, Zhenhua; Kim, Yoo Jung; Goldberg, Liat; Varga, Tamas; Kuehl, W. Michael; Aplan, Peter D.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Bergsagel, P. Leif] Mayo Clin, Ctr Comprehens Canc, Scottsdale, AZ 85259 USA.
RP Aplan, PD (reprint author), NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
EM aplanp@mail.nih.gov
RI Aplan, Peter/K-9064-2016
FU National Cancer Institute, NIH; Japan Society for the Promotion of
Science
FX We thank Drs. Paul Meltzer and Ilan Kirsch, and members of the P.D.A.
laboratory for helpful discussions; Haruto Onozawa for technical
assistance; and the National Institutes of Health (NIH) Mini-sequencing
core for Sanger sequencing. This work was supported by the intramural
program of the National Cancer Institute, NIH. M.O. was supported by the
Japan Society for the Promotion of Science Postdoctoral Fellowships for
Research Abroad program.
NR 47
TC 21
Z9 21
U1 1
U2 18
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 27
PY 2014
VL 111
IS 21
BP 7729
EP 7734
DI 10.1073/pnas.1321889111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH8TO
UT WOS:000336411300055
PM 24821809
ER
PT J
AU Halemano, K
Guo, KJ
Heilman, KJ
Barrett, BS
Smith, DS
Hasenkrug, KJ
Santiago, ML
AF Halemano, Kalani
Guo, Kejun
Heilman, Karl J.
Barrett, Bradley S.
Smith, Diana S.
Hasenkrug, Kim J.
Santiago, Mario L.
TI Immunoglobulin somatic hypermutation by APOBEC3/Rfv3 during retroviral
infection
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE humoral immunity; restriction factor; antibody repertoire profiling;
affinity maturation; Friend retrovirus
ID IN-VIVO; AFFINITY MATURATION; HIV-1 INFECTION; VIRUS-INFECTION; GENE;
DEAMINATION; LEUKEMIA; DNA; RECEPTOR; MICE
AB Somatic hypermutation (SHM) is an integral process in the development of high-affinity antibodies that are important for recovery from viral infections and vaccine-induced protection. Ig SHM occurs predominantly in germinal centers (GC) via the enzymatic activity of activation-induced deaminase (AID). In contrast, the evolutionarily related apolipoprotein B mRNA-editing enzyme, catalytic polypeptide 3 (APOBEC3) proteins are known to restrict retroviruses, including HIV-1. We previously reported that mouse APOBEC3 encodes Recovery from Friend virus 3 (Rfv3), a classical resistance gene in mice that promotes the neutralizing antibody response against retrovirus infection. We now show that APOBEC3/Rfv3 complements AID in driving Ig SHM during retrovirus infection. Analysis of antibody sequences from retrovirus-specific hybridomas and GC B cells from infected mice revealed Ig heavy-chain V genes with significantly increased C-to-T and G-to-A transitions in wild-type as compared with APOBEC3-defective mice. The context of the mutations was consistent with APOBEC3 but not AID mutational activity. These findings help explain the role of APOBEC3/Rfv3 in promoting the neutralizing antibody responses essential for recovery from retroviral infection and highlight APOBEC3-mediated deamination as a previously unidentified mechanism for antibody diversification in vivo.
C1 [Halemano, Kalani; Guo, Kejun; Heilman, Karl J.; Barrett, Bradley S.; Smith, Diana S.; Santiago, Mario L.] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA.
[Halemano, Kalani; Santiago, Mario L.] Univ Colorado Denver, Dept Microbiol & Immunol, Aurora, CO 80045 USA.
[Hasenkrug, Kim J.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Santiago, ML (reprint author), Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA.
EM mario.santiago@ucdenver.edu
FU National Institutes of Health (NIH) [R01 AI090795]; University of
Colorado Department of Medicine Early Career Scholar Program; NIH
Division of Intramural Research; American Society for Microbiology
FX We thank W. Greene, L. Wysocki, R. Pelanda, R. Torres, L. Pujunauski, J.
Hagman, C. Dege, L. van Dyk, E. Janoff, D. Frank, and B. Palmer for
reagents, technical advice and/or assistance. This work was supported by
National Institutes of Health (NIH) Grant R01 AI090795 (to M. L. S.),
the University of Colorado Department of Medicine Early Career Scholar
Program (to M. L. S.), and by the NIH Division of Intramural Research
(to K. J. Hasenkrug). K.H. was the recipient of a Robert D. Watkins
Predoctoral Fellowship from the American Society for Microbiology.
NR 40
TC 17
Z9 17
U1 2
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 27
PY 2014
VL 111
IS 21
BP 7759
EP 7764
DI 10.1073/pnas.1403361111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH8TO
UT WOS:000336411300060
PM 24821801
ER
PT J
AU Anizan, S
Ellefsen, K
Concheiro, M
Suzuki, M
Rice, KC
Baumann, MH
Huestis, MA
AF Anizan, Sebastien
Ellefsen, Kayla
Concheiro, Marta
Suzuki, Masaki
Rice, Kenner C.
Baumann, Michael H.
Huestis, Marilyn A.
TI 3,4-Methylenedioxypyrovalerone (MDPV) and metabolites quantification in
human and rat plasma by liquid chromatography-high resolution mass
spectrometry
SO ANALYTICA CHIMICA ACTA
LA English
DT Article
DE MDPV; Synthetic cathinones; LC-MS/MS; HRMS; Metabolites
ID BATH SALTS; SYNTHETIC CATHINONES; DESIGNER DRUG; IN-VITRO;
3,4-DIHYDROXYMETHAMPHETAMINE; AMPHETAMINE; MEPHEDRONE; TOXICOLOGY
AB Synthetic cathinones are recreational drugs that mimic the effects of illicit stimulants like cocaine, amphetamine or Ecstasy. Among the available synthetic cathinones in the United States, 3,4-methylenedioxypyrovalerone (MDPV) is commonly abused and associated with dangerous side effects. MDPV is a dopamine transporter blocker 10-fold more potent than cocaine as a locomotor stimulant in rats. Previous in vitro and in vivo studies examining MDPV metabolism reported 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV) as the two primary metabolites. We developed and validated a liquid chromatography-high resolution mass spectrometry method to quantify MDPV and its primary metabolites in 100 mu L human and rat plasma. Plasma hydrolysis was followed by protein precipitation before analysis. Limits of detection were 0.1 mu g L (1), with linear ranges from 0.25 to 1000 mu g L (1). Process efficiency, matrix effect, total imprecision (%CV) and accuracy (%target) were 36-93%, from -8 to 12%, 2.1 to 7.3% and 86 to 109%, respectively. MDPV and metabolites were stable at room temperature for 24 h, 4 degrees C for 72 h and after 3 freeze-thaw cycles with less than 10% variability. Human-rat plasma cross validation demonstrated that rat plasma could be accurately quantified against a human plasma calibration curve. As proof of this method, rat plasma specimens were analyzed after intraperitoneal and subcutaneous dosing with MDPV (0.5 mg kg (1)). MDPV, 3,4-catechol-PV and 4-OH-3-MeO-PV concentrations ranged from not detected to 107.5 mu g L (1) prior to and up to 8 h after dosing. This method provides a simultaneous quantification of MDPV and two metabolites in plasma with good selectivity and sensitivity. Published by Elsevier B.V.
C1 [Anizan, Sebastien; Ellefsen, Kayla; Concheiro, Marta; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Ellefsen, Kayla] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA.
[Suzuki, Masaki; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Suzuki, Masaki; Rice, Kenner C.] NIAAA, NIH, Baltimore, MD USA.
[Baumann, Michael H.] NIDA, Designer Drug Res Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Biomed Res Ctr BRC, NIH, 251 Bayview Blvd,Suite 200 Room 05A721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse
(NIDA); National Institute on Alcohol Abuse and Alcoholism (NIAAA);
National Institutes of Health (NIH)
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse (NIDA), and the National Institute on
Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health
(NIH).
NR 29
TC 14
Z9 14
U1 2
U2 34
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0003-2670
EI 1873-4324
J9 ANAL CHIM ACTA
JI Anal. Chim. Acta
PD MAY 27
PY 2014
VL 827
BP 54
EP 63
DI 10.1016/j.aca.2014.04.015
PG 10
WC Chemistry, Analytical
SC Chemistry
GA AH2BN
UT WOS:000335925800008
PM 24832995
ER
PT J
AU Sidharthan, S
Kim, CW
Murphy, AA
Zhang, XZ
Yang, J
Lempicki, RA
Sneller, MC
Kottilil, S
AF Sidharthan, Sreetha
Kim, Cheol-Woo
Murphy, Alison A.
Zhang, Xiaozhen
Yang, Jun
Lempicki, Richard A.
Sneller, Michael C.
Kottilil, Shyam
TI Hepatitis C-associated mixed cryoglobulinemic vasculitis induces
differential gene expression in peripheral mononuclear cells
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE hepatitis C; mixed cryoglobulinemia; vasculitis; interferon-stimulated
genes
ID HUMAN-IMMUNODEFICIENCY-VIRUS; EXTRAHEPATIC MANIFESTATIONS; HCV
INFECTION; RECRUITMENT; THERAPY; LIVER; PATHOGENESIS; REPLICATION;
COINFECTION; CHEMOKINES
AB This study examines the distinct gene expression profile of peripheral blood mononuclear cells from patients with chronic hepatitis C infection and mixed cryoglobulinemic (MC) vasculitis. Our DNA microarray analysis indicates that hepatitis C virus (HCV)-associated MC vasculitis is characterized by compromised neutrophil function, impaired chemotaxis, and increased interferon-stimulated gene (ISG) expression, contributing to overall MC pathogenesis and end-organ damage. Increased ISG expression is suggestive of an enhanced endogenous interferon gene signature. PBMC depletion assays demonstrate that this increased expression is likely due to an activation of monocytes and not a direct result of B cell expansion. Notably, this monocyte activation of ISG expression in HCV-associated MC vasculitis suggests a poor predictor status of interferon-based treatment. Further analysis of PBMC gene expression profiles before and after in vivo B cell depletion therapy is critical to completely understanding the mechanisms of MC vasculitis pathogenesis.
C1 [Sidharthan, Sreetha] NIH, Dept Crit Care Med, Ctr Clin, US Dept HHS, Bethesda, MD 20892 USA.
[Kim, Cheol-Woo] Inha Univ, Dept Internal Med, Inchon, South Korea.
[Murphy, Alison A.; Zhang, Xiaozhen; Sneller, Michael C.; Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Yang, Jun; Lempicki, Richard A.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD USA.
RP Kottilil, S (reprint author), NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11N204, Bethesda, MD 20892 USA.
EM skottili@niaid.nih.gov
FU intramural program of the National Institute of Allergy and Infectious
Diseases at the National Institutes of Health, Bethesda, MD, USA
FX This study has been funded in whole with the federal funds from the
intramural program of the National Institute of Allergy and Infectious
Diseases at the National Institutes of Health, Bethesda, MD, USA.
Disclaimer: the views or policies of the Department of Health and Human
Services are not necessarily reflected in this content. The U.S.
Government does not endorse any trade names, commercial products, or
organizations mentioned.
NR 30
TC 2
Z9 3
U1 0
U2 1
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PD MAY 27
PY 2014
VL 5
BP 1
EP 13
AR 248
DI 10.3389/fimmu.2014.00248
PG 13
WC Immunology
SC Immunology
GA CH7OD
UT WOS:000354225600001
PM 24904592
ER
PT J
AU Romero, R
Hassan, SS
Gajer, P
Tarca, AL
Fadrosh, DW
Bieda, J
Chaemsaithong, P
Miranda, J
Chaiworapongsa, T
Ravel, J
AF Romero, Roberto
Hassan, Sonia S.
Gajer, Pawel
Tarca, Adi L.
Fadrosh, Douglas W.
Bieda, Janine
Chaemsaithong, Piya
Miranda, Jezid
Chaiworapongsa, Tinnakorn
Ravel, Jacques
TI The vaginal microbiota of pregnant women who subsequently have
spontaneous preterm labor and delivery and those with a normal delivery
at term
SO MICROBIOME
LA English
DT Article
DE Infection-induced preterm delivery; Histologic chorioamnionitis;
Prematurity; Vaginal flora; Vaginal microbiome
ID AMNIOTIC-FLUID INFECTION; LOW-BIRTH-WEIGHT; ASYMPTOMATIC BACTERIAL
VAGINOSIS; POLYMERASE-CHAIN-REACTION; RIBOSOMAL-RNA GENES; INTRAAMNIOTIC
INFECTION; UREAPLASMA-UREALYTICUM; INTACT MEMBRANES; PREMATURE LABOR;
RISK-FACTOR
AB Background: This study was undertaken to determine whether the vaginal microbiota of pregnant women who subsequently had a spontaneous preterm delivery is different from that of women who had a term delivery.
Results: This was a nested case-control study of pregnant women who had a term delivery (controls) and those who had a spontaneous preterm delivery before 34 weeks of gestation (cases). Samples of vaginal fluid were collected longitudinally and stored at -70 degrees C until assayed. A microbial survey using pyrosequencing of V1-V3 regions of 16S rRNA genes was performed. We tested the hypothesis of whether the relative abundance of individual microbial species (phylotypes) was different between women who had a term versus preterm delivery. A suite of bioinformatic and statistical tools, including linear mixed effects models and generalized estimating equations, was used. We show that: 1) the composition of the vaginal microbiota during normal pregnancy changed as a function of gestational age, with an increase in the relative abundance of four Lactobacillus spp., and decreased in anaerobe or strict-anaerobe microbial species as pregnancy progressed; 2) no bacterial taxa differed in relative abundance between women who had a spontaneous preterm delivery and those who delivered at term; and 3) no differences in the frequency of the vaginal community state types (CST I, III, IV-B) between women who delivered at term and those who delivered preterm were detected.
Conclusions: The bacterial taxa composition and abundance of vaginal microbial communities, characterized with 16S rRNA gene sequence-based techniques, were not different in pregnant women who subsequently delivered a preterm neonate versus those who delivered at term.
C1 [Romero, Roberto; Hassan, Sonia S.; Tarca, Adi L.; Bieda, Janine; Chaemsaithong, Piya; Miranda, Jezid; Chaiworapongsa, Tinnakorn] NIH, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,Eunice Kennedy Shriver Natl In, Bethesda, MD 20892 USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynaecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynaecol, Detroit, MI 48201 USA.
[Gajer, Pawel; Fadrosh, Douglas W.; Ravel, Jacques] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
[Gajer, Pawel; Ravel, Jacques] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Bieda, Janine; Chaiworapongsa, Tinnakorn] Hutzel Womens Hosp, Detroit Med Ctr, Detroit, MI 48201 USA.
RP Romero, R (reprint author), NIH, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,Eunice Kennedy Shriver Natl In, Bldg 10, Bethesda, MD 20892 USA.
EM prbchiefstaff@med.wayne.edu; pgajer@gmail.com
OI Ravel, Jacques/0000-0002-0851-2233
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This work was funded, in part, by the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS. The authors
wish to acknowledge the contributions of the patients who volunteered
for these studies, the medical and healthcare personnel involved in the
research effort, and colleagues who contributed to the discussions which
eventually led to the conduct of the study. We are particularly grateful
to Dr. Sharon Hillier of the University of Pittsburgh, Dr. Jack Sobel of
Wayne State University, Dr. Ronald Lamont of the University of Southern
Denmark, Dr. David Relman of Stanford University, Dr. Sorin Draghici of
Wayne State University.
NR 155
TC 47
Z9 47
U1 5
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2049-2618
J9 MICROBIOME
JI Microbiome
PD MAY 27
PY 2014
VL 2
AR 18
DI 10.1186/2049-2618-2-18
PG 15
WC Microbiology
SC Microbiology
GA CU0FT
UT WOS:000363192200001
PM 24987521
ER
PT J
AU Kelsey, JS
Geczy, T
Lewin, NE
Kedei, N
Hill, CS
Selezneva, JS
Valle, CJ
Woo, W
Gorshkova, I
Blumberg, PM
AF Kelsey, Jessica S.
Geczy, Tamas
Lewin, Nancy E.
Kedei, Noemi
Hill, Colin S.
Selezneva, Julia S.
Valle, Christopher J.
Woo, Wonhee
Gorshkova, Inna
Blumberg, Peter M.
TI Charge Density Influences C1 Domain Ligand Affinity and Membrane
Interactions
SO CHEMBIOCHEM
LA English
DT Article
DE diacylglycerols; ingenol 3-angelate; phorbol esters; protein kinase C
ID PROTEIN-KINASE-C; NONPROMOTING 12-DEOXYPHORBOL 13-ESTERS;
CONFORMATIONALLY CONSTRAINED ANALOGS; SITE-DIRECTED MUTAGENESIS; LATENT
HIV-1 EXPRESSION; PROSTATE-CANCER CELLS; INGENOL MEBUTATE GEL; CD-1
MOUSE SKIN; PHORBOL ESTER; BRYOSTATIN 1
AB The C1 domain, which represents the recognition motif on protein kinase C for the lipophilic second messenger diacylglycerol and its ultrapotent analogues, the phorbol esters, has emerged as a promising therapeutic target for cancer and other indications. Potential target selectivity is markedly enhanced both because binding reflects ternary complex formation between the ligand, C1 domain, and phospholipid, and because binding drives membrane insertion of the C1 domain, permitting aspects of the C1 domain surface outside the binding site, per se, to influence binding energetics. Here, focusing on charged residues identified in atypical C1 domains which contribute to their loss of ligand binding activity, we showed that increasing charge along the rim of the binding cleft of the protein kinase C delta C1 b domain raises the requirement for anionic phospholipids. Correspondingly, it shifts the selectivity of C1 domain translocation to the plasma membrane, which is more negatively charged than internal membranes. This change in localization is most pronounced in the case of more hydrophilic ligands, which provide weaker membrane stabilization than do the more hydrophobic ligands and thus contributes an element to the structure-activity relations for C1 domain ligands. Coexpressing pairs of C1-containing constructs with differing charges each expressing a distinct fluorescent tag provided a powerful tool to demonstrate the effect of increasing charge in the C1 domain.
C1 [Kelsey, Jessica S.; Geczy, Tamas; Lewin, Nancy E.; Kedei, Noemi; Hill, Colin S.; Selezneva, Julia S.; Valle, Christopher J.; Woo, Wonhee; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
[Gorshkova, Inna] Natl Inst Biomed Imaging & Bioengn, Biomed Engn & Phys Sci Shared Resource Program, NIH, Bethesda, MD 20892 USA.
RP Blumberg, PM (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bldg 37,Room 4048 37 Convent Dr MSC 4255, Bethesda, MD 20892 USA.
EM blumberp@dc37a.nci.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH);
Center for Cancer Research (CCR); National Cancer Institute (NCI) [Z1A
BC 005270]; National Institute of Biomedical Imaging and Bioengineering
(BEPS)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), Center for Cancer Research (CCR),
National Cancer Institute (NCI; Z1A BC 005270), and the National
Institute of Biomedical Imaging and Bioengineering (BEPS). Imaging was
done in the CCR Confocal Microscopy Core Facility, NCI.
NR 51
TC 2
Z9 2
U1 0
U2 8
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1439-4227
EI 1439-7633
J9 CHEMBIOCHEM
JI ChemBioChem
PD MAY 26
PY 2014
VL 15
IS 8
BP 1131
EP 1144
DI 10.1002/cbic.201400041
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA AJ3QN
UT WOS:000337582200011
PM 24777910
ER
PT J
AU Calleri, E
Pochetti, G
Dossou, KSS
Laghezza, A
Montanari, R
Capelli, D
Prada, E
Loiodice, F
Massolini, G
Bernier, M
Moaddel, R
AF Calleri, Enrica
Pochetti, Giorgio
Dossou, Katina S. S.
Laghezza, Antonio
Montanari, Roberta
Capelli, Davide
Prada, Ellen
Loiodice, Fulvio
Massolini, Gabriella
Bernier, Michel
Moaddel, Ruin
TI Resveratrol and Its Metabolites Bind to PPARs
SO CHEMBIOCHEM
LA English
DT Article
DE biochromatography; isothermal titration calorimetry; PPARs; resveratrol;
transactivation assays; X-ray crystallography
ID ACTIVATED RECEPTOR-GAMMA; FRONTAL AFFINITY-CHROMATOGRAPHY;
CRYSTAL-STRUCTURE; ALPHA ACTIVATION; GENE-EXPRESSION; IN-VITRO;
AGONISTS; MECHANISM; DOMAIN; DIFFERENTIATION
AB Resveratrol, a modulator of several signaling proteins, can exert off-target effects involving the peroxisome proliferator-activated receptor (PPAR) transcription factors. However, evidence for the direct interaction between this polyphenol and PPARs is lacking. Here, we addressed the hypothesis that resveratrol and its metabolites control aspects of PPAR transcriptional activity through direct interaction with PPARs. Bioaffinity chromatographic studies with the immobilized ligand-binding domains (LBDs) of PPAR and PPAR and isothermal titration calorimetry allowed the binding affinities of resveratrol, resveratrol 3-O-glucuronide, resveratrol 4-O-glucuronide, and resveratrol 3-O-sulfate to both PPAR-LBDs to be determined. Interaction of resveratrol, resveratrol 3-O-glucuronide, and resveratrol 4-O-glucuronide with PPAR-LBD occurred with binding affinities of 1.4, 1.1, and 0.8 mu M, respectively, although only resveratrol bound to the PPAR alpha-LBD with a binding affinity of 2.7 mu M. Subsequently, X-ray crystallographic studies were carried out to characterize resveratrol binding to the PPAR gamma-LBD at the molecular level. The electron density map from the crystal structure of the complex between PPAR gamma-LBD and resveratrol revealed the presence of one molecule of resveratrol bound to the LBD of PPAR gamma, with the ligand occupying a position close to that of other known PPAR gamma ligands. Transactivation assays were also performed in HepG2 cells, with the results showing that resveratrol was not a PPAR agonist but instead was able to displace rosiglitazone from PPAR gamma and Wy-14643 from PPAR alpha with IC50 values of (27.4 +/- 1.8) mu M and (31.7 +/- 2.5) mu M, respectively. We propose that resveratrol acts as a PPAR antagonist through its direct interaction with PPAR gamma and PPAR alpha.
C1 [Calleri, Enrica; Prada, Ellen; Massolini, Gabriella] Univ Pavia, Dipartimento Sci Farmaco, I-27100 Pavia, Italy.
[Pochetti, Giorgio; Montanari, Roberta; Capelli, Davide] Consiglio Nazl Ric Montelibretti, Ist Cristallog, I-00015 Rome, Italy.
[Dossou, Katina S. S.; Bernier, Michel; Moaddel, Ruin] NIA, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
[Laghezza, Antonio; Loiodice, Fulvio] Univ Bari Aldo Moro, Dipartimento Farm Sci Farmaco, I-70126 Bari, Italy.
RP Moaddel, R (reprint author), NIA, Biomed Res Ctr, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM moaddelru@grc.nia.nih.gov
OI CALLERI, ENRICA/0000-0002-4246-460X; Bernier,
Michel/0000-0002-5948-368X; Laghezza, Antonio/0000-0001-6221-6155
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health; Ministero dell'Istruzione, dell'Universita e della
Ricerca [PRIN 2009K7R7NA]; Ministero dell'Universita e della Ricerca
Scientifica [2009Z8YTYC]
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging, National Institutes of Health (R.M.)
and financial support from the Ministero dell'Istruzione,
dell'Universita e della Ricerca (PRIN 2009K7R7NA to F.L.), and by a
grant from the Ministero dell'Universita e della Ricerca Scientifica
(grant no. 2009Z8YTYC to E.C.). There are no financial conflicts.
NR 39
TC 16
Z9 17
U1 2
U2 23
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1439-4227
EI 1439-7633
J9 CHEMBIOCHEM
JI ChemBioChem
PD MAY 26
PY 2014
VL 15
IS 8
BP 1154
EP 1160
DI 10.1002/cbic.201300754
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA AJ3QN
UT WOS:000337582200013
PM 24796862
ER
PT J
AU Liu, RJ
Dai, ZY
Yeager, M
Irizarry, RA
Ritchie, ME
AF Liu, Ruijie
Dai, Zhiyin
Yeager, Meredith
Irizarry, Rafael A.
Ritchie, Matthew E.
TI KRLMM: an adaptive genotype calling method for common and low frequency
variants
SO BMC BIOINFORMATICS
LA English
DT Article
DE Genotyping; Clustering; Microarray data analysis
ID GENOME-WIDE ASSOCIATION; ALGORITHM; POPULATION; BEADCHIPS; RARE; MAP
AB Background: SNP genotyping microarrays have revolutionized the study of complex disease. The current range of commercially available genotyping products contain extensive catalogues of low frequency and rare variants. Existing SNP calling algorithms have difficulty dealing with these low frequency variants, as the underlying models rely on each genotype having a reasonable number of observations to ensure accurate clustering.
Results: Here we develop KRLMM, a new method for converting raw intensities into genotype calls that aims to overcome this issue. Our method is unique in that it applies careful between sample normalization and allows a variable number of clusters k (1, 2 or 3) for each SNP, where k is predicted using the available data. We compare our method to four genotyping algorithms (GenCall, GenoSNP, Illuminus and OptiCall) on several Illumina data sets that include samples from the HapMap project where the true genotypes are known in advance. All methods were found to have high overall accuracy (> 98%), with KRLMM consistently amongst the best. At low minor allele frequency, the KRLMM, OptiCall and GenoSNP algorithms were observed to be consistently more accurate than GenCall and Illuminus on our test data.
Conclusions: Methods that tailor their approach to calling low frequency variants by either varying the number of clusters (KRLMM) or using information from other SNPs (OptiCall and GenoSNP) offer improved accuracy over methods that do not (GenCall and Illuminus). The KRLMM algorithm is implemented in the open-source crlmm package distributed via the Bioconductor project (http://www.bioconductor.org).
C1 [Liu, Ruijie; Dai, Zhiyin; Ritchie, Matthew E.] Walter & Eliza Hall Inst Med Res, Mol Med Div, Parkville, Vic 3052, Australia.
[Yeager, Meredith] NCI Frederick, Canc Genom Res Lab, SAIC Frederick Inc, Frederick, MD 20877 USA.
[Irizarry, Rafael A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Ritchie, Matthew E.] Univ Melbourne, Dept Math & Stat, Parkville, Vic 3010, Australia.
[Ritchie, Matthew E.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.
RP Irizarry, RA (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, CLSB 11007,450 Brookline Ave, Boston, MA 02215 USA.
EM rafa@jimmy.harvard.edu; mritchie@wehi.edu.au
OI Ritchie, Matthew/0000-0002-7383-0609
FU NHMRC [1050661]; Victorian State Government; Australian Government NHMRC
IRIISS; NIH [R01GM083084]
FX We thank Gordon Smyth for advice on regression analysis. This research
was supported by NHMRC Project grant 1050661 (RL, MR), Victorian State
Government Operational Infrastructure Support, Australian Government
NHMRC IRIISS and NIH grant R01GM083084 (RI).
NR 26
TC 0
Z9 0
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD MAY 23
PY 2014
VL 15
AR 158
DI 10.1186/1471-2105-15-158
PG 11
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA AK2IS
UT WOS:000338243300001
PM 24886250
ER
PT J
AU Moktan, H
Guiraldelli, MF
Eyster, CA
Zhao, WX
Lee, CY
Mather, T
Camerini-Otero, RD
Sung, P
Zhou, DHH
Pezza, RJ
AF Moktan, Hem
Guiraldelli, Michel F.
Eyster, Craig A.
Zhao, Weixing
Lee, Chih-Ying
Mather, Timothy
Camerini-Otero, R. Daniel
Sung, Patrick
Zhou, Donghua H.
Pezza, Roberto J.
TI Solution Structure and DNA-binding Properties of the Winged Helix Domain
of the Meiotic Recombination HOP2 Protein
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NMR STRUCTURE DETERMINATION; CHROMOSOME SEGREGATION; HOP2-MND1 COMPLEX;
OPERATOR COMPLEX; CHEMICAL-SHIFTS; MEIOSIS; MND1; INSIGHTS; REVEALS;
RAD51
AB The HOP2 protein is required for efficient double-strand break repair which ensures the proper synapsis of homologous chromosomes and normal meiotic progression. We previously showed that in vitro HOP2 shows two distinctive activities: when it is incorporated into a HOP2-MND1 heterodimer, it stimulates DMC1 and RAD51 recombination activities, and the purified HOP2 alone is proficient in promoting strand invasion. The structural and biochemical basis of HOP2 action in recombination are poorly understood; therefore, they are the focus of this work. Herein, we present the solution structure of the amino-terminal portion of mouse HOP2, which contains a typical winged helix DNA-binding domain. Together with NMR spectral changes in the presence of double-stranded DNA, protein docking on DNA, and mutation analysis to identify the amino acids involved in DNA coordination, our results on the three-dimensional structure of HOP2 provide key information on the fundamental structural and biochemical requirements directing the interaction of HOP2 with DNA. These results, in combination with mutational experiments showing the role of a coiled-coil structural feature involved in HOP2 self-association, allow us to explain important aspects of the function of HOP2 in recombination.
C1 [Moktan, Hem; Zhou, Donghua H.] Oklahoma State Univ, Dept Phys, Stillwater, OK 74078 USA.
[Guiraldelli, Michel F.; Eyster, Craig A.; Lee, Chih-Ying; Pezza, Roberto J.] Oklahoma Med Res Fdn, Cell Cycle & Canc Biol Program, Oklahoma City, OK 73104 USA.
[Zhao, Weixing; Sung, Patrick] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
[Mather, Timothy] Oklahoma Med Res Fdn, Cardiovasc Biol Program, Oklahoma City, OK 73104 USA.
[Mather, Timothy] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73104 USA.
[Camerini-Otero, R. Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
[Pezza, Roberto J.] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73126 USA.
RP Pezza, RJ (reprint author), Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA.
EM Roberto-Pezza@omrf.org
FU NIGMS, National Institutes of Health [1P20GM103636]; Oklahoma Center for
the Advancement of Science and Technology Grant [HR10-48S]; National
Institutes of Health [GM097713]; Oklahoma Center for the Advancement of
Science and Technology [HR12-050]
FX This work was supported by NIGMS, National Institutes of Health Award
1P20GM103636 and by Oklahoma Center for the Advancement of Science and
Technology Grant HR10-48S (to R. J. P.). This work was also supported by
National Institutes of Health Grant GM097713 (to D. H. Z.) and Oklahoma
Center for the Advancement of Science and Technology Grant HR12-050 (to
D. H. Z.).
NR 43
TC 6
Z9 6
U1 0
U2 14
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 23
PY 2014
VL 289
IS 21
BP 14682
EP 14691
DI 10.1074/jbc.M114.548180
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AI9JE
UT WOS:000337248100025
PM 24711446
ER
PT J
AU Peters, DE
Szabo, R
Friis, S
Shylo, NA
Sales, KU
Holmbeck, K
Bugge, TH
AF Peters, Diane E.
Szabo, Roman
Friis, Stine
Shylo, Natalia A.
Sales, Katiuchia Uzzun
Holmbeck, Kenn
Bugge, Thomas H.
TI The Membrane-anchored Serine Protease Prostasin (CAP1/PRSS8) Supports
Epidermal Development and Postnatal Homeostasis Independent of Its
Enzymatic Activity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MATRIPTASE-ACTIVATION; PROTEOLYTIC CASCADE; BARRIER FUNCTION; MUTATIONS;
DIFFERENTIATION; CHANNELS; CLOSURE; MICE; CELL
AB The membrane-anchored serine protease prostasin (CAP1/PRSS8) is part of a cell surface proteolytic cascade that is essential for epithelial barrier formation and homeostasis. Here, we report the surprising finding that prostasin executes these functions independent of its own enzymatic activity. Prostasin null (Prss8(-/-)) mice lack barrier formation and display fatal postnatal dehydration. In sharp contrast, mice homozygous for a point mutation in the Prss8 gene, which causes the substitution of the active site serine within the catalytic histidine-aspartate-serine triad with alanine and renders prostasin catalytically inactive (Prss8(Cat-/Cat-) mice), develop barrier function and are healthy when followed for up to 20 weeks. This striking difference could not be explained by genetic modifiers or by maternal effects, as these divergent phenotypes were displayed by Prss8(-/-) and Prss8Cat(-/Cat-) mice born within the same litter. Furthermore, Prss8Cat(-/Cat-) mice were able to regenerate epidermal covering following cutaneous wounding. This study provides the first demonstration that essential in vivo functions of prostasin are executed by a non-enzymatic activity of this unique membrane-anchored serine protease.
C1 [Peters, Diane E.; Szabo, Roman; Friis, Stine; Shylo, Natalia A.; Sales, Katiuchia Uzzun; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Peters, Diane E.] Tufts Univ, Sch Med, Program Pharmacol & Expt Therapeut, Boston, MA 02111 USA.
[Friis, Stine] Univ Copenhagen, Dept Cellular & Mol Med, Fac Hlth Sci, DK-2200 Copenhagen, Denmark.
[Holmbeck, Kenn] Natl Inst Dent & Craniofacial Res, Connect Tissue Remodeling Sect, NIH, Bethesda, MD 20892 USA.
[Sales, Katiuchia Uzzun] Natl Inst Dent & Craniofacial Res, Clin Res Core, NIH, Bethesda, MD 20892 USA.
RP Bugge, TH (reprint author), Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Rm 211, Bethesda, MD 20892 USA.
EM thomas.bugge@nih.gov
FU NIDCR Intramural Research Program; Harboe Foundation; Lundbeck
Foundation; Foundation of 17.12.1981
FX This work was supported by the NIDCR Intramural Research Program (to K.
H. and T. H. B.), by The Harboe Foundation, The Lundbeck Foundation, and
the Foundation of 17.12.1981 (to S. F.).
NR 24
TC 11
Z9 11
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 23
PY 2014
VL 289
IS 21
BP 14740
EP 14749
DI 10.1074/jbc.M113.541318
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AI9JE
UT WOS:000337248100030
PM 24706745
ER
PT J
AU Kohler, D
Devanathan, V
Franz, CBD
Eldh, T
Novakovic, A
Roth, JM
Granja, T
Birnbaumer, L
Rosenberger, P
Beer-Hammer, S
Nurnberg, B
AF Koehler, David
Devanathan, Vasudharani
Franz, Claudia Bernardo de Oliveira
Eldh, Therese
Novakovic, Ana
Roth, Judith M.
Granja, Tiago
Birnbaumer, Lutz
Rosenberger, Peter
Beer-Hammer, Sandra
Nuernberg, Bernd
TI G alpha(i2)- and G alpha(i3)- Deficient Mice Display Opposite Severity
of Myocardial Ischemia Reperfusion Injury
SO PLOS ONE
LA English
DT Article
ID G-PROTEIN; PERTUSSIS TOXIN; DISEASE; CARDIOMYOCYTES; INHIBITION;
MIGRATION; CYCLASE; HEART
AB G-protein-coupled receptors (GPCRs) are the most abundant receptors in the heart and therefore are common targets for cardiovascular therapeutics. The activated GPCRs transduce their signals via heterotrimeric G-proteins. The four major families of G-proteins identified so far are specified through their alpha-subunit: G alpha(i), G alpha(s), G alpha(q) and G(12/13). G alpha(i)-proteins have been reported to protect hearts from ischemia reperfusion injury. However, determining the individual impact of G alpha(i2) or G alpha(i3) on myocardial ischemia injury has not been clarified yet. Here, we first investigated expression of G alpha(i2) and G alpha(i3) on transcriptional level by quantitative PCR and on protein level by immunoblot analysis as well as by immunofluorescence in cardiac tissues of wild-type, G alpha(i2), and G alpha(i3)-deficient mice. G alpha(i2) was expressed at higher levels than G alpha(i3) in murine hearts, and irrespective of the isoform being knocked out we observed an up regulation of the remaining G alpha i-protein. Myocardial ischemia promptly regulated cardiac mRNA and with a slight delay protein levels of both G alpha(i2) and G alpha(i3), indicating important roles for both G alpha(i) isoforms. Furthermore, ischemia reperfusion injury in G alpha(i2)- and G alpha(i3)-deficient mice exhibited opposite outcomes. Whereas the absence of G alpha(i2) significantly increased the infarct size in the heart, the absence of G alpha(i3) or the concomitant upregulation of G alpha(i2) dramatically reduced cardiac infarction. In conclusion, we demonstrate for the first time that the genetic ablation of G alpha(i) proteins has protective or deleterious effects on cardiac ischemia reperfusion injury depending on the isoform being absent.
C1 [Koehler, David; Franz, Claudia Bernardo de Oliveira; Roth, Judith M.; Granja, Tiago; Rosenberger, Peter] Eberhard Karls Univ Hosp & Clin, Dept Anesthesiol & Intens Care Med, Inst Expt & Clin Pharmacol & Toxicol, Tubingen, Germany.
[Koehler, David; Devanathan, Vasudharani; Franz, Claudia Bernardo de Oliveira; Eldh, Therese; Novakovic, Ana; Roth, Judith M.; Granja, Tiago; Rosenberger, Peter; Beer-Hammer, Sandra; Nuernberg, Bernd] Interfac Ctr Pharmacogen & Drug Res, Tubingen, Germany.
[Devanathan, Vasudharani; Eldh, Therese; Novakovic, Ana; Beer-Hammer, Sandra; Nuernberg, Bernd] Eberhard Karls Univ Hosp & Clin, Inst Expt & Clin Pharmacol & Toxicol, Dept Pharmacol & Expt Therapy, Tubingen, Germany.
[Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Div Intramural Res, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Beer-Hammer, S (reprint author), Eberhard Karls Univ Hosp & Clin, Inst Expt & Clin Pharmacol & Toxicol, Dept Pharmacol & Expt Therapy, Tubingen, Germany.
EM sandra.beer-hammer@uni-tuebingen.de; bernd.nuernberg@uni-tuebingen.de
FU Deutsche Forschungsgemeinschaft [SFB 612, MO2252/1]; Tuebingen
University; NIH [Z01-ES-101643]
FX This work was supported by grants of the Deutsche Forschungsgemeinschaft
(SFB 612 to B.N. and MO2252/1 to D. K.), the Open Access Publishing Fund
of Tuebingen University and the Intramural Research Program of the NIH
(project Z01-ES-101643 to L. B.). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 29
TC 9
Z9 9
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 23
PY 2014
VL 9
IS 5
AR e98325
DI 10.1371/journal.pone.0098325
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI4ML
UT WOS:000336839400066
PM 24858945
ER
PT J
AU Paoletta, S
Tosh, DK
Salvemini, D
Jacobson, KA
AF Paoletta, Silvia
Tosh, Dilip K.
Salvemini, Daniela
Jacobson, Kenneth A.
TI Structural Probing of Off-Target G Protein-Coupled Receptor Activities
within a Series of Adenosine/Adenine Congeners
SO PLOS ONE
LA English
DT Article
ID SEROTONIN RECEPTORS; DRUG DESIGN; NUCLEOSIDES; AGONISTS; 2-ARYLETHYNYL;
SUBSTITUTIONS; PROMISCUITY; SELECTIVITY; ANTAGONISTS; ACTIVATION
AB We studied patterns of off-target receptor interactions, mostly at G protein-coupled receptors (GPCRs) in the mu M range, of nucleoside derivatives that are highly engineered for nM interaction with adenosine receptors (ARs). Because of the considerable interest of using AR ligands for treating diseases of the CNS, we used the Psychoactive Drug Screening Program (PDSP) for probing promiscuity of these adenosine/adenine congeners at 41 diverse receptors, channels and a transporter. The step-wise truncation of rigidified, trisubstituted (at N degrees, C2, and 5' positions) nucleosides revealed unanticipated interactions mainly with biogenic amine receptors, such as adrenergic receptors and serotonergic receptors, with affinities as high as 61 nM. The unmasking of consistent sets of structure activity relationship (SAR) at novel sites suggested similarities between receptor families in molecular recognition. Extensive molecular modeling of the GPCRs affected suggested binding modes of the ligands that supported the patterns of SAR at individual receptors. In some cases, the ligand docking mode closely resembled AR binding and in other cases the ligand assumed different orientations. The recognition patterns for different GPCRs were clustered according to which substituent groups were tolerated and explained in light of the complementarity with the receptor binding site. Thus, some likely off-target interactions, a concern for secondary drug effects, can be predicted for analogues of this set of substructures, aiding the design of additional structural analogues that either eliminate or accentuate certain off-target activities. Moreover, similar analyses could be performed for unrelated structural families for other GPCRs.
C1 [Paoletta, Silvia; Tosh, Dilip K.; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Salvemini, Daniela] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA.
RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU National Institutes of Health (Intramural Research Program of the
NIDDK); National Institutes of Health [R01HL077707]
FX This research was supported by the National Institutes of Health
(Intramural Research Program of the NIDDK and R01HL077707). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 40
TC 12
Z9 12
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 23
PY 2014
VL 9
IS 5
AR e97858
DI 10.1371/journal.pone.0097858
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI4ML
UT WOS:000336839400028
PM 24859150
ER
PT J
AU Xiong, Y
Zhang, LS
Kebebew, E
AF Xiong, Yin
Zhang, Lisa
Kebebew, Electron
TI MiR-20a Is Upregulated in Anaplastic Thyroid Cancer and Targets LIMK1
SO PLOS ONE
LA English
DT Article
ID BREAST-CANCER; MIR-17-92 CLUSTER; TUMOR-METASTASIS; PROSTATE-CANCER;
CELL-LINE; MICRORNA; INVASION; EXPRESSION; KINASE; PROLIFERATION
AB Background: There have been conflicting reports regarding the function of miR-20a in a variety of cancer types and we previously found it to be dysregulated in sporadic versus familial papillary thyroid cancer. In this study, we studied the expression of miR-20a in normal, benign and malignant thyroid samples, and its effect on thyroid cancer cells in vitro and in vivo.
Methodology/Principal Findings: The expression of miR-20a in normal, benign and malignant thyroid tissue was determined by quantitative RT-PCR. Thyroid cancer cells were transfected with miR-20a and the effect on cellular proliferation, tumor spheroid formation, and invasion was evaluated. Target genes of miR-20 were determined by genome-wide mRNA expression analysis with miR-20a overexpression in thyroid cancer cells and target prediction database. Target genes were validated by quantitative PCR and immunoblotting, and luciferase assays. MiR-20a expression was significantly higher in anaplastic thyroid cancer than in differentiated thyroid cancer, and benign and normal thyroid tissues. MiR-20a significantly inhibited thyroid cancer cell proliferation in vitro (p<0.01) and in vivo (p<0.01), tumor spheroid formation (p<0.05) and invasion (p<0.05) in multiple thyroid cancer cell lines. We found that LIMK1 was a target of miR-20a in thyroid cancer cell lines and direct knockdown of LIMK1 recapitulated the effect of miR-20a in thyroid cancer cells.
Conclusions/Significance: To our knowledge, this is the first study to demonstrate that miR-20a plays a role as a tumor suppressor in thyroid cancer cells and targets LIMK1. Our findings suggest the upregulated expression of miR-20a in anaplastic thyroid cancer counteracts thyroid cancer progression and may have therapeutic potential.
C1 [Xiong, Yin; Zhang, Lisa; Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
FU National Institutes of Health, National Cancer Institute
FX This work was funded by the National Institutes of Health, National
Cancer Institute. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 34
TC 22
Z9 22
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 23
PY 2014
VL 9
IS 5
AR e96103
DI 10.1371/journal.pone.0096103
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI4ML
UT WOS:000336839400001
PM 24858712
ER
PT J
AU Gromowski, GD
Firestone, CY
Hanson, CT
Whitehead, SS
AF Gromowski, Gregory D.
Firestone, Cai-Yen
Hanson, Christopher T.
Whitehead, Stephen S.
TI Japanese encephalitis virus vaccine candidates generated by
chimerization with dengue virus type 4
SO VACCINE
LA English
DT Article
DE Japanese encephalitis virus; Chimeric virus; Live-attenuated vaccine
ID ANTIBODY-MEDIATED NEUTRALIZATION; RHESUS-MONKEYS; PHYLOGENETIC ANALYSIS;
PROTECTIVE EFFICACY; CAPSID PROTEIN; CORE PROTEIN; FLAVIVIRUS;
IMMUNOGENICITY; CLEAVAGE; REPLICATION
AB Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis worldwide and vaccination is one of the most effective ways to prevent disease. A suitable live-attenuated JEV vaccine could be formulated with a live-attenuated tetravalent dengue vaccine for the control of these viruses in endemic areas. Toward this goal, we generated chimeric virus vaccine candidates by replacing the precursor membrane (prM) and envelope (E) protein structural genes of recombinant dengue virus type 4 (rDEN4) or attenuated vaccine candidate rDEN4 Delta 30 with those of wild-type JEV strain India/78. Mutations were engineered in E, NS3 and NS4B protein genes to improve replication in Vero cells. The chimeric viruses were attenuated in mice and some elicited modest but protective levels of immunity after a single dose. One particular chimeric virus, bearing E protein mutation Q264H, replicated to higher titer in tissue culture and was significantly more immunogenic in mice. The results are compared with live-attenuated JEV vaccine strain SA14-14-2. Published by Elsevier Ltd.
C1 [Gromowski, Gregory D.; Firestone, Cai-Yen; Hanson, Christopher T.; Whitehead, Stephen S.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Gromowski, GD (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM gromowskig@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases Intramural
Research Program; National Institutes of Health
FX We would like to thank the NIAID Comparative Medicine Branch for
assisting with animal studies, Dr. Jose Bustos-Arriaga for assisting
with flow cytometry, and Drs. Ted Pierson and Kim Dowd for supplying
reagents and expertise for the RVP assay. This work was supported by the
National Institute of Allergy and Infectious Diseases Intramural
Research Program, National Institutes of Health.
NR 49
TC 6
Z9 6
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD MAY 23
PY 2014
VL 32
IS 25
BP 3010
EP 3018
DI 10.1016/j.vaccine.2014.03.062
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AI2UG
UT WOS:000336713000015
PM 24699473
ER
PT J
AU Weisz, A
Ridge, CD
Roque, JA
Mazzola, EP
Ito, Y
AF Weisz, Adrian
Ridge, Clark D.
Roque, Jose A.
Mazzola, Eugene P.
Ito, Yoichiro
TI Preparative separation of two subsidiary colors of FD&C Yellow No. 5
(Tartrazine) using spiral high-speed counter-current chromatography
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE Spiral high-speed counter-current chromatography; Highly polar
organic/high-ionic strength aqueous two-phase solvent systems; FD&C
Yellow No. 5; Tartrazine; Subsidiary colors; NMR
ID TUBING SUPPORT ROTOR; ACID-BASE EQUILIBRIA; QUINOLINE YELLOW;
AZO-HYDRAZONE; PURIFICATION; COMPONENTS; SYSTEMS; DYES; SALT
AB Specifications in the U.S. Code of Federal Regulations for the color additive FD&C Yellow No. 5 (Color Index No. 19140) limit the level of the tetrasodium salt of 4-[(4',5-disulfo[1,1'-biphenyl]-2-yl)hydrazono]-4,5-dihydro-5-oxo-1-(4-sulfophenyl)-1H-pyrazole-3-carboxylic acid and that of the trisodium salt of 4,4'-[4,5-dihydro-5-oxo-4-[(4-sulfophenyl)hydrazono]-1H-pyrazol-1,3-diyl]bis[benzenesulfonic acid], which are subsidiary colors abbreviated as Pk5 and Pk7, respectively. Small amounts of Pk5 and Pk7 are needed by the U.S. Food and Drug Administration for confirmatory analyses and for development of analytical methods. The present study describes the use of spiral high-speed counter-current chromatography (HSCCC) to separate the closely related minor components Pk5 and Pk7 from a sample of FD&C Yellow No. 5 containing similar to 3.5% Pk5 and similar to 0.7% Pk7. The separations were performed with highly polar organic/high-ionic strength aqueous two-phase solvent systems that were chosen by applying the recently introduced method known as graphic optimization of partition coefficients (Zeng et al., 2013). Multiple similar to 1.0 g portions of FD&C Yellow No. 5 (totaling 6.4g dye) were separated, using the upper phase of the solvent system 1-butanol/abs. ethanol/saturated ammonium sulfate/water, 1.7:0.3:1:1, v/v/v/v, as the mobile phase. After removing the ammonium sulfate from the HSCCC-collected fractions, these separations resulted in an enriched dye mixture (similar to 160 mg) of which Pk5 represented similar to 46% and Pk7, similar to 21%. Separation of the enriched mixture, this time using the lower phase of that solvent system as the mobile phase, resulted in 61 mg of Pk5 collected in fractions whose purity ranged from 88.0% to 92.7%. Pk7 (20.7 mg, similar to 83% purity) was recovered from the upper phase of the column contents. Application of this procedure also resulted in purifying the major component of FD&C Yellow No. 5 to >99% purity. The separated compounds were characterized by high-resolution mass spectrometry and several H-1 and C-13 nuclear magnetic resonance spectroscopic techniques. Published by Elsevier B.V.
C1 [Weisz, Adrian; Roque, Jose A.] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Ridge, Clark D.; Mazzola, Eugene P.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
EM adrian.weisz@fda.hhs.gov
FU Intramural NIH HHS [ZIA HL005107-06]
NR 37
TC 7
Z9 7
U1 6
U2 35
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
EI 1873-3778
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD MAY 23
PY 2014
VL 1343
BP 91
EP 100
DI 10.1016/j.chroma.2014.03.059
PG 10
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA AH5UE
UT WOS:000336195800012
PM 24755184
ER
PT J
AU Raj, DK
Nixon, CP
Nixon, CE
Dvorin, JD
DiPetrillo, CG
Pond-Tor, S
Wu, HW
Jolly, G
Pischel, L
Lu, AL
Michelow, IC
Cheng, L
Conteh, S
McDonald, EA
Absalon, S
Holte, SE
Friedman, JF
Fried, M
Duffy, PE
Kurtis, JD
AF Raj, Dipak K.
Nixon, Christian P.
Nixon, Christina E.
Dvorin, Jeffrey D.
DiPetrillo, Christen G.
Pond-Tor, Sunthorn
Wu, Hai-Wei
Jolly, Grant
Pischel, Lauren
Lu, Ailin
Michelow, Ian C.
Cheng, Ling
Conteh, Solomon
McDonald, Emily A.
Absalon, Sabrina
Holte, Sarah E.
Friedman, Jennifer F.
Fried, Michal
Duffy, Patrick E.
Kurtis, Jonathan D.
TI Antibodies to PfSEA-1 block parasite egress from RBCs and protect
against malaria infection
SO SCIENCE
LA English
DT Article
ID PLASMODIUM-FALCIPARUM; HUMAN RESISTANCE; ERYTHROCYTES; INVASION;
VACCINE; GROWTH
AB Novel vaccines are urgently needed to reduce the burden of severe malaria. Using a differential whole-proteome screening method, we identified Plasmodium falciparum schizont egress antigen-1 (PfSEA-1), a 244-kilodalton parasite antigen expressed in schizont-infected red blood cells (RBCs). Antibodies to PfSEA-1 decreased parasite replication by arresting schizont rupture, and conditional disruption of PfSEA-1 resulted in a profound parasite replication defect. Vaccination of mice with recombinant Plasmodium berghei PbSEA-1 significantly reduced parasitemia and delayed mortality after lethal challenge with the Plasmodium berghei strain ANKA. Tanzanian children with antibodies to recombinant PfSEA-1A (rPfSEA-1A) did not experience severe malaria, and Kenyan adolescents and adults with antibodies to rPfSEA-1A had significantly lower parasite densities than individuals without these antibodies. By blocking schizont egress, PfSEA-1 may synergize with other vaccines targeting hepatocyte and RBC invasion.
C1 [Raj, Dipak K.; Nixon, Christian P.; Nixon, Christina E.; Pond-Tor, Sunthorn; Wu, Hai-Wei; Pischel, Lauren; Lu, Ailin; Michelow, Ian C.; Cheng, Ling; McDonald, Emily A.; Friedman, Jennifer F.; Kurtis, Jonathan D.] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Ctr Int Hlth Res, Providence, RI 02903 USA.
[Dvorin, Jeffrey D.; DiPetrillo, Christen G.; Absalon, Sabrina] Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Dvorin, Jeffrey D.; DiPetrillo, Christen G.; Absalon, Sabrina] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Wu, Hai-Wei; Michelow, Ian C.; Friedman, Jennifer F.] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Dept Pediat, Providence, RI 02903 USA.
[Jolly, Grant; Kurtis, Jonathan D.] Brown Univ, Warren Alpert Med Sch, Rhode Isl Hosp, Dept Pathol & Lab Med, Providence, RI 02906 USA.
[Conteh, Solomon; Fried, Michal; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20892 USA.
[Holte, Sarah E.] Univ Washington, Fred Hutchinson Canc Res Ctr, Program Biostat & Biomath, Dept Biostat & Global Hlth, Seattle, WA 98109 USA.
RP Kurtis, JD (reprint author), Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Ctr Int Hlth Res, Providence, RI 02903 USA.
EM jonathan_kurtis@brown.edu
OI Absalon, Sabrina/0000-0002-4167-3071; Friedman,
Jennifer/0000-0001-5804-9921
FU U.S. National Institutes of Health (NIH) [R01-AI52059]; Bill & Melinda
Gates Foundation [1364]; Intramural Research Program of the National
Institute of Allergy and Infectious Diseases-NIH; NIH [R01-AI076353,
R01-AI102907, DP2-AI112219, T32-DA013911, 1K08AI100997-01A1]; internal
Lifespan Hospital System Research Pilot Award Grant
FX The authors thank the Mother Offspring Malaria Study project staff for
their efforts in collecting clinical data, processing samples, and
interpreting malaria blood smears, as well as the study participants and
their families. Ethical clearance was obtained from the institutitional
review boards of the Seattle Biomedical Research Institute and Rhode
Island Hospital; the Medical Research Coordinating Committee of the
National Institute for Medical Research, Tanzania; and the Kenyan
Medical Research Institute. We thank A. Muehlenbachs for assistance in
interpreting the electron microscopy images, B. Morrison for assistance
with data management, and D. Lanar for the LSA proteins. This work was
supported by grants from the U.S. National Institutes of Health (NIH)
(grant R01-AI52059) and the Bill & Melinda Gates Foundation (grant 1364)
to P. E. D., the Intramural Research Program of the National Institute
of Allergy and Infectious Diseases-NIH, and grants from NIH (grant
R01-AI076353) and an internal Lifespan Hospital System Research Pilot
Award Grant to J.D.K., and grants from NIH to J.D.D. (R01-AI102907 and
DP2-AI112219). C.E.N. (grant T32-DA013911) and I.C.M. (grant
1K08AI100997-01A1) were supported by NIH. We also acknowledge research
core services provided by the Rhode Island Hospital imaging core (G.
Hovanesian) and core services supported by Lifespan/Tufts/Brown Center
for Aids Research (P30AI042853) and Center for Biomedical Research
Excellence (P20GM103421). The DNA sequence for PfSEA-1 is available in
PlasmoDB (www.Plasmodb.org) as ID no. PF3D7_1021800. The work presented
in this manuscript has been submitted in partial support of patent
application PCT/US12/67404 filed with the U.S. Patent Office. J.D.K.,
J.F.F., M.F., and P.E.D. designed the study; J.D.K., D.K.R., J.F.F., M.
F., and P. E. D. drafted the manuscript; M. F. and P. E. D. conducted
the field-based sample and epidemiologic data collection; C.P.N.
conducted the differential screening; D. K. R, L. P., A. L., C.E.N., and
L. C. performed the in vitro growth assays; D. K. R. and G.J. performed
the immunolocalization; D. K. R. performed the gene knockout studies; C.
G. D., E. A. M., S. A., and J.D.D. performed the conditional gene
knockdown studies; I. C. M. performed the single-nucleotide polymorphism
detection; S.P.-T., L.C., and H.-W.W. performed the antibody detection
assays; S.P.-T. expressed and purified rPf SEA-1A and rPbSEA-1A; D.K.R.,
C.E.N., and S. C. performed the vaccination studies; J.F.F., J.D.K., and
S.E.H. performed the statistical analyses; and J.D.K., J.F.F., M.F., and
P.E.D. supervised the study. The authors declare no competing financial
interests.
NR 26
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U1 1
U2 20
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD MAY 23
PY 2014
VL 344
IS 6186
BP 871
EP 877
DI 10.1126/science.1254417
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH6IL
UT WOS:000336233800040
PM 24855263
ER
PT J
AU Wiestner, A
AF Wiestner, Adrian
TI Predicting treatment outcomes in CLL
SO BLOOD
LA English
DT Editorial Material
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MUTATIONS; NOTCH1; TRIAL; SF3B1
C1 NIH, Bethesda, MD 20892 USA.
RP Wiestner, A (reprint author), NIH, Bethesda, MD 20892 USA.
NR 10
TC 0
Z9 0
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 22
PY 2014
VL 123
IS 21
BP 3212
EP 3214
DI 10.1182/blood-2014-04-565325
PG 5
WC Hematology
SC Hematology
GA AQ2LA
UT WOS:000342616300002
PM 24855188
ER
PT J
AU Herman, SEM
Mustafa, RZ
Gyamfi, JA
Pittaluga, S
Chang, S
Chang, B
Farooqui, M
Wiestner, A
AF Herman, Sarah E. M.
Mustafa, Rashida Z.
Gyamfi, Jennifer A.
Pittaluga, Stefania
Chang, Stella
Chang, Betty
Farooqui, Mohammed
Wiestner, Adrian
TI Ibrutinib inhibits BCR and NF-kappa B signaling and reduces tumor
proliferation in tissue-resident cells of patients with CLL
SO BLOOD
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; TYROSINE KINASE BTK; IN-VIVO; TARGETING
BTK; OPEN-LABEL; LYMPHOMA; ACTIVATION; PCI-32765; THERAPY; MALIGNANCIES
AB Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental factors for proliferation and survival. In particular, tissue-resident CLL cells show prominent activation of both B-cell receptor (BCR) and NF-kappa B pathways. We evaluated the in vivo effects of ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor on tumor cell activation and proliferation in the blood, lymph node, and bone marrow of patients with CLL. Applying validated pathway-specific gene signatures, we detected a rapid and sustained downregulation of BCR and NF-kappa B signaling in CLL cells from both the peripheral blood and tissue compartments during ibrutinib treatment. Ibrutinib reduced phosphorylation of PLC gamma 2 and ERK and decreased nuclear protein expression of NF-kappa B p50. Ibrutinib significantly decreased tumor proliferation and expression of surface activation markers CD69 and CD86, independent of prognostic factors such as IGHV mutational status, chromosome 17p deletion, or prior treatment history. Interestingly, stronger inhibition of BCR signaling in lymph node resident CLL cells after one dose of ibrutinib was associated with a higher rate of nodal response at the end of cycle 2. Together, these data validate on-target effects of BTK inhibition in the tissue compartments and demonstrate that ibrutinib effectively inhibits pathways that promote tumor cell activation and proliferation in vivo. This study is registered at www.clinicaltrials.gov as #NCT01500733.
C1 [Herman, Sarah E. M.; Mustafa, Rashida Z.; Gyamfi, Jennifer A.; Farooqui, Mohammed; Wiestner, Adrian] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Pittaluga, Stefania] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Chang, Stella; Chang, Betty] Pharmacyclics Inc, Sunnyvale, CA USA.
RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM adrian.wiestner@nih.gov
FU Intramural Research Program, the National, Heart, Lung and Blood
Institute, the National Institutes of Health
FX This work was supported by the Intramural Research Program, the
National, Heart, Lung and Blood Institute, the National Institutes of
Health.
NR 49
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U1 0
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 22
PY 2014
VL 123
IS 21
BP 3286
EP 3295
DI 10.1182/blood-2014-02-548610
PG 10
WC Hematology
SC Hematology
GA AQ2LA
UT WOS:000342616300015
PM 24659631
ER
PT J
AU Hollingshead, MG
Stockwin, LH
Alcoser, SY
Newton, DL
Orsburn, BC
Bonomi, CA
Borgel, SD
Divelbiss, R
Dougherty, KM
Hager, EJ
Holbeck, SL
Kaur, G
Kimmel, DJ
Kunkel, MW
Millione, A
Mullendore, ME
Stotler, H
Collins, J
AF Hollingshead, Melinda G.
Stockwin, Luke H.
Alcoser, Sergio Y.
Newton, Dianne L.
Orsburn, Benjamin C.
Bonomi, Carrie A.
Borgel, Suzanne D.
Divelbiss, Raymond
Dougherty, Kelly M.
Hager, Elizabeth J.
Holbeck, Susan L.
Kaur, Gurmeet
Kimmel, David J.
Kunkel, Mark W.
Millione, Angelena
Mullendore, Michael E.
Stotler, Howard
Collins, Jerry
TI Gene expression profiling of 49 human tumor xenografts from in vitro
culture through multiple in vivo passages - strategies for data mining
in support of therapeutic studies
SO BMC GENOMICS
LA English
DT Article
DE Xenograft models; Affymetrix HG-U133 Plus 2.0 array; cDNA microarray;
NCI-60 cell line screen; Transcriptomic stability; Transcriptomic
expression; in vitro to in vivo transition
ID CELL-LINES; MESSENGER-RNA; CANCER CELLS; CHEMOSENSITIVITY; MICROARRAYS;
RESISTANCE; MIGRATION; INVASION; PATHWAY; GROWTH
AB Background: Development of cancer therapeutics partially depends upon selection of appropriate animal models. Therefore, improvements to model selection are beneficial.
Results: Forty-nine human tumor xenografts at in vivo passages 1, 4 and 10 were subjected to cDNA microarray analysis yielding a dataset of 823 Affymetrix HG-U133 Plus 2.0 arrays. To illustrate mining strategies supporting therapeutic studies, transcript expression was determined: 1) relative to other models, 2) with successive in vivo passage, and 3) during the in vitro to in vivo transition. Ranking models according to relative transcript expression in vivo has the potential to improve initial model selection. For example, combining p53 tumor expression data with mutational status could guide selection of tumors for therapeutic studies of agents where p53 status purportedly affects efficacy (e.g., MK-1775). The utility of monitoring changes in gene expression with extended in vivo tumor passages was illustrated by focused studies of drug resistance mediators and receptor tyrosine kinases. Noteworthy observations included a significant decline in HCT-15 colon xenograft ABCB1 transporter expression and increased expression of the kinase KIT in A549 with serial passage. These trends predict sensitivity to agents such as paclitaxel (ABCB1 substrate) and imatinib (c-KIT inhibitor) would be altered with extended passage. Given that gene expression results indicated some models undergo profound changes with in vivo passage, a general metric of stability was generated so models could be ranked accordingly. Lastly, changes occurring during transition from in vitro to in vivo growth may have important consequences for therapeutic studies since targets identified in vitro could be over-or under-represented when tumor cells adapt to in vivo growth. A comprehensive list of mouse transcripts capable of cross-hybridizing with human probe sets on the HG-U133 Plus 2.0 array was generated. Removal of the murine artifacts followed by pairwise analysis of in vitro cells with respective passage 1 xenografts and GO analysis illustrates the complex interplay that each model has with the host microenvironment.
Conclusions: This study provides strategies to aid selection of xenograft models for therapeutic studies. These data highlight the dynamic nature of xenograft models and emphasize the importance of maintaining passage consistency throughout experiments.
C1 [Hollingshead, Melinda G.] NCI, Biol Testing Branch, Frederick, MD 21702 USA.
[Stockwin, Luke H.; Newton, Dianne L.; Bonomi, Carrie A.; Borgel, Suzanne D.; Divelbiss, Raymond; Dougherty, Kelly M.; Kimmel, David J.; Millione, Angelena; Mullendore, Michael E.; Stotler, Howard] Leidos Biomed Res Inc, Biol Testing Branch, Dev Therapeut Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Alcoser, Sergio Y.; Hager, Elizabeth J.] NCI, Biol Testing Branch, Dev Therapeut Program, Frederick, MD 21702 USA.
[Orsburn, Benjamin C.] Thermo Fisher, Indianapolis, IN USA.
[Holbeck, Susan L.; Kunkel, Mark W.] NCI, Informat Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Kaur, Gurmeet] NCI, Mol Pharmacol Branch, Dev Therapeut Program, Frederick, MD 21702 USA.
[Collins, Jerry] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Hollingshead, MG (reprint author), NCI, Biol Testing Branch, 1050 Boyles St,Bldg 1043,Room 11, Frederick, MD 21702 USA.
EM hollingm@mail.nih.gov
RI Alcoser, Sergio/G-9074-2012
OI Alcoser, Sergio/0000-0002-6896-2551
FU National Cancer Institute; National Institutes of Health
[HHSN261200800001E]; Developmental Therapeutics Program in the Division
of Cancer Treatment and Diagnosis of the National Cancer Institute
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was supported [in part] by the Developmental Therapeutics
Program in the Division of Cancer Treatment and Diagnosis of the
National Cancer Institute. NCI-Frederick is accredited by AAALAC
International and follows the Public Health Service Policy for the Care
and Use of Laboratory Animals. All animals used in this research project
were cared for and used humanely according to the following policies:
The U.S. Public Health Service Policy on Humane Care and Use of Animals
(1996); the Guide for the Care and Use of Laboratory Animals Eighth
Edition; and the U.S. Government Principles for Utilization and Care of
Vertebrate Animals Used in Testing, Research, and Training (1985). All
studies were approved by the NCI at Frederick Animal Care and Use
Committee (ACUC) prior initiation of work. The NCI at Frederick ACUC
operates under an active Office of Laboratory Animal Welfare assurance.
NR 39
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U1 1
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD MAY 22
PY 2014
VL 15
AR 393
DI 10.1186/1471-2164-15-393
PG 16
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AI2IO
UT WOS:000336681300001
PM 24885658
ER
PT J
AU Yang, H
Volfovsky, N
Rattray, A
Chen, XF
Tanaka, H
Strathern, J
AF Yang, Hui
Volfovsky, Natalia
Rattray, Alison
Chen, Xiongfong
Tanaka, Hisashi
Strathern, Jeffrey
TI GAP-Seq: a method for identification of DNA palindromes
SO BMC GENOMICS
LA English
DT Article
DE Palindrome; Gene amplification; Inversion-PCR; GAP-Seq; GAPF;
Breakpoint; MCF7; Genome instability; Cancer; Human diseases
ID CANCER CELL-LINES; COMPARATIVE GENOMIC HYBRIDIZATION; RECENT SEGMENTAL
DUPLICATIONS; BREAST-CANCER; GENE AMPLIFICATION; INVERTED REPEATS; COPY
NUMBER; REARRANGEMENTS; MECHANISMS; EVOLUTION
AB Background: Closely spaced long inverted repeats, also known as DNA palindromes, can undergo intrastrand annealing to form DNA hairpins. The ability to form these hairpins results in genome instability, difficulties in maintaining clones in Escherichia coli and major problems for most DNA sequencing approaches. Because of their role in genomic instability and gene amplification in some human cancers, it is important to develop systematic approaches to detect and characterize DNA palindromes.
Results: We developed a new protocol to identify palindromes that couples the S1 nuclease treated Cot0 DNA (GAPF) with high-throughput sequencing (GAP-Seq). Unlike earlier protocols, it does not involve restriction enzymatic digestion prior to DNA snap-back thereby preserving longer DNA sequences. It also indicates the location of the novel junction, which can then be recovered. Using MCF-7 breast cancer cell line as the proof-of-principle analysis, we have identified 35 palindrome candidates and physically characterized the top 5 candidates and their junctions. Because this protocol eliminates many of the false positives that plague earlier techniques, we have improved palindrome identification.
Conclusions: The GAP-Seq approach underscores the importance of developing new tools for identifying and characterizing palindromes, and provides a new strategy to systematically assess palindromes in genomes. It will be useful for studying human cancers and other diseases associated with palindromes.
C1 [Yang, Hui; Rattray, Alison; Strathern, Jeffrey] Canc Res & Dev Ctr, Frederick Natl Lab Canc Res, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
[Volfovsky, Natalia; Chen, Xiongfong] SAIC Frederick Inc, ISP ABCC7, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Tanaka, Hisashi] Cleveland Clin, Lerner Res Inst, Dept Mol Genet, Cleveland, OH 44195 USA.
RP Strathern, J (reprint author), Canc Res & Dev Ctr, Frederick Natl Lab Canc Res, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
EM strathej@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research, Frederick National Laboratory for Cancer Research
[HHSN261200800001E, R01CA149385]
FX The authors thank Dr. Adrian Lee for MCF-7 subline genomic DNA
(MCF-7-neo, MCF-7-BK, MCF-7-B, MCF-7-C) and Dr. John Weinstein for
MCF-7-NCI60 genomic DNA, Dr. Robert Stephens for helpful discussions,
Dr. Duncan Donohue for providing the R-script for the prototype of the
data visualization of Figure 4, Claudia Stewart for Roche 454
sequencing, Sandra Burkett for cell culture, Dr. Pieter Faber for
Illumina sequencing, Dr. Thomas Schneider for discussion of mathematic
equations and Dr. Sharon Moore for critique of the manuscript. This work
was supported by the National Institutes of Health, National Cancer
Institute, Center for Cancer Research, Frederick National Laboratory for
Cancer Research (the Intramural Research Program, HHSN261200800001E to
N.V. and X.C., R01CA149385 to H.T.).
NR 48
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U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD MAY 22
PY 2014
VL 15
AR 394
DI 10.1186/1471-2164-15-394
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AI5PP
UT WOS:000336921800001
PM 24885769
ER
PT J
AU Mandl, JN
Germain, RN
AF Mandl, Judith N.
Germain, Ronald N.
TI Focusing in on T Cell Cross-Reactivity
SO CELL
LA English
DT Editorial Material
AB To provide broad immunity to a vast array of foreign antigens with a limited number of T lymphocytes, each cell has to recognize many targets. By implementing a strategy to identify T cell receptor (TCR) ligands and investigating at a fine granularity their structure and sequence relationship, Birnbaum et al. demonstrate the surprisingly tight focus of such T cell cross-reactivity.
C1 [Mandl, Judith N.; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
RP Mandl, JN (reprint author), NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
EM mandlj@niaid.nih.gov; rgermain@niaid.nih.gov
NR 5
TC 0
Z9 0
U1 0
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD MAY 22
PY 2014
VL 157
IS 5
BP 1006
EP 1008
DI 10.1016/j.cell.2014.05.002
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AH9CG
UT WOS:000336437200003
PM 24855938
ER
PT J
AU Warner, KD
Homan, P
Weeks, KM
Smith, AG
Abell, C
Ferre-D'Amare, AR
AF Warner, Katherine Deigan
Homan, Philip
Weeks, Kevin M.
Smith, Alison G.
Abell, Chris
Ferre-D'Amare, Adrian R.
TI Validating Fragment-Based Drug Discovery for Biological RNAs: Lead
Fragments Bind and Remodel the TPP Riboswitch Specifically
SO CHEMISTRY & BIOLOGY
LA English
DT Article
ID THI-BOX RIBOSWITCH; GENE-REGULATION; CRYSTALLOGRAPHY; SOFTWARE; LIGAND
AB Thiamine pyrophosphate (TPP) riboswitches regulate essential genes in bacteria by changing conformation upon binding intracellular TPP. Previous studies using fragment-based approaches identified small molecule "fragments" that bind this gene-regulatory mRNA domain. Crystallographic studies now show that, despite having micromolar K(d)s, four different fragments bind the TPP riboswitch site-specifically, occupying the pocket that recognizes the aminopyrimidine of TPP. Unexpectedly, the unoccupied site that would recognize the pyrophosphate of TPP rearranges into a structure distinct from that of the cognate complex. This idiosyncratic fragment-induced conformation, also characterized by small-angle X-ray scattering and chemical probing, represents a possible mechanism for adventitious ligand discrimination by the riboswitch, and suggests that off-pathway conformations of RNAs can be targeted for drug development. Our structures, together with previous screening studies, demonstrate the feasibility of fragment-based drug discovery against RNA targets.
C1 [Warner, Katherine Deigan; Ferre-D'Amare, Adrian R.] NHLBI, Bethesda, MD 20892 USA.
[Warner, Katherine Deigan; Abell, Chris] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
[Homan, Philip; Weeks, Kevin M.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
[Smith, Alison G.] Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England.
RP Ferre-D'Amare, AR (reprint author), NHLBI, 50 South Dr,MSC 8012, Bethesda, MD 20892 USA.
EM adrian.ferre@nih.gov
OI Smith, Alison/0000-0001-6511-5704
FU National Institute for General Medical Sciences, NIH; US Department of
Energy; NIH [GM098662]; BBSRC of the UK; NIH-Oxford/Cambridge Research
Scholars program; intramural program of the National Heart, Lung and
Blood Institute, NIH
FX We thank the staff at beamlines 24-ID-C of APS and 5.0.1 and 5.0.2 of
ALS for crystallographic data collection support; N. Baird, Y.-X. Wang,
and X. Fang for assistance with SAXS; G. Piszczek for assistance with
ITC; and N. Baird, C. Jones, M. Lau, J. Posakony, S. Ryder, A. Serganov,
M. Warner, and J. Zhang for discussions. This work is partly based on
research conducted at ALS on the BCSB beamlines and at APS on the NE-CAT
beamlines, all of which are supported by the National Institute for
General Medical Sciences, NIH. Use of ALS and APS was supported by the
US Department of Energy. This work was supported in part by the NIH
(grant GM098662 to K. M. W.), the BBSRC of the UK, and the
NIH-Oxford/Cambridge Research Scholars program. This work was supported
in part by the intramural program of the National Heart, Lung and Blood
Institute, NIH.
NR 24
TC 20
Z9 20
U1 0
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
EI 1879-1301
J9 CHEM BIOL
JI Chem. Biol.
PD MAY 22
PY 2014
VL 21
IS 5
BP 591
EP 595
DI 10.1016/j.chembiol.2014.03.007
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AH8XW
UT WOS:000336422500008
PM 24768306
ER
PT J
AU Wang, HC
Godage, HY
Riley, AM
Weaver, JD
Shears, SB
Potter, BVL
AF Wang, Huanchen
Godage, Himali Y.
Riley, Andrew M.
Weaver, Jeremy D.
Shears, Stephen B.
Potter, Barry V. L.
TI Synthetic Inositol Phosphate Analogs Reveal that PPIP5K2 Has a
Surface-Mounted Substrate Capture Site that Is a Target for Drug
Discovery
SO CHEMISTRY & BIOLOGY
LA English
DT Article
ID DIPHOSPHOINOSITOL POLYPHOSPHATES; ANTHRANILATE
PHOSPHORIBOSYLTRANSFERASE; TELOMERE LENGTH; PYROPHOSPHATES; MECHANISM;
KINASE; DIPHOSPHATE; INHIBITION; PROVIDES; ENZYMES
AB Diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2) is one of the mammalian PPIP5K isoforms responsible for synthesis of diphosphoinositol polyphosphates (inositol pyrophosphates; PP-InsPs), regulatory molecules that function at the interface of cell signaling and organismic homeostasis. The development of drugs that inhibit PPIP5K2 could have both experimental and therapeutic applications. Here, we describe a synthetic strategy for producing naturally occurring 5-PP-InsP(4), as well as several inositol polyphosphate analogs, and we study their interactions with PPIP5K2 using biochemical and structural approaches. These experiments uncover an additional ligand-binding site on the surface of PPIP5K2, adjacent to the catalytic pocket. This site facilitates substrate capture from the bulk phase, prior to transfer into the catalytic pocket. In addition to demonstrating a "catch-and-pass" reaction mechanism in a small molecule kinase, we demonstrate that binding of our analogs to the substrate capture site inhibits PPIP5K2. This work suggests that the substrate-binding site offers new opportunities for targeted drug design.
C1 [Wang, Huanchen; Weaver, Jeremy D.; Shears, Stephen B.] NIEHS, Inositol Signaling Grp, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Godage, Himali Y.; Riley, Andrew M.; Potter, Barry V. L.] Univ Bath, Dept Pharm & Pharmacol, Wolfson Lab Med Chem, Bath BA2 7AY, Avon, England.
RP Shears, SB (reprint author), NIEHS, Inositol Signaling Grp, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM shears@niehs.nih.gov; b.v.l.potter@bath.ac.uk
RI Riley, Andrew/F-3526-2013
FU Wellcome Trust [082837, 101010]; Intramural Research Program of the
NIH/National Institute of Environmental Health Sciences (NIEHS); US
Department of Energy, Office of Science, Office of Basic Energy Sciences
[W-31-109-Eng-38]
FX We thank the Wellcome Trust (program grant 082837 to A.M.R. and
B.V.L.P.) for support. B.V.L.P. is a Wellcome Trust Senior Investigator
(grant 101010). This research was also supported by the Intramural
Research Program of the NIH/National Institute of Environmental Health
Sciences (NIEHS). X-ray data were collected at Southeast Regional
Collaborative Access Team (SERCAT) 22-beamline at the Advanced Photon
Source (APS), Argonne National Laboratory. Supporting institutions may
be found at http://www.ser-cat.org/members.html. Use of the APS was
supported by the US Department of Energy, Office of Science, Office of
Basic Energy Sciences, under contract no. W-31-109-Eng-38. We also thank
the NIEHS collaborative crystallography group for assistance with data
collection.
NR 29
TC 11
Z9 11
U1 4
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
EI 1879-1301
J9 CHEM BIOL
JI Chem. Biol.
PD MAY 22
PY 2014
VL 21
IS 5
BP 689
EP 699
DI 10.1016/j.chembiol.2014.03.009
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AH8XW
UT WOS:000336422500018
PM 24768307
ER
PT J
AU Arighi, CN
Wu, CH
Cohen, KB
Hirschman, L
Krallinger, M
Valencia, A
Lu, ZY
Wilbur, JW
Wiegers, TC
AF Arighi, Cecilia N.
Wu, Cathy H.
Cohen, Kevin B.
Hirschman, Lynette
Krallinger, Martin
Valencia, Alfonso
Lu, Zhiyong
Wilbur, John W.
Wiegers, Thomas C.
TI BioCreative-IV virtual issue
SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
LA English
DT Editorial Material
ID GENE NORMALIZATION; INFORMATION; ONTOGENE; BIOLOGY; II.5; TEXT; PIE
C1 [Arighi, Cecilia N.; Wu, Cathy H.] Univ Delaware, Ctr Bioinformat & Computat Biol, Newark, DE 19716 USA.
[Cohen, Kevin B.] Univ Colorado Denver, Sch Med, Ctr Computat Pharmacol, Aurora, CO USA.
[Hirschman, Lynette] Mitre Corp, Bedford, MA 01730 USA.
[Krallinger, Martin; Valencia, Alfonso] Spanish Natl Canc Res Ctr, Struct & Computat Biol Grp, Madrid, Spain.
[Lu, Zhiyong; Wilbur, John W.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Wiegers, Thomas C.] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA.
RP Arighi, CN (reprint author), Univ Delaware, Ctr Bioinformat & Computat Biol, Newark, DE 19716 USA.
EM arighi@dbi.udel.edu
RI Valencia, Alfonso/I-3127-2015;
OI Valencia, Alfonso/0000-0002-8937-6789; Arighi,
Cecilia/0000-0002-0803-4817
NR 35
TC 10
Z9 10
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1758-0463
J9 DATABASE-OXFORD
JI Database
PD MAY 22
PY 2014
AR bau039
DI 10.1093/database/bau039
PG 6
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA AH6RB
UT WOS:000336257300001
ER
PT J
AU Rai, G
Joshi, N
Jung, JE
Liu, Y
Schultz, L
Yasgar, A
Perry, S
Diaz, G
Zhang, QL
Kenyon, V
Jadhav, A
Simeonov, A
Lo, EH
van Leyen, K
Maloney, DJ
Holman, TR
AF Rai, Ganesha
Joshi, Netra
Jung, Joo Eun
Liu, Yu
Schultz, Lena
Yasgar, Adam
Perry, Steve
Diaz, Giovanni
Zhang, Qiangli
Kenyon, Victor
Jadhav, Ajit
Simeonov, Anton
Lo, Eng H.
van Leyen, Klaus
Maloney, David J.
Holman, Theodore R.
TI Potent and Selective Inhibitors of Human Reticulocyte 12/15-Lipoxygenase
as Anti-Stroke Therapies
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID PLATELET-TYPE 12-LIPOXYGENASE; SPONGE-DERIVED TERPENOIDS; TRANSIENT
FOCAL ISCHEMIA; PANCREATIC-CANCER CELLS; OXIDATIVE STRESS; HUMAN
15-LIPOXYGENASE; 5-LIPOXYGENASE INHIBITION; MAMMALIAN 15-LIPOXYGENASE;
GLUTATHIONE DEPLETION; RHEUMATOID-ARTHRITIS
AB A key challenge facing drug discovery today is variability of the drug target between species, such as with 12/15-lipoxygenase (12/15-LOX), which contributes to ischemic brain injury, but its human and rodent isozymes have different inhibitor specificities. In the current work, we have utilized a quantitative high-throughput (qHTS) screen to identify compound 1 (ML351), a novel chemotype for 12/15-LOX inhibition that has nanomolar potency (IC50 = 200 nM) against human 12/15-LOX and is protective against oxidative glutamate toxicity in mouse neuronal HT22 cells. In addition, it exhibited greater than 250-fold selectivity versus related LOX isozymes, was a mixed inhibitor, and did not reduce the active-site ferric ion. Lastly, 1 significantly reduced infarct size following permanent focal ischemia in a mouse model of ischemic stroke. As such, this represents the first report of a selective inhibitor of human 12/15-LOX with demonstrated in vivo activity in proof-of-concept mouse models of stroke.
C1 [Jung, Joo Eun; Liu, Yu; Lo, Eng H.; van Leyen, Klaus] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA.
[Rai, Ganesha; Schultz, Lena; Yasgar, Adam; Jadhav, Ajit; Simeonov, Anton; Maloney, David J.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Joshi, Netra; Perry, Steve; Diaz, Giovanni; Zhang, Qiangli; Kenyon, Victor; Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
RP van Leyen, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA.
EM klaus_vanleyen@hms.harvard.edu; maloneyd@mail.nih.gov;
tholman@chemistry.ucsc.edu
FU National Institute of Health [R01 GM56062, R01 NS049430, R01 NS069939];
Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research [R03 MH081283, U54MH084681]; National
Center for Advancing Translational Sciences; NIH [S10-RR20939];
California Institute for Quantitative Biosciences
FX We thank Sam Michael and Richard Jones for automation support; Paul
Shinn and Danielle van Leer for assistance with compound management;
William Leister, Heather Baker, James Bougie, Elizabeth Fernandez, and
Christopher Leclair for analytical chemistry and purification support;
Kimloan Nguyen for in vitro ADME data; and Eric Hoobler for helping with
the COX assays. Financial support was from the National Institute of
Health (grants R01 GM56062 (T.R.H.), R01 NS049430 (K.v.L.), and R01
NS069939) and the Molecular Libraries Initiative of the National
Institutes of Health Roadmap for Medical Research (R03 MH081283
(T.R.H.)). G.R., L.S., A.Y., A.J., A.S., and D.J.M. were supported by
the intramural research program of the National Center for Advancing
Translational Sciences and the Molecular Libraries Initiative of the
National Institutes of Health Roadmap for Medical Research
(U54MH084681). Additional financial support was from NIH (S10-RR20939
(T.R.H.)) and the California Institute for Quantitative Biosciences for
the UCSC MS Facility (T.R.H.).
NR 79
TC 21
Z9 21
U1 4
U2 13
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD MAY 22
PY 2014
VL 57
IS 10
BP 4035
EP 4048
DI 10.1021/jm401915r
PG 14
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AI0BB
UT WOS:000336510100010
PM 24684213
ER
PT J
AU Singh, S
Prasad, NR
Chufan, EE
Patel, BA
Wang, YJ
Chen, ZS
Ambudkar, SV
Talele, TT
AF Singh, Satyakam
Prasad, Nagarajan Rajendra
Chufan, Eduardo E.
Patel, Bhargav A.
Wang, Yi-Jun
Chen, Zhe-Sheng
Ambudkar, Suresh V.
Talele, Tanaji T.
TI Design and Synthesis of Human ABCB1 (P-Glycoprotein) Inhibitors by
Peptide Coupling of Diverse Chemical Scaffolds on Carboxyl and Amino
Termini of (S)-Valine-Derived Thiazole Amino Acid
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID ATP-DEPENDENT TRANSPORTERS; RESISTANCE REVERSAL AGENTS;
MULTIDRUG-RESISTANCE; DRUG TRANSPORTERS; POTENT MODULATOR;
MAMMALIAN-CELLS; IN-VIVO; BINDING; CANCER; PHARMACOPHORE
AB P-glycoprotein (P-gp) serves as a therapeutic target for the development of multidrug resistance reversal agents. In this study, we synthesized 21 novel compounds by peptide coupling at corresponding carboxyl and amino termini of (S)-valine-based bis-thiazole and monothiazole derivatives with diverse chemical scaffolds. Using calcein-AM efflux assay, we identified compound 28 (IC50 = 1.0 mu M) carrying 3,4,5-trimethoxybenzoyl and 2-aminobenzophenone groups, respectively, at the amino and carboxyl termini of the monothiazole zwitter-ion. Compound 28 inhibited the photolabeling of P-gp with [I-125]-iodoarylazidoprazosin with IC50 = 0.75 mu M and stimulated the basal ATP hydrolysis of P-gp in a concentration-dependent manner (EC50 ATPase = 0.027 mu M). Compound 28 at 3 mu M reduced resistance in cytotoxicity assay to paclitaxel in P-gp-expressing SW620/Ad300 and HEK/ABCB1 cell lines. Biochemical and docking studies showed site-1 to be the preferable binding site for 28 within the drug-binding pocket of human P-gp.
C1 [Singh, Satyakam; Patel, Bhargav A.; Wang, Yi-Jun; Chen, Zhe-Sheng; Talele, Tanaji T.] St Johns Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Queens, NY 11439 USA.
[Prasad, Nagarajan Rajendra; Chufan, Eduardo E.; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM ambudkar@mail.nih.gov; talelet@stjohns.edu
RI Wang, Yi-Jun/K-3218-2016
FU Department of Pharmaceutical Sciences of St. John's University; St.
John's University [579-1110]; NIH, National Cancer Institute, Center for
Cancer Research; Indian Council of Medical Research, New Delhi
[Indo/FRC/452(Y-19)/2012-13IHD]
FX This research was supported by the Department of Pharmaceutical Sciences
of St. John's University and St. John's University Seed Grant no.
579-1110 to T.T.T. Drs. N.R.P., E.E.C., and S.V.A. were supported by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. Financial support from Indian Council of
Medical Research, New Delhi, in the form of International Fellowship for
Young Indian Biomedical Scientists to Dr. N.R.P. is gratefully
acknowledged (Indo/FRC/452(Y-19)/2012-13IHD). We acknowledge Drs. Susan
E. Bates and Robert W. Robey (NCI, NIH, Bethesda, MD) for providing
SW620 and SW620/Ad300 cell lines. We thank Dr. Stephen Aller (The
University of Alabama at Birmingham, Birmingham, AL) for generously
providing human apo-state P-gp homology model. We thank George Leiman
for editorial assistance. S.S. and T.T.T. are thankful to Dr. Sanjai
Kumar and Dibyendu Dana (Queens College-CUNY, Queens, NY) for assisting
in ESI-MS and HRMS analyses.
NR 37
TC 13
Z9 13
U1 1
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD MAY 22
PY 2014
VL 57
IS 10
BP 4058
EP 4072
DI 10.1021/jm401966m
PG 15
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AI0BB
UT WOS:000336510100012
PM 24773054
ER
PT J
AU Lv, PC
Agama, K
Marchand, C
Pommier, Y
Cushman, M
AF Lv, Peng-Cheng
Agama, Keli
Marchand, Christophe
Pommier, Yves
Cushman, Mark
TI Design, Synthesis, and Biological Evaluation of O-2-Modified
Indenoisoquinolines as Dual Topoisomerase I-Tyrosyl-DNA
Phosphodiesterase I Inhibitors
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID POTENTIAL ANTICANCER AGENTS; PHOSPHOLIPASE-D SUPERFAMILY; CLEAVAGE
COMPLEXES; CAMPTOTHECIN RESISTANCE; CATALYTIC MECHANISM; COVALENT
COMPLEXES; ANTITUMOR-ACTIVITY; CRYSTAL-STRUCTURE; STRAND BREAKS;
CELL-LINE
AB Tyrosyl-DNA phosphodiesterase I (TDP1) repairs stalled topoisomerase I (Topl) DNA covalent complexes and has been proposed to be a promising and attractive target for cancer treatment. Inhibitors of TDPI could conceivably act synergistically with Topl inhibitors and thereby potentiate the effects of Top! poisons. This study describes the successful design and synthesis of 2-position-modified indenoisoquinolines as dual Topl TDPI inhibitors using a structure-based drug design approach. Enzyme inhibition studies indicate that indenoisoquinolines modified at the 2-position with three-carbon side chains ending with amino substituents show both promising Top! and TDP1 inhibitory activity. Molecular modeling of selected target compounds bound to Topl and TDPI was used to rationalize the enzyme inhibition results and structure activity relationship analysis.
C1 [Lv, Peng-Cheng; Cushman, Mark] Purdue Univ, Dept Med Chem & Mol Pharmacol, Coll Pharm, W Lafayette, IN 47907 USA.
[Lv, Peng-Cheng; Cushman, Mark] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA.
[Agama, Keli; Marchand, Christophe; Pommier, Yves] NCI, Dev Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Agama, Keli; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Cushman, M (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, Coll Pharm, W Lafayette, IN 47907 USA.
EM cushman@purdue.edu
FU National Institutes of Health (NIH) [UO1 CA89566]; Intramural Research
Program, Center for Cancer Research, National Cancer Institute, NIH [Z01
BC 006161, Z01 BC 006150]; Developmental Therapeutics Program at the
National Cancer Institute [NO1-CO-56000]
FX This work was made possible by the National Institutes of Health (NIH)
through support from research grant UO1 CA89566 and was supported by the
Intramural Research Program, Center for Cancer Research, National Cancer
Institute, NIH (Z01 BC 006161 and Z01 BC 006150). In vitro cytotoxicity
testing was performed by the Developmental Therapeutics Program at the
National Cancer Institute under contract NO1-CO-56000.
NR 71
TC 13
Z9 14
U1 1
U2 29
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD MAY 22
PY 2014
VL 57
IS 10
BP 4324
EP 4336
DI 10.1021/jm500294a
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AI0BB
UT WOS:000336510100030
PM 24800942
ER
PT J
AU Liang, TJ
Ghany, MG
AF Liang, T. Jake
Ghany, Marc G.
TI Therapy of Hepatitis C - Back to the Future
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID VIRUS-INFECTION; SOFOSBUVIR; BOCEPREVIR
C1 [Liang, T. Jake; Ghany, Marc G.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Liang, TJ (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
NR 19
TC 47
Z9 47
U1 0
U2 7
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAY 22
PY 2014
VL 370
IS 21
BP 2043
EP 2047
DI 10.1056/NEJMe1403619
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA AH4UZ
UT WOS:000336125500013
PM 24795199
ER
PT J
AU Martinez-Bakker, M
Bakker, KM
King, AA
Rohani, P
AF Martinez-Bakker, Micaela
Bakker, Kevin M.
King, Aaron A.
Rohani, Pejman
TI Human birth seasonality: latitudinal gradient and interplay with
childhood disease dynamics
SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE birth; seasonality; measles; disease; latitude
ID HUMAN-REPRODUCTION; RECURRENT EPIDEMICS; INFECTIOUS-DISEASES; HOUSE
FINCHES; UNITED-STATES; MEASLES; TRANSMISSION; VACCINATION; PATTERNS;
RATES
AB More than a century of ecological studies have demonstrated the importance of demography in shaping spatial and temporal variation in population dynamics. Surprisingly, the impact of seasonal recruitment on infectious disease systems has received much less attention. Here, we present data encompassing 78 years of monthly natality in the USA, and reveal pronounced seasonality in birth rates, with geographical and temporal variation in both the peak birth timing and amplitude. The timing of annual birth pulses followed a latitudinal gradient, with northern states exhibiting spring/summer peaks and southern states exhibiting autumn peaks, a pattern we also observed throughout the Northern Hemisphere. Additionally, the amplitude of United States birth seasonality was more than twofold greater in southern states versus those in the north. Next, we examined the dynamical impact of birth seasonality on childhood disease incidence, using a mechanistic model of measles. Birth seasonality was found to have the potential to alter the magnitude and periodicity of epidemics, with the effect dependent on both birth peak timing and amplitude. In a simulation study, we fitted an susceptible-exposed-infected-recovered model to simulated data, and demonstrated that ignoring birth seasonality can bias the estimation of critical epidemiological parameters. Finally, we carried out statistical inference using historical measles incidence data from New York City. Our analyses did not identify the predicted systematic biases in parameter estimates. This may be owing to the well-known frequency-locking between measles epidemics and seasonal transmission rates, or may arise from substantial uncertainty in multiple model parameters and estimation stochasticity.
C1 [Martinez-Bakker, Micaela; Bakker, Kevin M.; King, Aaron A.; Rohani, Pejman] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Martinez-Bakker, Micaela; Bakker, Kevin M.; King, Aaron A.; Rohani, Pejman] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
[King, Aaron A.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA.
[King, Aaron A.; Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Martinez-Bakker, M (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
EM bakkerma@umich.edu
RI Martinez-Bakker, Micaela/J-3721-2013
OI Martinez-Bakker, Micaela/0000-0002-9248-9450
FU NSF; Research and Policy in Infectious Disease Dynamics programme of the
Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; National
Institutes of Health [R01AI101155]
FX M.M.B. is supported by the NSF Graduate Research Fellowship Programme.
P.R. and A.A.K. are supported by the Research and Policy in Infectious
Disease Dynamics programme of the Science and Technology Directorate,
Department of Homeland Security, the Fogarty International Center,
National Institutes of Health and by a research grant from the National
Institutes of Health (R01AI101155).
NR 59
TC 13
Z9 13
U1 3
U2 25
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8452
EI 1471-2954
J9 P ROY SOC B-BIOL SCI
JI Proc. R. Soc. B-Biol. Sci.
PD MAY 22
PY 2014
VL 281
IS 1783
AR 20132438
DI 10.1098/rspb.2013.2438
PG 8
WC Biology; Ecology; Evolutionary Biology
SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences &
Ecology; Evolutionary Biology
GA AF0NP
UT WOS:000334411600001
PM 24695423
ER
PT J
AU Orecchioni, M
Bedognetti, D
Sgarrella, F
Marincola, FM
Bianco, A
Delogu, LG
AF Orecchioni, Marco
Bedognetti, Davide
Sgarrella, Francesco
Marincola, Francesco M.
Bianco, Alberto
Delogu, Lucia Gemma
TI Impact of carbon nanotubes and graphene on immune cells
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Review
DE Carbon nanotubes; Graphene; Graphene oxide; Nanomedicine; Immune system;
Cells; Therapy; Diagnosis
ID NLRP3 INFLAMMASOME ACTIVATION; ASBESTOS-LIKE PATHOGENICITY; IN-VITRO;
RAW 264.7; SIGNALING PATHWAYS; PULMONARY TOXICITY; CONTRAST AGENTS;
CELLULAR ACTIVATION; PRISTINE GRAPHENE; PHAGOCYTIC-CELLS
AB It has been recently proposed that nanomaterials, alone or in concert with their specific biomolecular conjugates, can be used to directly modulate the immune system, therefore offering a new tool for the enhancement of immune-based therapies against infectious disease and cancer. Here, we revised the publications on the impact of functionalized carbon nanotubes (f-CNTs), graphene and carbon nanohorns on immune cells. Whereas f-CNTs are the nanomaterial most widely investigated, we noticed a progressive increase of studies focusing on graphene in the last couple of years. The majority of the works (56%) have been carried out on macrophages, following by lymphocytes (30% of the studies). In the case of lymphocytes, T cells were the most investigated (22%) followed by monocytes and dendritic cells (7%), mixed cell populations (peripheral blood mononuclear cells, 6%), and B and natural killer (NK) cells (1%). Most of the studies focused on toxicity and biocompatibility, while mechanistic insights on the effect of carbon nanotubes on immune cells are generally lacking. Only very recently high-throughput gene-expression analyses have shed new lights on unrecognized effects of carbon nanomaterials on the immune system. These investigations have demonstrated that some f-CNTs can directly elicitate specific inflammatory pathways. The interaction of graphene with the immune system is still at a very early stage of investigation. This comprehensive state of the art on biocompatible f-CNTs and graphene on immune cells provides a useful compass to guide future researches on immunological applications of carbon nanomaterials in medicine.
C1 [Orecchioni, Marco; Sgarrella, Francesco; Delogu, Lucia Gemma] Univ Sassari, Dipartimento Chim & Farm, I-07100 Sassari, Italy.
[Bedognetti, Davide; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Bedognetti, Davide; Marincola, Francesco M.] NIH, Trans Natl Inst Hlth Ctr Human Immunol, Bethesda, MD 20892 USA.
[Bedognetti, Davide; Marincola, Francesco M.] Sidra Med & Res Ctr, Res Branch, Doha, Qatar.
[Bianco, Alberto] CNRS, Inst Biol Mol & Cellulaire, Lab Immunopathol & Chim Therapeut, F-67000 Strasbourg, France.
RP Bianco, A (reprint author), CNRS, Inst Biol Mol & Cellulaire, Lab Immunopathol & Chim Therapeut, F-67000 Strasbourg, France.
EM a.bianco@ibmc-cnrs.unistra.fr; lgdelogu@uniss.it
OI Bedognetti, Davide/0000-0002-5857-773X
FU Fondazione Banco di Sardegna [186/2011.0484, 2013.1308]; Sardinia Region
[CRP-59720]; Intramural Research program of the U. S. National
Institutes of Health (Department of Transfusion Medicine, Clinical
Center); Gianfranco Del Prete The future: medicine, biology and
nanotechnology Award
FX This work was partly supported by the Fondazione Banco di Sardegna
(grant No 186/2011.0484, 2013.1308 To L. G. D.), the Sardinia Region
(grant No CRP-59720 to L. G. D.). This work was supported in part by the
Intramural Research program of the U. S. National Institutes of Health
(Department of Transfusion Medicine, Clinical Center) and "Gianfranco
Del Prete The future: medicine, biology and nanotechnology Award" to L.
G. D. A. B. wishes to thank the CNRS. L. G. D. wishes to thank the
Sardinian Region for an invited professorship to A.
NR 114
TC 29
Z9 29
U1 8
U2 91
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD MAY 21
PY 2014
VL 12
AR 138
DI 10.1186/1479-5876-12-138
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AK5MQ
UT WOS:000338469300003
PM 24885781
ER
PT J
AU Barnes, SJ
Cheetham, CEJ
AF Barnes, Samuel J.
Cheetham, Claire E. J.
TI A Role for Short-Lived Synapses in Adult Cortex?
SO JOURNAL OF NEUROSCIENCE
LA English
DT Editorial Material
ID IN-VIVO; SPINE STABILITY; NEOCORTEX; GROWTH
C1 [Barnes, Samuel J.] Kings Coll London, MRC, Ctr Dev Neurobiol, London SE1 1UL, England.
[Cheetham, Claire E. J.] NINDS, Bethesda, MD 20892 USA.
RP Cheetham, CEJ (reprint author), NINDS, 35 Convent Dr, Bethesda, MD 20892 USA.
EM claire.cheetham@nih.gov
RI Barnes, Samuel/I-5805-2015; Cheetham, Claire/A-2612-2017
OI Cheetham, Claire/0000-0002-4038-1501
NR 11
TC 1
Z9 1
U1 1
U2 5
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAY 21
PY 2014
VL 34
IS 21
BP 7044
EP 7046
DI 10.1523/JNEUROSCI.1108-14.2014
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA AI5HB
UT WOS:000336895200002
PM 24849340
ER
PT J
AU Zavala, BA
Tan, HL
Little, S
Ashkan, K
Hariz, M
Foltynie, T
Zrinzo, L
Zaghloul, KA
Brown, P
AF Zavala, Baltazar A.
Tan, Huiling
Little, Simon
Ashkan, Keyoumars
Hariz, Marwan
Foltynie, Thomas
Zrinzo, Ludvic
Zaghloul, Kareem A.
Brown, Peter
TI Midline Frontal Cortex Low-Frequency Activity Drives Subthalamic Nucleus
Oscillations during Conflict
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE conflict; midline frontal cortex; subthalamic nucleus; theta
oscillations
ID ANTERIOR CINGULATE CORTEX; DEEP BRAIN-STIMULATION; INCREASES
RESPONSE-TIME; PARKINSONS-DISEASE; BASAL GANGLIA; DECISION-MAKING;
TASK-DIFFICULTY; IMPULSE CONTROL; THETA ENERGY; EEG-DATA
AB Making the right decision from conflicting information takes time. Recent computational, electrophysiological, and clinical studies have implicated two brain areas as being crucial in assuring sufficient time is taken for decision-making under conditions of conflict: the medial prefrontal cortex and the subthalamic nucleus (STN). Both structures exhibit an elevation of activity at low frequencies (<10 Hz) during conflict that correlates with the amount of time taken to respond. This suggests that the two sites could become functionally coupled during conflict. To establish the nature of this interaction we recorded from deep-brain stimulation electrodes implanted bilaterally in the STN of 13 Parkinson's disease patients while they performed a sensory integration task involving randomly moving dots. By gradually increasing the number of dots moving coherently in one direction, we were able to determine changes in the STN associated with response execution. Furthermore, by occasionally having 10% of the dots move in the opposite direction as the majority, we were able to identify an independent increase in STN theta-delta activity triggered by conflict. Crucially, simultaneous midline frontal electroencephalographic recordings revealed an increase in the theta-delta band coherence between the two structures that was specific to high-conflict trials. Activity over the midline frontal cortex was Granger causal to that in STN. These results establish the cortico-subcortical circuit enabling successful choices to be made under conditions of conflict and provide support for the hypothesis that the brain uses frequency-specific channels of communication to convey behaviorally relevant information.
C1 [Zavala, Baltazar A.; Tan, Huiling; Little, Simon; Brown, Peter] Univ Oxford, Nuffield Dept Clin Neurol, John Radcliffe Hosp, Expt Neurol Grp, Oxford OX3 9DU, England.
[Zavala, Baltazar A.; Zaghloul, Kareem A.] NIH, Surg Neurol Branch, Bethesda, MD 20814 USA.
[Ashkan, Keyoumars] Kings Coll London, Dept Neurosurg, Kings Coll Hosp, London SE5 9RS, England.
[Hariz, Marwan; Foltynie, Thomas; Zrinzo, Ludvic] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1 3BG, England.
RP Brown, P (reprint author), Univ Oxford, Nuffield Dept Clin Neurol, John Radcliffe Hosp, Level 6,West Wing, Oxford OX3 9DU, England.
EM peter.brown@ndcn.ox.ac.uk
RI Brown, Peter/J-4307-2016;
OI Brown, Peter/0000-0002-5201-3044; Tan, Huiling /0000-0001-8038-3029
FU Rhodes Trust; National Institutes of Health Oxford-Cambridge fellowship;
Department of Health National Institute for Health Research UCL
Biomedical Research Center; Monument Trust; Parkinson's Appeal for Deep
Brain Stimulation; Medical Research Council; Department of Health
National Institute for Health Research Oxford Biomedical Research
Centre; Wellcome Trust
FX B.Z. is supported by the Rhodes Trust and the National Institutes of
Health Oxford-Cambridge fellowship. M.H., T. F., and L.Z. are funded by
the Department of Health National Institute for Health Research UCL
Biomedical Research Center, The Monument Trust, and Parkinson's Appeal
for Deep Brain Stimulation. P. B. and H. T. are funded by the Medical
Research Council, and P. B. further funded by the Department of Health
National Institute for Health Research Oxford Biomedical Research
Centre. S. L. is funded by the Wellcome Trust. This work was partly
carried out in the NIHR cognitive health Clinical Research Facility,
Oxford. We thank Mr Alex Green and Prof Aziz for letting us enlist the
help of case 1.
NR 60
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Z9 27
U1 5
U2 18
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAY 21
PY 2014
VL 34
IS 21
BP 7322
EP 7333
DI 10.1523/JNEUROSCI.1169-14.2014
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA AI5HB
UT WOS:000336895200026
PM 24849364
ER
PT J
AU de Renty, C
DePamphilis, ML
Ullah, Z
AF de Renty, Christelle
DePamphilis, Melvin L.
Ullah, Zakir
TI Cytoplasmic Localization of p21 Protects Trophoblast Giant Cells from
DNA Damage Induced Apoptosis
SO PLOS ONE
LA English
DT Article
ID STEM-CELLS; CDK INHIBITORS; MICE LACKING; CYCLE EXIT; DOWN-REGULATION;
MOUSE EMBRYOS; DIFFERENTIATION; KINASE; PHOSPHORYLATION; PROLIFERATION
AB Proliferating trophoblast stem cells (TSCs) can differentiate into nonproliferating but viable trophoblast giant cells (TGCs) that are resistant to DNA damage induced apoptosis. Differentiation is associated with selective up-regulation of the Cip/Kip cyclin-dependent kinase inhibitors p57 and p21; expression of p27 remains constant. Previous studies showed that p57 localizes to the nucleus in TGCs where it is essential for endoreplication. Here we show that p27 also remains localized to the nucleus during TSC differentiation where it complements the role of p57. Unexpectedly, p21 localized to the cytoplasm where it was maintained throughout both the G-and S-phases of endocycles, and where it prevented DNA damage induced apoptosis. This unusual status for a Cip/Kip protein was dependent on site-specific phosphorylation of p21 by the Akt1 kinase that is also up-regulated in TGCs. Although cytoplasmic p21 is widespread among cancer cells, among normal cells it has been observed only in monocytes. The fact that it also occurs in TGCs reveals that p57 and p21 serve nonredundant functions, and suggests that the role of p21 in suppressing apoptosis is restricted to terminally differentiated cells.
C1 [de Renty, Christelle; DePamphilis, Melvin L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Ullah, Zakir] Lahore Univ Management Sci, Sch Sci & Engn, Dept Biol, Lahore, Pakistan.
RP Ullah, Z (reprint author), Lahore Univ Management Sci, Sch Sci & Engn, Dept Biol, Lahore, Pakistan.
EM zakirullah@lums.edu.pk
FU NICHD; LUMS University
FX This work was supported by the NICHD intramural research program and by
LUMS University. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 72
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Z9 4
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 21
PY 2014
VL 9
IS 5
AR e97434
DI 10.1371/journal.pone.0097434
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3AL
UT WOS:000336730600028
PM 24848107
ER
PT J
AU Malik, N
Wang, XT
Shah, S
Efthymiou, AG
Yan, B
Heman-Ackah, S
Zhan, M
Rao, M
AF Malik, Nasir
Wang, Xiantao
Shah, Sonia
Efthymiou, Anastasia G.
Yan, Bin
Heman-Ackah, Sabrina
Zhan, Ming
Rao, Mahendra
TI Comparison of the Gene Expression Profiles of Human Fetal Cortical
Astrocytes with Pluripotent Stem Cell Derived Neural Stem Cells
Identifies Human Astrocyte Markers and Signaling Pathways and
Transcription Factors Active in Human Astrocytes
SO PLOS ONE
LA English
DT Article
ID DEVELOPING SPINAL-CORD; CENTRAL-NERVOUS-SYSTEM; PRECURSOR CELLS;
MOUSE-BRAIN; NEURONS; GLIOGENESIS; EFFICIENT; PROTEIN; DIFFERENTIATION;
DISEASE
AB Astrocytes are the most abundant cell type in the central nervous system (CNS) and have a multitude of functions that include maintenance of CNS homeostasis, trophic support of neurons, detoxification, and immune surveillance. It has only recently been appreciated that astrocyte dysfunction is a primary cause of many neurological disorders. Despite their importance in disease very little is known about global gene expression for human astrocytes. We have performed a microarray expression analysis of human fetal astrocytes to identify genes and signaling pathways that are important for astrocyte development and maintenance. Our analysis confirmed that the fetal astrocytes express high levels of the core astrocyte marker GFAP and the transcription factors from the NFI family which have been shown to play important roles in astrocyte development. A group of novel markers were identified that distinguish fetal astrocytes from pluripotent stem cell-derived neural stem cells (NSCs) and NSC-derived neurons. As in murine astrocytes, the Notch signaling pathway appears to be particularly important for cell fate decisions between the astrocyte and neuronal lineages in human astrocytes. These findings unveil the repertoire of genes expressed in human astrocytes and serve as a basis for further studies to better understand astrocyte biology, especially as it relates to disease.
C1 [Malik, Nasir; Wang, Xiantao; Shah, Sonia; Efthymiou, Anastasia G.; Heman-Ackah, Sabrina; Rao, Mahendra] NIAMS, NIH, Bethesda, MD 20892 USA.
[Yan, Bin] Hong Kong Baptist Univ, Dept Biol, Hong Kong, Hong Kong, Peoples R China.
[Zhan, Ming] Weill Cornell Med Coll, Methodist Hosp Res Inst, Houston, TX USA.
[Rao, Mahendra] NIH Ctr Regenerat Med, NIH, Bethesda, MD USA.
RP Malik, N (reprint author), NIAMS, NIH, Bethesda, MD 20892 USA.
EM malikn@mail.nih.gov
OI Efthymiou, Anastasia/0000-0002-1769-5078
FU National Institutes of Health (NIH) Common Fund
FX This research was supported by the National Institutes of Health (NIH)
Common Fund. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 50
TC 11
Z9 11
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 21
PY 2014
VL 9
IS 5
AR e96139
DI 10.1371/journal.pone.0096139
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3AL
UT WOS:000336730600009
PM 24848099
ER
PT J
AU Sugiyama, N
Murayama, A
Suzuki, R
Watanabe, N
Shiina, M
Liang, TJ
Wakita, T
Kato, T
AF Sugiyama, Nao
Murayama, Asako
Suzuki, Ryosuke
Watanabe, Noriyuki
Shiina, Masaaki
Liang, T. Jake
Wakita, Takaji
Kato, Takanobu
TI Single Strain Isolation Method for Cell Culture-Adapted Hepatitis C
Virus by End-Point Dilution and Infection
SO PLOS ONE
LA English
DT Article
ID TRANS-ENCAPSIDATION; PROTEIN; MUTATIONS; PARTICLES; SYSTEM;
IDENTIFICATION; REPLICATION; CHIMPANZEES; ADAPTATION; GENOME
AB The hepatitis C virus (HCV) culture system has enabled us to clarify the HCV life cycle and essential host factors for propagation. However, the virus production level of wild-type JFH-1 (JFH-1/wt) is limited, and this leads to difficulties in performing experiments that require higher viral concentrations. As the cell culture-adapted JFH-1 has been reported to have robust virus production, some mutations in the viral genome may play a role in the efficiency of virus production. In this study, we obtained cell culture-adapted virus by passage of full-length JFH-1 RNA-transfected Huh-7.5.1 cells. The obtained virus produced 3 log-fold more progeny viruses as compared with JFH-1/wt. Several mutations were identified as being responsible for robust virus production, but, on reverse-genetics analysis, the production levels of JFH-1 with these mutations did not reach the level of cell culture-adapted virus. By using the single strain isolation method by end-point dilution and infection, we isolated two strains with additional mutations, and found that these strains have the ability to produce more progeny viruses. On reverse-genetics analysis, the strains with these additional mutations were able to produce robust progeny viruses at comparable levels as cell culture-adapted JFH-1 virus. The strategy used in this study will be useful for identifying strains with unique characteristics, such as robust virus production, from a diverse population, and for determining the responsible mutations for these characteristics.
C1 [Sugiyama, Nao; Murayama, Asako; Suzuki, Ryosuke; Watanabe, Noriyuki; Wakita, Takaji; Kato, Takanobu] Natl Inst Infect Dis, Dept Virol 2, Tokyo, Japan.
[Shiina, Masaaki] Shin Yurigaoka Gen Hosp, Dept Gastroenterol & Hepatol, Kawasaki, Kanagawa, Japan.
[Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Kato, T (reprint author), Natl Inst Infect Dis, Dept Virol 2, Tokyo, Japan.
EM takato@nih.go.jp
FU Japan Society for the Promotion of Science; Ministry of Health, Labour
and Welfare of Japan; Ministry of Education, Culture, Sports, Science
and Technology of Japan
FX This work was supported in part by Grants-in-Aid for Scientific Research
from the Japan Society for the Promotion of Science, from the Ministry
of Health, Labour and Welfare of Japan, and from the Ministry of
Education, Culture, Sports, Science and Technology of Japan. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 38
TC 3
Z9 3
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 21
PY 2014
VL 9
IS 5
AR e98168
DI 10.1371/journal.pone.0098168
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3AL
UT WOS:000336730600094
PM 24848954
ER
PT J
AU Xiang, Y
Eyers, F
Young, IG
Rosenberg, HF
Foster, PS
Yang, M
AF Xiang, Yang
Eyers, Fiona
Young, Ian G.
Rosenberg, Helene F.
Foster, Paul S.
Yang, Ming
TI Identification of MicroRNAs Regulating the Developmental Pathways of
Bone Marrow Derived Mast Cells
SO PLOS ONE
LA English
DT Article
ID C-KIT LIGAND; IMMUNE-RESPONSES; EXPRESSION; MURINE; DISEASE;
MASTOCYTOSIS; ACTIVATION; LINEAGES; DECREASE; SURVIVAL
AB Background: MicroRNAs (miRNAs) play important roles in leukocyte differentiation, although those utilised for specific programs and key functions remain incompletely characterised. As a global approach to gain insights into the potential regulatory role of miRNA in mast cell differentiation we characterised expression in BM cultures from the initiation of differentiation. In cultures enriched in differentiating mast cells we characterised miRNA expression and identified miRNA targeting the mRNA of putative factors involved in differentiation pathways and cellular identity. Detailed pathway analysis identified a unique miRNA network that is intimately linked to the mast cell differentiation program.
Methodology/Principal Findings: We identified 86 unique miRNAs with expression patterns that were up-or downregulated at 5-fold or more during bone marrow derived mast cells (BMMC) development. By employing TargetScan and MeSH databases, we identified 524 transcripts involved in 30 canonical pathways as potentially regulated by these specific 86 miRNAs. Furthermore, by applying miRanda and IPA analyses, we predict that 7 specific miRNAs of this group are directly associated with the expression of c-Kit and Fc epsilon RI alpha and likewise, that 18 miRNAs promote expression of Mitf, GATA1 and c/EBP alpha three core transcription factors that direct mast cell differentiation. Furthermore, we have identified 11 miRNAs that may regulate the expression of STATs-3, -5a/b, GATA2 and GATA3 during differentiation, along with 13 miRNAs that target transcripts encoding Ndst2, mMCP4 and mMCP6 and thus may regulate biosynthesis of mast cell secretory mediators.
Conclusions/Significance: This investigation characterises changes in miRNA expression in whole BM cultures during the differentiation of mast cells and predicts functional links between miRNAs and their target mRNAs for the regulation of development. This information provides an important resource for further investigations of the contributions of miRNAs to mast cell differentiation and function.
C1 [Xiang, Yang; Eyers, Fiona; Foster, Paul S.; Yang, Ming] Univ Newcastle, Fac Hlth, Sch Biomed Sci & Pharm, Ctr Asthma & Resp Dis, Callaghan, NSW 2308, Australia.
[Xiang, Yang; Eyers, Fiona; Foster, Paul S.; Yang, Ming] Hunter Med Res Inst, Callaghan, NSW, Australia.
[Xiang, Yang] Cent S Univ, Xiangya Sch Med, Dept Physiol, Changsha, Hunan, Peoples R China.
[Young, Ian G.] Australian Natl Univ, John Curtin Sch Med Res, Dept Mol Biosci, Canberra, ACT 2601, Australia.
[Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Foster, PS (reprint author), Univ Newcastle, Fac Hlth, Sch Biomed Sci & Pharm, Ctr Asthma & Resp Dis, Callaghan, NSW 2308, Australia.
EM Paul.Foster@newcastle.edu.au; Ming.Yang@newcastle.edu.au
FU National Health and Medical Research Council of Australia; Australian
Research Council; Cooperative Research Centre for Asthma and Airways;
National Institute of Allergy and Infectious Diseases Division of
Intramural Research
FX The authors are supported by the National Health and Medical Research
Council of Australia, the Australian Research Council, the Cooperative
Research Centre for Asthma and Airways and National Institute of Allergy
and Infectious Diseases Division of Intramural Research. The funding
bodies had no further role in study design; in the collection, analysis
and interpretation of data; in the writing of the report; or in the
decision to submit the paper for publication.
NR 47
TC 9
Z9 10
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 21
PY 2014
VL 9
IS 5
AR e98139
DI 10.1371/journal.pone.0098139
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3AL
UT WOS:000336730600091
PM 24848502
ER
PT J
AU Highfill, SL
Cui, YZ
Giles, AJ
Smith, JP
Zhang, H
Morse, E
Kaplan, RN
Mackall, CL
AF Highfill, Steven L.
Cui, Yongzhi
Giles, Amber J.
Smith, Jillian P.
Zhang, Hua
Morse, Elizabeth
Kaplan, Rosandra N.
Mackall, Crystal L.
TI Disruption of CXCR2-Mediated MDSC Tumor Trafficking Enhances Anti-PD1
Efficacy
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID RENAL-CELL CARCINOMA; SUPPRESSOR-CELLS; MYELOID CELLS; CANCER;
EXPRESSION; RECEPTOR; INTERLEUKIN-8; IMMUNOTHERAPY; PD-1;
RHABDOMYOSARCOMA
AB Suppression of the host's immune system plays a major role in cancer progression. Tumor signaling of programmed death 1 (PD1) on T cells and expansion of myeloid-derived suppressor cells (MDSCs) are major mechanisms of tumor immune escape. We sought to target these pathways in rhabdomyosarcoma (RMS), the most common soft tissue sarcoma of childhood. Murine RMS showed high surface expression of PD-L1, and anti-PD1 prevented tumor growth if initiated early after tumor inoculation; however, delayed anti-PD1 had limited benefit. RMS induced robust expansion of CXCR2(+)CD11b(+)Ly6G(hi) MDSCs, and CXCR2 deficiency prevented CD11b(+)Ly6G(hi) MDSC trafficking to the tumor. When tumor trafficking of MDSCs was inhibited by CXCR2 deficiency, or after anti-CXCR2 monoclonal antibody therapy, delayed anti-PD1 treatment induced significant antitumor effects. Thus, CXCR2+ CD11b(+) Ly6G(hi) MDSCs mediate local immunosuppression, which limits the efficacy of checkpoint blockade in murine RMS. Human pediatric sarcomas also produce CXCR2 ligands, including CXCL8. Patients with metastatic pediatric sarcomas display elevated serum CXCR2 ligands, and elevated CXCL8 is associated with diminished survival in this population. We conclude that accumulation of MDSCs in the tumor bed limits the efficacy of checkpoint blockade in cancer. We also identify CXCR2 as a novel target for modulating tumor immune escape and present evidence that CXCR2+ CD11b+ Ly6Ghi MDSCs are an important suppressive myeloid subset in pediatric sarcomas. These findings present a translatable strategy to improve the efficacy of checkpoint blockade by preventing trafficking of MDSCs to the tumor site.
C1 [Highfill, Steven L.; Cui, Yongzhi; Giles, Amber J.; Smith, Jillian P.; Zhang, Hua; Morse, Elizabeth; Kaplan, Rosandra N.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Mackall, CL (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM cm35c@nih.gov
FU NIH Intramural Research Program; Liddy Shriver Sarcoma Initiative
FX This work was supported in part by the NIH Intramural Research Program
as well as by funding from the Liddy Shriver Sarcoma Initiative.
NR 48
TC 54
Z9 57
U1 1
U2 20
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAY 21
PY 2014
VL 6
IS 237
AR 237ra67
DI 10.1126/scitranslmed.3007974
PG 13
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AI2DY
UT WOS:000336668800007
PM 24848257
ER
PT J
AU Schmidt, TM
Alam, NM
Chen, S
Kofuji, P
Li, W
Prusky, GT
Hattar, S
AF Schmidt, Tiffany M.
Alam, Nazia M.
Chen, Shan
Kofuji, Paulo
Li, Wei
Prusky, Glen T.
Hattar, Samer
TI A Role for Melanopsin in Alpha Retinal Ganglion Cells and Contrast
Detection
SO NEURON
LA English
DT Article
ID CAT RETINA; SPATIAL VISION; MOUSE; SYSTEM; PROJECTIONS; ADAPTATION;
IRRADIANCE; NEURONS; RATS; MICE
AB Distinct subclasses of retinal ganglion cells (RGCs) mediate vision and nonimage-forming functions such as circadian photoentrainment. This distinction stems from studies that ablated melanopsin-expressing intrinsically photosensitive RGCs (ipRGCs) and showed deficits in nonimage-forming behaviors, but not image vision. However, we show that the ON alpha RGC, a conventional RGC type, is intrinsically photosensitive in mammals. In addition to their classical response to fast changes in contrast through rod/cone signaling, melanopsin expression allows ON alpha RGCs to signal prior light exposure and environmental luminance over long periods of time. Consistent with the high contrast sensitivity of ON alpha RGCs, mice lacking either melanopsin or ON alpha RGCs have behavioral deficits in contrast sensitivity. These findings indicate a surprising role for melanopsin and ipRGCs in vision.
C1 [Schmidt, Tiffany M.; Hattar, Samer] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
[Alam, Nazia M.; Prusky, Glen T.] Weill Cornell Med Coll, Burke Med Res Inst, Dept Physiol & Biophys, White Plains, NY 10605 USA.
[Chen, Shan; Li, Wei] NEI, NIH, Bethesda, MD 20892 USA.
[Kofuji, Paulo] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA.
[Hattar, Samer] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21218 USA.
RP Schmidt, TM (reprint author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
EM tmschmidt@jhu.edu
RI Schmidt, Tiffany/A-9660-2012; Schmidt, Tiffany /L-7598-2014;
OI Schmidt, Tiffany/0000-0002-4791-6775; Schmidt, Tiffany
/0000-0002-4791-6775; Kofuji, Paulo/0000-0002-4840-9986
FU National Institutes of Health [GM076430, EY022543]; NIH; Burke
Foundation
FX We would like to thank Drs. Marnie Halpern, Rejji Kuruvilla, Haiqing
Zhao, Robert F. Miller, and Stewart Hendry for comments on the
manuscript. We would also like to thank Dr. Cara Altimus, Ms. Diane Vig,
and Mr. Nathan Schmidt for technical assistance. This work was funded by
National Institutes of Health grants GM076430 (S. H.) and EY022543 (T.
M. S.), the NIH Intramural Research Program (W. L.), and the Burke
Foundation (G. T. P.). G. T. P. is a principal at Cerebral Mechanics,
which manufactures equipment and software used in this study.
NR 33
TC 41
Z9 41
U1 4
U2 20
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD MAY 21
PY 2014
VL 82
IS 4
BP 781
EP 788
DI 10.1016/j.neuron.2014.03.022
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA AH8IA
UT WOS:000336379800009
PM 24853938
ER
PT J
AU Jinsmaa, Y
Sullivan, P
Gross, D
Cooney, A
Sharabi, Y
Goldstein, DS
AF Jinsmaa, Yunden
Sullivan, Patricia
Gross, Daniel
Cooney, Adele
Sharabi, Yehonatan
Goldstein, David S.
TI Divalent metal ions enhance DOPAL-induced oligomerization of
alpha-synuclein
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Alpha-synuclein; Oligomerization; Dopamine; Copper; DOPAL; Parkinson
disease
ID TOXIC DOPAMINE METABOLITE; PARKINSONS-DISEASE; LEWY BODIES;
3,4-DIHYDROXYPHENYLACETALDEHYDE; AGGREGATION; COPPER; IRON; OXIDATION;
FERRITIN; BINDING
AB Parkinson disease (PD) features profound striatal dopamine depletion and Lewy bodies containing abundant precipitated alpha-synuclein. Mechanisms linking alpha-synucleinopathy with the death of dopamine neurons remain incompletely understood. One such link may be 3,4-dihydroxyphenylacetaldehyde (DOPAL). All of the intra-neuronal metabolism of dopamine passes through DOPAL, which is toxic. DOPAL also potently oligomerizes alpha-synuclein and alpha-synuclein oligomers are thought to be pathogenic in PD. Another implicated factor in PD pathogenesis is metal ions, and alpha-synuclein contains binding sites for these ions. In this study we tested whether divalent metal ions augment DOPAL-induced oligomerization of alpha-synuclein in cell-free system and in PC12 cells conditionally over-expressing alpha-synuclein. Incubation with divalent metal ions augmented DOPAL-induced oligomerization of alpha-synuclein (Cu2+ > Fe2+ > Mn2+), whereas monovalent Cu1+ and trivalent Fe3+ were without effect. Other dopamine metabolites, dopamine itself, and metal ions alone or in combination with dopamine, also had no effect. Antioxidant treatment with ascorbic acid and divalent cation chelation with EDTA attenuated the augmentation by Cu2+ of DOPAL-induced alpha-synuclein oligomerization. Incubation of PC12 cells with L-DOPA markedly increased intracellular DOPAL content and promoted alpha-synuclein dimerization. Co-incubation with Cu2+ amplified (p = 0.01), while monoamine oxidase inhibition prevented, L-DOPA-related dimerization of alpha-synuclein (p = 0.01). We conclude that divalent metal ions augment DOPAL-induced oligomerization of alpha-synuclein. Drugs that interfere with this interaction might constitute a novel approach for future treatment or prevention approaches. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Jinsmaa, Yunden; Sullivan, Patricia; Gross, Daniel; Cooney, Adele; Sharabi, Yehonatan; Goldstein, David S.] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA.
RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC-1620,Bldg 10,5N220, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU NINDS
FX We thank Dr. Kenneth L. Kirk for providing the DOPAL used in our
experiments. The research was supported by the intramural research
program of the NINDS.
NR 21
TC 16
Z9 16
U1 0
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
EI 1872-7972
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD MAY 21
PY 2014
VL 569
BP 27
EP 32
DI 10.1016/j.neulet.2014.03.016
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA AH8AI
UT WOS:000336356100006
PM 24670480
ER
PT J
AU Kris, MG
Johnson, BE
Berry, LD
Kwiatkowski, DJ
Iafrate, AJ
Wistuba, II
Varella-Garcia, M
Franklin, WA
Aronson, SL
Su, PF
Shyr, Y
Camidge, DR
Sequist, LV
Glisson, BS
Khuri, FR
Garon, EB
Pao, W
Rudin, C
Schiller, J
Haura, EB
Socinski, M
Shirai, K
Chen, HD
Giaccone, G
Ladanyi, M
Kugler, K
Minna, JD
Bunn, PA
AF Kris, Mark G.
Johnson, Bruce E.
Berry, Lynne D.
Kwiatkowski, David J.
Iafrate, A. John
Wistuba, Ignacio I.
Varella-Garcia, Marileila
Franklin, Wilbur A.
Aronson, Samuel L.
Su, Pei-Fang
Shyr, Yu
Camidge, D. Ross
Sequist, Lecia V.
Glisson, Bonnie S.
Khuri, Fadlo R.
Garon, Edward B.
Pao, William
Rudin, Charles
Schiller, Joan
Haura, Eric B.
Socinski, Mark
Shirai, Keisuke
Chen, Heidi
Giaccone, Giuseppe
Ladanyi, Marc
Kugler, Kelly
Minna, John D.
Bunn, Paul A.
TI Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select
Targeted Drugs
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID PROTEIN EXPRESSION; MUTATIONS; ADENOCARCINOMA; GENE; EGFR; GEFITINIB;
THERAPY; IDENTIFICATION; MULTICENTER; SENSITIVITY
AB IMPORTANCE Targeting oncogenic drivers (genomic alterations critical to cancer development and maintenance) has transformed the care of patients with lung adenocarcinomas. The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials.
OBJECTIVES To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s) and measure survival.
DESIGN, SETTING, AND PARTICIPANTS From 2009 through 2012, 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers. Information was collected on patients, therapies, and survival.
INTERVENTIONS Tumors were tested for 10 oncogenic drivers, and results were used to select matched targeted therapies.
MAIN OUTCOMES AND MEASURES Determination of the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival.
RESULTS From 2009 through 2012, tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes (patients with full genotyping). An oncogenic driver was found in 466 of 733 patients (64%). Among these 733 tumors, 182 tumors (25%) had the KRAS driver; sensitizing EGFR, 122 (17%); ALK rearrangements, 57 (8%); other EGFR, 29 (4%); 2 or more genes, 24 (3%); ERBB2 (formerly HER2), 19 (3%); BRAF, 16 (2%); PIK3CA, 6 (<1%); MET amplification, 5 (<1%); NRAS, 5 (<1%); MEK1, 1 (<1%); AKT1, 0. Results were used to select a targeted therapy or trial in 275 of 1007 patients (28%). The median survival was 3.5 years (interquartile range [IQR], 1.96-7.70) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years (IQR, 0.88-6.20) for the 318 patients with any oncogenic driver(s) who did not receive genotype-directed therapy (propensity score-adjusted hazard ratio, 0.69 [95% CI, 0.53-0.9], P = .006).
CONCLUSIONS AND RELEVANCE Actionable drivers were detected in 64% of lung adenocarcinomas. Multiplexed testing aided physicians in selecting therapies. Although individuals with drivers receiving a matched targeted agent lived longer, randomized trials are required to determine if targeting therapy based on oncogenic drivers improves survival.
C1 [Kris, Mark G.; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
[Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Berry, Lynne D.; Su, Pei-Fang; Shyr, Yu; Pao, William; Chen, Heidi] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Kwiatkowski, David J.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Iafrate, A. John; Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Wistuba, Ignacio I.; Glisson, Bonnie S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Varella-Garcia, Marileila; Franklin, Wilbur A.; Camidge, D. Ross; Kugler, Kelly; Bunn, Paul A.] Univ Colorado, Canc Ctr Denver, Aurora, CO USA.
[Aronson, Samuel L.] Partners HealthCare Ctr Personalized Genet Med, Boston, MA USA.
[Khuri, Fadlo R.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
[Garon, Edward B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Rudin, Charles] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Schiller, Joan; Minna, John D.] Univ Texas Southwestern, Med Ctr, Dallas, TX USA.
[Haura, Eric B.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Socinski, Mark] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Shirai, Keisuke] Med Univ S Carolina, Charleston, SC USA.
[Giaccone, Giuseppe] NCI, Bethesda, MD 20892 USA.
[Giaccone, Giuseppe] Georgetown Univ, Sch Med, Washington, DC USA.
RP Kris, MG (reprint author), Mem Sloan Kettering Canc Ctr, 300 E 66th St, New York, NY 10065 USA.
EM krism@mskcc.org
RI Giaccone, Giuseppe/E-8297-2017;
OI Giaccone, Giuseppe/0000-0002-5023-7562; Kris, Mark/0000-0002-7317-5341
FU National Institutes of Health, National Cancer Institute [HSS NIH NCI
1RC2CA148394-010]
FX This study was entirely supported by a grant from the National
Institutes of Health, National Cancer Institute (HSS NIH NCI
1RC2CA148394-010).
NR 41
TC 305
Z9 326
U1 5
U2 37
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 21
PY 2014
VL 311
IS 19
BP 1998
EP 2006
DI 10.1001/jama.2014.3741
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AH4UA
UT WOS:000336122800022
PM 24846037
ER
PT J
AU Buxbaum, JD
Bolshakova, N
Brownfeld, JM
Anney, RJL
Bender, P
Bernier, R
Cook, EH
Coon, H
Cuccaro, M
Freitag, CM
Hallmayer, J
Geschwind, D
Klauck, SM
Nurnberger, JI
Oliveira, G
Pinto, D
Poustka, F
Scherer, SW
Shih, A
Sutcliffe, JS
Szatmari, P
Vicente, AM
Vieland, V
Gallagher, L
AF Buxbaum, Joseph D.
Bolshakova, Nadia
Brownfeld, Jessica M.
Anney, Richard J. L.
Bender, Patrick
Bernier, Raphael
Cook, Edwin H.
Coon, Hilary
Cuccaro, Michael
Freitag, Christine M.
Hallmayer, Joachim
Geschwind, Daniel
Klauck, Sabine M.
Nurnberger, John I.
Oliveira, Guiomar
Pinto, Dalila
Poustka, Fritz
Scherer, Stephen W.
Shih, Andy
Sutcliffe, James S.
Szatmari, Peter
Vicente, Astrid M.
Vieland, Veronica
Gallagher, Louise
TI The Autism Simplex Collection: an international, expertly phenotyped
autism sample for genetic and phenotypic analyses
SO MOLECULAR AUTISM
LA English
DT Article
ID DE-NOVO MUTATIONS; COPY NUMBER VARIATION; SPECTRUM DISORDERS;
COMMUNICATION CHECKLIST; GENOME; INDIVIDUALS; SCALE; RISK;
IDENTIFICATION; VALIDATION
AB Background: There is an urgent need for expanding and enhancing autism spectrum disorder (ASD) samples, in order to better understand causes of ASD.
Methods: In a unique public-private partnership, 13 sites with extensive experience in both the assessment and diagnosis of ASD embarked on an ambitious, 2-year programto collect samples for genetic and phenotypic research and begin analyses on these samples. The program was called The Autism Simplex Collection (TASC). TASC sample collection began in 2008 and was completed in 2010, and included nine sites from North America and four sites from Western Europe, as well as a centralized Data Coordinating Center.
Results: Over 1,700 trios are part of this collection, with DNA from transformed cells now available through the National Institute of Mental Health (NIMH). Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule-Generic (ADOS-G) measures are available for all probands, as are standardized IQ measures, Vineland Adaptive Behavioral Scales (VABS), the Social Responsiveness Scale (SRS), Peabody Picture Vocabulary Test (PPVT), and physical measures (height, weight, and head circumference). At almost every site, additional phenotypic measures were collected, including the Broad Autism Phenotype Questionnaire (BAPQ) and Repetitive Behavior Scale-Revised (RBS-R), as well as the non-word repetition scale, Communication Checklist (Children's or Adult), and Aberrant Behavior Checklist (ABC). Moreover, for nearly 1,000 trios, the Autism Genome Project Consortium (AGP) has carried out Illumina 1 M SNP genotyping and called copy number variation (CNV) in the samples, with data being made available through the National Institutes of Health (NIH). Whole exome sequencing (WES) has been carried out in over 500 probands, together with ancestry matched controls, and this data is also available through the NIH. Additional WES is being carried out by the Autism Sequencing Consortium (ASC), where the focus is on sequencing complete trios. ASC sequencing for the first 1,000 samples (all from whole-blood DNA) is complete and data will be released in 2014. Data is being made available through NIH databases (database of Genotypes and Phenotypes (dbGaP) and National Database for Autism Research (NDAR)) with DNA released in Dist 11.0. Primary funding for the collection, genotyping, sequencing and distribution of TASC samples was provided by Autism Speaks and the NIH, including the National Institute of Mental Health (NIMH) and the National Human Genetics Research Institute (NHGRI).
Conclusions: TASC represents an important sample set that leverages expert sites. Similar approaches, leveraging expert sites and ongoing studies, represent an important path towards further enhancing available ASD samples.
C1 [Buxbaum, Joseph D.; Brownfeld, Jessica M.; Pinto, Dalila] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, Dept Psychiat, New York, NY 10029 USA.
[Bolshakova, Nadia; Anney, Richard J. L.; Gallagher, Louise] Autism Genet Grp, Sch Med, Dept Psychiat, Trin Coll, Dublin 8, Ireland.
[Bender, Patrick] NIMH, Bethesda, MD 20892 USA.
[Bernier, Raphael] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Cook, Edwin H.] Univ Illinois, Inst Juvenile Res, Dept Psychiat, Chicago, IL 60608 USA.
[Coon, Hilary] Univ Utah, Dept Psychiat, Sch Med, Salt Lake City, UT 84108 USA.
[Cuccaro, Michael] Univ Miami, John P Hussman Inst Human Genom, Miami, FL 33101 USA.
[Freitag, Christine M.; Poustka, Fritz] JW Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60528 Frankfurt, Germany.
[Hallmayer, Joachim] Stanford Sch Med, Dept Psychiat & Behav Sci Child & Adolescent Psyc, Stanford, CA USA.
[Geschwind, Daniel] Univ Calif Los Angeles, Dept Neurol, Sch Med, Los Angeles, CA 90095 USA.
[Klauck, Sabine M.] German Canc Res Ctr, D-69120 Heidelberg, Germany.
[Nurnberger, John I.] Indiana Univ, Dept Psychiat, Sch Med, Indianapolis, IN 46202 USA.
[Oliveira, Guiomar] Ctr Hosp, Unidade Neurodesenvolvimento & Autismo, Serv Ctr Desenvolvimento Crianca, P-3000602 Coimbra, Portugal.
[Oliveira, Guiomar] Ctr Hosp, Ctr Invest & Form Clin, Pediat Hosp, P-3000602 Coimbra, Portugal.
[Oliveira, Guiomar] Univ Coimbra, P-3000602 Coimbra, Portugal.
[Oliveira, Guiomar] Univ Clin Pediat, P-3000602 Coimbra, Portugal.
[Oliveira, Guiomar] Univ Coimbra, Inst Biomed Imaging & Life Sci, Fac Med, P-3000602 Coimbra, Portugal.
[Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Dept Mol Genet, Toronto, ON M5G 1X8, Canada.
[Scherer, Stephen W.] McLaughlin Ctr, Toronto, ON M5G 1X8, Canada.
[Scherer, Stephen W.] Univ Toronto, Toronto, ON M5G 1X8, Canada.
[Shih, Andy] Autism Speaks, New York, NY 10016 USA.
[Sutcliffe, James S.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Vanderbilt Kennedy Ctr, Nashville, TN 37232 USA.
[Sutcliffe, James S.] Vanderbilt Univ, Ctr Human Genet Res & Mol Neurosci, Nashville, TN 37232 USA.
[Szatmari, Peter] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON L8N 3Z5, Canada.
[Vicente, Astrid M.] Inst Nacl Saude Dr Ricardo Jorge, P-1649016 Lisbon, Portugal.
[Vicente, Astrid M.] Inst Gulbenkian Ciencias, P-2781901 Oeiras, Portugal.
[Vicente, Astrid M.] BioFIG Ctr Biodivers Funct & Integrat Genom, P-1749016 Lisbon, Portugal.
[Vieland, Veronica] Ohio State Univ, Res Inst, Nationwide Childrens Hosp, Columbus, OH 43210 USA.
RP Buxbaum, JD (reprint author), Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, Dept Psychiat, New York, NY 10029 USA.
EM joseph.buxbaum@mssm.edu; lgallagh@tcd.ie
RI Scherer, Stephen /B-3785-2013; Sutcliffe, James/C-1348-2012;
OI Scherer, Stephen /0000-0002-8326-1999; Sutcliffe,
James/0000-0001-5200-6007; Coon, Hilary/0000-0002-8877-5446; Gallagher,
Louise/0000-0001-9462-2836; Nurnberger, John/0000-0002-7674-1767;
Buxbaum, Joseph/0000-0001-8898-8313; Anney, Richard/0000-0002-6083-407X;
Oliveira, Guiomar/0000-0002-7049-1277
FU National Institutes of Health [MH094303, MH100233]
FX The TASC consortium collection and genotyping was supported by Autism
Speaks. Funding for the sequencing and distribution of TASC samples was
provided by the National Institutes of Health (MH094303 and MH100233).
We thank Dr. Bernie Devlin for thoughtful comments on the manuscript.
NR 43
TC 9
Z9 9
U1 4
U2 14
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2040-2392
J9 MOL AUTISM
JI Mol. Autism
PD MAY 20
PY 2014
VL 5
AR 34
DI 10.1186/2040-2392-5-34
PG 8
WC Genetics & Heredity; Neurosciences
SC Genetics & Heredity; Neurosciences & Neurology
GA CC6BL
UT WOS:000350449400001
PM 25392729
ER
PT J
AU Fliedner, SMJ
Engel, T
Lendvai, NK
Shankavaram, U
Nolting, S
Wesley, R
Elkahloun, AG
Ungefroren, H
Oldoerp, A
Lampert, G
Lehnert, H
Timmers, H
Pacak, K
AF Fliedner, Stephanie M. J.
Engel, Tobias
Lendvai, Nikoletta K.
Shankavaram, Uma
Noelting, Svenja
Wesley, Robert
Elkahloun, Abdel G.
Ungefroren, Hendrik
Oldoerp, Angela
Lampert, Gary
Lehnert, Hendrik
Timmers, Henri
Pacak, Karel
TI Anti-Cancer Potential of MAPK Pathway Inhibition in
Paragangliomas-Effect of Different Statins on Mouse Pheochromocytoma
Cells
SO PLOS ONE
LA English
DT Article
ID SIGNALING PATHWAYS; MEVALONATE PATHWAY; MELANOMA-CELLS; SPORADIC
PHEOCHROMOCYTOMA; REDUCTASE INHIBITORS; GERMLINE MUTATIONS; RET
PROTOONCOGENE; SOMATIC MUTATIONS; INDUCE APOPTOSIS; DOWN-REGULATION
AB To date, malignant pheochromocytomas and paragangliomas (PHEOs/PGLs) cannot be effectively cured and thus novel treatment strategies are urgently needed. Lovastatin has been shown to effectively induce apoptosis in mouse PHEO cells (MPC) and the more aggressive mouse tumor tissue-derived cells (MTT), which was accompanied by decreased phosphorylation of mitogen-activated kinase (MAPK) pathway players. The MAPK pathway plays a role in numerous aggressive tumors and has been associated with a subgroup of PHEOs/PGLs, including K-RAS-, RET-, and NF1-mutated tumors. Our aim was to establish whether MAPK signaling may also play a role in aggressive, succinate dehydrogenase (SDH) B mutation-derived PHEOs/PGLs. Expression profiling and western blot analysis indicated that specific aspects of MAPK-signaling are active in SDHB PHEOs/PGLs, suggesting that inhibition by statin treatment could be beneficial. Moreover, we aimed to assess whether the anti-proliferative effect of lovastatin on MPC and MTT differed from that exerted by fluvastatin, simvastatin, atorvastatin, pravastatin, or rosuvastatin. Simvastatin and fluvastatin decreased cell proliferation most effectively and the more aggressive MTT cells appeared more sensitive in this respect. Inhibition of MAPK1 and 3 phosphorylation following treatment with fluvastatin, simvastatin, and lovastatin was confirmed by western blot. Increased levels of CASP-3 and PARP cleavage confirmed induction of apoptosis following the treatment. At a concentration low enough not to affect cell proliferation, spontaneous migration of MPC and MTT was significantly inhibited within 24 hours of treatment. In conclusion, lipophilic statins may present a promising therapeutic option for treatment of aggressive human paragangliomas by inducing apoptosis and inhibiting tumor spread.
C1 [Fliedner, Stephanie M. J.; Engel, Tobias; Lendvai, Nikoletta K.; Noelting, Svenja; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Fliedner, Stephanie M. J.; Ungefroren, Hendrik; Oldoerp, Angela; Lehnert, Hendrik] Univ Med Ctr Schleswig Holstein, Dept Med 1, Lubeck, Germany.
[Engel, Tobias; Timmers, Henri] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands.
[Shankavaram, Uma] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Noelting, Svenja] Queen Mary Univ London, William Harvey Res Inst, Dept Endocrinol, London, England.
[Noelting, Svenja] Queen Mary Univ London, Barts & London Sch Med, Barts Canc Inst, London, England.
[Wesley, Robert] NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Elkahloun, Abdel G.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Fliedner, SMJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
EM Stephanie.fliedner@uksh.de
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Human Genome Research Institute, National
Institutes of Health, Bethesda, MD, USA; 1st Department of Medicine,
University Medical Center Schleswig-Holstein, Lubeck, Germany
FX Funding was provided by the Intramural Research Programs of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
and the National Human Genome Research Institute, National Institutes of
Health, Bethesda, MD, USA and the 1st Department of Medicine, University
Medical Center Schleswig-Holstein, Lubeck, Germany. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 54
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Z9 5
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 20
PY 2014
VL 9
IS 5
AR e97712
DI 10.1371/journal.pone.0097712
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0UW
UT WOS:000339563400048
PM 24846270
ER
PT J
AU Martinu, T
Kinnier, CV
Sun, J
Kelly, FL
Nelson, ME
Garantziotis, S
Foster, WM
Palmer, SM
AF Martinu, Tereza
Kinnier, Christine V.
Sun, Jesse
Kelly, Francine L.
Nelson, Margaret E.
Garantziotis, Stavros
Foster, W. Michael
Palmer, Scott M.
TI Allogeneic Splenocyte Transfer and Lipopolysaccharide Inhalations Induce
Differential T Cell Expansion and Lung Injury: A Novel Model of
Pulmonary Graft-versus-Host Disease
SO PLOS ONE
LA English
DT Article
ID IDIOPATHIC PNEUMONIA SYNDROME; ALLERGIC AIRWAY INFLAMMATION; INNATE
IMMUNE ACTIVATION; BONE-MARROW TRANSPLANT; INHALED LIPOPOLYSACCHARIDE;
BRONCHIOLITIS OBLITERANS; DENDRITIC CELLS; HYPERRESPONSIVENESS; MICE;
HYPERREACTIVITY
AB Background: Pulmonary GVHD (pGVHD) is an important complication of hematopoietic cell transplant (HCT) and is thought to be a consequence of the HCT conditioning regimen, allogeneic donor cells, and posttransplant lung exposures. We have previously demonstrated that serial inhaled lipopolysaccharide (LPS) exposures potentiate the development of pGVHD after murine allogeneic HCT. In the current study we hypothesized that allogeneic lymphocytes and environmental exposures alone, in the absence of a pre-conditioning regimen, would cause features of pGVHD and would lead to a different T cell expansion pattern compared to syngeneic cells.
Methods: Recipient Rag1(-/-) mice received a transfer of allogeneic (Allo) or syngeneic (Syn) spleen cells. After 1 week of immune reconstitution, mice received 5 daily inhaled LPS exposures and were sacrificed 72 hours after the last LPS exposure. Lung physiology, histology, and protein levels in bronchoalveolar lavage (BAL) were assessed. Lung cells were analyzed by flow cytometry.
Results: Both Allo and Syn mice that undergo LPS exposures (AlloLPS and SynLPS) have prominent lymphocytic inflammation in their lungs, resembling pGVHD pathology, not seen in LPS-unexposed or non-transplanted controls. Compared to SynLPS, however, AlloLPS have significantly increased levels of BAL protein and enhancement of airway hyperreactivity, consistent with more severe lung injury. This injury in AlloLPS mice is associated with an increase in CD8 T cells and effector CD4 T cells, as well as a decrease in regulatory to effector CD4 T cell ratio. Additionally, cytokine analysis is consistent with a preferential Th1 differentiation and upregulation of pulmonary CCL5 and granzyme B.
Conclusions: Allogeneic lymphocyte transfer into lymphocyte-deficient mice, followed by LPS exposures, causes features of pGVHD and lung injury in the absence of a pre-conditioning HCT regimen. This lung disease associated with an expansion of allogeneic effector T cells provides a novel model to dissect mechanisms of pGVHD independent of conditioning.
C1 [Martinu, Tereza; Kelly, Francine L.; Nelson, Margaret E.; Foster, W. Michael; Palmer, Scott M.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Kinnier, Christine V.] Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA.
[Sun, Jesse] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Garantziotis, Stavros] NIEHS, Resp Biol Branch, Res Triangle Pk, NC 27709 USA.
RP Martinu, T (reprint author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
EM tereza.martinu@duke.edu
RI Garantziotis, Stavros/A-6903-2009
OI Garantziotis, Stavros/0000-0003-4007-375X
FU Parker B. Francis Fellowship Program Award; division of intramural
research, NIEHS; [NIH/NHLBI 1P50-HL084917-01]; [NIH 1 K24
HL91140-01A2]; [RR024 127-03]
FX This research was supported by the following grants: NIH/NHLBI
1P50-HL084917-01 (SCCOR), Project 3 (SMP), Training core (to TM); NIH 1
K24 HL91140-01A2 (SMP); RR024 127-03 (TM) (KL2); and Parker B. Francis
Fellowship Program Award (TM). This research was also supported, in
part, by the division of intramural research, NIEHS. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 46
TC 1
Z9 1
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 20
PY 2014
VL 9
IS 5
AR e97951
DI 10.1371/journal.pone.0097951
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0UW
UT WOS:000339563400074
PM 24844383
ER
PT J
AU Acuner-Ozbabacan, ES
Engin, BH
Guven-Maiorov, E
Kuzu, G
Muratcioglu, S
Baspinar, A
Chen, Z
Van Waes, C
Gursoy, A
Keskin, O
Nussinov, R
AF Acuner-Ozbabacan, Ece Saliha
Engin, Billur Hatice
Guven-Maiorov, Emine
Kuzu, Guray
Muratcioglu, Serena
Baspinar, Alper
Chen, Zhong
Van Waes, Carter
Gursoy, Attila
Keskin, Ozlem
Nussinov, Ruth
TI The structural network of Interleukin-10 and its implications in
inflammation and cancer
SO BMC GENOMICS
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTIONS; AMYLOID PRECURSOR PROTEIN; HUMAN TISSUE
KALLIKREINS; TUMOR-DEVELOPMENT; INTERFACE MOTIFS; IMMUNE-RESPONSE;
BREAST-CANCER; IN-VITRO; CELL; RECEPTOR
AB Background: Inflammation has significant roles in all phases of tumor development, including initiation, progression and metastasis. Interleukin-10 (IL-10) is a well-known immuno-modulatory cytokine with an anti-inflammatory activity. Lack of IL-10 allows induction of pro-inflammatory cytokines and hinders anti-tumor immunity, thereby favoring tumor growth. The IL-10 network is among the most important paths linking cancer and inflammation. The simple node-and-edge network representation is useful, but limited, hampering the understanding of the mechanistic details of signaling pathways. Structural networks complete the missing parts, and provide details. The IL-10 structural network may shed light on the mechanisms through which disease-related mutations work and the pathogenesis of malignancies.
Results: Using PRISM (a PRotein Interactions by Structural Matching tool), we constructed the structural network of IL-10, which includes its first and second degree protein neighbor interactions. We predicted the structures of complexes involved in these interactions, thereby enriching the available structural data. In order to reveal the significance of the interactions, we exploited mutations identified in cancer patients, mapping them onto key proteins of this network. We analyzed the effect of these mutations on the interactions, and demonstrated a relation between these and inflammation and cancer. Our results suggest that mutations that disrupt the interactions of IL-10 with its receptors (IL-10RA and IL-10RB) and alpha 2-macroglobulin (A2M) may enhance inflammation and modulate anti-tumor immunity. Likewise, mutations that weaken the A2M-APP (amyloid precursor protein) association may increase the proliferative effect of APP through preventing beta-amyloid degradation by the A2M receptor, and mutations that abolish the A2M-Kallikrein-13 (KLK13) interaction may lead to cell proliferation and metastasis through the destructive effect of KLK13 on the extracellular matrix.
Conclusions: Prediction of protein-protein interactions through structural matching can enrich the available cellular pathways. In addition, the structural data of protein complexes suggest how oncogenic mutations influence the interactions and explain their potential impact on IL-10 signaling in cancer and inflammation.
C1 [Acuner-Ozbabacan, Ece Saliha; Engin, Billur Hatice; Guven-Maiorov, Emine; Kuzu, Guray; Muratcioglu, Serena; Baspinar, Alper; Gursoy, Attila; Keskin, Ozlem] Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Rumelifeneri Yolu, Sariyer Istanbu, Turkey.
[Acuner-Ozbabacan, Ece Saliha; Engin, Billur Hatice; Guven-Maiorov, Emine; Kuzu, Guray; Muratcioglu, Serena; Baspinar, Alper; Gursoy, Attila; Keskin, Ozlem] Koc Univ, Coll Engn, TR-34450 Rumelifeneri Yolu, Sariyer Istanbu, Turkey.
[Nussinov, Ruth] Leidos Biomedical Res Inc, Canc & Inflammat Program, Frederick Natl Lab Canc Res, NCI, Frederick, MD 21702 USA.
[Chen, Zhong; Van Waes, Carter] Natl Inst Deafness & Commun Disorders, Clin Genom Unit, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), Leidos Biomedical Res Inc, Canc & Inflammat Program, Frederick Natl Lab Canc Res, NCI, Frederick, MD 21702 USA.
EM nussinor@helix.nih.gov
RI Gursoy, Attila/E-9565-2015;
OI Gursoy, Attila/0000-0002-2297-2113; Guven Maiorov,
Emine/0000-0002-7388-9811
FU NIDCD/NIH Intramural projects [Z01-DC-00073, Z01-DC-00074]; Federal
funds from the National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Scientific and Technological Research Council of
Turkey (TUBITAK) [113E164]; Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research
FX Zhong Chen and Carter Van Waes are funded by NIDCD/NIH Intramural
projects Z01-DC-00073 and Z01-DC-00074. This project has been funded in
whole or in part with Federal funds from the National Cancer Institute,
National Institutes of Health, under contract number HHSN261200800001E.
This work is partially supported by the Scientific and Technological
Research Council of Turkey (TUBITAK) Grant Number 113E164. The content
of this publication does not necessarily reflect the views or policies
of the Department of Health and Human Services, nor does mention of
trade names, commercial products, or organizations imply endorsement by
the U.S. Government. This research was supported (in part) by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 77
TC 11
Z9 13
U1 2
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD MAY 20
PY 2014
VL 15
SU 4
AR S2
DI 10.1186/1471-2164-15-S4-S2
PG 17
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AJ2CR
UT WOS:000337463200002
PM 25056661
ER
PT J
AU Newburger, JW
Sleeper, LA
Frommelt, PC
Pearson, GD
Mahle, WT
Chen, S
Dunbar-Masterson, C
Mital, S
Williams, IA
Ghanayem, NS
Goldberg, CS
Jacobs, JP
Krawczeski, CD
Lewis, AB
Pasquali, SK
Pizarro, C
Gruber, PJ
Atz, AM
Khaikin, S
Gaynor, JW
Ohye, RG
AF Newburger, Jane W.
Sleeper, Lynn A.
Frommelt, Peter C.
Pearson, Gail D.
Mahle, William T.
Chen, Shan
Dunbar-Masterson, Carolyn
Mital, Seema
Williams, Ismee A.
Ghanayem, Nancy S.
Goldberg, Caren S.
Jacobs, Jeffrey P.
Krawczeski, Catherine D.
Lewis, Alan B.
Pasquali, Sara K.
Pizarro, Christian
Gruber, Peter J.
Atz, Andrew M.
Khaikin, Svetlana
Gaynor, J. William
Ohye, Richard G.
CA Pediat Heart Network Investigators
TI Transplantation-Free Survival and Interventions at 3 Years in the Single
Ventricle Reconstruction Trial
SO CIRCULATION
LA English
DT Article
DE cardiac surgical procedures; heart defects, congenital; heart diseases;
heart ventricles; Norwood procedures
ID AORTOPULMONARY COLLATERAL VESSELS; PULMONARY-ARTERY CONDUIT;
BLALOCK-TAUSSIG SHUNT; LEFT-HEART SYNDROME; NORWOOD PROCEDURE;
RISK-FACTORS; FONTAN; QUANTIFICATION; OPERATION; MORTALITY
AB Background-In the Single Ventricle Reconstruction (SVR) trial, 1-year transplantation-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt (MBTS). At 3 years, we compared transplantation-free survival, echocardiographic right ventricular ejection fraction, and unplanned interventions in the treatment groups.
Methods and Results-Vital status and medical history were ascertained from annual medical records, death indexes, and phone interviews. The cohort included 549 patients randomized and treated in the SVR trial. Transplantation-free survival for the RVPAS versus MBTS groups did not differ at 3 years (67% versus 61%; P=0.15) or with all available follow-up of 4.8 +/- 1.1 years (log-rank P=0.14). Pre-Fontan right ventricular ejection fraction was lower in the RVPAS group than in the MBTS group (41.7 +/- 5.1% versus 44.7 +/- 6.0%; P=0.007), and right ventricular ejection fraction deteriorated in RVPAS (P=0.004) but not MBTS (P=0.40) subjects (pre-Fontan minus 14-month mean, -3.25 +/- 8.24% versus 0.99 +/- 8.80%; P=0.009). The RVPAS versus MBTS treatment effect had nonproportional hazards (P=0.004); the hazard ratio favored the RVPAS before 5 months (hazard ratio=0.63; 95% confidence interval, 0.45-0.88) but the MBTS beyond 1 year (hazard ratio=2.22; 95% confidence interval, 1.07-4.62). By 3 years, RVPAS subjects had a higher incidence of catheter interventions (P<0.001) with an increasing HR over time (P=0.005): <5 months, 1.14 (95% confidence interval, 0.81-1.60); from 5 months to 1 year, 1.94 (95% confidence interval, 1.02-3.69); and >1 year, 2.48 (95% confidence interval, 1.28-4.80).
Conclusions-By 3 years, the Norwood procedure with RVPAS compared with MBTS was no longer associated with superior transplantation-free survival. Moreover, RVPAS subjects had slightly worse right ventricular ejection fraction and underwent more catheter interventions with increasing hazard ratio over time.
C1 [Newburger, Jane W.; Dunbar-Masterson, Carolyn] Boston Childrens Hosp, Boston, MA 02115 USA.
[Newburger, Jane W.; Dunbar-Masterson, Carolyn] Harvard Univ, Sch Med, Boston, MA USA.
[Sleeper, Lynn A.; Chen, Shan] New England Res Inst, Watertown, MA 02172 USA.
[Frommelt, Peter C.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA.
[Frommelt, Peter C.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Pearson, Gail D.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Mahle, William T.] Emory Univ, Atlanta, GA 30322 USA.
[Mital, Seema; Khaikin, Svetlana] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Williams, Ismee A.] Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY USA.
[Goldberg, Caren S.; Ohye, Richard G.] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Jacobs, Jeffrey P.] Congenital Heart Inst Florida, St Petersburg, FL USA.
[Krawczeski, Catherine D.] Cincinnati Childrens Med Ctr, Cincinnati, OH USA.
[Lewis, Alan B.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Pasquali, Sara K.] Duke Univ, North Carolina Consortium, Durham, NC 27706 USA.
[Pasquali, Sara K.] E Carolina Univ, Greenville, NC 27858 USA.
[Pasquali, Sara K.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Pizarro, Christian] Nemours Cardiac Ctr, Wilmington, DE USA.
[Gruber, Peter J.] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA.
[Gruber, Peter J.] Univ Utah, Salt Lake City, UT USA.
[Atz, Andrew M.] Med Univ S Carolina, Charleston, SC USA.
[Gaynor, J. William] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Gaynor, J. William] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
RP Newburger, JW (reprint author), Boston Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA.
EM jane.newburger@cardio.chboston.org
FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279,
HL068281, HL068285, HL068288, HL068290, HL068292, HL085057]
FX This work was supported by grants (HL068269, HL068270, HL068279,
HL068281, HL068285, HL068288, HL068290, HL068292, and HL085057) from the
National Heart, Lung, and Blood Institute. This work is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Heart, Lung, and Blood Institute or
National Institutes of Health.
NR 21
TC 47
Z9 47
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAY 20
PY 2014
VL 129
IS 20
BP 2013
EP +
DI 10.1161/CIRCULATIONAHA.113.006191
PG 25
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AI6KA
UT WOS:000336981400009
PM 24705119
ER
PT J
AU Mai, PL
Loud, JT
Greene, MH
AF Mai, Phuong L.
Loud, Jennifer T.
Greene, Mark H.
TI A Major Step Forward for BRCA1/2-Related Cancer Risk Management
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID REDUCING SALPINGO-OOPHORECTOMY; QUALITY-OF-LIFE; BRCA1/2 MUTATION
CARRIERS; OVARIAN-CANCER; FALLOPIAN-TUBE; PROPHYLACTIC OOPHORECTOMY;
FAMILY-HISTORY; WOMEN; BREAST; CARCINOMA
C1 [Mai, Phuong L.; Loud, Jennifer T.; Greene, Mark H.] NCI, NIH, Rockville, MD 20850 USA.
RP Mai, PL (reprint author), NCI, NIH, Rockville, MD 20850 USA.
NR 35
TC 5
Z9 5
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
BP 1531
EP U21
DI 10.1200/JCO.2013.54.8925
PG 4
WC Oncology
SC Oncology
GA AI3BI
UT WOS:000336733000003
PM 24687832
ER
PT J
AU Blanch-Hartigan, D
Forsythe, LP
Alfano, CM
Smith, T
Nekhlyudov, L
Ganz, PA
Rowland, JH
AF Blanch-Hartigan, Danielle
Forsythe, Laura P.
Alfano, Catherine M.
Smith, Tenbroeck
Nekhlyudov, Larissa
Ganz, Patricia A.
Rowland, Julia H.
TI Provision and Discussion of Survivorship Care Plans Among Cancer
Survivors: Results of a Nationally Representative Survey of Oncologists
and Primary Care Physicians
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID FOLLOW-UP CARE; SURVEILLANCE MAMMOGRAPHY; OUTCOMES RESEARCH; PREVENTIVE
CARE; PATIENT; COMMUNICATION; QUALITY; VIEWS; GENDER
AB Purpose
Survivorship care planning should involve discussions between providers and cancer survivors to address survivors' needs and optimize adherence. We examined the frequency and factors associated with oncologists' and primary care physicians' (PCPs) reports of provision of written survivorship care plans (SCPs) and discussion of survivorship care recommendations with survivors.
Methods
A nationally representative sample of 1,130 oncologists and 1,020 PCPs was surveyed about survivorship care practices with survivors. Logistic regression models predicted multilevel factors associated with providing SCPs or discussing recommendations with survivors.
Results
Although a majority of oncologists (64%) reported always/almost always discussing survivorship care recommendations with survivors, fewer also discussed who survivors should see for cancer-related and other follow-up care (32%); fewer still also provided a written SCP to the survivor (< 5%). Survivorship care recommendations and provider responsibility were not regularly discussed by PCPs and survivors (12%). Oncologists who reported detailed training about late and long-term effects of cancer were more likely to provide written SCPs (odds ratio [OR], 1.73; 95% CI, 1.22 to 2.44) and discuss survivorship care planning with survivors (OR, 2.02; 95% CI, 1.51 to 2.70). PCPs who received SCPs from oncologists were 9x more likely (95% CI, 5.74 to 14.82) to report survivorship discussions with survivors.
Conclusion
A minority of both PCPs and oncologists reported consistently discussing and providing SCPs to cancer survivors. Training and knowledge specific to survivorship care and coordinated care between PCPs and oncologists were associated with increased survivorship discussions with survivors. These nationally representative data provide a useful benchmark to assess implementation of new efforts to improve the follow-up care of survivors. (C) 2014 by American Society of Clinical Oncology
C1 [Blanch-Hartigan, Danielle; Alfano, Catherine M.; Rowland, Julia H.] NCI, Rockville, MD 20850 USA.
[Forsythe, Laura P.] Patient Ctr Outcomes Res Inst, Washington, DC USA.
[Smith, Tenbroeck] Amer Canc Soc, Atlanta, GA 30329 USA.
[Nekhlyudov, Larissa] Harvard Univ, Sch Med, Boston, MA USA.
[Nekhlyudov, Larissa] Harvard Vanguard Med Associates, Boston, MA USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
RP Blanch-Hartigan, D (reprint author), NCI, Off Canc Survivorship, 9609 Med Ctr Dr,MSC 9764, Rockville, MD 20850 USA.
EM danielle.hartigan@nih.gov
FU NCI NIH HHS [HHSN261200700068C]; PHS HHS [HHSN261200700068C]
NR 38
TC 38
Z9 38
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
BP 1578
EP 1585
DI 10.1200/JCO.2013.51.7540
PG 8
WC Oncology
SC Oncology
GA AI3BI
UT WOS:000336733000012
PM 24752057
ER
PT J
AU Andersen, BL
DeRubeis, RJ
Berman, BS
Gruman, J
Champion, VL
Massie, MJ
Holland, JC
Partridge, AH
Bak, K
Somerfield, MR
Rowland, JH
AF Andersen, Barbara L.
DeRubeis, Robert J.
Berman, Barry S.
Gruman, Jessie
Champion, Victoria L.
Massie, Mary Jane
Holland, Jimmie C.
Partridge, Ann H.
Bak, Kate
Somerfield, Mark R.
Rowland, Julia H.
TI Screening, Assessment, and Care of Anxiety and Depressive Symptoms in
Adults With Cancer: An American Society of Clinical Oncology Guideline
Adaptation
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; PATIENT HEALTH QUESTIONNAIRE; STATE WORRY
QUESTIONNAIRE; BREAST-CANCER; MAJOR DEPRESSION; COGNITIVE THERAPY;
PSYCHOMETRIC PROPERTIES; SURVIVORSHIP CARE; RATING-SCALE; METAANALYSIS
AB Purpose
A Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer was identified for adaptation.
Methods
American Society of Clinical Oncology (ASCO) has a policy and set of procedures for adapting clinical practice guidelines developed by other organizations. The guideline was reviewed for developmental rigor and content applicability.
Results
On the basis of content review of the pan-Canadian guideline, the ASCO panel agreed that, in general, the recommendations were clear, thorough, based on the most relevant scientific evidence, and presented options that will be acceptable to patients. However, for some topics addressed in the pan-Canadian guideline, the ASCO panel formulated a set of adapted recommendations based on local context and practice beliefs of the ad hoc panel members. It is recommended that all patients with cancer be evaluated for symptoms of depression and anxiety at periodic times across the trajectory of care. Assessment should be performed using validated, published measures and procedures. Depending on levels of symptoms and supplementary information, differing treatment pathways are recommended. Failure to identify and treat anxiety and depression increases the risk for poor quality of life and potential disease-related morbidity and mortality. This guideline adaptation is part of a larger survivorship guideline series.
Conclusion
Although clinicians may not be able to prevent some of the chronic or late medical effects of cancer, they have a vital role in mitigating the negative emotional and behavioral sequelae. Recognizing and treating effectively those who manifest symptoms of anxiety or depression will reduce the human cost of cancer. (C) 2014 by American Society of Clinical Oncology
C1 [Andersen, Barbara L.] Ohio State Univ, Columbus, OH 43210 USA.
[DeRubeis, Robert J.] Univ Penn, Philadelphia, PA 19104 USA.
[Berman, Barry S.] Broward Hlth Med Ctr, Ft Lauderdale, FL USA.
[Gruman, Jessie] Ctr Adv Hlth, Washington, DC USA.
[Champion, Victoria L.] Indiana Univ, Indianapolis, IN 46204 USA.
[Massie, Mary Jane; Holland, Jimmie C.] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Andersen, Barbara L.; Bak, Kate; Somerfield, Mark R.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA.
[Rowland, Julia H.] NCI, Bethesda, MD 20892 USA.
RP Andersen, BL (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA.
EM guidelines@asco.org
FU NCI NIH HHS [K05 CA098133]
NR 86
TC 77
Z9 80
U1 10
U2 24
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
BP 1605
EP U118
DI 10.1200/JCO.2013.52.4611
PG 16
WC Oncology
SC Oncology
GA AI3BI
UT WOS:000336733000015
PM 24733793
ER
PT J
AU Prasad, V
Massey, PR
Fojo, T
AF Prasad, Vinay
Massey, Paul R.
Fojo, Tito
TI Oral Anticancer Drugs: How Limited Dosing Options and Dose Reductions
May Affect Outcomes in Comparative Trials and Efficacy in Patients
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RENAL-CELL CARCINOMA; PHASE-II-TRIAL; METASTATIC BREAST-CANCER; ADVANCED
HEPATOCELLULAR-CARCINOMA; RANDOMIZED DISCONTINUATION TRIAL; TYROSINE
KINASE INHIBITOR; CHRONIC MYELOID-LEUKEMIA; RESISTANT PROSTATE-CANCER;
PROGRESSION-FREE SURVIVAL; MEDULLARY-THYROID CANCER
AB Historically, cancer medicine has avoided the problem of unequal dosing by comparing maximum-tolerated doses of intravenous regimens with proportionate dose reductions for toxicity. However, in recent years, with the development of numerous oral anticancer agents, dosing options are arbitrarily and increasingly limited by the size of pills. We contend that an underappreciated consequence of pill size is unequal dosing in comparative clinical trials and that this can have an impact on outcomes. We discuss how comparative effectiveness trials can be unbalanced and how the use of doses that are not sustainable might affect outcomes, especially marginal ones. We further argue that because of their poor tolerability and their limited dosing options, which often result in large dose adjustments in response to toxicity, the real-world clinical effectiveness of oral anticancer agents may be diminished and may not emulate results achieved in registration trials. (C) 2014 by American Society of Clinical Oncology
C1 [Prasad, Vinay; Fojo, Tito] NCI, NIH, Bethesda, MD 20892 USA.
[Massey, Paul R.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Prasad, V (reprint author), NCI, Ctr Canc Res, NIH, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM vinayak.prasad@nih.gov
NR 111
TC 17
Z9 17
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
BP 1620
EP U129
DI 10.1200/JCO.2013.53.0204
PG 11
WC Oncology
SC Oncology
GA AI3BI
UT WOS:000336733000016
PM 24711558
ER
PT J
AU Huang, RK
Baxa, U
Aldrian, G
Ahmed, AB
Wall, JS
Mizuno, N
Antzutkin, O
Steven, AC
Kajava, AV
AF Huang, Rick K.
Baxa, Ulrich
Aldrian, Gudrun
Ahmed, Abdullah B.
Wall, Joseph S.
Mizuno, Naoko
Antzutkin, Oleg
Steven, Alasdair C.
Kajava, Andrey V.
TI Conformational Switching in PolyGln Amyloid Fibrils Resulting from a
Single Amino Acid Insertion
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID TRANSMISSION ELECTRON-MICROSCOPY; SOLID-STATE NMR; BETA-SOLENOID
PROTEINS; URE2P PRION FILAMENTS; HUNTINGTONS-DISEASE; POLYGLUTAMINE;
PARALLEL; IMAGE; FORM; ORGANIZATION
AB The established correlation between neurodegenerative disorders and intracerebral deposition of polyglutamine aggregates motivates attempts to better understand their fibrillar structure. We designed polyglutamines with a few lysines inserted to overcome the hindrance of extreme insolubility and two D-lysines to limit the lengths of beta-strands. One is 33 amino acids long (PolyQKd-33) and the other has one fewer glutamine (PolyQKd-32). Both form well-dispersed fibrils suitable for analysis by electron microscopy. Electron diffraction confirmed cross-beta structures in both fibrils. Remarkably, the deletion of just one glutamine residue from the middle of the peptide leads to substantially different amyloid structures. PolyQKd-32 fibrils are consistently 10-20% wider than PolyQKd-33, as measured by negative staining, cryo-electron microscopy, and scanning transmission electron microscopy. Scanning transmission electron microscopy analysis revealed that the PolyQKd-32 fibrils have 50% higher mass-per-length than PolyQKd-33. This distinction can be explained by a superpleated beta-structure model for PolyQKd-33 ;and a model with two beta-solenoid protofibrils for PolyQKd-32. These data provide evidence for beta-arch-containing structures in polyglutamine fibrils and open future possibilities for structure-based drug design.
C1 [Huang, Rick K.; Baxa, Ulrich; Mizuno, Naoko; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
[Baxa, Ulrich] Frederick Natl Lab Canc Res, Electron Microscopy Lab, Canc Res Technol Program, Leidos Biomed Res, Frederick, MD USA.
[Aldrian, Gudrun; Ahmed, Abdullah B.; Kajava, Andrey V.] Univ Montpellier 1 & 2, CNRS, Ctr Rech Biochim Macromol, Montpellier, France.
[Kajava, Andrey V.] Inst Biol Computat, Montpellier, France.
[Kajava, Andrey V.] Univ ITMO, St Petersburg 197101, Russia.
[Wall, Joseph S.] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA.
[Mizuno, Naoko] Max Planck Inst Biochem, Dept Struct Cell Biol, D-82152 Martinsried, Germany.
[Antzutkin, Oleg] Lulea Univ Technol, S-95187 Lulea, Sweden.
[Antzutkin, Oleg] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.
RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
EM stevena@mail.nih.gov; andrey.kajava@crbm.cnrs.fr
RI Kajava, Andrey/E-1107-2014
OI Kajava, Andrey/0000-0002-2342-6886
FU intramural research program of National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS); NCI [HHSN261200800001E];
Overseas Scholarship Scheme Phase II grant by the Higher Education
Commission of Pakistan
FX This work was supported in part by the intramural research program of
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) and by the NCI under contract HHSN261200800001E, and by an
Overseas Scholarship Scheme Phase II grant by the Higher Education
Commission of Pakistan to A.B.A.
NR 41
TC 2
Z9 2
U1 1
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD MAY 20
PY 2014
VL 106
IS 10
BP 2134
EP 2142
DI 10.1016/j.bpj.2014.03.047
PG 9
WC Biophysics
SC Biophysics
GA AH7ZF
UT WOS:000336353200008
PM 24853742
ER
PT J
AU Wilson, SH
AF Wilson, Samuel H.
TI The dark side of DNA repair
SO ELIFE
LA English
DT Editorial Material
ID HUMAN CANCERS; MUTATIONS
C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
NR 6
TC 1
Z9 1
U1 0
U2 5
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD MAY 20
PY 2014
VL 3
AR e03068
DI 10.7554/eLife.03068
PG 3
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AH6PM
UT WOS:000336253000001
PM 24844708
ER
PT J
AU Ehrlich, LS
Medina, GN
Photiadis, S
Whittredge, PB
Watanabe, S
Taraska, JW
Carter, CA
AF Ehrlich, Lorna S.
Medina, Gisselle N.
Photiadis, Sara
Whittredge, Paul B.
Watanabe, Susan
Taraska, Justin W.
Carter, Carol A.
TI Tsg101 regulates P1(4,5)P-2/Ca2+ signaling for HIV-1 Gag assembly
SO FRONTIERS IN MICROBIOLOGY
LA English
DT Article
DE HIV-1; Gag assembly; L domain; Tsg101; P1(4,5)P-2; IP3R; Ca2+ signaling;
ER-PM junction
ID VIRUS TYPE-1 GAG; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR;
INFECTIOUS-ANEMIA VIRUS; PLASMA-MEMBRANE; INTRACELLULAR TRAFFICKING;
TYROSINE PHOSPHORYLATION; MOLECULAR DETERMINANTS; ENDOPLASMIC-RETICULUM;
MYRISTATE EXPOSURE; PHOSPHOLIPASE-C
AB Our previous studies identified the 1,4,5-inositol trisphosphate receptor (IP3R), a channel mediating release of Ca2+ from ER stores, as a cellular factor differentially associated with HIV-1 Gag that might facilitate ESCRT function in virus budding. Channel opening requires activation that is initiated by binding of 1,4,5-triphosphate (IP3), a product of phospholipase C (PLC)-mediated P1(4,5)P-2 hydrolysis. The store emptying that follows stimulates store refilling which requires intact P1(4,5)P-2. Raising cytosolic Ca2+ promotes viral particle production and our studies indicate that IP3R and the ER Ca2+ store are the physiological providers of Ca2+ for Gag assembly and release. Here, we show that Gag modulates ER store gating and refilling. Cells expressing Gag exhibited a higher cytosolic Ca2+ level originating from the ER store than control cells, suggesting that Gag induced release of store Ca2+. This property required the PTAP motif in Gag that recruits Tsg101, an ESCRT-1 component. Consistent with cytosolic Ca2+ elevation, Gag accumulation at the plasma membrane was found to require continuous IP3R activation. Like other IP3R channel modulators, Gag was detected in physical proximity to the ER and to endogenous IP3R, as indicated respectively by total internal reflection fluorescence (TIRE) and immunoelectron microscopy (IEM) or indirect immunofluorescence. Reciprocal co-immunoprecipitation suggested that Gag and IP3R proximity is favored when the PTAP motif in Gag is intact. Gag expression was also accompanied by increased P1(4,5)P-2 accumulation at the plasma membrane, a condition favoring store refilling capacity. Supporting this notion, Gag particle production was impervious to treatment with 2-aminoethoxydiphenyl borate, an inhibitor of a refilling coupling interaction. In contrast, particle production by a Gag mutant lacking the PTAP motif was reduced. We conclude that a functional PTAP L domain, and by inference Tsg101 binding, confers Gag with an ability to modulate both ER store Ca2+ release and ER store refilling.
C1 [Ehrlich, Lorna S.; Medina, Gisselle N.; Photiadis, Sara; Watanabe, Susan; Carter, Carol A.] SUNY Stony Brook, Stony Brook, NY 11794 USA.
[Whittredge, Paul B.; Taraska, Justin W.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Carter, CA (reprint author), SUNY Stony Brook, Life Sci Bldg Rm 248, Stony Brook, NY 11794 USA.
EM carol.carter@stonybrook.edu
RI Taraska, Justin/H-8876-2016
OI Taraska, Justin/0000-0001-5355-9535
FU NIH [AI068463, GM111028]; NIAID; intramural research program of the
National Heart and Lung Institute, NIH
FX We thank Dr. S. Scarlata for instruction and use of instrumentation in
her laboratory for Ca2+ measurement. We thank Indralatha
Jayatilaka for technical assistance and Susan van Horn and the Stony
Brook University Central Microscopy Imaging Electron Microscopy Core
Facility for services. This study was supported by the following: NIH
R01 awards AI068463 and GM111028 to Carol A. Carter; NIAID ARRA
supplemental funding to Carol A. Carter. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript. Paul B. Whittredge and Justin W. Taraska
are supported by the intramural research program of the National Heart
and Lung Institute, NIH.
NR 72
TC 1
Z9 1
U1 0
U2 11
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-302X
J9 FRONT MICROBIOL
JI Front. Microbiol.
PD MAY 20
PY 2014
VL 5
AR 234
DI 10.3389/fmicb.2014.00234
PG 15
WC Microbiology
SC Microbiology
GA AH4IN
UT WOS:000336090700003
PM 24904548
ER
PT J
AU Zhang, SP
Luo, J
Zhu, L
Stinchcomb, DG
Campbell, D
Carter, G
Gilkeson, S
Feuer, EJ
AF Zhang, Shunpu
Luo, Jun
Zhu, Li
Stinchcomb, David G.
Campbell, Dave
Carter, Ginger
Gilkeson, Scott
Feuer, Eric J.
TI Confidence intervals for ranks of age-adjusted rates across states or
counties
SO STATISTICS IN MEDICINE
LA English
DT Article
DE age-adjusted rate; rank; simultaneous confidence interval
ID BONFERRONI PROCEDURE; MULTIPLE TESTS; LEAGUE TABLES
AB Health indices provide information to the general public on the health condition of the community. They can also be used to inform the government's policy making, to evaluate the effect of a current policy or healthcare program, or for program planning and priority setting. It is a common practice that the health indices across different geographic units are ranked and the ranks are reported as fixed values. We argue that the ranks should be viewed as random and hence should be accompanied by an indication of precision (i.e., the confidence intervals). A technical difficulty in doing so is how to account for the dependence among the ranks in the construction of confidence intervals. In this paper, we propose a novel Monte Carlo method for constructing the individual and simultaneous confidence intervals of ranks for age-adjusted rates. The proposed method uses as input age-specific counts (of cases of disease or deaths) and their associated populations. We have further extended it to the case in which only the age-adjusted rates and confidence intervals are available. Finally, we demonstrate the proposed method to analyze US age-adjusted cancer incidence rates and mortality rates for cancer and other diseases by states and counties within a state using a website that will be publicly available. The results show that for rare or relatively rare disease (especially at the county level), ranks are essentially meaningless because of their large variability, while for more common disease in larger geographic units, ranks can be effectively utilized. Copyright (c) 2014 John Wiley & Sons, Ltd.
C1 [Zhang, Shunpu] Univ Nebraska, Dept Stat, Lincoln, NE 68583 USA.
[Luo, Jun; Campbell, Dave; Carter, Ginger] Informat Management Serv Inc, Calverton, MD 20705 USA.
[Zhu, Li; Feuer, Eric J.] NCI, Stat Methodol & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Stinchcomb, David G.] Westat Corp, Rockville, MD 20850 USA.
RP Zhang, SP (reprint author), Univ Nebraska, Dept Stat, Lincoln, NE 68583 USA.
EM szhang3@unl.edu
NR 14
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD MAY 20
PY 2014
VL 33
IS 11
BP 1853
EP 1866
DI 10.1002/sim.6071
PG 14
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA AG7BJ
UT WOS:000335572700005
PM 24420973
ER
PT J
AU Chrispin, J
Jain, A
Soliman, EZ
Guallar, E
Alonso, A
Heckbert, SR
Bluemke, DA
Lima, JAC
Nazarian, S
AF Chrispin, Jonathan
Jain, Aditya
Soliman, Elsayed Z.
Guallar, Eliseo
Alonso, Alvaro
Heckbert, Susan R.
Bluemke, David A.
Lima, Joao A. C.
Nazarian, Saman
TI Association of Electrocardiographic and Imaging Surrogates of Left
Ventricular Hypertrophy With Incident Atrial Fibrillation MESA
(Multi-Ethnic Study of Atherosclerosis)
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE atrial fibrillation; cardiac magnetic resonance imaging;
electrocardiography; left ventricular hypertrophy
ID CARDIOVASCULAR MAGNETIC-RESONANCE; II RECEPTOR BLOCKADE; HEART-FAILURE;
FOLLOW-UP; HYPERTENSION; DIAGNOSIS; CRITERIA; RISK; MASS;
ECHOCARDIOGRAPHY
AB Objectives This study sought to examine the association between left ventricular hypertrophy (LVH), defined by cardiac magnetic resonance (CMR) and electrocardiography (ECG), with incident atrial fibrillation (AF).
Background Previous studies of the association between AF and LVH were based primarily on echocardiographic measures of LVH.
Methods The MESA (Multi-Ethnic Study of Atherosclerosis) enrolled 4,942 participants free of clinically recognized cardiovascular disease. Incident AF was based on MESA-ascertained hospital-discharge International Classification of Diseases codes and Centers for Medicare and Medicaid Services inpatient hospital claims. CMR-LVH was defined as left ventricular mass >= 95th percentile of the MESA population distribution. Eleven ECG-LVH criteria were assessed. The association of LVH with incident AF was evaluated using multivariable Cox proportional hazards models adjusted for CVD risk factors.
Results During a median follow-up of 6.9 years, 214 incident AF events were documented. Participants with AF were more likely to be older, hypertensive, and overweight. The risk of AF was greater in participants with CMR-derived LVH (hazard ratio [HR]: 2.04, 95% confidence interval [CI]: 1.15 to 3.62). AF was associated with ECG-derived LVH measure of Sokolow-Lyon voltage product after adjusting for CMR-LVH (HR: 1.83, 95% CI: 1.06 to 3.14, p=0.02). The associations with AF for CMR-LVH and Sokolow-Lyon voltage product were attenuated when adjusted for CMR left atrial volumes.
Conclusions In a multiethnic cohort of participants without clinically detected cardiovascular disease, both CMR and ECG-derived LVH were associated with incident AF. ECG-LVH showed prognostic significance independent of CMR-LVH. The association was attenuated when adjusted for CMR left atrial volumes. (C) 2014 by the American College of Cardiology Foundation
C1 [Chrispin, Jonathan; Jain, Aditya; Lima, Joao A. C.; Nazarian, Saman] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
[Soliman, Elsayed Z.] Wake Forest Univ, Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Dept Epidemiol, Winston Salem, NC 27109 USA.
[Soliman, Elsayed Z.] Wake Forest Univ, Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Dept Prevent & Internal Med,Cardiol Sect, Winston Salem, NC 27109 USA.
[Guallar, Eliseo] Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Dept Epidemiol, Baltimore, MD USA.
[Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Dept Epidemiol & Community Hlth, Minneapolis, MN USA.
[Heckbert, Susan R.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Ctr Clin, NIH, Bethesda, MD USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
RP Chrispin, J (reprint author), Div Cardiol, Carnegie 568,600 N Wolfe St, Baltimore, MD 21287 USA.
EM chrispin@jhmi.edu
RI Alonso, Alvaro/A-4917-2010;
OI Alonso, Alvaro/0000-0002-2225-8323; Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169];
National Center for Research Resources [UL1-RR-024156, UL1-RR-025005];
National Institutes of Health [K23HL089333, R01HL116280];
Biosense-Webster Incorporated
FX This research was supported by contracts N01-HC-95159 through
N01-HC-95169 from the National Heart, Lung, and Blood Institute and by
grants UL1-RR-024156 and UL1-RR-025005 from the National Center for
Research Resources. Dr. Nazarian is supported by grants K23HL089333 and
R01HL116280 from the National Institutes of Health. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health. Dr.
Nazarian is a scientific advisor and principle investigator for
Biosense-Webster Incorporated and has received research funding to Johns
Hopkins University from Biosense-Webster Incorporated. All other authors
have reported that they have no relationships relevant to the contents
of this paper to disclose. Drs. Chrispin and Jain contributed equally to
this manuscript. Kristian Wachtell, MD, acted as Guest Editor for this
paper.
NR 38
TC 11
Z9 13
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAY 20
PY 2014
VL 63
IS 19
BP 2007
EP 2013
DI 10.1016/j.jacc.2014.01.066
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AH1NN
UT WOS:000335887800010
PM 24657688
ER
PT J
AU Zhang, LP
Syed, ZA
Hard, IV
Lim, JM
Wells, L
Ten Hagen, KG
AF Zhang, Liping
Syed, Zulfeqhar Ali
Hard, Iris van Dijk
Lim, Jae-Min
Wells, Lance
Ten Hagen, Kelly G.
TI O-Glycosylation regulates polarized secretion by modulating Tango1
stability
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE mucin; peritrophic membrane; proventriculus; Drosophila; familial
tumoral calcinosis
ID POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; FAMILIAL TUMORAL
CALCINOSIS; RETICULUM EXIT SITES; UDP-GALNAC; DROSOPHILA-MELANOGASTER;
COLLAGEN SECRETION; EXPRESSION; PROTEIN; GLYCOPROTEOME; MUTATIONS
AB Polarized secretion is crucial in many tissues. The conserved protein modification, O-glycosylation, plays a role in regulating secretion. However, the mechanisms by which this occurs are unknown. Here, we demonstrate that an O-glycosyltransferase functions as a novel regulator of secretion and secretory vesicle formation in vivo by glycosylating the essential Golgi/endoplasmic reticulum protein, Tango1 (Transport and Golgi organization 1), and conferring protection from furin-mediated proteolysis. Loss of the O-glycosyltransferase PGANT4 resulted in Tango1 cleavage, loss of secretory granules, and disrupted apical secretion. The secretory defects seen upon loss of pgant4 could be rescued either by overexpression of Tango1 or by knockdown of a specific furin (Dfur2) in vivo. Our studies elucidate a novel regulatory mechanism whereby secretion is influenced by the yin/yang of O-glycosylation and proteolytic cleavage. Moreover, our data have broader implications for the potential treatment of diseases resulting from the loss of O-glycosylation by modulating the activity of specific proteases.
C1 [Zhang, Liping; Ten Hagen, Kelly G.] Natl Inst Dent & Craniofacial Res, Dev Glycobiol Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Syed, Zulfeqhar Ali] Univ Gothenburg, Inst Biomed, Dept Med Genet, SE-40530 Gothenburg, Sweden.
[Hard, Iris van Dijk] Univ Gothenburg, Inst Hlth & Care Sci, SE-40530 Gothenburg, Sweden.
[Lim, Jae-Min] Changwon Natl Univ, Dept Chem, Chang Won 641773, Gyeongnam, South Korea.
[Lim, Jae-Min; Wells, Lance] Univ Georgia, Complex Carbohydrate Res Ctr, Dept Biochem & Mol Biol, Athens, GA 30602 USA.
RP Ten Hagen, KG (reprint author), Natl Inst Dent & Craniofacial Res, Dev Glycobiol Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM Kelly.Tenhagen@nih.gov
FU National Institute of Dental and Craniofacial Research, National
Institutes of Health [Z01-DE-000713]; National Institutes of
Health/National Institute of General Medical Sciences (National Center
for Biomedical Glycomics) [P41GM103490]; Basic Science Research Program;
Priority Research Centers Program through the National Research
Foundation of Korea (NRF) - Ministry of Education, Science and
Technology [NRF 2011-0013961, NRF 2010-0029634]
FX We thank the members of our laboratory for comments and feedback; Drs.
L. Tabak, L. Angerer, and R. Angerer for many helpful discussions and
insight; Drs. R. Cummings and T. Ju for the kind gift of the Tn
antibody; Drs. L. Fessler and J. Fessler for the kind gift of the
papilin antibody; and Drs. J. Kennison and D. Andrew, the Vienna
Drosophila RNAi Center, the Bloomington Stock Center, and the
Developmental Studies Hybridoma Bank for fly stocks and other reagents.
This work was supported by the Intramural Research Program of the
National Institute of Dental and Craniofacial Research, National
Institutes of Health Grant Z01-DE-000713 (to K. G. T. H.); National
Institutes of Health/National Institute of General Medical Sciences
(National Center for Biomedical Glycomics, Grant P41GM103490, L. W.
Senior Investigator); and the Basic Science Research Program and the
Priority Research Centers Program through the National Research
Foundation of Korea (NRF) funded by the Ministry of Education, Science
and Technology Grants NRF 2011-0013961 and NRF 2010-0029634 (to J.-M.L).
NR 38
TC 15
Z9 15
U1 2
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 20
PY 2014
VL 111
IS 20
BP 7296
EP 7301
DI 10.1073/pnas.1322264111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH5KP
UT WOS:000336168100037
PM 24799692
ER
PT J
AU Tal, A
Arbel-Goren, R
Costantino, N
Court, DL
Stavans, J
AF Tal, Asaf
Arbel-Goren, Rinat
Costantino, Nina
Court, Donald L.
Stavans, Joel
TI Location of the unique integration site on an Escherichia coli
chromosome by bacteriophage lambda DNA in vivo
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE target location; establishment of lysogeny; viral transduction
ID SEPARATE CELL HALVES; GENE-TRANSFER; PHAGE-LAMBDA; LIVING CELLS;
SEGREGATION; INFECTION; RECOMBINATION; ASSOCIATION; MEMBRANE; PLASMID
AB The search for specific sequences on long genomes is a key process in many biological contexts. How can specific target sequences be located with high efficiency, within physiologically relevant times? We addressed this question for viral integration, a fundamental mechanism of horizontal gene transfer driving prokaryotic evolution, using the infection of Escherichia coli bacteria with bacteriophage lambda and following the establishment of a lysogenic state. Following the targeting process in individual live E. coli cells in real time revealed that lambda DNA remains confined near the entry point of a cell following infection. The encounter between the 15-bp-long target sequence on the chromosome and the recombination site on the viral genome is facilitated by the directed motion of bacterial DNA generated during chromosome replication, in conjunction with constrained diffusion of phage DNA. Moving the native bacterial integration site to different locations on the genome and measuring the integration frequency in these strains reveals that the frequencies of the native site and a site symmetric to it relative to the origin are similar, whereas both are significantly higher than when the integration site is moved near the terminus, consistent with the replication-driven mechanism we propose. This novel search mechanism is yet another example of the exquisite coevolution of lambda with its host.
C1 [Tal, Asaf; Arbel-Goren, Rinat; Stavans, Joel] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
[Costantino, Nina; Court, Donald L.] NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
RP Stavans, J (reprint author), Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
EM courtd@mail.nih.gov; joel.stavans@weizmann.ac.il
FU Yeda-Sela Center of the Weizmann Institute of Science; National
Institutes of Health, National Cancer Institute, Center for Cancer
Research
FX We thank S. Austin for comments and plasmids, L. Thomason for the gift
of lambda strain cI857 bor::kanR, and O. Kobiler, and J.
Sawitzke for a careful reading of the manuscript. This work was
supported in part by the Yeda-Sela Center of the Weizmann Institute of
Science (J. S.), and by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research (D.L.C.).
NR 42
TC 9
Z9 9
U1 4
U2 17
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 20
PY 2014
VL 111
IS 20
BP 7308
EP 7312
DI 10.1073/pnas.1324066111
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH5KP
UT WOS:000336168100039
PM 24799672
ER
PT J
AU Yang, GJ
Murray, JD
Repovs, G
Cole, MW
Savic, A
Glasser, MF
Pittenger, C
Krystal, JH
Wang, XJ
Pearlson, GD
Glahn, DC
Anticevic, A
AF Yang, Genevieve J.
Murray, John D.
Repovs, Grega
Cole, Michael W.
Savic, Aleksandar
Glasser, Matthew F.
Pittenger, Christopher
Krystal, John H.
Wang, Xiao-Jing
Pearlson, Godfrey D.
Glahn, David C.
Anticevic, Alan
TI Altered global brain signal in schizophrenia
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE resting-state; global signal; psychiatric illness
ID RESTING-STATE FMRI; FUNCTIONAL CONNECTIVITY MRI; DEFAULT NETWORK;
WORKING-MEMORY; DYSCONNECTIVITY; DYSFUNCTION; FLUCTUATIONS; REGRESSION;
DISORDERS; COGNITION
AB Neuropsychiatric conditions like schizophrenia display a complex neurobiology, which has long been associated with distributed brain dysfunction. However, no investigation has tested whether schizophrenia shows alterations in global brain signal (GS), a signal derived from functional MRI and often discarded as a meaningless baseline in many studies. To evaluate GS alterations associated with schizophrenia, we studied two large chronic patient samples (n = 90, n = 71), comparing them to healthy subjects (n = 220) and patients diagnosed with bipolar disorder (n = 73). We identified and replicated increased cortical power and variance in schizophrenia, an effect predictive of symptoms yet obscured by GS removal. Voxel-wise signal variance was also increased in schizophrenia, independent of GS effects. Both findings were absent in bipolar patients, confirming diagnostic specificity. Biologically informed computational modeling of shared and nonshared signal propagation through the brain suggests that these findings may be explained by altered net strength of overall brain connectivity in schizophrenia.
C1 [Yang, Genevieve J.; Savic, Aleksandar; Pittenger, Christopher; Krystal, John H.; Pearlson, Godfrey D.; Glahn, David C.; Anticevic, Alan] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA.
[Pearlson, Godfrey D.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06511 USA.
[Yang, Genevieve J.; Pittenger, Christopher; Anticevic, Alan] Yale Univ, Interdept Neurosci Program, New Haven, CT 06511 USA.
[Pittenger, Christopher; Anticevic, Alan] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
[Yang, Genevieve J.; Savic, Aleksandar; Pittenger, Christopher; Krystal, John H.; Anticevic, Alan] Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, New Haven, CT 06519 USA.
[Murray, John D.; Wang, Xiao-Jing] NYU, Ctr Neural Sci, New York, NY USA.
[Repovs, Grega] Univ Ljubljana, Dept Psychol, Ljubljana 1000, Slovenia.
[Cole, Michael W.] Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA.
[Savic, Aleksandar] Univ Zagreb, Univ Psychiat Hosp Vrapce, Zagreb 10000, Croatia.
[Glasser, Matthew F.] Washington Univ, Dept Anat & Neurobiol, St Louis, MO 63130 USA.
[Krystal, John H.; Anticevic, Alan] NIAAA, Ctr Translat Neurosci Alcoholism, New Haven, CT 06519 USA.
[Wang, Xiao-Jing] New York Univ, New York Univ East China Normal Univ Joint Inst B, Shanghai, Peoples R China.
[Pearlson, Godfrey D.; Glahn, David C.] Hartford Hosp, Olin Neuropsychiat Res Ctr, Inst Living, Hartford, CT 06106 USA.
RP Anticevic, A (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA.
EM alan.anticevic@yale.edu
RI Murray, John/B-2835-2009; Cole, Michael/G-1056-2010
OI Murray, John/0000-0003-4115-8181; Cole, Michael/0000-0003-4329-438X
FU National Institutes of Health [DP50D012109-02, MH080912, MH096801,
MH43775, MH077945, MH074797, T32GM 007205]; National Institute on
Alcohol Abuse and Alcoholism [2P50AA012870-11]; Fulbright Foundation;
National Alliance for Research on Schizophrenia and Depression Young
Investigator Award; [R01-MH062349]
FX We thank Dr. David Van Essen for helpful comments during manuscript
preparation; Dr. Francis Song for assistance with implementing
anatomical connectivity into the model; and Dr. Vince Calhoun for
assistance with the publicly available Center for Biomedical Research
Excellence dataset. Financial support was provided by National
Institutes of Health Grants DP50D012109-02 [to A.A., PI (principal
investigator)], MH080912 (to D.C.G., PI), MH096801 (to M.W.C., PI), and
MH43775, MH077945, and MH074797 (to G.D.P., PI); National Institute on
Alcohol Abuse and Alcoholism Grant 2P50AA012870-11 (to J.H.K., PI); the
Fulbright Foundation (A.S.); the National Alliance for Research on
Schizophrenia and Depression Young Investigator Award (to A.A., PI);
Grant R01-MH062349 (to J.D.M. and X.-J.W.); and National Institutes of
Health Grant T32GM 007205 (to G.J.Y.).
NR 44
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PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 20
PY 2014
VL 111
IS 20
BP 7438
EP 7443
DI 10.1073/pnas.1405289111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH5KP
UT WOS:000336168100061
PM 24799682
ER
PT J
AU Thomson, R
Genovese, G
Canon, C
Kovacsics, D
Higgins, MK
Carrington, M
Winkler, CA
Kopp, J
Rotimi, C
Adeyemo, A
Doumatey, A
Ayodo, G
Alper, SL
Pollak, MR
Friedman, DJ
Raper, J
AF Thomson, Russell
Genovese, Giulio
Canon, Chelsea
Kovacsics, Daniella
Higgins, Matthew K.
Carrington, Mark
Winkler, Cheryl A.
Kopp, Jeffrey
Rotimi, Charles
Adeyemo, Adebowale
Doumatey, Ayo
Ayodo, George
Alper, Seth L.
Pollak, Martin R.
Friedman, David J.
Raper, Jayne
TI Evolution of the primate trypanolytic factor APOL1
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID TRYPANOSOME LYTIC FACTOR; DNA-SEQUENCING DATA; HUMAN SERUM; AFRICAN
TRYPANOSOMES; BRUCEI-GAMBIENSE; HUMAN GENOME; RESISTANCE; VARIANTS;
PROTEIN; ASSOCIATION
AB ApolipoproteinL1 (APOL1) protects humans and some primates against several African trypanosomes. APOL1 genetic variants strongly associated with kidney disease in African Americans have additional trypanolytic activity against Trypanosoma brucei rhodesiense, the cause of acute African sleeping sickness. We combined genetic, physiological, and biochemical studies to explore coevolution between the APOL1 gene and trypanosomes. We analyzed the APOL1 sequence in modern and archaic humans and baboons along with geographic distribution in present day Africa to understand how the kidney risk variants evolved. Then, we tested Old World monkey, human, and engineered APOL1 variants for their ability to kill human infective trypanosomes in vivo to identify the molecular mechanism whereby human trypanolytic APOL1 variants evade T. brucei rhodesiense virulence factor serum resistance-associated protein (SRA). For one APOL1 kidney risk variant, a two-residue deletion of amino acids 388 and 389 causes a shift in a single lysine residue that mimics the Old World monkey sequence, which augments trypanolytic activity by preventing SRA binding. A second human APOL1 kidney risk allele, with an amino acid substitution that also restores sequence alignment with Old World monkeys, protected against T. brucei rhodesiense due in part to reduced SRA binding. Both APOL1 risk variants induced tissue injury in murine livers, the site of transgenic gene expression. Our study shows that both genetic variants of human APOL1 that protect against T. brucei rhodesiense have recapitulated molecular signatures found in Old World monkeys and raises the possibility that APOL1 variants have broader innate immune activity that extends beyond trypanosomes.
C1 [Thomson, Russell; Canon, Chelsea; Kovacsics, Daniella; Raper, Jayne] NYU, Dept Microbiol, Sch Med, New York, NY 10016 USA.
[Genovese, Giulio; Alper, Seth L.; Pollak, Martin R.; Friedman, David J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02215 USA.
[Friedman, David J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Vasc Biol Res, Boston, MA 02215 USA.
[Genovese, Giulio; Pollak, Martin R.] Broad Inst Harvard & Massachusetts Inst Technol, Boston, MA 02215 USA.
[Canon, Chelsea; Kovacsics, Daniella; Raper, Jayne] CUNY Hunter Coll, Dept Biol Sci, New York, NY 10065 USA.
[Higgins, Matthew K.] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
[Carrington, Mark] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England.
[Winkler, Cheryl A.] NCI, Basic Res Lab, Ctr Canc Res, NIH,Leidos Biomed Res Inc,Frederick Natl Lab, Frederick, MD 21702 USA.
[Kopp, Jeffrey] NIH, Kidney Dis Sect, Bethesda, MD 20892 USA.
[Rotimi, Charles; Adeyemo, Adebowale; Doumatey, Ayo] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Ayodo, George] Kenya Govt Med Res Ctr, Kisumu, Kenya.
[Ayodo, George] Univ Minnesota, Sch Med, Div Pediat, Minneapolis, MN 55454 USA.
RP Friedman, DJ (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02215 USA.
EM dfriedma@bidmc.harvard.edu; raper@genectr.hunter.cuny.edu
OI Kopp, Jeffrey/0000-0001-9052-186X; Higgins, Matthew/0000-0002-2870-1955;
Adeyemo, Adebowale/0000-0002-3105-3231
FU National Institutes of Health (NIH)/National Institute of Allergy and
Infectious Diseases (NIAID) [R01AI041233]; National Science Foundation
[IOS-1249166]; NIH/NIAID Training Grant [T32 AI007180]; NIH/National
Institute of Diabetes and Digestive and Kidney Diseases Grant (NIDDK)
[DK76868]; Doris Duke Charitable Foundation; Satellite Healthcare
Foundation Coplon Award; NIH/National Institue on Minority Health and
Health Disparities Grant [R01MD007092]; Wellcome Trust [085256/Z/08/Z,
087692/Z/08/Z]; NIH Intramural Research Program of the Center for
Research on Genomics and Global Health [Z01HG200362]; NIH/NIDDK; Doris
Duke Clinical Scientist Development Award; National Cancer Institute
FX This work was supported by National Institutes of Health (NIH)/National
Institute of Allergy and Infectious Diseases (NIAID) Grant R01AI041233
(to J.R.), National Science Foundation Bread Award IOS-1249166 (to
J.R.), NIH/NIAID Training Grant T32 AI007180 (to R.T.), NIH/National
Institute of Diabetes and Digestive and Kidney Diseases Grant (NIDDK)
DK76868 (to D.J.F.), the Doris Duke Charitable Foundation (D.J.F.),
Satellite Healthcare Foundation Coplon Award (to D.J.F.), NIH/National
Institue on Minority Health and Health Disparities Grant R01MD007092 (to
M.R.P.), Wellcome Trust Project Grants 085256/Z/08/Z (to M.C.) and
087692/Z/08/Z (to M.K.H.), NIH Intramural Research Program of the Center
for Research on Genomics and Global Health Grant Z01HG200362 (to C.R.),
and the NIH/NIDDK and National Cancer Institute Intramural Research
Programs (C.A.W. and J.K.). D.J.F. is a recipient of a Doris Duke
Clinical Scientist Development Award.
NR 46
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PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 20
PY 2014
VL 111
IS 20
BP E2130
EP E2139
DI 10.1073/pnas.1400699111
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH5KP
UT WOS:000336168100010
PM 24808134
ER
PT J
AU Kadri, SS
O'Grady, NP
AF Kadri, Sameer S.
O'Grady, Naomi P.
TI Review: Short and long courses of antibiotics do not differ for
mortality in ventilator-associated pneumonia
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
C1 [Kadri, Sameer S.; O'Grady, Naomi P.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Kadri, SS (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 0
U2 1
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAY 20
PY 2014
VL 160
IS 10
AR JC3
DI 10.7326/0003-4819-160-10-201405200-02003
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA AJ0MJ
UT WOS:000337347100002
PM 24842437
ER
PT J
AU Wisniewski, J
Hajj, B
Chen, JJ
Mizuguchi, G
Xiao, H
Wei, D
Dahan, M
Wu, C
AF Wisniewski, Jan
Hajj, Bassam
Chen, Jiji
Mizuguchi, Gaku
Xiao, Hua
Wei, Debbie
Dahan, Maxime
Wu, Carl
TI Imaging the fate of histone Cse4 reveals de novo replacement in S phase
and subsequent stable residence at centromeres
SO ELIFE
LA English
DT Article
DE centromere; kinetochore; Cse4 nucleosome; histone CENP-A; chaperone
Scm3; multifocus microscopy; 3D-PALM; photoconvertible fluorescent
protein
ID BUDDING YEAST KINETOCHORE; SACCHAROMYCES-CEREVISIAE; CENP-A; FISSION
YEAST; NONHISTONE SCM3; CHAPERONE SCM3; H3 VARIANT; PROTEIN; NUCLEOSOME;
LOCALIZATION
AB The budding yeast centromere contains Cse4, a specialized histone H3 variant. Fluorescence pulse-chase analysis of an internally tagged Cse4 reveals that it is replaced with newly synthesized molecules in S phase, remaining stably associated with centromeres thereafter. In contrast, C-terminally-tagged Cse4 is functionally impaired, showing slow cell growth, cell lethality at elevated temperatures and extra-centromeric nuclear accumulation. Recent studies using such strains gave conflicting findings regarding the centromeric abundance and cell cycle dynamics of Cse4. Our findings indicate that internally tagged Cse4 is a better reporter of the biology of this histone variant. Furthermore, the size of centromeric Cse4 clusters was precisely mapped with a new 3D-PALM method, revealing substantial compaction during anaphase. Cse438 specific chaperone Scm3 displays steady-state, stoichiometric co-localization with Cse4 at centromeres throughout the cell cycle, while undergoing exchange with a nuclear pool. These findings suggest that a stable Cse4 nucleosome is maintained by dynamic chaperone-in-residence Scm3.
C1 [Wisniewski, Jan; Hajj, Bassam; Chen, Jiji; Mizuguchi, Gaku; Dahan, Maxime; Wu, Carl] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
[Wisniewski, Jan; Mizuguchi, Gaku; Xiao, Hua; Wei, Debbie; Wu, Carl] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Wu, C (reprint author), Howard Hughes Med Inst, Janelia Farm Res Campus, Ashburn, VA 20147 USA.
EM wisniewskij@janelia.hhmi.org; wuc@janelia.hhmi.org
RI Dahan, Maxime /F-1740-2010
FU Center for Cancer Research; NCI; NIH; Janelia Farm Research Campus,
HHMI; Fulbright fellowship
FX We thank Manjunatha Shivaraju and Jennifer Gerton (Stowers Institute for
Medical Research, Kansas City) for the C-terminally tagged Cse4-GFP
strain, Gleb Shtengel (Janelia Farm, Ashburn) for advice and preparation
of coverslips with immobilized Gold Nanorods, Richard Baker for
communicating unpublished results, and Mohamed El Beheiry for use of
ViSP software during its development. We are grateful to members of
Transcription Imaging Consortium (HHMI Janelia Farm, Ashburn) and our
laboratories for helpful discussions. This work was supported by the
Center for Cancer Research, NCI, NIH, and the Janelia Farm Research
Campus, HHMI. M. D. acknowledges the support of a Fulbright fellowship.
NR 63
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U1 0
U2 0
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD MAY 20
PY 2014
VL 3
AR e02203
DI 10.7554/eLife.02203
PG 38
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AH6PM
UT WOS:000336253000002
PM 24844245
ER
PT J
AU Abraham, J
Robidoux, A
Tan, AR
Buyse, ME
Wolmark, N
Jacobs, SA
AF Abraham, Jame
Robidoux, Andre
Tan, Antoinette R.
Buyse, Marc E.
Wolmark, Norman
Jacobs, Samuel A.
TI Phase II randomized clinical trial evaluating neoadjuvant chemotherapy
regimens with weekly paclitaxel (WP) or eribulin (E) followed by
doxorubicin and cyclophosphamide (AC) in women with locally advanced
HER2-negative breast cancer (LABC): NSABP FB-9
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Cleveland Clin, Cleveland, OH 44106 USA.
NSABP, Montreal, PQ, Canada.
Univ Montreal, Ctr Hosp, Montreal, PQ, Canada.
NSABP, New Brunswick, NJ USA.
Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
Int Inst Drug Dev, Louvain La Neuve, Belgium.
NSABP, Pittsburgh, PA USA.
Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 1058
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202479
ER
PT J
AU Allegra, CJ
Yothers, G
O'Connell, MJ
Roh, MS
Lopa, SH
Petrelli, NJ
Beart, RW
Sharif, S
Wolmark, N
AF Allegra, Carmen Joseph
Yothers, Greg
O'Connell, Michael J.
Roh, Mark S.
Lopa, Samia H.
Petrelli, Nicholas J.
Beart, Robert W.
Sharif, Saima
Wolmark, Norman
TI Final results from NSABP protocol R-04: Neoadjuvant chemoradiation (RT)
comparing continuous infusion (CIV) 5-FU with capecitabine (Cape) with
or without oxaliplatin (Ox) in patients with stage II and III rectal
cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Florida, Gainesville, FL USA.
NSABP Biostat Ctr, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
NSABP, Pittsburgh, PA USA.
NSABP, Orlando, FL USA.
Orlando Hlth, UF Hlth Canc Ctr, Orlando, FL USA.
Helen F Graham Canc Ctr & Res Inst, Newark, DE USA.
NSABP, Glendale, CA USA.
Glendale Mem Hosp, Glendale, CA USA.
Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
NR 0
TC 6
Z9 6
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 3603
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203119
ER
PT J
AU Apolo, AB
Tomita, Y
Lee, MJ
Lee, S
Frosch, A
Steinberg, SM
Gulley, JL
Schlom, J
Bottaro, DP
Trepel, JB
AF Apolo, Andrea Borghese
Tomita, Yusuke
Lee, Min-Jung
Lee, Sunmin
Frosch, Ari
Steinberg, Seth M.
Gulley, James L.
Schlom, Jeffrey
Bottaro, Donald P.
Trepel, Jane B.
TI Effect of cabozantinib on immunosuppressive subsets in metastatic
urothelial carcinoma.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NIH, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA.
NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 6
Z9 6
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 4501
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203307
ER
PT J
AU Apolo, AB
Parnes, HL
Madan, RA
Gulley, JL
Trepel, JB
Lee, MJ
Lee, S
Steinberg, SM
John, S
Velasco, SVA
Figg, WD
Dahut, WL
AF Apolo, Andrea Borghese
Parnes, Howard L.
Madan, Ravi Amrit
Gulley, James L.
Trepel, Jane B.
Lee, Min-Jung
Lee, Sunmin
Steinberg, Seth M.
John, Simone
Velasco, Sylvia Vania Alarcon
Figg, William Douglas
Dahut, William L.
TI A phase I study of gemcitabine, carboplatin, and lenalidomide for
treatment of patients with advanced/metastatic urothelial carcinoma (UC)
and other solid tumors
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NIH, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e15527
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200673
ER
PT J
AU Arnaldez, FI
Gombos, E
Terwilliger, T
Mendoza, A
Yeung, C
Neckers, L
Helman, LJ
AF Arnaldez, Fernanda Irene
Gombos, Erin
Terwilliger, Toby
Mendoza, Arnulfo
Yeung, Choh
Neckers, Len
Helman, Lee J.
TI Heat-shock protein 90 inhibition in pediatric sarcomas.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Pediat Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA.
NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10057
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204596
ER
PT J
AU Ashraf, M
Kirkwood, JM
Ernstoff, MS
Tawbl, HH
Frankel, PH
Ruel, N
Kendra, KL
Olencki, T
Khushalani, NI
Logan, TF
Margolin, KA
Chen, AP
Tarhini, AA
AF Ashraf, Madeeha
Kirkwood, John M.
Ernstoff, Marc S.
Abdul-Hassan, Hussein Tawbl
Frankel, Paul Henry
Ruel, Nora
Kendra, Karl Lynn
Olencki, Thomas
Khushalani, NIkhil I.
Logan, Theodore F.
Margolin, Kim Allyson
Chen, Alice P.
Tarhini, Ahmad A.
TI NCI 8628: A randomized phase II study of ziv-aflibercept (Z) and
high-dose interleukin-2 (HD IL-2) or HD IL-2 alone for inoperable stage
III or IV melanoma-Efficacy and biomarker study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Norris Cotton Canc Ctr, Dartmouth Hitchcock Med Ctr, Lebanon, NH USA.
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA.
City Hope Natl Med Ctr, Duarte, CA 91010 USA.
Ohio State Univ, Columbus, OH 43210 USA.
Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
Univ Washington, Seattle, WA 98195 USA.
NCI, Bethesda, MD 20892 USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA TPS9120
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202251
ER
PT J
AU Bae, WK
Cho, SH
Chung, IJ
Furth, PA
Hennighausen, L
AF Bae, Woo Kyun
Cho, Sang-Hee
Chung, Ik-Joo
Furth, Priscilla A.
Hennighausen, Lothar
TI The histone methyltransferase EZH2 and breast cancer development: EZH2
and H3K27me3 correlation with prognosis of ER-positive cancers.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NIDDK, NIH, Bethesda, MD 20892 USA.
Chonnam Natl Univ, Sch Med, Gwangju, South Korea.
Chonnam Natl Univ, Hwasun Hosp, Hwasuneup, South Korea.
Georgetown Univ, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e11537
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200034
ER
PT J
AU Banerjee, A
Jakacki, R
Onar-Thomas, A
Wu, SJ
Nicolaides, T
Turner, D
Richardson, S
Young-Poussaint, T
Phillips, JJ
Prados, M
Packer, R
Qaddoumi, IA
Gururangan, S
Goldman, S
Pollack, I
Doyle, LA
Stewart, CF
Boyett, JM
Fouladi, M
AF Banerjee, Anuradha
Jakacki, Regina
Onar-Thomas, Arzu
Wu, Shengjie
Nicolaides, Theodore
Turner, David
Richardson, Stacye
Young-Poussaint, Tina
Phillips, Joanna J.
Prados, Michael
Packer, Roger
Qaddoumi, Ibrahim A.
Gururangan, Sridharan
Goldman, Stewart
Pollack, Ian
Doyle, L. Austin
Stewart, Clinton F.
Boyett, James M.
Fouladi, Maryam
TI A phase I study of AZD6244 in children with recurrent or refractory
low-grade gliomas: A Pediatric Brain Tumor Consortium report.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Calif San Francisco, San Francisco, CA 94143 USA.
Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
Childrens Hosp, Boston, MA 02115 USA.
Childrens Natl Med Ctr, Washington, DC 20010 USA.
Duke Univ, Med Ctr, Durham, NC USA.
Childrens Mem Hosp, Chicago, IL 60614 USA.
Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
NCI, Rockville, MD USA.
Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
NR 0
TC 3
Z9 3
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10065
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204604
ER
PT J
AU Bates, GE
Taub, RN
Matushansky, I
Uldrick, TS
Khandker, M
Bressler, Y
Wang, Y
AF Bates, Gleneara Elizabeth
Taub, Robert N.
Matushansky, Igor
Uldrick, Thomas S.
Khandker, Maya
Bressler, Yaakov
Wang, Yi
TI A phase I/II study of azacitidine in combination with temozolomide in
patients with unresectable or metastatic soft tissue sarcoma or
malignant mesothelioma.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Columbia Univ, Med Ctr, New York, NY USA.
Novartis Pharmaceut, E Hanover, NJ USA.
NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10560
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204693
ER
PT J
AU Bazhenova, L
Giaccone, G
Nemunaitis, JJ
Juhasz, E
Ramiau, R
van den Heuvel, MM
Lal, R
Dunlop, D
Garon, EB
Chu, QS
Jain, MM
Carrier, E
Moses, S
Shawler, D
Fakhrai, H
AF Bazhenova, Lyudmila
Giaccone, Giuseppe
Nemunaitis, John J.
Juhasz, Erzsebet
Ramiau, Rodryg
van den Heuvel, Michel M.
Lal, Rohit
Dunlop, David
Garon, Edward B.
Chu, Quincy S.
Jain, Minish Mahendra
Carrier, Ewa
Moses, Steven
Shawler, Daniel
Fakhrai, Habib
TI An international, multicenter, randomized, double-blind phase III study
of maintenance belagenpumatucel-l in non-small cell lung cancer (NSCLC):
Updated analysis of patients enrolled within 12 weeks of completion of
chemotherapy.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 UC San Diego Moores Canc Ctr, La Jolla, CA USA.
Georgetown Univ, Washington, DC USA.
NCI, Bethesda, MD 20892 USA.
Mary Crowley Canc Res Ctr, Dallas, TX USA.
Koranyi Natl Inst Pulmonol, Budapest, Hungary.
Independent Publ Hlth Care Ctr, Greater Poland Ctr Pulm Dis & TB, Poznan, Poland.
Antonie van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
Guys & St Thomas NHS Fdn Trust, London, England.
Glasgow Royal Infirm, Glasgow G4 0SF, Lanark, Scotland.
Univ Calif Los Angeles, Los Angeles, CA USA.
Cross Canc Ctr, Edmonton, AB, Canada.
Noble Hosp, Pune, Maharashtra, India.
NovaRx Corp, San Diego, CA USA.
NR 0
TC 0
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 8056
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204119
ER
PT J
AU Besse, B
Garassino, MC
Rajan, A
Novello, S
Mazieres, J
Weiss, GJ
Ciomei, M
Martignoni, M
Petroccione, A
Davite, C
Giaccone, G
AF Besse, Benjamin
Garassino, Marina Chiara
Rajan, Arun
Novello, Silvia
Mazieres, Julien
Weiss, Glen J.
Ciomei, Marina
Martignoni, Marcella
Petroccione, Anna
Davite, Cristina
Giaccone, Giuseppe
TI A phase II study of milciclib (PHA-848125AC) in patients (pts) with
thymic carcinoma (TC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Gustave Roussy, Villejuif, France.
Fdn IRCSS Ist Nazl Tumori, Milan, Italy.
NCI, NIH, Bethesda, MD 20892 USA.
Azienda Osped Univ San Luigi, Orbassano, Italy.
Hop De Larrey, Toulouse, France.
Goodyear, Canc Treatment Ctr Amer, Western Reg Med Ctr, Scottsdale, AZ USA.
Nerviano Med Sci, Nerviano, Italy.
CLin Org Strategies & Solut CLIOSS, NMS Grp, Nerviano, Italy.
Georgetown Univ, Washington, DC USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 6
Z9 6
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 7526
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203962
ER
PT J
AU Better, M
Pugach, O
Lu, L
Somerville, R
Kassim, S
Kochenderfer, J
Rosenberg, SA
Marshall, MA
Bot, A
Nolop, KB
Roberts, M
Feldman, S
AF Better, Marc
Pugach, Omar
Lu, Lily
Somerville, Robert
Kassim, Sadik
Kochenderfer, James
Rosenberg, Steven A.
Marshall, Margaret A.
Bot, Adrian
Nolop, Keith B.
Roberts, Margo
Feldman, Steven
TI Rapid cell expansion (RACE) technology for production of engineered
autologons T-cell therapy: Path toward manageable multicenter clinical
trials in aggressive NHL with anti-CD19 CAR
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Kite Pharma, Santa Monica, CA USA.
NCI, Surg Branch, Bethesda, MD 20892 USA.
NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 3079
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202970
ER
PT J
AU Bhutani, M
Turkbey, B
Tan, E
Korde, N
Kwok, M
Manasanch, EE
Tageja, N
Mailankody, S
Roschewski, MJ
Mulquin, M
Lamping, E
Weiss, BM
Mena, E
Lindenberg, L
Calvo, KR
Maric, I
Choyke, PL
Kurdziel, KA
Landgren, O
AF Bhutani, Manisha
Turkbey, Baris
Tan, Esther
Korde, Neha
Kwok, Mary
Manasanch, Elisabet E.
Tageja, Nishant
Mailankody, Sham
Roschewski, Mark J.
Mulquin, Marcia
Lamping, Elizabeth
Weiss, Brendan M.
Mena, Esther
Lindenberg, Liza
Calvo, Katherine R.
Maric, Irina
Choyke, Peter L.
Kurdziel, Karen A.
Landgren, Ola
TI Focal bone marrow processes and early bone lesions in patients with
multiple myeloma (MM) precursor diseases: A prospective study using
molecular imaging.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NIH, Hematol Sect, Dept Lab Med, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 8587
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204266
ER
PT J
AU Bhutani, M
Lee, MJ
Tomita, Y
Lee, S
Frosch, A
Carlsten, M
Steinberg, SM
Korde, N
Landgren, O
Trepel, JB
AF Bhutani, Manisha
Lee, Min-Jung
Tomita, Yusuke
Lee, Sunmin
Frosch, Ari
Carlsten, Mattias
Steinberg, Seth M.
Korde, Naha
Landgren, Ola
Trepel, Jane B.
TI Early biomarkers of response to carfilzomib in multiple myeloma (MM.):
Modulation of CXCR4 and induction of autophagy
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e19572
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201435
ER
PT J
AU Bible, KC
Suman, VJ
Molina, JR
Smallridge, RC
Maples, WJ
Menefee, ME
Rubin, J
Karlin, NJ
Sideras, K
Morris, JC
McIver, B
Hay, ID
Fatourechi, V
Burton, JK
Traynor, AM
Flynn, PJ
Goh, BC
Isham, CR
Harris, PJ
Erlichman, C
AF Bible, Keith Christopher
Suman, Vera J.
Molina, Julian R.
Smallridge, Robert C.
Maples, William James
Menefee, Michael E.
Rubin, Joseph
Karlin, Nina J.
Sideras, Kostandinos
Morris, John C.
McIver, Bryan
Hay, Ian D.
Fatourechi, Vahab
Burton, Jill K.
Traynor, Anne M.
Flynn, Patrick J.
Goh, Boon C.
Isham, Crescent R.
Harris, Pamela Jo
Erlichman, Charles
TI A multicenter international phase 2 trial of pazopanib in metastatic and
progressive medullary thyroid carcinoma: MC057H
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mayo Clin, Rochester, MN USA.
Mayo Clin, Jacksonville, FL 32224 USA.
Mayo Clin, Scottsdale, AZ USA.
Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
Metro Minnesota Community Clin Oncol Program, St Louis Pk, MN USA.
Natl Univ Hlth Syst, Singapore, Singapore.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 6026
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203618
ER
PT J
AU Bottaro, DP
Lee, YH
Agarwal, PK
Apolo, AB
AF Bottaro, Donald P.
Lee, Young H.
Agarwal, Piyush K.
Apolo, Andrea Borghese
TI Met signaling in urothelial carcinoma of the bladder.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
NIH, Urol Oncol Branch, NCI, Bethesda, MD 20892 USA.
NIH, NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 4551
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203356
ER
PT J
AU Brancato, SJ
Stamatakis, L
Apolo, AB
Fowler, S
Schlom, J
Gulley, JL
Agarwal, PK
AF Brancato, Sam Joseph
Stamatakis, Lambros
Apolo, Andrea Borghese
Fowler, Sarah
Schlom, Jeffrey
Gulley, James L.
Agarwal, Plyush K.
TI A randomized, prospective, phase II study to determine the efficacy of
BCG given in combination with panvac versus BCG alone in adults with
high grade non-muscle invasive bladder cancer who failed at least one
induction course of BCG.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NIH, Bethesda, MD 20892 USA.
NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Lab Tumor Immunol & Biol, Med Oncol Branch, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016; Brancato, Sam/K-3266-2014
OI Gulley, James/0000-0002-6569-2912; Brancato, Sam/0000-0002-3760-5818
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA TPS4590
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202114
ER
PT J
AU Bunch, KP
Noonan, AM
Lee, JM
O'Sullivan, CCM
Houston, ND
Ekwede, I
Chen, JQ
Herrmann, M
Cao, L
Takebe, N
Burns, J
Weng, DE
Kohn, EC
Annunziata, CM
AF Bunch, Kristen Paige
Noonan, Anne M.
Lee, Jung-min
O'Sullivan, Ciara Catherine Maria
Houston, Nicole D.
Ekwede, Irene
Chen, Jin-Qiu
Herrmann, Michelle
Cao, Liang
Takebe, Naoko
Burns, Jennifer
Weng, David Edward
Kohn, Elise C.
Annunziata, Christina M.
TI Pharmacodynamic biomarkers from phase II study of the SMAC (Second
Mitochondrial-Derived Activator of Caspases)-mimetic birinapant
(TL32711; NSC 756502) in relapsed platinum-resistant epithelial ovarian
cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer
(FTC) (NCT01681368).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Ctr Canc Res, Womens Malignancies Branch, Bethesda, MD USA.
NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Collaborat Prot Technol Resource, Cell Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
Canc Therapy Evaluat Program, Invest Drug Branch, Rockville, MD USA.
TetraL Pharmaceut, Malvern, PA USA.
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 5585
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203569
ER
PT J
AU Campian, JL
Ye, XB
Gladstone, DE
Ambady, P
Borrello, I
Golightly, M
Karen, KEK
King, E
Holdhoff, M
Karp, JE
Grossman, SA
AF Campian, Jian Li
Ye, Xiaobu
Gladstone, Douglas Edward
Ambady, Prakash
Borrello, Ivan
Golightly, Marc
Karen, Karen E. King
King, E.
Holdhoff, Matthias
Karp, Judith E.
Grossman, Stuart A.
TI Feasibility of lymphocyte harvesting and reinfusion in patients with
newly diagnosed high-grade gliomas.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Washington Univ, St Louis, MO USA.
Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
NCI, Bethesda, MD 20892 USA.
Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
Stony Brook Med, Stony Brook, NY USA.
Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 2094
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202758
ER
PT J
AU Castro, KM
Spain, P
Teixeira-Poit, S
Das, IP
Adjei, BA
Siegel, RD
Clauser, S
Halpern, MT
AF Castro, Kathleen M.
Spain, Pamela
Teixeira-Poit, Stephanie
Das, Irene Prabhu
Adjei, Brenda A.
Siegel, Robert D.
Clauser, Steven
Halpern, Michael T.
TI Sustaining quality cancer care in the NCI Community Cancer Centers
Program (NCCCP).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Rockville, MD USA.
RTI Int, Res Triangle Pk, NC USA.
NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD USA.
NCI, Rockville, MD USA.
Hartford Hosp Helen & Harry Gray Canc Ctr, Hartford, CT USA.
Patient Ctr Outcomes Res Inst, Washington, DC USA.
RTI Int, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 6536
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203722
ER
PT J
AU Chen, EX
Winquist, E
Ho, C
Gitlitz, BJ
Ohr, J
Razzak, ARA
Slu, LL
Zwlebel, JA
Oza, AM
Wang, LS
Chin, S
Malpage, A
Yu, C
Mejia, E
Gevaudan, L
Mohita, P
AF Chen, Eric Xueyu
Winquist, Eric
Ho, Cheryl
Gitlitz, Barbara Jennifer
Ohr, James
Razzak, Albiruni R. A.
Slu, Llllian L.
Zwlebel, James A.
Oza, Amit M.
Wang, Lisa
Chin, Soo
Malpage, Anne
Yu, Carleen
Mejia, Edward
Gevaudan, Lori
Mohita, Prachi
TI Vorinostat (VOR) and capecitabine (CAP) in recurrent and/or metastatic
squamous cell carcinoma ahead and neck (RMHNSCC): A study of the
Princess Margaret Phase II Consortium
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Princess Margaret Canc Ctr, Toronto, ON, Canada.
London Hlth Sci Ctr, London, ON, Canada.
British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
USC Norris Comprehens Canc Ctr, Los Angeles, CA USA.
Univ Pittsburgh, Div Hematol Oncol, Pittsburgh, PA USA.
Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada.
NCI, Rockville, MD USA.
Princess Margaret Canc Ctr, Dept Biostat, Toronto, ON, Canada.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
BC Canc Agcy, Vancouver, BC, Canada.
Univ So Calif, Los Angeles, CA USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e17001
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200911
ER
PT J
AU Chen, YB
Thomas, A
Berman, AW
Miettinen, M
Hassan, R
Rajan, A
AF Chen, Yuanbin
Thomas, Anish
Berman, Arlene W.
Miettinen, Markku
Hassan, Raffit
Rajan, Arun
TI Mesothelin expression in thymic epithelial tumors (TETs)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 [Chen, Yuanbin; Thomas, Anish; Berman, Arlene W.; Miettinen, Markku; Hassan, Raffit; Rajan, Arun] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 7607
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204065
ER
PT J
AU Chow, LQM
Smith, DC
Tan, AR
Denlinger, CS
Wang, D
Shepard, DR
Chaudhary, A
Lin, Y
Koshiji, M
AF Chow, Laura Quan Man
Smith, David C.
Tan, Antoinette R.
Denlinger, Crystal Shereen
Wang, Ding
Shepard, Dale Randall
Chaudhary, Archana
Lin, Yong
Koshiji, Minori
TI Phase II study evaluating the effect of concomitant ramucirmamb
(IMC-1121B; RAM) on the pharmacokinetics (PK) of paclitaxel (PTX) and
the PK of RAM as monotherapy in patients (pts) vth advanced malignant
solid tumors.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Washington, Seattle, WA 98195 USA.
Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
NSABP, New Brunswick, NJ USA.
Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
Henry Ford Hlth Syst, Josephine Ford Canc Ctr, Detroit, MI USA.
Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
Eli Lilly & Co, Indianapolis, IN 46285 USA.
ImClone Syst, Bridgewater, NJ USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e13554
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200244
ER
PT J
AU Chuk, MK
Widemann, BC
Ahern, CH
Reid, JM
Kim, A
Wright, JJ
Lodish, M
Fox, E
Weigel, B
Blaney, S
AF Chuk, Meredith K.
Widemann, Brigitte C.
Ahern, Charlotte H.
Reid, Joel M.
Kim, AeRang
Wright, John Joseph
Lodish, Maya
Fox, Elizabeth
Weigel, Brenda
Blaney, Susan
TI A phase I study of cabozantinib (XL184) in children and adolescents with
recurrent or refractory solid tumors, including CNS tumors: A Children's
Oncology Group phase I consortium trial.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
Baylor Coll Med, Houston, TX 77030 USA.
Mayo Clin, Dept Oncol, Rochester, MN USA.
Childrens Natl Med Ctr, Washington, DC 20010 USA.
NCI, Rockville, MD USA.
NIH, Bethesda, MD 20892 USA.
Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
Univ Minnesota, Minneapolis, MN USA.
Texas Childrens Canc Ctr, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10078
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204617
ER
PT J
AU Collins, KP
Geller, DA
Marsh, JW
Kim, KH
Tsung, A
Kamarck, T
Green, A
Santiago, L
Kirk, K
Labash, C
Sun, WJ
Buysse, D
Steel, JL
AF Collins, Kevin P.
Geller, David A.
Marsh, J. Wallis
Kim, Kevin H.
Tsung, Allan
Kamarck, Thomas
Green, Anna
Santiago, Lesenia
Kirk, Karlie
Labash, Chanelle
Sun, Weijing
Buysse, Daniel
Steel, Jennifer Lynne
TI Sleep problems and increased risk of mortality in the context of
advanced cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Pittsburgh, Pittsburgh, PA USA.
NSABP, Pittsburgh, PA USA.
Univ Pittsburgh, Med Ctr, Liver Canc Ctr, Pittsburgh, PA USA.
UPMC Neuroendocrine Canc Treatment Ctr, Pittsburgh, PA USA.
Univ Pittsburgh, Med Ctr, Comprehens Liver Canc Ctr, Pittsburgh, PA USA.
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 9649
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204533
ER
PT J
AU Connolly, RM
Jankowitz, RC
Zahnow, CA
Zhang, Z
Rudek, MA
Slater, S
Powers, P
Jeter, S
Brufsky, A
Piekarz, R
Herman, JG
Ahuja, N
Somlo, G
Garcia, AA
Baylin, S
Davidson, NE
Stearns, V
AF Connolly, Roisin M.
Jankowitz, Rachel Catherine
Zahnow, Cynthia A.
Zhang, Zhe
Rudek, Michelle A.
Slater, Shannon
Powers, Penny
Jeter, Stacie
Brufsky, Adam
Piekarz, Richard
Herman, James Gordon
Ahuja, Nita
Somlo, George
Garcia, Agustin A.
Baylin, Stephen
Davidson, Nancy E.
Stearns, Vered
TI Phase 2 study investigating the safety, efficacy, and surrogate
biomarkers of response to 5-azacitidine (5-AZA) and entinostat in
advanced breast cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
Univ Pittsburgh, Med Ctr, Womens Canc Program, Magee Womens Hosp, Pittsburgh, PA USA.
Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
NCI, Rockville, MD USA.
City Hope Canc Ctr, Duarte, CA USA.
Univ So Calif, Los Angeles, CA USA.
Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 569
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202343
ER
PT J
AU Denicoff, A
Massett, HA
Souhan, E
Cave, L
Welch, JJ
Seibel, N
Little, RF
Mann, BS
DiPiazza, K
Rossmann, MK
Stine, SH
Lambersky, R
DeSanto, F
Fonzi, F
Schrag, D
Abrams, RA
Adelstein, DJ
Brown, PD
Mooney, MM
Abrams, JS
AF Denicoff, Andrea
Massett, Holly A.
Souhan, Erin
Cave, Lynn
Welch, John J.
Seibel, Nita
Little, Richard F.
Mann, Bhupinder Singh
DiPiazza, Kate
Rossmann, Megan K.
Stine, Sharon Hartson
Lambersky, Ruth
DeSanto, Frank
Fonzi, Frances
Schrag, Deborah
Abrams, Ross A.
Adelstein, David J.
Brown, Paul D.
Mooney, Margaret M.
Abrams, Jeffrey S.
TI NCI pilot intervention program to assist accrual for challenging
late-phase clinical trials.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Rockville, MD USA.
Emmes Corp, Rockville, MD USA.
NCI, Bethesda, MD 20892 USA.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
EMMES Corp, Rockville, MD USA.
Westat Corp, Rockville, MD USA.
Radiat Therapy Oncol Grp, Philadelphia, PA USA.
Coalit Canc Cooperat Groups, Philadelphia, PA USA.
SWOG, Ann Arbor, MI USA.
NSABP, Pittsburgh, PA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Rush Univ, Med Ctr, Chicago, IL 60612 USA.
Cleveland Clin, Cleveland, OH 44106 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 6617
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203801
ER
PT J
AU Di Fabio, F
Rosati, G
Lolli, IR
Ruggeri, EM
Cluffreda, L
Ferrari, D
Tumolo, S
Rostl, G
Tralongo, P
Ferrara, R
Alabiso, O
Chiara, S
Ianniello, GP
Di Costanzo, F
Frassoldati, A
Iacono, C
Clerico, M
Pavesl, L
Bernardo, G
Pinto, C
AF Di Fabio, Francesca
Rosati, Gerardo
Lolli, Ivan Roberto
Ruggeri, Enzo Maria
Cluffreda, Libero
Ferrari, Daris
Tumolo, Salvatore
Rostl, Giovanni
Tralongo, Paolo
Ferrara, Raimondo
Alabiso, Oscar
Chiara, Silvana
Ianniello, Giovanni Paolo
Di Costanzo, Francesco
Frassoldati, Antonio
Iacono, Carmelo
Clerico, Mario
Pavesl, Lorenzo
Bernardo, Giovanni
Pinto, Carmine
TI Italian observational study in patients with metastatic colorectal
cancer (mCRC) treated with first-line cetaximab based regimen (ObservEr
study)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Orsola Malpighi Hosp, Med Oncol Unit, Bologna, Italy.
San Carlo Hosp, Med Oncol Unit, Potenza, Italy.
IRCCS Saveri de Bellis, Med Oncol Unit, Castellana Grotte Ba, Italy.
Belcolle Hosp, Med Oncol Unit, Viterbo, Italy.
Molinette Mauriziano Hosp, Med Oncol Unit, Turin, Italy.
San Paolo Hosp, Med Oncol Unit, Milan, Italy.
St Maria degli Angeli Hosp, Med Oncol Unit, Pordenone, Italy.
Ca Foncello Hosp, Med Oncol Unit, Treviso, Italy.
G Di Maria Hosp, Med Oncol Unit, Avola, Italy.
Dimiccoli Hosp, Med Oncol Unit, Barletta, Italy.
Maggiore della Carita Hosp, Med Oncol Unit, Novara, Italy.
Natl Canc Inst, Med Oncol Unit, Genoa, Italy.
St Anna & St Sebastian Hosp, Med Oncol Unit, Caserta, Italy.
Careggi Hosp, Med Oncol, Florence, Italy.
St Anna Hosp, Med Oncol Unit, Ferrara, Italy.
M Patemo Hosp, Med Oncol Unit, Ragusa, Italy.
Infermi Hosp, Med Oncol Unit, Biella, Italy.
IRCCS Salvatore Maugeri Fdn, Med Oncol Unit, Pavia, Italy.
IRCCS Maugeri Fdn, Med Oncol Unit, Pavia, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e14600
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200366
ER
PT J
AU Dimond, EP
Zon, R
St Germain, DC
Denicoff, A
Carrigan, A
Dempsey, K
McCaskill-Stevens, WJ
Gonzalez, MM
Berger, MZ
Gansauer, LJ
Bearden, JD
Wilkinson, K
Bryant, DM
Bell, MC
Lavasseur, B
Stella, P
Good, MJ
Igo, K
Quinones, O
Grubbs, SS
AF Dimond, Eileen P.
Zon, Robin
St Germain, Diane C.
Denicoff, Andrea
Carrigan, Angela
Dempsey, Kandie
McCaskill-Stevens, Worta J.
Gonzalez, Maria Magdalena
Berger, Mitchell Z.
Gansauer, Lucy Jean
Bearden, James D.
Wilkinson, Kathy
Bryant, Donna M.
Bell, Maria Caroline
Lavasseur, Beth
Stella, Phil
Good, Marjorie J.
Igo, Kathleen
Quinones, Octavio
Grubbs, Stephen S.
TI The clinical trial assessment of infrastructure matrix tool (CT AIM) to
improve the quality of research conduct in the community
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Rockville, MD USA.
Michiana Hematol Oncol PC, South Bend, IN USA.
Leidos Biomed Res Inc, Frederick, MD USA.
Helen F Graham Canc Ctr, Newark, DE USA.
St Joseph Hosp, Orange, CA USA.
Canc Program Our Lady Lake & Mary Bird Perkins, Baton Rouge, LA USA.
Spartanburg Reg Med Ctr, Spartanburg, SC USA.
Billings Clin, Billings, MT USA.
Sioux Valley Univ Hosp, Sioux Falls, SD USA.
St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA.
DMS Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
Helen F Graham Canc Ctr Christiana Care, Newark, DE USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 6512
PG 2
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203698
ER
PT J
AU Ding, Y
Black, A
Hsing, AW
Andriole, GL
AF Ding, Yan
Black, Amanda
Hsing, Ann W.
Andriole, Gerald L.
TI Genetic variant in fragile histidine triad gene (FHIT) and mortality in
prostate and breast cancers: Results from the Prostate, Lung, Colon,
Ovarian Cancer Screening Trial (PLCO) and Women's Health Initiative
(WHI).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 City Hope Natl Med Ctr, Duarte, CA USA.
NCI, Bethesda, MD 20892 USA.
Canc Prevent Inst Calif, Fremont, CA USA.
Washington Univ, Sch Med, Barnes Jewish Hosp, St Louis, MO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 5076
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203468
ER
PT J
AU Dix, DB
Gratias, EJ
Seibel, N
Anderson, JR
Mullen, EA
Geller, JI
Khanna, G
Kalapurakal, JA
Perlman, EJ
Ehrlich, PF
Malogolowkin, MH
Grundy, PE
Dome, J
AF Dix, David B.
Gratias, Eric J.
Seibel, Nita
Anderson, James Robert
Mullen, Elizabeth Anne
Geller, James I.
Khanna, Geetika
Kalapurakal, John A.
Perlman, Elizabeth Jones
Ehrlich, Peter F.
Malogolowkin, Marcio H.
Grundy, Paul Edward
Dome, Jeffrey
TI Treatment of stage IV favorable histology Wilms tumor with incomplete
lung metastasis response after chemotherapy: A report from Children's
Oncology Group study AREN0533.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada.
TC Thompson Childrens Hosp, Chattanooga, TN USA.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
Univ Nebraska Med Ctr, Coll Publ Hlth, Omaha, NE USA.
Dana Farber Canc Inst, Boston Childrens Canc & Blood Disorders Ctr, Boston, MA 02115 USA.
Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
Washington Univ, Sch Med, St Louis, MO USA.
Northwestern Memor Hosp, Chicago, IL USA.
Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Midwest Childrens Canc Ctr, Milwaukee, WI USA.
Stollery Childrens Hosp, Edmonton, AB, Canada.
Childrens Natl Med Ctr, Washington, DC 20010 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10001
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204540
ER
PT J
AU Do, KT
Wilsker, D
Balasubramanian, P
Zlott, J
Jeong, W
Lawrence, SM
Kinders, RJ
Collins, J
Chen, AP
Doroshow, JH
Kummar, S
AF Do, Khanh Tu
Wilsker, Deborah
Balasubramanian, Priya
Zlott, Jennifer
Jeong, Woondong
Lawrence, Scott M.
Kinders, Robert J.
Collins, Jerry
Chen, Alice P.
Doroshow, James H.
Kummar, Shivaani
TI Phase I trial of AZD1775 (MK1775), a wee1 kinase inhibitor, in patients
with refractory solid tumors
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Frederick, MD 21701 USA.
NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
SAIC Frederick Inc, Frederick, MD USA.
Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
NCI, Rockville, MD USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 1
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 2503
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202768
ER
PT J
AU Dosani, T
Korde, N
Manasanch, EE
Bhutani, M
Tageja, N
Mailankody, S
Roschewski, MJ
Kwok, M
Kazandjian, DG
Landgren, O
Maric, I
AF Dosani, Talib
Korde, Neha
Manasanch, Elisabet Esteve
Bhutani, Manisha
Tageja, Nishant
Mailankody, Sham
Roschewski, Mark J.
Kwok, Mary
Kazandjian, Dickran Gano
Landgren, Ola
Maric, Irina
TI Large granular lymphocyte (LGL) subsets in smoldering multiple myeloma
(SMM): Immunophenotypic profiles that predict progression to multiple
myeloma (MM).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NIH, Hematol Sect, Dept Lab Med, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 8597
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204275
ER
PT J
AU Dueck, AC
Hillman, DW
Kottschade, LA
Halyard, MY
Sloan, JA
Flickinger, LM
Wolff, AC
Harris, L
Gralow, J
Pritchard, KI
Ellard, S
Le-Lindqwister, N
Boyle, FM
De Azambuja, E
McCaskill-Stevens, WJ
Zujewski, JA
Piccart-Gebhart, MJ
Perez, EA
AF Dueck, Amylou C.
Hillman, David W.
Kottschade, Lisa A.
Halyard, Michele Y.
Sloan, Jeff A.
Flickinger, Lynn M.
Wolff, Antonio C.
Harris, Lyndsay
Gralow, Julie
Pritchard, Kathleen I.
Ellard, Susan
Le-Lindqwister, Nguyet
Boyle, Frances M.
De Azambuja, Evandro
McCaskill-Stevens, Worta J.
Zujewski, Jo Anne
Piccart-Gebhart, Martine J.
Perez, Edith A.
TI Quality of life (QOL) among patients (pts) with HER2+breast cancer (bc)
treated with adjuvant lapatinib and/or trastuzumab in the ALTTO study
(BIG 2-06, Alliance N063D).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mayo Clin, Scottsdale, AZ USA.
Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA.
Mayo Clin, Rochester, MN USA.
Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
Case Western Seidman Canc Ctr, Cleveland, OH USA.
Seattle Canc Care Alliance, Seattle, WA USA.
Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
Univ Toronto, Toronto, ON, Canada.
British Columbia Canc Agcy, Ctr Southern Interior, Kelowna, BC, Canada.
Illinois CancerCare Peoria, Peoria, IL USA.
Patricial Rigchie Ctr Canc Care & Res, Sydney, NSW, Australia.
Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium.
NCI, Rockville, MD USA.
NCI, Bethesda, MD 20892 USA.
Inst Jules Bordet, Breast Int Grp, B-1000 Brussels, Belgium.
Mayo Clin, Jacksonville, FL 32224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 647
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202420
ER
PT J
AU Duffy, AG
Ulahannan, SV
Fioravanti, S
Walker, M
Figg, WD
Compton, K
Venkatesan, A
Abi-Jaoudoh, N
Wood, BJ
Greten, TF
AF Duffy, Austin G.
Ulahannan, Susanna Varkey
Fioravanti, Suzanne
Walker, Melissa
Figg, William Douglas
Compton, Kathryn
Venkatesan, Aradhana
Abi-Jaoudoh, Nadine
Wood, Bradford J.
Greten, Tim F.
TI A pilot study of tremelimumab, a monoclonal antibody against CTLA-4, in
combination with either trans catheter arterial chemoembolization (TACE)
or radiofrequency ablation (RFA) in patients with hepatocellular
carcinoma (HCC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
NCI, Ctr Intervent Oncol, Bethesda, MD 20892 USA.
NIH, Ctr Clin, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e15133
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200532
ER
PT J
AU EI-Khoueiry, AB
O'Donnell, R
Mack, PC
Blanchard, S
Bahary, N
Jiang, YX
Wright, JJ
Chen, HX
Lenz, HJ
Gandara, DR
AF EI-Khoueiry, Anthony B.
O'Donnell, Robert
Mack, Philip C.
Blanchard, Suzette
Bahary, Nathan
Jiang, Yixing
Wright, John Joseph
Chen, Helen X.
Lenz, Heinz-Josef
Gandara, David R.
TI A phase I trial of of cixutumumab (C) (IMC-A12) and sorafenib (S) for
treatment of advanced hepatocellular carcinoma (HCC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 USC Norris Comprehens Canc Ctr, Los Angeles, CA USA.
Univ Calif Davis, Sacramento, CA 95817 USA.
UC Davis Comprehens Canc Ctr, Sacramento, CA USA.
City Hope Natl Med Ctr, Duarte, CA USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
Univ Maryland, Baltimore, MD 21201 USA.
NCI, Rockville, MD USA.
NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 4105
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203268
ER
PT J
AU Folio, L
Derderian, V
Steinberg, SM
Turkbey, E
Apolo, AB
AF Folio, Les
Derderian, Vana
Steinberg, Seth M.
Turkbey, Evrim
Apolo, Andrea Borghese
TI Assessing tumor response using CT density-volume trajectory in
metastatic bladder cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
NIH, NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 4539
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203344
ER
PT J
AU Forde, PM
Hooker, CM
Rubinstein, L
Hann, CL
Harris, PJ
AF Forde, Patrick M.
Hooker, Craig M.
Rubinstein, Larry
Hann, Christine L.
Harris, Pamela Jo
TI Analysis of small cell lung cancer (SCLC) patients (Pts) treated on
cancer therapy evaluation program (CTEP)-sponsored phase I trials:
1992-2012.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
Biometr Res Branch, Bethesda, MD USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 7524
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203960
ER
PT J
AU Fukuda, YK
Huang, E
Finnigan, S
Ivy, SP
Rubinstein, L
Takebe, N
AF Fukuda, Yoko Korenaga
Huang, Erich
Finnigan, Shanda
Ivy, S. Percy
Rubinstein, Larry
Takebe, Naoko
TI Risks and benefits of phase 1 oncology trials, 2001 through 2012.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 MedStar Washington Hosp Ctr, Washington, DC USA.
NCI, Div Canc Treatment & Diag, Biometr Res Branch, Rockville, MD USA.
NCI, Rockville, MD USA.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
Div Canc Treatment & Diag, Bethesda, MD USA.
Canc Therapy Evaluat Program, Invest Drug Branch, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 2552
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202817
ER
PT J
AU Garin, SS
Robinson, P
Juarez, P
Pan, DY
Hays, R
AF Garin, Sherri Sheinfeld
Robinson, Paul
Juarez, Paul
Pan, Deyu
Hays, Ron
TI The impact of place on health-related quality of life among US cancer
survivors
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI SAIC, New York, NY USA.
Chades R Drew Hlth Sci Univ, Los Angeles, CA USA.
Univ Calif Los Angeles, Los Angeles, CA USA.
Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e17642
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201100
ER
PT J
AU Ghafoor, A
Calvo, KR
Corrigan-Cummins, M
Simakova, O
Costello, R
Yuan, C
Stetler-Stevenson, M
Korde, N
Roschewski, MJ
Landgren, O
Maric, I
AF Ghafoor, Azam
Calvo, Katherine R.
Corrigan-Cummins, Meghan
Simakova, Olga
Costello, Rene
Yuan, Constance
Stetler-Stevenson, Maryallce
Korde, Neha
Roschewski, Mark J.
Landgren, Ola
Maric, Irina
TI Immunephenotypic profiles of plasma cells and tumor burden in patients
with smoldering myeloma (SMM) and monoclonal gammopathy of undetermined
significance (MGUS)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
NIH, Hematol Sect, Dept Lab Med, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Multiple Myeloma Sect, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Pathol Lab, CCR, NIH, Bethesda, MD 20892 USA.
NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e19589
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201447
ER
PT J
AU Giamanco, NM
Jee, YH
Shriver, CD
Summers, TA
Wellstein, A
Baron, J
AF Giamanco, Nicole Michelle
Jee, Youn Hee
Shriver, Craig D.
Summers, Thomas A.
Wellstein, Anton
Baron, Jeffrey
TI Midkine and pleiotrophin concentrations in biopsy needle washout of
breast masses.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Walter Reed Natl Mil Med Ctr, Dept Pediat, Bethesda, MD USA.
NICHHD, Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
Walter Reed Natl Mil Med Ctr, John P Murtha Canc Ctr, Bethesda, MD USA.
Walter Reed Natl Mil Med Ctr, Dept Pathol & Lab Serv, Bethesda, MD USA.
Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
NICHHD, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e22104
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201836
ER
PT J
AU Glynn, SA
Wallace, T
Downey, R
Seufert, C
Schetter, A
Giles, FJ
Sullivan, F
Dorsey, T
Goldman, R
Yan, PS
Wang-Johanning, F
Ambs, S
AF Glynn, Sharon A.
Wallace, Tiffany
Downey, Ronan
Seufert, Caleb
Schetter, Aaron
Giles, Francis J.
Sullivan, Frank
Dorsey, Tiffany
Goldman, Radoslav
Yan, Peisha
Wang-Johanning, Feng
Ambs, Stefan
TI The potential of peripheral blood HERV-K expression as a biomarker for
diagnosis with prostate cancer in older men.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Natl Univ Ireland Galway, Prostate Canc Inst, Galway, Ireland.
NCI, Bethesda, MD 20892 USA.
Natl Univ Ireland Galway, Galway, Ireland.
Natl Univ Ireland, HRB Clin Res Facil, Dublin, Ireland.
Univ Dublin Trinity Coll, Dublin 2, Ireland.
Galway Univ Hosp, Galway, Ireland.
Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
SRI Int, Menlo Pk, CA 94025 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 5049
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203441
ER
PT J
AU Good, MJ
Hurley, PA
Mesfin, E
AF Good, Marjorie J.
Hurley, Patricia A.
Mesfin, Eden
TI The road to assessing clinical trial-associated workload
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Rockville, MD USA.
Amer Soc Clin Oncol, Alexandria, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e17587
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201051
ER
PT J
AU Gucalp, A
Morris, PG
Zhou, XK
Giri, DD
Iyengar, NM
Crew, KD
Hershman, DL
Garber, JE
Nangla, JR
Cook, ED
Vornik, L
Dunn, BK
Heckman-Stoddard, BM
Foster, K
Brown, P
Dannenberg, A
Hudis, CA
AF Gucalp, Ayca
Morris, Patrick Glyn
Zhou, Xi Kathy
Giri, Dilip D.
Iyengar, Neil M.
Crew, Katherine D.
Hershman, Dawn L.
Garber, Judy Ellen
Nangla, Julie R.
Cook, Elise D.
Vornik, Lana
Dunn, Barbara Karen
Heckman-Stoddard, Brandy M.
Foster, Kathleen
Brown, Powel
Dannenberg, Andrew
Hudis, Clifford A.
CA UT MD Anderson Early Phase
TI A multicenter phase II study of docosahexaenoic acid (DHA) in patients
(pts) with a history of breast cancer (BC), premalignant lesions, or
benign breast disease
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Weill Cornell Med Coll, New York, NY USA.
Columbia Univ, Med Ctr, New York, NY USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Baylor Coll Med, Houston, TX 77030 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Canc Prevent Div, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA TPS1615
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202013
ER
PT J
AU Haluska, P
Bernath, AM
Ballman, KV
Dueck, AC
Linden, HM
Goetz, MP
Northfelt, DW
Hou, XN
Tenner, KS
Tienchaiananda, P
Flickinger, LM
Chen, BY
Chen, HX
Lingle, WL
Pellegrino, CM
Sponzo, RW
Reinholz, MM
Perez, EA
AF Haluska, Paul
Bernath, Albert M.
Ballman, Karla V.
Dueck, Amylou C.
Linden, Hannah M.
Goetz, Matthew P.
Northfelt, Donald W.
Hou, Xiaonan
Tenner, Kathleen S.
Tienchaiananda, Piyawan
Flickinger, Lynn M.
Chen, Beiyun
Chen, Helen X.
Lingle, Wilma L.
Pellegrino, Christine M.
Sponzo, Robert W.
Reinholz, Monica Madden
Perez, Edith A.
CA Alliance Clinical Trials Oncology
TI Randomized phase II trial of capecitabine and lapatinib with or without
cixutumumab in patients with HER2+breast cancer previously treated with
trastuzumab and an anthracycline and/or a taxane: NCCTG N0733
(Alliance).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mayo Clin, Rochester, MN USA.
Geisinger Hlth Syst, Danville, PA USA.
Mayo Clin, Scottsdale, AZ USA.
Univ Washington, Seattle, WA 98195 USA.
Ramathibodi Hosp, Bangkok, Thailand.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
Montefiore Med Ctr, New York, NY USA.
Glens Falls Hosp, Glens Falls, NY USA.
Mayo Clin, Jacksonville, FL 32224 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 632
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202405
ER
PT J
AU Han, TJ
Lee, A
Mister, D
Miller, AH
Torres, MA
AF Han, Tatiana Jihae
Lee, Anna
Mister, Donna
Miller, Andrew H.
Torres, Mylin Ann
TI The influence of childhood trauma on fatigue and depression in breast
cancer patients during and after radiotherapy
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Emory Univ, Dept Radiat Oncol, Winship Canc Inst, Atlanta, GA 30322 USA.
Mercer Univ, Sch Med, Macon, GA 31207 USA.
Emory Univ, Sch Med, Atlanta, GA USA.
Emory Univ, NSABP, Atlanta, GA 30322 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e20567
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201551
ER
PT J
AU Hanasoge, S
Wang, XJ
Chen, ZJ
Mister, D
Miller, AH
Torres, MA
AF Hanasoge, Sheela
Wang, Xiaojing
Chen, Zhengjia
Mister, Donna
Miller, Andrew H.
Torres, Mylin Ann
TI The influence of radiotherapy on sleep disturbances in breast cancer
patients.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Emory Univ, Winship Canc Inst, Dept Radiat Oncol, Atlanta, GA 30322 USA.
Emory Univ, Winship Canc Inst, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA.
Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
Emory Univ, Sch Med, Atlanta, GA USA.
Emory Univ, Winship Canc Inst, NSABP, Atlanta, GA 30322 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 1092
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202513
ER
PT J
AU Hassan, R
Alley, EW
Kindler, HL
Antonia, SJ
Jahan, TM
Jacobs-Small, M
Hull, J
McDougall, K
Lemmens, E
Murphy, A
Grous, JJ
Dubensky, T
Brockstedt, DG
AF Hassan, Raffit
Alley, Evan W.
Kindler, Hedy Lee
Antonia, Scott Joseph
Jahan, Thierry Marie
Jacobs-Small, Mona
Hull, Jennifer
McDougall, Katherine
Lemmens, Ed
Murphy, Aimee
Grous, John J.
Dubensky, Thomas
Brockstedt, Dirk G.
TI Antimesothelin vaccine CRS-207 plus chemotherapy as front-line treatment
for malignant pleural mesothelioma (MPM).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
Univ Chicago, Chicago, IL 60637 USA.
Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
Aduro BioTech Inc, Berkeley, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 7532
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203968
ER
PT J
AU Heery, CR
Singh, H
Marte, JL
Madan, RA
Coyne, GHO
Farsaci, B
Rodell, TC
Palena, C
Schlom, J
Gulley, JL
AF Heery, Christopher Ryan
Singh, Harpreet
Marte, Jennifer L.
Madan, Ravi Amrit
Coyne, Geraldine Helen O'Sullivan
Farsaci, Benedetto
Rodell, Timothy C.
Palena, Claudia
Schlom, Jeffrey
Gulley, James L.
TI NCI experience using yeast-brachyury vaccine (GI-6301) in patients (pt)
with advanced chordonia.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA.
NIH, Genitourinary Malignancies Branch, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
Ctr Canc Res, Tumor Immunol & Biol Lab, Bethesda, MD USA.
Globelmmune Inc, Louisville, CO USA.
NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 3081
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202972
ER
PT J
AU Heery, CR
Coyne, GHO
Madan, RA
Schlom, J
von Heydebreck, A
Cuillerot, JM
Sabzevari, H
Gulley, JL
AF Heery, Christopher Ryan
Coyne, Geraldine Helen O'Sullivan
Madan, Ravi Amrit
Schlom, Jeffrey
von Heydebreck, Anja
Cuillerot, Jean-Marie
Sabzevari, Helen
Gulley, James L.
TI Phase I open-label, multiple ascending dose trial of MSB0010718C, an
anti-PD-L1 monoclonal antibody, in advanced solid malignancies.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA.
NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
Merck KGaA, Darmstadt, Germany.
EMD Serono, Billerica, MA USA.
EMD Serono, Rockland, MA USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 1
Z9 1
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 3064
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202955
ER
PT J
AU Hershman, DL
Unger, JM
Crew, KD
Dakhil, SR
Awad, D
Greenlee, H
Minasian, LM
Hansen, L
Lew, D
Gralow, J
Wade, JL
Meyskens, FL
Moinpour, C
AF Hershman, Dawn L.
Unger, Joseph M.
Crew, Katherine D.
Dakhil, Shaker R.
Awad, Danielle
Greenlee, Heather
Minasian, Lori M.
Hansen, Lisa
Lew, Danika
Gralow, Julie
Wade, James Lloyd
Meyskens, Frank L.
Moinpour, Carol
TI Omega-3 fatty acids for aromatase inhibitor-induced musculoskeletal
symptoms in women with early-stage breast cancer (SWOG S0927).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Columbia Univ, Med Ctr, New York, NY USA.
SWOG Stat Ctr, Seattle, WA USA.
Wichita Community Clin Oncol Program, Wichita, KS USA.
NCI, Bethesda, MD 20892 USA.
Legacy Good Samaritan Hosp, Portland, OR USA.
Southwest Oncol Grp, Ctr Stat, Seattle, WA USA.
Seattle Canc Care Alliance, Seattle, WA USA.
Canc Care Ctr Decatur, Decatur, IL USA.
Chao Family Comprehens Canc Ctr, Orange, CA USA.
Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 9532
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204416
ER
PT J
AU Heske, C
Yeung, C
Cao, L
Wan, XL
Helman, LJ
AF Heske, Christine
Yeung, Choh
Cao, Liang
Wan, Xiaolin
Helman, Lee J.
TI Identification of PDGFR-beta activation as a potential bypass resistance
pathway in a rhabdomyosarcoma (RMS) model of acquired resistance to
IGF-I receptor blockade.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
NCI, Pediat Oncol, CCR, NIH, Bethesda, MD 20892 USA.
NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10046
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204585
ER
PT J
AU Hinrichs, CS
Stevanovic, S
Draper, L
Somerville, R
Wunderlich, J
Restifo, NP
Sherry, R
Giao, PQ
Kammula, US
Yang, JC
Rosenberg, SA
AF Hinrichs, Christian S.
Stevanovic, Sanja
Draper, Lindsey
Somerville, Robert
Wunderlich, John
Restifo, Nicholas P.
Sherry, Richard
Giao, Phan Q.
Kammula, Udal S.
Yang, James C.
Rosenberg, Steven A.
TI HPV-targeted tumor-infiltrating lymphocytes for cervical cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Bethesda, MD 20892 USA.
NCI, Surg Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA LBA3008
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201958
ER
PT J
AU Hoffman-Censits, JH
Vaughn, DJ
Lin, JQ
Keefe, SM
Haas, NB
Kelly, WK
Hyslop, T
McGulre, M
Robinson, J
Khadar, K
Nanda, S
Kennedy, B
Apolo, AB
AF Hoffman-Censits, Jean H.
Vaughn, David J.
Lin, Jianqing
Keefe, Stephen Michael
Haas, Naomi B.
Kelly, William Kevin
Hyslop, Terry
McGulre, Monica
Robinson, Janelle
Khadar, Kahle
Nanda, Swati
Kennedy, Brooke
Apolo, Andrea Borghese
TI A phase II study of cabazitaxel in patients with urothelial carcinoma
who have disease progression following platinum based chemotherapy.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
Duke Canc Inst, Dept Biostat & Bioinformat, Durham, NC USA.
NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e15519
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200667
ER
PT J
AU Hong, TS
Szymonifka, J
Yothers, G
Blaszkowsky, LS
Russo, AL
Wo, JYL
Mamon, HJ
Kwak, EL
Zhu, AX
Allen, JN
Clark, JW
Ryan, DP
AF Hong, Theodore S.
Szymonifka, Jackie
Yothers, Greg
Blaszkowsky, Lawrence Scott
Russo, Andrea Lyn
Wo, Jennifer Yon-Li
Mamon, Harvey J.
Kwak, Eunice Lee
Zhu, Andrew X.
Allen, Jill N.
Clark, Jeffrey W.
Ryan, David P.
TI Validation of the NSABP neoadjuvant rectal score (NAR) in a prospective
phase II study evaluating an experimental regimen and a standard
chemoradiation cohort with molecular genotyping.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Biostat, Boston, MA 02114 USA.
Natl Surg Adjuvant Breast & Bowel Project, Biostat Ctr, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Harvard Radiat Oncol Program, Boston, MA USA.
Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 3599
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203115
ER
PT J
AU Hubbard, JM
Kim, GP
Bored, MJ
Qin, R
Lensing, J
Wright, JJ
Erlichman, C
Grothey, A
AF Hubbard, Joleen Marie
Kim, George P.
Bored, Mitesh J.
Qin, Rui
Lensing, Janet
Wright, John Joseph
Erlichman, Charles
Grothey, Axel
TI Phase I trial of FOLFIRI in combination with sorafenib and bevacizumab
in patients with advanced gastrointestinal malignancies.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mayo Clin, Rochester, MN USA.
Mayo Clin, Jacksonville, FL 32224 USA.
Mayo Clin, Scottsdale, AZ USA.
Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA.
NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 2539
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202804
ER
PT J
AU Jasielec, J
Kimball, AS
Cohen, KS
Kline, JP
Rapoport, A
Petrich, AM
Nabhan, C
Thomas, S
Doyle, LA
Stadler, WM
Karrison, T
Smith, SM
AF Jasielec, Jagoda
Kimball, Amy Sarah
Cohen, Kenneth Stuart
Kline, Justin Paul
Rapoport, Aaron
Petrich, Adam Matthew
Nabhan, Chadi
Thomas, Sachdev
Doyle, Laurence A.
Stadler, Walter Michael
Karrison, Theodore
Smith, Sonali M.
TI Temsirolimus (TEM) and lenalidomide (LEN) in relapsed/refractory Hodgkin
lymphoma including in patients with prior exposure to brentuximab
vedotin (BV).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Chicago, Chicago, IL 60637 USA.
Univ Maryland, Baltimore, MD 21201 USA.
Northwestern Univ, Chicago, IL 60611 USA.
Illinois Canc Ctr, Peoria, IL USA.
NCI, Rockville, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 8567
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204246
ER
PT J
AU Jawed, I
Wilkerson, J
Pichun, MEB
Duffy, AG
Fojo, AT
AF Jawed, Irfan
Wilkerson, Julia
Pichun, Mauricio Emmanuel Burotto
Duffy, Austin G.
Fojo, Antonio Tito
TI Effect of chemotherapy on the progress in colorectal cancer survival in
the past two decades.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Lawrence Mem Hosp Oncol Ctr, Lawrence, KS USA.
NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 3642
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203158
ER
PT J
AU Jones, JA
Andritsos, LA
Lucas, DM
Lozanski, G
Hutchinson, T
Sexton, JL
Harris, PJ
Grever, MR
AF Jones, Jeffrey Alan
Andritsos, Leslie A.
Lucas, David M.
Lozanski, Gerard
Hutchinson, Terri
Sexton, Jennifer L.
Harris, Pamela Jo
Grever, Michael R.
TI Preliminary safety and efficacy of the Bruton's tyrosine kinase (BTK)
inhibitor ibrutinib (IBR) in patients (pts) with hairy cell leukemia
(HCL).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Ohio State Univ, Columbus, OH 43210 USA.
Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 4
Z9 4
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 7063
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203880
ER
PT J
AU Joshi, J
Mounier, N
Xue, XN
Wang, D
Ribera, JM
Wyen, C
Dunleavy, K
Little, RF
Wilson, WH
Noy, A
Sparano, JA
Barta, SK
AF Joshi, Jitesh
Mounier, Nicolas
Xue, Xiaonan
Wang, Dan
Ribera, Josep-Maria
Wyen, Christoph
Dunleavy, Kieron
Little, Richard F.
Wilson, Wyndham Hopkins
Noy, Ariela
Sparano, Joseph A.
Barta, Stefan K.
TI CNS involvement in patients with AIDS-related lymphomas.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA.
Ctr Hosp Univ Archet, Nice, France.
Albert Einstein Coll Med, Bronx, NY 10467 USA.
Hosp Badalona Germans Trias & Pujol, Barcelona, Spain.
Univ Hosp Cologne, Cologne, Germany.
NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Montefiore Med Ctr, Bronx, NY 10467 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 8570
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204249
ER
PT J
AU Karzal, F
Shah, AA
Ojemuyiwa, MA
Madan, RA
Apolo, AB
Dawson, NA
Arlen, PM
Theoret, MR
Wright, JJ
Chen, C
Trepel, JB
Couvillon, A
Chun, G
Harold, N
Steinberg, SM
Price, DK
Gulley, JL
Figg, WD
Dahut, WL
AF Karzal, Fatima
Shah, Avani Atul
Ojemuyiwa, Michelle A.
Madan, Ravi Amrit
Apolo, Andrea Borghese
Dawson, Nancy Ann
Arlen, Phillp M.
Theoret, Marc Robert
Wright, John Joseph
Chen, Clara
Trepel, Jane B.
Couvillon, Anna
Chun, Guinevere
Harold, Nancy
Steinberg, Seth M.
Price, Douglas K.
Gulley, James L.
Figg, William Douglas
Dahut, William L.
TI A safety study of cabozantinib (C) plus docetaxel (D) and prednisone (P)
in metastatic castrate-resistant prostate cancer (mCRPC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA.
NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Clin Ctr, NIH, Bethesda, MD 20892 USA.
NCI, Rockville, MD USA.
NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA.
NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 5072
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203464
ER
PT J
AU Kaveney, AD
Mehnert, JM
Tan, AR
Aisner, J
Moss, RA
Gibbon, D
Adams, S
Fischer, J
Scott, P
Gable, C
Doyle, A
DiPaola, RS
Stein, MN
AF Kaveney, Amanda D.
Mehnert, Janice M.
Tan, Antoinette R.
Aisner, Joseph
Moss, Rebecca Anne
Gibbon, Darlene
Adams, Shari
Fischer, Jane
Scott, Pamela
Gable, Christian
Doyle, Austin
DiPaola, Robert S.
Stein, Mark N.
TI A phase I trial of MK-2206 and hydroxychloroquine(HCQ) in solid tumors,
melanoma, renal, and prostate cancer to examine the role of antophagy in
tomorigenesis
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 New Jersey Robert Wood Johnson Hosp, Inst Canc, New Brunswick, NJ USA.
Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
NSABP, New Brunswick, NJ USA.
Rutgers Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
Canc Inst New Jersey, New Brunswick, NJ USA.
Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
NCI, Rockville, MD USA.
Rutgers Biomed & Hlth Sci, New Brunswick, NJ USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA TPS2640
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202041
ER
PT J
AU Keat, NJ
Law, K
McConnell, A
Calvo, FM
Negrouk, A
Lacombe, DA
Welch, J
Trimble, EL
Gross, T
De Schaetzen, G
Brachot, JM
Pauporta, I
O'Riordan, M
Seymour, MT
AF Keat, Nicola Jane
Law, Kate
McConnell, Andrea
Calvo, Fabian M.
Negrouk, Anastasia
Lacombe, Denis A.
Welch, Jack
Trimble, Edward Lloyd
Gross, Thomas
De Schaetzen, Gaetan
Brachot, Jeanne-Mane
Pauporta, Iris
O'Riordan, Maura
Seymour, Matthew T.
TI The international rare cancers initiative.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Canc Res UK, London, England.
Univ Paris 07, Hop St Louis, APHP, Lab Pharmacol,INSERM,IUH, Paris, France.
European Org Res Treatment Canc, Brussels, Belgium.
NCI, Bethesda, MD 20892 USA.
NCI, Ctr Global Hlth, NIH, DHHS, Rockville, MD USA.
EORTC Headquarters, Brussels, Belgium.
Natl Canc Inst, Boulogne, France.
NCI Ctr Global Hlth, Brussels, Belgium.
Natl Inst Hlth, Res Canc Res Network, Leeds, W Yorkshire, England.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e17504
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200965
ER
PT J
AU Kehl, KL
Landrum, MB
Arora, NK
Ganz, PA
van Ryn, M
Mack, JW
Keating, NL
AF Kehl, Kenneth L.
Landrum, Mary Beth
Arora, Neeraj K.
Ganz, Patricia A.
van Ryn, Michelle
Mack, Jennifer W.
Keating, Nancy Lynn
TI Decisions about cancer treatment: Matching of actual to preferred roles
and patient ratings of care
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
NCI, NIH, Bethesda, MD 20892 USA.
Univ Calif Los Angeles, Los Angeles, CA USA.
Univ Minnesota, Minneapolis, MN USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 6533
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203719
ER
PT J
AU Kehl, KL
Arora, NK
Schrag, D
Ayanian, J
Clauser, S
Klabunde, CN
Kahn, KL
Fletcher, RH
Keating, NL
AF Kehl, Kenneth L.
Arora, Neeraj K.
Schrag, Deborah
Ayanian, John
Clauser, Steven
Klabunde, Carrie N.
Kahn, Katherine Leslie
Fletcher, Robert H.
Keating, Nancy Lynn
TI Discussions about clinical trials among patients with lung and
colorectal cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
NCI, NIH, Bethesda, MD 20892 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 6509
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203695
ER
PT J
AU Khanna, P
Hollingshead, MG
Parchment, RE
Kinders, RJ
Tomaszewskl, JE
Doroshow, JH
Srivastava, AK
AF Khanna, Payal
Hollingshead, Melinda G.
Parchment, Ralph E.
Kinders, Robert J.
Tomaszewskl, Joseph E.
Doroshow, James H.
Srivastava, Apurva K.
TI Pharmacodynamic assay for evaluation of first-in-class pyrovate
kinase-M2 activators in tumors
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Leidos Biomed Res Inc, Fredrick Natl Lab Canc Res, Frederick, MD USA.
NCI, Frederick, MD 21701 USA.
Frederick Natl Lab Canc Res, Ledios Biomed, Frederick, MD USA.
NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 2551
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202816
ER
PT J
AU Kim, A
Reinke, DK
Cichowski, K
Perentesis, JP
Wolters, P
Martin, S
Dombl, E
Steinberg, SM
Widemann, BC
AF Kim, AeRang
Reinke, Denise K.
Cichowski, Karen
Perentesis, John Peter
Wolters, Pamela
Martin, Stacl
Dombl, Eva
Steinberg, Seth M.
Widemann, Brigitte C.
TI SARC023: Phase I/II trial of ganetespib in combination with sirolimus
for refractory sarcomas and malignant peripheral nerve sheath tumors
(MPNST).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA.
Sarcoma Alliance Res Collaborat, Ann Arbor, MI USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA TPS10603
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202268
ER
PT J
AU Konstantinopoulos, P
Makker, V
Barry, WT
Liu, J
Horowitz, NS
Birrer, MJ
Doyle, LA
Berlin, ST
Whalen, C
Van Hummelen, P
Coleman, RL
Aghajanian, C
Mills, GB
Matulonis, U
Westin, SN
Myers, AP
AF Konstantinopoulos, Panagiotis
Makker, Vicky
Barry, William Thomas
Liu, Joyce
Horowitz, Neil S.
Birrer, Michael J.
Doyle, L. Austin
Berlin, Suzanne T.
Whalen, Christin
Van Hummelen, Paul
Coleman, Robert L.
Aghajanian, Carol
Mills, Gordon B.
Matulonis, Ursula
Westin, Shannon Neville
Myers, Andrea P.
TI Phase II, single stage, cohort expansion study of MK-2206 in recurrent
endometrial serous cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NCI, Rockville, MD USA.
Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Novartis Inst BioMed Res, Cambridge, MA USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 5515
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203500
ER
PT J
AU Kummar, S
Williams, M
Lih, CJ
Chen, AP
Rubinstein, L
Antony, R
Polley, E
Zhao, YD
Conley, BA
Simon, R
Doroshow, JH
AF Kummar, Shivaani
Williams, Mickey
Lih, Chih-Jian
Chen, Alice P.
Rubinstein, Larry
Antony, Ramya
Polley, Eric
Zhao, Yingdong
Conley, Barbara A.
Simon, Richard
Doroshow, James H.
TI NCI mpact: National Cancer Institute molecular profiling-based
assignment of cancer therapy.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Bethesda, MD 20892 USA.
Leidos Biomed Res Inc, Frederick, MD USA.
Div Canc Treatment & Diag, Bethesda, MD USA.
NCI, Div Canc Treatment & Diag, Rockville, MD USA.
NIH, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA TPS2642
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202043
ER
PT J
AU Lai, C
Cole, D
Shovlin, M
Widemann, BC
Dunleavy, K
Wilson, WH
AF Lai, Catherine
Cole, Diane
Shovlin, Margaret
Widemann, Brigitte C.
Dunleavy, Kieron
Wilson, Wyndham Hopkins
TI Pharmacokinetics and tolerability of doxorubicin in newly diagnosed
lymphoma patients with hepatic impairment.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
Pediat Oncol Branch, Bethesda, MD USA.
NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 8547
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204226
ER
PT J
AU Lam, CJK
Curtis, RE
Dores, G
Engels, EA
Caporaso, N
Poillack, A
Young, HA
Levine, PH
Elmi, AF
Fraumeni, JF
Tucker, MA
Morton, LM
AF Lam, Clara J. K.
Curtis, Rochelle E.
Dores, Graca
Engels, Eric A.
Caporaso, Neil
Poillack, Aaron
Young, Heather A.
Levine, Paul H.
Elmi, Angelo F.
Fraumeni, Joseph F.
Tucker, Margaret A.
Morton, Lindsay M.
TI Risk factors for melanoma among survivors of non-Hodgkin lymphoma in the
US elderly population.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Rockville, MD USA.
NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
Dept Vet Affairs Med Ctr, Oklahoma City, OK USA.
NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
NCI, Bethesda, MD 20892 USA.
Hadassah Univ Hosp, IL-91120 Jerusalem, Israel.
Hebrew Univ Jerusalem, Sch Med, IL-91010 Jerusalem, Israel.
George Washington Univ, Washington, DC USA.
George Washington Univ, Dept Epidemiol & Biostat, Washington, DC USA.
George Washington Univ, Sch Publ Hlth & Hlth Sci, Washington, DC USA.
NCI, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 1533
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202585
ER
PT J
AU Land, SR
Walcott, FL
Liu, Q
Wickerham, DL
Costantino, JP
Ganz, PA
AF Land, Stephanie R.
Walcott, Farzana L.
Liu, Qing
Wickerham, Donald Lawrence
Costantino, Joseph P.
Ganz, Patricia A.
TI Patient-reported outcomes and behavioral risk factors as predictors of
chemoprevention adherence among women in the National Surgical Adjuvant
Breast and Bowel Program (NSABP) Breast Cancer Prevention P-1 trial.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Rockville, MD USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
Allegheny Gen Hosp, Pittsburgh, PA 15212 USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Biostat, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
Univ Calif Los Angeles, Los Angeles Sch Med & Publ Hlth, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 1512
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202564
ER
PT J
AU Land, SR
Toll, B
Warren, GW
Brandon, TH
Mitchell, SA
Dresler, CM
Gritz, ER
Schnoll, R
Sarna, L
Moinpour, C
Ostroff, JS
Khuri, FR
Buckner, JC
Cummings, KM
Herbst, RS
Shields, PG
Duffy, S
Rigotti, N
Prindiville, SA
Abrams, JS
AF Land, Stephanie R.
Toll, Benjamin
Warren, Graham Walter
Brandon, Thomas H.
Mitchell, Sandra A.
Dresler, Carolyn M.
Gritz, Ellen R.
Schnoll, Robert
Sarna, Linda
Moinpour, Carol
Ostroff, Jamie S.
Khuri, Fadio Raja
Buckner, Jan C.
Cummings, Kenneth Michael
Herbst, Roy S.
Shields, Peter G.
Duffy, Sonia
Rigotti, Nancy
Prindiville, Sheila Ann
Abrams, Jeffrey S.
CA Natl Canc Inst Amer Assoc Canc Res
TI Standardizing measurement of tobacco use in cancer clinical trials
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Rockville, MD USA.
Yale Univ, New Haven, CT USA.
Med Univ S Carolina, Charleston, SC 29425 USA.
Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
Arkansas Dept Hlth, Little Rock, AR 72205 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Univ Penn, Philadelphia, PA 19104 USA.
Univ Calif Los Angeles, Los Angeles, CA USA.
Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
Mayo Clin, Rochester, MN USA.
Yale Univ, Sch Med, Dept Med Oncol, New Haven, CT USA.
Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NCI, Coordinating Ctr Clin Trails, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e17658
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201112
ER
PT J
AU Lee, JM
Annunziata, CM
Hays, JL
Choyke, PL
Cao, L
Yu, MS
Azad, NS
Houston, ND
Minasian, LM
Gordon, N
Chen, HX
Wright, JJ
Kohn, EC
AF Lee, Jung-Min
Annunziata, Christina M.
Hays, John L.
Choyke, Peter L.
Cao, Liang
Yu, Minshu
Azad, Nilofer Saba
Houston, Nicole D.
Minasian, Lori M.
Gordon, Nicolas
Chen, Helen X.
Wright, John Joseph
Kohn, Elise C.
TI A phase II study of intermittent sorafenib with bevacizumab (B) in
B-naive and prior B-exposed epithelial ovarian cancer (EOC) patients.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Mol Signaling Sect, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
NCI, Bethesda, MD 20892 USA.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
NCI, Rockville, MD USA.
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
NR 0
TC 2
Z9 2
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 5553
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203537
ER
PT J
AU Lee, JM
Liu, J
Choyke, PL
Elbuluk, O
Turkbey, IB
Trepei, JB
Lee, MJ
Cao, L
Houston, ND
Gordon, N
Figg, WD
Barry, WT
Matulonis, U
Birrer, MJ
Ivy, P
Kohn, EC
AF Lee, Jung-min
Liu, Joyce
Choyke, Peter L.
Elbuluk, Osama
Turkbey, Ismail B.
Trepei, Jane B.
Lee, Min-Jung
Cao, Liang
Houston, Nicole D.
Gordon, Nicolas
Figg, William Douglas
Barry, William Thomas
Matulonis, Ursula
Birrer, Michael J.
Ivy, Percy
Kohn, Elise C.
TI Biomarker correlates from the randomized phase 2 trial of the PARP
inhibitor olaparib (O) with or without the antiangiogenic TKI cediranib
(C) in recurrent platinum-sensitive ovarian cancer (NCT01116648).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NIH, Bethesda, MD 20892 USA.
NIH, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
Duke Univ, Med Ctr, Durham, NC USA.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 5535
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203519
ER
PT J
AU Lheureux, S
Ledermann, JA
Kaye, SB
Gourley, C
Friedlander, M
Bowtell, D
De Greve, J
deFazio, A
Shapira-Frommer, R
De Bono, JS
Audeh, MW
Kohn, EC
Alsop, K
Scott, CL
Matulonis, U
Kaufman, B
Burger, B
Robertson, JD
Ho, T
Oza, AM
AF Lheureux, Stephanie
Ledermann, Jonathan A.
Kaye, Stanley B.
Gourley, Charlie
Friedlander, Michael
Bowtell, David
De Greve, Jacques
deFazio, Anna
Shapira-Frommer, Ronnie
De Bono, Johann Sebastian
Audeh, M. William
Kohn, Elise C.
Alsop, Kathryn
Scott, Clare L.
Matulonis, Ursula
Kaufman, Bella
Burger, Brent
Robertson, Jane D.
Ho, Tony
Oza, Amit M.
TI Characterization of ovarian cancer long-term responders on olaparib.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Princess Margaret Canc Ctr, Toronto, ON, Canada.
UCL, Inst Canc, London, England.
Inst Canc Res, Drug Dev Unit, London SW3 6JB, England.
Royal Marsden NHS Fdn Trust, London, England.
Edinburgh Canc Res UK Ctr, Edinburgh, Midlothian, Scotland.
Prince Wales Hosp, Sydney, NSW, Australia.
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
Univ Hosp Brussels, UZ Brussel, Familial Canc Clin & Med Oncol, Brussels, Belgium.
Univ Sydney, Westmead Inst Canc Res, Westmead Millennium Inst, Sydney, NSW 2006, Australia.
Tel Aviv Univ, Sackler Fac Med, Ella Inst Res & Treatment Melanoma, Sheba Med Ctr, IL-52621 Tel Hashomer, Israel.
Royal Marsden NHS Fdn Trust, Sutton, Surrey, England.
Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
NCI, NIH, Bethesda, MD 20892 USA.
Royal Melbourne Hosp, Parkville, Vic, Australia.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Chaim Sheba Med Ctr, Inst Oncol, Breast Canc Unit, IL-52621 Tel Hashomer, Israel.
AstraZeneca, Macclesfield, Cheshire, England.
AstraZeneca, Wilmington, DE USA.
Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada.
RI De Greve, Jacques/J-4939-2012
OI De Greve, Jacques/0000-0002-2389-0742
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 5534
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203518
ER
PT J
AU Liebman, MF
Brien, W
Parulekar, WR
Gelmon, KA
Shepherd, LE
Ligibel, JA
Hershman, DL
Rastogi, P
Mayer, IA
Hobday, TJ
Lemieux, J
Thompson, AM
Pritchard, KI
Whelan, TJ
Mukherjee, S
Chalchal, HI
Bernstein, V
Stambolic, V
Chen, BSE
Goodwin, PJ
AF Liebman, Mira F.
Brien, William
Parulekar, Wendy R.
Gelmon, Karen A.
Shepherd, Lois E.
Ligibel, Jennifer A.
Hershman, Dawn L.
Rastogi, Priya
Mayer, Ingrid A.
Hobday, Timothy J.
Lemieux, Julie
Thompson, Alastair Mark
Pritchard, Kathleen I.
Whelan, Timothy Joseph
Mukherjee, Som
Chalchal, Haji I.
Bernstein, Vanessa
Stambolic, Vuk
Chen, Bingshu E.
Goodwin, Pamela Jean
CA Univ Toronto
TI Vitamin B12 (Vit B12) biochemical (BCH) deficiency (DEF) in non-diabetic
breast cancer (BC) patients on NCIC CTG MA.32: A phase III randomized
adjuvant BC trial comparing metformin (Met) to placebo (Pl).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Toronto, Univ Hlth Network, Toronto, ON, Canada.
Queens Univ, Canc Res Inst, NCIC Clin Trials Grp, Kingston, ON, Canada.
Univ British Columbia, British Columbia Canc Agcy, NCIC Clin Trials Grp, Vancouver, BC V5Z 1M9, Canada.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
Columbia Univ, Med Ctr, New York, NY USA.
Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA.
Mayo Clin, Coll Med, Rochester, MN USA.
CHU Quebec, Ctr Rech, Unite Rech Sante Populat, Hop St Sacrement, Quebec City, PQ, Canada.
Dundee Canc Ctr, Dundee, Scotland.
Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
Univ Toronto, Toronto, ON, Canada.
Juravinski Canc Ctr, Hamilton, ON, Canada.
Allan Blair Canc Ctr, Regina, SK, Canada.
Univ British Columbia, Vancouver Isl Ctr, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada.
Univ Toronto, Princess Margaret Hosp, Univ Hlth Network, Ontario Canc Inst, Toronto, ON, Canada.
Univ Toronto, Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
RI Whelan, Timothy/D-3185-2017
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 542
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202316
ER
PT J
AU Lin, NU
Gabrail, NY
Sarantopoulos, J
Schwartzberg, LS
Kesari, S
Bates, SE
Anders, CK
Elias, AD
Castaigne, JP
Iordanova, V
Lawrence, B
Kurzrock, R
AF Lin, Nancy U.
Gabrail, Nashat Y.
Sarantopoulos, John
Schwartzberg, Lee Steven
Kesari, Santosh
Bates, Susan Elaine
Anders, Carey K.
Elias, Anthony D.
Castaigne, Jean-Paul
Iordanova, Vihra
Lawrence, Betty
Kurzrock, Razelle
TI Evaluation of CNS and peripheral antitumor activity of ANG1005 in
patients with brain metastases from breast tumors and other advanced
solid tumors
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Gabrail Canc Ctr, Canton, OH USA.
Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, Inst Drug Dev, San Antonio, TX 78229 USA.
Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
Univ Calif San Diego, La Jolla, CA 92093 USA.
NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA.
Univ Colorado, Ctr Canc, Aurora, CO USA.
Angiochem Inc, Montreal, PQ, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 2523
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202788
ER
PT J
AU Liu, J
Barry, WT
Birrer, MJ
Lee, JM
Buckanovich, RJ
Fleming, GF
Rimel, BJ
Buss, MK
Nattam, SR
Hurteau, J
Luo, WX
Cauy, P
Obermayer, E
Whalen, C
Lee, H
Winer, EP
Kohn, EC
Ivy, SP
Matulonis, U
AF Liu, Joyce
Barry, William Thomas
Birrer, Michael J.
Lee, Jung-min
Buckanovich, Ronald J.
Fleming, Gini F.
Rimel, B. J.
Buss, Mary K.
Nattam, Sreenivasa R.
Hurteau, Jean
Luo, Weixiu
Quy, Philippa
Obermayer, Elizabeth
Whalen, Christin
Lee, Hang
Winer, Eric P.
Kohn, Elise C.
Ivy, S. Percy
Matulonis, Ursula
TI A randomized phase 2 trial comparing efficacy of the combination of the
PAR? inhibitor olaparib and the antiangiogenic cediranib against
olaparib alone in recurrent platinum-sensitive ovarian cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NCI, NIH, Bethesda, MD 20892 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Ft Wayne Med Oncol & Hematol, Ft Wayne, IN USA.
Univ Chicago, Northshore Univ Hlth Syst, Evanston, IL USA.
Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA LBA5500
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201959
ER
PT J
AU Loupakis, F
Cremolini, C
Lonardi, S
Tomasello, G
Ronzoni, M
Zaniboni, A
Tonini, G
Valsuani, C
Chiara, S
Boni, C
Marcucci, L
Negri, F
Barone, C
Vitello, S
D'Amico, M
Granetto, C
Fontanini, G
Tomcikova, D
Boni, L
Falcone, A
AF Loupakis, Fotios
Cremolini, Chiara
Lonardi, Sara
Tomasello, Gianluca
Ronzoni, Monica
Zaniboni, Alberto
Tonini, Giuseppe
Valsuani, Chiara
Chiara, Silvana
Boni, Corrado
Marcucci, Lorenzo
Negri, Francesca
Barone, Carlo
Vitello, Stefano
D'Amico, Mauro
Granetto, Cristina
Fontanini, Gabriella
Tomcikova, Daniela
Boni, Luca
Falcone, Alfredo
TI Subgroup analyses in RAS mutant, BRAF mutant and all-wt mCRC pts treated
with FOLFOXIRI plus bevacizumab (bev) or FOLFIRI plus bev in the TRIBE
study.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Azienda Osped Univ Pisana, UO Oncol Med 2, Pisa, Italy.
Azienda Osped Univ Pisana, UO Oncol Med 2, Ist Toscano Tumori, Pisa, Italy.
Ist Oncol Veneto IOV IRCCS, Med Oncol 1, Padua, Italy.
Ist Ospitalieri Cremona, Cremona, Italy.
Ist Sci San Raffaele, Dipartimento Oncol Med, Milan, Italy.
Casa Cura Poliambulanza, Dept Med Oncol, Brescia, Italy.
Campus Biomed Univ Rome, Dept Med Oncol, Rome, Italy.
Osped Versilia, UO Oncol Med, Viareggio, Italy.
Natl Canc Inst, Med Oncol Unit, Genoa, Italy.
Santa Maria Nuova Hosp, Reggio Emilia, Italy.
USL 5 Pontedera, Div Med Oncol, Pontedera, Italy.
Univ Hosp Parma, Med Oncol Unit, Parma, Italy.
Univ Cattolica Sacro Cuore, I-00168 Rome, Italy.
Osped St Elia, UO Oncol, Caltanissetta, Italy.
EO Osped Galliera, Genoa, Italy.
Azienda Sanit Osped S Croce & Carle, UO Oncol Med, Cuneo, Italy.
Azienda Osped Univ Pisana, Pisa, Italy.
Ist Toscano Tumori, Florence, Italy.
ITT, AOU Careggi, Clin Trial Coordinating Ctr, Florence, Italy.
NR 0
TC 5
Z9 5
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 3519
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203035
ER
PT J
AU Lu, YY
Xu, WP
Ji, JF
Fang, H
Sourbier, C
Qu, JH
Wang, CP
Wang, XW
Yang, YP
Neckers, L
AF Lu, Yin Ying
Xu, Wanping
Ji, Junfang
Fang, Hun
Sourbier, Carole
Qu, Jianhui
Wang, Chunping
Wang, Xin Wei
Yang, Yongping
Neckers, Len
TI Molecular chaperone HSP90 regulation of the alternative splicing of numb
as a clue for HCC progression.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Beijing 302 Hosp, Ctr Therapeut Res Hepatocarcinoma, Beijing, Peoples R China.
NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
Univ Hawaii, Ctr Canc, Canc Biol Program, Honolulu, HI 96822 USA.
NIAAA, Lab Liver Dis, NIH, Rockville, MD 20852 USA.
NCI, NIH, Bethesda, MD 20892 USA.
Ctr Therapeut Res Hepatocarcinoma, Beijing, Peoples R China.
302 Hosp PLA, Ctr Therapeut Res Hepatocellular Carcinoma, Beijing, Peoples R China.
NCI, Liver Carcinogenesis Sect, Lab Human Carcinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA.
302 Mil Hosp China, Beijing, Peoples R China.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e15114
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200515
ER
PT J
AU Ma, CX
Gao, F
Naughton, M
Pluard, TJ
Sorscher, S
Creekmore, AN
Guo, ZF
Dehdashti, F
Park, BH
Lockhart, AC
Doyle, LA
Ellis, MJ
Erlanger, B
AF Ma, Cynthia X.
Gao, Feng
Naughton, Michael
Pluard, Timothy J.
Sorscher, Steven
Creekmore, Allison N.
Guo, Zhanfang
Dehdashti, Farrokh
Park, Ben Ho
Lockhart, Albert C.
Doyle, L. Austin
Ellis, Matthew J.
Erlanger, Bracha
TI A phase I study of the AKT inhibitor MK-2206 plus hormonal therapy in
postmenopausal women with estrogen receptor positive (ER plus )
metastatic breast cancer (MBC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA.
Washington Univ, Div Oncol, St Louis, MO USA.
Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
Washington Univ, St Louis, MO USA.
NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 553
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202327
ER
PT J
AU Maher, VE
Kacuba, A
Ning, YMM
Murgo, AJ
Ibrahim, A
Farrell, AT
Keegan, P
Justice, RL
Pazdur, R
AF Maher, Virginia Ellen
Kacuba, Alice
Ning, Yangmin M.
Murgo, Anthony J.
Ibrahim, Amna
Farrell, Ann T.
Keegan, Patricia
Justice, Robert L.
Pazdur, Richard
TI Special protocol assessments: 10 years of experience in FDA's Office of
Hematology and Oncology Produets
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 US FDA, Silver Spring, MD USA.
NCI, US FDA, Silver Spring, MD USA.
NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e17511
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200971
ER
PT J
AU Malecek, K
Grigoryan, A
Zhong, S
Gu, WJ
Johnson, LA
Rosenberg, SA
Cardozo, T
Krogsgaard, M
AF Malecek, Karolina
Grigoryan, Arsen
Zhong, Shi
Gu, Wei Jun
Johnson, Laura A.
Rosenberg, Steven A.
Cardozo, Timothy
Krogsgaard, Michelle
TI Specific increase in T-cell potency via structure-based design of a
T-cell receptor for adoptive immunotherapy.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NYU Med Sch, New York, NY USA.
Xiangxue Pharmaceut Co, Guangzhou, Guangdong, Peoples R China.
NYU, New York, NY USA.
Univ Penn, Philadelphia, PA 19104 USA.
NCI, Bethesda, MD 20892 USA.
New York Univ Langone Med Ctr, New York, NY USA.
New York Univ Sch Med, Dept Pathol, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 3063
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202954
ER
PT J
AU Mamounas, EP
White, JR
Bandos, H
Julian, TB
Kahn, AJ
Shaitelman, SF
Torres, MA
McCloskey, SA
Vicini, FA
Ganz, PA
Paik, S
Gupta, N
Costantino, JP
Curran, WJ
Wolmark, N
AF Mamounas, Eleftherios P.
White, Julia R.
Bandos, Hanna
Julian, Thomas B.
Kahn, Atif J.
Shaitelman, Simona Flora
Torres, Mylin Ann
McCloskey, Susan Ann
Vicini, Frank A.
Ganz, Patricia A.
Paik, Soonmyung
Gupta, Nilendu
Costantino, Joseph P.
Curran, Walter John
Wolmark, Norman
TI NSABP B-51/RTOG 1304: Randomized phase III clinical trial evaluating the
role of postmastectomy chest wall and regional nodal XRT (CWRNRT) and
post-lumpectomy RNRT in patients (pts) with documented positive axillary
(Ax) nodes before neoadjuvant chemotherapy (NC) who convert to
pathologically negative Ax nodes after NC.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Natl Surg Adjuvant Breast & Bowel Project NSABP, Orlando, FL USA.
Orlando Hlth, UF Hlth Canc Ctr, Orlando, FL USA.
Ohio State Univ, Med Ctr, Columbus, OH 43210 USA.
NSABP Biostat Ctr, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
NSABP, Pittsburgh, PA USA.
Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
NSABP, New Brunswick, NJ USA.
Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
Univ Texas MD Anderson Canc Ctr, Radiat Therapy Oncol Grp, Houston, TX 77030 USA.
NSABP, Atlanta, GA USA.
Emory Univ, Winship Canc Inst, Dept Radiat Oncol, Atlanta, GA 30322 USA.
NSABP, Los Angeles, CA USA.
Univ Calif Los Angeles, Los Angeles, CA USA.
NSABP, Beaumont, TX USA.
21st Century Oncol, Farmington Hills, MI USA.
Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Pittsburgh, PA USA.
Yonsei Univ, Coll Med, Dept Med Oncol, Pittsburgh, PA USA.
Ohio State Univ, Radiat Therapy Oncol Grp, Columbus, OH 43210 USA.
NSABP Biostat Ctr, Pittsburgh, PA USA.
Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA TPS1141
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202004
ER
PT J
AU Massett, HA
Atkinson, N
Brittle, C
Adler, J
Roach, N
Bailey, R
Good, MJ
Burgess, D
Mooney, MM
Abrams, JS
AF Massett, Holly A.
Atkinson, Nancy
Brittle, Christine
Adler, Jeanne
Roach, Nancy
Bailey, Robert
Good, Marjorie J.
Burgess, Danielle
Mooney, Margaret M.
Abrams, Jeffrey S.
TI A randomized, controlled study comparing NCI's original and revised
informed consent templates
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Rockville, MD USA.
Westat Corp, Rockville, MD USA.
Salter Mitchell, Alexandria, VA USA.
Colorectal Canc Coalit, Alexandria, VA USA.
Fight Colorectal Canc, Kansas City, MO USA.
NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 6523
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203709
ER
PT J
AU Meany, HJ
Dome, J
Hinds, PS
Bagatell, R
Shusterman, S
Widemann, BC
Stern, E
London, WB
Kim, A
Fox, E
Rodriguez-Galindo, C
Minturn, JE
AF Meany, Holly Jane
Dome, Jeffrey
Hinds, Pamela S.
Bagatell, Rochelle
Shusterman, Suzanne
Widemann, Brigitte C.
Stern, Emily
London, Wendy B.
Kim, AeRang
Fox, Elizabeth
Rodriguez-Galindo, Carlos
Minturn, Jane E.
TI Phase 1 study of sorafenib and irinotecan in pediatric patients with
relapsed or refractory solid tumors.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Childrens Natl Med Ctr, Washington, DC 20010 USA.
Childrens Hosp, Philadelphia, PA 19104 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10052
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204591
ER
PT J
AU Merchant, MS
Bernstein, DB
Delbrook, C
Wright, M
Mackall, C
AF Merchant, Melinda S.
Bernstein, Donna B.
Delbrook, Cindy
Wright, Matthew
Mackall, Crystal
TI Metastatic melanoma presenting during childhood: NCI Pediatric Oncology
Branch experience.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NCI, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10075
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204614
ER
PT J
AU Moore, HCF
Unger, JM
Phillips, KA
Boyle, FM
Nitre, E
Porter, DJ
Francis, PA
Minasian, LM
Gelber, RD
Goldstein, LJ
Gomez, HL
Vallejos, C
Partridge, AH
Dakhil, SR
Martino, S
Barlow, WE
Fabian, CJ
Meyskens, FL
Hortobagyi, GN
Albain, KS
AF Moore, Halle C. F.
Unger, Joseph M.
Phillips, Kelly-Anne
Boyle, Frances M.
Nitre, Erika
Porter, David James
Francis, Prudence A.
Minasian, Lori M.
Gelber, Richard D.
Goldstein, Lori J.
Gomez, Henry Leonidas
Vallejos, Carlos
Partridge, Ann H.
Dakhil, Shaker R.
Martino, Silvana
Barlow, William E.
Fabian, Carol J.
Meyskens, Frank L.
Hortobagyi, Gabriel N.
Albain, Kathy S.
TI Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230)
of LHRH analog during chemotherapy (CT) to reduce ovarian failure in
early-stage, hormone receptor-negative breast cancer: An international
Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Cleveland Clin, Cleveland, OH 44106 USA.
SWOG Stat Ctr, Seattle, WA USA.
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
Mater Hosp, Sydney, NSW, Australia.
Natl Inst Oncol, Budapest, Hungary.
Auckland City Hosp, Dept Oncol, Auckland, New Zealand.
Peter MacCallum Canc Ctr, East Melbourne, Australia.
NCI, Bethesda, MD 20892 USA.
Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
Inst Nacl Enfermedades Neoplas, Lima, Peru.
ONCOSALUD, Lima, Peru.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Wichita Community Clin Oncol Program, Wichita, KS USA.
Angeles Clin & Res Inst, Santa Monica, CA USA.
Canc Res & Biostat, Seattle, WA USA.
Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
Chao Family Comprehens Canc Ctr, Orange, CA USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Loyola Univ, Med Ctr, Maywood, IL 60153 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA LBA505
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201957
ER
PT J
AU Ning, YMM
Kim, T
Maher, VE
Ibrahim, A
Murgo, AJ
Farrell, AT
Keegan, P
Justice, RL
Pazdur, R
AF Ning, Yangmin M.
Kim, Tamy
Maher, Virginia Ellen
Ibrahim, Amna
Murgo, Anthony J.
Farrell, Ann T.
Keegan, Patricia
Justice, Robert L.
Pazdur, Richard
TI FDA breakthrough therapy designation of oncology-products: The
first-year experience.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, US FDA, Silver Spring, MD USA.
US FDA, Rockville, MD 20857 USA.
US FDA, Silver Spring, MD USA.
NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e17502
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200964
ER
PT J
AU O'Reilly, EM
Lowery, MA
Segal, MF
Smith, SC
Moore, MJ
Kindler, HL
Golan, T
Segal, A
Salo-Mullen, EE
Hollywood, E
Epstein, AS
Capanu, M
Moynahan, ME
Fusco, A
Stadler, ZK
Do, RKG
Chen, AP
Yu, KH
Tang, LH
Kelsen, DP
AF O'Reilly, Eileen Mary
Lowery, Maeve Aine
Segal, Michal Fani
Smith, Sloane C.
Moore, Malcolm J.
Kindler, Hedy Lee
Golan, Talia
Segal, Amiel
Salo-Mullen, Erin E.
Hollywood, Ellen
Epstein, Andrew S.
Capanu, Marinela
Moynahan, Mary Ellen
Fusco, Anne
Stadler, Zsofia Kinga
Do, Richard Kinh Gian
Chen, Alice P.
Yu, Kenneth H.
Tang, Laura H.
Kelsen, David Paul
TI Phase IB trial of cisplatin (C), gemcitabine (G), and veliparib (V) in
patients with known or potential BRCA or PALB2-mutated pancreas
adenocarcinoma (PC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Princess Margaret Canc Ctr, Toronto, ON, Canada.
Univ Chicago, Chicago, IL 60637 USA.
Sheba Med Ctr, Tel Hashomer, Israel.
Shaare Zedek Med Ctr, Inst Oncol, Jerusalem, Israel.
Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA.
Natl Canc Inst, Bethesda, MD USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Weill Cornell Med Coll, New York, NY USA.
Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 4023
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203186
ER
PT J
AU O'Sullivan, CCM
Bradbury, I
De Azambuja, E
Perez, EA
Rastogi, P
Spielmann, M
Joensuu, H
Ballman, KV
Costantino, JP
Delaloge, S
Zardavas, D
Piccart-Gebhart, MJ
Zujewski, J
Holmes, EM
Gelber, RD
AF O'Sullivan, Ciara Catherine Maria
Bradbury, Ian
De Azambuja, Evandro
Perez, Edith A.
Rastogi, Priya
Spielmann, Marc
Joensuu, Heikki
Ballman, Karla V.
Costantino, Joseph P.
Delaloge, Suzette
Zardavas, Dimitrios
Piccart-Gebhart, Martine J.
Zujewski, JoAnne
Holmes, Eileen McCormick
Gelber, Richard D.
TI Efficacy of adjuvant trastuzumab (T) compared with no T for patients
(pts) with HER2-positive breast cancer and tumors <= 2cm: A
meta-analysis of the randomized trastuzumab trials.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Bethesda, MD 20892 USA.
Fronfier Sci, Kincraig, England.
Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium.
Mayo Clin, Jacksonville, FL 32224 USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
Inst Gustave Roussy, Villejuif, France.
Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland.
Mayo Clin, Rochester, MN USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Natl Surg Adjuvant Breast & Bowel Project, Biostat Ctr, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA USA.
Inst Cancerol Gustave Roussy, Villejuif, France.
Breast Int Grp, Inst Jules Bordet, Brussels, Belgium.
Frontier Sci Scotland, Kingussie, Inverness, Scotland.
Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 508
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202282
ER
PT J
AU Ojemuyiwa, MA
Karzai, F
Shah, AA
Theoret, MR
Harold, N
Chun, G
Figg, WD
Apolo, AB
Price, DK
Madan, RA
Gulley, JL
Dahut, WL
AF Ojemuyiwa, Michelle A.
Karzai, Fatima
Shah, Avani Atul
Theoret, Marc Robert
Harold, Nancy
Chun, Guinevere
Figg, William Douglas
Apolo, Andrea Borghese
Price, Douglas K.
Madan, Ravi Amrit
Gulley, James L.
Dahut, William L.
TI A safety study of trebananib (AMG 386) and abiraterone in metastatic
castration-resistant prostate cancer (mCRPC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
NCI, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Clin Ctr, NIH, Bethesda, MD 20892 USA.
NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 5074
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203466
ER
PT J
AU Parsons, HM
Schmidt, S
Harlan, LC
Kent, EE
Lynch, C
Smith, AW
Keegan, THM
AF Parsons, Helen M.
Schmidt, Susanne
Harlan, Linda C.
Kent, Erin E.
Lynch, Charles
Smith, Ashley Wilder
Keegan, Theresa H. M.
TI Young and uninsured: Insurance patterns of recently diagnosed adolescent
and young adult cancer survivors in the AYA HOPE study.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Rockville, MD USA.
Univ Iowa, Iowa City, IA USA.
Canc Prevent Inst Calif, Fremont, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10086
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204625
ER
PT J
AU Peppone, LJ
Janelsins, MC
Flannery, MA
Tejani, MA
Peoples, AR
Kamen, CS
Atkins, JN
Giguere, JK
Gaur, R
Frizzell, B
Mustian, KM
AF Peppone, Luke Joseph
Janelsins, Michelle Christine
Flannery, Marie Anne
Tejani, Mohamedtaki Abdulaziz
Peoples, Anita Roselyn
Kamen, Charles Stewart
Atkins, James Norman
Giguere, Jeffrey K.
Gaur, Rakesh
Frizzell, Bart
Mustian, Karen Michelle
TI Cancer patients and their information needs for prediction of symptom
burden during and after treatment: Implications for symptom management.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Rochester, Med Ctr, Dept Surg, Rochester, NY 14642 USA.
Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
Natl Surg Adjuvant Breast & Bowel Project, Goldsboro, NC USA.
SCCC CCOP, Goldsboro, NC USA.
Canc Ctr Carolinas, Seneca, SC USA.
St Lukes Canc Inst, Kansas City, MO USA.
High Point Reg Canc Ctr, High Point, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 9650
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204534
ER
PT J
AU Phillips, AA
Fields, P
Hermine, O
Taylor, G
DelloukIna, ML
Horwitz, SM
Ramos, JC
Menlane, JC
Barta, SK
Or, KM
Kurman, MR
Saunders, A
Grebennik, DO
Conlon, K
AF Phillips, Adrienne Alise
Fields, Paul
Hermine, Olivier
Taylor, Graham
DelloukIna, Maria L.
Horwitz, Steven M.
Ramos, Juan Carlos
Menlane, Jean Cafame
Barta, Stefan K.
Or, Karen M.
Kurman, Michael R.
Saunders, Andrew
Grebennik, Dmitri O.
Conlon, Kevin
TI Anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) or investigator's
choice of chemotherapy in subjects with relapsed or refractory adult
T-cell leukemia-lymphoma (ATL)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Columbia Univ, New York, NY USA.
Guys Hosp, London SE1 9RT, England.
Hop Necker Enfants Malad, Paris, France.
St Marys Hosp, London, England.
Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
CHU Ft France, Fort De France, Martinique.
Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA.
Kyowa Hakko Kirin Pharma, Princeton, NJ USA.
Kyowa Hakko Kirin Pharma Inc, Upper Saddle River, NJ USA.
Kyowa Hakko Kirin Pharma Inc, Edinburgh, Midlothian, Scotland.
Kyowa Hakko Kirin Pharma Inc, Princeton, NJ USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA TPS8622
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202224
ER
PT J
AU Piccart-Gebhart, MJ
Holmes, AP
Baselga, J
De Azambuja, E
Dueck, AC
Viale, G
Zujewski, JA
Goldhirsch, A
Santillana, S
Pritchard, KI
Wolff, AC
Jackisch, C
Lang, I
Untch, M
Smith, IE
Boyle, F
Xu, BH
Gomez, HL
Gelber, RD
Perez, EA
AF Piccart-Gebhart, Martine J.
Holmes, Andrew Peter
Baselga, Jose
De Azambuja, Evandro
Dueck, Amylou C.
Viale, Giuseppe
Zujewski, Jo Anne
Goldhirsch, Aron
Santillana, Sergio
Pritchard, Kathleen I.
Wolff, Antonio C.
Jackisch, Christian
Lang, Istvan
Untch, Michael
Smith, Ian E.
Boyle, Frances
Xu, Binghe
Gomez, Henry Leonidas
Gelber, Richard D.
Perez, Edith A.
TI First results from the phase III ALTTO trial (BIG 2-06; NCCTG [Alliance]
N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L),
trastuzumab alone (T), their sequence (T -> L), or their combination T
plus L) in the adjuvant treatment of HER2-positive early breast cancer
(EBC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Inst Jules Bordet, Breast Int Grp, B-1000 Brussels, Belgium.
Frontier Sci Scotland Ltd, Kincraig, Scotland.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium.
Mayo Clin, Scottsdale, AZ USA.
European Inst Oncol, Div Pathol, Milan, Italy.
NCI, Bethesda, MD 20892 USA.
European Inst Oncol, Div Med Oncol, Milan, Italy.
GlaxoSmithKline, Malvern, PA USA.
Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
Univ Toronto, Toronto, ON, Canada.
Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
Sane Kliniken Offenbach, Offenbach, Germany.
Orszagos Onkol Intezet, Budapest, Hungary.
Helios Klinikum Berlin Buch, Berlin, Germany.
Royal Marsden NHS Fdn Trust, London, England.
Univ Sydney, Mater Hosp, Patricia Ritchie Ctr Canc Care & Res, Sydney, NSW 2006, Australia.
Chinese Acad Med Sci, Canc Hosp, Beijing 100730, Peoples R China.
Inst Nacl Enfermedades Neoplas, Lima, Peru.
Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
Mayo Clin, Jacksonville, FL 32224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA LBA4
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201956
ER
PT J
AU Pichun, MEB
Bala, S
Edgerly, M
Wilkerson, J
Velarde, M
Kotz, HL
Bates, SE
Fojo, AT
AF Pichun, Mauricio Emmanuel Burotto
Bala, Sanjeeve
Edgerly, Maureen
Wilkerson, Julia
Velarde, Margarita
Kotz, Herbert L.
Bates, Susan Elaine
Fojo, Antonio Tito
TI Phase 2 clinical trial of ixabepilone in metastatic cervical carcinoma.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NIH, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 5593
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203577
ER
PT J
AU Polley, E
Monks, A
Morris, J
Rapisarda, A
Kaur, G
Mertins, S
Connelly, J
Slivers, T
Delosh, R
Laudeman, J
Ogle, C
Reinhart, R
Evans, D
Teicher, BA
AF Polley, Eric
Monks, Anne
Morris, Joel
Rapisarda, Annemarie
Kaur, Gurmeet
Mertins, Susan
Connelly, John
Slivers, Thomas
Delosh, Rene
Laudeman, Julie
Ogle, Chad
Reinhart, Russell
Evans, David
Teicher, Beverly A.
TI Sarcoma gene expression and response to approved and investigational
agents: Focus on osteosaccoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Div Canc Treatment & Diag, Rockville, MD USA.
SAIC Frederick Inc, Natl Canc Inst Frederick, Frederick, MD USA.
NCI, DCTD, Bethesda, MD 20892 USA.
Natl Lab Canc Res, Mol Pharmacol Branch, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e22067
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201801
ER
PT J
AU Puhalla, S
Beumer, JH
Pahuja, S
Appleman, LJ
Tawbi, HAH
Stoller, RG
Lee, JJ
Lin, Y
Kiesel, B
Yu, J
Tan, AR
Belani, CP
Chew, HK
Garcia, AA
Morgan, R
Giranda, VL
Shepherd, SP
Chen, AP
Chu, E
AF Puhalla, Shannon
Beumer, Jan Hendrik
Pahuja, Shalu
Appleman, Leonard Joseph
Tawbi, Hussein Abdul-Hassan
Stoller, Ronald G.
Lee, James J.
Lin, Yan
Kiesel, Brian
Yu, Jing
Tan, Antoinette R.
Belani, Chandra Prakash
Chew, Helen K.
Garcia, Agustin A.
Morgan, Robert
Giranda, Vincent L.
Shepherd, Stacie Peacock
Chen, Alice P.
Chu, Edward
TI Final results of a phase 1 study of single-agent veliparib (V) in
patients (pis) with either BRCA1/2-mutated cancer (BRCA plus ),
platinum-refractory ovarian, or basal-like breast cancer (BRCA-wt).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Pittsburgh, Magee Womens Hosp, Med Ctr, Womens Canc Program, Pittsburgh, PA 15213 USA.
Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA.
Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
Penn State Hershey Canc Inst, Hershey, PA USA.
Univ Calif Davis, Sacramento, CA 95817 USA.
Univ So Calif, Los Angeles, CA USA.
City Hope Natl Med Ctr, Duarte, CA USA.
Abbott Labs, Abbott Pk, IL 60064 USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 2570
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202835
ER
PT J
AU Reiss, KA
Herman, JM
Zahurak, M
Brade, AM
Dawson, LA
Scardina, A
Joffe, C
Petito, E
Hacker-Prietz, A
Chen, AP
Temkin, SM
Horiba, N
Siu, LL
Azad, NS
AF Reiss, Kim Anna
Herman, Joseph M.
Zahurak, Marianna
Brade, Anthony M.
Dawson, Laura A.
Scardina, Angela
Joffe, Caitlin
Petito, Emily
Hacker-Prietz, Amy
Chen, Alice P.
Temkin, Sarah Madhu
Horiba, Naomi
Siu, Lillian L.
Azad, Nilofer Saba
TI A phase I study of veliparib (ABT-888) in combination with low-dose
fractionated whole abdominal radiation therapy (LDFWAR) in patients with
advanced solid malignancies and peritoneal carcinomatosis.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
NCI, Bethesda, MD 20892 USA.
Univ Maryland, Baltimore, MD 21201 USA.
Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 4139
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203301
ER
PT J
AU Rodriguez, J
Patel, S
Alpaugh, RK
Palazzo, J
Berger, AC
Avery, TP
Jaslow, RJ
Anne, PR
Simone, NL
Tsangaris, TN
Cristofanilli, M
AF Rodriguez, Joanna
Patel, Sheel
Alpaugh, R. Katherine
Palazzo, Juan
Berger, Adam C.
Avery, Tiffany P.
Jaslow, Rebecca J.
Anne, Pramila R.
Simone, Nicole Lynn
Tsangaris, Theodore N.
Cristofanilli, Massimo
TI A retrospective review of clinical and pathologic aspects of
inflammatory breast cancer: Clues for risk-adapted monitoring and
therapy.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Med Oncol, Philadelphia, PA 19107 USA.
Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg, Philadelphia, PA 19107 USA.
Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
Thomas Jefferson Univ, Dept Radiat Oncol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
NCI, Bethesda, MD 20892 USA.
Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e11506
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200008
ER
PT J
AU Rubinstein, WS
Kattman, BL
Malheiro, AJ
Lee, JM
Maglott, DR
Hem, V
Ovetsky, M
Song, GF
Wallin, C
Katz, KS
Villamarin-Salomon, R
Gu, BS
Fomous, C
Ostell, JM
AF Rubinstein, Wendy S.
Kattman, Brandi L.
Malheiro, Adriana J.
Lee, Jennifer M.
Maglott, Donna R.
Hem, Vichet
Ovetsky, Michael
Song, Guangfeng
Wallin, Craig
Katz, Kenneth S.
Villamarin-Salomon, Ricardo
Gu, Baoshan
Fomous, Cathy
Ostell, James M.
TI The NIH genetic testing registry: Hereditary, pharmacogenetic, and
somatic tests for oncology practice
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 [Rubinstein, Wendy S.; Kattman, Brandi L.; Malheiro, Adriana J.; Lee, Jennifer M.; Maglott, Donna R.; Hem, Vichet; Ovetsky, Michael; Song, Guangfeng; Wallin, Craig; Katz, Kenneth S.; Villamarin-Salomon, Ricardo; Gu, Baoshan; Fomous, Cathy; Ostell, James M.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 11104
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204837
ER
PT J
AU Sargent, DJ
Shi, Q
Yothers, G
Tejpar, S
Bertagnolli, MM
Thibodeau, SN
Andre, T
Labianca, R
Gallinger, S
Hamilton, SR
Monges, G
Pogue-Geile, KL
Paik, S
Klingbiel, D
Roth, A
Pavey, ES
Kim, GP
Sinicrope, FA
AF Sargent, Daniel J.
Shi, Qian
Yothers, Greg
Tejpar, Sabine
Bertagnolli, Monica M.
Thibodeau, Stephen N.
Andre, Thierry
Labianca, Roberto
Gallinger, Steven
Hamilton, Stanley R.
Monges, Genevieve
Pogue-Geile, Katherine L.
Paik, Soonmyung
Klingbiel, Dirk
Roth, Arnaud
Pavey, Emily S.
Kim, George P.
Sinicrope, Frank A.
CA ACCENT Collaborative Grp
TI Prognostic impact of deficient mismatch repair (dMMR) in 7,803 stage
II/III colon cancer (CC) patients (pts): A pooled individual pt data
analysis of 17 adjuvant trials in the ACCENT database.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mayo Clin, Rochester, MN USA.
Natl Surg Adjuvant Breast & Bowel Project Biostat, Pittsburgh, PA USA.
Univ Pittsburgh Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA USA.
Univ Leuven, KUL, Leuven, Belgium.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Mayo Clin Coll Med, Rochester, MN USA.
Hop La Pitie Salpetriere, Paris, France.
Osped Riuniti Bergamo, Dept Oncol, I-24100 Bergamo, Italy.
Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Inst J Paoli I Calmettes, F-13009 Marseille, France.
NSABP, Pittsburgh, PA USA.
Yonsei Univ Coll Med, NSABP, Pittsburgh, PA USA.
Yonsei Univ Coll Med, Severance Biomed Sci Inst, Pittsburgh, PA USA.
Yonsei Univ Coll Med, Dept Med Oncol, Pittsburgh, PA USA.
Swiss Grp Clin Canc Res, Bern, Switzerland.
Univ Hosp Geneva, Geneva, Switzerland.
Mayo Clin, Jacksonville, FL 32224 USA.
NR 0
TC 5
Z9 5
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 3507
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203023
ER
PT J
AU Seibel, N
Hunsberger, S
O'Mara, AM
Budd, T
Friedman, SH
Finnigan, S
Lewis, DR
Freyer, DR
AF Seibel, Nita
Hunsberger, Sally
O'Mara, Ann M.
Budd, Troy
Friedman, Steven H.
Finnigan, Shanda
Lewis, Denise R.
Freyer, David Robert
TI Adolescent and young adult oncology (AYAO) patient enrollments onto
National Cancer Institute (NCI)-supported trials from 2000 to 2010.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
Canc Prevent Div, Bethesda, MD USA.
NCI, Rockville, MD USA.
Childrens Hosp, Los Angeles, CA 90027 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10058
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204597
ER
PT J
AU Shoushtari, AN
D'Angelo, SP
Keohan, ML
Dickson, MA
Gounder, MM
Abdullah, AK
Erinjeri, JP
Bluth, MJ
Ustoyev, Y
Condy, MM
Streicher, H
Takebe, N
DeMatteo, RP
Schwartz, GK
Tap, WD
Carvajal, RD
AF Shoushtari, Alexander Noor
D'Angelo, Sandra P.
Keohan, Mary Louise
Dickson, Mark Andrew
Gounder, Mrinal M.
Abdullah, Abdul Karim
Erinjeri, Joseph Patrick
Bluth, Mark J.
Ustoyev, Yelena
Condy, Mercedes M.
Streicher, Howard
Takebe, Naoko
DeMatteo, Ronald P.
Schwartz, Gary K.
Tap, William D.
Carvajal, Richard D.
TI Combined KIT and CTLA-4 blockade in patients with refractory GIST and
other advanced sarcomas.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
Invest Drug Branch, Canc Therapy Evaluat Program, Rockville, MD USA.
Columbia Univ, Med Ctr, New York, NY USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10521
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204654
ER
PT J
AU Singh, H
Heery, CR
Marte, JL
Farsaci, B
Madan, RA
Coyne, GHO
Palena, C
Rodell, TC
Schlom, J
Gulley, JL
AF Singh, Harpreet
Heery, Christopher Ryan
Marte, Jennifer L.
Farsaci, Bonedetto
Madan, Ravi Amrit
Coyne, Geraldine Helen O'Sullivan
Palena, Claudia
Rodell, Timothy C.
Schlom, Jeffrey
Gulley, James L.
TI A phase I study of a yeast-based therapeutic cancer vaccine, GI-6301,
targeting brachyury in patients with metastatic carcinoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Genitourinary Malignancies Branch, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA.
Ctr Canc Res, Lab Tumor Immunol & Biol, Bethesda, MD USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
NCI, Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA.
Globeimmune Inc, Louisville, CO USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e14026
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200276
ER
PT J
AU Soliman, HH
Minton, SE
Ismail-Khan, R
Han, HS
Janssen, W
Vahanlan, NN
Link, CJ
Strelcher, H
Sullivan, D
Antonia, SJ
AF Soliman, Hatem Hussein
Minton, Susan E.
Ismail-Khan, Roohi
Han, Hyo S.
Janssen, William
Vahanlan, Nicholas N.
Link, Charles J.
Strelcher, Howard
Sullivan, Daniel
Antonia, Scott Joseph
TI A phase 2 study of Ad.p53 DC vaccine in combination with indoximod in
metastatic solid tumors.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
NewLink Genet, Ames, IA USA.
NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA TPS3125
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202063
ER
PT J
AU Somlo, G
Frankel, PH
Luu, TH
Ma, C
Arun, B
Garcia, A
Cigler, T
Cream, L
Harvey, HA
Sparano, JA
Nanda, R
Chew, HK
Moynihan, TJ
Vandat, LT
Goetz, MP
Hurria, A
Mortimer, JE
Gandara, DR
Chen, A
Weitzel, JN
AF Somlo, George
Frankel, Paul Henry
Luu, Thehang H.
Ma, Cynthia
Arun, Banu
Garcia, Agustin
Cigler, Tessa
Cream, Leah
Harvey, Harold A.
Sparano, Joseph A.
Nanda, Rita
Chew, Helen K.
Moynihan, Timothy Jerome
Vandat, Linda T.
Goetz, Matthew P.
Hurria, Arti
Mortimer, Joanne E.
Gandara, David R.
Chen, Alice
Weitzel, Jeffrey N.
TI Phase II trial of single agent PARP inhibitor ABT-888 (veliparib [vel])
followed by postprogression therapy of vel with carboplatin (carb) in
patients (pts) with stage BRCA-associated metastatic breast cancer
(MBC): California Cancer Consortium trial PHII-96
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 City Hope Natl Med Ctr, Duarte, CA USA.
City Hope Beckman Res Inst, Duarte, CA USA.
City Hope Canc Ctr, Beckman Res Inst, Duarte, CA USA.
Washington Univ, Sch Med, St Louis, MO USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Univ So Calif, Los Angeles, CA USA.
Weill Cornell Med Coll, New York, NY USA.
Penn State MS Hershey Med Ctr, Hershey, PA USA.
Hematol Oncol Div, Hershey, PA USA.
Penn State Hershey Canc Inst, Hershey, PA USA.
Montefiore Med Ctr, Bronx, NY 10467 USA.
Univ Chicago, Chicago, IL 60637 USA.
Univ Calif Davis, Sacramento, CA 95817 USA.
Mayo Clin, Rochester, MN USA.
UC Davis Comprehens Canc Ctr, Sacramento, CA USA.
NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 1021
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202443
ER
PT J
AU Spigel, DR
Cereda, R
Litten, JB
Allen, AR
Glaccone, G
Socinski, MA
Camidge, DR
Besse, B
AF Spigel, David R.
Cereda, Roberta
Litten, Jason B.
Allen, Andrew R.
Glaccone, Giuseppe
Socinski, Mark A.
Camidge, D. Ross
Besse, Benjamin
TI A single arm, open-label, phase II study to assess the efficacy of
locitanib in patients with FGFR1-amplified surmounts NSCLC (sqNSCLC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Sarah Cannon Res Inst, Nashville, TN USA.
EOS SpA, Milan, Italy.
Clovis Oncol Inc, San Francisco, CA USA.
Georgetown Univ, Washington, DC USA.
NCI, Bethesda, MD 20892 USA.
Univ Pittsburgh Med Ctr UPMC Canc Pavil, Pittsburgh, PA USA.
Univ Colorado, Ctr Canc, Aurora, CO USA.
Gustave Roussy, Villejuif, France.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA TPS8119
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202199
ER
PT J
AU Stevens, PL
Lenihan, DJ
Ky, B
Warneke, CL
Johnson, MM
Abramson, VG
Mayer, IA
Adams, PT
Campbell, MG
Cheema, PS
Moore, DF
Yeshwant, C
Carver, JR
Fisch, M
AF Stevens, Patrick Lawson
Lenihan, Daniel John
Ky, Bonnie
Warneke, Carla L.
Johnson, Marcy M.
Abramson, Vandana Gupta
Mayer, Ingrid A.
Adams, Paul T.
Campbell, Mark G.
Cheema, Puneet S.
Moore, Dennis Frederic
Yeshwant, Chilakamarri
Carver, Joseph R.
Fisch, Michael
TI Prediction and early detection of anthracycline-related cardiotoxicity
using cardiac biomarkers.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA.
Vanderbilt Univ, Nashville, TN 37235 USA.
Univ Penn, Philadelphia, PA 19104 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA.
Genesys Reg Med Ctr, Natl Surg Adjuvant Breast & Bowel Project, Flint, MI USA.
Canc & Hem Ctr Western Michigan PC, Grand Rapids, MI USA.
Healtheast Care, St Paul, MN USA.
Canc Ctr Kansas, Wichita, KS USA.
Cent Illinois CCOP, Springfield, IL USA.
Hosp Univ Penn, Philadelphia, PA 19104 USA.
NR 0
TC 1
Z9 1
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 9644
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204528
ER
PT J
AU Swartz, C
Recio, L
Phillips, S
Maynor, T
Flgg, WD
AF Swartz, Carol
Recio, Leslie
Phillips, Suzanne
Maynor, Timothy
Flgg, William Douglas
TI Development of a CYP1B1*3 genotyping assay and mechanism of action
studies related to docetaxel treatment in CRPC.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Integrated Syst Lab, Res Triangle Pk, NC USA.
NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e16036
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200792
ER
PT J
AU Tawbi, HAH
Chu, E
Lin, Y
Hyman, DM
Goel, S
Rudek, MA
Dowlati, A
LoRusso, P
Mulkerin, D
Chew, HK
Kiesel, B
Pollice, L
Appleman, LJ
Puhalla, S
Stoller, RG
Lee, JJ
Ivy, P
Beumer, JH
AF Tawbi, Hussein Abdul-Hassan
Chu, Edward
Lin, Yan
Hyman, David Michael
Goel, Sanjay
Rudek, Michelle A.
Dowlati, Afshin
LoRusso, Patricia
Mulkerin, Daniel
Chew, Helen K.
Kiesel, Brian
Pollice, Laura
Appleman, Leonard Joseph
Puhalla, Shannon
Stoller, Ronald G.
Lee, James J.
Ivy, Percy
Beumer, Jan H.
CA NCI-Organ Dysfunction Working Grp
TI Early phase I study of the PARP inhibitor veliparib (ART-888) alone or
in combination with carboplatia/paclitaxel (CP) in patients with varying
degrees of hepatic or renal dysfunction: A study of the NCI-Organ
Dysfunction Working Group (ODG).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Albert Einstein Canc Ctr, New York, NY USA.
Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
Case Western Reserve Univ, Univ Hosp Seidman Canc Ctr, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA.
Univ Calif Davis, Sacramento, CA 95817 USA.
Univ Pittsburgh, Ctr Canc, Med Ctr, Pittsburgh, PA USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
Univ Pittsburgh, Magee Womens Hosp, Med Ctr, Womens Canc Program, Pittsburgh, PA 15213 USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 2572
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202837
ER
PT J
AU Thomas, A
Rajan, A
Berman, AW
Brzezniak, CE
Spittler, AJ
Carter, CA
Guha, U
Wang, Y
Szabo, E
Loehrer, PJ
Giaccone, G
AF Thomas, Anish
Rajan, Arun
Berman, Arlene W.
Brzezniak, Christina E.
Spittler, Aaron John
Carter, Corey Allan
Guha, Udayan
Wang, Yisong
Szabo, Eva
Loehrer, Patrick J.
Giaccone, Giuseppe
TI Phase II trial of sunitinib in patients with thymic epithelial tumors
(TET).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
NCI, Bethesda, MD 20892 USA.
Georgetown Univ, Washington, DC USA.
NR 0
TC 4
Z9 4
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 7525
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203961
ER
PT J
AU Tolaney, SM
Guo, H
Barry, WT
Larrabee, K
Brock, JE
Wagle, N
Van Allen, EM
Paweletz, C
Ivanova, E
Janne, PA
Overmoyer, B
Wright, JJ
Shapiro, G
Winer, EP
Krop, IE
AF Tolaney, Sara M.
Guo, Hao
Barry, William Thomas
Larrabee, Katherine
Brock, Jane E.
Wagle, Nikhil
Van Allen, Eliezer Mendel
Paweletz, Cloud
Ivanova, Elena
Janne, Pasi A.
Overmoyer, Beth
Wright, John Joseph
Shapiro, Geoffrey
Winer, Eric P.
Krop, Ian E.
TI A phase II study of tivantinib (ARQ-197) for metastatic triple-negative
breast cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA.
NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 1106
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202526
ER
PT J
AU Ulahannan, SV
Rahma, OE
Liewehr, DJ
Steinberg, SM
Duffy, AG
AF Ulahannan, Susanna V.
Rahma, Osama E.
Liewehr, David J.
Steinberg, Seth M.
Duffy, Austin G.
TI Systemic chemotherapy for the treatment of advanced biliary tract
carcinoma (BTC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NIH, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e15129
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200528
ER
PT J
AU Varticovski, L
Kim, S
Nickerson, M
Grontved, L
Lao, QZ
Thompson, B
Theodorescu, D
Hager, G
AF Varticovski, Lyuba
Kim, Sohyoung
Nickerson, Michael
Grontved, Lars
Lao, Qizong
Thompson, Bethtrice
Theodorescu, Dan
Hager, Gordon
TI Bladder cancer global unbiased chromatin landscape characterization by
DHS-seq to identify novel features unique for each stage of progression
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Ctr Clin, NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Frederick, MD 21701 USA.
Univ Southern Denmark, Odense, Denmark.
Howard Univ, Washington, DC 20059 USA.
Univ Virginia, Charlottesville, VA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e15500
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613200650
ER
PT J
AU von Mehren, M
George, S
Heinrich, MC
Schuetze, S
Belinsky, MG
Janeway, KA
Rink, L
Ganjoo, KN
Yu, JQ
Yap, JT
Wright, JJ
Van den Abbeele, AD
AF von Mehren, Margaret
George, Suzanne
Heinrich, Michael C.
Schuetze, Scott
Belinsky, Martin G.
Janeway, Katherine A.
Rink, Lori
Ganjoo, Kristen N.
Yu, Jian Qin
Yap, Jeffrey T.
Wright, John Joseph
Van den Abbeele, Annick D.
TI Results of SARC 022, a phase II multicenter study of linsitinib in
pediatric and adult wild-type (WT) gastrointestinal stromal tumors
(GIST).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
OHSU Knight Canc Inst, Portland, OR USA.
Portland VA Med Ctr, Portland, OR USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Stanford Univ, Palo Alto, CA 94304 USA.
Huntsman Canc Inst, Salt Lake City, UT USA.
NCI, Rockville, MD USA.
NR 0
TC 1
Z9 1
U1 3
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10507
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204640
ER
PT J
AU Von Minckwitz, G
O'Shaughnessy, J
Winer, EP
Wolmark, N
Geyer, CE
Huober, JB
Loibl, S
Sikov, WM
Untch, M
McKee, MD
Giranda, VL
Rugo, HS
AF Von Minckwitz, Gunter
O'Shaughnessy, Joyce
Winer, Eric P.
Wolmark, Norman
Geyer, Charles E.
Huober, Jens Bodo
Loibl, Sibylle
Sikov, William M.
Untch, Michael
McKee, Mark D.
Giranda, Vincent L.
Rugo, Hope S.
TI Phase III study evaluating safety and efficacy of the addition of
veliparib plus carboplatin versus the addition of carboplatin to
standard neoadjuvant chemotherapy in subjects with early-stage
triple-negative breast cancer (TNBC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Goethe Univ Frankfurt, German Breast Grp, D-60054 Frankfurt, Germany.
Baylor Charles A Sammons Canc Ctr, Texas Oncol, Dallas, TX USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
Virginia Commonwealth Univ, Sch Med, Richmond, VA USA.
Univ Ulm, D-89069 Ulm, Germany.
Sana Klinikum Offenbach, German Breast Grp, Neu Isenburg, Germany.
Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
Helios Klinikum Berlin Buch, Berlin, Germany.
AbbVie Inc, N Chicago, IL USA.
UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA.
NR 0
TC 1
Z9 1
U1 2
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA TPS1149
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202012
ER
PT J
AU Wagner, LM
Fouladi, M
Ahmed, A
Krailo, MD
Weigel, B
DuBois, SG
Doyle, A
Chen, HX
Blaney, S
AF Wagner, Lars M.
Fouladi, Maryam
Ahmed, Atif
Krailo, Mark D.
Weigel, Brenda
DuBois, Steven G.
Doyle, Austin
Chen, Helen X.
Blaney, Susan
TI Phase II trial of cixutumumab in combination with temsirolimus in
pediatric patients with recurrent or refractory sarcoma: A report from
the Children's Oncology Group.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Kentucky, Lexington, KY USA.
Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
Childrens Mercy Hosp & Clin, Kansas City, MO USA.
Childrens Oncol Grp, Arcadia, CA USA.
Univ Minnesota, Minneapolis, MN USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
NCI, Rockville, MD USA.
NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
Texas Childrens Canc Ctr, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10066
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204605
ER
PT J
AU Wan, X
Yeung, C
Heske, C
Mendoza, A
Helman, LJ
AF Wan, Xiaolin
Yeung, Choh
Heske, Christine
Mendoza, Arnulfo
Helman, Lee J.
TI IGF-IR inhibition effect on a yes/SFK bypass resistance pathway:
Rational basis for cotargeting IGF-IR and yes/SFK kinase in
rhabdomyosarcoma.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Pediat Oncol, CCR, NIH, Bethesda, MD 20892 USA.
NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10045
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204584
ER
PT J
AU Wang, YS
Meltzer, PS
Lau, C
Thomas, A
Rajan, A
Giaccone, G
AF Wang, Yisong
Meltzer, Paul S.
Lau, Christopher
Thomas, Anish
Rajan, Arun
Giaccone, Giuseppe
TI Recurrence of epigenetic gene mutations in thymic epithelial carcinomas
revealed by targeted exome sequencing of cancer-associated genes.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Georgetown Univ, Washington, DC USA.
NCI, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 7529
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203965
ER
PT J
AU Weekes, CD
Lamberts, LE
Borad, MJ
Voortman, J
McWilliams, RR
Diamond, JR
De Vries, E
Verheul, HMW
Lieu, CH
Yue, HB
Wang, YL
Scales, S
Samineni, D
Wood, K
Brunstein, F
Maslyar, DJ
Kim, GP
AF Weekes, Colin D.
Lamberts, Laetitia E.
Borad, Mitesh J.
Voortman, Johannes
McWilliams, Robert R.
Diamond, Jennifer Robinson
De Vries, Elisabeth
Verheul, Henk M. W.
Lieu, Christopher Hanyoung
Yue, Huibin
Wang, Yulei
Scales, Suzie
Samineni, Divya
Wood, Katie
Brunstein, Flavia
Maslyar, Daniel J.
Kim, George P.
TI A phase I study of DMOT4039A, an antibody-drug conjugate (ADC) targeting
mesothelin (MSLN), in patients (pts) with unresectable pancreatic (PC)
or piatinum-resistant ovarian cancer (OC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Colorado, Ctr Canc, Aurora, CO USA.
Univ Med Ctr Groningen, Dept Med Oncol, NL-9713 AV Groningen, Netherlands.
Mayo Clin, Scottsdale, AZ USA.
NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
Mayo Clin, Rochester, MN USA.
Univ Colorado Denver, Div Med Oncol, Aurora, CO USA.
Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, Amsterdam, Netherlands.
Univ Colorado, Denver, CO 80202 USA.
Genentech Inc, San Francisco, CA USA.
Genentech Inc, San Francisco, CA 94080 USA.
Mayo Clin, Jacksonville, FL 32224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 2529
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202794
ER
PT J
AU Weinstein, JN
Kim, J
Creighton, CJ
Akbani, R
Hoadley, KA
Kim, WY
Morgan, MB
Hinoue, T
Rosenberg, JE
Bajorin, DF
Hansel, DE
Al-Ahmadie, H
Gordenin, D
Stuart, JM
Robertson, G
Kucherlapati, R
Laird, PW
Mills, GB
Kwiatkowski, DJ
Lerner, SP
AF Weinstein, John N.
Kim, Jaegil
Creighton, Chad J.
Akbani, Rehan
Hoadley, Katherine A.
Kim, William Y.
Morgan, Margaret B.
Hinoue, Toshinori
Rosenberg, Jonathan E.
Bajorin, Dean F.
Hansel, Donna E.
Al-Ahmadie, Hikmat
Gordenin, Dmitry
Stuart, Joshua M.
Robertson, Gordon
Kucherlapati, Raju
Laird, Peter W.
Mills, Gordon B.
Kwiatkowski, David J.
Lerner, Seth P.
CA Canc Genome Atlas Bladder Canc
TI Comprehensive molecular profiling of urothelial bladder cancer at the
DNA, RNA, and protein levels: A TCGA project.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Broad Inst Harvard & MIT, Cambridge, MA USA.
Baylor Coll Med, Houston, TX 77030 USA.
Univ N Carolina, Chapel Hill, NC USA.
Univ So Calif, Los Angeles, CA USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Cleveland Clin, Cleveland, OH 44106 USA.
NIEHS, Res Triangle Pk, NC 27709 USA.
Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
BC Canc Agcy, Vancouver, BC, Canada.
Harvard Univ, Sch Med, Boston, MA USA.
USC Norris Comprehens Canc Ctr, Los Angeles, CA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 4509
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203314
ER
PT J
AU Widemann, BC
Schwartz, S
Thomas, E
Chauhan, N
King, T
Howard, SC
AF Widemann, Brigitte C.
Schwartz, Stefan
Thomas, Emma
Chauhan, Nikhil
King, Thomas
Howard, Scott C.
TI Immunogenicity and safety of glucarpidase for methotrexate toxicity.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
Charite, D-13353 Berlin, Germany.
BTG, London, England.
BTG Int Inc, London, PA, England.
BTG Int Inc, W Conshohocken, PA USA.
St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e20648
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201621
ER
PT J
AU Widemann, BC
Marcus, LJ
Fisher, MJ
Weiss, BD
Kim, A
Dombi, E
Baldwin, A
Whitcomb, P
Martin, S
Gillespie, A
Doyle, A
AF Widemann, Brigitte C.
Marcus, Leigh Jessica
Fisher, Michael J.
Weiss, Brian D.
Kim, AeRang
Dombi, Eva
Baldwin, Andrea
Whitcomb, Patricia
Martin, Staci
Gillespie, Andrea
Doyle, Austin
TI Phase 1 study of the MEK1/2 inhibitor selumetinib (AZD6244) hydrogen
sulfate in children and young adults with neurofibromatosis type 1 (NF1)
and inoperable plexiform neurofibromas (PNs).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
Childrens Natl Med Ctr, Washington, DC 20010 USA.
Childrens Hosp, Philadelphia, PA 19104 USA.
Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Rockville, MD USA.
NR 0
TC 10
Z9 10
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10018
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204557
ER
PT J
AU Wigle, DA
Mandrekar, SJ
Allen-Ziegler, K
Gesthalter, Y
Holland, P
Aubry, MC
Limburg, PJ
Avi, S
Szabo, E
AF Wigle, Dennis A.
Mandrekar, Sumithra J.
Allen-Ziegler, Katie
Gesthalter, Yaron
Holland, Paul
Aubry, Marie-Christine
Limburg, Paul J.
Avi, Spira
Szabo, Eva
TI Pioglitazone as a candidate chemoprevention agent for lung cancer: A
pilot window trial in early stage NSCLC.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mayo Clin, Rochester, MN USA.
Boston Univ, Sch Med, Boston, MA 02118 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 1581
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202632
ER
PT J
AU Wilson, M
Dhani, NC
Hirte, HW
Welch, S
Steed, H
Martin, LP
Lheureux, S
Martin-Lorente, C
Mackay, H
Butler, MO
Wang, L
Quintos, J
Allen, K
Roman, L
Wright, JJ
Oza, AM
AF Wilson, Michelle
Dhani, Neesha C.
Hirte, Hai W.
Welch, Stephen
Steed, Helen
Martin, Lalnie P.
Lheureux, Stephanie
Martin-Lorente, Cristina
Mackay, Helen
Butler, Marcus O.
Wang, Lisa
Quintos, Judy
Allen, Katie
Roman, Lynda
Wright, John Joseph
Oza, Amit M.
TI Phase II study of XL184 (cabozantinib) in recurrent or metastatic
endometrial cancer: A trial or the PMH, Chicago, and California Phase II
Consortia
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Princess Margaret Canc Ctr, Dept Oncol, Toronto, ON, Canada.
Univ Toronto, Princess Margaret Canc Ctr, Univ Hlth Network, Div Med Oncol & Hematol,Dept Med, Toronto, ON, Canada.
Juravinski Canc Ctr, Hamilton, ON, Canada.
London Reg Canc Program, London, ON, Canada.
Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
Princess Margaret Canc Ctr, Toronto, ON, Canada.
Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada.
Princess Margaret Canc Ctr, Dept Biostat, Toronto, ON, Canada.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
USC Norris Comprehens Canc Ctr, Los Angeles, CA USA.
NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA TPS5629
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202167
ER
PT J
AU Wolmark, N
Mamounas, EP
Baehner, FL
Butler, SM
Tang, G
Jamshidian, F
Sing, AP
Shak, S
Paik, S
AF Wolmark, Norman
Mamounas, Eleftherios P.
Baehner, Frederick L.
Butler, Steven M.
Tang, Gong
Jamshidian, Farid
Sing, Amy P.
Shak, Steven
Paik, Soonmyung
TI Recurrence score and quantitative ER expression to predict in late
distant recurrence risk in ER+ BC after 5 years of tamoxifen.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Allegheny Gen Hosp, Allegheny Canc Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA.
NSABP, Orlando, FL USA.
UF Hlth Canc Ctr, Orlando Hlth, Orlando, FL USA.
Genomic Hlth Inc, Redwood City, CA USA.
NSABP Biostat Ctr, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
Yonsei Univ, Coll Med, NSABP, Pittsburgh, PA USA.
Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Pittsburgh, PA USA.
Yonsei Univ, Coll Med, Dept Med Oncol, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 3
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 11024
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204757
ER
PT J
AU Wong, JR
Morton, LM
Tucker, MA
Abramson, DH
Seddon, J
Sampson, J
Kleinerman, R
AF Wong, Jeannette R.
Morton, Lindsay M.
Tucker, Margaret A.
Abramson, David H.
Seddon, Johanna
Sampson, Joshua
Kleinerman, Ruth
TI Risk of subsequent malignant neoplasms in long-term retinoblastoma
survivors following chemotherapy and radiotherapy.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Rockville, MD USA.
NCI, Bethesda, MD 20892 USA.
NIH, Bethesda, MD 20892 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 10079
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613204618
ER
PT J
AU Wright, M
AF Wright, Matthew
TI Safety of percutaneous, image guided biopsy in a series of children and
young adults with pediatric sarcomas
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 [Wright, Matthew] NCI, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e21026
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201717
ER
PT J
AU Yang, SX
Rubinstein, L
Nguyen, D
Tomaszewski, JE
Takebe, N
Ivy, P
Doroshow, JH
AF Yang, Sherry X.
Rubinstein, Larry
Dat Nguyen
Tomaszewski, Joseph E.
Takebe, Naoko
Ivy, Percy
Doroshow, James H.
TI Association of Notch-1 phenotype with clinical stage progression in
non-small cell lung cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
Div Canc Treatment & Diag, Bethesda, MD USA.
NCI, Bethesda, MD 20892 USA.
Canc Therapy Evaluat Program, Invest Drug Branch, Rockville, MD USA.
NR 0
TC 3
Z9 3
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA e22123
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613201852
ER
PT J
AU Yothers, G
George, TJ
Petrelli, NJ
O'Connell, MJ
Beart, RW
Allegra, CJ
Roh, MS
Lopa, SH
Colangelo, LH
Sharif, S
Wolmark, N
AF Yothers, Greg
George, Thomas J.
Petrelli, Nicholas J.
O'Connell, Michael J.
Beart, Robert W.
Allegra, Carmen Joseph
Roh, Mark S.
Lopa, Samia H.
Colangelo, Linda H.
Sharif, Saima
Wolmark, Norman
TI Neoadjuvant rectal cancer (RC) score to predict survival: Potential
surrogate endpoint for early phase trials.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Natl Surg Adjuvant Breast & Bowel Project Biostat, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
NSABP, Gainesville, FL USA.
Univ Florida, Gainesville, FL USA.
NSABP, Newark, DE USA.
Helen F Graham Canc Ctr & Res Inst, Newark, DE USA.
NSABP, Pittsburgh, PA USA.
NSABP, Glendale, CA USA.
Glendale Mem Hosp, Glendale, CA USA.
NSABP, Orlando, FL USA.
UF Hlth Canc Ctr Orlando Hlth, Orlando, FL USA.
NSABP Biostat Ctr, Pittsburgh, PA USA.
Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 3533
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203049
ER
PT J
AU Younes, A
Zinzani, PL
Sehn, LH
Johnson, PWM
Gascoyne, RD
Ahmedi, T
Bellew, KM
Verrneulen, J
Zhuang, SH
Zhuang
Staudt, LM
Wilson, WH
AF Younes, Anas
Zinzani, Pier Luigi
Sehn, Laurie Helen
Johnson, Peter W. M.
Gascoyne, Randy D.
Ahmedi, Tahamtan
Bellew, Kevin M.
Verrneulen, Jessica
Zhuang, Sen Hong
Sun, Stevan
Staudt, Louis M.
Wilson, Wyndham Hopkins
TI A randomized, double-blind, placebo-controlled phase 3 study of
ibrutinib in combination with rituximab, cyclophosphamide, doxorubicin,
vincristine, and prednisone (R-CHOP) us subjects with newly diagnosed
nongerminal center B-cell subtype of diffuse large B-cell lymphoma
(DLBCL)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Univ Bologna, Inst Hematol & Med Oncol, Bologna, Italy.
British Columbia Canc Agcy, Ctr Lymphoid Canc, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada.
Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
Univ Southampton, Canc Res UK Ctr, Southampton, Hants, England.
British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada.
Janssen Res & Dev, Raritan, NJ USA.
Janssen Res & Dev, Spring House, PA USA.
Janssen Res & Dev, Leiden, Netherlands.
NCI, Bethesda, MD 20892 USA.
RI Zinzani, Pier Luigi/J-9182-2016
OI Zinzani, Pier Luigi/0000-0002-2112-2651
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA TPS8615
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613202217
ER
PT J
AU Zeidner, JF
Foster, MC
Blackford, A
Litzow, MR
Morris, L
Strickland, SA
Lancet, JE
Bose, P
Levy, MY
Tibes, R
Gojo, I
Gocke, CD
Rosner, GL
Greer, J
Cain, JM
Little, RF
Wright, JJ
Doyle, LA
Smith, BD
Karp, JE
AF Zeidner, Joshua F.
Foster, Matthew C.
Blackford, Amanda
Litzow, Mark Robert
Morris, Lawrence
Strickland, Stephen Anthony
Lancet, Jeffrey E.
Bose, Prithviraj
Levy, M. Yair
Tibes, Raoul
Gojo, Ivana
Gocke, Christopher D.
Rosner, Gary L.
Greer, Jacqueline
Cain, Joan M.
Little, Richard F.
Wright, John Joseph
Doyle, L. Austin
Smith, B. Douglas
Karp, Judith E.
TI Randomized multicenter phase II trial of timed-sequential therapy with
flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus
"7+3" for adults with newly diagnosed acute myeloid leukemia (AML).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology
CY MAY 30-JUN 03, 2014
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA.
Mayo Clin, Rochester, MN USA.
BMT Grp Georgia, Atlanta, GA USA.
Vanderbilt Univ, Med Ctr, Nashville, TN 37235 USA.
Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
VCU Masey Canc Ctr, Richmond, VA USA.
Texas Oncol Baylor Charles Sammons Canc Ctr, Dallas, TX USA.
Mayo Clin, Scottsdale, AZ USA.
Natl Canc Inst, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2014
VL 32
IS 15
SU S
MA 7002
PG 1
WC Oncology
SC Oncology
GA CN7KL
UT WOS:000358613203822
ER
PT J
AU Butler, CL
Lucas, O
Wuchty, S
Xue, B
Uversky, VN
White, M
AF Butler, Carrie L.
Lucas, Olivier
Wuchty, Stefan
Xue, Bin
Uversky, Vladimir N.
White, Michael
TI Identifying Novel Cell Cycle Proteins in Apicomplexa Parasites through
Co-Expression Decision Analysis
SO PLOS ONE
LA English
DT Article
ID TOXOPLASMA-GONDII; PLASMODIUM-FALCIPARUM; FUNCTIONAL-ANALYSIS; INTRINSIC
DISORDER; MALARIA; REVEALS; SEQUENCE; GENES; IDENTIFICATION;
CYTOSKELETON
AB Hypothetical proteins comprise roughly half of the predicted gene complement of Toxoplasma gondii and Plasmodium falciparum and represent the largest class of uniquely functioning proteins in these parasites. Following the idea that functional relationships can be informed by the timing of gene expression, we devised a strategy to identify the core set of apicomplexan cell division cycling genes with important roles in parasite division, which includes many uncharacterized proteins. We assembled an expanded list of orthologs from the T. gondii and P. falciparum genome sequences (2781 putative orthologs), compared their mRNA profiles during synchronous replication, and sorted the resulting set of dual cell cycle regulated orthologs (744 total) into protein pairs conserved across many eukaryotic families versus those unique to the Apicomplexa. The analysis identified more than 100 ortholog gene pairs with unknown function in T. gondii and P. falciparum that displayed co-conserved mRNA abundance, dynamics of cyclical expression and similar peak timing that spanned the complete division cycle in each parasite. The unknown cyclical mRNAs encoded a diverse set of proteins with a wide range of mass and showed a remarkable conservation in the internal organization of ordered versus disordered structural domains. A representative sample of cyclical unknown genes (16 total) was epitope tagged in T. gondii tachyzoites yielding the discovery of new protein constituents of the parasite inner membrane complex, key mitotic structures and invasion organelles. These results demonstrate the utility of using gene expression timing and dynamic profile to identify proteins with unique roles in Apicomplexa biology.
C1 [Butler, Carrie L.; Lucas, Olivier; Xue, Bin; Uversky, Vladimir N.] Univ S Florida, Morsani Coll Med, Dept Mol Med, Tampa, FL USA.
[White, Michael] Univ S Florida, Coll Publ Hlth, Dept Global Hlth, Tampa, FL 33620 USA.
[White, Michael] Univ S Florida, Florida Ctr Drug Discovery & Innovat, Tampa, FL USA.
[Wuchty, Stefan] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
RP White, M (reprint author), Univ S Florida, Coll Publ Hlth, Dept Global Hlth, Tampa, FL 33620 USA.
EM mwhite.usf@gmail.com
RI Uversky, Vladimir/F-4515-2011
OI Uversky, Vladimir/0000-0002-4037-5857
FU National Institutes of Health [R01-AI077662, R01-AI089885]
FX This work was supported by grants from the National Institutes of Health
to MWW (R01-AI077662 and R01-AI089885). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 66
TC 2
Z9 2
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 19
PY 2014
VL 9
IS 5
AR e97625
DI 10.1371/journal.pone.0097625
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN9SK
UT WOS:000340948600052
PM 24841368
ER
PT J
AU Krupovic, M
Makarova, KS
Forterre, P
Prangishvili, D
Koonin, EV
AF Krupovic, Mart
Makarova, Kira S.
Forterre, Patrick
Prangishvili, David
Koonin, Eugene V.
TI Casposons: a new superfamily of self-synthesizing DNA transposons at the
origin of prokaryotic CRISPR-Cas immunity
SO BMC BIOLOGY
LA English
DT Article
DE Mobile genetic elements; CRISPR-Cas system; Adaptive immunity;
Transposons; Archaea; DNA polymerases
ID INSERTION SEQUENCES; ESCHERICHIA-COLI; GENOME SEQUENCE; EVOLUTION;
PROTEIN; ELEMENTS; ARCHAEA; SYSTEMS; VIRUSES; EUKARYOTES
AB Background: Diverse transposable elements are abundant in genomes of cellular organisms from all three domains of life. Although transposons are often regarded as junk DNA, a growing body of evidence indicates that they are behind some of the major evolutionary innovations. With the growth in the number and diversity of sequenced genomes, previously unnoticed mobile elements continue to be discovered.
Results: We describe a new superfamily of archaeal and bacterial mobile elements which we denote casposons because they encode Cas1 endonuclease, a key enzyme of the CRISPR-Cas adaptive immunity systems of archaea and bacteria. The casposons share several features with self-synthesizing eukaryotic DNA transposons of the Polinton/Maverick class, including terminal inverted repeats and genes for B family DNA polymerases. However, unlike any other known mobile elements, the casposons are predicted to rely on Cas1 for integration and excision, via a mechanism similar to the integration of new spacers into CRISPR loci. We identify three distinct families of casposons that differ in their gene repertoires and evolutionary provenance of the DNA polymerases. Deep branching of the casposon-encoded endonuclease in the Cas1 phylogeny suggests that casposons played a pivotal role in the emergence of CRISPR-Cas immunity.
Conclusions: The casposons are a novel superfamily of mobile elements, the first family of putative self-synthesizing transposons discovered in prokaryotes. The likely contribution of capsosons to the evolution of CRISPR-Cas parallels the involvement of the RAG1 transposase in vertebrate immunoglobulin gene rearrangement, suggesting that recruitment of endonucleases from mobile elements as ready-made tools for genome manipulation is a general route of evolution of adaptive immunity.
C1 [Krupovic, Mart; Forterre, Patrick; Prangishvili, David] Inst Pasteur, Unit Biol Mol Gene Chez Extremophiles, F-75015 Paris, France.
[Makarova, Kira S.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Krupovic, M (reprint author), Inst Pasteur, Unit Biol Mol Gene Chez Extremophiles, 25 Rue Docteur Roux, F-75015 Paris, France.
EM krupovic@pasteur.fr; koonin@ncbi.nlm.nih.gov
RI Krupovic, Mart/I-4209-2012
OI Krupovic, Mart/0000-0001-5486-0098
FU European Molecular Biology Organization [ASTF 82-2014]; US Department of
Health and Human Services; European Union [340440]; Agence nationale de
la recherche (ANR) program BLANC, project EXAVIR
FX MK was partly supported by the European Molecular Biology Organization
(ASTF 82-2014). EVK and KSM are supported by intramural funds of the US
Department of Health and Human Services (to the National Library of
Medicine). PF is supported by the European Union's Seventh Framework
Program (FP/2007-2013) / Project EVOMOBIL - ERC Grant Agreement no.
340440. DP is supported by the Agence nationale de la recherche (ANR)
program BLANC, project EXAVIR.
NR 77
TC 36
Z9 36
U1 3
U2 43
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7007
J9 BMC BIOL
JI BMC Biol.
PD MAY 19
PY 2014
VL 12
AR 36
DI 10.1186/1741-7007-12-36
PG 12
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AI4CY
UT WOS:000336814400001
PM 24884953
ER
PT J
AU Gombold, J
Karakasidis, S
Niksa, P
Podczasy, J
Neumann, K
Richardson, J
Sane, N
Johnson-Leva, R
Randolph, V
Sadoff, J
Minor, P
Schmidt, A
Duncan, P
Sheets, RL
AF Gombold, James
Karakasidis, Stephen
Niksa, Paula
Podczasy, John
Neumann, Kitti
Richardson, James
Sane, Nandini
Johnson-Leva, Renita
Randolph, Valerie
Sadoff, Jerald
Minor, Phillip
Schmidt, Alexander
Duncan, Paul
Sheets, Rebecca L.
TI Systematic evaluation of in vitro and in vivo adventitious virus assays
for the detection of viral contamination of cell banks and biological
products
SO VACCINE
LA English
DT Article; Proceedings Paper
CT 4th Vaccine Technology Conference in the Engineering Conferences
International (ECI)
CT 4th Vaccine Technology Conference in the Engineering Conferences
International (ECI)
CY MAY 20-24, 2012
CY MAY 20-24, 2012
CL Albufeira, PORTUGAL
CL Albufeira, PORTUGAL
DE Vaccines; Viral safety; In vitro; In vivo; Adventitious agents; 3Rs
AB Viral vaccines and the cell substrates used to manufacture them are subjected to tests for adventitious agents, including viruses, contaminate. Some of the compendial methods (in vivo and in vitro in cell culture) were established in the mid-20th century. These methods have not been subjected to current assay validation, as new methods would need to be. This study was undertaken to provide insight into the breadth (selectivity) and sensitivity (limit of detection) of the routine methods, two such validation parameters. Sixteen viral stocks were prepared and characterized. These stocks were tested in serial dilutions by the routine methods to establish which viruses were detected by which methods and above what limit of detection. Sixteen out of sixteen viruses were detected in vitro, though one (bovine viral diarrhea virus) required special conditions to detect and another (rubella virus) was detected with low sensitivity. Many were detected at levels below 1 TCID50 or PFU (titers were established on the production cell line in most cases). In contrast, in vivo, only 6/11 viruses were detected, and 4 of these were detected only at amounts one or more logs above 1 TCID50 or PFU. Only influenza virus and vesicular stomatitis virus were detected at lower amounts in vivo than in vitro. Given the call to reduce, refine, or replace (3Rs) the use of animals in product safety testing and the emergence of new technologies for the detection of viruses, a re-examination of the current adventitious virus testing strategies seems warranted. Suggested pathways forward are offered. Published by Elsevier Ltd.
C1 [Gombold, James; Karakasidis, Stephen; Podczasy, John; Neumann, Kitti] Charles River Labs, Malvern, PA 19355 USA.
[Niksa, Paula] Charles River Labs, Wilmington, MA 01887 USA.
[Richardson, James; Sane, Nandini; Johnson-Leva, Renita] Adv BioSci Labs, Rockville, MD 20850 USA.
[Randolph, Valerie] Wyeth, Pearl River, NY 10965 USA.
[Sadoff, Jerald] Crucell, NL-2301 CA Leiden, Netherlands.
[Minor, Phillip] Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England.
[Schmidt, Alexander] GSK Vaccines, NIH, NIAID, B-1330 Rixensart, Belgium.
[Duncan, Paul] Merck & Co Inc, West Point, PA 19486 USA.
[Sheets, Rebecca L.] NIAID, NIH, Div Aids, Bethesda, MD 20892 USA.
RP Sheets, RL (reprint author), NIAID, NIH, Div Aids, 67008 Rockledge Dr,Rm 5145, Bethesda, MD 20892 USA.
EM rsheets@grimalkinpartners.com
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services
[HHSN266200400045C]
FX This project has been funded in whole or in part with federal funds from
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services, under
Contract No. HHSN266200400045C.
NR 11
TC 5
Z9 5
U1 1
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD MAY 19
PY 2014
VL 32
IS 24
SI SI
BP 2916
EP 2926
DI 10.1016/j.vaccine.2014.02.021
PG 11
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AI2RD
UT WOS:000336704900025
PM 24681273
ER
PT J
AU Shinomiya, K
Karuppudurai, T
Lin, TY
Lu, ZY
Lee, CH
Meinertzhagen, IA
AF Shinomiya, Kazunori
Karuppudurai, Thangavel
Lin, Tzu-Yang
Lu, Zhiyuan
Lee, Chi-Hon
Meinertzhagen, Ian A.
TI Candidate Neural Substrates for Off-Edge Motion Detection in Drosophila
SO CURRENT BIOLOGY
LA English
DT Article
ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; ACTIVATED POTASSIUM CHANNEL;
VISUAL-SYSTEM; SPECTRAL PREFERENCE; SENSITIVE PATHWAYS; WILD-TYPE;
VISION; FLY; MELANOGASTER; CIRCUIT
AB Background: In the fly's visual motion pathways, two cell types-T4 and T5-are the first known relay neurons to signal small-field direction-selective motion responses [1]. These cells then feed into large tangential cells that signal wide-field motion. Recent studies have identified two types of columnar neurons in the second neuropil, or medulla, that relay input to 14 from L1, the ON-channel neuron in the first neuropil, or lamina, thus providing a candidate substrate for the elementary motion detector (EMD) [2]. Interneurons relaying the OFF channel from L1's partner, L2, to T5 are so far not known, however.
Results: Here we report that multiple types of transmedulla (Tm) neurons provide unexpectedly complex inputs to T5 at their terminals in the third neuropil, or lobula. From the L2 pathway, single-column input comes from Tm1 and Tm2 and multiple-column input from Tm4 cells. Additional input to T5 comes from Tm9, the medulla target of a third lamina interneuron, L3, providing a candidate substrate for L3's combinatorial action with L2 [3]. Most numerous, Tm2 and Tm9's input synapses are spatially segregated on T5's dendritic arbor, providing candidate anatomical substrates for the two arms of a 15 EMD circuit; Tm1 and Tm2 provide a second. Transcript profiling indicates that T5 expresses both nicotinic and muscarinic cholinoceptors, qualifying T5 to receive cholinergic inputs from Tm9 and Tm2, which both express choline acetyltransferase (ChAT).
Conclusions: We hypothesize that T5 computes small-field motion signals by integrating multiple cholinergic Tm inputs using nicotinic and muscarinic cholinoceptors.
C1 [Shinomiya, Kazunori; Lu, Zhiyuan; Meinertzhagen, Ian A.] Dalhousie Univ, Life Sci Ctr, Dept Psychol & Neurosci, Halifax, NS B3H 4R2, Canada.
[Meinertzhagen, Ian A.] Dalhousie Univ, Life Sci Ctr, Dept Biol, Halifax, NS B3H 4R2, Canada.
[Karuppudurai, Thangavel; Lin, Tzu-Yang; Lee, Chi-Hon] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuronal Connect, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Meinertzhagen, IA (reprint author), Dalhousie Univ, Life Sci Ctr, Dept Psychol & Neurosci, Halifax, NS B3H 4R2, Canada.
EM iam@dal.ca
OI Meinertzhagen, Ian/0000-0002-6578-4526
FU NIH [EY-03592]; Eunice Kennedy Shriven National Institute of Child
Health and Human Development, NIH [Z01-HD008776]; Government of Canada
Post-Doctoral Research Fellowship from Foreign Affairs and International
Trade Canada (DFAIT)
FX This work was supported by NIH grant EY-03592 (to I.A.M.) and the
Intramural Research Program of the Eunice Kennedy Shriven National
Institute of Child Health and Human Development, NIH (grant Z01-HD008776
to C.-H. L.). During part of his work, K.S. was in receipt of a
Government of Canada Post-Doctoral Research Fellowship from Foreign
Affairs and International Trade Canada (DFAIT). We thank Jane Anne Home
(Dalhousie) for assistance in making the EM reconstructions, Chun-Yuan
Ting (NIH) for assistance in analyzing synaptic distribution and
immunohistochemistry, Mark Stopfer (NIH) for helpful discussions, and
Axel Borst (Martinsried) for reagents and communicated intelligence.
NR 59
TC 29
Z9 29
U1 2
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
EI 1879-0445
J9 CURR BIOL
JI Curr. Biol.
PD MAY 19
PY 2014
VL 24
IS 10
BP 1062
EP 1070
DI 10.1016/j.cub.2014.03.051
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AH7UE
UT WOS:000336340000028
PM 24768048
ER
PT J
AU Beach, JR
Shao, L
Remmert, K
Li, D
Betzig, E
Hammer, JA
AF Beach, Jordan R.
Shao, Lin
Remmert, Kirsten
Li, Dong
Betzig, Eric
Hammer, John A., III
TI Nonmuscle Myosin II Isoforms Coassemble in Living Cells
SO CURRENT BIOLOGY
LA English
DT Article
ID LIVE CELLS; STRUCTURED ILLUMINATION; FILAMENTS; DEFECTS; TAIL;
PHOSPHORYLATION; MICROSCOPY; MIGRATION; DYNAMICS; ADHESION
AB Nonmuscle myosin II (NM II) powers myriad developmental and cellular processes, including embryogenesis, cell migration, and cytokinesis [1]. To exert its functions, monomers of NM II assemble into bipolar filaments that produce a contractile force on the actin cytoskeleton. Mammalian cells express up to three isoforms of NM II (NM IIA, IIB, and IIC), each of which possesses distinct biophysical properties and supports unique as well as redundant cellular functions [2-8]. Despite previous efforts [9-13], it remains unclear whether NM II isoforms assemble in living cells to produce mixed (heterotypic) bipolar filaments or whether filaments consist entirely of a single isoform (homotypic). We addressed this question using fluorescently tagged versions of NM IIA, IIB, and IIC, isoform-specific immunostaining of the endogenous proteins, and two-color total internal reflection fluorescence structured-illumination microscopy, or TIRF-SIM, to visualize individual myosin II bipolar filaments inside cells. We show that NM II isoforms coassemble into heterotypic filaments in a variety of settings, including various types of stress fibers, individual filaments throughout the cell, and the contractile ring. We also show that the differential distribution of NM IIA and NM IIB typically seen in confocal micrographs of well-polarized cells is reflected in the composition of individual bipolar filaments. Interestingly, this differential distribution is less pronounced in freshly spread cells, arguing for the existence of a sorting mechanism acting over time. Together, our work argues that individual NM II isoforms are potentially performing both isoform-specific and isoform-redundant functions while coassembled with other NM II isoforms.
C1 [Beach, Jordan R.; Remmert, Kirsten; Hammer, John A., III] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
[Shao, Lin; Li, Dong; Betzig, Eric] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
RP Beach, JR (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
EM jordan.beach@nih.gov; hammerj@nhibi.nih.gov
FU Intramural NIH HHS [Z01 HL000514-24]
NR 30
TC 38
Z9 38
U1 2
U2 44
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
EI 1879-0445
J9 CURR BIOL
JI Curr. Biol.
PD MAY 19
PY 2014
VL 24
IS 10
BP 1160
EP 1166
DI 10.1016/j.cub.2014.03.071
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AH7UE
UT WOS:000336340000042
PM 24814144
ER
PT J
AU Zipprer, EM
Neggers, M
Kushwaha, A
Rayavara, K
Desai, SA
AF Zipprer, Elizabeth M.
Neggers, McKinzie
Kushwaha, Ambuj
Rayavara, Kempaiah
Desai, Sanjay A.
TI A kinetic fluorescence assay reveals unusual features of Ca++ uptake in
Plasmodium falciparum-infected erythrocytes
SO MALARIA JOURNAL
LA English
DT Article
DE Calcium channels; Malaria parasites; Human erythrocytes; Fluo-8;
Fluorescence kinetics; Antimalarial drug discovery
ID RED-BLOOD-CELLS; SURFACE ANION CHANNEL; THROUGHPUT SCREENING ASSAYS;
MALARIA-PARASITE; CALCIUM-TRANSPORT; NUTRIENT-UPTAKE; RESISTANCE; CA2+;
SELECTIVITY; VALIDATION
AB Background: To facilitate development within erythrocytes, malaria parasites increase their host cell uptake of diverse solutes including Ca++. The mechanism and molecular basis of increased Ca++ permeability remains less well studied than that of other solutes.
Methods: Based on an appropriate Ca++ affinity and its greater brightness than related fluorophores, Fluo-8 was selected and used to develop a robust fluorescence-based assay for Ca++ uptake by human erythrocytes infected with Plasmodium falciparum.
Results: Both uninfected and infected cells exhibited a large Ca++-dependent fluorescence signal after loading with the Fluo-8 dye. Probenecid, an inhibitor of erythrocyte organic anion transporters, abolished the fluorescence signal in uninfected cells; in infected cells, this agent increased fluorescence via mechanisms that depend on parasite genotype. Kinetic fluorescence measurements in 384-well microplates revealed that the infected cell Ca++ uptake is not mediated by the plasmodial surface anion channel (PSAC), a parasite nutrient channel at the host membrane; it also appears to be distinct from mammalian Ca++ channels. Imaging studies confirmed a low intracellular Ca++ in uninfected cells and higher levels in both the host and parasite compartments of infected cells. Parasite growth inhibition studies revealed a conserved requirement for extracellular Ca++.
Conclusions: Nondestructive loading of Fluo-8 into human erythrocytes permits measurement of Ca++ uptake kinetics. The greater Ca++ permeability of cells infected with malaria parasites is apparent when probenecid is used to inhibit Fluo-8 efflux at the host membrane. This permeability is mediated by a distinct pathway and may be essential for intracellular parasite development. The miniaturized assay presented here should help clarify the precise transport mechanism and may identify inhibitors suitable for antimalarial drug development.
C1 [Zipprer, Elizabeth M.; Neggers, McKinzie; Kushwaha, Ambuj; Rayavara, Kempaiah; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
EM sdesai@niaid.nih.gov
FU Intramural NIAID Research Opportunities program (INRO); Intramural
Research Program of the National Institutes of Health, National
Institute of Allergy and Infectious Diseases, USA
FX EMZ and MN received support from the Intramural NIAID Research
Opportunities program (INRO). This research was supported by the
Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases, USA.
NR 48
TC 2
Z9 2
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD MAY 18
PY 2014
VL 13
AR 184
DI 10.1186/1475-2875-13-184
PG 11
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA AI1SJ
UT WOS:000336632100001
PM 24885754
ER
PT J
AU Murphy, SC
Hermsen, CC
Douglas, AD
Edwards, NJ
Petersen, I
Fahle, GA
Adams, M
Berry, AA
Billman, ZP
Gilbert, SC
Laurens, MB
Leroy, O
Lyke, KE
Plowe, CV
Seilie, AM
Strauss, KA
Teelen, K
Hill, AVS
Sauerwein, RW
AF Murphy, Sean C.
Hermsen, Cornelus C.
Douglas, Alexander D.
Edwards, Nick J.
Petersen, Ines
Fahle, Gary A.
Adams, Matthew
Berry, Andrea A.
Billman, Zachary P.
Gilbert, Sarah C.
Laurens, Matthew B.
Leroy, Odile
Lyke, Kristen E.
Plowe, Christopher V.
Seilie, Annette M.
Strauss, Kathleen A.
Teelen, Karina
Hill, Adrian V. S.
Sauerwein, Robert W.
TI External Quality Assurance of Malaria Nucleic Acid Testing for Clinical
Trials and Eradication Surveillance
SO PLOS ONE
LA English
DT Article
ID REAL-TIME PCR; POLYMERASE-CHAIN-REACTION; SEQUENCE-BASED AMPLIFICATION;
PLASMODIUM-FALCIPARUM DNA; RAPID DIAGNOSTIC-TESTS; NONREPLICATING
SPOROZOITE VACCINE; MEDIATED ISOTHERMAL AMPLIFICATION; T-CELL IMMUNITY;
INFECTED MOSQUITOS; ENDEMIC AREA
AB Nucleic acid testing (NAT) for malaria parasites is an increasingly recommended diagnostic endpoint in clinical trials of vaccine and drug candidates and is also important in surveillance of malaria control and elimination efforts. A variety of reported NAT assays have been described, yet no formal external quality assurance (EQA) program provides validation for the assays in use. Here, we report results of an EQA exercise for malaria NAT assays. Among five centers conducting controlled human malaria infection trials, all centers achieved 100% specificity and demonstrated limits of detection consistent with each laboratory's pre-stated expectations. Quantitative bias of reported results compared to expected results was generally <0.5 log(10) parasites/mL except for one laboratory where the EQA effort identified likely reasons for a general quantitative shift. The within-laboratory variation for all assays was low at <10% coefficient of variation across a range of parasite densities. Based on this study, we propose to create a Molecular Malaria Quality Assessment program that fulfills the need for EQA of malaria NAT assays worldwide.
C1 [Murphy, Sean C.; Billman, Zachary P.; Seilie, Annette M.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Murphy, Sean C.; Billman, Zachary P.; Seilie, Annette M.] Univ Washington, Ctr Emerging & Re Emerging Infect Dis, Seattle, WA 98195 USA.
[Hermsen, Cornelus C.; Teelen, Karina; Sauerwein, Robert W.] Radboud Univ Nijmegen Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands.
[Douglas, Alexander D.; Edwards, Nick J.; Gilbert, Sarah C.; Hill, Adrian V. S.] Univ Oxford, Jenner Inst, Oxford, England.
[Petersen, Ines; Leroy, Odile] European Vaccine Initiat, Heidelberg, Germany.
[Fahle, Gary A.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Adams, Matthew; Berry, Andrea A.; Laurens, Matthew B.; Lyke, Kristen E.; Plowe, Christopher V.; Strauss, Kathleen A.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA.
[Adams, Matthew; Berry, Andrea A.; Laurens, Matthew B.; Lyke, Kristen E.; Plowe, Christopher V.; Strauss, Kathleen A.] Univ Maryland, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21201 USA.
RP Murphy, SC (reprint author), Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
EM murphysc@uw.edu
RI Douglas, Alexander/E-7040-2012; Sauerwein, Robert/C-8519-2013; Hermsen,
C.C./L-4368-2015; Laurens, Matthew/E-7293-2013
OI Edwards, Nick/0000-0002-7030-7839; Douglas,
Alexander/0000-0002-5410-7562; Laurens, Matthew/0000-0003-3874-581X
FU UW Center for AIDS Research [AI27757]; non-UW labs
FX This work was supported using intra-Departmental funds (to SCM) and
resources from the UW Center for AIDS Research (AI27757). Testing at
non-UW labs was paid for by those institutions using in-house support.
No commercial funding was used for this study. Study design, data
collection, analysis, decision to publish and preparation of the
manuscript were wholly the responsibility of the listed authors and no
one else. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 76
TC 6
Z9 6
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 16
PY 2014
VL 9
IS 5
AR e97398
DI 10.1371/journal.pone.0097398
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM1NZ
UT WOS:000339614800042
PM 24838112
ER
PT J
AU Kumar, S
Yedjou, CG
Tchounwou, PB
AF Kumar, Sanjay
Yedjou, Clement G.
Tchounwou, Paul B.
TI Arsenic trioxide induces oxidative stress, DNA damage, and mitochondrial
pathway of apoptosis in human leukemia (HL-60) cells
SO JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
LA English
DT Article
DE Arsenic trioxide; Oxidative stress; DNA damage; Apoptosis; HL-60 cells
ID ACUTE PROMYELOCYTIC LEUKEMIA; DOWN-REGULATION; CANCER CELLS; IN-VITRO;
COMPLETE REMISSION; CARCINOMA CELLS; RETINOIC ACID; CYCLE ARREST;
INDUCTION; LINES
AB Background: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), which accounts for approximately 10% of all acute myloid leukemia cases. It is a blood cancer that is formed by chromosomal mutation. Each year in the United States, APL affects about 1,500 patients of all age groups and causes approximately 1.2% of cancer deaths. Arsenic trioxide (ATO) has been used successfully for treatment of APL patients, and both induction and consolidated therapy have resulted in complete remission. Recently published studies from our laboratory have demonstrated that ATO pharmacology as an anti-leukemic drug is associated with cytotoxic and genotoxic effects in leukemia cells.
Methods: In the present study, we further investigated the detailed molecular mechanism of ATO-mediated intrinsic pathway of apoptosis; using HL-60 cells as a test model. Oxidative stress was assessed by spectrophotometric measurements of MDA and GSH levels while genotoxicity was determined by single cell gel electrophoresis (Comet assay). Apoptosis pathway was analyzed by Western blot analysis of Bax, Bcl2 and caspase 3 expression, as well as immunocytochemistry and confocal imaging of Bax and Cyt c translocation and mitochondrial membrane potential depolarization.
Results: ATO significantly (p < 0.05) induces oxidative stress, DNA damage, and caspase 3 activityin HL-60 cells in a dose-dependent manner. It also activated the intrinsic pathway of apoptosis by significantly modulating (p < 0.05) the expression and translocation of apoptotic molecules and decreasing the mitochondrial membrane potential in leukemia cells.
Conclusion: Taken together, our research demonstrated that ATO induces mitochondrial pathway of apoptosis in HL-60 cells. This apoptotic signaling is modulated via oxidative stress, DNA damage, and change in mitochondrial membrane potential, translocation and upregulation of apoptotic proteins leading programmed cell death.
C1 [Kumar, Sanjay; Yedjou, Clement G.; Tchounwou, Paul B.] Jackson State Univ, Coll Sci Engn & Technol, Cell & Toxicogen Res Lab, NIH NIMHD RCMI Ctr Environm Hlth, Jackson, MS 39217 USA.
RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, Cell & Toxicogen Res Lab, NIH NIMHD RCMI Ctr Environm Hlth, 1400 Lunch St,Box18750, Jackson, MS 39217 USA.
EM paul.b.tchounwou@jsums.edu
FU National Institutes of Health through the RCMI Center for Environmental
Health at Jackson State University [G12MD007581]
FX The research described in this publication was made possible by a grant
from the National Institutes of Health (Grant No. G12MD007581) through
the RCMI Center for Environmental Health at Jackson State University.
NR 51
TC 18
Z9 18
U1 1
U2 18
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-9966
J9 J EXP CLIN CANC RES
JI J. Exp. Clin. Cancer Res.
PD MAY 16
PY 2014
VL 33
AR 42
DI 10.1186/1756-9966-33-42
PG 12
WC Oncology
SC Oncology
GA AI6OQ
UT WOS:000336995300001
PM 24887205
ER
PT J
AU Zhang, L
Beaucher, M
Cheng, Y
Rong, YKS
AF Zhang, Liang
Beaucher, Michelle
Cheng, Yan
Rong, Yikang S.
TI Coordination of transposon expression with DNA replication in the
targeting of telomeric retrotransposons in Drosophila
SO EMBO JOURNAL
LA English
DT Article
DE CST complex; Drosophila telomere; telomere replication; telomeric
transposon
ID NON-LTR RETROTRANSPOSONS; CHROMOSOME ENDS; HET-A; MELANOGASTER
TELOMERES; PROTEIN; ELONGATION; RETROVIRUS; ELEMENTS; MAINTENANCE;
CENTROMERES
AB In Drosophila, a group of retrotransposons is mobilized exclusively to telomeres in a sequence-independent manner. How they target chromosome ends is not understood. Here, we focused on the telomeric element HeT-A and characterized the cell cycle expression and cytological distribution of its protein and RNA products. We determined the timing of telomere replication by creating a single lacO-marked telomere and provide evidence suggesting that transposon expression and recruitment to telomeres is linked to telomere replication. The HeT-A-encoded ORF1p protein is expressed predominantly in S phase, particularly in early S phase. Orf1p binds HeT-A transcripts and forms spherical structures at telomeres undergoing DNA replication. HeT-A sphere formation requires Verrocchio, a putative homolog of the conserved Stn1 telomeric protein. Our results suggest that coupling of telomere elongation and telomere replication is a universal feature, and raise the possibility that transposon recruitment to Drosophila telomeres is mechanistically related to telomerase recruitment in other organisms. Our study also supports a co-adaptive relationship between the Drosophila host and HeT-A mobile elements.
C1 [Zhang, Liang; Beaucher, Michelle; Cheng, Yan; Rong, Yikang S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Rong, YKS (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM rongy@mail.nih.gov
FU intramural research program of the National Cancer Institute
FX We thank Ms. Sara Brinda and Ms. Flavia Amariei for their technical
assistance. We thank Drs. Bob Levis, Mary-Lou Pardue, Bruce Paterson,
and members of our laboratory for comments on the manuscript. We thank
Dr. Jemima Barrowman at NCI for editing the manuscript. Research in the
laboratory is supported by the intramural research program of the
National Cancer Institute.
NR 49
TC 8
Z9 8
U1 3
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0261-4189
EI 1460-2075
J9 EMBO J
JI Embo J.
PD MAY 16
PY 2014
VL 33
IS 10
BP 1148
EP 1158
DI 10.1002/embj.201386940
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AH9WN
UT WOS:000336495900007
PM 24733842
ER
PT J
AU Biswas, D
Hrabie, JA
Saavedra, JE
Cao, Z
Keefer, LK
Ivanic, J
Holland, RJ
AF Biswas, Debanjan
Hrabie, Joseph A.
Saavedra, Joseph E.
Cao, Zhao
Keefer, Larry K.
Ivanic, Joseph
Holland, Ryan J.
TI Aminolysis of an N-Diazeniumdiolated Amidine as an Approach to
Diazeniumdiolated Ammonia
SO JOURNAL OF ORGANIC CHEMISTRY
LA English
DT Article
ID BASIS-SETS; OXIDE; CHEMISTRY; RELEASE; AMINES
AB Recent theoretical studies have suggested that the parent diazeniumdiolate ion, H2N-N(O)=NO- ("diazeniumdiolated ammonia"), might be stable enough to be isolated and that it could potentially serve as a uniquely advantageous prodrug form of bioactive nitroxyl (HNO). Here, we report on an attempt to isolate its O-2-benzylated derivative by aminolysis of the C=N bond in PhC(NH2)=N-N(O)=NOBn. The reaction proved remarkably sluggish in comparison to aminolysis of unsubstituted benzamidine, and the desired product could not be isolated, apparently because of base sensitivity of the NH2 group. Consistent with this interpretation, O-benzylhydroxylamine and N2O were recovered from the reaction mixture in high yields, along with N,N'-dibutylbenzamidine. Theoretical calculations rationalize the observed slow aminolysis by demonstrating that the diazeniumdiolate group greatly suppresses the electrophilicity of the adjacent C=N carbon center, rendering attack at that position endothermic. The data provide significant insights into the challenges inherent to the pursuit of diazeniumdiolated ammonia.
C1 [Biswas, Debanjan; Hrabie, Joseph A.; Keefer, Larry K.; Holland, Ryan J.] Leidos Biomed Res Inc, Drug Design Sect, Biol Chem Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Saavedra, Joseph E.; Cao, Zhao] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Ivanic, Joseph] Leidos Biomed Res Inc, Adv Biomed Comp Ctr, Informat Syst Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Holland, RJ (reprint author), Leidos Biomed Res Inc, Drug Design Sect, Biol Chem Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM hollandrj@mail.nih.gov
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
FX This project has been funded with federal funds from the National Cancer
Institute, National Institutes of Health, under Contract No.
HHSN261200800001E, and by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. We thank Dr.
Sergey Tarasov and Ms. Marzena A. Dyba of the Biophysics Resource in the
Structural Biophysics Laboratory, NCI-Frederick, for assistance with the
high-resolution mass spectrometry studies.
NR 18
TC 0
Z9 0
U1 0
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-3263
J9 J ORG CHEM
JI J. Org. Chem.
PD MAY 16
PY 2014
VL 79
IS 10
BP 4512
EP 4516
DI 10.1021/jo500551n
PG 5
WC Chemistry, Organic
SC Chemistry
GA AH5VS
UT WOS:000336199800030
PM 24766285
ER
PT J
AU Davis, MI
Gross, S
Shen, M
Straley, KS
Pragani, R
Lea, WA
Popovici-Muller, J
DeLaBarre, B
Artin, E
Thorne, N
Auld, DS
Li, ZY
Dang, L
Boxer, MB
Simeonov, A
AF Davis, Mindy I.
Gross, Stefan
Shen, Min
Straley, Kimberly S.
Pragani, Rajan
Lea, Wendy A.
Popovici-Muller, Janeta
DeLaBarre, Byron
Artin, Erin
Thorne, Natasha
Auld, Douglas S.
Li, Zhuyin
Dang, Lenny
Boxer, Matthew B.
Simeonov, Anton
TI Biochemical, Cellular, and Biophysical Characterization of a Potent
Inhibitor of Mutant Isocitrate Dehydrogenase IDH1
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Dehydrogenase; Drug Discovery; Enzyme Inhibitors; Glioblastoma; Small
Molecules; AML; IDH1; Isocitrate Dehydrogenase; Enzyme
ID ONCOMETABOLITE 2-HYDROXYGLUTARATE; CANCER GENOME; GLIOMA-CELLS;
MUTATIONS; LEUKEMIA
AB Background: IDH1 R132H, implicated in glioblastoma and AML, produces the oncometabolite 2-HG. Results: A detailed binding mechanism of a small molecule inhibitor (ML309) is proposed. Conclusion: ML309 competes with -KG but is uncompetitive with NADPH and rapidly and reversibly affects cellular 2-HG levels. Significance: Understanding IDH1 R132H inhibition sets the stage for targeting IDH1 R132H for the treatment of cancer.
Two mutant forms (R132H and R132C) of isocitrate dehydrogenase 1 (IDH1) have been associated with a number of cancers including glioblastoma and acute myeloid leukemia. These mutations confer a neomorphic activity of 2-hydroxyglutarate (2-HG) production, and 2-HG has previously been implicated as an oncometabolite. Inhibitors of mutant IDH1 can potentially be used to treat these diseases. In this study, we investigated the mechanism of action of a newly discovered inhibitor, ML309, using biochemical, cellular, and biophysical approaches. Substrate binding and product inhibition studies helped to further elucidate the IDH1 R132H catalytic cycle. This rapidly equilibrating inhibitor is active in both biochemical and cellular assays. The (+) isomer is active (IC50 = 68 nm), whereas the (-) isomer is over 400-fold less active (IC50 = 29 m) for IDH1 R132H inhibition. IDH1 R132C was similarly inhibited by (+)-ML309. WT IDH1 was largely unaffected by (+)-ML309 (IC50 >36 m). Kinetic analyses combined with microscale thermophoresis and surface plasmon resonance indicate that this reversible inhibitor binds to IDH1 R132H competitively with respect to -ketoglutarate and uncompetitively with respect to NADPH. A reaction scheme for IDH1 R132H inhibition by ML309 is proposed in which ML309 binds to IDH1 R132H after formation of the IDH1 R132H NADPH complex. ML309 was also able to inhibit 2-HG production in a glioblastoma cell line (IC50 = 250 nm) and had minimal cytotoxicity. In the presence of racemic ML309, 2-HG levels drop rapidly. This drop was sustained until 48 h, at which point the compound was washed out and 2-HG levels recovered.
C1 [Davis, Mindy I.; Shen, Min; Pragani, Rajan; Lea, Wendy A.; Thorne, Natasha; Auld, Douglas S.; Li, Zhuyin; Boxer, Matthew B.; Simeonov, Anton] NIH, NIH Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD 20892 USA.
[Gross, Stefan; Straley, Kimberly S.; Popovici-Muller, Janeta; DeLaBarre, Byron; Artin, Erin; Dang, Lenny] Agios Pharmaceut Inc, Cambridge, MA 02139 USA.
[Auld, Douglas S.] Ctr Prote Chem, Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
RP Simeonov, A (reprint author), NIH, NIH Chem Genom Ctr, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20892 USA.
EM asimeono@mail.nih.gov
FU Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research, National Institutes of Health [U54
MH084681]
FX This research was supported by the Molecular Libraries Initiative of the
National Institutes of Health Roadmap for Medical Research, National
Institutes of Health (U54 MH084681).
NR 24
TC 31
Z9 31
U1 2
U2 27
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 16
PY 2014
VL 289
IS 20
BP 13717
EP 13725
DI 10.1074/jbc.M113.511030
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AH2XF
UT WOS:000335984600006
PM 24668804
ER
PT J
AU Sassa, A
Caglayan, M
Dyrkheeva, NS
Beard, WA
Wilson, SH
AF Sassa, Akira
Caglayan, Melike
Dyrkheeva, Nadezhda S.
Beard, William A.
Wilson, Samuel H.
TI Base Excision Repair of Tandem Modifications in a Methylated CpG
Dinucleotide
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Base Excision Repair; DNA Damage; DNA Methylation; DNA Polymerase;
Oxidative Stress; 8-Oxoguanine; DNA Demethylation; DNA Glycosylase
ID THYMINE-DNA GLYCOSYLASE; POLYMERASE-BETA; HUMAN-CELLS; 8-OXOGUANINE-DNA
GLYCOSYLASE; APURINIC ENDONUCLEASE-1; SUBSTRATE-SPECIFICITY; OXIDATIVE
DAMAGE; AP-ENDONUCLEASE; INITIAL STEPS; MAMMALIAN DNA
AB Background: Base excision repair is an important pathway for cytosine demethylation at the CpG dinucleotide for epigenetic control. Results: A deaminated 5-methylcytosine (thymine) and an adjacent oxidized guanine (7,8-dihydro-8-oxoguanine) retard base excision repair of each lesion. Conclusion: Altered in-tandem CpG dinucleotide is a poor substrate for base excision repair. Significance: Oxidized guanine in a CpG dinucleotide interferes with active DNA demethylation.
Cytosine methylation and demethylation in tracks of CpG dinucleotides is an epigenetic mechanism for control of gene expression. The initial step in the demethylation process can be deamination of 5-methylcytosine producing the TpG alteration and T:G mispair, and this step is followed by thymine DNA glycosylase (TDG) initiated base excision repair (BER). A further consideration is that guanine in the CpG dinucleotide may become oxidized to 7,8-dihydro-8-oxoguanine (8-oxoG), and this could affect the demethylation process involving TDG-initiated BER. However, little is known about the enzymology of BER of altered in-tandem CpG dinucleotides; e.g. Tp8-oxoG. Here, we investigated interactions between this altered dinucleotide and purified BER enzymes, the DNA glycosylases TDG and 8-oxoG DNA glycosylase 1 (OGG1), apurinic/apyrimidinic (AP) endonuclease 1, DNA polymerase , and DNA ligases. The overall TDG-initiated BER of the Tp8-oxoG dinucleotide is significantly reduced. Specifically, TDG and DNA ligase activities are reduced by a 3-flanking 8-oxoG. In contrast, the OGG1-initiated BER pathway is blocked due to the 5-flanking T:G mispair; this reduces OGG1, AP endonuclease 1, and DNA polymerase activities. Furthermore, in TDG-initiated BER, TDG remains bound to its product AP site blocking OGG1 access to the adjacent 8-oxoG. These results reveal BER enzyme specificities enabling suppression of OGG1-initiated BER and coordination of TDG-initiated BER at this tandem alteration in the CpG dinucleotide.
C1 [Sassa, Akira; Caglayan, Melike; Dyrkheeva, Nadezhda S.; Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Dyrkheeva, Nadezhda S.] Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU National Institutes of Health [Z01-ES050158, Z01-ES050159]; Eli Lilly
and Co.; United States Department of State, as part of the United
States-Russia Collaboration in the Biomedical Sciences NIH Visiting
Fellows Program
FX This work was supported, in whole or in part, by National Institutes of
Health Grants Z01-ES050158 and Z01-ES050159 (NIEHS).; Supported in part
by Eli Lilly and Co. and the United States Department of State, as part
of the United States-Russia Collaboration in the Biomedical Sciences NIH
Visiting Fellows Program.
NR 80
TC 8
Z9 11
U1 2
U2 10
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 16
PY 2014
VL 289
IS 20
BP 13996
EP 14008
DI 10.1074/jbc.M114.557769
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AH2XF
UT WOS:000335984600030
PM 24695738
ER
PT J
AU Chen, SR
Chen, H
Yuan, WX
Wess, J
Pan, HL
AF Chen, Shao-Rui
Chen, Hong
Yuan, Wei-Xiu
Wess, Juergen
Pan, Hui-Lin
TI Differential Regulation of Primary Afferent Input to Spinal Cord by
Muscarinic Receptor Subtypes Delineated Using Knockout Mice
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Acetylcholinesterase; Cholinergic Receptor; Gene Knockout; Glutamate;
Neurons; Pain; Synaptic Plasticity; Acetylcholine; Muscarinic; Spinal
Cord
ID DORSAL-HORN NEURONS; METABOTROPIC GLUTAMATE RECEPTORS; SUBSTANTIA
GELATINOSA NEURONS; ACETYLCHOLINE-RECEPTOR; CHOLINERGIC RECEPTORS;
AUTORADIOGRAPHIC LOCALIZATION; CHOLINESTERASE INHIBITION;
SYNAPTIC-TRANSMISSION; GABA(B) RECEPTORS; GLYCINERGIC INPUT
AB Background: Activation of muscarinic receptors reduces pain at the spinal level. Results: M-2 and M-4 subtypes mediate muscarinic inhibition of sensory nerve input. M-5 subtype stimulation directly increases sensory input or indirectly inhibits it through metabotropic glutamate receptors. Conclusion: M-2, M-4, and M-5 subtypes differentially regulate nociceptive input to the spinal cord. Significance: This study demonstrates how individual muscarinic receptor subtypes control pain transmission.
Stimulation of muscarinic acetylcholine receptors (mAChRs) inhibits nociceptive transmission at the spinal level. However, it is unclear how each mAChR subtype regulates excitatory synaptic input from primary afferents. Here we examined excitatory postsynaptic currents (EPSCs) of dorsal horn neurons evoked by dorsal root stimulation in spinal cord slices from wild-type and mAChR subtype knock-out (KO) mice. In wild-type mice, mAChR activation with oxotremorine-M decreased the amplitude of monosynaptic EPSCs in approximate to 67% of neurons but increased it in approximate to 10% of neurons. The inhibitory effect of oxotremorine-M was attenuated by the M-2/M-4 antagonist himbacine in the majority of neurons, and the remaining inhibition was abolished by group II/III metabotropic glutamate receptor (mGluR) antagonists in wild-type mice. In M-2/M-4 double-KO mice, oxotremorine-M inhibited monosynaptic EPSCs in significantly fewer neurons (approximate to 26%) and increased EPSCs in significantly more neurons (33%) compared with wild-type mice. Blocking group II/III mGluRs eliminated the inhibitory effect of oxotremorine-M in M-2/M-4 double-KO mice. In M-2 single-KO and M-4 single-KO mice, himbacine still significantly reduced the inhibitory effect of oxotremorine-M. However, the inhibitory and potentiating effects of oxotremorine-M on EPSCs in M-3 single-KO and M-1/M-3 double-KO mice were similar to those in wild-type mice. In M-5 single-KO mice, oxotremorine-M failed to potentiate evoked EPSCs, and its inhibitory effect was abolished by himbacine. These findings indicate that activation of presynaptic M-2 and M-4 subtypes reduces glutamate release from primary afferents. Activation of the M-5 subtype either directly increases primary afferent input or inhibits it through indirectly stimulating group II/III mGluRs.
C1 [Chen, Shao-Rui; Chen, Hong; Yuan, Wei-Xiu; Pan, Hui-Lin] Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Perioperat Med, Ctr Neurosci & Pain Res, Houston, TX 77030 USA.
[Wess, Juergen] NIDDK, Bioorgan Chem Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Pan, HL (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Perioperat Med, Unit 110, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM huilinpan@mdanderson.org
FU National Institutes of Health [NS073935, NS045602]; N. G. and Helen T.
Hawkins Endowment; Intramural Research Program of NIDDK, National
Institutes of Health
FX This work was supported, in whole or in part, by National Institutes of
Health Grants NS073935 and NS045602. This work was also supported by a
grant from the N. G. and Helen T. Hawkins Endowment (to H.-L. P.).;
Supported by the Intramural Research Program of NIDDK, National
Institutes of Health.
NR 44
TC 5
Z9 5
U1 2
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 16
PY 2014
VL 289
IS 20
BP 14321
EP 14330
DI 10.1074/jbc.M114.550384
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AH2XF
UT WOS:000335984600057
PM 24695732
ER
PT J
AU Fauci, AS
AF Fauci, Anthony S.
TI Untitled
SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION
LA English
DT News Item
C1 NIAID, NIH, Bethesda, MD 20892 USA.
RP Fauci, AS (reprint author), NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER VETERINARY MEDICAL ASSOC
PI SCHAUMBURG
PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA
SN 0003-1488
EI 1943-569X
J9 JAVMA-J AM VET MED A
JI JAVMA-J. Am. Vet. Med. Assoc.
PD MAY 15
PY 2014
VL 244
IS 10
BP 1103
EP 1104
PG 2
WC Veterinary Sciences
SC Veterinary Sciences
GA CA6CE
UT WOS:000348995200001
ER
PT J
AU Greer, YE
Westlake, CJ
Gao, B
Bharti, K
Shiba, Y
Xavier, CP
Pazour, GJ
Yang, YZ
Rubin, JS
AF Greer, Yoshimi Endo
Westlake, Christopher J.
Gao, Bo
Bharti, Kapil
Shiba, Yoko
Xavier, Charles P.
Pazour, Gregory J.
Yang, Yingzi
Rubin, Jeffrey S.
TI Casein kinase 1 delta functions at the centrosome and Golgi to promote
ciliogenesis
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID INTRAFLAGELLAR TRANSPORT; PRIMARY CILIUM; CILIARY MEMBRANE; I FAMILY;
PROTEIN; COMPLEX; TRAFFICKING; RAB11; MICROTUBULES; ORGANIZATION
AB Inhibition of casein kinase 1 delta (CK1 delta) blocks primary ciliogenesis in human telomerase reverse transcriptase immortalized retinal pigmented epithelial and mouse inner medullary collecting duct cells-3. Mouse embryonic fibroblasts (MEFs) and retinal cells from Csnk1d (CK1 delta)-null mice also exhibit ciliogenesis defects. CK1 delta catalytic activity and centrosomal localization signal (CLS) are required to rescue cilia formation in MEFs(Csnk1d null). Furthermore, expression of a truncated derivative containing the CLS displaces full-length CK1 delta from the centrosome and decreases ciliary length in control MEFs, suggesting that centrosomal CK1 delta has a role in ciliogenesis. CK1 delta inhibition also alters pericentrosomal or ciliary distribution of several proteins involved in ciliary transport, including Ras-like in rat brain11A, Ras-like in rat brain-8A, centrosomal protein of 290 kDa, pericentriolar material protein 1, and polycystin-2, as well as the Golgi distribution of its binding partner, A-kinase anchor protein 450 (AKAP450). As reported for AKAP450, CK1 delta was required for microtubule nucleation at the Golgi and maintenance of Golgi integrity. Overexpression of an AKAP450 fragment containing the CK1 delta-binding site inhibits Golgi-derived microtubule nucleation, Golgi distribution of intraflagellar transport protein 20 homologue, and ciliogenesis. Our results suggest that CK1 delta mediates primary ciliogenesis by multiple mechanisms, one involving its centrosomal function and another dependent on its interaction with AKAP450 at the Golgi, where it is important for maintaining Golgi organization and polarized trafficking of multiple factors that mediate ciliary transport.
C1 [Greer, Yoshimi Endo; Shiba, Yoko; Xavier, Charles P.; Rubin, Jeffrey S.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA.
[Westlake, Christopher J.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
[Gao, Bo; Yang, Yingzi] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA.
[Bharti, Kapil] NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA.
[Pazour, Gregory J.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
RP Rubin, JS (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA.
EM rubinj@mail.nih.gov
FU National Institutes of Health [GM060992]; Intramural Research Program of
the National Institutes of Health, National Cancer Institute
FX We thank Eli Lilly for providing the CK1 delta monoclonal antibody 128A
and Irina Kaverina and Sean Munro, respectively, for providing the
plasmids encoding AKAP450/159-463-GFP and GFPAKAP450/3643-3908. We also
appreciate comments on the manuscript from Sergei Sokol and Kyeongmi Kim
(Mount Sinai School of Medicine, New York, NY). This research was
supported by Grant GM060992 from the National Institutes of Health to
G.J.P. and the Intramural Research Program of the National Institutes of
Health, National Cancer Institute.
NR 49
TC 10
Z9 11
U1 0
U2 3
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD MAY 15
PY 2014
VL 25
IS 10
BP 1629
EP 1640
DI 10.1091/mbc.E13-10-0598
PG 12
WC Cell Biology
SC Cell Biology
GA AM2AP
UT WOS:000339650800009
PM 24648492
ER
PT J
AU Poletto, M
Lirussi, L
Wilson, DM
Tell, G
AF Poletto, Mattia
Lirussi, Lisa
Wilson, David M., III
Tell, Gianluca
TI Nucleophosmin modulates stability, activity, and nucleolar accumulation
of base excision repair proteins
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID RNA QUALITY-CONTROL; DNA-DAMAGE; LYSINE RESIDUES; CELLS; P53;
TRANSCRIPTION; INTERACTS; STABILIZATION; LOCALIZATION; DAUNORUBICIN
AB Nucleophosmin (NPM1) is a multifunctional protein that controls cell growth and genome stability via a mechanism that involves nucleolar-cytoplasmic shuttling. It is clear that NPM1 also contributes to the DNA damage response, yet its exact function is poorly understood. We recently linked NPM1 expression to the functional activation of the major abasic endonuclease in mammalian base excision repair (BER), apurinic/apyrimidinic endonuclease 1 (APE1). Here we unveil a novel role for NPM1 as a modulator of the whole BER pathway by 1) controlling BER protein levels, 2) regulating total BER capacity, and 3) modulating the nucleolar localization of several BER enzymes. We find that cell treatment with the genotoxin cisplatin leads to concurrent relocalization of NPM1 and BER components from nucleoli to the nucleoplasm, and cellular experiments targeting APE1 suggest a role for the redistribution of nucleolar BER factors in determining cisplatin toxicity. Finally, based on the use of APE1 as a representative protein of the BER pathway, our data suggest a function for BER proteins in the regulation of ribogenesis.
C1 [Poletto, Mattia; Lirussi, Lisa; Tell, Gianluca] Univ Udine, Dept Med & Biol Sci, I-33100 Udine, Italy.
[Wilson, David M., III] NIA, Lab Mol Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Tell, G (reprint author), Univ Udine, Dept Med & Biol Sci, I-33100 Udine, Italy.
EM gianluca.tell@uniud.it
OI Tell, Gianluca/0000-0001-8845-6448
FU Associazione Italiana per la Ricerca sul Cancro [IG10269, IG14038];
Intramural Research Program at the National Institutes of Health,
National Institute on Aging
FX We acknowledge Bruce Demple and Alex Pines for critical comments on the
manuscript and the National Center for Advancing Translational Sciences
for providing the APE1-specific inhibitor (compound # 3). This work was
supported by grants from the Associazione Italiana per la Ricerca sul
Cancro (IG10269 and IG14038) to G. T. and in part by the Intramural
Research Program at the National Institutes of Health, National
Institute on Aging, to D. M. W.
NR 45
TC 14
Z9 14
U1 0
U2 6
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD MAY 15
PY 2014
VL 25
IS 10
BP 1641
EP 1652
DI 10.1091/mbc.E13-12-0717
PG 12
WC Cell Biology
SC Cell Biology
GA AM2AP
UT WOS:000339650800010
PM 24648491
ER
PT J
AU Ball, CB
Rodriguez, KF
Stumpo, DJ
Ribeiro-Neto, F
Korach, KS
Blackshear, PJ
Birnbaumer, L
Ramos, SBV
AF Ball, Christopher B.
Rodriguez, Karina F.
Stumpo, Deborah J.
Ribeiro-Neto, Fernando
Korach, Kenneth S.
Blackshear, Perry J.
Birnbaumer, Lutz
Ramos, Silvia B. V.
TI The RNA-Binding Protein, ZFP36L2, Influences Ovulation and Oocyte
Maturation
SO PLOS ONE
LA English
DT Article
ID LUTEINIZING-HORMONE RECEPTOR; HUMAN CHORIONIC-GONADOTROPIN; EARLY
EMBRYONIC-DEVELOPMENT; MESSENGER-RIBONUCLEIC-ACID; OVARIAN
FOLLICULAR-FLUID; TO-CELL COMMUNICATION; MEIOTIC ARREST; CYCLIC-AMP;
IN-VITRO; GRAAFIAN-FOLLICLES
AB ZFP36L2 protein destabilizes AU-rich element-containing transcripts and has been implicated in female fertility. In the C57BL/6NTac mouse, a mutation in Zfp36l2 that results in the decreased expression of a form of ZFP36L2 in which the 29 N-terminal amino acid residues have been deleted, Delta N-ZFP36L2, leads to fertilized eggs that arrest at the two-cell stage. Interestingly, homozygous Delta N-Zfp36l2 females in the C57BL/6NTac strain release 40% fewer eggs than the WT littermates (Ramos et al., 2004), suggesting an additional defect in ovulation and/or oocyte maturation. Curiously, the same Delta N-Zfp36l2 mutation into the SV129 strain resulted in anovulation, prompting us to investigate a potential problem in ovulation and oocyte maturation. Remarkably, only 20% of Delta N-Zfp36l2 oocytes in the 129S6/SvEvTac strain matured ex vivo, suggesting a defect on the oocyte meiotic maturation process. Treatment of Delta N-Zfp36l2 oocytes with a PKA inhibitor partially rescued the meiotic arrested oocytes. Furthermore, cAMP levels were increased in Delta N-Zfp36l2 oocytes, linking the cAMP/PKA pathway and Delta N-Zfp36l2 with meiotic arrest. Since ovulation and oocyte maturation are both triggered by LHR signaling, the downstream pathway was investigated. Adenylyl cyclase activity was increased in Delta N-Zfp36l2 ovaries only upon LH stimulation. Moreover, we discovered that ZFP36L2 interacts with the 3'UTR of LHR mRNA and that decreased expression levels of Zfp36l2 correlates with higher levels of LHR mRNA in synchronized ovaries. Furthermore, overexpression of ZFP36L2 decreases the endogenous expression of LHR mRNA in a cell line. Therefore, we propose that lack of the physiological down regulation of LHR mRNA levels by ZFP36L2 in the ovaries is associated with anovulation and oocyte meiotic arrest.
C1 [Ball, Christopher B.; Ramos, Silvia B. V.] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Chapel Hill, NC 27515 USA.
[Rodriguez, Karina F.; Korach, Kenneth S.] NIEHS, Lab Reprod & Dev Toxicol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Stumpo, Deborah J.; Ribeiro-Neto, Fernando; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
[Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Ramos, SBV (reprint author), Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Chapel Hill, NC 27515 USA.
EM sramos@med.unc.edu
OI Korach, Kenneth/0000-0002-7765-418X
FU National Institutes of Health [K08 HD069597]; Institute for Biological
Recognition and Catalysis, Inc.; UNC TraCS [550KR11128]; NIH, NIEHS
[Z01-ES70065, Z01-ES090080-15, Z01-ES101643]
FX This work was supported by the National Institutes of Health Grant K08
HD069597 (to S. B. R.); Institute for Biological Recognition and
Catalysis, Inc. (to S. B. R.), UNC TraCS grant # 550KR11128 (to S. B.
R.) and by the Intramural Research Program of the NIH, NIEHS Z01-ES70065
(to K. S. K.), Z01-ES090080-15 (to P.J.B.) and Z01-ES101643 (to L. B.).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 48
TC 2
Z9 2
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 15
PY 2014
VL 9
IS 5
AR e97324
DI 10.1371/journal.pone.0097324
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3UI
UT WOS:000336789500049
PM 24830504
ER
PT J
AU Moslehi, R
Ambroggio, X
Nagarajan, V
Kumar, A
Dzutsev, A
AF Moslehi, Roxana
Ambroggio, Xavier
Nagarajan, Vijayaraj
Kumar, Anil
Dzutsev, Amiran
TI Nucleotide excision repair/transcription gene defects in the fetus and
impaired TFIIH-mediated function in transcription in placenta leading to
preeclampsia
SO BMC GENOMICS
LA English
DT Article
ID DNA-REPAIR; XERODERMA-PIGMENTOSUM; COCKAYNE-SYNDROME; INTERACTION
NETWORKS; CLINICAL-FEATURES; XPD GENE; TRICHOTHIODYSTROPHY; MUTATIONS;
EXPRESSION; DEFICIENT
AB Background: Preeclampsia is a significant cause of maternal and fetal mortality and morbidity worldwide. We previously reported associations between trichothiodystrophy (TTD) nucleotide excision repair (NER) and transcription gene mutations in the fetus and the risk of gestational complications including preeclampsia. TTD NER/transcription genes, XPD, XPB and TTD-A, code for subunits of Transcription Factor (TF) IIH. Interpreting XPD mutations in the context of available biochemical data led us to propose adverse effects on CDK-activating kinase (CAK) subunit of TFIIH and TFIIH-mediated functions as a relevant mechanism in preeclampsia. In order to gain deeper insight into the underlying biologic mechanisms involving TFIIH-mediated functions in placenta, we analyzed NER/transcription and global gene expression profiles of normal and preeclamptic placentas and studied gene regulatory networks.
Results: We found high expression of TTD NER/transcription genes in normal human placenta, above the mean of their expression in all organs. XPD and XPB were consistently expressed from 14 to 40 weeks gestation while expression of TTD-A was strongly negatively correlated (r = -0.7, P < 0.0001) with gestational age. Analysis of gene expression patterns of placentas from a case-control study of preeclampsia using Algorithm for Reconstruction of Accurate Cellular Networks (ARACNE) revealed GTF2E1, a component of TFIIE which modulates TFIIH, among major regulators of differentially-expressed genes in preeclampsia. The basal transcription pathway was among the largest dysregulated protein-protein interaction networks in this preeclampsia dataset. Within the basal transcription pathway, significantly down-regulated genes besides GTF2E1 included those coding for the CAK complex of TFIIH, namely CDK7, CCNH, and MNAT1. Analysis of other relevant gene expression and gene regulatory network data also underscored the involvement of transcription pathways and identified JUNB and JUND (components of transcription factor AP-1) as transcription regulators of the network involving the TTD genes, GTF2E1, and selected gene regulators implicated in preeclampsia.
Conclusions: Our results indicate that TTD NER/transcription genes are expressed in placenta during gestational periods critical to preeclampsia development. Our overall findings suggest that impairment of TFIIH-mediated function in transcription in placenta is a likely mechanism leading to preeclampsia and provide etiologic clues which may be translated into therapeutic and preventive measures.
C1 [Moslehi, Roxana; Kumar, Anil] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Rensselaer, NY 12144 USA.
[Moslehi, Roxana] SUNY Albany, Canc Res Ctr, Rensselaer, NY 12144 USA.
[Ambroggio, Xavier] Rosetta Design Grp LLC, Burlington, VT 05401 USA.
[Nagarajan, Vijayaraj] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20814 USA.
[Dzutsev, Amiran] Leidos Biomed Res Inc, Frederick, MD 21701 USA.
[Dzutsev, Amiran] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA.
RP Moslehi, R (reprint author), SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Rensselaer, NY 12144 USA.
EM rmoslehi@albany.edu; dzutseva@mail.nih.gov
FU Center for Social and Demographic Analysis (CSDA) at University at
Albany from NICHD [R24 HD044943]; Intramural Research Program of the
NIH; National Cancer Institute
FX The authors are grateful to Drs. James L. Mills and Caroline Signore at
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), NIH for their significant contributions. Technical
support provided by Mr. H. Martinez at University at Albany is
appreciated. This study was supported in part by a grant to the Center
for Social and Demographic Analysis (CSDA) at University at Albany from
NICHD (R24 HD044943) and a research award to RM from CSDA. This research
was also supported in part by the Intramural Research Program of the
NIH, National Cancer Institute. Opinions, findings and conclusions
expressed here are those of the authors and do not necessarily reflect
the views of the funding agencies. The content of this publication does
not necessarily reflect the policies of the Department of Health and
Human Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.
NR 49
TC 2
Z9 2
U1 4
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD MAY 15
PY 2014
VL 15
AR 373
DI 10.1186/1471-2164-15-373
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AI2HC
UT WOS:000336677300002
PM 24885447
ER
PT J
AU Jia, JP
Bosley, AD
Thompson, A
Hoskins, JW
Cheuk, A
Collins, I
Parikh, H
Xiao, Z
Ylaya, K
Dzyadyk, M
Cozen, W
Hernandez, BY
Lynch, CF
Loncarek, J
Altekruse, SF
Zhang, LZ
Westlake, CJ
Factor, VM
Thorgeirsson, S
Bamlet, WR
Hewitt, SM
Petersen, GM
Andresson, T
Amundadottir, LT
AF Jia, Jinping
Bosley, Allen D.
Thompson, Abbey
Hoskins, Jason W.
Cheuk, Adam
Collins, Irene
Parikh, Hemang
Xiao, Zhen
Ylaya, Kris
Dzyadyk, Marta
Cozen, Wendy
Hernandez, Brenda Y.
Lynch, Charles F.
Loncarek, Jadranka
Altekruse, Sean F.
Zhang, Lizhi
Westlake, Christopher J.
Factor, Valentina M.
Thorgeirsson, Snorri
Bamlet, William R.
Hewitt, Stephen M.
Petersen, Gloria M.
Andresson, Thorkell
Amundadottir, Laufey T.
TI CLPTM1L Promotes Growth and Enhances Aneuploidy in Pancreatic Cancer
Cells
SO CANCER RESEARCH
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; NONMUSCLE MYOSIN-II; LUNG-CANCER;
SUSCEPTIBILITY LOCI; TERT-CLPTM1L LOCUS; VARIANTS; RISK; 5P15.33; TERT;
METAANALYSIS
AB Genome-wide association studies (GWAS) of 10 different cancers have identified pleiotropic cancer predisposition loci across a region of chromosome 5p15.33 that includes the TERT and CLPTM1L genes. Of these, susceptibility alleles for pancreatic cancer have mapped to the CLPTM1L gene, thus prompting an investigation of the function of CLPTM1L in the pancreas. Immunofluorescence analysis indicated that CLPTM1L localized to the endoplasmic reticulum where it is likely embedded in the membrane, in accord with multiple predicted transmembrane domains. Overexpression of CLPTM1L enhanced growth of pancreatic cancer cells in vitro (1.3-1.5-fold; P-DAY7 < 0.003) and in vivo (3.46-fold; P-DAY68 = 0.039), suggesting a role in tumor growth; this effect was abrogated by deletion of two hydrophilic domains. Affinity purification followed by mass spectrometry identified an interaction between CLPTM1L and non-muscle myosin II (NMM-II), a protein involved in maintaining cell shape, migration, and cytokinesis. The two proteins colocalized in the cytoplasm and, after treatment with a DNA-damaging agent, at the centrosomes. Overexpression of CLPTM1L and depletion of NMM-II induced aneuploidy, indicating that CLPTM1L may interfere with normal NMM-II function in regulating cytokinesis. Immunohistochemical analysis revealed enhanced staining of CLPTM1L in human pancreatic ductal adenocarcinoma (n = 378) as compared with normal pancreatic tissue samples (n 17; P = 1.7 x 10(-4)). Our results suggest that CLPTM1L functions as a growth-promoting gene in the pancreas and that overexpression may lead to an abrogation of normal cytokinesis, indicating that it should be considered as a plausible candidate gene that could explain the effect of pancreatic cancer susceptibility alleles on chr5p15.33. (C)2014 AACR.
C1 [Jia, Jinping; Thompson, Abbey; Hoskins, Jason W.; Collins, Irene; Parikh, Hemang; Dzyadyk, Marta; Amundadottir, Laufey T.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Cheuk, Adam] NCI, Pediat Oncol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Ylaya, Kris; Hewitt, Stephen M.] NCI, Pathol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Altekruse, Sean F.] NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Factor, Valentina M.; Thorgeirsson, Snorri] NCI, Expt Carcinogenesis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Bosley, Allen D.; Xiao, Zhen; Andresson, Thorkell] NCI, Lab Prote & Analyt Technol, Leidos Biomed Res, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Loncarek, Jadranka] NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA.
[Westlake, Christopher J.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21701 USA.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Hernandez, Brenda Y.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA.
[Zhang, Lizhi; Bamlet, William R.; Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
RP Amundadottir, LT (reprint author), NIH, Lab Translat Genom, Div Canc Epidemiol & Genet, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA.
EM amundadottirl@mail.nih.gov
RI Amundadottir, Laufey/L-7656-2016;
OI Amundadottir, Laufey/0000-0003-1859-8971; Hewitt,
Stephen/0000-0001-8283-1788; Hoskins, Jason/0000-0001-6944-1996
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health (NIH)
[HHSN2612 00800001E]
FX This study was supported in part by the Intramural Research Program of
the Division of Cancer Epidemiology and Genetics, National Cancer
Institute, National Institutes of Health (NIH) under Contract No.
HHSN2612 00800001E.
NR 48
TC 18
Z9 18
U1 0
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD MAY 15
PY 2014
VL 74
IS 10
BP 2785
EP 2795
DI 10.1158/0008-5472.CAN-13-3176
PG 11
WC Oncology
SC Oncology
GA AI2WW
UT WOS:000336720700014
PM 24648346
ER
PT J
AU Bates, SE
AF Bates, Susan E.
TI The Language of Pharmacodynamics
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
C1 NCI, Bethesda, MD 20892 USA.
RP Bates, SE (reprint author), NCI, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [ZIA BC010622-10]
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAY 15
PY 2014
VL 20
IS 10
BP 2524
EP 2524
DI 10.1158/1078-0432.CCR-14-0739
PG 1
WC Oncology
SC Oncology
GA AI2WU
UT WOS:000336720200004
PM 24831274
ER
PT J
AU Figg, WD
Newell, DR
AF Figg, William Douglas
Newell, David R.
TI Pharmacologic Biomarkers in the Development of Stratified Cancer
Medicine
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CIRCULATING TUMOR DNA; SURROGATE END-POINTS; ACQUIRED-RESISTANCE; DRUG
DEVELOPMENT; VALIDATION; TOXICITY; ONCOLOGY; UTILITY; CELLS
AB Clinical pharmacologic research plays a vital role in cancer drug development. In recent years, biomarker studies have become integral to this process, specifically the use of pharmacologic biomarkers in the development of targeted therapies and their translation to clinical practice. In this overview, we discuss the validation of pharmacodynamics (PD) biomarkers and highlight the circulating tumor DNA as a promising cancer biomarker to illustrate how PD 'biomarkers can be powerful tools for guiding treatment strategies. We provide insights into PD biomarker approaches for future development of novel therapies and their role in cancer medicine. (C) 2014 AACR.
C1 [Figg, William Douglas] NCI, Clin Pharmacol Program, Off Clin Director,Ctr Canc Res,NIH, Mol Pharmacol Sect & Genitourinary Malignancies B, Bethesda, MD 20892 USA.
[Newell, David R.] Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England.
RP Figg, WD (reprint author), NCI, NIH, 10 Ctr Dr,9000 Rockville Pike,Bldg 10 Room 5A01, Bethesda, MD 20892 USA.
EM figgw@helix.nih.gov; herbie.newell@ncl.ac.uk
RI Figg Sr, William/M-2411-2016
FU Astex Pharmaceuticals
FX D.R. Newell reports receiving commercial research grants and speakers
bureau honoraria from Astex Pharmaceuticals and is a consultant/advisory
board member for Astex Pharmaceuticals. No potential conflicts of
interest were disclosed by the other author.
NR 29
TC 2
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U1 0
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAY 15
PY 2014
VL 20
IS 10
BP 2525
EP 2529
DI 10.1158/1078-0432.CCR-14-0511
PG 5
WC Oncology
SC Oncology
GA AI2WU
UT WOS:000336720200005
PM 24831275
ER
PT J
AU Kinders, R
Ferry-Galow, K
Wang, LH
Srivastava, AK
Ji, JP
Parchment, RE
AF Kinders, Robert
Ferry-Galow, Kate
Wang, Lihua
Srivastava, Apurva K.
Ji, Jiuping (Jay)
Parchment, Ralph E.
TI Implementation of Validated Pharmacodynamic Assays in Multiple
Laboratories: Challenges, Successes, and Limitations
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CIRCULATING TUMOR-CELLS; ADP-RIBOSE POLYMERASE; 0 CLINICAL-TRIAL;
BREAST-CANCER; DEPENDENT APOPTOSIS; COLORECTAL-CANCER; SIGNALING
PATHWAY; DOWN-REGULATION; PROTEIN FAMILY; LEUKEMIA-CELLS
AB There is a "life cycle" of pharmacodynamic (PD) biomarker assays that guides the development and clinical implementation in our laboratories. The well-recognized elements of analytical assay validation and demonstration of fitness-for-purpose of the biomarker, specimen collection, handling, and assay methods are only a part of the required activities. Assay transfer across laboratories and testing on actual human clinical specimens are vital for understanding assay performance and robustness. In our experience, this patient specimen-centered approach has required assay method modifications, some unexpected, but which were critical to successful implementation in clinical trials. In addition, dispersing assays throughout the National Cancer Institute's clinical trials network has required the development of calibrator and control materials as well as formal training courses for smooth implementation. One measure of success of this approach has been that a number of the assays developed at NCI's Frederick National Laboratory have ultimately reached the stage of commercialization, enabling wide accessibility of the PD biomarker assays by the research community.
C1 [Kinders, Robert; Ferry-Galow, Kate; Wang, Lihua; Srivastava, Apurva K.; Parchment, Ralph E.] Frederick Natl Lab Canc Res, Lab Human Toxicol & Pharmacol, Frederick, MD USA.
[Ji, Jiuping (Jay)] Frederick Natl Lab Canc Res, Appl Dev Res Directorate, Natl Canc Target Validat Lab, Frederick, MD USA.
[Ji, Jiuping (Jay)] Leidos Biomed Res Inc, Frederick, MD 21702 USA.
RP Kinders, R (reprint author), Leidos Biomed Res Inc, Appl Dev Directorate, Lab Human Toxicol & Pharmacol, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM kindersr@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 46
TC 5
Z9 5
U1 2
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAY 15
PY 2014
VL 20
IS 10
BP 2578
EP 2586
DI 10.1158/1078-0432.CCR-14-0476
PG 9
WC Oncology
SC Oncology
GA AI2WU
UT WOS:000336720200010
PM 24831280
ER
PT J
AU Bartlett, EK
Fetsch, PA
Filie, AC
Abati, A
Steinberg, SM
Wunderlich, JR
White, DE
Stephens, DJ
Marincola, FM
Rosenberg, SA
Kammula, US
AF Bartlett, Edmund K.
Fetsch, Patricia A.
Filie, Armando C.
Abati, Andrea
Steinberg, Seth M.
Wunderlich, John R.
White, Donald E.
Stephens, Daniel J.
Marincola, Francesco M.
Rosenberg, Steven A.
Kammula, Udai S.
TI Human Melanoma Metastases Demonstrate Nonstochastic Site-Specific
Antigen Heterogeneity That Correlates with T-cell Infiltration
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID FINE-NEEDLE-ASPIRATION; MALIGNANT-MELANOMA; CANCER METASTASIS; VISCERAL
METASTASES; IN-VIVO; TUMOR; EXPRESSION; IMMUNOTHERAPY; LYMPHOCYTES;
TYROSINASE
AB Purpose: Metastasis heterogeneity presents a significant obstacle to the development of targeted cancer therapeutics. In this study, we sought to establish from a large series of human melanoma metastases whether there exists a determined pattern in tumor cellular heterogeneity that may guide the development of future targeted immunotherapies.
Experimental Design: From a cohort of 1,514 patients with metastatic melanoma, biopsies were procured over a 17-year period from 3,086 metastatic tumors involving various anatomic sites. To allow specific tumor cell profiling, we used established immunohistochemical methods to perform semiquantitative assessment for a panel of prototypic melanocyte differentiation antigens (MDA), including gp100, MART-1, and tyrosinase. To gain insight into the endogenous host immune response against these tumors, we further characterized tumor cell expression of MHC I and MHC II and, also, the concomitant CD4(+) and CD8(+) T-cell infiltrate.
Results: Tumor cell profiling for MDA expression demonstrated an anatomic site-specific pattern of antigen expression that was highest in brain, intermediate in soft tissues/lymph nodes, and lowest in visceral metastases. Hierarchical clustering analysis supported that melanoma metastases have a phylogenetically determined, rather than a stochastic, pattern of antigen expression that varies by anatomic site. Furthermore, tyrosinase expression was more frequently lost in metastatic sites outside of the brain and was uniquely correlated with both endogenous CD8(+) and CD4(+) T-cell infiltrates.
Conclusion: Site-specific antigen heterogeneity represents a novel attribute for human melanoma metastases that should be considered in future therapy development and when assessing the responsiveness to antigen-specific immunotherapies. (C) 2014 AACR.
C1 [Bartlett, Edmund K.; Wunderlich, John R.; White, Donald E.; Stephens, Daniel J.; Rosenberg, Steven A.; Kammula, Udai S.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Fetsch, Patricia A.; Filie, Armando C.; Abati, Andrea] NCI, Cytopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar.
RP Kammula, US (reprint author), NCI, Surg Branch, Ctr Canc Res, 10 Ctr Dr,Bldg 10 Hatfield CRC,Rm 3-5930, Bethesda, MD 20892 USA.
EM udai_kammula@nih.gov
OI Bartlett, Edmund/0000-0002-0923-153X
FU Intramural Research Program of the NIH, NCI, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, NCI, Center for Cancer Research.
NR 38
TC 6
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U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAY 15
PY 2014
VL 20
IS 10
BP 2607
EP 2616
DI 10.1158/1078-0432.CCR-13-2690
PG 10
WC Oncology
SC Oncology
GA AI2WU
UT WOS:000336720200013
PM 24647571
ER
PT J
AU Palmieri, D
Duchnowska, R
Woditschka, S
Hua, E
Qian, YZ
Biernat, W
Sosinska-Mielcarek, K
Gril, B
Stark, AM
Hewitt, SM
Liewehr, DJ
Steinberg, SM
Jassem, J
Steeg, PS
AF Palmieri, Diane
Duchnowska, Renata
Woditschka, Stephan
Hua, Emily
Qian, Yongzhen
Biernat, Wojciech
Sosinska-Mielcarek, Katarzyna
Gril, Brunilde
Stark, Andreas M.
Hewitt, Stephen M.
Liewehr, David J.
Steinberg, Seth M.
Jassem, Jacek
Steeg, Patricia S.
TI Profound Prevention of Experimental Brain Metastases of Breast Cancer by
Temozolomide in an MGMT-Dependent Manner
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CELL LUNG-CANCER; NERVOUS-SYSTEM METASTASES; PHASE-II TRIAL; LOW-GRADE
GLIOMAS; SOLID TUMORS; IN-VIVO; CLINICAL-TRIALS; BLOOD-BRAIN;
CHEMOTHERAPY; LAPATINIB
AB Purpose: Brain metastases of breast cancer cause neurocognitive damage and are incurable. We evaluated a role for temozolomide in the prevention of brain metastases of breast cancer in experimental brain metastasis models.
Experimental Design: Temozolomide was administered in mice following earlier injection of braintropic HER2-positive JIMT-1-BR3 and triple-negative 231-BR-EGFP sublines, the latter with and without expression of O-6-methylguanine-DNA methyltransferase (MGMT). In addition, the percentage of MGMT-positive tumor cells in 62 patient-matched sets of breast cancer primary tumors and resected brain metastases was determined immunohistochemically.
Results: Temozolomide, when dosed at 50, 25, 10, or 5 mg/kg, 5 days per week, beginning 3 days after inoculation, completely prevented the formation of experimental brain metastases from MGMT-negative 231-BR-EGFP cells. At a 1 mg/kg dose, temozolomide prevented 68% of large brain metastases, and was ineffective at a dose of 0.5 mg/kg. When the 50 mg/kg dose was administered beginning on days 18 or 24, temozolomide efficacy was reduced or absent. Temozolomide was ineffective at preventing brain metastases in MGMT-transduced 231-BR-EGFP and MGMT-expressing JIMT-1-BR3 sublines. In 62 patient-matched sets of primary breast tumors and resected brain metastases, 43.5% of the specimens had concordant low MGMT expression, whereas in another 14.5% of sets high MGMT staining in the primary tumor corresponded with low staining in the brain metastasis.
Conclusions: Temozolomide profoundly prevented the outgrowth of experimental brain metastases of breast cancer in an MGMT-dependent manner. These data provide compelling rationale for investigating the preventive efficacy of temozolomide in a clinical setting.
C1 [Palmieri, Diane; Woditschka, Stephan; Hua, Emily; Gril, Brunilde; Steeg, Patricia S.] NCI, Womens Malignancies Branch, NIH, Bethesda, MD 20892 USA.
[Hewitt, Stephen M.; Jassem, Jacek] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Liewehr, David J.; Steinberg, Seth M.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
[Qian, Yongzhen] NCI, Lab Anim Sci Program, SAIC Frederick, NIH, Frederick, MD 21701 USA.
[Duchnowska, Renata] Mil Inst Med, Dept Oncol, Warsaw, Poland.
[Biernat, Wojciech] Med Univ, Dept Pathomorphol, Gdansk, Poland.
[Jassem, Jacek] Med Univ, Dept Oncol & Radiotherapy, Gdansk, Poland.
[Sosinska-Mielcarek, Katarzyna] Reg Canc Ctr, Gdansk, Poland.
[Stark, Andreas M.] Klin Neurochirurg UKSH Campus Kiel, Kiel, Germany.
RP Steeg, PS (reprint author), NCI, 37-1126 NIH, Bethesda, MD 20892 USA.
EM steegp@mail.nih.gov
RI Palmieri, Diane/B-4258-2015;
OI Hewitt, Stephen/0000-0001-8283-1788
FU Intramural program of the National Cancer Institute; U.S. Department of
Defense Breast Cancer Research Program [W81 XWH-062-0033]; Intramural
grant of the Medical University of Gdansk (Gdansk, Poland) [ST-51]
FX This work was supported by the Intramural program of the National Cancer
Institute and U.S. Department of Defense Breast Cancer Research Program,
grant number: W81 XWH-062-0033, and an Intramural grant of the Medical
University of Gdansk (Gdansk, Poland), grant number ST-51.
NR 51
TC 12
Z9 12
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAY 15
PY 2014
VL 20
IS 10
BP 2727
EP 2739
DI 10.1158/1078-0432.CCR-13-2588
PG 13
WC Oncology
SC Oncology
GA AI2WU
UT WOS:000336720200024
PM 24634373
ER
PT J
AU Lu, X
Mazur, SJ
Lin, T
Appella, E
Xu, Y
AF Lu, X.
Mazur, S. J.
Lin, T.
Appella, E.
Xu, Y.
TI The pluripotency factor nanog promotes breast cancer tumorigenesis and
metastasis
SO ONCOGENE
LA English
DT Article
DE nanog; breast cancer; tumorigenesis; metastasis
ID EMBRYONIC STEM-CELLS; GENE-EXPRESSION; SIGNALING PATHWAYS;
TUMOR-DEVELOPMENT; MAMMARY-GLAND; ES CELLS; GENOME; OCT4; MIGRATION;
CARCINOMA
AB Nanog is a transcription factor required for maintaining the pluripotency of embryonic stem cells, and is not expressed in most normal adult tissues. However, recent studies have indicated that Nanog is overexpressed in many types of human cancers, including breast cancer. To elucidate the physiological roles of Nanog in tumorigenesis, we developed an inducible Nanog transgenic mouse model, in which the expression of Nanog in adult tissues can be induced via LoxP/Cre-mediated deletion. Our findings indicate that overexpression of Nanog in the mammary gland is not sufficient to induce mammary tumor. However, when coexpressed with Wnt-1 in the mouse mammary gland, it promotes mammary tumorigenesis and metastasis. In this context, Nanog promotes the migration and invasion of breast cancer cells. Microarray analysis has shown that the ectopic expression of Nanog deregulates the expression of numerous genes associated with tumorigenesis and metastasis, such as the PDGFR alpha gene. Our findings demonstrate the involvement of Nanog in breast cancer metastasis, and provide the basis for the reported correlation between Nanog expression and poor prognosis of human breast cancer patients. As Nanog is not expressed in most adult tissues, these findings identify Nanog as a potential therapeutic target in the treatment of Nanog-expressing metastatic breast cancer.
C1 [Lu, X.; Xu, Y.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
[Mazur, S. J.; Appella, E.] NCI, Lab Cell Biol, NIH, Bethesda, MD 20892 USA.
[Lin, T.] Guangdong Prov Acad Chinese Med Sci, Ctr Regenerat Med & Translat Med, Guangzhou, Guangdong, Peoples R China.
RP Xu, Y (reprint author), Univ Calif San Diego, Div Biol Sci, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM yangxu@ucsd.edu
RI Lin, Tongxiang/I-4695-2013
OI Lin, Tongxiang/0000-0001-7033-6982
FU NIH [CA94254, CA124834]; Intramural Research Program of the National
Cancer Institute, National Institutes of Health
FX We thank Y Li for providing the Wnt-1 transgenic mice. This work was
supported by NIH grants (CA94254 and CA124834) to YX and by the
Intramural Research Program of the National Cancer Institute, National
Institutes of Health.
NR 52
TC 31
Z9 33
U1 2
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD MAY 15
PY 2014
VL 33
IS 20
BP 2655
EP 2664
DI 10.1038/onc.2013.209
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA AH9YT
UT WOS:000336502700011
PM 23770853
ER
PT J
AU Selker, HP
Udelson, JE
Massaro, JM
Ruthazer, R
D'Agostino, RB
Griffith, JL
Sheehan, PR
Desvigne-Nickens, P
Rosenberg, Y
Tian, X
Vickery, EM
Atkins, JM
Aufderheide, TP
Sayah, AJ
Pirrallo, RG
Levy, MK
Richards, ME
Braude, DA
Doyle, DD
Frascone, RJ
Kosiak, DJ
Leaming, JM
Van Gelder, CM
Walter, GP
Wayne, MA
Woolard, RH
Beshansky, JR
AF Selker, Harry P. a
Udelson, James E.
Massaro, Joseph M.
Ruthazer, Robin
D'Agostino, Ralph B.
Griffith, John L.
Sheehan, Patricia R.
Desvigne-Nickens, Patrice
Rosenberg, Yves
Tian, Xin
Vickery, Ellen M.
Atkins, James M.
Aufderheide, Tom P.
Sayah, Assaad J.
Pirrallo, Ronald G.
Levy, Michael K.
Richards, Michael E.
Braude, Darren A.
Doyle, Delanor D.
Frascone, Ralph J.
Kosiak, Donald J.
Leaming, James M.
Van Gelder, Carin M.
Walter, Gert-Paul
Wayne, Marvin A.
Woolard, Robert H.
Beshansky, Joni R.
TI One-Year Outcomes of Out-of-Hospital Administration of Intravenous
Glucose, Insulin, and Potassium (GIK) in Patients With Suspected Acute
Coronary Syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic
Enhancement During Initial Assessment and Treatment in Emergency Care]
Trial)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; PREDICTIVE INSTRUMENT; INFARCTION;
INFUSION; MORTALITY; MULTICENTER; THERAPY; ASSIST; HEART
AB The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefits. Here we report 1-year outcomes. Prespecified 1-year end points of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF). Of 871 participants randomized to GIK versus placebo, death occurred within 1 year in 11.6% versus 13.5%, respectively (unadjusted hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.57 to 1.23, p = 0.36). The composite of cardiac arrest or 1-year mortality was 12.8% versus 17.0% (HR 0.71, 95% CI 0.50 to 1.02, p = 0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% versus 17.2% (FIR 0.98, 95% CI 0.70 to 1.37, p = 0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% versus 20.4% (HR 0.85, 95% CI 0.62 to 1.16, p = 0.30). In patients presenting with suspected ST elevation myocardial infarction, HRs for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33 to 1.27, p = 0.21), 0.52 (95% CI 0.30 to 0.92, p = 0.03), 0.63 (95% CI 0.35 to 1.16, p = 0.14), and 0.51 (95% CI 0.30 to 0.87, p = 0.01). In patients with suspected acute coronary syndromes, serious end points generally were lower with GIK than placebo, but the differences were not statistically significant. However, in those with ST elevation myocardial infarction, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Selker, Harry P. a; Ruthazer, Robin; Beshansky, Joni R.] Tufts Med Ctr, Ctr Cardiovasc Hlth Serv Res, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA.
[Udelson, James E.] Tufts Med Ctr, Div Cardiol, Boston, MA USA.
[Udelson, James E.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA.
[Sheehan, Patricia R.; Vickery, Ellen M.] Tufts Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA USA.
[Sheehan, Patricia R.; Vickery, Ellen M.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Massaro, Joseph M.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA.
[D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Griffith, John L.] Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA.
[Desvigne-Nickens, Patrice; Rosenberg, Yves; Tian, Xin] NHLBI, NIH, Bethesda, MD 20892 USA.
[Atkins, James M.] Univ Texas Southwestern, Sch Med, Dept Med, Dallas, TX USA.
[Aufderheide, Tom P.; Pirrallo, Ronald G.] Med Coll Wisconsin, Dept Emergency Med, Milwaukee, WI 53226 USA.
[Sayah, Assaad J.] Cambridge Hlth Alliance, Dept Emergency Med, Cambridge, MA USA.
[Levy, Michael K.] Alaska Reg Hosp, Dept Emergency Med, Anchorage, AK USA.
[Richards, Michael E.; Braude, Darren A.] Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Med, Albuquerque, NM 87131 USA.
[Braude, Darren A.] Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Anesthesiol, Albuquerque, NM 87131 USA.
[Doyle, Delanor D.] Med Ctr Cent Georgia, Dept Emergency Med, Macon, GA USA.
[Frascone, Ralph J.] Regions Hosp Emergency Med Serv, St Paul, MN USA.
[Kosiak, Donald J.] Avera Med Grp, Sioux Falls, SD USA.
[Leaming, James M.] Penn State Hershey Med Ctr, Dept Emergency Med, Hershey, PA USA.
[Van Gelder, Carin M.] Johnson Mem Hosp, Dept Emergency Med, Stafford, CT USA.
[Van Gelder, Carin M.] Windham Community Mem Hosp, Dept Emergency Med, Willimantic, CT USA.
[Walter, Gert-Paul] Emerson Hosp, Dept Emergency Med, Concord, MA USA.
[Wayne, Marvin A.] Peace Hlth St Joseph Med Ctr, Dept Emergency Med, Bellingham, WA USA.
[Woolard, Robert H.] Texas Tech Univ, Ctr Hlth Sci, Dept Emergency Med, El Paso, TX USA.
RP Selker, HP (reprint author), Tufts Med Ctr, Ctr Cardiovasc Hlth Serv Res, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA.
EM hselker@tuftsmedicalcenter.org
FU National Heart, Lung and Blood Institute (NHLBI) by way of a National
Institutes of Health (NIB) Cooperative Agreement [U01HL077821,
U01HL077826, U01HL077823]; NIH The National Center for Research
Resources [UL1RR025752]
FX This study was supported by grants U01HL077821, U01HL077826, and
U01HL077823 from the National Heart, Lung and Blood Institute (NHLBI) by
way of a National Institutes of Health (NIB) Cooperative Agreement. Role
of the Sponsor: Drs. Desvigne-Nickens, Rosenberg, and Tian from NIMBI,
respectively, were involved as part of the NIH Cooperative Agreement
process in the design and conduct of the study; collection, management,
analysis, and interpretation of the data; and preparation, review, and
approval of the manuscript. The contents of this article are solely the
responsibility of the authors and do not necessarily represent the
official views of the NHLBI or the NIH The National Center for Research
Resources provided support for specimen processing and testing by way of
grant UL1RR025752. Insulin was donated by Eli Lilly and Company,
Indianapolis, Indiana. Electrocardiograph-based decision support
software was donated by Physio-Control, Redmond, Washington, and Zoll
Medical, Chelmsford, Massachusetts. The National Center for Research
Resources, Eli Lilly and Company, Physio-Control, and Zoll Medical did
not participate in the design and conduct of the study; the collection,
management, analysis, and interpretation of the data; and preparation,
review, or approval of the manuscript.
NR 19
TC 12
Z9 12
U1 0
U2 3
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD MAY 15
PY 2014
VL 113
IS 10
BP 1599
EP 1605
DI 10.1016/j.amjcard.2014.02.010
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AH7UA
UT WOS:000336339600002
PM 24792735
ER
PT J
AU Pelser, C
Arem, H
Pfeiffer, RM
Elena, JW
Alfano, CM
Hollenbeck, AR
Park, Y
AF Pelser, Colleen
Arem, Hannah
Pfeiffer, Ruth M.
Elena, Joanne W.
Alfano, Catherine M.
Hollenbeck, Albert R.
Park, Yikyung
TI Prediagnostic Lifestyle Factors and Survival After Colon and Rectal
Cancer Diagnosis in the National Institutes of Health ( NIH)-AARP Diet
and Health Study
SO CANCER
LA English
DT Article
DE colorectal cancer; survivors; diet; body mass index; smoking; lifestyle
ID BODY-MASS INDEX; TREATMENT-RELATED TOXICITY; COLORECTAL-CANCER;
PHYSICAL-ACTIVITY; ASSOCIATION; RECURRENCE; OUTCOMES; IMPACT;
GUIDELINES; NUTRITION
AB BACKGROUNDFew studies have examined the relationship of lifestyle factors with mortality among patients with colorectal cancer.
METHODSAmong NIH-AARP Diet and Health study participants, 4213 colon and 1514 rectal cancer cases were identified through linkage to state cancer registries and determined date and cause of death using the National Death Index. Lifestyle factors were assessed at baseline and included: healthy diet (measured by Healthy Eating Index 2005 [HEI-2005]), body mass index (BMI), physical activity, alcohol consumption and smoking. The association of factors was examined individually and combined into a lifestyle score with 5-year mortality from all-causes, colorectal cancer, and cardiovascular disease (CVD). Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models.
RESULTSAmong colon cancer survivors, smokers had increased risk of total mortality (RR=1.74; 95% CI=1.45-2.08) and colorectal cancer mortality (RR=1.46; 95% CI=1.17-1.82), compared to never smokers. Obese (BMI,30) individuals had increased risk of all death (RR=1.19; 95% CI=1.02-1.39) and CVD death (RR=1.84; 95% CI=1.05-3.23), compared to normal weight (BMI, 18.5 to<25) individuals. Compared to those with the lowest lifestyle score, those with the highest score had a 34% lower risk of all-cause mortality (RR=0.66; 95% CI=0.50-0.87). Among rectal cancer survivors, individuals in the highest quintile of HEI-2005 scores had reduced all-cause mortality (RR=0.60; 95% CI=0.42-0.86) compared to those in the lowest. Higher combined lifestyle scores were associated with a 46% lower risk of total mortality (0.54; 0.32-0.91).
CONCLUSIONSHealthier lifestyle before cancer diagnosis was associated with improved overall survival after diagnosis with colorectal cancer. Cancer 2014;120:1540-1547 2014.
Several modifiable lifestyle factors measured prediagnosis were related to survival among patients with colorectal cancer. A combined lifestyle score consisting of meeting recommendations for diet, body weight, physical activity, alcohol intake, and smoking was also associated with reduced all-cause mortality.
C1 [Pelser, Colleen] NCI, Canc Prevent Fellowship Program, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Pelser, Colleen; Arem, Hannah; Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Elena, Joanne W.] NCI, Clin & Translat Epidemiol Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Pelser, C (reprint author), Univ Maryland, Greenebaum Canc Ctr, Room N9E02, Baltimore, MD 21201 USA.
EM cpelser@umm.edu
OI Park, Yikyung/0000-0002-6281-489X
FU National Institutes of Health, National Cancer Institute
FX Funding provided by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute.
NR 24
TC 29
Z9 29
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAY 15
PY 2014
VL 120
IS 10
BP 1540
EP 1547
DI 10.1002/cncr.28573
PG 8
WC Oncology
SC Oncology
GA AG4BJ
UT WOS:000335363400016
PM 24591061
ER
PT J
AU Fredriksson, K
Mishra, A
Lam, JK
Mushaben, EM
Cuento, RA
Meyer, KS
Yao, XL
Keeran, KJ
Nugent, GZ
Qu, X
Yu, ZX
Yang, YQ
Raghavachari, N
Dagur, PK
McCoy, JP
Levine, SJ
AF Fredriksson, Karin
Mishra, Amarjit
Lam, Jonathan K.
Mushaben, Elizabeth M.
Cuento, Rosemarie A.
Meyer, Katharine S.
Yao, Xianglan
Keeran, Karen J.
Nugent, Gayle Z.
Qu, Xuan
Yu, Zu-Xi
Yang, Yanqin
Raghavachari, Nalini
Dagur, Pradeep K.
McCoy, J. Philip
Levine, Stewart J.
TI The Very Low Density Lipoprotein Receptor Attenuates House Dust
Mite-Induced Airway Inflammation by Suppressing Dendritic Cell-Mediated
Adaptive Immune Responses
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NONINTEGRIN DC-SIGN; C-TYPE LECTIN; VLDL RECEPTOR;
PLASMINOGEN-ACTIVATOR; APOLIPOPROTEIN-E; NEURONAL MIGRATION; MICE
LACKING; ASTHMA; ALLERGEN; PROTEIN
AB The very low density lipoprotein receptor (VLDLR) is a member of the low-density lipoprotein receptor family that binds multiple ligands and plays a key role in brain development. Although the VLDLR mediates pleiotropic biological processes, only a limited amount of information is available regarding its role in adaptive immunity. In this study, we identify an important role for the VLDLR in attenuating house dust mite (HDM)-induced airway inflammation in experimental murine asthma. We show that HDM-challenged Vldlr(-/-) mice have augmented eosinophilic and lymphocytic airway inflammation with increases in Th2 cytokines, C-C chemokines, IgE production, and mucous cell metaplasia. A genome-wide analysis of the lung transcriptome identified that mRNA levels of CD209e (DC-SIGNR4), a murine homolog of DC-SIGN, were increased in the lungs of HDM-challenged Vldlr(-/-) mice, which suggested that the VLDLR might modify dendritic cell (DC) function. Consistent with this, VLDLR expression by human monocyte-derived DCs was increased by HDM stimulation. In addition, 55% of peripheral blood CD11c(+) DCs from individuals with allergy expressed VLDLR under basal conditions. Lastly, the adoptive transfer of HDMpulsed, CD11c(+) bone marrow-derived DCs (BMDCs) from Vldlr(-/)- mice to the airways of wild type recipient mice induced augmented eosinophilic and lymphocytic airway inflammation upon HDM challenge with increases in Th2 cytokines, C-C chemokines, IgE production, and mucous cell metaplasia, as compared with the adoptive transfer of HDM-pulsed, CD11c(+) BMDCs from wild type mice. Collectively, these results identify a novel role for the VLDLR as a negative regulator of DC-mediated adaptive immune responses in HDM-induced allergic airway inflammation.
C1 [Fredriksson, Karin; Mishra, Amarjit; Lam, Jonathan K.; Mushaben, Elizabeth M.; Cuento, Rosemarie A.; Meyer, Katharine S.; Yao, Xianglan; Levine, Stewart J.] NHLBI, Lab Asthma & Lung Inflammat, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Keeran, Karen J.; Nugent, Gayle Z.] NHLBI, Anim Surg & Resources Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Qu, Xuan; Yu, Zu-Xi] NHLBI, Pathol Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Yang, Yanqin; Raghavachari, Nalini] NHLBI, DNA Sequencing & Genom Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Dagur, Pradeep K.; McCoy, J. Philip] NHLBI, Flow Cytometry Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Levine, SJ (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA.
EM levines@nhlbi.nih.gov
RI MISHRA, AMARJIT/D-7504-2016
OI MISHRA, AMARJIT/0000-0002-3777-0338
FU Division of Intramural Research, National Heart, Lung, and Blood
Institute
FX This work was supported by the Division of Intramural Research, National
Heart, Lung, and Blood Institute.
NR 57
TC 4
Z9 4
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD MAY 15
PY 2014
VL 192
IS 10
BP 4497
EP 4509
DI 10.4049/jimmunol.1301234
PG 13
WC Immunology
SC Immunology
GA AH2TI
UT WOS:000335973600006
PM 24733846
ER
PT J
AU Olivares-Zavaleta, N
Whitmire, WM
Kari, L
Sturdevant, GL
Caldwell, HD
AF Olivares-Zavaleta, Norma
Whitmire, William M.
Kari, Laszlo
Sturdevant, Gail L.
Caldwell, Harlan D.
TI CD8(+) T Cells Define an Unexpected Role in Live-Attenuated Vaccine
Protective Immunity against Chlamydia trachomatis Infection in Macaques
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID GENITAL-TRACT; TRANSCRIPTIONAL REGULATOR; ORAL IMMUNIZATION;
NONHUMAN-PRIMATES; CD4(+); PLASMID; GENES
AB Trachoma, caused by the obligate intracellular organism Chlamydia trachomatis, is the world's leading cause of preventable blindness for which a vaccine is needed. We have previously shown that a plasmid-deficient live-attenuated trachoma vaccine delivered ocularly to macaques elicited either solid or partial protective immunity against a virulent ocular challenge. Solidly protected macaques shared the same MHC class II alleles implicating CD4(+) T cells in superior protective immunity. Understandably, we sought to define T cell immune correlates in these animals to potentially improve vaccine efficacy. In this study, following a 2-y resting period, these macaques were boosted i.m. with the live-attenuated trachoma vaccine and their peripheral T cell anamnestic responses studied. Both solidly and partially protected macaques exhibited a CD4(+) and CD8(+) T cell anamnestic response following booster immunization. CD8(+) but not CD4(+) T cells from solidly protected macaques proliferated against soluble chlamydial Ag. We observed a more rapid T cell inflammatory cytokine response in tears of solidly protected animals following ocular rechallenge. Most notably, depletion of CD8(+) T cells in solidly protected macaques completely abrogated protective immunity. Collectively, our findings support the conclusion that CD8(+) T cells play an important but unexpected role in liveattenuated trachoma vaccine-mediated protective immunity.
C1 [Olivares-Zavaleta, Norma; Whitmire, William M.; Kari, Laszlo; Sturdevant, Gail L.; Caldwell, Harlan D.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Caldwell, HD (reprint author), NIAID, Rocky Mt Labs, 903 South 4th St, Hamilton, MT 59840 USA.
EM hcaldwell@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 26
TC 10
Z9 10
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD MAY 15
PY 2014
VL 192
IS 10
BP 4648
EP 4654
DI 10.4049/jimmunol.1400120
PG 7
WC Immunology
SC Immunology
GA AH2TI
UT WOS:000335973600022
PM 24711617
ER
PT J
AU Greenlee-Wacker, MC
Rigby, KM
Kobayashi, SD
Porter, AR
DeLeo, FR
Nauseef, WM
AF Greenlee-Wacker, Mallary C.
Rigby, Kevin M.
Kobayashi, Scott D.
Porter, Adeline R.
DeLeo, Frank R.
Nauseef, William M.
TI Phagocytosis of Staphylococcus aureus by Human Neutrophils Prevents
Macrophage Efferocytosis and Induces Programmed Necrosis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID FRANCISELLA-TULARENSIS; APOPTOTIC CELLS; RECEPTOR; INFLAMMASOME;
NECROPTOSIS; DESTRUCTION; RECRUITMENT; ACTIVATION; INFECTION; SURVIVAL
AB Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) pose a significant threat to human health. Polymorphonuclear leukocytes (PMN) are the first responders during staphylococcal infection, but 15-50% of the initial ingested inoculum survives within the PMN phagosome and likely contributes directly or indirectly to disease pathogenesis. We hypothesize that surviving intracellular CA-MRSA undermine effective phagocyte-mediated defense by causing a decrease in macrophage uptake of PMN containing viable S. aureus and by promoting PMN lysis. In support of this hypothesis, PMN harboring viable CAMRSA strain USA300 (PMN-SA) upregulated the "don't eat me"signal CD47, remained bound to the surface, and were inefficiently ingested by macrophages. In addition, coculture with PMN-SA altered the macrophage phenotype. Compared to macrophages fed USA300 alone, macrophages challenged with PMN-SA produced more IL-8 and less IL-1 receptor antagonist, TNF-a, activated caspase-1, and IL-1 beta. Although they exhibited some features of apoptosis within 3 h following ingestion of S. aureus, including phosphatidylserine exposure and mitochondrial membrane depolarization, PMN-SA had sustained levels of proliferating cell nuclear Ag expression, absence of caspase activation, and underwent lysis within 6 h following phagocytosis. PMN lysis was dependent on receptor-interacting protein 1, suggesting that PMN-SA underwent programmed necrosis or necroptosis. These data are the first demonstration, to our knowledge, that bacteria can promote sustained expression of proliferating cell nuclear Ag and that human PMN undergo necroptosis. Together, these findings demonstrate that S. aureus surviving within PMN undermine the innate immune response and may provide insight into the pathogenesis of S. aureus disease.
C1 [Greenlee-Wacker, Mallary C.; Nauseef, William M.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Inflammat Program, Vet Adm Med Ctr, Iowa City, IA 52240 USA.
[Greenlee-Wacker, Mallary C.; Nauseef, William M.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Vet Adm Med Ctr, Iowa City, IA 52240 USA.
[Rigby, Kevin M.] Univ Utah, Sch Med, Program Mol Med, Salt Lake City, UT 84112 USA.
[Kobayashi, Scott D.; Porter, Adeline R.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Nauseef, WM (reprint author), Univ Iowa, Roy J & Lucille A Carver Coll Med, Inflammat Program, D160 MTF,2501 Crosspark Rd, Coralville, IA 52241 USA.
EM william-nauseef@uiowa.edu
OI DeLeo, Frank/0000-0003-3150-2516
FU T32 Training Grant from the University of Iowa [2T32AI007260-26A1];
National Institutes of Health [AI70958, AI044642]; Intramural Research
Program of the National Institute of Allergy and Infectious Diseases,
National Institutes of Health; merit review award
FX This work was supported by T32 Training Grant 2T32AI007260-26A1 from the
University of Iowa and the National Institutes of Health (to M.C.G.-W.),
National Institutes of Health Grants AI70958 and AI044642 (to W.M.N.),
and the Intramural Research Program of the National Institute of Allergy
and Infectious Diseases, National Institutes of Health (to F.R.D.). The
Nauseef laboratory was supported by a merit review award and use of
facilities at the Iowa City Department of Veterans Affairs Medical
Center, Iowa City, IA.
NR 40
TC 41
Z9 41
U1 1
U2 12
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD MAY 15
PY 2014
VL 192
IS 10
BP 4709
EP 4717
DI 10.4049/jimmunol.1302692
PG 9
WC Immunology
SC Immunology
GA AH2TI
UT WOS:000335973600028
PM 24729616
ER
PT J
AU Yoo, DG
Winn, M
Pang, L
Moskowitz, SM
Malech, HL
Leto, TL
Rada, B
AF Yoo, Dae-goon
Winn, Matthew
Pang, Lan
Moskowitz, Samuel M.
Malech, Harry L.
Leto, Thomas L.
Rada, Balazs
TI Release of Cystic Fibrosis Airway Inflammatory Markers from Pseudomonas
aeruginosa-Stimulated Human Neutrophils Involves NADPH Oxidase-Dependent
Extracellular DNA Trap Formation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID RESPIRATORY EPITHELIUM; PEROXIDASE-ACTIVITY; PULMONARY-FUNCTION; SPUTUM
BIOMARKERS; HYPOCHLOROUS ACID; INNATE IMMUNITY; LUNG-FUNCTION;
RISK-FACTORS; MYELOPEROXIDASE; INFECTION
AB Cystic fibrosis (CF) airways are characterized by bacterial infections, excess mucus production, and robust neutrophil recruitment. The main CF airway pathogen is Pseudomonas aeruginosa. Neutrophils are not capable of clearing the infection. Neutrophil primary granule components, myeloperoxidase (MPO) and human neutrophil elastase (HNE), are inflammatory markers in CF airways, and their increased levels are associated with poor lung function. Identifying the mechanism of MPO and HNE release from neutrophils is of high clinical relevance for CF. In this article, we show that human neutrophils release large amounts of neutrophil extracellular traps (NETs) in the presence of P. aeruginosa. Bacteria are entangled in NETs and colocalize with extracellular DNA. MPO, HNE, and citrullinated histone H4 are all associated with DNA in Pseudomonas-triggered NETs. Both laboratory standard strains and CF isolates of P. aeruginosa induce DNA, MPO, and HNE release from human neutrophils. The increase in peroxidase activity of neutrophil supernatants after Pseudomonas exposure indicates that enzymatically active MPO is released. P. aeruginosa induces a robust respiratory burst in neutrophils that is required for extracellular DNA release. Inhibition of the cytoskeleton prevents Pseudomonas-initiated superoxide production and DNA release. NADPH oxidase inhibition suppresses Pseudomonas-induced release of active MPO and HNE. Blocking MEK/ERK signaling results in only minimal inhibition of DNA release induced by Pseudomonas. Our data describe in vitro details of DNA, MPO, and HNE release from neutrophils activated by P. aeruginosa. We propose that Pseudomonas-induced NET formation is an important mechanism contributing to inflammatory conditions characteristic of CF airways.
C1 [Yoo, Dae-goon; Winn, Matthew; Pang, Lan; Rada, Balazs] Univ Georgia, Coll Vet Med, Dept Infect Dis, Athens, GA 30602 USA.
[Moskowitz, Samuel M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Moskowitz, Samuel M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Malech, Harry L.; Leto, Thomas L.] NIAID, Host Def Lab, NIH, Rockville, MD 20852 USA.
RP Rada, B (reprint author), Univ Georgia, Coll Vet Med, Dept Infect Dis, 501 DW Brooks Dr, Athens, GA 30602 USA.
EM radab@uga.edu
OI Malech, Harry/0000-0001-5874-5775
FU startup funds from the Office of the Vice President for Research,
University of Georgia; Intramural Research Program of the National
Institutes of Health, National Institute of Allergy and Infectious
Diseases
FX This work was supported by startup funds from the Office of the Vice
President for Research, University of Georgia (to B.R.) and by the
Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases.
NR 58
TC 20
Z9 21
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD MAY 15
PY 2014
VL 192
IS 10
BP 4728
EP 4738
DI 10.4049/jimmunol.1301589
PG 11
WC Immunology
SC Immunology
GA AH2TI
UT WOS:000335973600030
PM 24740504
ER
PT J
AU Imamichi, H
Natarajan, V
Adelsberger, JW
Rehm, CA
Lempicki, RA
Das, B
Hazen, A
Imamichi, T
Lane, HC
AF Imamichi, Hiromi
Natarajan, Ven
Adelsberger, Joseph W.
Rehm, Catherine A.
Lempicki, Richard A.
Das, Biswajit
Hazen, Allison
Imamichi, Tomozumi
Lane, H. Clifford
TI Lifespan of effector memory CD4(+) T cells determined by
replication-incompetent integrated HIV-1 provirus
SO AIDS
LA English
DT Article
DE genetic marker; integration; replication-incompetent; provirus; in-vivo
persistence of CD4-positive T lymphocytes; HIV-1
ID IMMUNODEFICIENCY-VIRUS TYPE-1; IMMUNOLOGICAL MEMORY; VIF PROTEIN;
IN-VIVO; HYPERMUTATION; INFECTION; DNA; NAIVE; SEQUENCES; TURNOVER
AB Objective:
Determining the precise lifespan of human T-cell is challenging due to the inability of standard techniques to distinguish between dividing and dying cells. Here, we measured the lifespan of a pool of T cells that were derived from a single cell 'naturally' labelled with a single integrated clone of a replication-incompetent HIV-1 provirus.
Design/methods:
Utilizing a combination of techniques, we were able to sequence/map an integration site of a unique provirus with a stop codon at position 42 of the HIV-1 protease. In-vitro reconstruction of this provirus into an infectious clone confirmed its inability to replicate. By combining cell separation and integration site-specific PCR, we were able to follow the fate of this single provirus in multiple T-cell subsets over a 20-year period. As controls, a number of additional integrated proviruses were also sequenced.
Results:
The replication-incompetent HIV-1 provirus was solely contained in the pool of effector memory CD4(+) T cells for 17 years. The percentage of the total effector memory CD4(+) T cells containing the replication-incompetent provirus peaked at 1% with a functional half-life of 11.1 months. In the process of sequencing multiple proviruses, we also observed high levels of lethal mutations in the peripheral blood pool of proviruses.
Conclusion:
These data indicate that human effector memory CD4(+) T cells are able to persist in vivo for more than 17 years without detectably reverting to a central memory phenotype. A secondary observation is that the fraction of the pool of integrated HIV-1 proviruses capable of replicating may be considerably less than the 12% currently noted in the literature.
C1 [Imamichi, Hiromi; Rehm, Catherine A.; Lane, H. Clifford] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Natarajan, Ven; Adelsberger, Joseph W.; Lempicki, Richard A.; Das, Biswajit; Hazen, Allison; Imamichi, Tomozumi] Leidos Biomed Res Inc, Clin Serv Program, Appl & Dev Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Lane, HC (reprint author), CRC, 9000 Rockville Pike,Bldg 10,Rm 4-1479,MSC 1460, Bethesda, MD 20892 USA.
EM CLANE@niaid.nih.gov
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health (Bethesda, Maryland); National Cancer Institute,
National Institutes of Health [HHSN261200800001E]
FX This work was funded through the intramural research programme of the
National Institute of Allergy and Infectious Diseases of the National
Institutes of Health (Bethesda, Maryland) and in part with federal funds
from the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial products
or organizations imply endorsement by the U.S. Government.
NR 38
TC 13
Z9 13
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD MAY 15
PY 2014
VL 28
IS 8
BP 1091
EP 1099
DI 10.1097/QAD.0000000000000223
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AG8FK
UT WOS:000335654000002
PM 24492253
ER
PT J
AU Ellen, JM
Kapogiannis, B
Fortenberry, JD
Xu, JH
Willard, N
Duval, A
Pace, J
Loeb, J
Monte, D
Bethel, J
AF Ellen, Jonathan M.
Kapogiannis, Bill
Fortenberry, J. Dennis
Xu, Jiahong
Willard, Nancy
Duval, Anna
Pace, Jill
Loeb, Jackie
Monte, Dina
Bethel, James
CA Adolescent Med Trials Network HIV
TI HIV viral load levels and CD4(+) cell counts of youth in 14 cities
SO AIDS
LA English
DT Article
DE CD4+ cell count; viral load; HIV; linkage to care; youth
ID PREVENTION; INFECTION; RISK; TRANSMISSION; CARE; MEN
AB Objectives:
To describe the HIV viral load and CD4(+) cell counts of youth (12-24 years) in 14 cities from March 2010 through November 2011.
Methods:
Baseline HIV viral load and CD4(+) cell count data were electronically abstracted in a central location and in an anonymous manner through a random computer-generated coding system without any ability to link codes to individual cases.
Results:
Among 1409 HIV reported cases, 852 participants had data on both viral load and CD4(+) cell counts. Of these youth, 34% had CD4(+) cell counts of 350 or less, 27% had cell counts from 351 to 500, and 39% had CD4(+) cell counts greater than 500. Youth whose transmission risk was male-to-male sexual contact had higher viral loads compared with youth whose transmission risk was perinatal or heterosexual contact. Greater than 30% of those who reported male-to-male sexual contact had viral loads greater than 50 000 copies, whereas less than 20% of heterosexual contact youth had viral loads greater than 50 000 copies. There were no differences noted in viral load by type of testing site.
Conclusion:
Most HIV-infected youth have CD4(+) cell counts and viral load levels associated with high rates of sexual transmission. Untreated, these youth may directly contribute to high rates of ongoing transmission. It is essential that any public health test and treat strategy place a strong emphasis on youth, particularly young MSM.
C1 [Ellen, Jonathan M.] All Childrens Hosp Johns Hopkins Med, St Petersburg, FL 33701 USA.
[Kapogiannis, Bill; Pace, Jill] NICHHD, NIH, Bethesda, MD 20892 USA.
[Fortenberry, J. Dennis] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Xu, Jiahong; Loeb, Jackie; Monte, Dina; Bethel, James] WESTAT Corp, Rockville, MD 20850 USA.
[Willard, Nancy; Duval, Anna] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Ellen, JM (reprint author), All Childrens Hosp Johns Hopkins Med, 501 6th Ave, St Petersburg, FL 33701 USA.
EM jellen@jhmi.edu
FU Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) from
the National Institutes of Health through the National Institute of
Child Health and Human Development [U01 HD 040533, U01 HD 040474];
National Institute on Drug Abuse; National Institute on Mental Health
FX ATN 093 was supported by The Adolescent Medicine Trials Network for
HIV/AIDS Interventions (ATN) from the National Institutes of Health (U01
HD 040533 and U01 HD 040474) through the National Institute of Child
Health and Human Development (B. Kapogiannis, C. Worrell), with
supplemental funding from the National Institutes on Drug Abuse (K.
Davenny) and Mental Health (P. Brouwers, S. Allison).
NR 18
TC 1
Z9 2
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD MAY 15
PY 2014
VL 28
IS 8
BP 1213
EP 1219
DI 10.1097/QAD.0000000000000183
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AG8FK
UT WOS:000335654000014
PM 25028912
ER
PT J
AU Longosz, AF
Mehta, SH
Kirk, GD
Margolick, JB
Brown, J
Quinn, TC
Eshleman, SH
Laeyendecker, O
AF Longosz, Andrew F.
Mehta, Shruti H.
Kirk, Gregory D.
Margolick, Joseph B.
Brown, Joelle
Quinn, Thomas C.
Eshleman, Susan H.
Laeyendecker, Oliver
TI Incorrect identification of recent HIV infection in adults in the United
States using a limiting-antigen avidity assay
SO AIDS
LA English
DT Article
DE incidence; people who inject drugs; misclassification; limiting-antigen
avidity; HIV; MSM
ID CAPTURE ENZYME-IMMUNOASSAY; ANTIRETROVIRAL TREATMENT; TYPE-1
SEROCONVERSION; SPECIFICITY; COHORT
AB Objectives:
To evaluate factors associated with misclassification by the limiting-antigen avidity (LAg-avidity) assay among individuals with long-standing HIV infection.
Design:
Samples were obtained from the Multicenter AIDS Cohort Study and AIDS Linked to the IntraVenous Experience cohort (1089 samples from 667 individuals, 595 samples collected 2-4 years and 494 samples collected 4-8 years after HIV seroconversion). Paired samples from both time points were available for 422 (63.3%) of the 667 individuals.
Methods:
Samples were considered to be misclassified if the LAg-avidity assay result was 1.5 or less normalized optical density (OD-n) units.
Results:
Overall, 4.8% (52/1089) of the samples were misclassified, including 1.8% [16/884, 95% confidence interval (CI) 1.09-3.06%] of samples from individuals with viral loads above 400 copies/ml and 1.4% (10/705) of samples from individuals with viral loads above 400 copies/ml and CD4(+) cell counts above 200 cells/mu l (95% CI 0.68-2.60%). Age, race, sex, and mode of HIV acquisition were not associated with misclassification. In an adjusted analysis, viral load below 400 copies/ml [adjusted odds ratio (aOR) 3.72, 95% CI 1.61-8.57], CD4(+) cell count below 50 cells/mu l (aOR 5.41, 95% CI 1.86-15.74), and low LAg-avidity result (<= 1.5 OD-n) from the earlier time point (aOR 5.60, 95% CI 1.55-20.25) were significantly associated with misclassification.
Conclusions:
The manufacturer of the LAg-avidity assay recommends excluding individuals from incidence surveys who are receiving antiretroviral therapy, are elite suppressors, or have AIDS (CD4(+) cell count <200 cells/mu l). The results of this study indicate that those exclusions do not remove all sources of assay misclassification among individuals with long-standing HIV infection.
C1 [Longosz, Andrew F.; Quinn, Thomas C.; Laeyendecker, Oliver] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Baltimore, MD USA.
[Mehta, Shruti H.; Kirk, Gregory D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Margolick, Joseph B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Brown, Joelle] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Quinn, Thomas C.; Laeyendecker, Oliver] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
RP Laeyendecker, O (reprint author), NIAID, LIR, NIH, 855 North Wolfe St,Room 538A, Baltimore, MD USA.
EM olaeyen1@jhmi.edu
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU National Institute of Allergy and Infectious Diseases (NIAID), National
Institute of Drug Abuse (NIDA); Department of Health and Human Services
[UM1-AI068613]; NIH, NIAID [R01-A134826, K22-AI092150-01, R01-A134265];
NICHD [R01-HD 050180]; Division of Intramural Research, NIAID, NIH;
National Institute of Mental Health (NIMH), Office of AIDS Research,
National Institutes of Health (NIH); [R01-AI095068]
FX The HIV Prevention Trials Network (HPTN), funded by the National
Institute of Allergy and Infectious Diseases (NIAID), National Institute
of Drug Abuse (NIDA) and the National Institute of Mental Health (NIMH),
Office of AIDS Research, National Institutes of Health (NIH), Department
of Health and Human Services (UM1-AI068613 - Eshleman); and R01-AI095068
(Eshleman/Brookmeyer). Multicenter AIDS Cohort Study (U01 AI35042-21)
and the AIDS Linked to the IntraVenous Experience (2R56DA004334-27). The
studies that collected samples used for analysis were funded by the NIH,
NIAID (R01-A134826, K22-AI092150-01, and R01-A134265), NICHD (R01-HD
050180), and additional support was provided by the Division of
Intramural Research, NIAID, NIH.
NR 30
TC 12
Z9 12
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD MAY 15
PY 2014
VL 28
IS 8
BP 1227
EP 1232
DI 10.1097/QAD.0000000000000221
PG 6
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AG8FK
UT WOS:000335654000016
PM 24513567
ER
PT J
AU Rowley, CA
Ikeda, AK
Seidel, M
Anaebere, TC
Antalek, MD
Seamon, C
Conrey, AK
Mendelsohn, L
Nichols, J
Gorbach, AM
Kato, GJ
Ackerman, H
AF Rowley, Carol A.
Ikeda, Allison K.
Seidel, Miles
Anaebere, Tiffany C.
Antalek, Matthew D.
Seamon, Catherine
Conrey, Anna K.
Mendelsohn, Laurel
Nichols, James
Gorbach, Alexander M.
Kato, Gregory J.
Ackerman, Hans
TI Microvascular oxygen consumption during sickle cell pain crisis
SO BLOOD
LA English
DT Article
ID NEAR-INFRARED SPECTROSCOPY; DISEASE; METABOLISM; MECHANISMS; PULMONARY;
INJURY; SEPSIS
AB Sickle cell disease is an inherited blood disorder characterized by chronic hemolytic anemia and episodic vaso-occlusive pain crises. Vaso-occlusion occurs when deoxygenated hemoglobin S polymerizes and erythrocytes sickle and adhere in the microvasculature, a process dependent on the concentration of hemoglobin S and the rate of deoxygenation, among other factors. We measured oxygen consumption in the thenar eminence during brachial artery occlusion in sickle cell patients and healthy individuals. Microvascular oxygen consumption was greater in sickle cell patients than in healthy individuals (median [interquartile range]; sickle cell: 0.91 [0.75-1.07] vs healthy: 0.75 [0.62-0.94] -Delta HbO(2)/min, P < .05) and was elevated further during acute pain crisis (crisis: 1.10 [0.78-1.30] vs recovered: 0.88 [0.76-1.03] -Delta HbO(2)/min, P < .05). Increased microvascular oxygen consumption during pain crisis could affect the local oxygen saturation of hemoglobin when oxygen delivery is limiting. Identifying the mechanisms of elevated oxygen consumption during pain crisis might lead to the development of new therapeutic interventions. This trial was registered at www.clinicaltrials.gov as #NCT01568710.
C1 [Rowley, Carol A.; Ikeda, Allison K.; Anaebere, Tiffany C.; Ackerman, Hans] NIAID, Lab Malaria & Vector Res, Rockville, MD 20852 USA.
[Seidel, Miles; Antalek, Matthew D.; Gorbach, Alexander M.] Natl Inst Biomed Imaging & Bioengn, Infrared Imaging & Thermometry Unit, Bethesda, MD USA.
[Seamon, Catherine; Conrey, Anna K.; Mendelsohn, Laurel; Nichols, James; Kato, Gregory J.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
RP Ackerman, H (reprint author), NIAID, Lab Malaria & Vector Res, 12735 Twinbrook Pkwy,Room 3E-28, Rockville, MD 20852 USA.
EM hans.ackerman@nih.gov
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU National Institutes of Health at the National Heart, Lung and Blood
Institute; National Institute of Allergy and Infectious Diseases;
National Institute of Biomedical Imaging and Bioengineering
FX This study was supported by the Intramural Research Program of the
National Institutes of Health at the National Heart, Lung and Blood
Institute, the National Institute of Allergy and Infectious Diseases,
and the National Institute of Biomedical Imaging and Bioengineering.
NR 21
TC 2
Z9 2
U1 0
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 15
PY 2014
VL 123
IS 20
BP 3101
EP 3104
DI 10.1182/blood-2013-11-533406
PG 4
WC Hematology
SC Hematology
GA AH1RU
UT WOS:000335899400017
PM 24665133
ER
PT J
AU Singh, OP
Hasker, E
Sacks, D
Boelaert, M
Sundar, S
AF Singh, Om Prakash
Hasker, Epco
Sacks, David
Boelaert, Marleen
Sundar, Shyam
TI Asymptomatic Leishmania Infection: A New Challenge for Leishmania
Control
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
DE visceral leishmaniasis; asymptomatic infection; immunity
ID INDIAN VISCERAL LEISHMANIASIS; KALA-AZAR; DONOVANI INFECTION;
RISK-FACTORS; SUBCLINICAL INFECTION; DIRECT AGGLUTINATION; INFANTUM
INFECTION; IMMUNE-RESPONSE; EASTERN SUDAN; ENDEMIC AREA
AB Visceral leishmaniasis (VL) is a serious parasitic disease, causing high morbidity and mortality in the developing world. The pathogenesis of VL is complex, and the clinical presentation ranges from asymptomatic infection to severe and fatal disease. Despite a wealth of research on the full-blown "clinical VL" syndrome, asymptomatic leishmania infections remain poorly understood. Asymptomatic infection could present a major challenge for control programs if its infectiousness is confirmed. In this viewpoint, we highlight the crucial knowledge gaps as well as the obstacles in research on asymptomatic leishmanial infection. Research in this area is essential for the development of more-effective VL control strategies.
C1 [Singh, Om Prakash; Sundar, Shyam] Banaras Hindu Univ, Inst Med Sci, Dept Med, Infect Dis Res Lab, Varanasi 221005, Uttar Pradesh, India.
[Hasker, Epco; Boelaert, Marleen] Inst Trop Med, Dept Publ Hlth, B-2000 Antwerp, Belgium.
[Sacks, David] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Sundar, S (reprint author), Banaras Hindu Univ, Inst Med Sci, Dept Med, Varanasi 221005, Uttar Pradesh, India.
EM drshyamsundar@hotmail.com
FU NIAID NIH HHS [P50 AI074321, P50AI074321]
NR 62
TC 21
Z9 24
U1 2
U2 15
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAY 15
PY 2014
VL 58
IS 10
BP 1424
EP 1429
DI 10.1093/cid/ciu102
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AH3RZ
UT WOS:000336044200016
PM 24585564
ER
PT J
AU Lim, JK
Tate, JP
Fultz, SL
Goulet, JL
Conigliaro, J
Bryant, KJ
Gordon, AJ
Gibert, C
Rimland, D
Goetz, MB
Klein, MB
Fiellin, DA
Justice, AC
Lo Re, V
AF Lim, Joseph K.
Tate, Janet P.
Fultz, Shawn L.
Goulet, Joseph L.
Conigliaro, Joseph
Bryant, Kendall J.
Gordon, Adam J.
Gibert, Cynthia
Rimland, David
Goetz, Matthew Bidwell
Klein, Marina B.
Fiellin, David A.
Justice, Amy C.
Lo Re, Vincent, III
TI Relationship Between Alcohol Use Categories and Noninvasive Markers of
Advanced Hepatic Fibrosis in HIV-Infected, Chronic Hepatitis C
Virus-Infected, and Uninfected Patients
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE alcohol; liver fibrosis; HIV; hepatitis C; FIB-4
ID VETERANS AGING COHORT; PLATELET RATIO INDEX; PREDICTING LIVER FIBROSIS;
SUBSTANCE USE DISORDERS; ASPARTATE-AMINOTRANSFERASE;
PSYCHIATRIC-DIAGNOSIS; SAMPLING VARIABILITY; CIRRHOSIS; VALIDATION;
TESTS
AB Background. It is unclear if the risk of liver disease associated with different levels of alcohol consumption is higher for patients infected with human immunodeficiency virus (HIV) or chronic hepatitis C virus (HCV). We evaluated associations between alcohol use categories and advanced hepatic fibrosis, by HIV and chronic HCV status.
Methods. We performed a cross-sectional study among participants in the Veterans Aging Cohort Study who reported alcohol consumption at enrollment (701 HIV/HCV-coinfected; 1410 HIV-monoinfected; 296 HCV-monoinfected; 1158 HIV/HCV-uninfected). Alcohol use category was determined by the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and alcohol-related diagnoses and was classified as nonhazardous drinking, hazardous/binge drinking, or alcohol-related diagnosis. Advanced hepatic fibrosis was defined by FIB-4 index >3.25.
Results. Within each HIV/HCV group, the prevalence of advanced hepatic fibrosis increased as alcohol use category increased. For each alcohol use category, advanced hepatic fibrosis was more common among HIV-infected than uninfected (nonhazardous: 6.7% vs 1.4%; hazardous/binge: 9.5% vs 3.0%; alcohol-related diagnosis: 19.0% vs 8.6%; P < .01) and chronic HCV-infected than uninfected (nonhazardous: 13.6% vs 2.5%; hazardous/binge: 18.2% vs 3.1%; alcohol-related diagnosis: 22.1% vs 6.5%; P < .01) participants. Strong associations with advanced hepatic fibrosis (adjusted odds ratio [95% confidence interval]) were observed among HIV/HCV-coinfected patients with nonhazardous drinking (14.2 [5.91-34.0]), hazardous/binge drinking (18.9 [7.98-44.8]), and alcohol-related diagnoses (25.2 [10.6-59.7]) compared with uninfected nonhazardous drinkers.
Conclusions. Advanced hepatic fibrosis was present at low levels of alcohol consumption, increased with higher alcohol use categories, and was more prevalent among HIV-infected and chronic HCV-infected patients than uninfected individuals. All alcohol use categories were strongly associated with advanced hepatic fibrosis in HIV/HCV-coinfected patients.
C1 [Lim, Joseph K.; Tate, Janet P.; Goulet, Joseph L.; Justice, Amy C.] Vet Affairs VA Connecticut Healthcare Syst, West Haven, CT USA.
[Lim, Joseph K.; Tate, Janet P.; Goulet, Joseph L.; Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA.
[Fultz, Shawn L.] US FDA, Ctr Tobacco Prod, Washington, DC 20204 USA.
Hofstra North Shore LIJ Sch Med, Lake Success, NY USA.
[Conigliaro, Joseph] North Shore LIJ Hlth Syst, Lake Success, NY USA.
[Bryant, Kendall J.] NIAAA, Bethesda, MD USA.
[Gordon, Adam J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Gordon, Adam J.] Pittsburgh VA Med Ctr, Pittsburgh, PA USA.
[Gibert, Cynthia] VA Med Ctr, Washington, DC USA.
[Gibert, Cynthia] George Washington Univ, Med Ctr, Washington, DC 20037 USA.
[Rimland, David] Atlanta VA Med Ctr, Atlanta, GA USA.
[Rimland, David] Emory Univ, Sch Med, Atlanta, GA 30322 USA.
[Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Klein, Marina B.] McGill Univ, Ctr Hlth, Chron Viral Illness Serv, Montreal, PQ, Canada.
[Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Publ Hlth, Yale Ctr Interdisciplinary Res AIDS, New Haven, CT USA.
[Lo Re, Vincent, III] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA.
[Lo Re, Vincent, III] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Lo Re, V (reprint author), Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, 836 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM vincentl@mail.med.upenn.edu
RI Lo Re, Vincent/N-7817-2015;
OI Goetz, Matthew/0000-0003-4542-992X; Fiellin, David/0000-0002-4006-010X;
Goulet, Joseph/0000-0002-0842-804X
FU National Institute on Alcohol Abuse and Alcoholism [U01 AA13566, R21
AA015894]; National Institute of Allergy and Infectious Diseases [K01
AI070001]
FX This study was supported by the National Institute on Alcohol Abuse and
Alcoholism (grant numbers U01 AA13566 to A. C. J. and R21 AA015894 to J.
K. L and A. C. J.) and the National Institute of Allergy and Infectious
Diseases (grant number K01 AI070001 to V. L. R.).
NR 60
TC 15
Z9 15
U1 1
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAY 15
PY 2014
VL 58
IS 10
BP 1449
EP 1458
DI 10.1093/cid/ciu097
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AH3RZ
UT WOS:000336044200020
PM 24569533
ER
PT J
AU Watanabe, M
Moon, KD
Vacchio, MS
Hathcock, KS
Hodes, RJ
AF Watanabe, Masashi
Moon, Kyung Duk
Vacchio, Melanie S.
Hathcock, Karen S.
Hodes, Richard J.
TI Downmodulation of Tumor Suppressor p53 by T Cell Receptor Signaling Is
Critical for Antigen-Specific CD4(+) T Cell Responses
SO IMMUNITY
LA English
DT Article
ID IN-VIVO ACTIVATION; CANCER-THERAPY; IMMUNE-SYSTEM; IL-2 RECEPTOR; CHAIN
GENE; MICE; MEMORY; MDM2; INTERLEUKIN-2; TUMORIGENESIS
AB Antigen specificity is critical in immune response and requires integration of antigen-specific signals with antigen-nonspecific signals such as those provided by cytokines. The mechanism integrating these pathways is incompletely understood. We report here that antigen-specific proliferative responses of CD4(+) T cells required downmodulation of tumor suppressor p53. In the absence of T cell receptor (TCR) signal, IL-2 induced sustained increase in p53 protein, which prevented proliferative responses despite strong signaling through the IL-2 receptor. In contrast, TCR signaling resulted in early termination of p53 protein expression by decreasing p53 mRNA as well as strong transcriptional induction of the p53-regulating protein Mdm2. Downmodulation of p53 in response to antigen stimulation was in fact critical for antigenspecific T cell proliferation, and preventing p53 degradation by inhibiting Mdm2 resulted in sustained p53 protein and prevented antigen-specific T cell proliferation. It is thus termination of p53 by TCR signaling that allows proliferative responses, enforcing antigen specificity.
C1 [Watanabe, Masashi; Moon, Kyung Duk; Vacchio, Melanie S.; Hathcock, Karen S.; Hodes, Richard J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Hodes, RJ (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
EM hodesr@31.nia.nih.gov
FU Intramural Research Program of the NIH; Uehara Memorial Foundation
FX We thank A. Singer, C. Harris, and M. Perry for critical reading of the
manuscript and insightful comments during the course of these studies.
This work was supported by the Intramural Research Program of the NIH.
M.W. was supported by the Uehara Memorial Foundation.
NR 39
TC 22
Z9 22
U1 1
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD MAY 15
PY 2014
VL 40
IS 5
BP 681
EP 691
DI 10.1016/j.immuni.2014.04.006
PG 11
WC Immunology
SC Immunology
GA AH3LW
UT WOS:000336026100008
PM 24792911
ER
PT J
AU Kuniholm, MH
Jung, M
Everhart, JE
Cotler, S
Heiss, G
McQuillan, G
Kim, RS
Strickler, HD
Thyagarajan, B
Youngblood, M
Kaplan, RC
Ho, GYF
AF Kuniholm, Mark H.
Jung, Molly
Everhart, James E.
Cotler, Scott
Heiss, Gerardo
McQuillan, Geraldine
Kim, Ryung S.
Strickler, Howard D.
Thyagarajan, Bharat
Youngblood, Marston
Kaplan, Robert C.
Ho, Gloria Y. F.
TI Prevalence of Hepatitis C Virus Infection in US Hispanic/Latino Adults:
Results From the NHANES 2007-2010 and HCHS/SOL Studies
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE hepatitis C virus; HCV; Hispanic; Latino; United States; prevalence;
antibody; RNA; risk factor
ID UNITED-STATES; LATINOS; DESIGN
AB Prevalence of hepatitis C virus (HCV) antibody has been reported in Mexican Americans, but its prevalence in other US Hispanic/Latino groups is unknown. We studied 2 populations of US Hispanic/Latino adults; 3210 from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 and 11 964 from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Age-standardized prevalence of HCV antibody was similar in NHANES 2007-2010 (1.5%) and HCHS/SOL (2.0%) but differed significantly by Hispanic/Latino background in HCHS/SOL (eg, 11.6% in Puerto Rican men vs 0.4% in South American men). These findings suggest that the HCV epidemic among US Hispanics/Latinos is heterogeneous.
C1 [Kuniholm, Mark H.; Jung, Molly; Kim, Ryung S.; Strickler, Howard D.; Kaplan, Robert C.; Ho, Gloria Y. F.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
[Everhart, James E.] NIDDK, Epidemiol & Data Syst Program, Div Digest Dis & Nutr, Bethesda, MD 20892 USA.
[Cotler, Scott] Loyola Univ, Med Ctr, Dept Med, Div Hepatol, Maywood, IL 60153 USA.
[Heiss, Gerardo; Youngblood, Marston] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[McQuillan, Geraldine] Ctr Dis Control & Prevent, Div Hlth & Nutr Examinat Surveys, Hyattsville, MD USA.
[Thyagarajan, Bharat] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
RP Kuniholm, MH (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Belfer Bldg,Rm 1308C,1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM mark.kuniholm@einstein.yu.edu
FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC65233];
University of Miami [N01-HC65234]; Albert Einstein College of Medicine
[N01-HC65235]; Northwestern University [N01-HC65236]; San Diego State
University [N01-HC65237]; National Center for Advancing Translational
Sciences (NCATS), through CTSA [UL1RR025750, KL2RR025749]
FX The Hispanic Community Health Study/Study of Latinos was carried out as
a collaborative study supported by contracts from the National Heart,
Lung, and Blood Institute (NHLBI) to the University of North Carolina
(N01-HC65233), University of Miami (N01-HC65234), Albert Einstein
College of Medicine (N01-HC65235), Northwestern University
(N01-HC65236), and San Diego State University (N01-HC65237). The
following Institutes/Centers/Offices contribute to the HCHS/SOL through
a transfer of funds to the NHLBI: National Institute on Minority Health
and Health Disparities, National Institute on Deafness and Other
Communication Disorders, National Institute of Dental and Craniofacial
Research, National Institute of Diabetes and Digestive and Kidney
Diseases, National Institute of Neurological Disorders and Stroke, NIH
Institution-Office of Dietary Supplements. M. H. K. is supported in part
by the National Center for Advancing Translational Sciences (NCATS),
through CTSA grants UL1RR025750 and KL2RR025749.
NR 8
TC 14
Z9 14
U1 2
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAY 15
PY 2014
VL 209
IS 10
BP 1585
EP 1590
DI 10.1093/infdis/jit672
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AH4CJ
UT WOS:000336073000012
PM 24423693
ER
PT J
AU Burbelo, PD
Bayat, A
Rhodes, CS
Hoh, R
Martin, JN
Fromentin, R
Chomont, N
Hutter, G
Kovacs, JA
Deeks, SG
AF Burbelo, Peter D.
Bayat, Ahmad
Rhodes, Craig S.
Hoh, Rebecca
Martin, Jeffrey N.
Fromentin, Remi
Chomont, Nicolas
Huetter, Gero
Kovacs, Joseph A.
Deeks, Steven G.
TI HIV Antibody Characterization as a Method to Quantify Reservoir Size
During Curative Interventions
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE antibodies; elite controllers; HIV-1; HIV-1 persistence; serology; viral
reservoirs
ID INFECTION; THERAPY; QUANTIFICATION; REPLICATION; PERSISTENCE
AB Quantitative humoral profiling of recent samples from a human immunodeficiency virus (HIV)-infected adult who was cured following a delta32/delta32 CCR5 stem cell transplant in 2007 revealed no antibodies against p24, matrix, nucleocapsid, integrase, protease, and gp120, but low levels of antibodies against reverse transcriptase, tat, and gp41. Antibody levels to these HIV proteins persisted at high and stable levels in most noncontrollers, elite controllers, and antiretroviral-treated subjects, but a rare subset of controllers had low levels of antibodies against matrix, reverse transcriptase, integrase, and/or protease. Comprehensive HIV antibody profiles may prove useful for monitoring curative interventions.
C1 [Burbelo, Peter D.] NIDCR, Clin Dent Res Core, Bethesda, MD 20892 USA.
[Bayat, Ahmad] NIH, Dept Perioperat Med, Ctr Clin, Bethesda, MD 20892 USA.
[Rhodes, Craig S.] Natl Inst Dent & Craniofacial Res, Lab Dev Biol, San Francisco, CA USA.
[Hoh, Rebecca; Martin, Jeffrey N.; Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Fromentin, Remi; Chomont, Nicolas] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL USA.
[Huetter, Gero] Heidelberg Univ, Inst Transfus Med & Immunol, Mannheim, Germany.
[Kovacs, Joseph A.] NIH, Crit Care Med Dept, NIH Clin Ctr, Bethesda, MD 20892 USA.
RP Burbelo, PD (reprint author), NIDCR, Clin Dent Res Core, NIH, 10 Ctr Dr,Bldg 10,Rm 5N102-106, Bethesda, MD 20892 USA.
EM burbelop@nidcr.nih.gov
FU Division of Intramural Research, National Institute of Dental and
Craniofacial Research; National Institutes of Health (NIH) Clinical
Center; Foundation for AIDS Research (amFAR), NIH [R24 AI067039];
American Foundation for AIDS Research [108264]
FX This work was supported by the Division of Intramural Research, National
Institute of Dental and Craniofacial Research, the National Institutes
of Health (NIH) Clinical Center. National Institutes of Health (NIH)
Clinical Center, the Delaney AIDS Research Enterprise (DARE,
U19AI096109), the Foundation for AIDS Research (amFAR), NIH Grant R24
AI067039, the National Institute of Allergy and Infectious Diseases
(NIAID; K24 AI069994), the University of California, San Francisco
(UCSF)/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763),
and the UCSF Clinical and Translational Research Institute Clinical
Research Center (UL1 RR024131). R. F. is supported by the American
Foundation for AIDS Research (amfAR fellowship 108264).
NR 15
TC 10
Z9 10
U1 0
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAY 15
PY 2014
VL 209
IS 10
BP 1613
EP 1617
DI 10.1093/infdis/jit667
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AH4CJ
UT WOS:000336073000015
PM 24286982
ER
PT J
AU Dahl, V
Gisslen, M
Hagberg, L
Peterson, J
Shao, W
Spudich, S
Price, RW
Palmer, S
AF Dahl, Viktor
Gisslen, Magnus
Hagberg, Lars
Peterson, Julia
Shao, Wei
Spudich, Serena
Price, Richard W.
Palmer, Sarah
TI An Example of Genetically Distinct HIV Type 1 Variants in Cerebrospinal
Fluid and Plasma During Suppressive Therapy
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE HIV; cerebrospinal fluid; CSF; central nervous system; CNS; suppressive;
therapy; compartmentalization; hypermutants; reservoir
ID TREATMENT INTENSIFICATION; ANTIRETROVIRAL THERAPY; INFECTION
AB We sequenced the genome of human immunodeficiency virus type 1 (HIV-1) recovered from 70 cerebrospinal fluid (CSF) specimens and 29 plasma samples and corresponding samples obtained before treatment initiation from 17 subjects receiving suppressive therapy. More CSF sequences than plasma sequences were hypermutants. We determined CSF sequences and plasma sequences in specimens obtained from 2 subjects after treatment initiation. In one subject, we found genetically distinct CSF and plasma sequences, indicating that they came from HIV-1 from 2 different compartments, one potentially the central nervous system, during suppressive therapy. In addition, there was little evidence of viral evolution in the CSF during therapy, suggesting that continuous virus replication is not the major cause of viral persistence in the central nervous system.
C1 [Dahl, Viktor; Palmer, Sarah] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
[Dahl, Viktor; Palmer, Sarah] Swedish Inst Communicable Dis Control, S-17182 Stockholm, Sweden.
[Gisslen, Magnus; Hagberg, Lars] Univ Gothenburg, Dept Infect Dis, Gothenburg, Sweden.
[Peterson, Julia; Price, Richard W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Shao, Wei] Sci Applicat Int Corp Frederick, Adv Biomed Comp Ctr, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Spudich, Serena] Yale Univ, Dept Neurol, New Haven, CT USA.
[Palmer, Sarah] Westmead Millennium Inst, Ctr Virus Res, Westmead, NSW, Australia.
[Palmer, Sarah] Univ Sydney, Sydney, NSW 2006, Australia.
RP Dahl, V (reprint author), Swedish Inst Communicable Dis Control, S-17182 Stockholm, Sweden.
EM viktor.dahl@smi.se
OI Dahl, Viktor/0000-0001-9921-5172
FU Foundation for AIDS Research [108021-49-RFRL]; National Institutes of
Health [R21 MH096619, R01 MH081772, UL1 RR024131/TR000004, P30
AI027763]; Swedish Research Council [2007-7092]; Sahlgrenska Academy,
University of Gothenburg, Sweden [ALFGBG-11067]
FX This work was supported by the Foundation for AIDS Research (grant
108021-49-RFRL); the National Institutes of Health (grants R21 MH096619,
R01 MH081772, UL1 RR024131/TR000004, and P30 AI027763); the Swedish
Research Council (grant 2007-7092); and Sahlgrenska Academy, University
of Gothenburg, Sweden (grant ALFGBG-11067).
NR 15
TC 10
Z9 10
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAY 15
PY 2014
VL 209
IS 10
BP 1618
EP 1622
DI 10.1093/infdis/jit805
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AH4CJ
UT WOS:000336073000016
PM 24338353
ER
PT J
AU Afonin, KA
Kasprzak, W
Bindewald, E
Puppala, PS
Diehl, AR
Hall, KT
Kim, TJ
Zimmermann, MT
Jernigan, RL
Jaeger, L
Shapiro, BA
AF Afonin, Kirill A.
Kasprzak, Wojciech
Bindewald, Eckart
Puppala, Praneet S.
Diehl, Alex R.
Hall, Kenneth T.
Kim, Tae Jin
Zimmermann, Michael T.
Jernigan, Robert L.
Jaeger, Luc
Shapiro, Bruce A.
TI Computational and experimental characterization of RNA cubic
nanoscaffolds
SO METHODS
LA English
DT Article
DE RNA nanotechnology; RNA architectonics; Anisotropic network model; RNA
nanostructure dynamics; RNA nanostructure characterization;
Nanostructure design; Native PAGE; TGGE
ID ELASTIC NETWORK MODELS; DNA-PACKAGING MOTOR; IN-SILICO; EMERGING FIELD;
NUCLEIC-ACIDS; TECTO-RNA; DELIVERY; NANOPARTICLES; MOTIONS; DESIGN
AB The fast-developing field of RNA nanotechnology requires the adoption and development of novel and faster computational approaches to modeling and characterization of RNA-based nano-objects. We report the first application of Elastic Network Modeling (ENM), a structure-based dynamics model, to RNA nanotechnology. With the use of an Anisotropic Network Model (ANM), a type of ENM, we characterize the dynamic behavior of non-compact, multi-stranded RNA-based nanocubes that can be used as nano-scale scaffolds carrying different functionalities. Modeling the nanocubes with our tool NanoTiler and exploring the dynamic characteristics of the models with ANM suggested relatively minor but important structural modifications that enhanced the assembly properties and thermodynamic stabilities. In silico and in vitro, we compared nanocubes having different numbers of base pairs per side, showing with both methods that the 10 bp-long helix design leads to more efficient assembly, as predicted computationally. We also explored the impact of different numbers of single-stranded nucleotide stretches at each of the cube corners and showed that cube flexibility simulations help explain the differences in the experimental assembly yields, as well as the measured nanomolecule sizes and melting temperatures. This original work paves the way for detailed computational analysis of the dynamic behavior of artificially designed multi-stranded RNA nanoparticles. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Afonin, Kirill A.; Puppala, Praneet S.; Diehl, Alex R.; Hall, Kenneth T.; Kim, Tae Jin; Shapiro, Bruce A.] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA.
[Kasprzak, Wojciech; Bindewald, Eckart] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Ctr Canc Res, Basic Sci Program,Nanobiol Program, Frederick, MD 21702 USA.
[Zimmermann, Michael T.; Jernigan, Robert L.] Iowa State Univ, Dept Biochem Biophys & Mol Biol, Ames, IA 50011 USA.
[Jaeger, Luc] Univ Calif Santa Barbara, Dept Chem & Biochem, Biomol Sci & Engn Program, Santa Barbara, CA 93106 USA.
RP Jaeger, L (reprint author), Univ Calif Santa Barbara, Dept Chem & Biochem, Biomol Sci & Engn Program, Santa Barbara, CA 93106 USA.
EM jaeger@chem.ucsb.edu; shapirbr@mail.nih.gov
OI Zimmermann, Michael/0000-0001-7073-0525
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Federal funds; Frederick National Laboratory
for Cancer Research, National Institutes of Health [HHSN261200800001E];
NIH [R01GM-079604]
FX The authors thank Faye Walker for technical assistance at early stages
of this paper, Dr. Buyong Ma and Dr. Hugo Martinez for helpful
discussions on certain aspects of the methods employed in this work.
This research was supported [in part] by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. This
project has been funded in whole or in part with Federal funds from the
Frederick National Laboratory for Cancer Research, National Institutes
of Health, under contract HHSN261200800001E (to WKK and EB). The content
of this publication does not necessarily reflect the views or policies
of the Department of Health and Human Services, nor does mention of
trade names, commercial products, or organizations imply endorsement by
the U.S. Government. This research was also supported by NIH grant No.
R01GM-079604 (to LJ).
NR 68
TC 9
Z9 9
U1 0
U2 28
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
EI 1095-9130
J9 METHODS
JI Methods
PD MAY 15
PY 2014
VL 67
IS 2
BP 256
EP 265
DI 10.1016/j.ymeth.2013.10.013
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AG7UI
UT WOS:000335623900019
PM 24189588
ER
PT J
AU Heilig, M
Schank, JR
AF Heilig, Markus
Schank, Jesse R.
TI Kappa-Opioid Receptor Antagonism: A Mechanism for Treatment of Relief
Drinking?
SO BIOLOGICAL PSYCHIATRY
LA English
DT Editorial Material
ID DEPENDENCE; RATS
C1 [Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Schank, Jesse R.] Univ Georgia, Coll Vet Med, Dept Physiol & Pharmacol, Athens, GA 30602 USA.
RP Heilig, M (reprint author), NIAAA, 10 Ctr Dr,10-1E-5334, Bethesda, MD 20892 USA.
EM markus.heilig@mail.nih.gov
OI Heilig, Markus/0000-0003-2706-2482
NR 10
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 15
PY 2014
VL 75
IS 10
BP 750
EP 751
DI 10.1016/j.biopsych.2014.03.004
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AG6DF
UT WOS:000335508000002
PM 24780009
ER
PT J
AU Dobbs, LK
Cunningham, CL
AF Dobbs, Lauren K.
Cunningham, Christopher L.
TI The role of the laterodorsal tegmental nucleus in methamphetamine
conditioned place preference and locomotor activity
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Electrolytic lesion; Methamphetamine; Reward; Locomotor activity;
Acetylcholine; Inbred mice (C57BL/6)
ID BEHAVIORAL SENSITIZATION; SUBSTANTIA-NIGRA; AREA; AMPHETAMINE; NEURONS;
MICE; RAT; PEDUNCULOPONTINE; ACETYLCHOLINE; SCOPOLAMINE
AB Methamphetamine (METH) indirectly stimulates the laterodorsal tegmental nucleus (LDT) acetylcholine (ACh) neurons to increase ACh within the ventral tegmental area (VTA). LDT ACh inhibition attenuates METH and saline locomotor activity. The aim of these experiments was to determine whether LDT ACh contributes to METH conditioned place preference (CPP). C57BL/6J mice received a bilateral electrolytic or sham lesion of the LDT. After recovery, mice received alternating pairings of METH (0.5 mg/kg) and saline with distinct tactile floor cues over 8 days. During preference tests, mice were given access to both floor types and time spent on each was recorded. Mice were tested again after exposure to both extinction and reconditioning trials. Brains were then processed for choline acetyltransferase immunohistochemistry to label LDT ACh neurons. Lesioned mice had significantly fewer LOT ACh neurons and showed increased saline and METH locomotor activity during the first conditioning trial compared to sham mice. Locomotor activity (saline and METH) was negatively correlated with the number of LDT ACh neurons. Lesioned and sham mice showed similar METH CPP following conditioning, extinction and reconditioning trials. LDT ACh neurons are not necessary for METH reward as indexed by CPP, but may be important for basal and METH-induced locomotor activity. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Dobbs, Lauren K.; Cunningham, Christopher L.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA.
RP Dobbs, LK (reprint author), NIAAA, NIH, Sect Neuronal Struct, 5625 Fishers Lane,Room TS-24MSC 9411, Bethesda, MD 20892 USA.
EM Lauren.dobbs@nih.gov
FU National Institutes of Health [R01AA007702, F31DA027295]; Department of
Behavioral Neuroscience and by an award from the Achievement Rewards for
College Scientists (ARCS) Foundation
FX Research reported in this paper was supported by the National Institutes
of Health under award numbers R01AA007702 and F31DA027295, by the
Department of Behavioral Neuroscience and by an award from the
Achievement Rewards for College Scientists (ARCS) Foundation. The
content is solely the responsibility of the authors and-does not
necessarily represent the official views of the National Institutes of
Health. The authors would like to thank Dr. Andrey Ryabinin for
assistance with the ChAT IHC procedure. The authors have no conflict of
interest to report.
NR 26
TC 4
Z9 4
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
EI 1872-7549
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD MAY 15
PY 2014
VL 265
BP 198
EP 202
DI 10.1016/j.bbr.2014.02.021
PG 5
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA AF8TV
UT WOS:000334989400024
PM 24569009
ER
PT J
AU Kim, DW
Park, JW
Willingham, MC
Cheng, SY
AF Kim, Dong Wook
Park, Jeong Won
Willingham, Mark C.
Cheng, Sheue-yann
TI A histone deacetylase inhibitor improves hypothyroidism caused by a TR1
mutant
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID THYROID-HORMONE RECEPTOR; LIGAND-BINDING DOMAIN; SUBEROYLANILIDE
HYDROXAMIC ACID; IN-VIVO; CLINICAL PHENOTYPE; COREPRESSOR NCOR1; NUCLEAR
RECEPTORS; RESISTANCE; MUTATION; MICE
AB Mutations of the thyroid hormone receptor gene (THRA) cause hypothyroidism in patients with growth and developmental retardation, and skeletal dysplasia. Genetic evidence indicates that the dominant negative activity of TR1 mutants underlies pathological manifestations. Using a mouse model of hypothyroidism caused by a dominant negative TR1PV mutant and its derived mouse model harboring a mutated nuclear receptor corepressor (NCOR1ID) (Thra1(PV/)Ncor1(ID/ID) mice), we recently showed that aberrant release of TR1 mutants from the NCOR1 repressor complex mediates dominant negative actions of TR1 mutants in vivo. We tested the hypothesis that deacetylation of nucleosomal histones associated with aberrant recruitment of corepressors by TR1 mutants underlies pathological phenotypic expression. We treated Thra1(PV/)and Thra1(PV/)Ncor1(ID/ID) mice with a histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxyamic acid (SAHA). SAHA significantly ameliorated the impaired growth, bone development and adipogenesis of Thra1(PV/) mice. In Thra1(PV/)Ncor1(ID/ID) mice, SAHA improved these abnormalities even further. We focused our molecular analyses on how SAHA improved the impaired adipogenesis leading to the lean phenotype. We found that SAHA reverted the impaired adipogenesis by de-repressing the expression of the two master regulators of adipogenesis, C/ebp and Ppar, as well as other adipogenic genes at both the mRNA and protein levels. Chromatin immunoprecipitation analyses indicated SAHA increased the extent of acetylation of nucleosomal H4K5 and H3 to re-activate adipogenic genes to reverting adipogenesis. Thus, HDAC confers in vivo aberrant actions of TR1 mutants. Importantly, for the first time, the present studies show that HDAC inhibitors are clearly beneficial for hypothyroidism and could be therapeutics for treatment.
C1 [Kim, Dong Wook; Park, Jeong Won; Willingham, Mark C.; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Cheng, SY (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
FU Intramural Research Program at the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX The present research was supported by the Intramural Research Program at
the Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 52
TC 6
Z9 6
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAY 15
PY 2014
VL 23
IS 10
BP 2651
EP 2664
DI 10.1093/hmg/ddt660
PG 14
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AF4PB
UT WOS:000334694800012
PM 24381310
ER
PT J
AU Ma, HY
Sun, DX
Cao, YF
Ai, CZ
Qu, YQ
Hu, CM
Jiang, CT
Dong, PP
Sun, XY
Hong, M
Tanaka, N
Gonzalez, FJ
Ma, XC
Fang, ZZ
AF Ma, Hai-Ying
Sun, Dong-Xue
Cao, Yun-Feng
Ai, Chun-Zhi
Qu, Yan-Qing
Hu, Cui-Min
Jiang, Changtao
Dong, Pei-Pei
Sun, Xiao-Yu
Hong, Mo
Tanaka, Naoki
Gonzalez, Frank J.
Ma, Xiao-Chi
Fang, Zhong-Ze
TI Herb-drug interaction prediction based on the high specific inhibition
of andrographolide derivatives towards UDP-glucuronosyltransferase (UGT)
2B7
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Andrographolide derivatives; Herb-drug interaction (HDI);
UDP-glucuronosyltransferases (UGTs); Adverse effects
ID ZIDOVUDINE GLUCURONIDATION; PANICULATA EXTRACT; IN-VITRO; ACID;
4-METHYLUMBELLIFERONE; PHARMACOKINETICS; SELECTIVITY; 1-NAPHTHOL;
BINDING; SITES
AB Herb-drug interaction strongly limits the clinical application of herbs and drugs, and the inhibition of herbal components towards important drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reasons. The present study aims to investigate the inhibition potential of andrographolide derivatives towards one of the most important phase II DMEs UDP-glucuronosyltransferases (UGTs). Recombinant UGT isoforms (except UGT1A4)-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and UGT1A4catalyzed trifluoperazine ( IFP) glucuronidation were employed to firstly screen the andrographolide derivatives' inhibition potential. High specific inhibition of andrographolide derivatives towards UGT2B7 was observed. The inhibition type and parameters (KO were determined for the compounds exhibiting strong inhibition capability towards UGT2B7, and human liver microsome (HLMs)-catalyzed zidovudine (AZT) glucuronidation probe reaction was used to furtherly confirm the inhibition behavior. In combination of inhibition parameters (KO and in vivo concentration of andrographolide and dehydroandrographolide, the potential in vivo inhibition magnitude was predicted. Additionally, both the in vitro inhibition data and computational modeling results provide important information for the modification of andrographolide derivatives as selective inhibitors of UGT2B7. Taken together, data obtained from the present study indicated the potential herb-drug interaction between Andrographis paniculata and the drugs mainly undergoing UGT2B7-catalyzed metabolic elimination, and the andrographolide derivatives as potential candidates for the selective inhibitors of UGT2B7. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Ma, Hai-Ying] China Med Univ, Affiliated Hosp 4, Shenyang 110032, Peoples R China.
[Sun, Dong-Xue] Shenyang Pharmaceut Univ, Sch Tradit Chinese Med, Shenyang 110016, Peoples R China.
[Cao, Yun-Feng; Ma, Xiao-Chi; Fang, Zhong-Ze] Liaoning Med Univ, Affiliated Hosp 1, Jinzhou 121001, Peoples R China.
[Cao, Yun-Feng; Ai, Chun-Zhi; Hu, Cui-Min; Sun, Xiao-Yu; Hong, Mo; Ma, Xiao-Chi; Fang, Zhong-Ze] Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian 116023, Peoples R China.
[Qu, Yan-Qing] Yantaishan Hosp, Yantai, Shandong, Peoples R China.
[Jiang, Changtao; Tanaka, Naoki; Gonzalez, Frank J.; Fang, Zhong-Ze] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Hu, Cui-Min] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20057 USA.
[Dong, Pei-Pei; Ma, Xiao-Chi] Dalian Med Univ, Acad Integrat Med, Dalian 116044, Peoples R China.
[Ma, Xiao-Chi] Med Univ, Coll Pharm, Pharmacokinet & Drug Transport Key Lab, Dalian, Peoples R China.
RP Ma, HY (reprint author), China Med Univ, Affiliated Hosp 4, 4 Chongshan Eastern Rd, Shenyang 110032, Peoples R China.
EM cmu4h-mhy@126.com; maxc1978@163.com; zzfang228@gmail.com
FU National Natural Science Foundation of China [81202586, 81073013,
81274047]
FX This work was supported by the National Natural Science Foundation of
China (no. 81202586, 81073013,81274047).
NR 25
TC 38
Z9 40
U1 7
U2 33
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD MAY 15
PY 2014
VL 277
IS 1
BP 86
EP 94
DI 10.1016/j.taap.2014.02.021
PG 9
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA AG0GZ
UT WOS:000335095200010
PM 24631340
ER
PT J
AU Anderson, WF
Rosenberg, PS
Katki, HA
AF Anderson, William F.
Rosenberg, Philip S.
Katki, Hormuzd A.
TI Tracking and Evaluating Molecular Tumor Markers With Cancer Registry
Data: HER2 and Breast Cancer
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID ESTROGEN-RECEPTOR; UNITED-STATES; ADJUVANT CHEMOTHERAPY; AGE
DISTRIBUTION; EXPRESSION; EPIDEMIOLOGY; SURVEILLANCE; TRASTUZUMAB;
ONCOGENE; SUBTYPES
C1 [Anderson, William F.; Rosenberg, Philip S.; Katki, Hormuzd A.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Katki, HA (reprint author), NCI, NIH, Room 7E606,9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM katkih@mail.nih.gov
RI Katki, Hormuzd/B-4003-2015
NR 30
TC 2
Z9 2
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD MAY 14
PY 2014
VL 106
IS 5
AR dju093
DI 10.1093/jnci/dju093
PG 3
WC Oncology
SC Oncology
GA AO8WM
UT WOS:000341636100022
ER
PT J
AU Cao, Y
Lindstrom, S
Schumacher, F
Stevens, VL
Albanes, D
Berndt, SI
Boeing, H
Bueno-de-Mesquita, HB
Canzian, F
Chamosa, S
Chanock, SJ
Diver, WR
Gapstur, SM
Gaziano, JM
Giovannucci, EL
Haiman, CA
Henderson, B
Johansson, M
Le Marchand, L
Palli, D
Rosner, B
Siddiq, A
Stampfer, M
Stram, DO
Tamimi, R
Travis, RC
Trichopoulos, D
Willett, WC
Yeager, M
Kraft, P
Hsing, AW
Pollak, M
Lin, XH
Ma, J
AF Cao, Yin
Lindstroem, Sara
Schumacher, Fredrick
Stevens, Victoria L.
Albanes, Demetrius
Berndt, Sonja I.
Boeing, Heiner
Bueno-de-Mesquita, H. Bas
Canzian, Federico
Chamosa, Saioa
Chanock, Stephen J.
Diver, W. Ryan
Gapstur, Susan M.
Gaziano, J. Michael
Giovannucci, Edward L.
Haiman, Christopher A.
Henderson, Brian
Johansson, Mattias
Le Marchand, Loic
Palli, Domenico
Rosner, Bernard
Siddiq, Afshan
Stampfer, Meir
Stram, Daniel O.
Tamimi, Rulla
Travis, Ruth C.
Trichopoulos, Dimitrios
Willett, Walter C.
Yeager, Meredith
Kraft, Peter
Hsing, Ann W.
Pollak, Michael
Lin, Xihong
Ma, Jing
TI Insulin-like Growth Factor Pathway Genetic Polymorphisms, Circulating
IGF1 and IGFBP3, and Prostate Cancer Survival
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; FACTOR-I; BINDING PROTEIN-3; OVARIAN-CANCER;
RISK; EXPRESSION; RECEPTOR; THERAPY; BREAST; TUMOR
AB Background The insulin-like growth factor (IGF) signaling pathway has been implicated in prostate cancer (PCa) initiation, but its role in progression remains unknown.
Methods Among 5887 PCa patients (704 PCa deaths) of European ancestry from seven cohorts in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium, we conducted Cox kernel machine pathway analysis to evaluate whether 530 tagging single nucleotide polymorphisms (SNPs) in 26 IGF pathway-related genes were collectively associated with PCa mortality. We also conducted SNP-specific analysis using stratified Cox models adjusting for multiple testing. In 2424 patients (313 PCa deaths), we evaluated the association of prediagnostic circulating IGF1 and IGFBP3 levels and PCa mortality. All statistical tests were two-sided.
Results The IGF signaling pathway was associated with PCa mortality (P = .03), and IGF2-AS and SSTR2 were the main contributors (both P = .04). In SNP-specific analysis, 36 SNPs were associated with PCa mortality with P-trend less than .05, but only three SNPs in the IGF2-AS remained statistically significant after gene-based corrections. Two were in linkage disequilibrium (r(2) = 1 for rs1004446 and rs3741211), whereas the third, rs4366464, was independent (r(2) = 0.03). The hazard ratios (HRs) per each additional risk allele were 1.19 (95% confidence interval [CI] = 1.06 to 1.34; P-trend = .003) for rs3741211 and 1.44 (95% CI = 1.20 to 1.73; P-trend < .001) for rs4366464. rs4366464 remained statistically significant after correction for all SNPs (P-trend.corr = .04). Prediagnostic IGF1 (HRhighest (vs lowest quartile) = 0.71; 95% CI = 0.48 to 1.04) and IGFBP3 (HR = 0.93; 95% Cl = 0.65 to 1.34) levels were not associated with PCa mortality.
Conclusions The IGF signaling pathway, primarily IGF2-AS and SSTR2 genes, may be important in PCa survival.
C1 [Cao, Yin; Lindstroem, Sara; Stampfer, Meir; Tamimi, Rulla; Trichopoulos, Dimitrios; Kraft, Peter; Ma, Jing] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Cao, Yin; Giovannucci, Edward L.; Stampfer, Meir; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Rosner, Bernard; Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Cao, Yin; Giovannucci, Edward L.; Stampfer, Meir; Tamimi, Rulla; Ma, Jing] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Cao, Yin; Giovannucci, Edward L.; Stampfer, Meir; Tamimi, Rulla; Ma, Jing] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Schumacher, Fredrick; Haiman, Christopher A.; Henderson, Brian; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Stevens, Victoria L.; Diver, W. Ryan; Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Albanes, Demetrius; Berndt, Sonja I.; Chanock, Stephen J.; Yeager, Meredith] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Boeing, Heiner] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, Nuthetal, Germany.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Canzian, Federico] Deutsch Krebsforschungszentrum, German Canc Res Ctr, Genom Epidemiol Grp C055, Heidelberg, Germany.
[Chamosa, Saioa] Basque Reg Hlth Dept & Biodonostia, Publ Hlth Div Gipuzkoa, Epidemiol Unit, Gipuzkoa, Spain.
[Chanock, Stephen J.; Yeager, Meredith] Frederick Natl Lab Canc Res, Core Genotyping Facil, Gaithersburg, MD USA.
[Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
[Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr, Boston, MA USA.
[Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA.
[Johansson, Mattias] Int Agcy Res Canc, F-69372 Lyon, France.
[Johansson, Mattias] Umea Univ, Dept Biobank Res, S-90187 Umea, Sweden.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Travis, Ruth C.] Univ Oxford, Canc Epidemiol Unit, Oxford, England.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Trichopoulos, Dimitrios] Hellen Hlth Fdn, Athens, Greece.
[Hsing, Ann W.] Stanford Canc Inst, Canc Prevent Inst Calif, Stanford, CA USA.
[Pollak, Michael] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Pollak, Michael] McGill Univ, Dept Oncol, Montreal, PQ, Canada.
RP Ma, J (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 181 Longwood Ave,Boston, Boston, MA 02115 USA.
EM yic576@mail.harvard.edu; jing.ma@channing.harvard.edu
OI Chamosa, Saioa/0000-0002-8321-4404; PALLI, Domenico/0000-0002-5558-2437
FU National Cancer Institute [U01-CA98233-07, U54CA155626, U01-CA98710-06,
U01-CA98216-06, U01-CA98758-07, CA141298]; National Cancer Institute of
Canada [019894]; Hellenic Health Foundation; Associazione Italiana per
la Ricerca sul Cancro-AIRC-Milan
FX This work was supported by the National Cancer Institute
(U01-CA98233-07, U54CA155626, U01-CA98710-06, U01-CA98216-06,
U01-CA98758-07, CA141298), National Cancer Institute of Canada (019894),
Hellenic Health Foundation, and Associazione Italiana per la Ricerca sul
Cancro-AIRC-Milan.
NR 35
TC 0
Z9 0
U1 0
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD MAY 14
PY 2014
VL 106
IS 5
AR dju218
DI 10.1093/jnci/dju218
PG 10
WC Oncology
SC Oncology
GA AO8WM
UT WOS:000341636100033
ER
PT J
AU Howlader, N
Altekruse, SF
Li, CI
Chen, VW
Clarke, CA
Ries, LAG
Cronin, KA
AF Howlader, Nadia
Altekruse, Sean F.
Li, Christopher I.
Chen, Vivien W.
Clarke, Christina A.
Ries, Lynn A. G.
Cronin, Kathleen A.
TI US Incidence of Breast Cancer Subtypes Defined by Joint Hormone Receptor
and HER2 Status
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID AFRICAN-AMERICAN WOMEN; POPULATION; ESTROGEN; SURVIVAL; RECOMMENDATIONS;
EPIDEMIOLOGY; PREDICTORS; EXPRESSION; MORTALITY; INTERVAL
AB Background In 2010, Surveillance, Epidemiology, and End Results (SEER) registries began collecting human epidermal growth factor 2 (HER2) receptor status for breast cancer cases.
Methods Breast cancer subtypes defined by joint hormone receptor (HR; estrogen receptor [ER] and progesterone receptor [PR]) and HER2 status were assessed across the 28% of the US population that is covered by SEER registries. Age-specific incidence rates by subtype were calculated for non-Hispanic (NH) white, NH black, NH Asian Pacific Islander (API), and Hispanic women. Joint HR/HER2 status distributions by age, race/ethnicity, county-level poverty, registry, stage, Bloom-Richardson grade, tumor size, and nodal status were evaluated using multivariable adjusted polytomous logistic regression. All statistical tests were two-sided.
Results Among case patients with known HR/HER2 status, 36 810 (72.7%) were found to be HR+/HER2(-), 6193 (12.2%) were triple-negative (HR-/HER2(-)), 5240 (10.3%) were HR+/HER2(+), and 2328 (4.6%) were HR-/HER2(+); 6912 (12%) had unknown HR/HER2 status. NH white women had the highest incidence rate of the HR+/HER2(-) subtype, and NH black women had the highest rate of the triple-negative subtype. Compared with women with the HR+/HER2(-) subtype, triple-negative patients were more likely to be NH black and Hispanic; HR+/HER2(+) patients were more likely to be NH API; and HR-/HER2(+) patients were more likely to be NH black, NH API, and Hispanic. Patients with triple-negative, HR+/HER2(+), and HR-/HER2(+) breast cancer were 10% to 30% less likely to be diagnosed at older ages compared with HR+ /HER2(-) patients and 6.4-fold to 20.0-fold more likely to present with high-grade disease.
Conclusions In the future, SEER data can be used to monitor clinical outcomes in women diagnosed with different molecular subtypes of breast cancer for a large portion (approximately 28%) of the US population.
C1 [Howlader, Nadia; Altekruse, Sean F.; Ries, Lynn A. G.; Cronin, Kathleen A.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Li, Christopher I.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Li, Christopher I.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Chen, Vivien W.] Louisiana State Univ, Hlth Sci Ctr, Louisiana Tumor Registry & Epidemiol Program, Sch Publ Hlth, New Orleans, LA USA.
[Clarke, Christina A.] Canc Prevent Inst Calif, Fremont, CA USA.
[Ries, Lynn A. G.] RiesSearch LLC, Rockville, MD USA.
RP Howlader, N (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM howladern@mail.nih.gov
FU Surveillance Research Program, Division of Cancer Control and Population
Sciences, National Cancer Institute, National Institutes of Health; SEER
FX Surveillance Research Program, Division of Cancer Control and Population
Sciences, National Cancer Institute, National Institutes of Health
contracts with SEER registries.
NR 33
TC 51
Z9 51
U1 1
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD MAY 14
PY 2014
VL 106
IS 5
AR dju055
DI 10.1093/jnci/dju055
PG 8
WC Oncology
SC Oncology
GA AO8WM
UT WOS:000341636100006
ER
PT J
AU Palena, C
Roselli, M
Litzinger, MT
Ferroni, P
Costarelli, L
Spila, A
Cavaliere, F
Huang, B
Fernando, RI
Hamilton, DH
Jochems, C
Tsang, KY
Cheng, Q
Lyerly, HK
Schlom, J
Guadagni, F
AF Palena, Claudia
Roselli, Mario
Litzinger, Mary T.
Ferroni, Patrizia
Costarelli, Leopoldo
Spila, Antonella
Cavaliere, Francesco
Huang, Bruce
Fernando, Romaine I.
Hamilton, Duane H.
Jochems, Caroline
Tsang, Kwong-Yok
Cheng, Qing
Lyerly, H. Kim
Schlom, Jeffrey
Guadagni, Fiorella
TI Overexpression of the EMT Driver Brachyury in Breast Carcinomas:
Association With Poor Prognosis
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; TRANSCRIPTION FACTOR BRACHYURY;
BASAL-LIKE PHENOTYPE; CANCER CELL-LINES; RECEPTOR EXPRESSION; GENE;
SNAIL; PROGRESSION; SUBTYPES; HORMONE
AB Background The epithelial-mesenchymal transition (EMT) has been implicated as an important process in tumor cell invasion, metastasis, and drug resistance. The transcription factor brachyury has recently been described as a driver of EMT of human carcinoma cells.
Methods Brachyury mRNA and protein expression was analyzed in human breast carcinomas and benign tissues. The role of brachyury in breast tumor prognosis and drug resistance and the ability of brachyury-specific T cells to lyse human breast carcinoma cells were also evaluated. Kaplan-Meier analyses were used to evaluate the association between brachyury expression and survival. All statistical tests were two-sided.
Results The level of brachyury expression in breast cancer cells was positively associated with their ability to invade the extracellular matrix, efficiently form mammospheres in vitro, and resist the cytotoxic effect of docetaxel. A comparison of survival among breast cancer patients treated with tamoxifen in the adjuvant setting who had tumors with high vs low brachyury mRNA expression demonstrated that high expression of brachyury is associated as an independent variable with higher risk of recurrence (hazard ratio [HR] = 7.5; 95% confidence interval [CI] = 2.4 to 23.5; P = 5.14 x 10(-4)) and distant metastasis (HR = 15.2; 95% CI = 3.5 to 66.3; P = 3.01 x 10(-4)). We also demonstrated that brachyury-specific T cells can lyse human breast carcinoma cells.
Conclusions The studies reported here provide the rationale for the use of a vaccine targeting brachyury for the therapy of human breast cancer, either as a monotherapy or in combination therapies.
C1 [Palena, Claudia; Litzinger, Mary T.; Huang, Bruce; Fernando, Romaine I.; Hamilton, Duane H.; Jochems, Caroline; Tsang, Kwong-Yok; Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Roselli, Mario] Tor Vergata Univ, Dept Internal Med, Med Oncol Unit, Rome, Italy.
[Ferroni, Patrizia; Spila, Antonella; Guadagni, Fiorella] IRCCS San Raffaele Pisana, Interinst Multidisciplinary Biobank, Dept Lab Med & Adv Biotechnol, Rome, Italy.
[Costarelli, Leopoldo] San Giovanni Addolorata Hosp, Dept Pathol, Rome, Italy.
[Cavaliere, Francesco] San Giovanni Addolorata Hosp, Dept Surg, Rome, Italy.
[Cheng, Qing; Lyerly, H. Kim] Duke Univ, Sch Med, Dept Surg, Durham, NC USA.
RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Rm 8B09, Bethesda, MD 20892 USA.
EM js141c@nih.gov
RI Cavaliere, Francesco/J-7635-2016; Ferroni, Patrizia/C-2705-2017;
OI Cavaliere, Francesco/0000-0001-6501-8648; Ferroni,
Patrizia/0000-0002-9877-8712; Roselli, Mario/0000-0002-2431-6689
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health; Italian Ministry of Instruction, University and
Research (MERIT) [RBNE08NKH7]; Department of Defense Breast Cancer
Research Program-Clinical Translational Research Award
[-W81XWH-12-1-0574]
FX This research was supported in part by the Intramural Research Program
of the Center for Cancer Research, National Cancer Institute, National
Institutes of Health; the Italian Ministry of Instruction, University
and Research (MERIT, grant code RBNE08NKH7); and Department of Defense
Breast Cancer Research Program-Clinical Translational Research Award
(Proposal Title, "Developing a HER3 Vaccine to Prevent Resistance to
Endocrine Therapy"/Principal Investigator: Dr. Herbert K. Lyerly/Period
of Performance: 30 September 2012-29 September 2017/Contract No.
-W81XWH-12-1-0574).
NR 46
TC 7
Z9 7
U1 2
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD MAY 14
PY 2014
VL 106
IS 5
AR dju054
DI 10.1093/jnci/dju054
PG 12
WC Oncology
SC Oncology
GA AO8WM
UT WOS:000341636100005
ER
PT J
AU Simmonett, AC
Pickard, FC
Schaefer, HF
Brooks, BR
AF Simmonett, Andrew C.
Pickard, Frank C.
Schaefer, Henry F., III
Brooks, Bernard R.
TI An efficient algorithm for multipole energies and derivatives based on
spherical harmonics and extensions to particle mesh Ewald
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID SOLID HARMONICS; BIOLOGICAL RECOGNITION; RECURRENCE RELATIONS; ADDITION
THEOREMS; COULOMB OPERATOR; AROMATIC RINGS; TENSOR THEORY; LARGE
SYSTEMS; 2 POINTS; EXPANSION
AB Next-generation molecular force fields deliver accurate descriptions of non-covalent interactions by employing more elaborate functional forms than their predecessors. Much work has been dedicated to improving the description of the electrostatic potential (ESP) generated by these force fields. A common approach to improving the ESP is by augmenting the point charges on each center with higher-order multipole moments. The resulting anisotropy greatly improves the directionality of the non-covalent bonding, with a concomitant increase in computational cost. In this work, we develop an efficient strategy for enumerating multipole interactions, by casting an efficient spherical harmonic based approach within a particle mesh Ewald (PME) framework. Although the derivation involves lengthy algebra, the final expressions are relatively compact, yielding an approach that can efficiently handle both finite and periodic systems without imposing any approximations beyond PME. Forces and torques are readily obtained, making our method well suited to modern molecular dynamics simulations. (C) 2014 AIP Publishing LLC.
C1 [Simmonett, Andrew C.; Pickard, Frank C.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[Simmonett, Andrew C.; Schaefer, Henry F., III] Univ Georgia, Ctr Computat Quantum Chem, Athens, GA 30602 USA.
RP Simmonett, AC (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM andrew.simmonett@nih.gov
FU National Science Foundation [CHE-1054286]; National Heart, Lung, and
Blood Institute
FX The work at UGA was supported by the National Science Foundation, under
Grant No. CHE-1054286. The work at the National Institutes of Health was
supported by the intramural research program of the National Heart,
Lung, and Blood Institute.
NR 61
TC 18
Z9 18
U1 1
U2 30
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
EI 1089-7690
J9 J CHEM PHYS
JI J. Chem. Phys.
PD MAY 14
PY 2014
VL 140
IS 18
AR 184101
DI 10.1063/1.4873920
PG 7
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA AI3SR
UT WOS:000336782700048
PM 24832247
ER
PT J
AU Thurber, KR
Tycko, R
AF Thurber, Kent R.
Tycko, Robert
TI Perturbation of nuclear spin polarizations in solid state NMR of
nitroxide-doped samples by magic-angle spinning without microwaves
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID LATTICE-RELAXATION; ROTATING SOLIDS; SPECTROSCOPY; SENSITIVITY; MAS;
DIFFUSION; RESONANCE; POLYMERS; C-13
AB We report solid state C-13 and H-1 nuclear magnetic resonance (NMR) experiments with magic-angle spinning (MAS) on frozen solutions containing nitroxide-based paramagnetic dopants that indicate significant perturbations of nuclear spin polarizations without microwave irradiation. At temperatures near 25 K, H-1 and cross-polarized C-13 NMR signals from N-15, C-13-labeled L-alanine in trinitroxide-doped glycerol/water are reduced by factors as large as six compared to signals from samples without nitroxide doping. Without MAS or at temperatures near 100 K, differences between signals with and without nitroxide doping are much smaller. We attribute most of the reduction of NMR signals under MAS near 25 K to nuclear spin depolarization through the cross-effect dynamic nuclear polarization mechanism, in which three-spin flips drive nuclear polarizations toward equilibrium with spin polarization differences between electron pairs. When T-1e is sufficiently long relative to the MAS rotation period, the distribution of electron spin polarization across the nitroxide electron paramagnetic resonance lineshape can be very different from the corresponding distribution in a static sample at thermal equilibrium, leading to the observed effects. We describe three-spin and 3000-spin calculations that qualitatively reproduce the experimental observations.
C1 [Thurber, Kent R.; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Thurber, KR (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM thurberk@niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases, a
component of the National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases, a
component of the National Institutes of Health. We thank Wai-Ming Yau
for synthesis of the nitroxide dopants. Numerical calculations used the
high-performance computational capabilities of the Biowulf Linux cluster
at the National Institutes of Health.
NR 37
TC 29
Z9 29
U1 6
U2 51
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0021-9606
EI 1089-7690
J9 J CHEM PHYS
JI J. Chem. Phys.
PD MAY 14
PY 2014
VL 140
IS 18
AR 184201
DI 10.1063/1.4874341
PG 11
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA AI3SR
UT WOS:000336782700064
PM 24832263
ER
PT J
AU Funk, E
Kottilil, S
Gilliam, B
Talwani, R
AF Funk, Emily
Kottilil, Shyam
Gilliam, Bruce
Talwani, Rohit
TI Tickling the TLR7 to cure viral hepatitis
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Review
DE Hepatitis C; Hepatitis B; Toll-like receptors; TLR7; Hepatitis treatment
ID TOLL-LIKE RECEPTORS; ADAPTIVE IMMUNE-RESPONSES; C VIRUS-INFECTION;
NONPARENCHYMAL LIVER-CELLS; B E-ANTIGEN; UNITED-STATES; DENDRITIC CELLS;
INNATE IMMUNITY; INTERFERON-ALPHA; NATURAL-HISTORY
AB Chronic hepatitis B and C are the leading causes of liver disease and liver transplantation worldwide. Ability to mount an effective immune response against both HBV and HCV is associated with spontaneous clearance of both infections, while an inability to do so leads to chronicity of both infections. To mount an effective immune response, both innate and adaptive immune responses must work in tandem. Hence, developing protective immunity to hepatitis viruses is an important goal in order to reduce the global burden of these two infections and prevent development of long-term complications. In this regard, the initial interactions between the pathogen and immune system are pivotal in determining the effectiveness of immune response and subsequent elimination of pathogens. Toll-like receptors (TLRs) are important regulators of innate and adaptive immune responses to various pathogens and are often involved in initiating and augmenting effective antiviral immunity. Immune-based therapeutic strategies that specifically induce type I interferon responses are associated with functional cure for both chronic HBV and HCV infections. Precisely, TLR7 stimulation mediates an endogenous type I interferon response, which is critical in development of a broad, effective and protective immunity against hepatitis viruses. This review focuses on anti-viral strategies that involve targeting TLR7 that may lead to development of protective immunity and eradication of hepatitis B.
C1 [Funk, Emily] NIH, Crit Care Med Dept, Clin Res Ctr, Bethesda, MD 20892 USA.
[Kottilil, Shyam] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
[Gilliam, Bruce; Talwani, Rohit] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
RP Talwani, R (reprint author), Univ Maryland, Sch Med, Inst Human Virol, 725 West Lombard St N151, Baltimore, MD 21201 USA.
EM rtalwani@ihv.umaryland.edu
FU Intramural Research Program of the NIH (National Institute of Allergy
and Infectious Diseases); Intramural Research Program of the NIH
(Clinical Research Center)
FX This research was supported by the Intramural Research Program of the
NIH (National Institute of Allergy and Infectious Diseases, and the
Clinical Research Center). The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
NR 75
TC 7
Z9 8
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD MAY 14
PY 2014
VL 12
AR 129
DI 10.1186/1479-5876-12-129
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AI5UR
UT WOS:000336935200001
PM 24884741
ER
PT J
AU Craig, VJ
Polverino, F
Laucho-Contreras, ME
Shi, YY
Liu, YS
Osorio, JC
Tesfaigzi, Y
Pinto-Plata, V
Gochuico, BR
Rosas, IO
Owen, CA
AF Craig, Vanessa J.
Polverino, Francesca
Laucho-Contreras, Maria E.
Shi, Yuanyuan
Liu, Yushi
Osorio, Juan C.
Tesfaigzi, Yohannes
Pinto-Plata, Victor
Gochuico, Bernadette R.
Rosas, Ivan O.
Owen, Caroline A.
TI Mononuclear Phagocytes and Airway Epithelial Cells: Novel Sources of
Matrix Metalloproteinase-8 (MMP-8) in Patients with Idiopathic Pulmonary
Fibrosis
SO PLOS ONE
LA English
DT Article
ID HUMAN NEUTROPHIL COLLAGENASE; TISSUE INHIBITOR; EXPRESSION;
INFLAMMATION; DISEASE; MICE; FIBROBLASTS; SARCOIDOSIS; APOPTOSIS; INJURY
AB Objectives: Matrix metalloproteinase-8 (MMP-8) promotes lung fibrotic responses to bleomycin in mice. Although prior studies reported that MMP-8 levels are increased in plasma and bronchoalveolar lavage fluid (BALF) samples from IPF patients, neither the bioactive forms nor the cellular sources of MMP-8 in idiopathic pulmonary fibrosis (IPF) patients have been identified. It is not known whether MMP-8 expression is dys-regulated in IPF leukocytes or whether MMP-8 plasma levels correlate with IPF outcomes. Our goal was to address these knowledge gaps.
Methods: We measured MMP-8 levels and forms in blood and lung samples from IPF patients versus controls using ELISAs, western blotting, and qPCR, and assessed whether MMP-8 plasma levels in 73 IPF patients correlate with rate of lung function decline and mortality. We used immunostaining to localize MMP-8 expression in IPF lungs. We quantified MMP-8 levels and forms in blood leukocytes from IPF patients versus controls.
Results: IPF patients have increased BALF, whole lung, and plasma levels of soluble MMP-8 protein. Active MMP-8 is the main form elevated in IPF lungs. MMP-8 mRNA levels are increased in monocytes from IPF patients, but IPF patients and controls have similar levels of MMP-8 in PMNs. Surprisingly, macrophages and airway epithelial cells are the main cells expressing MMP-8 in IPF lungs. Plasma and BALF MMP-8 levels do not correlate with decline in lung function and/or mortality in IPF patients.
Conclusion: Blood and lung MMP-8 levels are increased in IPF patients. Active MMP-8 is the main form elevated in IPF lungs. Surprisingly, blood monocytes, lung macrophages, and airway epithelial cells are the main cells in which MMP-8 is upregulated in IPF patients. Plasma and BALF MMP-8 levels are unlikely to serve as a prognostic biomarker for IPF patients. These results provide new information about the expression patterns of MMP-8 in IPF patients.
C1 [Craig, Vanessa J.; Polverino, Francesca; Laucho-Contreras, Maria E.; Shi, Yuanyuan; Liu, Yushi; Osorio, Juan C.; Pinto-Plata, Victor; Rosas, Ivan O.; Owen, Caroline A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Polverino, Francesca] Univ Parma, Dept Clin & Expt Med, I-43100 Parma, Italy.
[Polverino, Francesca; Shi, Yuanyuan; Liu, Yushi; Rosas, Ivan O.; Owen, Caroline A.] Lovelace Resp Res Inst, Pulm Fibrosis Program, Albuquerque, NM USA.
[Tesfaigzi, Yohannes; Owen, Caroline A.] Lovelace Resp Res Inst, Chron Obstruct Pulm Dis Program, Albuquerque, NM USA.
[Gochuico, Bernadette R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Owen, CA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
EM cowen@rics.bwh.harvard.edu
RI Polverino, Francesca/F-3816-2017;
OI Polverino, Francesca/0000-0001-9686-5698; Osorio, Juan
C/0000-0001-8090-1551
FU Public Health Service, National Heart, Lung, and Blood Institute Grants
[HL63137, HL086814, HL111835]; NIH [2T32 HL007633-26, 5T32 HD007466-15];
American Thoracic Society/Pulmonary Fibrosis Foundation; Brigham and
Women's Hospital-Lovelace Respiratory Research Institute Consortium;
Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health
FX This work was supported by the Public Health Service, National Heart,
Lung, and Blood Institute Grants HL63137, HL086814, HL111835, NIH 2T32
HL007633-26, NIH 5T32 HD007466-15 (www.grants.gov); the American
Thoracic Society/Pulmonary Fibrosis Foundation (www.thoracic.org); and
the Brigham and Women's Hospital-Lovelace Respiratory Research Institute
Consortium (http://brighamandwomens.org and http://www.lrri.org). This
work was supported, in part, by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 45
TC 4
Z9 4
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 14
PY 2014
VL 9
IS 5
AR e97485
DI 10.1371/journal.pone.0097485
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI4TJ
UT WOS:000336857400099
PM 24828408
ER
PT J
AU Ji, Y
Abrams, N
Zhu, W
Salinas, E
Yu, ZY
Palmer, DC
Jailwala, P
Franco, Z
Roychoudhuri, R
Stahlberg, E
Gattinoni, L
Restifo, NP
AF Ji, Yun
Abrams, Natalie
Zhu, Wei
Salinas, Eddie
Yu, Zhiya
Palmer, Douglas C.
Jailwala, Parthav
Franco, Zulmarie
Roychoudhuri, Rahul
Stahlberg, Eric
Gattinoni, Luca
Restifo, Nicholas P.
TI Identification of the Genomic Insertion Site of Pmel-1 TCR alpha and
beta Transgenes by Next-Generation Sequencing
SO PLOS ONE
LA English
DT Article
ID CD8(+) T-CELLS; SUPERIOR ANTITUMOR IMMUNITY; IN-VIVO; ADOPTIVE
IMMUNOTHERAPY; TUMOR-REGRESSION; DENDRITIC CELLS; STEM-CELLS; MEMORY;
EFFECTOR; ANTIGEN
AB The pmel-1 T cell receptor transgenic mouse has been extensively employed as an ideal model system to study the mechanisms of tumor immunology, CD8(+) T cell differentiation, autoimmunity and adoptive immunotherapy. The 'zygosity' of the transgene affects the transgene expression levels and may compromise optimal breeding scheme design. However, the integration sites for the pmel-1 mouse have remained uncharacterized. This is also true for many other commonly used transgenic mice created before the modern era of rapid and inexpensive next-generation sequencing. Here, we show that whole genome sequencing can be used to determine the exact pmel-1 genomic integration site, even with relatively "shallow" (8X) coverage. The results were used to develop a validated polymerase chain reaction-based genotyping assay. For the first time, we provide a quick and convenient polymerase chain reaction method to determine the dosage of pmel-1 transgene for this freely and publically available mouse resource. We also demonstrate that next-generation sequencing provides a feasible approach for mapping foreign DNA integration sites, even when information of the original vector sequences is only partially known.
C1 [Ji, Yun; Zhu, Wei; Gattinoni, Luca] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Abrams, Natalie; Salinas, Eddie; Jailwala, Parthav; Stahlberg, Eric] Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, Frederick, MD USA.
[Yu, Zhiya; Palmer, Douglas C.; Franco, Zulmarie; Roychoudhuri, Rahul; Restifo, Nicholas P.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ji, Y (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM jiyun@mail.nih.gov; restifo@nih.gov
RI Gattinoni, Luca/A-2281-2008; Ji, Yun/B-7245-2009; Palmer,
Douglas/B-9454-2008; Abrams, Natalie/F-4845-2011; Roychoudhuri,
Rahul/A-7442-2010;
OI Gattinoni, Luca/0000-0003-2239-3282; Ji, Yun/0000-0001-6340-7009;
Palmer, Douglas/0000-0001-5018-5734; Abrams,
Natalie/0000-0001-9698-2819; Roychoudhuri, Rahul/0000-0002-5392-1853;
Restifo, Nicholas P./0000-0003-4229-4580
FU National Cancer Institute, Center for Cancer Research of the US National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, Center for Cancer Research of the US National
Institutes of Health. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 75
TC 6
Z9 6
U1 1
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 14
PY 2014
VL 9
IS 5
AR e96650
DI 10.1371/journal.pone.0096650
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI4TJ
UT WOS:000336857400033
PM 24827921
ER
PT J
AU Sun, YC
Jarrett, CO
Bosio, CF
Hinnebusch, BJ
AF Sun, Yi-Cheng
Jarrett, Clayton O.
Bosio, Christopher F.
Hinnebusch, B. Joseph
TI Retracing the Evolutionary Path that Led to Flea-Borne Transmission of
Yersinia pestis
SO CELL HOST & MICROBE
LA English
DT Article
ID EARLY-PHASE TRANSMISSION; BIOFILM FORMATION; ADAPTIVE RADIATION;
CAENORHABDITIS-ELEGANS; DIGUANYLATE CYCLASE; ESCHERICHIA-COLI; MURINE
TOXIN; PLAGUE; VECTOR; PSEUDOTUBERCULOSIS
AB Yersinia pestis is an arthropod-borne bacterial pathogen that evolved recently from Yersinia pseudotuberculosis, an enteric pathogen transmitted via the fecal-oral route. This radical ecological transition can be attributed to a few discrete genetic changes from a still-extant recent ancestor, thus providing a tractable case study in pathogen evolution and emergence. Here, we determined the genetic and mechanistic basis of the evolutionary adaptation of Y. pestis to flea-borne transmission. Remarkably, only four minor changes in the bacterial progenitor, representing one gene gain and three gene losses, enabled transmission by flea vectors. All three loss-of-function mutations enhanced cyclic-di-GMP-mediatedbacterial biofilm formation in the flea foregut, which greatly increased transmissibility. Our results suggest a step-wise evolutionary model in which Y. pestisemerged as a flea-borne clone, with each genetic change incrementally reinforcing the transmission cycle. The model conforms well to the ecological theory of adaptive radiation.
C1 [Sun, Yi-Cheng; Jarrett, Clayton O.; Bosio, Christopher F.; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Hinnebusch, BJ (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, 903 South 4th St, Hamilton, MT 59840 USA.
EM jhinnebusch@niaid.nih.gov
FU Division of Intramural Research; NIAID; NIH from the Program for
Changjiang Scholars and Innovative Research Team in University
[IRT13007]
FX This work was supported by the Division of Intramural Research, NIAID,
NIH and grant IRT13007 from the Program for Changjiang Scholars and
Innovative Research Team in University to Y.-C. S. We thank J. Callison
for molecular biology assistance; K. Lawrence for help with HPLC, A.
Athman for help with preparing figures; and T. Schwan, M. Gottesman, J.
Shannon, J. Spinner, and I. Chouikha for review of the manuscript.
NR 55
TC 18
Z9 20
U1 9
U2 42
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD MAY 14
PY 2014
VL 15
IS 5
BP 578
EP 586
DI 10.1016/j.chom.2014.04.003
PG 9
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AH1XE
UT WOS:000335914300010
PM 24832452
ER
PT J
AU Fauci, AS
Marston, HD
AF Fauci, Anthony S.
Marston, Hilary D.
TI The Perpetual Challenge of Antimicrobial Resistance
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Fauci, Anthony S.; Marston, Hilary D.] NIAID, Bethesda, MD 20892 USA.
RP Fauci, AS (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM afauci@niaid.nih.gov
NR 9
TC 34
Z9 35
U1 0
U2 11
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 14
PY 2014
VL 311
IS 18
BP 1853
EP 1854
DI 10.1001/jama.2014.2465
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AH0GT
UT WOS:000335798100013
PM 24652442
ER
PT J
AU Lutambi, AM
Chitnis, N
Briet, OJT
Smith, TA
Penny, MA
AF Lutambi, Angelina Mageni
Chitnis, Nakul
Briet, Olivier J. T.
Smith, Thomas A.
Penny, Melissa A.
TI Clustering of Vector Control Interventions Has Important Consequences
for Their Effectiveness: A Modelling Study
SO PLOS ONE
LA English
DT Article
ID AFRICAN MOSQUITOS DIPTERA; TREATED BED NETS; ANOPHELES-GAMBIAE; MALARIA
TRANSMISSION; AEDES-AEGYPTI; CULICIDAE; POPULATION; DISPERSAL; DYNAMICS;
FUNESTUS
AB Vector control interventions have resulted in considerable reductions in malaria morbidity and mortality. When universal coverage cannot be achieved for financial or logistical reasons, the spatial arrangement of vector control is potentially important for optimizing benefits. This study investigated the effect of spatial clustering of vector control interventions on reducing the population of biting mosquitoes. A discrete-space continuous-time mathematical model of mosquito population dynamics and dispersal was extended to incorporate vector control interventions of insecticide treated bednets (ITNs), Indoor residual Spraying (IRS), and larviciding. Simulations were run at varying levels of coverage and degree of spatial clustering. At medium to high coverage levels of each of the interventions or in combination was more effective to spatially spread these interventions than to cluster them. Suggesting that when financial resources are limited, unclustered distribution of these interventions is more effective. Although it is often stated that locally high coverage is needed to achieve a community effect of ITNs or IRS, our results suggest that if the coverage of ITNs or IRS are insufficient to achieve universal coverage, and there is no targeting of high risk areas, the overall effects on mosquito densities are much greater if they are distributed in an unclustered way, rather than clustered in specific localities. Also, given that interventions are often delivered preferentially to accessible areas, and are therefore clustered, our model results show this may be inefficient. This study provides evidence that the effectiveness of an intervention can be highly dependent on its spatial distribution. Vector control plans should consider the spatial arrangement of any intervention package to ensure effectiveness is maximized.
C1 [Lutambi, Angelina Mageni; Chitnis, Nakul; Briet, Olivier J. T.; Smith, Thomas A.; Penny, Melissa A.] Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[Lutambi, Angelina Mageni; Chitnis, Nakul; Briet, Olivier J. T.; Smith, Thomas A.; Penny, Melissa A.] Univ Basel, Basel, Switzerland.
[Lutambi, Angelina Mageni] Ifakara Hlth Inst, Dar Es Salaam, Tanzania.
[Chitnis, Nakul] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Lutambi, AM (reprint author), Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
EM angelina-m.lutambi@unibas.ch
RI Smith, Thomas/B-5569-2015; Chitnis, Nakul/B-3105-2013; Penny,
Melissa/N-6838-2015; Briet, Olivier/K-1917-2015
OI Smith, Thomas/0000-0002-3650-9381; Penny, Melissa/0000-0002-4972-593X;
Briet, Olivier/0000-0003-1186-2688
FU Bill and Melinda Gates Foundation provided through Swiss TPH
FX Funding support was from the Bill and Melinda Gates Foundation provided
through Swiss TPH. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 60
TC 4
Z9 4
U1 3
U2 16
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 13
PY 2014
VL 9
IS 5
AR e97065
DI 10.1371/journal.pone.0097065
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH8EY
UT WOS:000336369200055
PM 24823656
ER
PT J
AU Yang, M
Eyers, F
Xiang, Y
Guo, M
Young, IG
Rosenberg, HF
Foster, PS
AF Yang, Ming
Eyers, Fiona
Xiang, Yang
Guo, Man
Young, Ian G.
Rosenberg, Helene F.
Foster, Paul S.
TI Expression Profiling of Differentiating Eosinophils in Bone Marrow
Cultures Predicts Functional Links between MicroRNAs and Their Target
mRNAs
SO PLOS ONE
LA English
DT Article
ID PERIPHERAL-BLOOD EOSINOPHILS; HEMATOPOIETIC STEM-CELLS; TOLL-LIKE
RECEPTORS; RHEUMATOID-ARTHRITIS; CATIONIC PROTEIN; INNATE IMMUNITY;
DEFICIENT MICE; MAST-CELLS; EX-VIVO; IN-VIVO
AB Background: MicroRNAs (miRNAs) are small non-coding RNAs that regulate complex transcriptional networks underpin immune responses. However, little is known about the specific miRNA networks that control differentiation of specific leukocyte subsets. In this study, we profiled miRNA expression during differentiation of eosinophils from bone marrow (BM) progenitors (bmEos), and correlated expression with potential mRNA targets involved in crucial regulatory functions. Profiling was performed on whole BM cultures to document the dynamic changes in miRNA expression in the BM microenvironment over the differentiation period. miRNA for network analysis were identified in BM cultures enriched in differentiating eosinophils, and chosen for their potential ability to target mRNA of factors that are known to play critical roles in eosinophil differentiation pathways or cell identify.
Methodology/Principal Findings: We identified 68 miRNAs with expression patterns that were up-or down-regulated 5-fold or more during bmEos differentiation. By employing TargetScan and MeSH databases, we identified 348 transcripts involved in 30 canonical pathways as potentially regulated by these miRNAs. Furthermore, by applying miRanda and Ingenuity Pathways Analysis (IPA), we identified 13 specific miRNAs that are temporally associated with the expression of IL-5R alpha and CCR3 and 14 miRNAs associated with the transcription factors GATA-1/2, PU.1 and C/EBP epsilon. We have also identified 17 miRNAs that may regulate the expression of TLRs 4 and 13 during eosinophil differentiation, although we could identify no miRNAs targeting the prominent secretory effector, eosinophil major basic protein.
Conclusions/Significance: This is the first study to map changes in miRNA expression in whole BM cultures during the differentiation of eosinophils, and to predict functional links between miRNAs and their target mRNAs for the regulation of eosinophilopoiesis. Our findings provide an important resource that will promote the platform for further understanding of the role of these non-coding RNAs in the regulation of eosinophil differentiation and function.
C1 [Yang, Ming; Eyers, Fiona; Foster, Paul S.] Univ Newcastle, Fac Hlth, Ctr Asthma & Resp Dis, Sch Biomed Sci & Pharm, Callaghan, NSW, Australia.
[Yang, Ming; Eyers, Fiona; Foster, Paul S.] Hunter Med Res Inst, Callaghan, NSW, Australia.
[Xiang, Yang; Guo, Man] Cent S Univ, Xiangya Sch Med, Dept Physiol, Changsha, Hunan, Peoples R China.
[Young, Ian G.] Australian Natl Univ, John Curtin Sch Med Res, Dept Mol Bioscience, Canberra, ACT 2601, Australia.
[Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Yang, M (reprint author), Univ Newcastle, Fac Hlth, Ctr Asthma & Resp Dis, Sch Biomed Sci & Pharm, Callaghan, NSW, Australia.
EM Ming.Yang@newcastle.edu.au; Paul.Foster@newcastle.edu.au
FU National Health and Medical Research Council of Australia; Australian
Research Council; Cooperative Research Centre for Asthma and Airways;
National Institute of Allergy and Infectious Diseases Division of
Intramural Research
FX The authors are supported by the National Health and Medical Research
Council of Australia, the Australian Research Council, the Cooperative
Research Centre for Asthma and Airways and National Institute of Allergy
and Infectious Diseases Division of Intramural Research. The funding
bodies had no further role in study design; in the collection, analysis
and interpretation of data; in the writing of the report; or in the
decision to submit the paper for publication.
NR 81
TC 2
Z9 3
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 13
PY 2014
VL 9
IS 5
AR e97537
DI 10.1371/journal.pone.0097537
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH8EY
UT WOS:000336369200128
PM 24824797
ER
PT J
AU Chung, JY
Braunschweig, T
Hong, SM
Kwon, DS
Eo, SH
Cho, H
Hewitt, SM
AF Chung, Joon-Yong
Braunschweig, Till
Hong, Seung-Mo
Kwon, David S.
Eo, Soo-Heang
Cho, HyungJun
Hewitt, Stephen M.
TI Assessment of vascular endothelial growth factor in formalin fixed,
paraffin embedded colon cancer specimens by means of a well-based
reverse phase protein array
SO PROTEOME SCIENCE
LA English
DT Article
DE Vascular endothelial growth factor; Formalin-fixed paraffin-embedded;
Colon cancer; Immunohistochemistry; Reverse-phase protein array
ID COLORECTAL-CANCER; FACTOR EXPRESSION; PROGNOSTIC VALUE; STAGE-II;
TISSUE; CARCINOMA; VEGF; PROLIFERATION; ANGIOGENESIS; SURVIVAL
AB Background: Vascular endothelial growth factor (VEGF) is a critical pro-angiogenic factor, found in a number of cancers, and a target of therapy. It is typically assessed by immunohistochemistry (IHC) in clinical research. However, IHC is not a quantitative assay and is rarely reproducible. We compared VEGF levels in colon cancer by IHC and a quantitative immunoassay on proteins isolated from formalin fixed, paraffin embedded tissues.
Results: VEGF expression was studied by means of a well-based reverse phase protein array (RPPA) and immunohistochemistry in 69 colon cancer cases, and compared with various clinicopathologic factors. Protein lysates derived from formalin fixed, paraffin embedded tissue contained measurable immunoreactive VEGF molecules. The VEGF expression level of well differentiated colon cancer was significantly higher than those with moderately and poorly differentiated carcinomas by immunohistochemistry (P = 0.04) and well-based RPPA (P = 0.04). VEGF quantification by well-based RPPA also demonstrated an association with nodal metastasis status (P = 0.05). In addition, the normalized VEGF value by well-based RPPA correlated (r= 0.283, P = 0.018). Furthermore, subgroup analysis by histologic type revealed that adenocarcinoma cases showed significant correlation (r = 0.315, P = 0.031) between well-based RPPA and IHC.
Conclusions: The well-based RPPA method is a high throughput and sensitive approach, is an excellent tool for quantification of marker proteins. Notably, this method may be helpful for more objective evaluation of protein expression in cancer patients.
C1 [Chung, Joon-Yong; Kwon, David S.; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Chung, Joon-Yong; Kwon, David S.; Hewitt, Stephen M.] NCI, Appl Mol Pathol Lab, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Braunschweig, Till] Rhein Westfal TH Aachen, Inst Pathol, D-52074 Aachen, Germany.
[Hong, Seung-Mo] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul 138736, South Korea.
[Eo, Soo-Heang; Cho, HyungJun] Korea Univ, Dept Stat, Seoul 136701, South Korea.
RP Hewitt, SM (reprint author), NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA.
EM genejock@helix.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788; Chung,
Joon-Yong/0000-0001-5041-5982
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute; Center for Cancer Research
FX We thank Kris Ylaya for technical assistance. This research was
supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute, Center for Cancer Research.
NR 33
TC 4
Z9 4
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1477-5956
J9 PROTEOME SCI
JI Proteome Sci.
PD MAY 13
PY 2014
VL 12
AR 27
DI 10.1186/1477-5956-12-27
PG 8
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA AI3NF
UT WOS:000336767600001
PM 24883046
ER
PT J
AU Marshall, PA
Adebamowo, CA
Adeyemo, AA
Ogundiran, TO
Strenski, T
Zhou, J
Rotimi, CN
AF Marshall, Patricia A.
Adebamowo, Clement A.
Adeyemo, Adebowale A.
Ogundiran, Temidayo O.
Strenski, Teri
Zhou, Jie
Rotimi, Charles N.
TI Voluntary participation and comprehension of informed consent in a
genetic epidemiological study of breast cancer in Nigeria
SO BMC MEDICAL ETHICS
LA English
DT Article
DE Informed consent; Genetic epidemiological research; Breast cancer;
Nigeria
ID INTERNATIONAL HEALTH RESEARCH; KENYAN COAST; COLLABORATIVE RESEARCH;
COMMUNITY ENGAGEMENT; BIOMEDICAL-RESEARCH; HAPMAP PROJECT; VACCINE
TRIAL; EXPERIENCES; RESEARCHERS; GUIDELINES
AB Background: Studies on informed consent to medical research conducted in low or middle-income settings have increased, including empirical investigations of consent to genetic research. We investigated voluntary participation and comprehension of informed consent among women involved in a genetic epidemiological study on breast cancer in an urban setting of Nigeria comparing women in the case and control groups.
Methods: Surveys were administered in face-to-face interviews with 215 participants following their enrollment in the genetic study (106 patients, 109 controls). Audio-taped in-depth interviews were conducted with a sub-sample of 17 (8%) women who completed the survey.
Results: The majority of all participants reported being told that participation in the genetic study was voluntary (97%), that they did not feel pressured to participate in the study (99%), and that they could withdraw from the study (81%). The majority of the breast cancer patients (83%) compared to 58% of women in the control group reported that the study purpose was to learn about the genetic inheritance of breast cancer (OR 3.44; 95% CI = 1.66, 7.14, p value = 0.001). Most participants reported being told about study procedures (95%) and study benefits (98%). Sixty-eight percent of the patients, compared to 47% of the control group reported being told about study risks (p-value < 0.001). Of the 165 married women, 19% reported asking permission from their husbands to enroll in the breast cancer study; no one sought permission from local elders. In-depth interviews highlight the use of persuasion and negotiation between a wife and her husband regarding study participation.
Conclusions: The global expansion of genetic and genomic research highlights our need to understand informed consent practices for studies in ethnically diverse cultural environments such as Africa. Quantitative and qualitative empirical investigations of the informed consent process for genetic and genomic research will further our knowledge of complex issues associated with communication of information, comprehension, decisional authority and voluntary participation. In the future, the development and testing of innovative strategies to promote voluntary participation and comprehension of the goals of genomic research will contribute to our understanding of strategies that enhance the consent process.
C1 [Marshall, Patricia A.] Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH 44106 USA.
[Adebamowo, Clement A.] Univ Maryland, Sch Med, Inst Human Virol, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Adebamowo, Clement A.] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Adeyemo, Adebowale A.; Zhou, Jie; Rotimi, Charles N.] NIH, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
[Ogundiran, Temidayo O.] Univ Coll Hosp, Div Oncol, Dept Surg, Ibadan, Nigeria.
[Strenski, Teri] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Marshall, PA (reprint author), Case Western Reserve Univ, Sch Med, Dept Bioeth, Room TA 227 10900 Euclid Ave, Cleveland, OH 44106 USA.
EM pam20@case.edu
OI Adeyemo, Adebowale/0000-0002-3105-3231
FU NIH/National Human Genome Research Institute [2 R01 HG002207-04];
National Center on Minority Health and Health Disparity (NCMHD);
National Center for Research Resources (NCRR); Center for Genetic
Research Ethics and Law, Case Western Reserve University (NIH/National
Human Genome Research Institute) [P50-HG-03390]
FX This work was supported by funding from NIH/National Human Genome
Research Institute (PI: P. Marshall, 2 R01 HG002207-04), the National
Center on Minority Health and Health Disparity (NCMHD), the National
Center for Research Resources (NCRR), the Center for Genetic Research
Ethics and Law, Case Western Reserve University (PI: P. Marshall,
NIH/National Human Genome Research Institute, P50-HG-03390). We thank
Richard Cooper and Elaine Prewitt for their support in research design
and data analysis.
NR 64
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Z9 9
U1 1
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6939
J9 BMC MED ETHICS
JI BMC Med. Ethics
PD MAY 13
PY 2014
VL 15
AR 38
DI 10.1186/1472-6939-15-38
PG 11
WC Ethics; Medical Ethics; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Biomedical Social
Sciences
GA AI1OO
UT WOS:000336620800001
PM 24885380
ER
PT J
AU Boudreau, HE
Casterline, BW
Burke, DJ
Leto, TL
AF Boudreau, H. E.
Casterline, B. W.
Burke, D. J.
Leto, T. L.
TI Wild-type and mutant p53 differentially regulate NADPH oxidase 4 in
TGF-beta-mediated migration of human lung and breast epithelial cells
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE NADPH oxidase; reactive oxygen species (ROS); cell migration;
transforming growth factor-beta (TGF-beta); epithelial-to-mesenchymal
transition (EMT); mutant p53
ID SMOOTH-MUSCLE-CELLS; FOCAL ADHESION KINASE; GROWTH-FACTOR-BETA; OXYGEN
SPECIES PRODUCTION; NOX4 NAD(P)H OXIDASE; MESENCHYMAL TRANSITION;
SIGNAL-TRANSDUCTION; ENDOTHELIAL-CELLS; TRANSFORMING
GROWTH-FACTOR-BETA-1; TRANSCRIPTIONAL REPRESSION
AB Background: Transforming growth factor-beta (TGF-beta) induces the epithelial-to-mesenchymal transition (EMT) leading to increased cell plasticity at the onset of cancer cell invasion and metastasis. Mechanisms involved in TGF-beta-mediated EMT and cell motility are unclear. Recent studies showed that p53 affects TGF-beta/SMAD3-mediated signalling, cell migration, and tumorigenesis. We previously demonstrated that Nox4, a Nox family NADPH oxidase, is a TGF-beta/SMAD3-inducible source of reactive oxygen species (ROS) affecting cell migration and fibronectin expression, an EMT marker, in normal and metastatic breast epithelial cells. Our present study investigates the involvement of p53 in TGF-beta-regulated Nox4 expression and cell migration.
Methods: We investigated the effect of wild-type p53 (WT-p53) and mutant p53 proteins on TGF-beta-regulated Nox4 expression and cell migration. Nox4 mRNA and protein, ROS production, cell migration, and focal adhesion kinase (FAK) activation were examined in three different cell models based on their p53 mutational status. H1299, a p53-null lung epithelial cell line, was used for heterologous expression of WT-p53 or mutant p53. In contrast, functional studies using siRNA-mediated knockdown of endogenous p53 were conducted in MDA-MB-231 metastatic breast epithelial cells that express p53-R280K and MCF-10A normal breast cells that have WT-p53.
Results: We found that WT-p53 is a potent suppressor of TGF-beta-induced Nox4, ROS production, and cell migration in p53-null lung epithelial (H1299) cells. In contrast, tumour-associated mutant p53 proteins (R175H or R280K) caused enhanced Nox4 expression and cell migration in both TGF-beta-dependent and TGF-beta-independent pathways. Moreover, knockdown of endogenous mutant p53 (R280K) in TGF-beta-treated MDA-MB-231 metastatic breast epithelial cells resulted in decreased Nox4 protein and reduced phosphorylation of FAK, a key regulator of cell motility. Expression of WT-p53 or dominant-negative Nox4 decreased TGF-beta-mediated FAK phosphorylation, whereas mutant p53 (R280K) increased phospho-FAK. Furthermore, knockdown of WT-p53 in MCF-10A normal breast epithelial cells increased basal Nox4 expression, whereas p53-R280K could override endogenous WT-p53 repression of Nox4. Remarkably, immunofluorescence analysis revealed MCF-10A cells expressing p53-R280K mutant showed an upregulation of Nox4 in both confluent and migrating cells.
Conclusions: Collectively, our findings define novel opposing functions for WT-p53 and mutant p53 proteins in regulating Nox4-dependent signalling in TGF-beta-mediated cell motility.
C1 [Boudreau, H. E.; Casterline, B. W.; Burke, D. J.; Leto, T. L.] NIAID, Host Def Lab, NIH, Rockville, MD 20852 USA.
RP Leto, TL (reprint author), NIAID, Host Def Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA.
EM tleto@nih.gov
FU Intramural Research Program of the NIH, National Institute of Allergy
and Infectious Diseases [ZO1-AI-000614]
FX This work was supported by funds from the Intramural Research Program of
the NIH, National Institute of Allergy and Infectious Diseases
(ZO1-AI-000614). We would like to thank Drs Lucy A Godley and Sharon H
Jackson for their careful review of this manuscript, and Joseph
Brzostowski for microscopy training and use of LIG core imaging
facility.
NR 85
TC 12
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U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAY 13
PY 2014
VL 110
IS 10
BP 2569
EP 2582
DI 10.1038/bjc.2014.165
PG 14
WC Oncology
SC Oncology
GA AH6OJ
UT WOS:000336250000023
PM 24714748
ER
PT J
AU Little, MP
Schaeffer, ML
Reulen, RC
Abramson, DH
Stovall, M
Weathers, R
de Vathaire, F
Diallo, I
Seddon, JM
Hawkins, MM
Tucker, MA
Kleinerman, RA
AF Little, M. P.
Schaeffer, M. L.
Reulen, R. C.
Abramson, D. H.
Stovall, M.
Weathers, R.
de Vathaire, F.
Diallo, I.
Seddon, J. M.
Hawkins, M. M.
Tucker, M. A.
Kleinerman, R. A.
TI Breast cancer risk after radiotherapy for heritable and non-heritable
retinoblastoma: a US-UK study
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE breast cancer; radiotherapy; alkylating agents; retinoblastoma; genetic
risk
ID ATOMIC-BOMB SURVIVORS; LONG-TERM SURVIVORS; BRCA2 MUTATION CARRIERS;
CHILDHOOD-CANCER; GENE-MUTATIONS; DIAGNOSTIC RADIATION; VISUAL
IMPAIRMENT; POOLED ANALYSIS; 2ND CANCER; FOLLOW-UP
AB Background: Retinoblastoma is a rare childhood eye cancer caused by germline or somatic mutations in the RB1 gene. Previous studies observed elevated breast cancer risk among retinoblastoma survivors. However, there has been no research on breast cancer risk in relation to radiation (primarily scatter radiation from the primary treatment) and genetic susceptibility of retinoblastoma survivors.
Methods: Two groups of retinoblastoma survivors from the US and UK were selected, and breast cancer risk analysed using a case-control methodology, nesting within the respective cohorts, matching on heritability (that is to say, having bilateral retinoblastoma or being unilateral cases with at least one relative with retinoblastoma), and using exact statistical methods. There were a total of 31 cases and 77 controls.
Results: Overall there was no significant variation of breast cancer risk with dose (P > 0.5). However, there was a pronounced and significant (P = 0.047) increase in the risk of breast cancer with increasing radiation dose for non-heritable retinoblastoma patients and a slight and borderline significant (P = 0.072) decrease in risk of breast cancer with increasing radiation dose for heritable retinoblastoma patients, implying significant (P = 0.024) heterogeneity in radiation risk between the heritable and non-heritable retinoblastoma groups; this was unaffected by the blindness status. There was no significant effect of any type of alkylating-agent chemotherapy on breast cancer risk (P > 0.5).
Conclusions: There is significant radiation-related risk of breast cancer for non-heritable retinoblastoma survivors but no excess risk for heritable retinoblastoma survivors, and no significant risk overall. However, these results are based on very small numbers of cases; therefore, they must be interpreted with caution.
C1 [Little, M. P.; Tucker, M. A.; Kleinerman, R. A.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Schaeffer, M. L.] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA 90095 USA.
[Reulen, R. C.; Hawkins, M. M.] Univ Birmingham, Sch Hlth & Populat Sci, Ctr Childhood Canc Survivor Studies, Dept Epidemiol & Publ Hlth, Birmingham B15 2TT, W Midlands, England.
[Abramson, D. H.] Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, New York, NY 10021 USA.
[Stovall, M.; Weathers, R.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[de Vathaire, F.; Diallo, I.] Inst Gustave Roussy, INSERM, Unit 1018, Radiat Epidemiol Grp, F-98000 Villejuif, France.
[Seddon, J. M.] Tufts Univ New England Med Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA 02111 USA.
RP Little, MP (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
EM mark.little@nih.gov
RI Tucker, Margaret/B-4297-2015; de Vathaire, Florent/L-2983-2016;
OI Kleinerman, Ruth/0000-0001-7415-2478; Little, Mark/0000-0003-0980-7567
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute (NCI), Division of Cancer Epidemiology and
Genetics
FX We are grateful for the technical assistance of Jeremy Miller and the
detailed and helpful comments of Dr Peter Inskip, Dr Ethel Gilbert, and
the two referees. This work was supported by the Intramural Research
Program of the National Institutes of Health, the National Cancer
Institute (NCI), Division of Cancer Epidemiology and Genetics.
NR 53
TC 4
Z9 4
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAY 13
PY 2014
VL 110
IS 10
BP 2623
EP 2632
DI 10.1038/bjc.2014.193
PG 10
WC Oncology
SC Oncology
GA AH6OJ
UT WOS:000336250000028
PM 24755883
ER
PT J
AU Simpson, EA
Sclafani, V
Paukner, A
Hamel, AF
Novak, MA
Meyer, JS
Suomi, SJ
Ferrari, PF
AF Simpson, Elizabeth A.
Sclafani, Valentina
Paukner, Annika
Hamel, Amanda F.
Novak, Melinda A.
Meyer, Jerrold S.
Suomi, Stephen J.
Ferrari, Pier Francesco
TI Inhaled oxytocin increases positive social behaviors in newborn macaques
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE imitation recognition; neonatal imitation; individual differences
ID AUTISM SPECTRUM DISORDERS; INTRANASAL OXYTOCIN; PLASMA OXYTOCIN; RHESUS
MACAQUES; DOSE-RESPONSE; NEURAL BASIS; AFFILIATION; BRAIN; ATTENTION;
MONKEYS
AB Early caregiver-infant interactions are critical for infants' socioemotional and cognitive development. Several hormones and neuromodulators, including oxytocin, affect these interactions. Exogenous oxytocin promotes social behaviors in several species, including human and nonhuman primates. Although exogenous oxytocin increases social function in adults-including expression recognition and affiliation-it is unknown whether oxytocin can increase social interactions in infants. We hypothesized that nebulized oxytocin would increase affiliative social behaviors and such effects would be modulated by infants' social skills, measured earlier in development. We also hypothesized that oxytocin's effects on social behaviors may be due to its anxiolytic effects. We tested these hypotheses in a blind study by nebulizing 7- to 14-d-old macaques (n = 28) with oxytocin or saline. Following oxytocin administration, infants' facial gesturing at a human caregiver increased, and infants' salivary oxytocin was positively correlated with the time spent in close proximity to a caregiver. Infants' imitative skill (measured earlier in development: 1-7 d of age) predicted oxytocin-associated increases in affiliative behaviors-lip smacking, visual attention to a caregiver, and time in close proximity to a caregiver-suggesting that infants with higher propensities for positive social interactions are more sensitive to exogenous oxytocin. Oxytocin also decreased salivary cortisol, but not stress-related behaviors (e.g., scratching), suggesting the possibility of some anxiolytic effects. To our knowledge, this study provides the first evidence that oxytocin increases positive social behaviors in newborns. This information is of critical importance for potential interventions aimed at ameliorating inadequate social behaviors in infants with higher likelihood of developing neurodevelopmental disorder.
C1 [Simpson, Elizabeth A.; Paukner, Annika; Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Comparat Ethol Lab, Poolesville, MD 20837 USA.
[Simpson, Elizabeth A.; Sclafani, Valentina; Ferrari, Pier Francesco] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy.
[Hamel, Amanda F.; Novak, Melinda A.; Meyer, Jerrold S.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA.
RP Simpson, EA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Comparat Ethol Lab, Poolesville, MD 20837 USA.
EM simpsonea@mail.nih.gov
OI Meyer, Jerrold/0000-0002-8382-7075; Simpson,
Elizabeth/0000-0003-2715-2533
FU Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), NICHD
[P01HD064653]; National Institutes of Health [RR11122]
FX We thank Ruth Woodward and Angela Ruggiero for technical assistance
administering oxytocin and collecting saliva. We thank Lydia Martin,
Grace Maloney, and Chris Catalfamo for behavioral reliability coding.
Thanks to Nathan Fox for feedback on an earlier version of this paper.
The Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), NICHD Grant
P01HD064653 (to P.F.F.), and National Institutes of Health Grant RR11122
(to M.A.N.) supported this research.
NR 76
TC 23
Z9 23
U1 5
U2 44
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 13
PY 2014
VL 111
IS 19
BP 6922
EP 6927
DI 10.1073/pnas.1402471111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH0GS
UT WOS:000335798000049
PM 24778211
ER
PT J
AU Chagas, AC
Ramirez, JL
Jasinskiene, N
James, AA
Ribeiro, JMC
Marinotti, O
Calvo, E
AF Chagas, Andrezza Campos
Ramirez, Jose Luis
Jasinskiene, Nijole
James, Anthony A.
Ribeiro, Jose M. C.
Marinotti, Osvaldo
Calvo, Eric
TI Collagen-binding protein, Aegyptin, regulates probing time and blood
feeding success in the dengue vector mosquito, Aedes aegypti
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE hematophagy; evolution; saliva; transgenesis; RNAi
ID SALIVARY-GLAND PROTEIN; YELLOW-FEVER MOSQUITO; VON-WILLEBRAND-FACTOR;
PLATELET-FUNCTION; ANOPHELES; GENE; DISEASE; AGGREGATION; ACTIVATION;
INSIGHT
AB Mosquito salivary glands have important roles in blood feeding and pathogen transmission. However, the biological relevance of many salivary components has yet to be determined. Aegyptin, a secreted salivary protein from Aedes aegypti, binds collagen and inhibits platelet aggregation and adhesion. We used a transgenic approach to study the relevance of Aegyptin in mosquito blood feeding. Aedes aegypti manipulated genetically to express gene-specific inverted-repeat RNA sequences exhibited significant reductions in Aegyptin mRNA accumulation (85-87%) and protein levels (>80-fold) in female mosquito salivary glands. Transgenic mosquitoes had longer probing times (78-300 s, P < 0.0001) when feeding on mice compared with controls (15-56 s), feeding success was reduced, and those feeding took smaller blood meals. However, no differences in feeding success or blood meal size were found in membrane feeding experiments using defibrinated human blood. Salivary gland extracts from transgenic mosquitoes failed to inhibit collagen-induced platelet aggregation in vitro. Reductions of Aegyptin did not affect salivary ADP-induced platelet aggregation inhibition or disturb anticlotting activities. Our results demonstrate the relevance of Aegyptin for A. aegypti blood feeding, providing further support for the hypothesis that platelet aggregation inhibition is a vital salivary function in blood feeding arthropods. It has been suggested that the multiple mosquito salivary components mediating platelet aggregation (i.e., Aegyptin, apyrase, D7) represent functional redundancy. Our findings do not support this hypothesis; instead, they indicate that multiple salivary components work synergistically and are necessary to achieve maximum blood feeding efficiency.
C1 [Chagas, Andrezza Campos; Ramirez, Jose Luis; Ribeiro, Jose M. C.; Calvo, Eric] NIAID, Lab Malaria & Vector Res, Rockville, MD 20852 USA.
[Jasinskiene, Nijole; James, Anthony A.; Marinotti, Osvaldo] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA.
[James, Anthony A.] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA.
RP Marinotti, O (reprint author), Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA.
EM omarinot@uci.edu; ecalvo@niaid.nih.gov
RI Ribeiro, Jose/J-7011-2015;
OI Marinotti, Osvaldo/0000-0002-7173-7160; Calvo, Eric/0000-0001-7880-2730;
Ribeiro, Jose/0000-0002-9107-0818
FU Intramural Research Program of the Division of Intramural Research,
NIAID, NIH; NIH NIAID [AI29746]
FX We thank V. M. Pham for technical support; Judy Coleman, Aniko Fazekas,
Andre Laughinghouse, and Kevin Lee for expert mosquito care;
DTM/National Institutes of Health (NIH) for providing platelet-rich
plasma; and Brenda Marshall [Department of Public Social Services,
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases (NIAID)] for editorial assistance. This work was
supported by the Intramural Research Program of the Division of
Intramural Research, NIAID, NIH. O.M., N.J., and A.A.J. were supported
in part by NIH NIAID Grant AI29746.
NR 38
TC 4
Z9 4
U1 1
U2 24
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 13
PY 2014
VL 111
IS 19
BP 6946
EP 6951
DI 10.1073/pnas.1404179111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH0GS
UT WOS:000335798000053
PM 24778255
ER
PT J
AU Kaila, VRI
Wikstrom, M
Hummer, G
AF Kaila, Ville R. I.
Wikstrom, Marten
Hummer, Gerhard
TI Electrostatics, hydration, and proton transfer dynamics in the membrane
domain of respiratory complex I
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE biological energy conversion; proton pumping; Grotthuss mechanism; QM/MM
ID COUPLED ELECTRON-TRANSFER; CYTOCHROME-C-OXIDASE; NADH-QUINONE
OXIDOREDUCTASE; MOLECULAR-MECHANISM; HYDROPHILIC DOMAIN;
CRYSTAL-STRUCTURE; ENERGETICS; CHAIN; PUMP; TRANSLOCATION
AB Complex I serves as the primary electron entry point into the mitochondrial and bacterial respiratory chains. It catalyzes the reduction of quinones by electron transfer from NADH, and couples this exergonic reaction to the translocation of protons against an electrochemical proton gradient. The membrane domain of the enzyme extends similar to 180 angstrom from the site of quinone reduction to the most distant proton pathway. To elucidate possible mechanisms of the long-range proton-coupled electron transfer process, we perform large-scale atomistic molecular dynamics simulations of the membrane domain of complex I from Escherichia coli. We observe spontaneous hydration of a putative proton entry channel at the NuoN/K interface, which is sensitive to the protonation state of buried glutamic acid residues. In hybrid quantum mechanics/classical mechanics simulations, we find that the observed water wires support rapid proton transfer from the protein surface to the center of the membrane domain. To explore the functional relevance of the pseudosymmetric inverted-repeat structures of the antiporter-like subunits NuoL/M/N, we constructed a symmetry-related structure of a possible alternate-access state. In molecular dynamics simulations, we find the resulting structural changes to be metastable and reversible at the protein backbone level. However, the increased hydration induced by the conformational change persists, with water molecules establishing enhanced lateral connectivity and pathways for proton transfer between conserved ionizable residues along the center of the membrane domain. Overall, the observed water-gated transitions establish conduits for the unidirectional proton translocation processes, and provide a possible coupling mechanism for the energy transduction in complex I.
C1 [Kaila, Ville R. I.] Tech Univ Munich, Dept Chem, D-85748 Garching, Germany.
[Kaila, Ville R. I.; Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Wikstrom, Marten] Univ Helsinki, Inst Biotechnol, Helsinki Bioenerget Grp, FI-00014 Helsinki, Finland.
[Hummer, Gerhard] Max Planck Inst Biophys, Dept Theoret Biophys, D-60438 Frankfurt, Germany.
RP Kaila, VRI (reprint author), Tech Univ Munich, Dept Chem, D-85748 Garching, Germany.
EM ville.kaila@ch.tum.de; gerhard.hummer@biophys.mpg.de
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health; Max Planck Society; European Molecular
Biology Organization Long-Term Fellowship; Sigrid Juselius Foundation;
Biocentrum Helsinki; Academy of Finland
FX We thank the high-performance Biowulf cluster (http://biowulf.nih.gov)
at the National Institutes of Health for computer time. This work was
supported by the Intramural Research Program of the National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes of
Health (V. R. I. K. and G. H); the Max Planck Society (G. H.); a
European Molecular Biology Organization Long-Term Fellowship (to V. R.
I. K.); and by grants from the Sigrid Juselius Foundation, Biocentrum
Helsinki, and the Academy of Finland (all to M.W.).
NR 46
TC 31
Z9 31
U1 4
U2 55
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 13
PY 2014
VL 111
IS 19
BP 6988
EP 6993
DI 10.1073/pnas.1319156111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH0GS
UT WOS:000335798000060
PM 24778264
ER
PT J
AU Cillo, AR
Sobolewski, MD
Bosch, RJ
Fyne, E
Piatak, M
Coffin, JM
Mellors, JW
AF Cillo, Anthony R.
Sobolewski, Michele D.
Bosch, Ronald J.
Fyne, Elizabeth
Piatak, Michael, Jr.
Coffin, John M.
Mellors, John W.
TI Quantification of HIV-1 latency reversal in resting CD4(+) T cells from
patients on suppressive antiretroviral therapy
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE HIV-1 persistence; HIV-1 eradication; HIV-1 cure; fractional provirus
expression
ID RALTEGRAVIR INTENSIFICATION; INFECTED INDIVIDUALS; PLASMA VIREMIA;
RESERVOIR; PERSISTENCE; EXPRESSION; MARKERS; DNA
AB Reversal of proviral latency is being pursued as a curative strategy for HIV-1 infection. Recent clinical studies of in vivo administration of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA; vorinostat) show increases in unspliced cellular HIV-1 RNA levels in resting CD4(+) T cells. A critical unknown, however, is the proportion of latent proviruses that can be transcriptionally reactivated by SAHA or T-cell activation. In this study, we quantified the fraction of HIV-1 proviruses in resting CD4(+) T cells from patients on suppressive antiretroviral therapy that were reactivated ex vivo with SAHA or antibodies to CD3/CD28. At concentrations of SAHA achieved clinically, only 0.079% of proviruses in resting CD4(+) T cells were reactivated to produce virions, compared with 1.5% of proviruses in cells treated with anti-CD3/CD28 antibodies after correcting for spontaneous virion production in the medium control. A significant positive correlation (rho = 0.67, P < 0.001) was found between levels of virions in the supernatant and unspliced cellular HIV-1 RNA following anti-CD3/CD28 treatment, but not following SAHA treatment (rho = 0.21, P = 0.99). These results reveal that the majority of HIV-1 proviruses are not reactivated by current therapeutic approaches and that more effective means of reversing proviral latency will likely be required to deplete HIV-1 reservoirs.
C1 [Cillo, Anthony R.; Sobolewski, Michele D.; Fyne, Elizabeth; Mellors, John W.] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15261 USA.
[Bosch, Ronald J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Piatak, Michael, Jr.] NCI, AIDS & Canc Virus Program, SAIC Freder Inc, Frederick, MD 21702 USA.
[Coffin, John M.] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
RP Coffin, JM (reprint author), Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
EM john.coffin@tufts.edu; jwm1@pitt.edu
FU Pitt AIDS Research Training Program [5 T32 AI065380-08]; Science
Applications and International Corporation (SAIC) through the National
Cancer Institute [25XS119]; F. M. Kirby Foundation
FX We thank the volunteers for participating in this study. Funding was
provided by the Pitt AIDS Research Training Program 5 T32 AI065380-08
and Science Applications and International Corporation (SAIC) Contract
25XS119 through the National Cancer Institute. J.M.C. was a research
professor of the American Cancer Society with support from the F. M.
Kirby Foundation.
NR 36
TC 71
Z9 71
U1 1
U2 16
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 13
PY 2014
VL 111
IS 19
BP 7078
EP 7083
DI 10.1073/pnas.1402873111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH0GS
UT WOS:000335798000075
PM 24706775
ER
PT J
AU Safronetz, D
Prescott, J
Feldmann, F
Haddock, E
Rosenke, R
Okumura, A
Brining, D
Dahlstrom, E
Porcella, SF
Ebihara, H
Scott, DP
Hjelle, B
Feldmann, H
AF Safronetz, David
Prescott, Joseph
Feldmann, Friederike
Haddock, Elaine
Rosenke, Rebecca
Okumura, Atsushi
Brining, Douglas
Dahlstrom, Eric
Porcella, Stephen F.
Ebihara, Hideki
Scott, Dana P.
Hjelle, Brian
Feldmann, Heinz
TI Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE New World hantaviruses; emerging pathogen; disease modeling
ID SIN-NOMBRE-VIRUS; PUUMALA HANTAVIRUS; CARDIOPULMONARY SYNDROME; ANDES
VIRUS; CYNOMOLGUS MACAQUES; INCUBATION PERIOD; IMMUNE-RESPONSE;
CELL-CULTURE; S-SEGMENT; INFECTION
AB The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases.
C1 [Safronetz, David; Prescott, Joseph; Haddock, Elaine; Ebihara, Hideki; Feldmann, Heinz] NIAID, Lab Virol, Rocky Mt Lab Res Technol Sect, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT 59840 USA.
[Feldmann, Friederike; Rosenke, Rebecca; Brining, Douglas; Scott, Dana P.] NIAID, Rocky Mt Vet Branch, Rocky Mt Lab Res Technol Sect, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT 59840 USA.
[Dahlstrom, Eric; Porcella, Stephen F.] NIAID, Genom Unit, Rocky Mt Lab Res Technol Sect, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT 59840 USA.
[Okumura, Atsushi] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
[Hjelle, Brian] Univ New Mexico Hlth Sci Ctr, Dept Pathol, Ctr Infect Dis & Immun, Albuquerque, NM 87131 USA.
[Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0J9, Canada.
RP Feldmann, H (reprint author), NIAID, Lab Virol, Rocky Mt Lab Res Technol Sect, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT 59840 USA.
EM feldmannh@niaid.nih.gov
RI Okumura, Atsushi/E-8012-2015
OI Okumura, Atsushi/0000-0002-7779-3059
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX We thank Edward Schreckendgust, Rocky Rivera, Sandy Skorupa, Kathleen
Meuchel, Jayne Faris, Amanda Weidow, Rachael LaCasse, Kimberly
Meade-White, Tina Thomas, Dan Long, Shelly Robertson, Aaron Carmody,
Sarah L. Anzick, Stacy M. Ricklefs, and Dan Bruno for scientific
discussions and technical assistance and Anita Mora and Heather Murphy
for preparing the graphics. This study was financially supported by the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 44
TC 20
Z9 20
U1 1
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 13
PY 2014
VL 111
IS 19
BP 7114
EP 7119
DI 10.1073/pnas.1401998111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH0GS
UT WOS:000335798000081
PM 24778254
ER
PT J
AU Wuchty, S
AF Wuchty, Stefan
TI Controllability in protein interaction networks
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID PHOSPHORYLATION NETWORKS; INTERACTION MAP; YEAST; RESOURCE;
EVOLUTIONARY; DATABASE
AB Recently, the focus of network research shifted to network controllability, prompting us to determine proteins that are important for the control of the underlying interaction webs. In particular, we determined minimum dominating sets of proteins (MDSets) in human and yeast protein interaction networks. Such groups of proteins were defined as optimized subsets where each non-MDSet protein can be reached by an interaction from an MDSet protein. Notably, we found that MDSet proteins were enriched with essential, cancer-related, and virus-targeted genes. Their central position allowed MDSet proteins to connect protein complexes and to have a higher impact on network resilience than hub proteins. As for their involvement in regulatory functions, MDSet proteins were enriched with transcription factors and protein kinases and were significantly involved in bottleneck interactions, regulatory links, phosphorylation events, and genetic interactions.
C1 [Wuchty, Stefan] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Wuchty, S (reprint author), Univ Miami, Dept Comp Sci, Coral Gables, FL 33146 USA.
EM wuchtys@cs.miami.edu
FU National Institutes of Health/Department of Health and Human Services
(Intramural Research program of the National Library of Medicine);
Department of Computer Science at the University of Miami
FX We thank A.-L. Barabasi, Peter Uetz, and Sawsan Khouri for fruitful
discussions. This work was supported by the National Institutes of
Health/Department of Health and Human Services (Intramural Research
program of the National Library of Medicine) as well as start-up funds
from the Department of Computer Science at the University of Miami.
NR 32
TC 50
Z9 51
U1 3
U2 33
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 13
PY 2014
VL 111
IS 19
BP 7156
EP 7160
DI 10.1073/pnas.1311231111
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH0GS
UT WOS:000335798000088
PM 24778220
ER
PT J
AU Fujiwara, I
Remmert, K
Piszczek, G
Hammer, JA
AF Fujiwara, Ikuko
Remmert, Kirsten
Piszczek, Grzegorz
Hammer, John A.
TI Capping protein regulatory cycle driven by CARMIL and V-1 may promote
actin network assembly at protruding edges
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cell migration; VASP
ID FILAMENT BARBED END; HOMOLOGY DOMAIN 3; ARP2/3 COMPLEX; MOTILITY;
NUCLEATION; POLYMERIZATION; MECHANISM; DYNAMICS; PROFILIN;
THYMOSIN-BETA-4
AB Although capping protein (CP) terminates actin filament elongation, it promotes Arp2/3-dependent actin network assembly and accelerates actin-based motility both in vitro and in vivo. In vitro, capping protein Arp2/3 myosin I linker (CARMIL) antagonizes CP by reducing its affinity for the barbed end and by uncapping CP-capped filaments, whereas the protein V-1/myotrophin sequesters CP in an inactive complex. Previous work showed that CARMIL can readily retrieve CP from the CP:V-1 complex, thereby converting inactive CP into a version with moderate affinity for the barbed end. Here we further clarify the mechanism of this exchange reaction, and we demonstrate that the CP:CARMIL complex created by complex exchange slows the rate of barbed-end elongation by rapidly associating with, and dissociating from, the barbed end. Importantly, the cellular concentrations of V-1 and CP determined here argue that most CP is sequestered by V-1 at steady state in vivo. Finally, we show that CARMIL is recruited to the plasma membrane and only at cell edges undergoing active protrusion. Assuming that CARMIL is active only at this location, our data argue that a large pool of freely diffusing, inactive CP (CP:V-1) feeds, via CARMIL-driven complex exchange, the formation of weak-capping complexes (CP:CARMIL) at the plasma membrane of protruding edges. In vivo, therefore, CARMIL should promote Arp2/3-dependent actin network assembly at the leading edge by promoting barbed-end capping there.
C1 [Fujiwara, Ikuko; Remmert, Kirsten; Hammer, John A.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
[Piszczek, Grzegorz] NHLBI, Ctr Biophys, NIH, Bethesda, MD 20892 USA.
RP Hammer, JA (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM hammerj@nhlbi.nih.gov
NR 43
TC 18
Z9 18
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 13
PY 2014
VL 111
IS 19
BP E1970
EP E1979
DI 10.1073/pnas.1313738111
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH0GS
UT WOS:000335798000010
PM 24778263
ER
PT J
AU Li, WD
Chen, CH
Saud, SM
Geng, L
Zhang, G
Liu, R
Hua, BJ
AF Li, Weidong
Chen, Cihui
Saud, Shakir M.
Geng, Liang
Zhang, Ge
Liu, Rui
Hua, Baojin
TI Fei-Liu-Ping ointment inhibits lung cancer growth and invasion by
suppressing tumor inflammatory microenvironment
SO BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
LA English
DT Article
DE Lung cancer; Fei-Liu-Ping ointment; Nuclear factor kappa light chain
enhancer of activated B cells; Inflammation; Invasion; Epithelial
mesenchymal transition; Cyclophosphamide
ID NF-KAPPA-B; EPITHELIAL-MESENCHYMAL TRANSITIONS; CHINESE MEDICINE; DRUG
DEVELOPMENT; UP-REGULATION; INVASIVENESS; PHARMACOLOGY; MACROPHAGES;
PROGRESSION; METASTASIS
AB Background: Lung cancer is one of the leading causes of cancer-related mortality worldwide. Conventional chemotherapy and radiotherapy are the primary therapeutic methods for lung cancer with the use of combination therapies gaining popularity. The frequency and duration of treatment, as well as, managing lung cancer by targeting multiple aspects of cancer biology is often limited by toxicity to the patient. There are many naturally occurring anticancer agents that have a high degree of efficacy and low toxicity, offering a viable and safe approach for the treatment of lung cancer. The herbs traditionally used in Chinese medicine for anticancer treatment offer great potential to enhance the efficacy of conventional therapy. In this study, we evaluated the synergistic effects of Fei-Liu-Ping (FLP) ointment in treating lung cancer; a known anticancer Chinese herbal based formula.
Methods: In this study, A549 human lung carcinoma cell line and Lewis lung carcinoma xenograft mouse model were used. In addition, we utilized an in vitro co-culture system to simulate the tumor microenvironment in order to evaluate the molecular mechanisms of FLP treatment.
Results: FLP treatment significantly inhibited tumor growth in the Lewis lung xenograft by 40 percent, compared to that of cyclophosphamide (CTX) of 62.02 percent. Moreover, combining FLP and CTX inhibited tumor growth by 83.23 percent. Upon evaluation, we found that FLP treatment reduced the concentration of serum pro-inflammatory cytokines IL-6, TNF-alpha, and IL-1 beta. In addition, we also found an improvement in E-cadherin expression and inhibition of N-cadherin and MMP9. We found similar findings in vitro when we co-cultured A549 cells with macrophages. FLP treatment inhibited A549 cell growth, invasion and metastasis, in part, through the regulation of NF-kappa B and altering the expression of E-cadherin, N-cadherin, MMP2 and MMP9.
Conclusions: FLP exerts anti-inflammatory properties in the tumor microenvironment, which may contribute to its anticancer effects. FLP treatment may be a promising therapy for inflammation associated lung cancer treatment alone, or in combination with conventional therapies and may prevent lung cancer metastasis.
C1 [Li, Weidong; Zhang, Ge; Liu, Rui; Hua, Baojin] China Acad Chinese Med Sci, Guanganmen Hosp, Dept Oncol, Beijing 100053, Peoples R China.
[Chen, Cihui] TCM, Zhejiang Prov Hosp, Dept Oncol, Hangzhou 310006, Zhejiang, Peoples R China.
[Saud, Shakir M.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Rockville, MD 21702 USA.
[Geng, Liang] Zhengzhou Univ, Henan Canc Hosp, Zhengzhou 450003, Henan, Peoples R China.
RP Hua, BJ (reprint author), China Acad Chinese Med Sci, Guanganmen Hosp, Dept Oncol, Beijing 100053, Peoples R China.
EM dr.huabaojin@hotmail.com
FU National Natural Science Foundation of China [81273718, 81102587,
2012T50199, 20110490559]; Ministry of Science and Technology of the
People's Republic of China [2010ZX09102-216]
FX We thank all the researchers who were involved in this study and we
thank Dr. Matthew R. Young for reviewing and revising this manuscript.
We also thank Xin Qi and Yingxia Pei for technical assistance. We also
thank Bingkui Piao for theory guidance of Chinese Medicine. This study
was supported by the grant from National Natural Science Foundation of
China. (No. 81273718; No. 81102587, No. 2012T50199, No. 20110490559) and
from Ministry of Science and Technology of the People's Republic of
China. (No. 2010ZX09102-216).
NR 40
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Z9 10
U1 1
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6882
J9 BMC COMPLEM ALTERN M
JI BMC Complement. Altern. Med.
PD MAY 12
PY 2014
VL 14
AR 153
DI 10.1186/1472-6882-14-153
PG 12
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA AI4TI
UT WOS:000336857300001
PM 24885825
ER
PT J
AU Evans, DS
Calton, MA
Kim, MJ
Kwok, PY
Miljkovic, I
Harris, T
Koster, A
Liu, YM
Tranah, GJ
Ahituv, N
Hsueh, WC
Vaisse, C
AF Evans, Daniel S.
Calton, Melissa A.
Kim, Mee J.
Kwok, Pui-Yan
Miljkovic, Iva
Harris, Tamara
Koster, Annemarie
Liu, Yongmei
Tranah, Gregory J.
Ahituv, Nadav
Hsueh, Wen-Chi
Vaisse, Christian
TI Genetic Association Study of Adiposity and Melanocortin-4 Receptor
(MC4R) Common Variants: Replication and Functional Characterization of
Non-Coding Regions
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; NERVOUS-SYSTEM; ADULT OBESITY;
LOCI; INDIVIDUALS; POLYMORPHISMS; METAANALYSIS; MUTATIONS; AFRICAN
AB Common genetic variants 3 ' of MC4R within two large linkage disequilibrium (LD) blocks spanning 288 kb have been associated with common and rare forms of obesity. This large association region has not been refined and the relevant DNA segments within the association region have not been identified. In this study, we investigated whether common variants in the MC4R gene region were associated with adiposity-related traits in a biracial population-based study. Single nucleotide polymorphisms (SNPs) in the MC4R region were genotyped with a custom array and a genome-wide array and associations between SNPs and five adiposity-related traits were determined using race-stratified linear regression. Previously reported associations between lower BMI and the minor alleles of rs2229616/Val103lle and rs52820871/lle251Leu were replicated in white female participants. Among white participants, rs11152221 in a proximal 3 ' LD block (closer to MC4R) was significantly associated with multiple adiposity traits, but SNPs in a distal 3 ' LD block (farther from MC4R) were not. In a case-control study of severe obesity, rs11152221 was significantly associated. The association results directed our follow-up studies to the proximal LD block downstream of MC4R. By considering nucleotide conservation, the significance of association, and proximity to the MC4R gene, we identified a candidate MC4R regulatory region. This candidate region was sequenced in 20 individuals from a study of severe obesity in an attempt to identify additional variants, and the candidate region was tested for enhancer activity using in vivo enhancer assays in zebrafish and mice. Novel variants were not identified by sequencing and the candidate region did not drive reporter gene expression in zebrafish or mice. The identification of a putative insulator in this region could help to explain the challenges faced in this study and others to link SNPs associated with adiposity to altered MC4R expression.
C1 [Evans, Daniel S.; Tranah, Gregory J.] Calif Pacific Med Ctr Res Inst, San Francisco, CA USA.
[Calton, Melissa A.; Hsueh, Wen-Chi; Vaisse, Christian] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
[Calton, Melissa A.; Hsueh, Wen-Chi; Vaisse, Christian] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Kim, Mee J.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Kim, Mee J.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Kwok, Pui-Yan] Univ Calif San Francisco, Inst Cardiovasc Res, Inst Human Genet, San Francisco, CA 94143 USA.
[Kwok, Pui-Yan] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Miljkovic, Iva] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Harris, Tamara; Koster, Annemarie] NIA, Bethesda, MD 20892 USA.
[Liu, Yongmei] Wake Forest Univ, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
RP Vaisse, C (reprint author), Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
EM vaisse@diabetes.ucsf.edu
RI Koster, Annemarie/E-7438-2010;
OI Miljkovic, Iva/0000-0002-3155-9777; Ahituv, Nadav/0000-0002-7434-8144
FU Intramural Research Program of the NIH; National Institute on Aging
(NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; NINR
[R01-NR012459]; NIDDK [1R01DK090382, R01DK060540]; NIA
[1R01AG032098-01A1]; National Institutes of Health [HHSN268200782096C];
NIH [T32 DK007418, T32 GM007175]; Pharmaceutical Sciences and
Pharmacogenomics; Amgen Research Excellence in Bioengineering and
Therapeutic Sciences Fellowship
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging (NIA), and by NIA contracts
N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, NIA grant R01-AG028050,
NINR grant R01-NR012459, and NIDDK grants 1R01DK090382 and R01DK060540.
The genome-wide association study was funded by NIA grant
1R01AG032098-01A1 to Wake Forest University Health Sciences and
genotyping services were provided by the Center for Inherited Disease
Research (CIDR). CIDR is fully funded through a federal contract from
the National Institutes of Health to The Johns Hopkins University,
contract number HHSN268200782096C. DSE was supported by NIH training
grant T32 DK007418. MAC was supported by NIH training grant T32
GM007175, Pharmaceutical Sciences and Pharmacogenomics. MJK was
supported in part by NIH training grant T32 GM007175 and the Amgen
Research Excellence in Bioengineering and Therapeutic Sciences
Fellowship. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 51
TC 3
Z9 3
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 12
PY 2014
VL 9
IS 5
AR e96805
DI 10.1371/journal.pone.0096805
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI1ZC
UT WOS:000336653300033
PM 24820477
ER
PT J
AU Narjoz, C
Favre, A
McMullen, J
Kiehl, P
Montemurro, M
Figg, WD
Beaune, P
de Waziers, I
Rochat, B
AF Narjoz, Celine
Favre, Amelie
McMullen, Justin
Kiehl, Philippe
Montemurro, Michael
Figg, William D.
Beaune, Philippe
de Waziers, Isabelle
Rochat, Bertrand
TI Important Role of CYP2J2 in Protein Kinase Inhibitor Degradation: A
Possible Role in Intratumor Drug Disposition and Resistance
SO PLOS ONE
LA English
DT Article
ID CYTOCHROME-P450 2J2; ANTICANCER AGENTS; MOLECULAR-MECHANISMS;
MASS-SPECTROMETRY; OVARIAN-CANCER; LUNG-CANCER; IMATINIB; METABOLISM;
EXPRESSION; IDENTIFICATION
AB We have investigated in vitro the metabolic capability of 3 extrahepatic cytochromes P-450, CYP1A1, 1B1 and 2J2, known to be over-expressed in various tumors, to biotransform 5 tyrosine kinase inhibitors (TKI): dasatinib, imatinib, nilotinib, sorafenib and sunitinib. Moreover, mRNA expression of CYP1A1, 1B1, 2J2 and 3A4 in 6 hepatocellular and 14 renal cell carcinoma tumor tissues and their surrounding healthy tissues, was determined. Our results show that CYP1A1, 1B1 and especially 2J2 can rapidly biotransform the studied TKIs with a metabolic efficiency similar to that of CYP3A4. The mRNA expression of CYP1A1, 1B1, 2J2 and 3A4 in tumor biopsies has shown i) the strong variability of CYP expression and ii) distinct outliers showing high expression levels (esp. CYP2J2) that are compatible with high intratumoral CYP activity and tumor-specific TKI degradation. CYP2J2 inhibition could be a novel clinical strategy to specifically increase the intratumoral rather than plasma TKI levels, improving TKI efficacy and extending the duration before relapse. Such an approach would be akin to beta-lactamase inhibition, a classical strategy to avoid antibiotic degradation and resistance.
C1 [Narjoz, Celine; Beaune, Philippe; de Waziers, Isabelle] Univ Paris 05, INSERM UMR S U775, Sorbonne Paris Cite, Paris, France.
[Narjoz, Celine; Beaune, Philippe] Hop Europeen Georges Pompidou, Serv Biochim, Unite Fonct Pharmacogenet & Oncol Mol, Paris, France.
[Favre, Amelie; McMullen, Justin; Kiehl, Philippe; Rochat, Bertrand] CHU Vaudois, Quantitat Mass Spectrometry Facil, Lausanne, Switzerland.
[Montemurro, Michael] Univ Zurich Hosp, CH-8091 Zurich, Switzerland.
[Figg, William D.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Rochat, B (reprint author), CHU Vaudois, Quantitat Mass Spectrometry Facil, Lausanne, Switzerland.
EM bertrand.rochat@chuv.ch
RI Figg Sr, William/M-2411-2016
NR 43
TC 3
Z9 4
U1 2
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 12
PY 2014
VL 9
IS 5
AR e95532
DI 10.1371/journal.pone.0095532
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI1ZC
UT WOS:000336653300006
PM 24819355
ER
PT J
AU Pineda, S
Milne, RL
Calle, ML
Rothman, N
de Maturana, EL
Herranz, J
Kogevinas, M
Chanock, SJ
Tardon, A
Marquez, M
Guey, LT
Garcia-Closas, M
Lloreta, J
Baum, E
Gonzalez-Neira, A
Carrato, A
Navarro, A
Silverman, DT
Real, FX
Malats, N
AF Pineda, Silvia
Milne, Roger L.
Luz Calle, M.
Rothman, Nathaniel
Lopez de Maturana, Evangelina
Herranz, Jesus
Kogevinas, Manolis
Chanock, Stephen J.
Tardon, Adonina
Marquez, Mirari
Guey, Lin T.
Garcia-Closas, Montserrat
Lloreta, Josep
Baum, Erin
Gonzalez-Neira, Anna
Carrato, Alfredo
Navarro, Arcadi
Silverman, Debra T.
Real, Francisco X.
Malats, Nuria
TI Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A
Comprehensive Analysis
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ARG72PRO POLYMORPHISM; URINARY-BLADDER;
SUSCEPTIBILITY; METAANALYSIS; REGRESSION; MUTATIONS; NEOPLASMS;
SELECTION; MARKERS
AB Introduction: Germline variants in TP63 have been consistently associated with several tumors, including bladder cancer, indicating the importance of TP53 pathway in cancer genetic susceptibility. However, variants in other related genes, including TP53 rs1042522 (Arg72Pro), still present controversial results. We carried out an in depth assessment of associations between common germline variants in the TP53 pathway and bladder cancer risk.
Material and Methods: We investigated 184 tagSNPs from 18 genes in 1,058 cases and 1,138 controls from the Spanish Bladder Cancer/EPICURO Study. Cases were newly-diagnosed bladder cancer patients during 1998-2001. Hospital controls were age-gender, and area matched to cases. SNPs were genotyped in blood DNA using Illumina Golden Gate and TaqMan assays. Cases were subphenotyped according to stage/grade and tumor p53 expression. We applied classical tests to assess individual SNP associations and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized logistic regression analysis to assess multiple SNPs simultaneously.
Results: Based on classical analyses, SNPs in BAK1 (1), IGF1R (5), P53AIP1 (1), PMAIP1 (2), SERINPB5 (3), TP63 (3), and TP73 (1) showed significant associations at p-value <= 0.05. However, no evidence of association, either with overall risk or with specific disease subtypes, was observed after correction for multiple testing (p-value >= 0.8). LASSO selected the SNP rs6567355 in SERPINB5 with 83% of reproducibility. This SNP provided an OR = 1.21, 95% CI 1.05-1.38, p-value = 0.006, and a corrected p-value = 0.5 when controlling for over-estimation.
Discussion: We found no strong evidence that common variants in the TP53 pathway are associated with bladder cancer susceptibility. Our study suggests that it is unlikely that TP53 Arg72Pro is implicated in the UCB in white Europeans. SERPINB5 and TP63 variation deserve further exploration in extended studies.
C1 [Pineda, Silvia; Milne, Roger L.; Lopez de Maturana, Evangelina; Herranz, Jesus; Marquez, Mirari; Guey, Lin T.; Baum, Erin; Gonzalez-Neira, Anna; Real, Francisco X.; Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain.
[Luz Calle, M.] Univ Vic, Dept Syst Biol, Vic, Spain.
[Rothman, Nathaniel; Chanock, Stephen J.; Garcia-Closas, Montserrat; Silverman, Debra T.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
[Kogevinas, Manolis; Lloreta, Josep] Hosp del Mar, Inst Municipal Invest Med, Barcelona, Spain.
[Tardon, Adonina] Univ Oviedo, Dept Prevent Med, Oviedo, Spain.
[Lloreta, Josep] Hosp del Mar IMAS, Dept Patol, Barcelona, Spain.
[Carrato, Alfredo] Hosp Univ Elche, Serv Oncol, Elche, Spain.
[Carrato, Alfredo] Hosp Univ Ramon y Cajal, Serv Oncol, Madrid, Spain.
[Navarro, Arcadi; Real, Francisco X.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.
[Navarro, Arcadi] Inst Biol Evolut UPF CSIC, Barcelona, Spain.
[Navarro, Arcadi] ICREA, Barcelona, Spain.
[Navarro, Arcadi] Inst Nacl Bioinformat, Barcelona, Spain.
RP Malats, N (reprint author), Spanish Natl Canc Res Ctr CNIO, Madrid, Spain.
EM nmalats@cnio.es
RI Lloreta, J/I-2112-2014; Navarro, Arcadi/F-1592-2011; Gonzalez-Neira,
Anna/C-5791-2015; Calle, M.Luz/D-2704-2015; Kogevinas,
Manolis/C-3918-2017; Herranz Valera, Jesus/M-8657-2014; Garcia-Closas,
Montserrat /F-3871-2015; Malats, Nuria/H-7041-2015; Real Arribas,
Francisco/H-5275-2015
OI Lloreta, J/0000-0003-1644-9470; Navarro, Arcadi/0000-0003-2162-8246;
Calle, M.Luz/0000-0001-9334-415X; Lopez de Maturana,
Evangelina/0000-0001-9425-3911; Herranz Valera,
Jesus/0000-0002-7385-1311; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Malats, Nuria/0000-0003-2538-3784; Real Arribas,
Francisco/0000-0001-9501-498X
FU Fondo de Investigacion Sanitaria, Spain [00/0745, PI051436, PI061614,
G03/174]; Red Tematica de Investigacion Cooperativa en Cancer, Spain
[RD06/0020-RTICC]; Marato TV3 [050830]; European Commission
[EU-FP7-HEALTH-F2-2008-201663-UROMOL]; US National Institutes of Health
[USA-NIH-RO1-CA089715]; Intramural Research Program of the Division of
Cancer Epidemiology and Genetics, National Cancer Institute at the
National Institutes of Health, USA; Consolider ONCOBIO (Ministerio de
Economia y Competitividad, Madrid, Spain)
FX This work was supported by the Fondo de Investigacion Sanitaria, Spain
(grant numbers 00/0745, PI051436, PI061614, G03/174); Red Tematica de
Investigacion Cooperativa en Cancer (grant number RD06/0020-RTICC),
Spain; Marato TV3 (grant number 050830); European Commission (grant
numbers EU-FP7-HEALTH-F2-2008-201663-UROMOL; US National Institutes of
Health (grant number USA-NIH-RO1-CA089715); and the Intramural Research
Program of the Division of Cancer Epidemiology and Genetics, National
Cancer Institute at the National Institutes of Health, USA; Consolider
ONCOBIO (Ministerio de Economia y Competitividad, Madrid, Spain). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 36
TC 4
Z9 5
U1 2
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 12
PY 2014
VL 9
IS 5
AR e89952
DI 10.1371/journal.pone.0089952
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI1ZC
UT WOS:000336653300001
PM 24818791
ER
PT J
AU Masuelli, L
Fantini, M
Benvenuto, M
Sacchetti, P
Giganti, MG
Tresoldi, I
Lido, P
Lista, F
Cavallo, F
Nanni, P
Schlom, J
Modesti, A
Bei, R
AF Masuelli, Laura
Fantini, Massimo
Benvenuto, Monica
Sacchetti, Pamela
Giganti, Maria Gabriella
Tresoldi, Ilaria
Lido, Paolo
Lista, Florigio
Cavallo, Federica
Nanni, Patrizia
Schlom, Jeffrey
Modesti, Andrea
Bei, Roberto
TI Intratumoral delivery of recombinant vaccinia virus encoding for
ErbB2/Neu inhibits the growth of salivary gland carcinoma cells
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE Vaccine; Cancer; Salivary glands; ErbB2/Neu; Vaccinia virus; Intratumor
ID MULTIPLE ERBB RECEPTORS; ANTI-ERBB-2 MONOCLONAL-ANTIBODIES;
CARCINOEMBRYONIC ANTIGEN CEA; PHASE-I TRIAL; IMMUNE-RESPONSES;
PROSTATE-CANCER; BREAST-CANCER; COSTIMULATORY MOLECULES; POXVIRUS
VACCINES; TRANSGENIC MICE
AB Background: The antitumor activity induced by intratumoral vaccination with poxvirus expressing a tumor antigen was shown to be superior to that induced by subcutaneous vaccination. Salivary gland carcinomas overexpress ErbB2. Trastuzumab, a monoclonal antibody to ErbB2, was proposed for salivary gland tumors treatment. We explored the effectiveness of intratumoral vaccination with the recombinant vaccinia virus ErbB2/Neu (rV-neuT) vaccine in hampering the growth of transplanted Neu-overexpressing BALB-neuT salivary gland cancer cells (SALTO) in BALB-neuT mice.
Methods: BALB-neuT male mice were subcutaneously injected with SALTO tumor cells and intratumorally vaccinated twice with different doses of either rV-neuT or V-wt (wild-type). Tumors were measured weekly. The presence of anti-ErbB2/Neu antibodies was assayed by ELISA, immunoprecipitation or indirect immunofluorescence. Biological activity of immune sera was investigated by analyzing antibody-dependent cellular cytotoxicity (ADCC), SALTO cells proliferation and apoptosis, ErbB2/Neu receptor down regulation and ERK1/2 phosphorylation. Anti-Neu T cell immunity was investigated by determining the release of IL-2 and IFN-gamma in T cells supernatant. Survival curves were determined using the Kaplan-Meier method and compared using the log-rank test. Differences in tumor volumes, number of apoptotic cells, titer of the serum, percentage of ADCC were evaluated through a two-tailed Student's t-test.
Results: rV-neuT intratumoral vaccination was able to inhibit the growth of SALTO cancer cells in a dose-dependent manner. The anti-Neu serum titer paralleled in vivo antitumor activity of rV-neuT vaccinated mice. rV-neuT immune serum was able to mediate ADCC, inhibition of SALTO cells proliferation, down regulation of the ErbB2/Neu receptor, inhibition of ERK1/2 phosphorylation and induction of apoptosis, thus suggesting potential mechanisms of in vivo tumor growth interference. In addition, spleen T cells of rV-neuT vaccinated mice released IFN-gamma and IL-2 upon in vitro stimulation with several Neu-specific peptides located in the extracellular domain of Neu sequence.
Conclusions: rV-neuT intratumoral vaccination could be employed to induce an efficient antitumor response and reject transplanted salivary gland tumors. Our findings may have important implications for the design of cancer vaccine protocols for the treatment of salivary gland tumors and other accessible tumors using intratumoral injection of recombinant vaccinia virus.
C1 [Masuelli, Laura; Sacchetti, Pamela] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy.
[Fantini, Massimo; Benvenuto, Monica; Giganti, Maria Gabriella; Tresoldi, Ilaria; Modesti, Andrea; Bei, Roberto] Univ Roma Tor Vergata, Dept Clin Sci & Translat Med, Rome, Italy.
[Lido, Paolo] Univ Roma Tor Vergata, Internal Med Residency Program, Rome, Italy.
[Lista, Florigio] Ctr Studi & Ric Sanita & Vet Esercito, Rome, Italy.
[Cavallo, Federica] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Ctr Mol Biotechnol, Turin, Italy.
[Nanni, Patrizia] Univ Bologna, Dept Expt Diagnost & Specialty Med, Bologna, Italy.
[Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Bei, R (reprint author), Univ Roma Tor Vergata, Dept Clin Sci & Translat Med, Rome, Italy.
EM bei@med.uniroma2.it
RI Cavallo, Federica/C-5666-2011; Benvenuto, Monica/K-2685-2016;
OI Cavallo, Federica/0000-0003-4571-1060; Benvenuto,
Monica/0000-0002-2520-1306; Nanni, Patrizia/0000-0001-5319-0803;
Fantini, Massimo/0000-0002-8164-2587
FU PRIN
FX This study was supported by a grant from PRIN (R. B). The authors wish
to thank Barbara Bulgarini for help in manuscript preparation. We wish
to thank Therion Biologics (Cambridge, MA) and Dr. G. Mazzara, which
kindly provided vaccinia viruses, IRBM P. Angeletti (Pomezia, Rome) for
peptides, and Dr. Eddi Di Marco (Istituto Tumori di Genova) for
providing LTR-Neu cells.
NR 71
TC 7
Z9 7
U1 0
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD MAY 10
PY 2014
VL 12
AR 122
DI 10.1186/1479-5876-12-122
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AI5TQ
UT WOS:000336932500002
PM 24886178
ER
PT J
AU Chen, BJ
Qin, J
AF Chen, Baojiang
Qin, Jing
TI Use of empirical likelihood to calibrate auxiliary information in partly
linear monotone regression models
SO STATISTICS IN MEDICINE
LA English
DT Article
DE empirical likelihood; auxiliary information; missing data; isotonic
regression
ID ADDITIVE ISOTONIC REGRESSION; ESTIMATORS; ALGORITHM
AB In statistical analysis, a regression model is needed if one is interested in finding the relationship between a response variable and covariates. When the response depends on the covariate, then it may also depend on the function of this covariate. If one has no knowledge of this functional form but expect for monotonic increasing or decreasing, then the isotonic regression model is preferable. Estimation of parameters for isotonic regression models is based on the pool-adjacent-violators algorithm (PAVA), where the monotonicity constraints are built in. With missing data, people often employ the augmented estimating method to improve estimation efficiency by incorporating auxiliary information through a working regression model. However, under the framework of the isotonic regression model, the PAVA does not work as the monotonicity constraints are violated. In this paper, we develop an empirical likelihood-based method for isotonic regression model to incorporate the auxiliary information. Because the monotonicity constraints still hold, the PAVA can be used for parameter estimation. Simulation studies demonstrate that the proposed method can yield more efficient estimates, and in some situations, the efficiency improvement is substantial. We apply this method to a dementia study. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Chen, Baojiang] Univ Nebraska Med Ctr, Dept Biostat, Omaha, NE 68198 USA.
[Qin, Jing] NIAID, NIH, Bethesda, MD 20892 USA.
RP Chen, BJ (reprint author), Univ Nebraska Med Ctr, Dept Biostat, Omaha, NE 68198 USA.
EM baojiang.chen@unmc.edu
FU National Institute on Aging grant [U01AG016976]; National Institute on
Aging [U01AG016976]
FX The authors thank the two referees for their constructive comments and
suggestions. Dr. Chen was supported in part by National Institute on
Aging grant U01AG016976. The National Alzheimer's Coordinating Center
database is supported by National Institute on Aging grant U01AG016976.
NR 22
TC 0
Z9 0
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD MAY 10
PY 2014
VL 33
IS 10
BP 1713
EP 1722
DI 10.1002/sim.6057
PG 10
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA AE5KS
UT WOS:000334028500006
PM 24323567
ER
PT J
AU Cadiz-Rivera, B
Fromm, G
de Vries, C
Fields, J
McGrath, KE
Fiering, S
Bulger, M
AF Cadiz-Rivera, Brenda
Fromm, George
de Vries, Christina
Fields, Jennifer
McGrath, Kathleen E.
Fiering, Steven
Bulger, Michael
TI The Chromatin "Landscape" of a Murine Adult beta-Globin Gene Is
Unaffected by Deletion of Either the Gene Promoter or a Downstream
Enhancer
SO PLOS ONE
LA English
DT Article
ID LOCUS-CONTROL REGION; HYPERSENSITIVE SITES; ERYTHROID-CELLS;
TRANSCRIPTION; EXPRESSION; SENSITIVITY; ACTIVATION; LINKING; PATTERN;
MICE
AB In mammals, the complex tissue-and developmental-specific expression of genes within the beta-globin cluster is known to be subject to control by the gene promoters, by a locus control region (LCR) located upstream of the cluster, and by sequence elements located across the intergenic regions. Despite extensive investigation, however, the complement of sequences that is required for normal regulation of chromatin structure and gene expression within the cluster is not fully defined. To further elucidate regulation of the adult beta-globin genes, we investigate the effects of two deletions engineered within the endogenous murine beta-globin locus. First, we find that deletion of the beta 2-globin gene promoter, while eliminating b2-globin gene expression, results in no additional effects on chromatin structure or gene expression within the cluster. Notably, our observations are not consistent with competition among the beta-globin genes for LCR activity. Second, we characterize a novel enhancer located 3' of the beta 2-globin gene, but find that deletion of this sequence has no effect whatsoever on gene expression or chromatin structure. This observation highlights the difficulty in assigning function to enhancer sequences identified by the chromatin "landscape" or even by functional assays.
C1 [Cadiz-Rivera, Brenda; Fromm, George; de Vries, Christina; McGrath, Kathleen E.; Bulger, Michael] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA.
[Cadiz-Rivera, Brenda; Fromm, George; de Vries, Christina; McGrath, Kathleen E.; Bulger, Michael] Ctr Pediat Biomed Res, Rochester, NY USA.
[Fromm, George] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Fields, Jennifer; Fiering, Steven] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Microbiol & Immunol, Hanover, NH 03756 USA.
RP Bulger, M (reprint author), Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA.
EM michael_bulger@urmc.rochester.edu
FU National Institutes of Health (NIH) [R01-DK070687-06A1]; Institutional
Ruth L. Kirschstein National Research Service Award [GM068411]
FX This work was supported by National Institutes of Health (NIH)
R01-DK070687-06A1. G. F. and B.C.-R. were supported in part by grant
number GM068411 from Institutional Ruth L. Kirschstein National Research
Service Award. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 27
TC 0
Z9 0
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 9
PY 2014
VL 9
IS 5
AR e92947
DI 10.1371/journal.pone.0092947
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI4LX
UT WOS:000336838000003
PM 24817273
ER
PT J
AU Simari, RD
Pepine, CJ
Traverse, JH
Henry, TD
Bolli, R
Spoon, DB
Yeh, E
Hare, JM
Schulman, IH
Anderson, RD
Lambert, C
Sayre, SL
Taylor, DA
Ebert, RF
Moye, LA
AF Simari, Robert D.
Pepine, Carl J.
Traverse, Jay H.
Henry, Timothy D.
Bolli, Roberto
Spoon, Daniel B.
Yeh, Ed
Hare, Joshua M.
Schulman, Ivonne Hernandez
Anderson, R. David
Lambert, Charles
Sayre, Shelly L.
Taylor, Doris A.
Ebert, Ray F.
Moye, Lemuel A.
TI Bone Marrow Mononuclear Cell Therapy for Acute Myocardial Infarction A
Perspective From the Cardiovascular Cell Therapy Research Network
SO CIRCULATION RESEARCH
LA English
DT Article
DE diagnostic imaging; myocardial infarction; population
ID LEFT-VENTRICULAR FUNCTION; RANDOMIZED PHASE-1 TRIAL; HEMATOPOIETIC
STEM-CELLS; ISCHEMIC CARDIOMYOPATHY; INTRACORONARY INJECTION; PROGENITOR
CELLS; HEART-FAILURE; DELIVERY; CCTRN; METAANALYSIS
AB To understand the role of bone marrow mononuclear cells in the treatment of acute myocardial infarction, this overview offers a retrospective examination of strengths and limitations of 3 contemporaneous trials with attention to critical design features and provides an analysis of the combined data set and implications for future directions in cell therapy for acute myocardial infarction.
C1 [Simari, Robert D.; Spoon, Daniel B.] Mayo Clin, Rochester, MN USA.
[Pepine, Carl J.; Anderson, R. David] Univ Florida, Sch Med, Gainesville, FL USA.
[Traverse, Jay H.] Univ Minnesota, Sch Med, Abbott NW Hosp, Minneapolis Heart Inst, Minneapolis, MN 55455 USA.
[Henry, Timothy D.] Cedars Sinai Heart Inst, Los Angeles, CA USA.
[Bolli, Roberto] Univ Louisville, Sch Med, Louisville, KY 40292 USA.
[Yeh, Ed] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Hare, Joshua M.; Schulman, Ivonne Hernandez] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA.
[Lambert, Charles] Florida Hosp Tampa Pepin Heart Inst, Tampa, FL USA.
[Sayre, Shelly L.; Moye, Lemuel A.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Houston, TX 77030 USA.
[Taylor, Doris A.] Texas Heart Inst, Houston, TX 77025 USA.
[Ebert, Ray F.] NHLBI, Bethesda, MD 20892 USA.
RP Moye, LA (reprint author), Univ Texas Sch Publ Hlth, Coordinating Ctr Clin Trials, 1200 Herman Pressler,E-1009, Houston, TX 77030 USA.
EM Lemmoye@msn.com
FU National Heart, Lung, and Blood Institute [UM1 HL087318-07]
FX Funding for the Cardiovascular Cell Therapy Research Network was
provided by the National Heart, Lung, and Blood Institute under
cooperative agreement UM1 HL087318-07.
NR 28
TC 25
Z9 25
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD MAY 9
PY 2014
VL 114
IS 10
BP 1564
EP 1568
DI 10.1161/CIRCRESAHA.114.303720
PG 5
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA AH2HF
UT WOS:000335941400013
PM 24812350
ER
PT J
AU Hart, J
Tillman, G
Kraut, MA
Chiang, HS
Strain, JF
Li, YF
Agrawal, AG
Jester, P
Gnann, JW
Whitley, RJ
AF Hart, John, Jr.
Tillman, Gail
Kraut, Michael A.
Chiang, Hsueh-Sheng
Strain, Jeremy F.
Li, Yufeng
Agrawal, Amy G.
Jester, Penny
Gnann, John W., Jr.
Whitley, Richard J.
CA NIAID Collaborative Antiviral Stud
West Nile Virus 2010 Protocol Team
TI West Nile virus neuroinvasive disease: neurological manifestations and
prospective longitudinal outcomes
SO BMC INFECTIOUS DISEASES
LA English
DT Article
DE West Nile virus; Encephalitis; Neurological deficit; 3MS; Coma
ID ACUTE FLACCID PARALYSIS; MR-IMAGING FINDINGS; UNITED-STATES; NEW-YORK;
INFECTION; EPIDEMIC; MENINGOENCEPHALITIS; ENCEPHALITIS; PROGNOSIS; MOTOR
AB Background: West Nile Virus (WNV) is a mosquito-borne flavivirus that has caused ongoing seasonal epidemics in the United States since 1999. It is estimated that = 1% of WNV-infected patients will develop neuroinvasive disease (West Nile encephalitis and/or myelitis) that can result in debilitating morbidities and long-term sequelae. It is essential to collect longitudinal information about the recovery process and to characterize predicative factors that may assist in therapeutic decision-making in the future.
Methods: We report a longitudinal study of the neurological outcomes (as measured by neurological examination, Glascow Coma Scale, and Modified Mini-Mental State Examination) for 55 subjects with WNV neuroinvasive disease (confirmed by positive CSF IgM) assessed on day 7, at discharge, and on days 14, 30, and 90. The neurological outcome measures were coma (presence and degree), global cognitive status, presence of cranial neuropathy, tremors and/or weakness.
Results: At initial clinical presentation 93% presented with a significant neurological deficit (49% with weakness, 35% with tremor, and 16% with cranial neuropathy). The number of patients with a cognitive deficit fell from 25 at initial evaluation to 9 at their last evaluation. Cranial neuropathy was present in 9 at onset and in only 4 patients at study conclusion. Of the 19 patients who had a tremor at enrollment, 11 continued to exhibit a tremor at follow-up. Seven patients died after initial enrollment in the study, with 5 of those having presented in a coma. The factors that predict either severity or long-term recovery of neurological function include age (older individuals were weaker at follow-up examination), gender (males recovered better from coma), and presentation in a coma with cranial nerve deficits (had a poorer recovery particularly with regard to cognition).
Conclusions: This study represents one of the largest clinical investigations providing prospectively-acquired neurological outcomes data among American patients with WNV central nervous system disease. The findings show that the factors that influence prognosis from the initial presentation include age, gender, and specific neurological deficits at onset.
C1 [Hart, John, Jr.; Tillman, Gail; Chiang, Hsueh-Sheng; Strain, Jeremy F.] Univ Texas Dallas, Ctr BrainHlth, Dallas, TX 75230 USA.
[Kraut, Michael A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Agrawal, Amy G.] NIH, Bethesda, MD 20892 USA.
[Gnann, John W., Jr.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Li, Yufeng; Jester, Penny; Whitley, Richard J.] Univ Alabama Birmingham, Birmingham, AL USA.
RP Hart, J (reprint author), Univ Texas Dallas, Ctr BrainHlth, Dallas, TX 75230 USA.
EM jhart@utdallas.edu
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Dept. of Health and Human Services [N01-AI-30025]
FX This project has been funded in whole or in part with Federal funds from
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Dept. of Health and Human Services, under contract
No. N01-AI-30025.
NR 31
TC 12
Z9 13
U1 3
U2 15
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD MAY 9
PY 2014
VL 14
AR 248
DI 10.1186/1471-2334-14-248
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA AH4CF
UT WOS:000336072600002
PM 24884681
ER
PT J
AU Novgorodov, SA
Riley, CL
Yu, J
Borg, KT
Hannun, YA
Proia, RL
Kindy, MS
Gudz, TI
AF Novgorodov, Sergei A.
Riley, Christopher L.
Yu, Jin
Borg, Keith T.
Hannun, Yusuf A.
Proia, Richard L.
Kindy, Mark S.
Gudz, Tatyana I.
TI Essential Roles of Neutral Ceramidase and Sphingosine in Mitochondrial
Dysfunction Due to Traumatic Brain Injury
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Brain; Cell Death; Mitochondria; Respiratory Chain; Sphingolipid
ID CYTOCHROME-C-OXIDASE; SUBCELLULAR-LOCALIZATION; CHRONIC ACTIVATION;
RESPIRATORY-CHAIN; MOLECULAR-CLONING; RAT-BRAIN; IN-VITRO; KINASE;
SPHINGOSINE-1-PHOSPHATE; SPHINGOLIPIDS
AB Background: A cardinal feature of many neurological disorders is mitochondrial dysfunction. Results: Knocking down neutral ceramidase reduces mitochondrial sphingosine, preserves mitochondrial function, and improves brain function recovery after trauma. Conclusion: Activation of the sphingosine-generating pathway plays a significant role in promoting mitochondrial injury. Significance: This is the first direct evidence of endogenous sphingosine involvement in regulation of mitochondrial function.
In addition to immediate brain damage, traumatic brain injury (TBI) initiates a cascade of pathophysiological events producing secondary injury. The biochemical and cellular mechanisms that comprise secondary injury are not entirely understood. Herein, we report a substantial deregulation of cerebral sphingolipid metabolism in a mouse model of TBI. Sphingolipid profile analysis demonstrated increases in sphingomyelin species and sphingosine concurrently with up-regulation of intermediates of de novo sphingolipid biosynthesis in the brain. Investigation of intracellular sites of sphingosine accumulation revealed an elevation of sphingosine in mitochondria due to the activation of neutral ceramidase (NCDase) and the reduced activity of sphingosine kinase 2 (SphK2). The lack of change in gene expression suggested that post-translational mechanisms are responsible for the shift in the activities of both enzymes. Immunoprecipitation studies revealed that SphK2 is complexed with NCDase and cytochrome oxidase (COX) subunit 1 in mitochondria and that brain injury hindered SphK2 association with the complex. Functional studies showed that sphingosine accumulation resulted in a decreased activity of COX, a rate-limiting enzyme of the mitochondrial electron transport chain. Knocking down NCDase reduced sphingosine accumulation in mitochondria and preserved COX activity after the brain injury. Also, NCDase knockdown improved brain function recovery and lessened brain contusion volume after trauma. These studies highlight a novel mechanism of secondary TBI involving a disturbance of sphingolipid-metabolizing enzymes in mitochondria and suggest a critical role for mitochondrial sphingosine in promoting brain injury after trauma.
C1 [Riley, Christopher L.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA.
[Yu, Jin; Kindy, Mark S.; Gudz, Tatyana I.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Novgorodov, Sergei A.; Kindy, Mark S.; Gudz, Tatyana I.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Borg, Keith T.] Med Univ S Carolina, Dept Emergency Med, Charleston, SC 29425 USA.
[Hannun, Yusuf A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA.
[Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Gudz, TI (reprint author), 114 Doughty St, Charleston, SC 29425 USA.
EM gudz@musc.edu
FU National Institutes of Health [P30 GM103339]; Veterans Affairs Merit
Awards [I01RX000206, I01BX001104, I01RX000331]; American Diabetes
Association [7-12-IN-28]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant P30 GM103339 (to S. A. N.). This work was also supported by
Veterans Affairs Merit Awards I01RX000206 (to T. I. G.), I01BX001104 (to
T. I. G.), and I01RX000331 (to M. S. K.). The Lipidomics Core Facility
at Medical University of South Carolina is supported in part by National
Institutes of Health Grant P30 GM103339.; Supported in part by American
Diabetes Association Innovation Grant 7-12-IN-28.
NR 64
TC 10
Z9 10
U1 2
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 9
PY 2014
VL 289
IS 19
BP 13142
EP 13154
DI 10.1074/jbc.M113.530311
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AG6IR
UT WOS:000335522800016
PM 24659784
ER
PT J
AU Liu, CH
Sheng, JZ
Krahn, JM
Perera, L
Xu, YM
Hsieh, PH
Dou, WF
Liu, J
Pedersen, LC
AF Liu, Chunhui
Sheng, Juzheng
Krahn, Juno M.
Perera, Lalith
Xu, Yongmei
Hsieh, Po-Hung
Dou, Wenfang
Liu, Jian
Pedersen, Lars C.
TI Molecular Mechanism of Substrate Specificity for Heparan Sulfate
2-O-Sulfotransferase
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Heparan Sulfate; Heparin; Heparin-binding Protein; Oligosaccharide;
Sulfotransferase
ID BIOSYNTHESIS; 3-O-SULFOTRANSFERASE; OLIGOSACCHARIDES; PROTEOGLYCANS;
C-5-EPIMERASE; DIVERSITY; SYSTEM; MODE; MICE
AB Background: Sulfotransferases with distinct specificities act in sequence in the heparan sulfate biosynthetic pathway. Results: The crystal structure of 2-O-sulfotransferase with bound substrate reveals its requirements for substrate recognition. Conclusion: The 2-O-sulfotransferase recognizes N-sulfate but excludes 6-O-sulfate on substrates. Significance: The results advance the understanding of cellular control for the biosynthesis of heparan sulfate.
Heparan sulfate (HS) is an abundant polysaccharide in the animal kingdom with essential physiological functions. HS is composed of sulfated saccharides that are biosynthesized through a complex pathway involving multiple enzymes. In vivo regulation of this process remains unclear. HS 2-O-sulfotransferase (2OST) is a key enzyme in this pathway. Here, we report the crystal structure of the ternary complex of 2OST, 3-phosphoadenosine 5-phosphate, and a heptasaccharide substrate. Utilizing site-directed mutagenesis and specific oligosaccharide substrate sequences, we probed the molecular basis of specificity and 2OST position in the ordered HS biosynthesis pathway. These studies revealed that Arg-80, Lys-350, and Arg-190 of 2OST interact with the N-sulfo groups near the modification site, consistent with the dependence of 2OST on N-sulfation. In contrast, 6-O-sulfo groups on HS are likely excluded by steric and electrostatic repulsion within the active site supporting the hypothesis that 2-O-sulfation occurs prior to 6-O-sulfation. Our results provide the structural evidence for understanding the sequence of enzymatic events in this pathway.
C1 [Liu, Chunhui; Sheng, Juzheng; Xu, Yongmei; Hsieh, Po-Hung; Dou, Wenfang; Liu, Jian] Univ N Carolina, Eshelman Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
[Liu, Chunhui; Sheng, Juzheng] Shandong Univ, Sch Pharmaceut Sci, Inst Biochem & Biotechnol Drug, Jinan 250012, Peoples R China.
[Krahn, Juno M.; Perera, Lalith; Pedersen, Lars C.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Dou, Wenfang] Jiangnan Univ, Sch Pharmaceut Sci, Lab Pharmaceut Engn, Wuxi 214122, Peoples R China.
RP Liu, J (reprint author), Univ N Carolina, Rm 303,Beard Hall, Chapel Hill, NC 27599 USA.
EM jian_liu@unc.edu
FU National Institutes of Health [GM102137, HL094463]; National Institutes
of Health, NIEHS [ZIAES102645, ZICES043010-28]; China Scholarship
Council
FX This work was supported, in whole or in part, by National Institutes of
Health Grants GM102137 and HL094463 and by the Intramural Research
Program of the National Institutes of Health, NIEHS Project ZIAES102645
and ZICES043010-28 (to L. C. P.).; Supported by the China Scholarship
Council.
NR 38
TC 14
Z9 15
U1 3
U2 31
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 9
PY 2014
VL 289
IS 19
BP 13407
EP 13418
DI 10.1074/jbc.M113.530535
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AG6IR
UT WOS:000335522800039
PM 24652287
ER
PT J
AU Shi, S
Leites, C
He, DL
Schwartz, D
Moy, W
Shi, JX
Duan, JB
AF Shi, Sandra
Leites, Catherine
He, Deli
Schwartz, Daniel
Moy, Winton
Shi, Jianxin
Duan, Jubao
TI MicroRNA-9 and MicroRNA-326 Regulate Human Dopamine D2 Receptor
Expression, and the MicroRNA-mediated Expression Regulation Is Altered
by a Genetic Variant
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Dopamine Receptors; Gene Expression; Gene Regulation; Genetic
Polymorphism; MicroRNA; Pharmacogenetics; DRD2
ID C957T POLYMORPHISM; PREFRONTAL CORTEX; MESSENGER-RNA; NT2 CELLS; DRD2
GENE; EXPERIMENTAL VALIDATION; ASSOCIATION ANALYSIS;
ANTIPSYCHOTIC-DRUGS; WORKING-MEMORY; SCHIZOPHRENIA
AB Background: Regulation of dopamine D2 receptor (DRD2) is pathophysiologically and pharmacologically important. Results: miR-9 and miR-326 target to the 3-UTR of DRD2, and endogenously inhibit DRD2 expression. A functional single nucleotide polymorphism alters such regulation. Conclusion:DRD2 is post-transcriptionally regulated by miR-326 and miR-9. Significance: The study suggests a pathophysiological and pharmacological role of miR-9 and miR-326 in neuropsychiatric disorders.
The human dopamine receptor D2 (DRD2) has been implicated in the pathophysiology of schizophrenia and other neuropsychiatric disorders. Most antipsychotic drugs influence dopaminergic transmission through blocking dopamine receptors, primarily DRD2. We report here the post-transcriptional regulation of DRD2 expression by two brain-expressed microRNAs (miRs), miR-326 and miR-9, in an ex vivo mode, and show the relevance of miR-mediated DRD2 expression regulation in human dopaminergic neurons and in developing human brains. Both miRs targeted the 3-UTR (untranslated region) of DRD2 in NT2 (neuron-committed teratocarcinoma, which endogenously expresses DRD2) and CHO (Chinese hamster ovary) cell lines, decreasing luciferase activity measured by a luciferase reporter gene assay. miR-326 overexpression reduced DRD2 mRNA and DRD2 receptor synthesis. Both antisense miR-326 and antisense miR-9 increased DRD2 protein abundance, suggesting an endogenous repression of DRD2 expression by both miRs. Furthermore, a genetic variant (rs1130354) within the DRD2 3-UTR miR-targeting site interferes with miR-326-mediated repression of DRD2 expression. Finally, co-expression analysis identified an inverse correlation of DRD2 expression with both miR-326 and miR-9 in differentiating dopaminergic neurons derived from human induced pluripotent stem cells (iPSCs) and in developing human brain regions implicated in schizophrenia. Our study provides empirical evidence suggesting that miR-326 and miR-9 may regulate dopaminergic signaling, and miR-326 and miR-9 may be considered as potential drug targets for the treatment of disorders involving abnormal DRD2 function, such as schizophrenia.
C1 [Shi, Sandra; Leites, Catherine; He, Deli; Schwartz, Daniel; Moy, Winton; Duan, Jubao] NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Evanston, IL 60201 USA.
[Shi, Sandra; Duan, Jubao] Univ Chicago, Dept Psychiat & Behav Sci, Chicago, IL 60637 USA.
[Shi, Jianxin] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Duan, JB (reprint author), NorthShore Univ HealthSyst, Res Inst, 1001 Univ Pl, Evanston, IL 60201 USA.
EM jduan@uchicago.edu
FU National Institutes of Health [R21MH102685]; Brain and Behavior Research
Foundation Young Investigator Award; NorthShore University HealthSystem
Research Career Development Award; NorthShore University HealthSystem
Pilot Award
FX This work was supported, in whole or in part, by National Institutes of
Health Grant R21MH102685 (to J.D.). This work was also supported by a
Brain and Behavior Research Foundation (formerly NARSAD) Young
Investigator Award, NorthShore University HealthSystem Research Career
Development Award, and the NorthShore University HealthSystem 2011 Pilot
Award (all to J.D.).
NR 83
TC 19
Z9 20
U1 0
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 9
PY 2014
VL 289
IS 19
BP 13434
EP 13444
DI 10.1074/jbc.M113.535203
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AG6IR
UT WOS:000335522800041
PM 24675081
ER
PT J
AU Lin, XY
Ruiz, J
Bajraktari, I
Ohman, R
Banerjee, S
Gribble, K
Kaufman, JD
Wingfield, PT
Griggs, RC
Fischbeck, KH
Mankodi, A
AF Lin, Xiaoyan
Ruiz, Janelle
Bajraktari, Ilda
Ohman, Rachel
Banerjee, Soojay
Gribble, Katherine
Kaufman, Joshua D.
Wingfield, Paul T.
Griggs, Robert C.
Fischbeck, Kenneth H.
Mankodi, Ami
TI Z-disc-associated, Alternatively Spliced, PDZ Motif-containing Protein (
ZASP) Mutations in the Actin-binding Domain Cause Disruption of Skeletal
Muscle Actin Filaments in Myofibrillar Myopathy
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Actin; Muscular Dystrophy; Protein Complex; Protein-Protein Interaction;
Skeletal Muscle; Actinin; Myofibrillar Myopathy; Myotilin; Z-disc; ZASP
ID GIRDLE MUSCULAR-DYSTROPHY; ONSET DISTAL MYOPATHY; ALPHA-ACTININ; DILATED
CARDIOMYOPATHY; LIM PROTEIN; Z-BAND; DESMIN POSITIVITY; SEVERE FORM;
IN-VIVO; Z-LINE
AB Background: The binding partners of the ZASP internal region that is mutated in zaspopathy are not yet known. Results: The internal region of ZASP binds to skeletal muscle -actin, and zaspopathy mutations cause actin disruption. Conclusion: ZASP mutations in the actin-binding domain are deleterious to the muscle Z-disc structure. Significance: ZASP-actin interaction expands the role of ZASP and defines the mechanism of zaspopathy.
The core of skeletal muscle Z-discs consists of actin filaments from adjacent sarcomeres that are cross-linked by -actinin homodimers. Z-disc-associated, alternatively spliced, PDZ motif-containing protein (ZASP)/Cypher interacts with -actinin, myotilin, and other Z-disc proteins via the PDZ domain. However, these interactions are not sufficient to maintain the Z-disc structure. We show that ZASP directly interacts with skeletal actin filaments. The actin-binding domain is between the modular PDZ and LIM domains. This ZASP region is alternatively spliced so that each isoform has unique actin-binding domains. All ZASP isoforms contain the exon 6-encoded ZASP-like motif that is mutated in zaspopathy, a myofibrillar myopathy (MFM), whereas the exon 8-11 junction-encoded peptide is exclusive to the postnatal long ZASP isoform (ZASP-Lex10). MFM is characterized by disruption of skeletal muscle Z-discs and accumulation of myofibrillar degradation products. Wild-type and mutant ZASP interact with -actin, -actinin, and myotilin. Expression of mutant, but not wild-type, ZASP leads to Z-disc disruption and F-actin accumulation in mouse skeletal muscle, as in MFM. Mutations in the actin-binding domain of ZASP-Lex10, but not other isoforms, cause disruption of the actin cytoskeleton in muscle cells. These isoform-specific mutation effects highlight the essential role of the ZASP-Lex10 isoform in F-actin organization. Our results show that MFM-associated ZASP mutations in the actin-binding domain have deleterious effects on the core structure of the Z-discs in skeletal muscle.
C1 [Lin, Xiaoyan; Ruiz, Janelle; Bajraktari, Ilda; Ohman, Rachel; Banerjee, Soojay; Gribble, Katherine; Fischbeck, Kenneth H.; Mankodi, Ami] NINDS, NIH, Neurogenet Branch, Bethesda, MD 20892 USA.
[Kaufman, Joshua D.; Wingfield, Paul T.] NIAMS, NIH, Prot Express Lab, Bethesda, MD 20892 USA.
[Griggs, Robert C.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA.
RP Mankodi, A (reprint author), NINDS, NIH, Neurogenet Branch, 35 Convent Dr,Bldg 35,Rm 2A-1002, Bethesda, MD 20892 USA.
EM ami.mankodi@nih.gov
FU NINDS, National Institute of Health
FX This work was supported by NINDS, National Institute of Health
intramural research funds, including the Henry F. McFarland Transition
to Independence Award (to A. M.).
NR 41
TC 9
Z9 9
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 9
PY 2014
VL 289
IS 19
BP 13615
EP 13626
DI 10.1074/jbc.M114.550418
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AG6IR
UT WOS:000335522800055
PM 24668811
ER
PT J
AU Ma, XJ
Espana-Serrano, L
Kim, WJ
Purayil, HT
Nie, ZZ
Daaka, Y
AF Ma, Xiaojie
Espana-Serrano, Laura
Kim, Wan-ju
Purayil, Hamsa Thayele
Nie, Zhongzhen
Daaka, Yehia
TI beta Arrestin1 Regulates the Guanine Nucleotide Exchange Factor RasGRF2
Expression and the Small GTPase Rac- mediated Formation of Membrane
Protrusion and Cell Motility
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Actin; Arrestin; Cell Migration; G Protein-coupled Receptors (GPCR);
Guanine Nucleotide Exchange Factor (GEF); Rac; Protrusion
ID PROTEASE-ACTIVATED RECEPTOR-2; COFILIN PHOSPHORYLATION; CYTOSKELETAL
DYNAMICS; SIGNAL-TRANSDUCTION; BETA-ARRESTINS; LIM-KINASE;
IDENTIFICATION; DOWNSTREAM; MIGRATION; PATHWAY
AB Background: G protein-coupled receptors (GPCRs) and arrestins have been shown to regulate cell motility. Results: Arrestin1 regulates cell migration through RasGRF2 (a dual guanine nucleotide exchange factor) gene expression and the small GTPase Rac activity. Conclusion: Arrestin1 may regulate cellular functions at the gene expression level. Significance: Arrestins may function at transcriptional and post-translational levels to regulate cell migration.
Arrestin proteins shuttle between the cytosol and nucleus and have been shown to regulate G protein-coupled receptor signaling, actin remodeling, and gene expression. Here, we tested the hypothesis that arrestin1 regulates actin remodeling and cell migration through the small GTPase Rac. Depletion of arrestin1 promotes Rac activation, leading to the formation of multipolar protrusions and increased cell circularity, and overexpression of a dominant negative form of Rac reverses these morphological changes. Small interfering RNA library screen identifies RasGRF2 as a target of arrestin1. RasGRF2 gene and protein expression levels are elevated following depletion of arrestin1, and the consequent activation of Rac results in dephosphorylation of cofilin that can promote actin polymerization and formation of multipolar protrusions, thereby retarding cell migration and invasion. Together, these results suggest that arrestin1 regulates rasgrf2 gene expression and Rac activation to affect membrane protrusion and cell migration and invasion.
C1 [Ma, Xiaojie; Espana-Serrano, Laura; Kim, Wan-ju; Purayil, Hamsa Thayele; Nie, Zhongzhen; Daaka, Yehia] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL 32610 USA.
RP Nie, ZZ (reprint author), NIGMS, NIH, Div Cell Biol & Biophys, 45 Ctr Dr,Rm 2AS13H,MSC6200, Bethesda, MD 20892 USA.
EM niezhong@nigms.nih.gov
RI THAYELE PURAYIL, HAMSA/E-7533-2015
FU National Institutes of Health from USPHS [K22CA124578]; NCI
[R01CA129155]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants K22CA124578 from USPHS (to Z. N.) and R01CA129155 from NCI
(to Y. D.).
NR 44
TC 4
Z9 4
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 9
PY 2014
VL 289
IS 19
BP 13638
EP 13650
DI 10.1074/jbc.M113.511360
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AG6IR
UT WOS:000335522800057
PM 24692549
ER
PT J
AU DuPont, RL
Lieberman, JA
AF DuPont, Robert L.
Lieberman, Jeffrey A.
TI Young Brains on Drugs
SO SCIENCE
LA English
DT Editorial Material
C1 [DuPont, Robert L.] US Natl Inst Drug Abuse, Bethesda, MD USA.
[DuPont, Robert L.] Inst Behav & Hlth Inc, Rockville, MD 20852 USA.
[Lieberman, Jeffrey A.] Amer Psychiat Assoc, Washington, DC 20005 USA.
[Lieberman, Jeffrey A.] Columbia Univ, Dept Psychiat, New York, NY USA.
RP DuPont, RL (reprint author), Inst Behav & Hlth Inc, Rockville, MD 20852 USA.
EM jlieberman@columbia.edu
NR 0
TC 5
Z9 5
U1 0
U2 17
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD MAY 9
PY 2014
VL 344
IS 6184
BP 557
EP 557
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG6OD
UT WOS:000335537400001
PM 24812368
ER
PT J
AU Mindell, JA
AF Mindell, Joseph A.
TI A SWELL Channel Indeed
SO SCIENCE
LA English
DT Editorial Material
C1 NINDS, Membrane Transport Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Mindell, JA (reprint author), NINDS, Membrane Transport Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
EM mindellj@ninds.nih.gov
OI Mindell, Joseph/0000-0002-6952-8247
NR 4
TC 0
Z9 0
U1 0
U2 9
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD MAY 9
PY 2014
VL 344
IS 6184
BP 585
EP 586
DI 10.1126/science.1254591
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG6OD
UT WOS:000335537400026
PM 24812387
ER
PT J
AU Tran, E
Turcotte, S
Gros, A
Robbins, PF
Lu, YC
Dudley, ME
Wunderlich, JR
Somerville, RP
Hogan, K
Hinrichs, CS
Parkhurst, MR
Yang, JC
Rosenberg, SA
AF Tran, Eric
Turcotte, Simon
Gros, Alena
Robbins, Paul F.
Lu, Yong-Chen
Dudley, Mark E.
Wunderlich, John R.
Somerville, Robert P.
Hogan, Katherine
Hinrichs, Christian S.
Parkhurst, Maria R.
Yang, James C.
Rosenberg, Steven A.
TI Cancer Immunotherapy Based on Mutation-Specific CD4+T Cells in a Patient
with Epithelial Cancer
SO SCIENCE
LA English
DT Article
ID CD4(+) T-CELLS; METASTATIC MELANOMA; ESTABLISHED MELANOMA;
TUMOR-REGRESSION; LUNG-CARCINOMA; IFN-GAMMA; IN-VIVO; LYMPHOCYTES; GENE;
RESPONSES
AB Limited evidence exists that humans mount a mutation-specific T cell response to epithelial cancers. We used a whole-exomic-sequencing-based approach to demonstrate that tumor-infiltrating lymphocytes (TIL) from a patient with metastatic cholangiocarcinoma contained CD4+ T helper 1 (T(H)1) cells recognizing a mutation in erbb2 interacting protein (ERBB2IP) expressed by the cancer. After adoptive transfer of TIL containing about 25% mutation-specific polyfunctional T(H)1 cells, the patient achieved a decrease in target lesions with prolonged stabilization of disease. Upon disease progression, the patient was retreated with a >95% pure population of mutation-reactive T(H)1 cells and again experienced tumor regression. These results provide evidence that a CD4+ T cell response against a mutated antigen can be harnessed to mediate regression of a metastatic epithelial cancer.
C1 [Tran, Eric; Turcotte, Simon; Gros, Alena; Robbins, Paul F.; Lu, Yong-Chen; Dudley, Mark E.; Wunderlich, John R.; Somerville, Robert P.; Hogan, Katherine; Hinrichs, Christian S.; Parkhurst, Maria R.; Yang, James C.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM sar@nih.gov
RI Lu, Yong-Chen/G-4520-2014;
OI Lu, Yong-Chen/0000-0002-0275-9825; Gros, Alena/0000-0002-1207-1880
FU Intramural Research Program of the NIH; NCI; [PRJNA243084]
FX We thank the Milstein Family Foundation for their generous support;
C.-C. R. Lee, Y. F. Li, A. Mixon, S. Farid, and J. Gartner for helpful
technical support and reagents; and the Surgery Branch clinical team for
outstanding patient care. The data presented in this manuscript are
tabulated in the main paper and the supplementary materials. The raw
whole-exome sequence data are available on the Sequence Read Archive
database: Bioproject PRJNA243084. This research was supported by the
Intramural Research Program of the NIH and NCI.
NR 25
TC 320
Z9 327
U1 7
U2 110
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD MAY 9
PY 2014
VL 344
IS 6184
BP 641
EP 645
DI 10.1126/science.1251102
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG6OD
UT WOS:000335537400046
PM 24812403
ER
PT J
AU Mayse, JD
Nelson, GM
Park, P
Gallagher, M
Lin, SC
AF Mayse, Jeffrey D.
Nelson, Geoffrey M.
Park, Pul
Gallagher, Michela
Lin, Shih-Chieh
TI Proactive and reactive inhibitory control in rats
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE stop signal; stop signal reaction time; reactive; proactive; inhibitory
control; impulsivity; executive function; decision making
ID REACTION-TIME-TASK; STOP-SIGNAL TASK; RESPONSE-INHIBITION; IMPULSIVE
CHOICE; PERFORMANCE; LESIONS; MODEL; ATTENTION; PARADIGM; CORTEX
AB Inhibiting actions inappropriate for the behavioral context, or inhibitory control, is essential for survival and involves both reactively stopping the current prepared action and proactively adjusting behavioral tendencies to increase future performance. A powerful paradigm widely used in basic and clinical research to study inhibitory control is the stop signal task (SST). Recent years have seen a surging interest in translating the SST to rodents to study the neural mechanisms underlying inhibitory control. However, significant differences in task designs and behavioral strategies between rodent and primate studies have made it difficult to directly compare the two literatures. In this study, we developed a rodent-appropriate SST and characterized both reactive and proactive control in rats. For reactive inhibitory control, we found that, unlike in primates, incorrect stop trials in rodents result from two independent types of errors: an initial failure-to-stop error or, after successful stopping, a subsequent failure-to-wait error. Conflating failure-to-stop and failure-to-wait errors systematically overestimates the covert latency of reactive inhibition, the stop signal reaction time (SSRT). To correctly estimate SSRT, we developed and validated a new method that provides an unbiased SSRT estimate independent of the ability to wait. For proactive inhibitory control, we found that rodents adjust both their reaction time and the ability to stop following failure-to-wait errors and successful stop trials, but not after failure-to-stop errors. Together, these results establish a valid rodent model that utilizes proactive and reactive inhibitory control strategies similar to primates, and highlight the importance of dissociating initial stopping from subsequent waiting in studying mechanisms of inhibitory control using rodents.
C1 [Mayse, Jeffrey D.; Gallagher, Michela] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD USA.
[Mayse, Jeffrey D.; Nelson, Geoffrey M.; Lin, Shih-Chieh] NIA, Neural Circuits & Cognit Unit, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA.
[Park, Pul] NIA, Neurocognit Aging Sect, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA.
RP Lin, SC (reprint author), NIA, Neural Circuits & Cognit Unit, Lab Behav Neurosci, NIH, 251 Bayview Blvd,Suite 100,9C220, Baltimore, MD 21224 USA.
EM shih-chieh.lin@nih.gov
OI Nelson, Geoffrey/0000-0001-9825-4241; Lin,
Shih-Chieh/0000-0003-3693-5476
FU Intramural Research Program of the National Institute on Aging, NIH,
USA; National Institute on Aging [AG045039-01A1]
FX We thank P. R. Rapp, P. C. Holland, N. W. Simon, and Z. Xu for critical
discussions and reading of the manuscript. This research is funded by
the Intramural Research Program of the National Institute on Aging, NIH,
USA and the National Institute on Aging grant AG045039-01A1.
NR 51
TC 5
Z9 5
U1 2
U2 2
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD MAY 8
PY 2014
VL 8
AR 104
DI 10.3389/fnins.2014.00104
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA AW7YM
UT WOS:000346477600001
PM 24847204
ER
PT J
AU Chen, MM
Crous-Bou, M
Setiawan, VW
Prescott, J
Olson, SH
Wentzensen, N
Black, A
Brinton, L
Chen, C
Chen, C
Cook, LS
Doherty, J
Friedenreich, CM
Hankinson, SE
Hartge, P
Henderson, BE
Hunter, DJ
Le Marchand, L
Liang, XL
Lissowska, J
Lu, LG
Orlow, I
Petruzella, S
Polidoro, S
Pooler, L
Rebbeck, TR
Risch, H
Sacerdote, C
Schumacher, F
Sheng, X
Shu, XO
Weiss, NS
Xia, L
Van den Berg, D
Yang, HP
Yu, H
Chanock, S
Haiman, C
Kraft, P
De Vivo, I
AF Chen, Maxine M.
Crous-Bou, Marta
Setiawan, Veronica W.
Prescott, Jennifer
Olson, Sara H.
Wentzensen, Nicolas
Black, Amanda
Brinton, Louise
Chen, Chu
Chen, Constance
Cook, Linda S.
Doherty, Jennifer
Friedenreich, Christine M.
Hankinson, Susan E.
Hartge, Patricia
Henderson, Brian E.
Hunter, David J.
Le Marchand, Loic
Liang, Xiaolin
Lissowska, Jolanta
Lu, Lingeng
Orlow, Irene
Petruzella, Stacey
Polidoro, Silvia
Pooler, Loreall
Rebbeck, Timothy R.
Risch, Harvey
Sacerdote, Carlotta
Schumacher, Frederick
Sheng, Xin
Shu, Xiao-ou
Weiss, Noel S.
Xia, Lucy
Van den Berg, David
Yang, Hannah P.
Yu, Herbert
Chanock, Stephen
Haiman, Christopher
Kraft, Peter
De Vivo, Immaculata
TI Exome-Wide Association Study of Endometrial Cancer in a Multiethnic
Population
SO PLOS ONE
LA English
DT Article
ID PROTEIN-S; GENE-EXPRESSION; PROSTATE-CANCER; RISK; SUSCEPTIBILITY;
METAANALYSIS; VARIANTS; OBESITY
AB Endometrial cancer (EC) contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome-wide association studies (GWAS) have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS) of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2). No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC.
C1 [Chen, Maxine M.; Crous-Bou, Marta; Chen, Constance; Hunter, David J.; Kraft, Peter; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA.
[Crous-Bou, Marta; Prescott, Jennifer; Hankinson, Susan E.; De Vivo, Immaculata] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Crous-Bou, Marta; Prescott, Jennifer; Hankinson, Susan E.; De Vivo, Immaculata] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Setiawan, Veronica W.; Henderson, Brian E.; Pooler, Loreall; Sheng, Xin; Xia, Lucy; Van den Berg, David; Haiman, Christopher] Univ So Calif, Los Angeles, CA USA.
[Olson, Sara H.; Liang, Xiaolin; Orlow, Irene; Petruzella, Stacey] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Wentzensen, Nicolas; Black, Amanda; Brinton, Louise; Yang, Hannah P.; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Chen, Chu] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Cook, Linda S.] Univ New Mexico, Albuquerque, NM 87131 USA.
[Cook, Linda S.; Friedenreich, Christine M.] CancerControl Alberta, Alberta Hlth Serv, Calgary, AB, Canada.
[Doherty, Jennifer] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA.
[Hankinson, Susan E.] Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Lu, Lingeng; Risch, Harvey] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Polidoro, Silvia; Sacerdote, Carlotta] Ctr Canc Prevent CPO Piemonte, Turin, Italy.
[Polidoro, Silvia; Sacerdote, Carlotta] Human Genet Fdn HuGeF, Turin, Italy.
[Rebbeck, Timothy R.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Schumacher, Frederick] Canc Prevent Inst Calif, Fremont, CA USA.
[Shu, Xiao-ou] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Weiss, Noel S.] Univ Washington, Seattle, WA 98195 USA.
RP De Vivo, I (reprint author), Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, 665 Huntington Ave, Boston, MA 02115 USA.
EM nhidv@channing.harvard.edu
RI Brinton, Louise/G-7486-2015;
OI Brinton, Louise/0000-0003-3853-8562; Chen, Maxine/0000-0001-7138-6228;
Sacerdote, Carlotta/0000-0002-8008-5096; Orlow,
Irene/0000-0001-6234-6961
FU NCI, NIH [1R01 CA134958, 2R01 CA082838, P01 CA087969, R01 CA49449,
CA54281, CA128008, R01CA83918, P30-CA008748]; NCI [5T32CA009001-38];
Spanish Ministry of Health, Carlos III Health Institute; NIH [RO1
CA105212, RO1 CA 87538, RO1 CA75977, RO3 CA80636, NO1 HD23166, R35
CA39779, KO5 CA92002]; Fred Hutchinson Cancer Research Center; National
Cancer Institute of Canada; Canadian Cancer Society; Canadian Institute
for Health Research; Alberta Innovates-Health Solutions; Alberta Cancer
Foundation through the Weekend to End Women's Cancers Breast Cancer
Chair; Canada Research Chairs program
FX The Nurses' Health Study (NHS) investigators are supported by the NCI,
NIH Grants Number 1R01 CA134958, 2R01 CA082838, P01 CA087969, and R01
CA49449. MMC is supported by training grant 5T32CA009001-38 from the
NCI. MCB is also supported by a Sara Borrell postdoctoral fellowship
from the Spanish Ministry of Health, Carlos III Health Institute. The
Multiethnic Cohort Study (MEC) is supported by the NCI, NHI Grants
Number CA54281, CA128008, and 2R01 CA082838. The Fred Hutchinson Cancer
Research Center (FHCRC) is supported by NCI, NIH Grant Number 2R01
CA082838, NIH RO1 CA105212, RO1 CA 87538, RO1 CA75977, RO3 CA80636, NO1
HD23166, R35 CA39779, KO5 CA92002 and funds from the Fred Hutchinson
Cancer Research Center. The EDGE Study (Estrogen, Diet, Genetics, and
Endometrial Cancer) is supported by NCI, NIH Grants Number 2R01
CA082838, R01CA83918 (Olson PI) and P30-CA008748 (Cancer Center Support
Grant). The Alberta Health Services Study (AHS) was supported by
operating grants obtained from the National Cancer Institute of Canada
with funds from the Canadian Cancer Society and the Canadian Institute
for Health Research. The AHS is also supported by NCI, NIH Grant Number
2R01 CA082838. Dr Christine Friedenreich is supported by career awards
from Alberta Innovates-Health Solutions and the Alberta Cancer
Foundation through the Weekend to End Women's Cancers Breast Cancer
Chair. Dr Linda Cook was supported through the Canada Research Chairs
program. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 34
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U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 8
PY 2014
VL 9
IS 5
AR e97045
DI 10.1371/journal.pone.0097045
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK1XT
UT WOS:000338213300113
PM 24810602
ER
PT J
AU Goncalves, BP
Huang, CY
Morrison, R
Holte, S
Kabyemela, E
Prevots, DR
Fried, M
Duffy, PE
AF Goncalves, Bronner P.
Huang, Chiung-Yu
Morrison, Robert
Holte, Sarah
Kabyemela, Edward
Prevots, D. Rebecca
Fried, Michal
Duffy, Patrick E.
TI Parasite Burden and Severity of Malaria in Tanzanian Children
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PLASMODIUM-FALCIPARUM MALARIA; SICKLE-CELL GENE; AFRICAN CHILDREN; RURAL
AREA; WEST-AFRICA; MORTALITY; MORBIDITY; TRANSMISSION; IMMUNITY; KENYA
AB BackgroundSevere Plasmodium falciparum malaria is a major cause of death in children. The contribution of the parasite burden to the pathogenesis of severe malaria has been controversial.
MethodsWe documented P. falciparum infection and disease in Tanzanian children followed from birth for an average of 2 years and for as long as 4 years.
ResultsOf the 882 children in our study, 102 had severe malaria, but only 3 had more than two episodes. More than half of first episodes of severe malaria occurred after a second infection. Although parasite levels were higher on average when children had severe rather than mild disease, most children (67 of 102) had high-density infection (>2500 parasites per 200 white cells) with only mild symptoms before severe malaria, after severe malaria, or both. The incidence of severe malaria decreased considerably after infancy, whereas the incidence of high-density infection was similar among all age groups. Infections before and after episodes of severe malaria were associated with similar parasite densities. Nonuse of bed nets, placental malaria at the time of a woman's second or subsequent delivery, high-transmission season, and absence of the sickle cell trait increased severe-malaria risk and parasite density during infections.
ConclusionsResistance to severe malaria was not acquired after one or two mild infections. Although the parasite burden was higher on average during episodes of severe malaria, a high parasite burden was often insufficient to cause severe malaria even in children who later were susceptible. The diverging rates of severe disease and high-density infection after infancy, as well as the similar parasite burdens before and after severe malaria, indicate that naturally acquired resistance to severe malaria is not explained by improved control of parasite density. (Funded by the National Institute of Allergy and Infectious Diseases and others.)
The pathogenesis of severe malaria due to Plasmodium falciparum remains controversial. In this study conducted over several years and involving 882 Tanzanian children, parasite burden was insufficient to explain the development of severe illness. Although almost 600,000 African children die each year from malaria,(1) most infections in children are mild.(2),(3) Fundamental questions about the pathogenesis of malaria remain unresolved, such as the relative contributions of parasite burden and host inflammation to severe disease.(4) In areas where transmission is stable, severe malaria is unlikely to occur after 5 years of age, presumably as a result of immunity,(5) and mathematical models suggest that protection against noncerebral severe malaria develops after one or two infections.(6) The mechanism of protective immunity is unclear; it might, for example, involve the reduction of parasite density or the blocking of ...
C1 [Goncalves, Bronner P.; Fried, Michal; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA.
[Goncalves, Bronner P.; Prevots, D. Rebecca] NIAID, Lab Clin Infect Dis, Epidemiol Unit, NIH, Rockville, MD 20852 USA.
[Huang, Chiung-Yu] NIAID, Biostat Res Branch, NIH, Rockville, MD 20852 USA.
[Morrison, Robert; Fried, Michal; Duffy, Patrick E.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Holte, Sarah] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Kabyemela, Edward; Fried, Michal; Duffy, Patrick E.] Muheza Designated Dist Hosp, Offspring Malaria Studies Project, Muheza, Tanzania.
RP Duffy, PE (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, Twinbrook 1,Rm 111,5640 Fishers Lane, Rockville, MD 20852 USA.
EM patrick.duffy@nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH); NIAID
extramural program [R01AI52059]; Fogarty International Center of the NIH
[D43 TW005509]; Foundation for the NIH through the Grand Challenges in
Global Health Initiative - Bill and Melinda Gates Foundation [1364]
FX Supported by the Intramural Research Program of the National Institute
of Allergy and Infectious Diseases (NIAID), National Institutes of
Health (NIH), and by grants from the NIAID extramural program
(R01AI52059), the Fogarty International Center (D43 TW005509) of the
NIH, and the Foundation for the NIH through the Grand Challenges in
Global Health Initiative, which is funded by the Bill and Melinda Gates
Foundation (1364).
NR 40
TC 28
Z9 28
U1 0
U2 13
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAY 8
PY 2014
VL 370
IS 19
BP 1799
EP 1808
DI 10.1056/NEJMoa1303944
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA AH3CD
UT WOS:000335997900008
PM 24806160
ER
PT J
AU Battiwalla, M
AF Battiwalla, Minoo
TI Abnl(17p) in AML: who will guard the guardian?
SO BLOOD
LA English
DT Editorial Material
ID ACUTE MYELOID-LEUKEMIA; KARYOTYPE; MUTATIONS; IMPACT
AB In this issue of Blood, Middeke and colleagues highlight the poor outcome of the abnormal (17p) [abnl(17p)] subgroup of cytogenetically adverse-risk acute myeloid leukemia (AML) even after allogeneic hematopoietic stem cell transplantation (HSCT).(1)
C1 Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Battiwalla, M (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA.
NR 10
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 8
PY 2014
VL 123
IS 19
BP 2906
EP 2907
DI 10.1182/blood-2014-04-565515
PG 2
WC Hematology
SC Hematology
GA AH1RF
UT WOS:000335897900003
PM 24810623
ER
PT J
AU Iqbal, J
Wright, G
Wang, C
Rosenwald, A
Gascoyne, RD
Weisenburger, DD
Greiner, TC
Smith, L
Guo, SP
Wilcox, RA
Teh, B
Lim, ST
Tan, SY
Rimsza, LM
Jaffe, ES
Campo, E
Martinez, A
Delabie, J
Braziel, RM
Cook, JR
Tubbs, RR
Ott, G
Geissinger, E
Gaulard, P
Piccaluga, PP
Pileri, SA
Au, WY
Nakamura, S
Seto, M
Berger, F
de Leval, L
Connors, JM
Armitage, J
Vose, J
Chan, WC
Staudt, LM
AF Iqbal, Javeed
Wright, George
Wang, Chao
Rosenwald, Andreas
Gascoyne, Randy D.
Weisenburger, Dennis D.
Greiner, Timothy C.
Smith, Lynette
Guo, Shuangping
Wilcox, Ryan A.
Teh, Bin Tean
Lim, Soon Thye
Tan, Soon Yong
Rimsza, Lisa M.
Jaffe, Elaine S.
Campo, Elias
Martinez, Antonio
Delabie, Jan
Braziel, Rita M.
Cook, James R.
Tubbs, Raymond R.
Ott, German
Geissinger, Eva
Gaulard, Philippe
Piccaluga, Pier Paolo
Pileri, Stefano A.
Au, Wing Y.
Nakamura, Shigeo
Seto, Masao
Berger, Francoise
de Leval, Laurence
Connors, Joseph M.
Armitage, James
Vose, Julie
Chan, Wing C.
Staudt, Louis M.
CA Lymphoma Leukemia Mol Profiling Pr
Int Peripheral T-cell Lymphoma Pro
TI Gene expression signatures delineate biological and prognostic subgroups
in peripheral T-cell lymphoma
SO BLOOD
LA English
DT Article
ID DENDRITIC CELLS; IDENTIFICATION; DIFFERENTIATION; RECOGNITION;
PREDICTION; PROFILES; EFFECTOR; SURVIVAL; FEATURES; SUBTYPES
AB Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P = .01). High expression of cytotoxic gene-signature within the TBX21 subgroup also showed poor clinical outcome (P = .05). InAITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P = .004).
C1 [Iqbal, Javeed; Wang, Chao; Greiner, Timothy C.; Guo, Shuangping] Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA.
[Wright, George; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Rosenwald, Andreas; Geissinger, Eva] Univ Wurzburg, Inst Pathol, Wurzburg, Germany.
[Gascoyne, Randy D.; Connors, Joseph M.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada.
[Weisenburger, Dennis D.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA.
[Smith, Lynette; Chan, Wing C.] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Biostat, Omaha, NE USA.
[Wilcox, Ryan A.] Univ Michigan, Dept Internal Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Teh, Bin Tean; Lim, Soon Thye; Tan, Soon Yong] Natl Canc Ctr, Singapore, Singapore.
[Teh, Bin Tean; Lim, Soon Thye; Tan, Soon Yong] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore.
[Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ USA.
[Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Campo, Elias; Martinez, Antonio] Univ Barcelona, Hosp Clin, Inst Invest Bomed August Pi & Sunyer, Barcelona, Spain.
[Delabie, Jan] Univ Oslo, Norwegian Radium Hosp, Dept Pathol, Oslo, Norway.
[Braziel, Rita M.] Oregon Hlth & Sci Univ, Dept Clin Pathol, Portland, OR 97201 USA.
[Cook, James R.; Tubbs, Raymond R.] Cleveland Clin, Dept Mol Pathol & Lab Med, Cleveland, OH 44106 USA.
[Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany.
[Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
[Gaulard, Philippe] Univ Paris Est, Grp Henri Mondor Albert Chenevier, INSERM, Dept Pathol,U955, Creteil, France.
[Piccaluga, Pier Paolo; Pileri, Stefano A.] Univ Bologna, S Orsola Malpighi Hosp, Inst Hematol & Med Oncol L&A Seragnoli, Bologna, Italy.
[Au, Wing Y.] Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China.
[Nakamura, Shigeo; Seto, Masao] Aichi Canc Ctr, Nagoya, Aichi 464, Japan.
[Berger, Francoise] Ctr Hosp Lyon Sud, Lyon, France.
[de Leval, Laurence] CHU Vaudois, Univ Inst Pathol, CH-1011 Lausanne, Switzerland.
[Armitage, James; Vose, Julie] Univ Nebraska Med Ctr, Dept Hematol Oncol, Omaha, NE USA.
RP Iqbal, J (reprint author), Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, 983135 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM jiqbal@unmc.edu; jochan@coh.org; lstaudt@mail.nih.gov
RI Nakamura, Shigeo/I-1571-2012; Campo, elias/O-7192-2016;
OI Campo, elias/0000-0001-9850-9793; Delabie, Jan/0000-0001-5023-0689;
Jaffe, Elaine/0000-0003-4632-0301
FU National Cancer Institute, National Institutes of Health
[1U01CA157581-01]; Lymphoma Foundation of America; Lymphoma Research
Foundation; Leukemia & Lymphoma Society; University of Nebraska Medical
Center-Clinical and Translational Research mentored Scholars program
pilot grant; Chinese Scholarship Council
FX The study was supported by the National Cancer Institute, National
Institutes of Health (1U01CA157581-01). J.I. is a recipient of the young
scientist award from the Lymphoma Foundation of America, a fellowship
from the Lymphoma Research Foundation, and the Translational Research
Program award from the Leukemia & Lymphoma Society, and has also
received a University of Nebraska Medical Center-Clinical and
Translational Research mentored Scholars program pilot grant. C.W. is a
recipient of a fellowship from the Chinese Scholarship Council.
NR 37
TC 66
Z9 71
U1 2
U2 12
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 8
PY 2014
VL 123
IS 19
BP 2915
EP 2923
DI 10.1182/blood-2013-11-536359
PG 9
WC Hematology
SC Hematology
GA AH1RF
UT WOS:000335897900009
PM 24632715
ER
PT J
AU Steward-Tharp, SM
Laurence, A
Kanno, Y
Kotlyar, A
Villarino, AV
Sciume, G
Kuchen, S
Resch, W
Wohlfert, EA
Jiang, K
Hirahara, K
Vahedi, G
Sun, HW
Feigenbaum, L
Milner, JD
Holland, SM
Casellas, R
Powrie, F
O'Shea, JJ
AF Steward-Tharp, Scott M.
Laurence, Arian
Kanno, Yuka
Kotlyar, Alex
Villarino, Alejandro V.
Sciume, Giuseppe
Kuchen, Stefan
Resch, Wolfgang
Wohlfert, Elizabeth A.
Jiang, Kan
Hirahara, Kiyoshi
Vahedi, Golnaz
Sun, Hong-wei
Feigenbaum, Lionel
Milner, Joshua D.
Holland, Steven M.
Casellas, Rafael
Powrie, Fiona
O'Shea, John J.
TI A mouse model of HIES reveals pro- and anti-inflammatory functions of
STAT3
SO BLOOD
LA English
DT Article
ID HYPER-IGE SYNDROME; INDUCED TH2 POLARIZATION; HYPERIMMUNOGLOBULINEMIA-E;
T-CELLS; B-CELLS; MUTATIONS; DISEASE; MICE; PATHOGENESIS; GENERATION
AB Mutations of STAT3 underlie the autosomal dominant form of hyperimmunoglobulin E syndrome (HIES). STAT3 has critical roles in immune cells and thus, hematopoietic stem cell transplantation (HSCT), might be a reasonable therapeutic strategy in this disease. However, STAT3 also has critical functions in nonhematopoietic cells and dissecting the protean roles of STAT3 is limited by the lethality associated with germline deletion of Stat3. Thus, predicting the efficacy of HSCT for HIES is difficult. To begin to dissect the importance of STAT3 in hematopoietic and nonhematopoietic cells as it relates to HIES, we generated a mouse model of this disease. We found that these transgenic mice recapitulate multiple aspects of HIES, including elevated serum IgE and failure to generate Th17 cells. We found that these mice were susceptible to bacterial infection that was partially corrected by HSCT using wild-type bone marrow, emphasizing the role played by the epithelium in the pathophysiology of HIES.
C1 [Steward-Tharp, Scott M.; Laurence, Arian; Kanno, Yuka; Kotlyar, Alex; Villarino, Alejandro V.; Sciume, Giuseppe; Jiang, Kan; Hirahara, Kiyoshi; Vahedi, Golnaz; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Steward-Tharp, Scott M.; Powrie, Fiona] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 2JD, England.
[Kuchen, Stefan; Resch, Wolfgang; Casellas, Rafael] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Wohlfert, Elizabeth A.] SUNY Buffalo, Dept Microbiol & Immunol, Sch Med & Biomed Sci, Buffalo, NY 14260 USA.
[Sun, Hong-wei] NIAMSD, Biodata Min & Discovery Sect, NIH, Bethesda, MD 20892 USA.
[Feigenbaum, Lionel] NCI, Lab Anim Sci Program, NIH, Frederick, MD 21701 USA.
[Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Holland, Steven M.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Laurence, A (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, 10 Ctr Dr,MSC 1930,Bldg 10,Room 13C120-11B, Bethesda, MD 20892 USA.
EM laurencea@mail.nih.gov
RI Kanno, Yuka/B-5802-2013; Laurence, Arian/A-8770-2009; Sciume,
Giuseppe/K-8985-2016; Hirahara, Kiyoshi/E-2460-2017;
OI Laurence, Arian/0000-0003-0942-8292; Sciume,
Giuseppe/0000-0003-0131-512X; Hirahara, Kiyoshi/0000-0002-9128-9449;
Kuchen, Stefan/0000-0003-4899-8132; Kanno, Yuka/0000-0001-5668-9319;
Villarino, Alejandro/0000-0001-8068-2176
FU Howard Hughes Medical Institute-National Institutes of Health; National
Institute of Arthritis and Musculoskeletal and Skin Diseases of the
National Institutes of Health
FX S.M.S.-T. is a member of the National Institutes of
Health-Oxford/Cambridge Scholars Program. A. K. and S.M.S.-T. were
funded by the Howard Hughes Medical Institute-National Institutes of
Health research scholar program.; This work was supported in part by the
Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases of the National Institutes of Health.
NR 46
TC 20
Z9 21
U1 0
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 8
PY 2014
VL 123
IS 19
BP 2978
EP 2987
DI 10.1182/blood-2013-09-523167
PG 10
WC Hematology
SC Hematology
GA AH1RF
UT WOS:000335897900016
PM 24632714
ER
PT J
AU Wang, PP
Zhou, ZH
Hu, AC
de Albuquerque, CP
Zhou, Y
Hong, LX
Sierecki, E
Ajiro, M
Kruhlak, M
Harris, C
Guan, KL
Zheng, ZM
Newton, AC
Sun, PQ
Zhou, HL
Fu, XD
AF Wang, Pingping
Zhou, Zhihong
Hu, Anchang
de Albuquerque, Claudio Ponte
Zhou, Yu
Hong, Lixin
Sierecki, Emma
Ajiro, Masahiko
Kruhlak, Michael
Harris, Curtis
Guan, Kun-Liang
Zheng, Zhi-Ming
Newton, Alexandra C.
Sun, Peiqing
Zhou, Huilin
Fu, Xiang-Dong
TI Both Decreased and Increased SRPK1 Levels Promote Cancer by Interfering
with PHLPP- Mediated Dephosphorylation of Akt
SO MOLECULAR CELL
LA English
DT Article
ID SPLICING-FACTOR; SR PROTEINS; CELLULAR SENESCENCE; TUMOR-SUPPRESSOR;
MAMMALIAN-CELLS; WIDE ANALYSIS; RNA; PHOSPHORYLATION; PHOSPHATASE;
ACTIVATION
AB Akt activation is a hallmark of human cancers. Here, we report a critical mechanism for regulation of Akt activity by the splicing kinase SRPK1, a downstream Akt target for transducing growth signals to regulate splicing. Surprisingly, we find that SRPK1 has a tumor suppressor function because ablation of SRPK1 in mouse embryonic fibroblasts induces cell transformation. We link the phenotype to constitutive Akt activation from genome-wide phosphoproteomics analysis and discover that downregulated SRPK1 impairs the recruitment of the Akt phosphatase PHLPP1 (pleckstrin homology (PH) domain leucine-rich repeat protein phosphatase) to Akt. Interestingly, SRPK1 overexpression is also tumorigenic because excess SRPK1 squelches PHLPP1. Thus, aberrant SRPK1 expression in either direction induces constitutive Akt activation, providing a mechanistic basis for previous observations that SRPK1 is downregulated in some cancer contexts and upregulated in others.
C1 [Wang, Pingping; Zhou, Zhihong; Hu, Anchang; de Albuquerque, Claudio Ponte; Zhou, Yu; Zhou, Huilin; Fu, Xiang-Dong] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
[de Albuquerque, Claudio Ponte; Zhou, Huilin] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
[Hong, Lixin; Sun, Peiqing] Scripps Res Inst, Dept Cell & Mol Biol, La Jolla, CA 92037 USA.
[Sierecki, Emma; Guan, Kun-Liang; Newton, Alexandra C.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
[Ajiro, Masahiko; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Bethesda, MD 20892 USA.
[Kruhlak, Michael] NCI, Expt Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Harris, Curtis] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA.
[Fu, Xiang-Dong] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.
RP Fu, XD (reprint author), Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
EM xdfu@ucsd.edu
RI Sierecki, Emma/A-4810-2012
FU NIH [GM052872, GM067946]
FX We thank members of the Fu lab for stimulating discussion during the
course of this investigation. This work was supported by NIH grants
(GM052872 to X.-D.F. and GM067946 to A.C.N.). H.Z. is an investigator of
the Ludwig Institute for Cancer Research.
NR 47
TC 25
Z9 26
U1 3
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD MAY 8
PY 2014
VL 54
IS 3
BP 378
EP 391
DI 10.1016/j.molcel.2014.03.007
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AH3ME
UT WOS:000336026900007
PM 24703948
ER
PT J
AU Liang, YH
Lavoie, M
Comeau, MA
Abou Elela, S
Ji, XH
AF Liang, Yu-He
Lavoie, Mathieu
Comeau, Marc-Andre
Abou Elela, Sherif
Ji, Xinhua
TI Structure of a Eukaryotic RNase III Postcleavage Complex Reveals a
Double-Ruler Mechanism for Substrate Selection
SO MOLECULAR CELL
LA English
DT Article
ID DOUBLE-STRANDED-RNA; RIBONUCLEASE-III; BINDING DOMAIN; HUMAN DICER;
CLEAVAGE ACTIVITY; ESCHERICHIA-COLI; MESSENGER-RNAS; YEAST; RNT1P;
RECOGNITION
AB Ribonuclease III (RNase III) enzymes are a family of double-stranded RNA (dsRNA)-specific endoribonucleases required for RNA maturation and gene regulation. Prokaryotic RNase III enzymes have been well characterized, but how eukaryotic RNase IIIs work is less clear. Here, we describe the structure of the Saccharomyces cerevisiae RNase III (Rnt1p) post-cleavage complex and explain why Rnt1p binds to RNA stems capped with an NGNN tetraloop. The structure shows specific interactions between a structural motif located at the end of the Rnt1p dsRNA-binding domain (dsRBD) and the guanine nucleotide in the second position of the loop. Strikingly, structural and biochemical analyses indicate that the dsRBD and N-terminal domains (NTDs) of Rnt1p function as two rulers that measure the distance between the tetraloop and the cleavage site. These findings provide a framework for understanding eukaryotic RNase IIIs.
C1 [Liang, Yu-He; Ji, Xinhua] NCI, Biomol Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
[Lavoie, Mathieu; Comeau, Marc-Andre; Abou Elela, Sherif] Univ Sherbrooke, Dept Microbiol & Infectiol, RNA Grp, Grp ARN, Sherbrooke, PQ J1E 4K8, Canada.
RP Abou Elela, S (reprint author), Univ Sherbrooke, Dept Microbiol & Infectiol, RNA Grp, Grp ARN, Sherbrooke, PQ J1E 4K8, Canada.
EM sherif.abou.elela@usherbrooke.ca; jix@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; Canadian
Institute of Health Research
FX We thank Catherine Desrosiers for help with protein purification, Jules
Gagnon for tetraloop sequence conservation analysis, and Donald Court,
George Mackie, and Alexander Wlodawer for discussion. X-ray diffraction
data were collected at the SER-CAT 22-ID beamline of the Advanced Photon
Source, Argonne National Laboratory. This research was supported by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research (X.J.) and a grant from the Canadian
Institute of Health Research (S.A.E.).
NR 47
TC 10
Z9 10
U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD MAY 8
PY 2014
VL 54
IS 3
BP 431
EP 444
DI 10.1016/j.molcel.2014.03.006
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AH3ME
UT WOS:000336026900011
PM 24703949
ER
PT J
AU Fang, EF
Scheibye-Knudsen, M
Brace, LE
Kassahun, H
SenGupta, T
Nilsen, H
Mitchell, JR
Croteau, DL
Bohr, VA
AF Fang, Evandro Fei
Scheibye-Knudsen, Morten
Brace, Lear E.
Kassahun, Henok
SenGupta, Tanima
Nilsen, Hilde
Mitchell, James R.
Croteau, Deborah L.
Bohr, Vilhelm A.
TI Defective Mitophagy in XPA via PARP-1 Hyperactivation and NAD(+)/SIRT1
Reduction
SO CELL
LA English
DT Article
ID PIGMENTOSUM GROUP-A; COCKAYNE-SYNDROME; XERODERMA-PIGMENTOSUM;
DNA-REPAIR; UNCOUPLING PROTEIN-2; PARKINSONS-DISEASE; MOUSE MODEL;
AUTOPHAGY; DAMAGE; MITOCHONDRIA
AB Mitochondrial dysfunction is a common feature in neurodegeneration and aging. We identify mitochondrial dysfunction in xeroderma pigmentosum group A (XPA), a nucleotide excision DNA repair disorder with severe neurodegeneration, in silico and in vivo. XPA-deficient cells show defective mitophagy with excessive cleavage of PINK1 and increased mitochondrial membrane potential. The mitochondrial abnormalities appear to be caused by decreased activation of the NAD(+)-SIRT1-PGC-1 alpha axis triggered by hyperactivation of the DNA damage sensor PARP1. This phenotype is rescued by PARP-1 inhibition or by supplementation with NAD(+) precursors that also rescue the lifespan defect in xpa-1 nematodes. Importantly, this pathogenesis appears common to ataxia-telangiectasia and Cockayne syndrome, two other DNA repair disorders with neurodegeneration, but absent in XPC, a DNA repair disorder without neurodegeneration. Our findings reveal a nuclear-mitochondrial crosstalk that is critical for the maintenance of mitochondrial health.
C1 [Fang, Evandro Fei; Scheibye-Knudsen, Morten; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Brace, Lear E.; Mitchell, James R.] Harvard Univ, Sch Med, Dept Genet & Complex Dis, Boston, MA 02115 USA.
[Kassahun, Henok; SenGupta, Tanima; Nilsen, Hilde] Univ Oslo, Ctr Biotechnol, N-0317 Oslo, Norway.
[Bohr, Vilhelm A.] Univ Copenhagen, Danish Ctr Hlth Aging, DK-2200 Copenhagen, Denmark.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
EM vbohr@nih.gov
OI Scheibye-Knudsen, Morten/0000-0002-6637-1280
FU Intramural Research Program of the NIH, National Institute on Aging;
research council of Norway; Luke O'Brien Foundation; National Science
Foundation Graduate Research Fellowship Program
FX We thank Drs. Kevin Becker, Yongqing Zhang, and Elin Lehrmann for their
help in performing microarray and data analysis, and Dr. Magdalena
Misiak for preparing rat neurons. We thank Drs. Mark Mattson and Peter
Sykora for reading this manuscript. This research was supported by the
Intramural Research Program of the NIH, National Institute on Aging.
H.N. was supported by a grant from the research council of Norway.
J.R.M. and L.E.B. were supported by the Luke O'Brien Foundation, and
L.E.B. was supported by the National Science Foundation Graduate
Research Fellowship Program.
NR 29
TC 86
Z9 86
U1 4
U2 33
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD MAY 8
PY 2014
VL 157
IS 4
BP 882
EP 896
DI 10.1016/j.cell.2014.03.026
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AG9UN
UT WOS:000335765500016
PM 24813611
ER
PT J
AU Naidoo, J
De Jesus-Cortes, H
Huntington, P
Estill, S
Morlock, LK
Starwalt, R
Mangano, TJ
Williams, NS
Pieper, AA
Ready, JM
AF Naidoo, Jacinth
De Jesus-Cortes, Hector
Huntington, Paula
Estill, Sandi
Morlock, Lorraine K.
Starwalt, Ruth
Mangano, Thomas J.
Williams, Noelle S.
Pieper, Andrew A.
Ready, Joseph M.
TI Discovery of a Neuroprotective Chemical,
(S)-N-(3-(3,6-Dibromo-9H-carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin
-2-amine [(-)-P7C3-S243], with Improved Druglike Properties
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID MOUSE MODEL; AMINOPROPYL CARBAZOLES; PARKINSONS-DISEASE; DERIVATIVES;
MPTP; NEUROTOXIN; EFFICACY
AB (-)-P7C3-S243 is a neuroprotective aminopropyl carbazole with improved druglike properties compared with previously reported compounds in the P7C3 class. It protects developing neurons in a mouse model of hippocampal neurogenesis and protects mature neurons within the substantia nigra in a mouse model of Parkinson's disease. A short, enantioselective synthesis provides the neuroprotective agent in optically pure form. It is nontoxic, orally bioavailable, metabolically stable, and able to cross the blood-brain barrier. As such, it represents a valuable lead compound for the development of drugs to treat neurodegenerative diseases and traumatic brain injury.
C1 [Naidoo, Jacinth; Huntington, Paula; Estill, Sandi; Morlock, Lorraine K.; Starwalt, Ruth; Williams, Noelle S.; Ready, Joseph M.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
[De Jesus-Cortes, Hector] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA.
[De Jesus-Cortes, Hector; Pieper, Andrew A.] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA.
[De Jesus-Cortes, Hector; Pieper, Andrew A.] Univ Iowa, Dept Neurol, Carver Coll Med, Iowa City, IA 52242 USA.
[De Jesus-Cortes, Hector; Pieper, Andrew A.] Univ Iowa, Dept Vet Affairs, Carver Coll Med, Iowa City, IA 52242 USA.
[Mangano, Thomas J.] Univ N Carolina, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
RP Pieper, AA (reprint author), Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA.
EM andrew-pieper@uiowa.edu; joseph.ready@utsouthwestern.edu
OI De Jesus-Cortes, Hector/0000-0001-6983-6963
FU Edward N. and Della C. Thome Memorial Foundation; Welch Foundation
[I-1612]; NSF [2012140236-02]; NIH [R01 MH087986]
FX We thank Prof. Jef De Brabander (UT Southwestern) for helpful
discussions regarding Cu-catalyzed amination and the NIH's Psychoactive
Drug Screening Program at the University of North Carolina. Funding was
provided by the Edward N. and Della C. Thome Memorial Foundation and the
Welch Foundation (I-1612) (to J.M.R.) and the NSF (2012140236-02) (to
H.D.J.-C.). Additional support was received from the NIH (R01 MH087986)
to A.A.P. and an unrestricted endowment provided to Steven L. McKnight
by an anonymous donor.
NR 28
TC 16
Z9 17
U1 0
U2 16
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD MAY 8
PY 2014
VL 57
IS 9
BP 3746
EP 3754
DI 10.1021/jm401919s
PG 9
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AH1KN
UT WOS:000335879100012
PM 24697290
ER
PT J
AU Pu, YM
Kang, JH
Sigano, DM
Peach, ML
Lewin, NE
Marquez, VE
Blumberg, PM
AF Pu, Yongmei
Kang, Ji-Hye
Sigano, Dina M.
Peach, Megan L.
Lewin, Nancy E.
Marquez, Victor E.
Blumberg, Peter M.
TI Diacylglycerol Lactones Targeting the Structural Features That
Distinguish the Atypical C1 Domains of Protein Kinase C zeta and iota
from Typical C1 Domains
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID CONFORMATIONALLY CONSTRAINED ANALOGS; HIGH BINDING-AFFINITY;
DAG-LACTONES; CRYSTAL-STRUCTURE; PHOSPHOLIPASE-D; PHORBOL ESTER; PK-C;
ISOFORMS; LIGAND; RAS
AB To explore the feasibility of developing ligands targeted to the atypical C1 domains of protein kinase C zeta and iota, we have prepared diacylglycerol lactones substituted with hydrophilic groups on their side chains, which potentially could interact with the arginine residues that distinguish the atypical C1 domains of PKC zeta and PKC?iota from typical C1 domains, and we have measured their binding to mutated versions of the C1b domain of PKC delta that incorporate one or more of these arginine residues. The most selective of the diacylglycerol lactones showed only a 10-fold reduction in binding affinity with the triple arginine mutant (N7R/S10R/L20R) compared to the wild-type, whereas phorbol 12,13-dibutyrate showed a 6000-fold loss of affinity. Molecular modeling confirms that these ligands are indeed able to interact with the arginine residues. Our results show that dramatic changes in selectivity can be obtained through appropriate substitution of diacylglycerol lactones.
C1 [Pu, Yongmei; Lewin, Nancy E.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kang, Ji-Hye; Sigano, Dina M.; Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Peach, Megan L.] Leidos Biomed Inc, Biol Chem Lab, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Blumberg, PM (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM blumberp@dc37a.nci.nih.gov
RI Sigano, Dina/M-6144-2014
OI Sigano, Dina/0000-0001-7489-9555
FU National Institutes of Health, Center for Cancer Research, National
Cancer Institute [Z1A BC 005270]; Federal funds from the Frederick
National Laboratory for Cancer Research, National Institutes of Health
[HHSN261200800001E]
FX This work was supported in part through the Intramural Research Program
of the National Institutes of Health, Center for Cancer Research,
National Cancer Institute (Project Z1A BC 005270) and in part with
Federal funds from the Frederick National Laboratory for Cancer
Research, National Institutes of Health, under Contract
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.
NR 44
TC 2
Z9 2
U1 2
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD MAY 8
PY 2014
VL 57
IS 9
BP 3835
EP 3844
DI 10.1021/jm500165n
PG 10
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AH1KN
UT WOS:000335879100018
PM 24684293
ER
PT J
AU Jayasekara, PS
Barrett, MO
Ball, CB
Brown, KA
Hammes, E
Balasubramanian, R
Harden, TK
Jacobson, KA
AF Jayasekara, P. Suresh
Barrett, Matthew O.
Ball, Christopher B.
Brown, Kyle A.
Hammes, Eva
Balasubramanian, Ramachandran
Harden, T. Kendall
Jacobson, Kenneth A.
TI 4-Alkyloxyimino Derivatives of Uridine-5 '-triphosphate: Distal
Modification of Potent Agonists as a Strategy for Molecular Probes of
P2Y(2), P2Y(4), and P2Y(6) Receptors
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID NUCLEOTIDE RECEPTORS; SELECTIVE AGONISTS; ANTAGONIST; ATP; UDP
AB Extended N-4-(3-arylpropyl)oxy derivatives of uridine-5 '-triphosphate were synthesized and potently stimulated phospholipase C stimulation in astrocytoma cells expressing G protein-coupled human (h) P2Y receptors (P2YRs) activated by UTP (P2Y(2/4)R) or UDP (P2Y(6)R). The potent P2Y(4)R-selective N-4-(3-phenylpropyl)oxy agonist was phenyl ring-substituted or replaced with terminal heterocyclic or naphthyl rings with retention of P2YR potency. This broad tolerance for steric bulk in a distal region was not observed for dinucleoside tetraphosphate agonists with both nucleobases substituted. The potent N-4-(3-(4-methoxyphenyl)-propyl)oxy analogue 19 (EC50: P2Y(2)R, 47 nM; P2Y(4)R, 23 nM) was functionalized for chain extension using click tethering of fluorophores as prosthetic groups. The BODIPY 630/650 conjugate 28 (MRS4162) exhibited EC50 values of 70, 66, and 23 nM at the hP2Y(2/4/6)Rs, respectively, and specifically labeled cells expressing the P2Y(6)R. Thus, an extended N-4-(3-arylpropyl)oxy group accessed a structurally permissive region on three G(q)-coupled P2YRs, and potency and selectivity were modulated by distal structural changes. This freedom of substitution was utilized to design of a pan-agonist fluorescent probe of a subset of uracil nucleotide-activated hP2YRs.
C1 [Jayasekara, P. Suresh; Hammes, Eva; Balasubramanian, Ramachandran; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Barrett, Matthew O.; Ball, Christopher B.; Brown, Kyle A.; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
RP Jacobson, KA (reprint author), NIDDK, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of General Medical Sciences [GM38213]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Diabetes and Digestive and Kidney
Diseases, and a grant (GM38213) from the National Institute of General
Medical Sciences. We thank Noel Whittaker (NIDDK) for mass spectral
determinations.
NR 34
TC 12
Z9 12
U1 1
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD MAY 8
PY 2014
VL 57
IS 9
BP 3874
EP 3883
DI 10.1021/jm500367e
PG 10
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AH1KN
UT WOS:000335879100021
PM 24712832
ER
PT J
AU Albert, S
Balaban, RS
Neufeld, EB
Rossmann, JS
AF Albert, Scott
Balaban, Robert S.
Neufeld, Edward B.
Rossmann, Jenn Stroud
TI Influence of the renal artery ostium flow diverter on hemodynamics and
atherogenesis
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
DE Renal artery; Ostium; Flow diverter; CFD; Cardiovascular;
Atherosclerosis; Abdominal aorta
ID ABDOMINAL-AORTA; BLOOD-FLOW; ATHEROSCLEROSIS; RABBITS; MODEL
AB The structure and function of the renal artery ostium flow diverter on the caudal side of the renal branch point were previously reported; in this study, we further evaluate the diverter's possible functions. The protrusion of this structure into the abdominal aorta suggests that the diverter may preferentially direct blood flow to the renal arteries, and that it may also influence flow patterns and recirculation known to be involved in atherogenesis. Three-dimensional computational fluid dynamics (CFD) simulations of steady and pulsatile blood flow are performed to investigate the influence of diverter size and position, and vascular geometry, on the flow patterns and fluid mechanical forces in the neighborhood of the diverter. CFD results show that the flow diverter does affect the blood distribution; depending on the diverter's position, the flow to the renal arteries may be increased or reduced. Calculated results also demonstrate the diverter's effect on the wall shear stress (WSS) distribution, and suggest that the diverter contributes to an atherogenic environment in the abdominal aorta, while being atheroprotective in the renal arteries themselves. These results support previous clinical findings, and suggest directions for further clinical study. The results of this work have direct implications in understanding the physiological significance of the diverter, and its potential role in the pathophysiological development of atherosclerosis. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Albert, Scott] Lafayette Coll, Chem & Biomol Engn Dept, Easton, PA 18042 USA.
[Balaban, Robert S.; Neufeld, Edward B.] NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA.
[Rossmann, Jenn Stroud] Lafayette Coll, Dept Mech Engn, Easton, PA 18042 USA.
RP Rossmann, JS (reprint author), Lafayette Coll, Dept Mech Engn, Easton, PA 18042 USA.
EM rossmanj@lafayette.edu
FU Lafayette College Departments of Mechanical and Chemical & Biomolecular
Engineering
FX The authors are grateful to the Lafayette College Departments of
Mechanical and Chemical & Biomolecular Engineering, which supported the
first author's completion of his undergraduate honors thesis on this
subject. They also acknowledge the helpful contributions of Becky
Rosenbauer, Peter Sun, Taimoor Sohail, Apratim Mukherjee, and Li-Yueh
Hsu.
NR 21
TC 4
Z9 4
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0021-9290
EI 1873-2380
J9 J BIOMECH
JI J. Biomech.
PD MAY 7
PY 2014
VL 47
IS 7
BP 1594
EP 1602
DI 10.1016/j.jbiomech.2014.03.006
PG 9
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA AI6VY
UT WOS:000337016300006
PM 24703300
ER
PT J
AU Snow, KK
Bell, MC
Stoddard, AM
Curto, TM
Wright, EC
Dienstag, JL
AF Snow, Kristin K.
Bell, Margaret C.
Stoddard, Anne M.
Curto, Teresa M.
Wright, Elizabeth C.
Dienstag, Jules L.
TI Processes to manage analyses and publications in a phase III multicenter
randomized clinical trial
SO TRIALS
LA English
DT Article
DE Publication guidelines; Publication processes; Publication management;
HALT-C trial; Authorship assignment; Authorship allocation
ID CHRONIC HEPATITIS-C; LONG-TERM TREATMENT; LOW-DOSE PEGINTERFERON;
STANDARD LABORATORY TESTS; LIVER-DISEASE PROGRESSION; SERUM FIBROSIS
MARKERS; QUALITY-OF-LIFE; CIRRHOSIS TRIAL; HEPATOCELLULAR-CARCINOMA;
COGNITIVE FUNCTION
AB Background: The timely publication of findings in peer-reviewed journals is a primary goal of clinical research. In clinical trials, the processes leading to publication can be complex from choice and prioritization of analytic topics through to journal submission and revisions. As little literature exists on the publication process for multicenter trials, we describe the development, implementation, and effectiveness of such a process in a multicenter trial.
Methods: The Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial included a data coordinating center (DCC) and clinical centers that recruited and followed more than 1,000 patients. Publication guidelines were approved by the steering committee, and the publications committee monitored the publication process from selection of topics to publication.
Results: A total of 73 manuscripts were published in 23 peer-reviewed journals. When manuscripts were closely tracked, the median time for analyses and drafting of manuscripts was 8 months. The median time for data analyses was 5 months and the median time for manuscript drafting was 3 months. The median time for publications committee review, submission, and journal acceptance was 7 months, and the median time from analytic start to journal acceptance was 18 months.
Conclusions: Effective publication guidelines must be comprehensive, implemented early in a trial, and require active management by study investigators. Successful collaboration, such as in the HALT-C trial, can serve as a model for others involved in multidisciplinary and multicenter research programs.
C1 [Snow, Kristin K.; Bell, Margaret C.; Stoddard, Anne M.; Curto, Teresa M.] New England Res Inst, Watertown, MA 02472 USA.
[Snow, Kristin K.] New Hampshire Dept Hlth & Human Serv, Bur Publ Hlth Stat & Informat, Div Publ Hlth Serv, Concord, NH 03301 USA.
[Wright, Elizabeth C.] NIDDK, Off Director, NIH, Bethesda, MD 20892 USA.
[Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Curto, TM (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA.
EM tcurto@neriscience.com
FU National Institute of Diabetes and Digestive and Kidney Diseases
[N01-DK-9-2326, N01-DK-9-2324, N01-DK- 9-2319, N01-DK-9-2327,
N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2325, N01-DK-9-2323,
N01-DK-9-2322, N01-DK-9-2318, N01-DK-9-2328]; Hoffmann-La Roche, through
a cooperative research and development agreement; National Institutes of
Health
FX We acknowledge the HALT-C Trial group for providing data for this
publication. The HALT-C trial was supported by National Institute of
Diabetes and Digestive and Kidney Diseases contracts N01-DK-9-2326,
N01-DK-9-2324, contract N01-DK- 9-2319, N01-DK-9-2327, N01-DK-9-2320,
N01-DK-9-2321, N01-DK-9-2325, N01-DK-9-2323, N01-DK-9-2322,
N01-DK-9-2318, and N01-DK-9-2328. Additional financial support was
provided by Hoffmann-La Roche, through a cooperative research and
development agreement with the National Institutes of Health.
NR 85
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Z9 0
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6215
J9 TRIALS
JI Trials
PD MAY 7
PY 2014
VL 15
AR 159
DI 10.1186/1745-6215-15-159
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AI3ZV
UT WOS:000336805600001
PM 24886378
ER
PT J
AU Knott, M
Best, RB
AF Knott, Michael
Best, Robert B.
TI Discriminating binding mechanisms of an intrinsically disordered protein
via a multi-state coarse-grained model
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID SINGLE-MOLECULE SPECTROSCOPY; CONFORMATIONAL SELECTION; INDUCED-FIT;
ADENYLATE KINASE; TRANSITION-STATE; COUPLED BINDING; TRANSFER-RNA;
DOMAIN; DYNAMICS; RECOGNITION
AB Many proteins undergo a conformational transition upon binding to their cognate binding partner, with intrinsically disordered proteins (IDPs) providing an extreme example in which a folding transition occurs. However, it is often not clear whether this occurs via an "induced fit" or "conformational selection" mechanism, or via some intermediate scenario. In the first case, transient encounters with the binding partner favour transitions to the bound structure before the two proteins dissociate, while in the second the bound structure must be selected from a subset of unbound structures which are in the correct state for binding, because transient encounters of the incorrect conformation with the binding partner are most likely to result in dissociation. A particularly interesting situation involves those intrinsically disordered proteins which can bind to different binding partners in different conformations. We have devised a multi-state coarse-grained simulation model which is able to capture the binding of IDPs in alternate conformations, and by applying it to the binding of nuclear coactivator binding domain (NCBD) to either ACTR or IRF-3 we are able to determine the binding mechanism. By all measures, the binding of NCBD to either binding partner appears to occur via an induced fit mechanism. Nonetheless, we also show how a scenario closer to conformational selection could arise by choosing an alternative non-binding structure for NCBD. (C) 2014 AIP Publishing LLC.
C1 [Knott, Michael; Best, Robert B.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
[Best, Robert B.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Knott, M (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England.
EM robertbe@helix.nih.gov
RI Best, Robert/H-7588-2016
OI Best, Robert/0000-0002-7893-3543
FU BBSRC [BB/H006885/1]; Royal Society University Research Fellowship at
Cambridge; National Institute of Diabetes and Digestive and Kidney
Diseases of the National Institutes of Health
FX We thank Chris Baker and David de Sancho for many helpful suggestions
and comments on the manuscript. M. K. and R. B. B. were supported by
BBSRC Award No. BB/H006885/1. R. B. B. was supported by a Royal Society
University Research Fellowship while at Cambridge and by the Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases of the National Institutes of Health.
NR 88
TC 12
Z9 12
U1 2
U2 20
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0021-9606
EI 1089-7690
J9 J CHEM PHYS
JI J. Chem. Phys.
PD MAY 7
PY 2014
VL 140
IS 17
AR 175102
DI 10.1063/1.4873710
PG 10
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA AH3TI
UT WOS:000336048000050
PM 24811666
ER
PT J
AU Justinova, Z
Redhi, GH
Goldberg, SR
Ferre, S
AF Justinova, Zuzana
Redhi, Godfrey H.
Goldberg, Steven R.
Ferre, Sergi
TI Differential Effects of Presynaptic versus Postsynaptic Adenosine A(2A)
Receptor Blockade on Delta(9)-Tetrahydrocannabinol (THC)
Self-Administration in Squirrel Monkeys
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE adenosine A2A receptor; cannabinoids; drug abuse; monkey;
self-administration; THC
ID VENTRAL TEGMENTAL AREA; NICOTINIC RECEPTORS; KYNURENIC ACID; DOPAMINE;
ABUSE; RAT; NEUROTRANSMISSION; ACCUMBENS; BEHAVIOR; RELEASE
AB Different doses of an adenosine A(2A) receptor antagonist MSX-3 [3,7-dihydro-8-[(1E)-2-(3-ethoxyphenyl) ethenyl]-7 methyl-3-[3( phosphooxy) propyl-1-(2 propynil)-1H-purine-2,6-dione] were found previously to either decrease or increase self-administration of cannabinoids delta-9-tetrahydrocannabinol (THC) or anandamide in squirrel monkeys. It was hypothesized that the decrease observed with a relatively low dose of MSX-3 was related to blockade of striatal presynaptic A(2A) receptors that modulate glutamatergic neurotransmission, whereas the increase observed with a higher dose was related to blockade of postsynapticA(2A) receptors localized in striatopallidal neurons. This hypothesis was confirmed in the present study by testing the effects of the preferential presynaptic and postsynaptic A(2A) receptor antagonists SCH-442416 [2-(2-furanyl)-7-[3-(4-methoxyphenyl) propyl]-7H-pyrazolo[4,3-e][1,2,4] triazolo[1,5-c] pyrimidin-5-amine] and KW-6002 [(E)-1, 3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione], respectively, in squirrel monkeys trained to intravenously selfadminister THC. SCH-442416 produced a significant shift to the right of the THC self-administration dose-response curves, consistent with antagonism of the reinforcing effects of THC. Conversely, KW-6002 produced a significant shift to the left, consistent with potentiation of the reinforcing effects of THC. These results show that selectively blocking presynaptic A(2A) receptors could provide a new pharmacological approach to the treatment of marijuana dependence and underscore corticostriatal glutamatergic neurotransmission as a possible main mechanism involved in the rewarding effects of THC.
C1 [Justinova, Zuzana; Redhi, Godfrey H.; Goldberg, Steven R.] Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Ferre, Sergi] Natl Inst Drug Abuse, Integrat Neurobiol Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
RP Ferre, S (reprint author), Natl Inst Drug Abuse, Integrat Neurobiol Sect, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM sferre@mail.nih.gov
RI Ferre, Sergi/K-6115-2014; Justinova, Zuzana/A-9109-2011
OI Ferre, Sergi/0000-0002-1747-1779; Justinova, Zuzana/0000-0001-5793-7484
FU Intramural Research Program of the National Institute on Drug Abuse
(NIDA), National Institutes of Health, Department of Health and Human
Services
FX This work was supported by the Intramural Research Program of the
National Institute on Drug Abuse (NIDA), National Institutes of Health,
Department of Health and Human Services. THC was provided by the NIDA
Drug Supply Program. We thank Dr. Leigh V. Panlilio for his excellent
assistance with statistical analysis.
NR 21
TC 10
Z9 10
U1 1
U2 14
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAY 7
PY 2014
VL 34
IS 19
BP 6480
EP 6484
DI 10.1523/JNEUROSCI.5073-13.2014
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA AH8IF
UT WOS:000336380500007
PM 24806674
ER
PT J
AU Ren, M
Cao, V
Ye, YZ
Manji, HK
Wang, KH
AF Ren, Ming
Cao, Vania
Ye, Yizhou
Manji, Husseini K.
Wang, Kuan Hong
TI Arc Regulates Experience-Dependent Persistent Firing Patterns in Frontal
Cortex
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE Arc/Arg3.1; experience dependent; frontal cortex; NMDA receptor;
persistent activity
ID IMMEDIATE-EARLY GENE; PREFRONTAL CORTEX; IN-VIVO; RECEPTOR TRAFFICKING;
SYNAPTIC PLASTICITY; NEURAL CIRCUITS; NMDA RECEPTORS; ACTIVE NEURONS;
MEMORY; ARC/ARG3.1
AB The brain encodes information about past experience in specific populations of neurons that communicate with one another by firing action potentials. Studies of experience-dependent neural plasticity have largely focused on individual synaptic changes in response to neuronal input. Indicative of the neuronal output transmitted to downstream neurons, persistent firing patterns are affected by prior experience in selective neuronal populations. However, little is known about the molecular and cellular mechanisms by which experience-related persistent firing patterns are regulated in specific neuronal populations. Using frontal cortical slices prepared from transgenic mice carrying a fluorescent reporter of Arc gene expression, this study investigates how behavioral experience and the activity-regulated Arc gene affect patterns of neuronal firing. We found that motor training increases Arc expression in subsets of excitatory neurons. Those neurons exhibit persistent firing in contrast to Arc-negative neurons from the same mice or neurons from the untrained mice. Furthermore, in mice carrying genetic deletion of Arc, the frontal cortical circuitry is still in place to initiate experience-dependent gene expression, but the level of persistent firing thereafter is diminished. Finally, our results showed that the emergence of persistent activity is associated with Arc-dependent changes in the function of NMDA-type glutamate receptors, rather than changes in AMPA-type receptors or membrane excitability. Our findings therefore reveal an Arc-dependent molecular pathway by which geneexperience interaction regulates the emergence of persistent firing patterns in specific neuronal populations.
C1 [Ren, Ming; Cao, Vania; Ye, Yizhou; Wang, Kuan Hong] NIMH, Unit Neural Circuits & Adapt Behav, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Manji, Husseini K.] NIMH, Lab Mol Pathophysiol & Expt Therapeut, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
RP Wang, KH (reprint author), NIMH, Unit Neural Circuits & Adapt Behav, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
EM wkuan@mail.nih.gov
RI Wang, Kuan Hong/J-1150-2016
OI Wang, Kuan Hong/0000-0002-2249-5417
FU National Institute of Mental Health (NIMH) Intramural Research Program;
National Alliance for Research on Schizophrenia and Depression Young
Investigator Award; NIMH Division of Intramural Research Programs; Genes
Cognition and Psychosis Program
FX This work was supported by the National Institute of Mental Health
(NIMH) Intramural Research Program (M.R., V.C., Y.Y., H.K.M., K.H.W.)
and a National Alliance for Research on Schizophrenia and Depression
Young Investigator Award (M.R.). We thank T.R. Insel, D.R. Weinberger,
P.S. Wang, M.E. Greenberg, and W.G. Chen for their critical reading of
the manuscript and helpful discussions, and E.J. Sherman for technical
editing. K.H.W. acknowledges the support of the NIMH Division of
Intramural Research Programs and the Genes Cognition and Psychosis
Program.
NR 53
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Z9 12
U1 1
U2 13
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAY 7
PY 2014
VL 34
IS 19
BP 6583
EP 6595
DI 10.1523/JNEUROSCI.0167-14.2014
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA AH8IF
UT WOS:000336380500016
PM 24806683
ER
PT J
AU Lin, HH
Yin, XY
Lunetta, KL
Dupuis, J
McManus, DD
Lubitz, SA
Magnani, JW
Joehanes, R
Munson, PJ
Larson, MG
Levy, D
Ellinor, PT
Benjamin, EJ
AF Lin, Honghuang
Yin, Xiaoyan
Lunetta, Kathryn L.
Dupuis, Josee
McManus, David D.
Lubitz, Steven A.
Magnani, Jared W.
Joehanes, Roby
Munson, Peter J.
Larson, Martin G.
Levy, Daniel
Ellinor, Patrick T.
Benjamin, Emelia J.
TI Whole Blood Gene Expression and Atrial Fibrillation: The Framingham
Heart Study
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; C-REACTIVE PROTEIN; FAMILIAL AGGREGATION;
RISK-FACTOR; DISEASE; HYPOXIA; PREVALENCE; NETWORKS; HYPERTENSION;
POLYMORPHISM
AB Background: Atrial fibrillation (AF) involves substantial electrophysiological, structural and contractile remodeling. We hypothesize that characterizing gene expression might uncover important pathways related to AF.
Methods and Results: We performed genome-wide whole blood transcriptomic profiling (Affymetrix Human Exon 1.0 ST Array) of 2446 participants (mean age 66 +/- 9 years, 55% women) from the Offspring cohort of Framingham Heart Study. The study included 177 participants with prevalent AF, 143 with incident AF during up to 7 years follow up, and 2126 participants with no AF. We identified seven genes statistically significantly up-regulated with prevalent AF. The most significant gene, PBX1 (P=2.8x10(-7)), plays an important role in cardiovascular development. We integrated differential gene expression with gene-gene interaction information to identify several signaling pathways possibly involved in AF-related transcriptional regulation. We did not detect any statistically significant transcriptomic associations with incident AF.
Conclusion: We examined associations of gene expression with AF in a large community-based cohort. Our study revealed several genes and signaling pathways that are potentially involved in AF-related transcriptional regulation.
C1 [Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02215 USA.
[Lin, Honghuang; Yin, Xiaoyan; Lunetta, Kathryn L.; Dupuis, Josee; McManus, David D.; Joehanes, Roby; Munson, Peter J.; Larson, Martin G.; Levy, Daniel; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Lin, Honghuang; Yin, Xiaoyan; Lunetta, Kathryn L.; Dupuis, Josee; McManus, David D.; Joehanes, Roby; Munson, Peter J.; Larson, Martin G.; Levy, Daniel; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Lunetta, Kathryn L.; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Worcester, MA USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Div Epidemiol, Dept Quantitat Hlth Sci, Worcester, MA USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[Joehanes, Roby; Munson, Peter J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Joehanes, Roby; Munson, Peter J.; Levy, Daniel] NHLBI, Populat Sci Branch, Div Intramural Res, Bethesda, MD 20892 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Ellinor, Patrick T.] Harvard Univ, Sch Med, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Lin, HH (reprint author), Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02215 USA.
EM hhlin@bu.edu
OI Lin, Honghuang/0000-0003-3043-3942; Benjamin, Emelia/0000-0003-4076-2336
FU NIH [R01HL092577, R01HL104156, K24HL105780, KL2RR031981]; American Heart
Association Awards [13EIA14220013, 09FTF2190028]; Intramural Research
Program of National Heart, Lung, and Blood Institute (Levy); National
Heart, Lung, and Blood Institute [N01-HC-25195, 6R01-NS 17950]
FX This work is supported by NIH grants R01HL092577 (Ellinor and Benjamin),
R01HL104156, K24HL105780 (Ellinor), KL2RR031981 (McManus), American
Heart Association Awards 13EIA14220013 (Ellinor) and 09FTF2190028
(Magnani), and the Intramural Research Program of National Heart, Lung,
and Blood Institute (Levy). The Framingham Heart Study is supported by
National Heart, Lung, and Blood Institute contract N01-HC-25195 and
6R01-NS 17950. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 54
TC 5
Z9 6
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 7
PY 2014
VL 9
IS 5
AR e96794
DI 10.1371/journal.pone.0096794
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG9HB
UT WOS:000335728900097
PM 24805109
ER
PT J
AU Szu, SC
Lin, KFY
Hunt, S
Chu, C
Thinh, D
AF Szu, Shousun C.
Lin, Kimi F. -Y.
Hunt, Steven
Chu, Chiayung
Nguyen Duc Thinh
TI Phase I clinical trial of O-acetylated pectin conjugate, a plant
polysaccharide based typhoid vaccine
SO VACCINE
LA English
DT Article
DE Phase I pectin-based; Typhoid conjugate vaccine; Safety immunogenicity;
Plant polysaccharide; Semi-synthetic
ID VI-CAPSULAR POLYSACCHARIDE; 2-TO 4-YEAR-OLD CHILDREN; IGG ANTI-VI;
IMMUNOLOGICAL-PROPERTIES; SALMONELLA-TYPHI; FEVER; ACID; DISEASES;
VIETNAM; ADULTS
AB Background: Typhoid fever remains an important cause of morbidity and mortality in the developing countries. Vi capsular polysaccharide conjugate vaccine demonstrated safety and efficacy in young children in high endemic regions. A novel typhoid conjugate vaccine based on plant polysaccharide pectin was studied in a phase I trial.
Methods: Fruit pectin, having the same carbohydrate backbone structure as Vi, was purified from citrus peel and used as the polysaccharide source to prepare a semi-synthetic typhoid conjugate vaccine. Pectin was chemically O-acetylated (OAcPec) to antigenically resemble Vi and conjugated to carrier protein rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. 25 healthy volunteers, 18-45 years old, were injected once with OAcPec-rEPA. Safety and IgG antibodies reactive with Vi and pectin were analyzed.
Results: No vaccine associated serious adverse reaction was reported. Six weeks after the injection of OAcPec-rEPA, 64% of the volunteers elicited >4-fold rise of anti-Vi IgG. At 26 weeks the level declined, but the difference between the levels at 6 and 26 weeks are not statistically significant. There is a direct correlation between the level of anti-Vi IgG before and after the injection (R-2 = 0.96). The anti-Vi IgG can be absorbed by Vi, but not by pectin. There was no corresponding increase of anti-pectin after the injection, indicating the antibody response to OAcPec-rEPA was specific to Vi. There is no Vi-rEPA data in US adults for comparison of immune responses. The OAcPec-rEPA elicited significantly less IgG anti-Vi in US adults than those by Vi-rEPA in Vietnamese adults.
Conclusion: The O-acetylated pectin conjugate, a plant based typhoid vaccine, is safe and immunogenic in adult volunteers. Published by Elsevier Ltd.
C1 [Szu, Shousun C.; Lin, Kimi F. -Y.; Hunt, Steven; Chu, Chiayung] NICHHD, NIH, Bethesda, MD 20892 USA.
[Nguyen Duc Thinh] Dept Agr, Div Food Safety, Ho Chi Ming City, Vietnam.
RP Szu, SC (reprint author), NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Szus@mail.nih.gov
OI Hunt, Steven/0000-0003-3533-0627
FU Intramural Research; Eunice Kennedy Shriver National Institute of Child
Health & Human Development; National Institutes of Health
FX The project was supported by the Intramural Research, Eunice Kennedy
Shriver National Institute of Child Health & Human Development, National
Institutes of Health. The authors thank The Pharmacy Development
Section, Clinical Center, NIH for preparation of the final container,
Ms. Dolores Bryla for administrative assistance in enrollment, Dr.
Jianping Li for technical assistance in analysis, Dr. Zuzana Kossaczka
for pre-clinical development, and Drs. John B. Robbins for helpful
discussions.
NR 36
TC 5
Z9 5
U1 1
U2 10
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD MAY 7
PY 2014
VL 32
IS 22
BP 2618
EP 2622
DI 10.1016/j.vaccine.2014.03.023
PG 5
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AH4RI
UT WOS:000336115300016
PM 24657719
ER
PT J
AU DeBuysscher, BL
Scott, D
Marzi, A
Prescott, J
Feldmann, H
AF DeBuysscher, Blair L.
Scott, Dana
Marzi, Andrea
Prescott, Joseph
Feldmann, Heinz
TI Single-dose live-attenuated Nipah virus vaccines confer complete
protection by eliciting antibodies directed against surface
glycoproteins
SO VACCINE
LA English
DT Article
DE Nipah virus; Vaccines; Recombinant vesicular stomatitis virus; Humoral
immune responses; Neutralizing antibodies; Serum transfer
ID VESICULAR STOMATITIS-VIRUS; LONG-TERM PROTECTION; T-CELL RESPONSES;
SUBUNIT VACCINE; HAMSTER MODEL; NEUTRALIZING ANTIBODIES; HENIPAVIRUS
INFECTION; CLINICAL-FEATURES; VIRAL ENTRY; IN-VIVO
AB Background: Nipah virus (NiV), a zoonotic pathogen causing severe respiratory illness and encephalitis in humans, emerged in Malaysia in 1998 with subsequent outbreaks on an almost annual basis since 2001 in parts of the Indian subcontinent. The high case fatality rate, human-to-human transmission, wide-ranging reservoir distribution and lack of licensed intervention options are making NiV a serious regional and potential global public health problem. The objective of this study was to develop a fast-acting, single-dose NiV vaccine that could be implemented in a ring vaccination approach during outbreaks.
Methods: In this study we have designed new live-attenuated vaccine vectors based on recombinant vesicular stomatitis viruses (rVSV) expressing NiV glycoproteins (G or F) or nucleoprotein (N) and evaluated their protective efficacy in Syrian hamsters, an established NiV animal disease model. We further characterized the humoral immune response to vaccination in hamsters using ELISA and neutralization assays and performed serum transfer studies.
Results: Vaccination of Syrian hamsters with a single dose of the rVSV vaccine vectors resulted in strong humoral immune responses with neutralizing activities found only in those animals vaccinated with rVSV expressing NiV G or F proteins. Vaccinated animals with neutralizing antibody responses were completely protected from lethal NiV disease, whereas animals vaccinated with rVSV expressing NiV N showed only partial protection. Protection of NiV G or F vaccinated animals was conferred by antibodies, most likely the neutralizing fraction, as demonstrated by serum transfer studies. Protection of N-vaccinated hamsters was not antibody-dependent indicating a role of adaptive cellular responses for protection.
Conclusions: The rVSV vectors expressing Nipah virus G or F are prime candidates for new 'emergency vaccines' to be utilized for NiV outbreak management. Published by Elsevier Ltd.
C1 [DeBuysscher, Blair L.; Marzi, Andrea; Prescott, Joseph; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA.
[DeBuysscher, Blair L.] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA.
[Scott, Dana] NIAID, Rocky Mt Vet Branch, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
RP Feldmann, H (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA.
EM feldmannh@niaid.nih.gov
FU Division of Intramural Research (DIR); National Institutes of Allergy
and Infection Diseases (NIAID); National Institutes of Health (NIH)
FX This work was supported by the Division of Intramural Research (DIR),
National Institutes of Allergy and Infection Diseases (NIAID), National
Institutes of Health (NIH). The authors would like to thank Dan Long,
Rebecca Rosenke, and Tina Thomas (Rocky Mountain Veterinary Branch, DIR,
NIAID, NIH) for histopathology work, Elaine Haddock (DIR, NIAID, NIH)
for BSL4 technical assistance and Anita Mora (DIR, NIAID, NIH) for
graphics.
NR 52
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U1 1
U2 13
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD MAY 7
PY 2014
VL 32
IS 22
BP 2637
EP 2644
DI 10.1016/j.vaccine.2014.02.087
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AH4RI
UT WOS:000336115300019
PM 24631094
ER
PT J
AU Insel, TR
AF Insel, Thomas R.
TI Mental Disorders in Childhood Shifting the Focus From Behavioral
Symptoms to Neurodevelopmental Trajectories
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID PSYCHOSIS; BURDEN
C1 NIMH, NIH, Bethesda, MD 20892 USA.
RP Insel, TR (reprint author), NIMH, NIH, NIMH Room 8129,6001 Execut Blvd, Bethesda, MD 20892 USA.
EM insel@mail.nih.gov
NR 10
TC 26
Z9 26
U1 2
U2 9
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 7
PY 2014
VL 311
IS 17
BP 1727
EP 1728
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AG4IG
UT WOS:000335382300011
PM 24794359
ER
PT J
AU Batshaw, ML
Groft, SC
Krischer, JP
AF Batshaw, Mark L.
Groft, Stephen C.
Krischer, Jeffrey P.
TI Research Into Rare Diseases of Childhood
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID CHILDREN
C1 [Batshaw, Mark L.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Groft, Stephen C.] NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Krischer, Jeffrey P.] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA.
RP Batshaw, ML (reprint author), Childrens Natl Med Ctr, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM mbatshaw@childrensnational.org
NR 7
TC 10
Z9 11
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 7
PY 2014
VL 311
IS 17
BP 1729
EP 1730
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AG4IG
UT WOS:000335382300012
PM 24794360
ER
PT J
AU Bezerra, JA
Spino, C
Magee, JC
Shneider, BL
Rosenthal, P
Wang, KS
Erlichman, J
Haber, B
Hertel, PM
Karpen, SJ
Kerkar, N
Loomes, KM
Molleston, JP
Murray, KF
Romero, R
Schwarz, KB
Shepherd, R
Suchy, FJ
Turmelle, YP
Whitington, PF
Moore, J
Sherker, AH
Robuck, PR
Sokol, RJ
AF Bezerra, Jorge A.
Spino, Cathie
Magee, John C.
Shneider, Benjamin L.
Rosenthal, Philip
Wang, Kasper S.
Erlichman, Jessi
Haber, Barbara
Hertel, Paula M.
Karpen, Saul J.
Kerkar, Nanda
Loomes, Kathleen M.
Molleston, Jean P.
Murray, Karen F.
Romero, Rene
Schwarz, Kathleen B.
Shepherd, Ross
Suchy, Frederick J.
Turmelle, Yumirle P.
Whitington, Peter F.
Moore, Jeffrey
Sherker, Averell H.
Robuck, Patricia R.
Sokol, Ronald J.
CA ChiLDREN
TI Use of Corticosteroids After Hepatoportoenterostomy for Bile Drainage in
Infants With Biliary Atresia The START Randomized Clinical Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID ADJUVANT STEROID-THERAPY; KASAI PORTOENTEROSTOMY; OUTCOMES; MANAGEMENT;
IMPROVE; FLOW
AB IMPORTANCE Biliary atresia is the most common cause of end-stage liver disease in children. Controversy exists as to whether use of steroids after hepatoportoenterostomy improves clinical outcome.
OBJECTIVE To determine whether the addition of high-dose corticosteroids after hepatoportoenterostomy is superior to surgery alone in improving biliary drainage and survival with the native liver.
DESIGN, SETTING, AND PATIENTS The multicenter, double-blind Steroids in Biliary Atresia Randomized Trial (START) was conducted in 140 infants (mean age, 2.3 months) between September 2005 and February 2011 in the United States; follow-up ended in January 2013.
INTERVENTIONS Participants were randomized to receive intravenous methylprednisolone (4 mg/kg/d for 2 weeks) and oral prednisolone (2 mg/kg/d for 2 weeks) followed by a tapering protocol for 9 weeks (n = 70) or placebo (n = 70) initiated within 72 hours of hepatoportoenterostomy.
MAIN OUTCOMES AND MEASURES The primary end point (powered to detect a 25% absolute treatment difference) was the percentage of participants with a serum total bilirubin level of less than 1.5 mg/dL with his/her native liver at 6 months posthepatoportoenterostomy. Secondary outcomes included survival with native liver at 24 months of age and serious adverse events.
RESULTS The proportion of participants with improved bile drainage was not statistically significantly improved by steroids at 6 months posthepatoportoenterostomy (58.6%[41/70] of steroids group vs 48.6%[34/70] of placebo group; adjusted relative risk, 1.14 [95% CI, 0.83 to 1.57]; P =.43). The adjusted absolute risk difference was 8.7%(95% CI, -10.4% to 27.7%). Transplant-free survival was 58.7% in the steroids group vs 59.4% in the placebo group (adjusted hazard ratio, 1.0 [95% CI, 0.6 to 1.8]; P = .99) at 24 months of age. The percentage of participants with serious adverse events was 81.4%[57/70] of the steroids group and 80.0%[56/70] of the placebo group (P > .99); however, participants receiving steroids had an earlier time of onset of their first serious adverse event by 30 days posthepatoportoenterostomy (37.2%[95% CI, 26.9% to 50.0%] of steroids group vs 19.0% [95% CI, 11.5% to 30.4%] of placebo group; P = .008).
CONCLUSIONS AND RELEVANCE Among infants with biliary atresia who have undergone hepatoportoenterostomy, high-dose steroid therapy following surgery did not result in statistically significant treatment differences in bile drainage at 6 months, although a small clinical benefit could not be excluded. Steroid treatment was associated with earlier onset of serious adverse events in children with biliary atresia.
C1 [Bezerra, Jorge A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Spino, Cathie; Magee, John C.; Moore, Jeffrey] Univ Michigan, Ann Arbor, MI 48109 USA.
[Shneider, Benjamin L.] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA.
[Rosenthal, Philip] UCSF Benioff Childrens Hosp, San Francisco, CA USA.
[Wang, Kasper S.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Wang, Kasper S.] Univ So Calif, Los Angeles, CA USA.
[Erlichman, Jessi; Haber, Barbara; Loomes, Kathleen M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Hertel, Paula M.; Shepherd, Ross] Baylor Coll Med, Houston, TX 77030 USA.
[Hertel, Paula M.; Shepherd, Ross] Texas Childrens Hosp, Houston, TX 77030 USA.
[Karpen, Saul J.; Romero, Rene] Emory Univ, Sch Med, Atlanta, GA USA.
[Karpen, Saul J.; Romero, Rene] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Kerkar, Nanda] Mt Sinai Sch Med, New York, NY USA.
[Molleston, Jean P.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Molleston, Jean P.] Riley Hosp Children, Indianapolis, IN USA.
[Murray, Karen F.] Seattle Childrens Hosp, Seattle, WA USA.
[Schwarz, Kathleen B.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Suchy, Frederick J.; Sokol, Ronald J.] Univ Colorado, Sch Med, Aurora, CO USA.
[Suchy, Frederick J.; Sokol, Ronald J.] Childrens Hosp Colorado, Aurora, CO USA.
[Turmelle, Yumirle P.] Washington Univ, Sch Med, St Louis, MO USA.
[Whitington, Peter F.] Lurie Childrens Hosp Chicago, Chicago, IL USA.
[Sherker, Averell H.; Robuck, Patricia R.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Bezerra, JA (reprint author), Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
EM jorge.bezerra@cchmc.org
FU National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK)
[DK62503, TR000424, DK62436, TR000150, DK62497, TR000077, DK62453,
TR000154, DK62445, DK62481, TR000003, DK62466, TR000005, DK62500,
TR000004, DK62452, TR000448, DK62470, DK84575, TR000423, DK84585,
TR000454, DK84536, TR000007, DK62456]; NIDDK; GlaxoSmithKline; Axcan
Pharma US Inc
FX The following National Institute of Diabetes, Digestive and Kidney
Diseases (NIDDK) grants supported the START study: DK62503 and TR000424
(awarded to Johns Hopkins University School of Medicine), DK62436 and
TR000150 (Lurie Children's Hospital of Chicago), DK62497 and TR000077
(Cincinnati Children's Hospital Medical Center), DK62453 and TR000154
(University of Colorado School of Medicine and Children's Hospital
Colorado, Aurora), DK62445 (Mount Sinai School of Medicine), DK62481 and
TR000003 (Children's Hospital of Philadelphia), DK62466 and TR000005
(Children's Hospital of Pittsburgh of UPMC), DK62500 and TR000004 (UCSF
Benioff Children's Hospital), DK62452 and TR000448 (Washington
University School of Medicine and St Louis Children's Hospital), DK62470
(Baylor College of Medicine and Texas Children's Hospital, Houston),
DK84575 and TR000423 (Seattle Children's Hospital), DK84538 and TR000130
(Children's Hospital Los Angeles and University of Southern California),
DK84585, DK62470, and TR000454 (Emory University School of Medicine and
Children's Healthcare of Atlanta), DK84536 and TR000007 (Indiana
University School of Medicine and Riley Hospital for Children), and
DK62456 (University of Michigan data coordinating center). The following
companies provided support for the START study, each of which provided
formula or medications as part of a cooperative agreement with the
NIDDK: GlaxoSmithKline supplied ranitidine; Axcan Pharma US Inc,
fat-soluble vitamins and tocopherol polyethylene glycol succinate; Axcan
Pharma US Inc, ursodiol until 2009; and Mead Johnson Nutrition,
Pregestimil.
NR 27
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U1 2
U2 10
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 7
PY 2014
VL 311
IS 17
BP 1750
EP 1759
DI 10.1001/jama.2014.2623
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA AG4IG
UT WOS:000335382300020
PM 24794368
ER
PT J
AU Dabelea, D
Mayer-Davis, EJ
Saydah, S
Imperatore, G
Linder, B
Divers, J
Bell, R
Badaru, A
Talton, JW
Crume, T
Liese, AD
Merchant, AT
Lawrence, JM
Reynolds, K
Dolan, L
Liu, LL
Hamman, RF
AF Dabelea, Dana
Mayer-Davis, Elizabeth J.
Saydah, Sharon
Imperatore, Giuseppina
Linder, Barbara
Divers, Jasmin
Bell, Ronny
Badaru, Angela
Talton, Jennifer W.
Crume, Tessa
Liese, Angela D.
Merchant, Anwar T.
Lawrence, Jean M.
Reynolds, Kristi
Dolan, Lawrence
Liu, Lenna L.
Hamman, Richard F.
CA SEARCH Diabet Youth Study
TI Prevalence of Type 1 and Type 2 Diabetes Among Children and Adolescents
From 2001 to 2009
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID CHILDHOOD TYPE-1; UNITED-STATES; INCREASING INCIDENCE; RISK-FACTORS; US
YOUTH; MELLITUS; SEARCH; POPULATION; OBESITY; COHORT
AB IMPORTANCE Despite concern about an "epidemic," there are limited data on trends in prevalence of either type 1 or type 2 diabetes across US race and ethnic groups.
OBJECTIVE To estimate changes in the prevalence of type 1 and type 2 diabetes in US youth, by sex, age, and race/ethnicity between 2001 and 2009.
DESIGN, SETTING, AND PARTICIPANTS Case patients were ascertained in 4 geographic areas and 1 managed health care plan. The study population was determined by the 2001 and 2009 bridged-race intercensal population estimates for geographic sites and membership counts for the health plan.
MAIN OUTCOMES AND MEASURES Prevalence (per 1000) of physician-diagnosed type 1 diabetes in youth aged 0 through 19 years and type 2 diabetes in youth aged 10 through 19 years.
RESULTS In 2001, 4958 of 3.3 million youth were diagnosed with type 1 diabetes for a prevalence of 1.48 per 1000 (95% CI, 1.44-1.52). In 2009, 6666 of 3.4 million youth were diagnosed with type 1 diabetes for a prevalence of 1.93 per 1000 (95% CI, 1.88-1.97). In 2009, the highest prevalence of type 1 diabetes was 2.55 per 1000 among white youth (95% CI, 2.48-2.62) and the lowest was 0.35 per 1000 in American Indian youth (95% CI, 0.26-0.47) and type 1 diabetes increased between 2001 and 2009 in all sex, age, and race/ethnic subgroups except for those with the lowest prevalence (age 0-4 years and American Indians). Adjusted for completeness of ascertainment, there was a 21.1% (95% CI, 15.6%-27.0%) increase in type 1 diabetes over 8 years. In 2001, 588 of 1.7 million youth were diagnosed with type 2 diabetes for a prevalence of 0.34 per 1000 (95% CI, 0.31-0.37). In 2009, 819 of 1.8 million were diagnosed with type 2 diabetes for a prevalence of 0.46 per 1000 (95% CI, 0.43-0.49). In 2009, the prevalence of type 2 diabetes was 1.20 per 1000 among American Indian youth (95% CI, 0.96-1.51); 1.06 per 1000 among black youth (95% CI, 0.93-1.22); 0.79 per 1000 among Hispanic youth (95% CI, 0.70-0.88); and 0.17 per 1000 among white youth (95% CI, 0.15-0.20). Significant increases occurred between 2001 and 2009 in both sexes, all age-groups, and in white, Hispanic, and black youth, with no significant changes for Asian Pacific Islanders and American Indians. Adjusted for completeness of ascertainment, there was a 30.5%(95% CI, 17.3%-45.1%) overall increase in type 2 diabetes.
CONCLUSIONS AND RELEVANCE Between 2001 and 2009 in 5 areas of the United States, the prevalence of both type 1 and type 2 diabetes among children and adolescents increased. Further studies are required to determine the causes of these increases.
C1 [Dabelea, Dana; Crume, Tessa; Hamman, Richard F.] Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO 80045 USA.
[Mayer-Davis, Elizabeth J.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[Saydah, Sharon; Imperatore, Giuseppina] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA.
[Linder, Barbara] NIDDK, Childhood Diabet Res Div Diabet Endocrinol & Meta, Bethesda, MD 20892 USA.
[Divers, Jasmin; Talton, Jennifer W.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Bell, Ronny] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Badaru, Angela] Childrens Hosp & Reg Med Ctr, Dept Pediat Endocrinol & Diabet, Seattle, WA USA.
[Liese, Angela D.; Merchant, Anwar T.] Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC USA.
[Lawrence, Jean M.; Reynolds, Kristi] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA.
[Dolan, Lawrence] Childrens Hosp Med Ctr, Dept Endocrinol, Cincinnati, OH USA.
[Liu, Lenna L.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
[Liu, Lenna L.] Seattle Childrens Hosp, Seattle, WA USA.
RP Dabelea, D (reprint author), Colorado Sch Publ Hlth, Dept Epidemiol, 13001 East 17th Pl,Campus Box B-119, Aurora, CO 80045 USA.
EM dana.dabelea@ucdenver.edu
FU CDC [PA00097, DP-05-069, DP-10-001]; National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK); NIDDK; National Institutes of
Health (NIH) National Center for Research Resources [UL1RR029882]; NIH
[UL1 TR00423]; Clinical and Translational Research Center [UL1
TR000154]; Diabetes and Endocrinology Research Center, NIH [P30
DK57516]; National Center for Research Resources [8 UL1 TR000077];
National Center for Advancing Translational Sciences, NIH; Children with
Medical Handicaps program; [U48/CCU919219]; [U01 DP000246];
[U18DP002714]; [U48/CCU819241-3]; [U01 DP000247]; [U18DP000247-06A1];
[U48/CCU519239]; [U01 DP000248]; [1U18DP002709]; [U48/CCU419249];
[U01 DP000254]; [U18DP002708-01]; [U58/CCU019235-4]; [U01 DP000244];
[U18DP002710-01]; [U01 DP000250]; [200-2010-35171]
FX SEARCH for Diabetes in Youth is funded by grants PA00097, DP-05-069, and
DP-10-001 from the CDC and by the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK). Additional funding was provided
to the CDC for these cooperative agreements by the NIDDK. The site
contracts grants are U48/CCU919219, U01 DP000246, and U18DP002714 to
Kaiser Permanente Southern California; U48/CCU819241-3, U01 DP000247,
and U18DP000247-06A1 to the University of Colorado Denver;
U48/CCU519239, U01 DP000248, and 1U18DP002709 to the Children's Hospital
Medical Center, Cincinnati, Ohio; U48/CCU419249, U01 DP000254, and
U18DP002708-01 to the University of North Carolina at Chapel Hill;
U58/CCU019235-4, U01 DP000244, and U18DP002710-01 to the University of
Washington School of Medicine; U48/CCU919219, U01 DP000250, and
200-2010-35171 to the Wake Forest University School of Medicine. This
project was also support by grants UL1RR029882 from the National
Institutes of Health (NIH) National Center for Research Resources to the
South Carolina Clinical & Translational Research [SCTR] Institute, at
the Medical University of South Carolina; UL1 TR00423 from the NIH
Clinical and Translational Science Award to the Seattle Children's
Hospital of the University of Washington; UL1 TR000154 from the Clinical
and Translational Research Center to the University of Colorado
Pediatric Clinical; P30 DK57516 from the Diabetes and Endocrinology
Research Center, NIH, to the Barbara Davis Center at the University of
Colorado at Denver; 8 UL1 TR000077 from the National Center for Research
Resources and the National Center for Advancing Translational Sciences,
NIH; and the Children with Medical Handicaps program managed by the Ohio
Department of Health.
NR 43
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U1 5
U2 63
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 7
PY 2014
VL 311
IS 17
BP 1778
EP 1786
DI 10.1001/jama.2014.3201
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AG4IG
UT WOS:000335382300023
PM 24794371
ER
PT J
AU Yanovski, SZ
Yanovski, JA
AF Yanovski, Susan Z.
Yanovski, Jack A.
TI Drugs for the Treatment of Obesity Reply
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD 20892 USA.
[Yanovski, Jack A.] NICHHD, Sect Growth & Obes, Bethesda, MD 20892 USA.
RP Yanovski, SZ (reprint author), NIDDK, 6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM sy29f@nih.gov
OI Yanovski, Jack/0000-0001-8542-1637
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 7
PY 2014
VL 311
IS 17
BP 1807
EP 1807
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA AG4IG
UT WOS:000335382300030
PM 24794379
ER
PT J
AU Tunnicliffe, EM
Scott, AD
Ferreira, P
Ariga, R
McGill, LA
Nielles-Vallespin, S
Neubauer, S
Pennell, DJ
Robson, MD
Firmin, DN
AF Tunnicliffe, Elizabeth M.
Scott, Andrew D.
Ferreira, Pedro
Ariga, Rina
McGill, Laura-Ann
Nielles-Vallespin, Sonia
Neubauer, Stefan
Pennell, Dudley J.
Robson, Matthew D.
Firmin, David N.
TI Intercentre reproducibility of cardiac apparent diffusion coefficient
and fractional anisotropy in healthy volunteers
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE Cardiovascular magnetic resonance; Cardiac diffusion tensor imaging;
Cardiac diffusion weighted imaging
ID IN-VIVO; MAGNETIC-RESONANCE; FIBER ARCHITECTURE; TENSOR MRI; SPIN
ECHOES; HUMAN HEART; MOTION; NOISE; INFARCTION; WATER
AB Background: Diffusion tensor cardiac magnetic resonance (DT-CMR) enables probing of the microarchitecture of the myocardium, but the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) reported in healthy volunteers have been inconsistent. The aim of this study was to validate a stimulated-echo diffusion sequence using phantoms, and to assess the intercentre reproducibility of in-vivo diffusion measures using the sequence.
Methods and results: A stimulated-echo, cardiac-gated DT-CMR sequence with a reduced-field-of-view, single-shot EPI readout was used at two centres with 3 T MRI scanners. Four alkane phantoms with known diffusivities were scanned at a single centre using a stimulated echo sequence and a spin-echo Stejskal-Tanner diffusion sequence. The median (maximum, minimum) difference between the DT-CMR sequence and Stejskal-Tanner sequence was 0.01 (0.04, 0.0006) x 10(-3) mm(2)/s (2%), and between the DT-CMR sequence and literature diffusivities was 0.02 (0.05, 0.006) x 10-3 mm2/s (4%). The same ten healthy volunteers were scanned using the DT-CMR sequence at the two centres less than seven days apart. Average ADC and FA were calculated in a single mid-ventricular, short axis slice. Intercentre differences were tested for statistical significance at the p < 0.05 level using paired t-tests. The mean DC standard deviation for all subjects averaged over both centres was 1.10 +/- 0.06 x 10(-3) mm(2)/s in systole and 1.20 +/- 0.09 x 10(-3) mm(2)/s in diastole; FA was 0.41 +/- 0.04 in systole and 0.54 +/- 0.03 in diastole. With similarly-drawn regions-of-interest, systolic ADC (difference 0.05 x 10(-3) mm(2)/s), systolic FA (difference 0.003) and diastolic FA (difference 0.01) were not statistically significantly different between centres (p > 0.05), and only the diastolic ADC showed a statistically significant, but numerically small, difference of 0.07 x 10(-3) mm(2)/s (p = 0.047). The intercentre, intrasubject coefficients of variance were: systolic ADC 7%, FA 6%; diastolic ADC 7%, FA 3%.
Conclusions: This is the first study to demonstrate the accuracy of a stimulated-echo DT-CMR sequence in phantoms, and demonstrates the feasibility of obtaining reproducible ADC and FA in healthy volunteers at separate centres with well-matched sequences and processing.
C1 [Tunnicliffe, Elizabeth M.; Ariga, Rina; Neubauer, Stefan; Robson, Matthew D.] Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford Ctr Clin Magnet Resonance Res, Oxford, England.
[Scott, Andrew D.; Ferreira, Pedro; McGill, Laura-Ann; Nielles-Vallespin, Sonia; Pennell, Dudley J.; Firmin, David N.] Royal Brompton Hosp, NIHR Cardiovasc BRU, London SW3 6LY, England.
[Scott, Andrew D.; Ferreira, Pedro; McGill, Laura-Ann; Nielles-Vallespin, Sonia; Pennell, Dudley J.; Firmin, David N.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Nielles-Vallespin, Sonia] NHLBI, NIH, DHHS, Bethesda, MD 20892 USA.
RP Tunnicliffe, EM (reprint author), Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford Ctr Clin Magnet Resonance Res, Oxford, England.
EM elizabeth.tunnicliffe@cardiov.ox.ac.uk
FU National Institute for Health Research (NIHR) Oxford Biomedical Research
Centre (BRC) based at The Oxford University Hospitals Trust at the
University of Oxford; NIHR Cardiovascular Biomedical Research Unit at
Royal Brompton Hospital and Imperial College, London
FX This work was supported by the National Institute for Health Research
(NIHR) Oxford Biomedical Research Centre (BRC) based at The Oxford
University Hospitals Trust at the University of Oxford, and the NIHR
Cardiovascular Biomedical Research Unit at Royal Brompton Hospital and
Imperial College, London. The views expressed are those of the authors
and not necessarily those of the National Health Service, the NIHR or
the Department of Health. We thank Jacqueline Birks, NIHR Oxford BRC
Senior Medical Statistician at the Oxford Centre for Statistics in
Medicine, for helpful statistical discussion.
NR 25
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U1 1
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
EI 1532-429X
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD MAY 6
PY 2014
VL 16
AR 31
DI 10.1186/1532-429X-16-31
PG 12
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA AK7EM
UT WOS:000338589100001
PM 24886285
ER
PT J
AU McKinnon, JE
Mailliard, RB
Swindells, S
Wilkin, TJ
Borowski, L
Roper, JM
Bastow, B
Kearney, M
Wiegand, A
Mellors, JW
Rinaldo, CR
AF McKinnon, John E.
Mailliard, Robbie B.
Swindells, Susan
Wilkin, Timothy J.
Borowski, LuAnn
Roper, Jillian M.
Bastow, Barbara
Kearney, Mary
Wiegand, Ann
Mellors, John W.
Rinaldo, Charles R.
CA A5201 Study Team
TI Baseline Natural Killer and T Cell Populations Correlation with
Virologic Outcome after Regimen Simplification to Atazanavir/Ritonavir
Alone (ACTG 5201)
SO PLOS ONE
LA English
DT Article
ID LOPINAVIR-RITONAVIR MONOTHERAPY; MAINTENANCE ANTIRETROVIRAL THERAPY;
HIV-1 INFECTION; INDUCTION THERAPY; 2 NUCLEOSIDES; 50 COPIES/ML; NK
CELLS; TRIAL; SUPPRESSION; RECEPTORS
AB Objectives: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification.
Methods: Thirty-four participants with virologic suppression >= 48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3(+)CD56(+)CD16(+)) cells and cell-associated markers (HLA-DR, CD's 38/69/94/95/158/279).
Results: Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) > 50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL > 50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92-55.3). Simplification was associated with transient increases in naive and CD25(+) CD4(+) T-cells, and had no impact on IA levels.
Conclusions: Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring.
C1 [McKinnon, John E.] Henry Ford Hosp Syst, Detroit, MI 48202 USA.
[Mailliard, Robbie B.; Borowski, LuAnn; Mellors, John W.; Rinaldo, Charles R.] Univ Pittsburgh, Pittsburgh, PA USA.
[Swindells, Susan] Univ Nebraska Med Ctr, Omaha, NE USA.
[Wilkin, Timothy J.] Weill Cornell Med Coll, New York, NY USA.
[Roper, Jillian M.] George Washington Univ, Washington, DC USA.
[Bastow, Barbara] Social & Sci Syst Inc, Silver Spring, MD USA.
[Kearney, Mary; Wiegand, Ann] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
RP McKinnon, JE (reprint author), Henry Ford Hosp Syst, Detroit, MI 48202 USA.
EM jmckinn3@hfhs.org
OI Mailliard, Robbie/0000-0001-5501-503X
FU NIH grants from the National Center for Research Resources (NCRR)
[1KL2-RR024154-03, UL1 RR024153]; National Cancer Institute (SAIC)
[2sXS119]; NIH grant from the National Institute of Allergy and
Infectious Diseases [AI069450]; [1R21-AI084423-02]; [U01-AI35041];
[U01-AI068636]; [R37-AI41870]
FX Financial support for this manuscript was received for JEM from NIH
grants 1KL2-RR024154-03, UL1 RR024153 from the National Center for
Research Resources (NCRR) and 1R21-AI084423-02. RBM has received
financial support from U01-AI35041, U01-AI068636 and R37-AI41870. JWM
has received financial support from the National Cancer Institute (SAIC
contract 2sXS119). SS was supported by NIH grant AI069450 from the
National Institute of Allergy and Infectious Diseases. CRR has received
support from U01-AI35041 and U01-AI068636. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 41
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U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 6
PY 2014
VL 9
IS 5
AR e95524
DI 10.1371/journal.pone.0095524
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ9KS
UT WOS:000338029800030
PM 24802242
ER
PT J
AU Vasconcelos, AR
Yshii, LM
Viel, TA
Buck, HS
Mattson, MP
Scavone, C
Kawamoto, EM
AF Vasconcelos, Andrea R.
Yshii, Lidia M.
Viel, Tania A.
Buck, Hudson S.
Mattson, Mark P.
Scavone, Cristoforo
Kawamoto, Elisa M.
TI Intermittent fasting attenuates lipopolysaccharide-induced
neuroinflammation and memory impairment
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE Intermittent fasting; Inflammation; TLR4; Memory
ID FACTOR-KAPPA-B; TOLL-LIKE RECEPTORS; ADULT HIPPOCAMPAL NEUROGENESIS;
AMYLOID BETA-PEPTIDE; ALZHEIMERS-DISEASE; NITRIC-OXIDE; CALORIC
RESTRICTION; NEUROTROPHIC FACTOR; TNF-ALPHA; COGNITIVE IMPAIRMENT
AB Background: Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown.
Methods: Rats on IF for 30 days received 1 mg/ kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses.
Results: Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-B activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1 alpha, IL-1 beta and TNF-alpha levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1 beta, IFN-gamma, RANTES, TNF-alpha and IL-6 levels.
Conclusions: Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.
C1 [Vasconcelos, Andrea R.; Yshii, Lidia M.; Scavone, Cristoforo; Kawamoto, Elisa M.] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 Sao Paulo, Brazil.
[Viel, Tania A.] Univ Sao Paulo, Sch Arts Sci & Humanities, BR-03828080 Sao Paulo, Brazil.
[Buck, Hudson S.] Santa Casa Sao Paulo Med Sch, Dept Physiol Sci, BR-01221020 Sao Paulo, Brazil.
[Mattson, Mark P.; Kawamoto, Elisa M.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Scavone, C (reprint author), Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 Sao Paulo, Brazil.
EM criscavone@usp.br
RI Kawamoto, Elisa/E-3485-2012; Buck, Hudson/E-7664-2013; YSHII,
Lidia/I-6039-2013
OI Kawamoto, Elisa/0000-0001-8637-414X; Buck, Hudson/0000-0002-1867-2441;
Scavone, Cristoforo/0000-0002-1206-0882; YSHII,
Lidia/0000-0002-1988-6855
FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP
[2008/58865-9, 2009/11915-4, 2006/57729-9]; University of Sao Paulo
[2011.1.9333.1.3]; National Institute on Aging Intramural Research
Program
FX We thank L Lima de Sa and D Andreotti for the technical assistance. This
research was supported by grants from Fundacao de Amparo a Pesquisa do
Estado de Sao Paulo-FAPESP to CS (2008/58865-9; 2009/11915-4), and to
EMK (2006/57729-9). It is also partially funded by the University of Sao
Paulo (Grant # 2011.1.9333.1.3, NAPNA) and the National Institute on
Aging Intramural Research Program. ARV is a PhD student and research
fellow from FAPESP. LMY and EMK are supported by postdoctorate
fellowships from FAPESP. CS is research fellow from Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico-CNPq.
NR 92
TC 23
Z9 24
U1 7
U2 17
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD MAY 6
PY 2014
VL 11
AR 85
DI 10.1186/1742-2094-11-85
PG 14
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA AI9MC
UT WOS:000337255700001
PM 24886300
ER
PT J
AU Halsey, CHC
Gustafson, DL
Rose, BJ
Wolf-Ringwall, A
Burnett, RC
Duval, DL
Avery, AC
Thamm, DH
AF Halsey, Charles H. C.
Gustafson, Daniel L.
Rose, Barbara J.
Wolf-Ringwall, Amber
Burnett, Robert C.
Duval, Dawn L.
Avery, Anne C.
Thamm, Douglas H.
TI Development of an in vitro model of acquired resistance to toceranib
phosphate (Palladia (R)) in canine mast cell tumor
SO BMC VETERINARY RESEARCH
LA English
DT Article
DE Canine mast cell tumor; Toceranib; c-kit; Acquired resistance
ID TYROSINE KINASE INHIBITORS; GASTROINTESTINAL STROMAL TUMORS;
P-GLYCOPROTEIN; C-KIT; FACTOR-RECEPTOR; CANCER-THERAPY; IMATINIB
RESISTANCE; TANDEM DUPLICATIONS; LUNG-CANCER; MDR1 GENE
AB Background: Mast cell tumors (MCTs) are the most common skin tumors in dogs and exhibit variable biologic behavior. Mutations in the c-kit proto-oncogene are associated with the tumorigenesis of MCTs, resulting in growth factor-independent and constitutive phosphorylation of the KIT receptor tyrosine kinase (RTK). Toceranib (TOC) phosphate (Palladia (R)) is a KIT RTK inhibitor that has biological activity against MCTs. Despite these benefits, patients ultimately develop resistance to TOC. Therefore, there is a need to identify distinguishing clinical and molecular features of resistance in this population.
Results: The canine C2 mastocytoma cell line contains an activating mutation in c-kit. Three TOC-resistant C2 sublines (TR1, TR2, TR3) were established over seven months by growing cells in increasing concentrations of TOC. TOC inhibited KIT phosphorylation and cell proliferation in a dose-dependent manner in the treatment-naive, parental C2 line (IC50 < 10 nM). In contrast, the three sublines were resistant to growth inhibition by TOC (IC50 > 1,000 nM) and phosphorylation of the KIT receptor was less inhibited compared to the TOC-sensitive C2 cells. Interestingly, sensitivity to three structurally distinct KIT RTK inhibitors was variable among the sublines, and all 3 sublines retained sensitivity to the cytotoxic agents vinblastine and lomustine. Sequencing of c-kit revealed secondary mutations in the juxtamembrane and tyrosine kinase domains of the resistant sublines. These included point mutations in TR1 (Q574R, M835T), TR2 (K724R), and TR3 (K580R, R584G, A620S). Additionally, chronic TOC exposure resulted in c-kit mRNA and KIT protein overexpression in the TOC-resistant sublines compared to the parental line. C2, TR1, TR2, and TR3 cells demonstrated minimal P-glycoprotein (P-gp) activity and no functional P-gp.
Conclusions: This study demonstrates the development of an in vitro model of acquired resistance to targeted therapy in canine MCTs harboring a c-kit-activating mutation. This model may be used to investigate the molecular basis of and strategies to overcome TOC resistance.
C1 [Halsey, Charles H. C.; Gustafson, Daniel L.; Duval, Dawn L.; Avery, Anne C.; Thamm, Douglas H.] Colorado State Univ, Cell & Mol Biol Program, Ft Collins, CO 80523 USA.
[Halsey, Charles H. C.; Burnett, Robert C.; Avery, Anne C.] Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
[Gustafson, Daniel L.; Rose, Barbara J.; Wolf-Ringwall, Amber; Duval, Dawn L.; Thamm, Douglas H.] Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Clin Sci, Ft Collins, CO 80523 USA.
[Gustafson, Daniel L.; Thamm, Douglas H.] Univ Colorado, Ctr Comprehens Canc, Aurora, CO USA.
[Halsey, Charles H. C.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Halsey, CHC (reprint author), Colorado State Univ, Cell & Mol Biol Program, Ft Collins, CO 80523 USA.
EM charles.halsey@nih.gov
RI Thamm, Douglas/I-5976-2013
OI Thamm, Douglas/0000-0002-8914-7767
FU NIH [9T32OD10437-11]
FX The authors would like to acknowledge Drs. Amy Trettien, Gina Michels,
and Phyllis Malpas at Zoetis for their critical review of the
manuscript. The authors thank Ms. Janna Yoshimoto for her technical
assistance with flow cytometry. This work and CHCH were supported by NIH
9T32OD10437-11.
NR 51
TC 3
Z9 3
U1 1
U2 19
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1746-6148
J9 BMC VET RES
JI BMC Vet. Res.
PD MAY 6
PY 2014
VL 10
AR 105
DI 10.1186/1746-6148-10-105
PG 12
WC Veterinary Sciences
SC Veterinary Sciences
GA AI6LU
UT WOS:000336987000001
PM 24885200
ER
PT J
AU Westwood, AJ
Beiser, A
DeCarli, C
Harris, TB
Chen, TC
He, XM
Roubenoff, R
Pikula, A
Au, R
Braverman, LE
Wolf, PA
Vasan, RS
Seshadri, S
AF Westwood, Andrew J.
Beiser, Alexa
DeCarli, Charles
Harris, Tamara B.
Chen, Tai C.
He, Xue-mei
Roubenoff, Ronenn
Pikula, Aleksandra
Au, Rhoda
Braverman, Lewis E.
Wolf, Philip A.
Vasan, Ramachandran S.
Seshadri, Sudha
TI Insulin-like growth factor-1 and risk of Alzheimer dementia and brain
atrophy
SO NEUROLOGY
LA English
DT Article
ID FACTOR BINDING-PROTEINS; COGNITIVE FUNCTION; IGF-I; CEREBROSPINAL-FLUID;
TAU-PHOSPHORYLATION; VOLUME CHANGES; DISEASE; HORMONE; SERUM;
HIPPOCAMPUS
AB Objective:To relate serum insulin-like growth factor-1 (IGF-1) to risk of Alzheimer disease (AD) dementia and to brain volumes in a dementia-free community sample spanning middle and older ages.Methods:Dementia-free Framingham participants from generation 1 (n = 789, age 79 4 years, 64% women) and generation 2 (n = 2,793, age 61 9 years, 55% women; total = 3,582, age 65 +/- 11 years, 57% women) had serum IGF-1 measured in 1990-1994 and 1998-2001, respectively, and were followed prospectively for incident dementia and AD dementia. Brain MRI was obtained in stroke- and dementia-free survivors of both generations 1 (n = 186) and 2 (n = 1,867) during 1999-2005. Baseline IGF-1 was related to risk of incident dementia using Cox models and to total brain and hippocampal volumes using linear regression in multivariable models adjusted for age, sex, APOE epsilon 4, plasma homocysteine, waist-hip ratio, and physical activity.Results:Mean IGF-1 levels were 144 +/- 60 g/L in generation 1 and 114 +/- 37 g/L in generation 2. We observed 279 cases of incident dementia (230 AD dementia) over a mean follow-up of 7.4 +/- 3.1 years. Persons with IGF-1 in the lowest quartile had a 51% greater risk of AD dementia (hazard ratio = 1.51, 95% confidence interval: 1.14-2.00; p = 0.004). Among persons without dementia, higher IGF-1 levels were associated with greater total brain volumes (/SD increment in IGF-1 was 0.55 +/- 0.24, p = 0.025; and 0.26 +/- 0.06, p < 0.001, for generations 1 and 2, respectively).Conclusion:Lower serum levels of IGF-1 are associated with an increased risk of developing AD dementia and higher levels with greater brain volumes even among middle-aged community-dwelling participants free of stroke and dementia. Higher levels of IGF-1 may protect against subclinical and clinical neurodegeneration.
C1 [Westwood, Andrew J.; Beiser, Alexa; Pikula, Aleksandra; Au, Rhoda; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Preventat Med, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02215 USA.
[Beiser, Alexa] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Beiser, Alexa; Pikula, Aleksandra; Au, Rhoda; Wolf, Philip A.; Vasan, Ramachandran S.; Seshadri, Sudha] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[DeCarli, Charles] Univ Calif Davis, Sacramento, CA 95817 USA.
[Harris, Tamara B.] NIA, Bethesda, MD 20892 USA.
[Chen, Tai C.; He, Xue-mei; Braverman, Lewis E.] Boston Univ, Med Ctr, Sect Endocrinol Diabet & Nutr, Boston, MA 02215 USA.
[Roubenoff, Ronenn] Novartis Inst Biomed Res, Cambridge, MA USA.
RP Seshadri, S (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA.
EM suseshad@bu.edu
OI Seshadri, Sudha/0000-0001-6135-2622; Ramachandran,
Vasan/0000-0001-7357-5970; Beiser, Alexa/0000-0001-8551-7778
FU Framingham Heart Study's National Heart, Lung, and Blood Institute
(NHLBI) [N01-HC-25195]; NHLBI [R01 HL089590]; National Institute on
Aging [R01 AG16495, AG 033040, AG08122, AG033193, AG031287,
P30AG013846]; American Heart Association [11CRP4930020]; BU-CTSI NIH
[UL1-TR000157]
FX Supported by the Framingham Heart Study's National Heart, Lung, and
Blood Institute (NHLBI) contract (N01-HC-25195) and by grants from the
NHLBI (R01 HL089590), the National Institute on Aging (R01 AG16495, AG
033040, AG08122, AG033193, and AG031287, P30AG013846), and the American
Heart Association (11CRP4930020). Partial support from BU-CTSI NIH grant
UL1-TR000157 is also acknowledged.
NR 37
TC 28
Z9 30
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAY 6
PY 2014
VL 82
IS 18
BP 1613
EP 1619
DI 10.1212/WNL.0000000000000382
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH9XB
UT WOS:000336497400010
PM 24706014
ER
PT J
AU Grool, AM
Geerlings, MI
Sigurdsson, S
Eiriksdottir, G
Jonsson, PV
Garcia, ME
Siggeirsdottir, K
Harris, TB
Sigmundsson, T
Gudnason, V
Launer, LJ
AF Grool, Anne M.
Geerlings, Mirjam I.
Sigurdsson, Sigurdur
Eiriksdottir, Gudny
Jonsson, Palmi V.
Garcia, Melissa E.
Siggeirsdottir, Kristin
Harris, Tamara B.
Sigmundsson, Thordur
Gudnason, Vilmundur
Launer, Lenore J.
TI Structural MRI correlates of apathy symptoms in older persons without
dementia AGES-Reykjavik Study
SO NEUROLOGY
LA English
DT Article
ID WHITE-MATTER HYPERINTENSITIES; MILD COGNITIVE IMPAIRMENT; GERIATRIC
DEPRESSION SCALE; LATE-LIFE DEPRESSION; ALZHEIMERS-DISEASE;
NEUROPSYCHIATRIC SYMPTOMS; PROGRESSION; ATROPHY; VALIDATION; WITHDRAWAL
AB Objective:We aimed to investigate the relation between apathy symptoms and structural brain changes on MRI, including white matter lesions (WMLs) and atrophy, in a large cohort of older persons.Methods:Cross-sectional analyses are based on 4,354 persons without dementia (aged 76 5 years) participating in the population-based Age, Gene/Environment Susceptibility-Reykjavik Study. Apathy symptoms were assessed with 3 items from the 15-item Geriatric Depression Scale. Brain volumes and total WML volume were estimated on 1.5-tesla MRI using an automated segmentation program; regional WML load was calculated using a semiquantitative scale. Regression analyses were adjusted for age, sex, education, intracranial volume, vascular risk factors, physical activity, brain infarcts, depressive symptoms, antidepressants, and cognitive status.Results:Compared to those with <2 apathy symptoms, participants with 2 apathy symptoms (49% of the cohort) had significantly smaller gray matter volumes (mean adjusted difference -3.6 mL, 95% confidence interval [CI] -6.2 to -1.0), particularly in the frontal and temporal lobes; smaller white matter volumes (mean adjusted difference -1.9 mL, 95% CI -3.6 to -0.3), mainly in the parietal lobe; and smaller thalamus volumes. They were also more likely to have WMLs in the frontal lobe (adjusted odds ratio = 1.08, 95% CI 0.9-1.3). Excluding participants with a depression diagnosis did not change the associations.Conclusions:In this older population without dementia, apathy symptoms are associated with a more diffuse loss of both gray and white matter volumes, independent of depression.
C1 [Grool, Anne M.; Geerlings, Mirjam I.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Grool, Anne M.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands.
[Geerlings, Mirjam I.; Garcia, Melissa E.; Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Jonsson, Palmi V.; Siggeirsdottir, Kristin; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Siggeirsdottir, Kristin] Janus Rehabil, Reykjavik, Iceland.
[Sigmundsson, Thordur] Landspitali Univ Hosp, Reykjavik, Iceland.
[Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
RP Launer, LJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
EM LaunerL@nia.nih.gov
RI Gudnason, Vilmundur/K-6885-2015
OI Gudnason, Vilmundur/0000-0001-5696-0084
FU NIH [N01-AG-12100]; National Institute on Aging Intramural Research
Program; Hjartavernd (the Icelandic Heart Association); Althingi (the
Icelandic Parliament)
FX The AGES-Reykjavik Study is funded by NIH contract N01-AG-12100, the
National Institute on Aging Intramural Research Program, Hjartavernd
(the Icelandic Heart Association), and Althingi (the Icelandic
Parliament).
NR 39
TC 11
Z9 12
U1 4
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAY 6
PY 2014
VL 82
IS 18
BP 1628
EP 1635
DI 10.1212/WNL.0000000000000378
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH9XB
UT WOS:000336497400012
PM 24739783
ER
PT J
AU Roth, JA
Etzioni, R
Waters, TM
Pettinger, M
Rossouw, JE
Anderson, GL
Chlebowski, RT
Manson, JE
Hlatky, M
Johnson, KC
Ramsey, SD
AF Roth, Joshua A.
Etzioni, Ruth
Waters, Teresa M.
Pettinger, Mary
Rossouw, Jacques E.
Anderson, Garnet L.
Chlebowski, Rowan T.
Manson, JoAnn E.
Hlatky, Mark
Johnson, Karen C.
Ramsey, Scott D.
TI Economic Return From the Women's Health Initiative Estrogen Plus
Progestin Clinical Trial
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID POSTMENOPAUSAL HORMONE-THERAPY; REPLACEMENT THERAPY; SAMPLE INFORMATION;
COST-EFFECTIVENESS; UNITED-STATES; FOLLOW-UP; BENEFITS; DISEASE; RISKS;
PREVENTION
AB Background: The findings of the Women's Health Initiative (WHI) estrogen plus progestin (E+P) trial led to a substantial reduction in use of combined hormone therapy (cHT) among postmenopausal women in the United States. The economic effect of this shift has not been evaluated relative to the trial's $260 million cost (2012 U. S. dollars).
Objective: To estimate the economic return from the WHI E+P trial.
Design: Decision model to simulate health outcomes for a "WHI scenario" with observed cHT use and a "no-WHI scenario" with cHT use extrapolated from the pretrial period.
Data Sources: Primary analyses of WHI outcomes, peer-reviewed literature, and government sources.
Target Population: Postmenopausal women in the United States, aged 50 to 79 years, who did not have a hysterectomy.
Time Horizon: 2003 to 2012.
Perspective: Payer.
Intervention: Combined hormone therapy.
Outcome Measures: Disease incidence, expenditure, quality-adjusted life-years, and net economic return.
Results of Base-Case Analysis: The WHI scenario resulted in 4.3 million fewer cHT users, 126 000 fewer breast cancer cases, 76 000 fewer cardiovascular disease cases, 263 000 more fractures, 145 000 more quality-adjusted life-years, and expenditure savings of $35.2 billion. The corresponding net economic return of the trial was $37.1 billion ($140 per dollar invested in the trial) at a willingness-to-pay level of $100 000 per quality-adjusted life-year.
Results of Sensitivity Analysis: The 95% CI for the net economic return of the trial was $23.1 to $51.2 billion.
Limitation: No evaluation of indirect costs or outcomes beyond 2012.
Conclusion: The WHI E+P trial made high-value use of public funds with a substantial return on investment. These results can contribute to discussions about the role of public funding for large, prospective trials with high potential for public health effects.
C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA.
Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
NHLBI, NIH, Bethesda, MD 20824 USA.
Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA 02215 USA.
Stanford Univ, Stanford Med Sch, Stanford, CA 94305 USA.
RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave North,M3-B-232, Seattle, WA 98109 USA.
EM sramsey@fhcrc.org
OI Anderson, Garnet/0000-0001-5087-7837
FU National Heart, Lung, and Blood Institute
FX National Heart, Lung, and Blood Institute.
NR 42
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U1 0
U2 3
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAY 6
PY 2014
VL 160
IS 9
BP 594
EP U128
DI 10.7326/M13-2348
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA AI0GO
UT WOS:000336524400002
PM 24798522
ER
PT J
AU Lauer, MS
AF Lauer, Michael S.
TI Investing in Clinical Science: Make Way for (Not-So-Uncommon) Outliers
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN; ESTROGEN; DISEASE;
HEART
C1 [Lauer, Michael S.] NHLBI, Bethesda, MD 20892 USA.
RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA.
EM lauerm@nhlbi.nih.gov
NR 10
TC 1
Z9 1
U1 0
U2 2
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAY 6
PY 2014
VL 160
IS 9
BP 651
EP 652
DI 10.7326/M14-0655
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AI0GO
UT WOS:000336524400010
PM 24798528
ER
PT J
AU Padayatty, SJ
Levine, M
AF Padayatty, Sebastian J.
Levine, Mark
TI Vitamin and Mineral Supplements in the Primary Prevention of
Cardiovascular Disease and Cancer
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
ID RANDOMIZED-TRIAL
C1 [Padayatty, Sebastian J.; Levine, Mark] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Padayatty, SJ (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
RI Padayatty, Sebastian/A-8581-2012
OI Padayatty, Sebastian/0000-0001-8758-3170
NR 5
TC 1
Z9 1
U1 0
U2 2
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAY 6
PY 2014
VL 160
IS 9
BP 654
EP 654
DI 10.7326/L14-5009
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA AI0GO
UT WOS:000336524400011
PM 24798530
ER
PT J
AU Yun, J
Finkel, T
AF Yun, Jeanho
Finkel, Toren
TI Mitohormesis
SO CELL METABOLISM
LA English
DT Review
ID MITOCHONDRIAL CALCIUM UNIPORTER; HYPOXIA-INDUCED TRANSCRIPTION; ELEGANS
LIFE-SPAN; C. ELEGANS; OXIDATIVE STRESS; GENE-EXPRESSION;
CAENORHABDITIS-ELEGANS; SIGNAL-TRANSDUCTION; CELL-PROLIFERATION;
ELECTRON-TRANSPORT
AB For many years, mitochondria were viewed as semiautonomous organelles, required only for cellular energetics. This view has been largely supplanted by the concept that mitochondria are fully integrated into the cell and that mitochondrial stresses rapidly activate cytosolic signaling pathways that ultimately alter nuclear gene expression. Remarkably, this coordinated response to mild mitochondrial stress appears to leave the cell less susceptible to subsequent perturbations. This response, termed mitohormesis, is being rapidly dissected in many model organisms. A fuller understanding of mitohormesis promises to provide insight into our susceptibility for disease and potentially provide a unifying hypothesis for why we age.
C1 [Yun, Jeanho; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
[Yun, Jeanho] Dong A Univ, Dept Biochem, Pusan 602714, South Korea.
[Yun, Jeanho] Dong A Univ, Coll Med, Mitochondria Hub Regulat Ctr, Pusan 602714, South Korea.
RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM finkelt@nih.gov
FU NIH; Leducq Foundation
FX We are grateful for the assistance of I. I. Rovira. This work was
supported NIH Intramural Funds and the Leducq Foundation.
NR 90
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U1 7
U2 39
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD MAY 6
PY 2014
VL 19
IS 5
BP 757
EP 766
DI 10.1016/j.cmet.2014.01.011
PG 10
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA AG6XB
UT WOS:000335561200006
PM 24561260
ER
PT J
AU Ilango, A
Kesner, AJ
Broker, CJ
Wang, DV
Ikemoto, S
AF Ilango, Anton
Kesner, Andrew J.
Broker, Carl J.
Wang, Dong V.
Ikemoto, Satoshi
TI Phasic excitation of ventral tegmental dopamine neurons potentiates the
initiation of conditioned approach behavior: parametric and
reinforcement-schedule analyses
SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE
LA English
DT Article
DE phasic firing; optogenetics; conditioning; operant; reinforcement
schedule; approach motivation; reward
ID NUCLEUS-ACCUMBENS DOPAMINE; REWARD-SEEKING BEHAVIOR; OLFACTORY TUBERCLE;
NEURAL ACTIVITY; RATS; STRIATUM; RELEASE; CHANNELRHODOPSIN-2;
AMPHETAMINE; RECOMBINASE
AB Midbrain dopamine neurons are implicated in motivation and learning. However, it is unclear how phasic excitation of dopamine neurons, which is implicated in learning, is involved in motivation. Here we used a self-stimulation procedure to examine how mice seek for optogenetically-induced phasic excitation of dopamine neurons, with an emphasis on the temporal dimension. TH-Cre transgenic mice received adeno-associated viral vectors encoding channelrhodopsin-2 into the ventral tegmental area, resulting in selective expression of the opsin in dopamine neurons. These mice were trained to press on a lever for photo-pulse trains that phasically excited dopamine neurons. They learned to self-stimulate in a fast, constant manner, and rapidly reduced pressing during extinction. We first determined effective parameters of photo-pulse trains in self-stimulation. Lever-press rates changed as a function of the manipulation of pulse number, duration, intensity, and frequency. We then examined effects of interval and ratio schedules of reinforcement on photo-pulse train reinforcement, which was contrasted with food reinforcement. Reinforcement with food inhibited lever pressing for a few seconds, after which pressing was robustly regulated in a goal-directed manner. In contrast, phasic excitation of dopamine neurons robustly potentiated the initiation of lever pressing; however, this effect did not last more than 1 s and quickly diminished. Indeed, response rates markedly decreased when lever pressing was reinforced with inter-reinforcement interval schedules of 3 or 10 s or ratio schedules requiring multiple responses per reinforcement. Thus, phasic excitation of dopamine neurons briefly potentiates the initiation of approach behavior with apparent lack of long-term motivational regulation.
C1 [Ilango, Anton; Kesner, Andrew J.; Broker, Carl J.; Wang, Dong V.; Ikemoto, Satoshi] NIDA, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA.
RP Ikemoto, S (reprint author), NIDA, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM satoshi.ikemoto@nih.gov
OI Ikemoto, Satoshi/0000-0002-0732-7386; Kesner, Andrew/0000-0002-3902-1955
FU National Institute on Drug Abuse, National Institutes of Health
FX The present work was supported by the Intramural Research Program of
National Institute on Drug Abuse, National Institutes of Health. We
thank the NIDA-IRP Optogenetics and Transgenic Technology Core for
providing viral vectors.
NR 40
TC 8
Z9 8
U1 0
U2 7
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5153
J9 FRONT BEHAV NEUROSCI
JI Front. Behav. Neurosci.
PD MAY 6
PY 2014
VL 8
AR 155
DI 10.3389/fnbeh.2014.00155
PG 13
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA AH2LG
UT WOS:000335952300001
PM 24834037
ER
PT J
AU Beard, WA
Wilson, SH
AF Beard, William A.
Wilson, Samuel H.
TI Structure and Mechanism of DNA Polymerase beta
SO BIOCHEMISTRY
LA English
DT Article
ID BASE-EXCISION-REPAIR; TEMPLATING 8-OXOGUANINE LESION; STATE
KINETIC-ANALYSIS; INDUCED-FIT MECHANISM; ACTIVE-SITE; CRYSTAL-STRUCTURE;
NUCLEOTIDE INCORPORATION; CELLULAR-TRANSFORMATION; CATALYTIC MECHANISM;
ENZYME SPECIFICITY
AB DNA polymerase (pol) beta is a small eukaryotic DNA polymerase composed of two domains. Each domain contributes an enzymatic activity (DNA synthesis and deoxyribose phosphate lyase) during the repair of simple base lesions. These domains are termed the polymerase and lyase domains, respectively. Pol beta has been an excellent model enzyme for studying the nucleotidyl transferase reaction and substrate discrimination at a molecular level. In this review, recent crystallographic studies of pol beta in various liganded and conformational states during the insertion of right and wrong nucleotides as well as during the bypass of damaged DNA (apurinic sites and 8-oxoguanine) are described. Structures of these catalytic intermediates provide unexpected insights into mechanisms by which DNA polymerases enhance genome stability. These structures also provide an improved framework that permits computational studies to facilitate the interpretation of detailed kinetic analyses of this model enzyme.
C1 [Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr,POB 12233,MD F3-01, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU Intramural Research Program of the National Institute of Environmental
Health Sciences [Z01-ES050158, Z01-ES050159]; National Institutes of
Health [1U19CA105010]
FX This research was supported by Research Projects Z01-ES050158 and
Z01-ES050159 (S.H.W.) of the Intramural Research Program of the National
Institute of Environmental Health Sciences and was in association with
National Institutes of Health Grant 1U19CA105010.
NR 79
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Z9 28
U1 0
U2 28
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAY 6
PY 2014
VL 53
IS 17
BP 2768
EP 2780
DI 10.1021/bi500139h
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AG9EC
UT WOS:000335720500003
PM 24717170
ER
PT J
AU Bebenek, K
Pedersen, LC
Kunkel, TA
AF Bebenek, Katarzyna
Pedersen, Lars C.
Kunkel, Thomas A.
TI Structure-Function Studies of DNA Polymerase lambda
SO BIOCHEMISTRY
LA English
DT Article
ID BASE-EXCISION-REPAIR; HUMAN POL-MU; HUMAN NUCLEAR EXTRACTS; GAP-FILLING
SYNTHESIS; RIBONUCLEOTIDE INCORPORATION; REPLICATION FIDELITY;
CRYSTAL-STRUCTURES; CATALYTIC CYCLE; THYMINE GLYCOL; BRCT DOMAIN
AB DNA polymerase lambda (pol lambda) functions in DNA repair with its main roles considered to be filling short gaps during repair of double-strand breaks by nonhomologous end joining and during base excision repair. As indicated by structural and biochemical studies over the past 10 years, pol lambda shares many common properties with other family X siblings (pol beta, pol mu, and terminal deoxynucleotidyl transferase) but also has unique structural features that determine its specific functions. In this review, we consider how structural studies over the past decade furthered our understanding of the behavior and biological roles of pol lambda.
C1 [Bebenek, Katarzyna; Pedersen, Lars C.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Bebenek, Katarzyna; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Bebenek, K (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM bebenek@niehs.nih.gov
FU Division of Intramural Research of the National Institute of
Environmental Health Sciences, National Institutes of Health [ES065070,
ES102645]
FX Work in the laboratories of T.A.K. and L.C.P. is supported by the
Division of Intramural Research of the National Institute of
Environmental Health Sciences, National Institutes of Health, via Grants
ES065070 and ES102645, respectively.
NR 86
TC 11
Z9 11
U1 2
U2 20
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAY 6
PY 2014
VL 53
IS 17
BP 2781
EP 2792
DI 10.1021/bi4017236
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AG9EC
UT WOS:000335720500004
PM 24716527
ER
PT J
AU Yang, W
AF Yang, Wei
TI An Overview of Y-Family DNA Polymerases and a Case Study of Human DNA
Polymerase eta
SO BIOCHEMISTRY
LA English
DT Article
ID PIGMENTOSUM-VARIANT PATIENTS; SYN THYMINE DIMER; ERROR-FREE BYPASS;
ACCURATE TRANSLESION SYNTHESIS; REV1 PROTEIN INTERACTS; SINGLE-BASE
DELETIONS; STRUCTURAL BASIS; SULFOLOBUS-SOLFATARICUS;
XERODERMA-PIGMENTOSUM; CRYSTAL-STRUCTURE
AB Y-Family DNA polymerases specialize in translesion synthesis, bypassing damaged bases that would otherwise block the normal progression of replication forks. Y-Family polymerases have unique structural features that allow them to bind damaged DNA and use a modified template base to direct nucleotide incorporation. Each Y-Family polymerase is unique and has different preferences for lesions to bypass and for dNTPs to incorporate. Y-Family polyrnerases are also characterized by a low catalytic efficiency, a low processivity, and a low fidelity on normal DNA. Recruitment of these specialized polymerases to replication forks is therefore regulated. The catalytic center of the Y-Family polymerases is highly conserved and homologous to that of high-fidelity and high-processivity DNA replicases. In this review, structural differences between Y-Family and A- and B-Family polymerases are compared and correlated with their functional differences. A time-resolved X-ray crystallographic study of the DNA synthesis reaction catalyzed by the Y-Family DNA polymerase human polyrnerase eta revealed transient elements that led to the nucleotidyl-transfer reaction.
C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Yang, W (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM wei.yang@nih.gov
RI Yang, Wei/D-4926-2011
OI Yang, Wei/0000-0002-3591-2195
FU National Institutes of Health Intramural Program [DK036146-07]
FX This work is funded by the National Institutes of Health Intramural
Program (DK036146-07).
NR 163
TC 41
Z9 41
U1 2
U2 28
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAY 6
PY 2014
VL 53
IS 17
BP 2793
EP 2803
DI 10.1021/bi500019s
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AG9EC
UT WOS:000335720500005
PM 24716551
ER
PT J
AU Sodt, AJ
Pastor, RW
AF Sodt, Alexander J.
Pastor, Richard W.
TI Molecular Modeling of Lipid Membrane Curvature Induction by a Peptide:
More than Simply Shape
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID BAR DOMAINS; AMPHIPATHIC HELICES; PHOSPHOLIPID-MEMBRANES; DYNAMICS
SIMULATIONS; BILAYER INTERACTIONS; ELASTIC PROPERTIES;
CRYSTAL-STRUCTURE; HEXAGONAL PHASES; CURVED MEMBRANES; SURFACE-TENSION
AB Molecular dynamics simulations of an amphipathic helix embedded in a lipid bilayer indicate that it will induce substantial positive curvature (e.g., a tube of diameter 20 nm at 16% surface coverage). The induction is twice that of a continuum model prediction that only considers the shape of the inclusion. The discrepancy is explained in terms of the additional presence of specific interactions described only by the molecular model. The conclusion that molecular shape alone is insufficient to quantitatively model curvature is supported by contrasting molecular and continuum models of lipids with large and small headgroups (choline and ethanolamine, respectively), and of the removal of a lipid tail (modeling a lyso-lipid). For the molecular model, curvature propensity is analyzed by computing the derivative of the free energy with respect to bending. The continuum model predicts that the inclusion will soften the bilayer near the headgroup region, an effect that may weaken curvature induction. The all-atom predictions are consistent with experimental observations of the degree of tubulation by amphipathic helices and variation of the free energy of binding to liposomes.
C1 [Sodt, Alexander J.; Pastor, Richard W.] NHLBI, NIH, Rockville, MD USA.
RP Sodt, AJ (reprint author), NHLBI, NIH, Rockville, MD USA.
EM alexsodt@gmail.com
FU Intramural Research Program of the National Institutes of Health,
National Heart, Lung and Blood Institute (NIMBI)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Heart, Lung and Blood Institute
(NIMBI), and utilized the high-performance computational capabilities at
the National Institutes of Health, Bethesda, MD (NIMBI LoBoS cluster).
NR 62
TC 16
Z9 16
U1 2
U2 58
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD MAY 6
PY 2014
VL 106
IS 9
BP 1958
EP 1969
DI 10.1016/j.bpj.2014.02.037
PG 12
WC Biophysics
SC Biophysics
GA AG7PM
UT WOS:000335610100018
PM 24806928
ER
PT J
AU Schmitt, JE
Neale, MC
Fassassi, B
Perez, J
Lenroot, RK
Wells, EM
Giedd, JN
AF Schmitt, J. Eric
Neale, Michael C.
Fassassi, Bilqis
Perez, Javier
Lenroot, Rhoshel K.
Wells, Elizabeth M.
Giedd, Jay N.
TI The dynamic role of genetics on cortical patterning during childhood and
adolescence
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE neurodevelopment; twin research
ID HUMAN CEREBRAL-CORTEX; AUTOMATED 3-D EXTRACTION; FALSE DISCOVERY RATE;
BRAIN STRUCTURE; GROWTH-CURVES; MRI DATA; THICKNESS; EVOLUTION;
SURFACES; CHILDREN
AB Longitudinal imaging and quantitative genetic studies have both provided important insights into the nature of human brain development. In the present study we combine these modalities to obtain dynamic anatomical maps of the genetic contributions to cortical thickness through childhood and adolescence. A total of 1,748 anatomic MRI scans from 792 healthy twins and siblings were studied with up to eight time points per subject. Using genetically informative latent growth curve modeling of 81,924 measures of cortical thickness, changes in the genetic contributions to cortical development could be visualized across the age range at high resolution. There was highly statistically significant (P < 0.0001) genetic variance throughout the majority of the cerebral cortex, with the regions of highest heritability including the most evolutionarily novel regions of the brain. Dynamic modeling of changes in heritability over time demonstrated that the heritability of cortical thickness increases gradually throughout late childhood and adolescence, with sequential emergence of three large regions of high heritability in the temporal poles, the inferior parietal lobes, and the superior and dorsolateral frontal cortices.
C1 [Schmitt, J. Eric] Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
[Neale, Michael C.; Perez, Javier] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA 23298 USA.
[Fassassi, Bilqis; Wells, Elizabeth M.; Giedd, Jay N.] NIMH, Pediat Imaging Unit, Bethesda, MD 20892 USA.
[Lenroot, Rhoshel K.] Univ New S Wales, Sch Psychiat & Neurosci Res Australia, Sydney, NSW 2052, Australia.
RP Schmitt, JE (reprint author), Hosp Univ Penn, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA.
EM eric.schmitt@stanfordalumni.org
RI Giedd, Jay/J-9644-2015
OI Giedd, Jay/0000-0003-2002-8978
FU National Institutes of Health [MH-20030, EB-004311]
FX This work was supported by National Institutes of Health Grants MH-20030
and EB-004311.
NR 44
TC 25
Z9 25
U1 2
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 6
PY 2014
VL 111
IS 18
BP 6774
EP 6779
DI 10.1073/pnas.1311630111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5RX
UT WOS:000335477300063
PM 24753564
ER
PT J
AU Takagi, Y
Farrow, RE
Billington, N
Nagy, A
Batters, C
Yang, Y
Sellers, JR
Molloy, JE
AF Takagi, Yasuharu
Farrow, Rachel E.
Billington, Neil
Nagy, Attila
Batters, Christopher
Yang, Yi
Sellers, James R.
Molloy, Justin E.
TI Myosin-10 produces its power-stroke in two phases and moves processively
along a single actin filament under low load
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE actomyosin; stable single alpha-helix; optical trapping; myosin X;
myosin-5a
ID MUSCLE HEAVY-MEROMYOSIN; SMOOTH-MUSCLE; OPTICAL TWEEZERS; MOLECULAR
MOTOR; COILED-COIL; STEP-SIZE; LEUCINE-ZIPPER; WORKING STROKE; BUNDLED
ACTIN; NECK LENGTH
AB Myosin-10 is an actin-based molecular motor that participates in essential intracellular processes such as filopodia formation/extension, phagocytosis, cell migration, and mitotic spindle maintenance. To study this motor protein's mechano-chemical properties, we used a recombinant, truncated form of myosin-10 consisting of the first 936 amino acids, followed by a GCN4 leucine zipper motif, to force dimerization. Negative-stain electron microscopy reveals that the majority of molecules are dimeric with a head-to-head contour distance of similar to 50 nm. In vitro motility assays show that myosin10 moves actin filaments smoothly with a velocity of similar to 310 nm/s. Steady-state and transient kinetic analysis of the ATPase cycle shows that the ADP release rate (similar to 13 s(-1)) is similar to the maximum ATPase activity (similar to 12-14 s(-1)) and therefore contributes to rate limitation of the enzymatic cycle. Single molecule optical tweezers experiments show that under intermediate load (similar to 0.5 pN), myosin-10 interacts intermittently with actin and produces a power stroke of similar to 17 nm, composed of an initial 15-nm and subsequent 2-nm movement. At low optical trap loads, we observed staircase-like processive movements of myosin-10 interacting with the actin filament, consisting of up to six similar to 35-nm steps per binding interaction. We discuss the implications of this load-dependent processivity of myosin-10 as a filopodial transport motor.
C1 [Takagi, Yasuharu; Billington, Neil; Nagy, Attila; Yang, Yi; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
[Farrow, Rachel E.; Batters, Christopher; Molloy, Justin E.] Natl Inst Med Res, MRC, Div Phys Biochem, London NW7 1AA, England.
RP Sellers, JR (reprint author), NHLBI, Lab Mol Physiol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM sellersj@nhlbi.nih.gov; jmolloy@nimr.mrc.ac.uk
FU National Natural Science Foundation of China [31270819]; NHLBI [HL004243
12]; Medical Research Council [U1175.70592]
FX We thank Keir C. Neuman and Earl Homsher for critical reading of the
manuscript, as well as for helpful discussions; David P. Corey (Harvard
University) for the cDNA clone of the Bos taurus myosin-10 heavy chain;
the Electron Microscopy Core Facility at the National Heart, Lung and
Blood Institute (NHLBI), National Institutes of Health (NIH), for the
use of the equipment; the members of the Laboratory of Molecular
Physiology, NHLBI, NIH; and the Division of Physical Biochemistry,
Medical Research Council National Institute for Medical Research, for
technical assistance. Y.Y. was supported by National Natural Science
Foundation of China Grant 31270819. This work was funded by the
intramural funds from NHLBI Grant HL004243 12 (to J.R.S.) and Medical
Research Council Grant U1175.70592 (to J.E.M.).
NR 75
TC 12
Z9 12
U1 1
U2 27
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 6
PY 2014
VL 111
IS 18
BP E1833
EP E1842
DI 10.1073/pnas.1320122111
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5RX
UT WOS:000335477300007
PM 24753602
ER
PT J
AU Burotto, M
Wilkerson, J
Stein, W
Motzer, R
Bates, S
Fojo, T
AF Burotto, Mauricio
Wilkerson, Julia
Stein, Wilfred
Motzer, Robert
Bates, Susan
Fojo, Tito
TI Continuing a Cancer Treatment Despite Tumor Growth May Be Valuable:
Sunitinib in Renal Cell Carcinoma as Example
SO PLOS ONE
LA English
DT Article
ID PHASE-III TRIAL; TYROSINE KINASE INHIBITORS; INTERFERON-ALPHA;
ACQUIRED-RESISTANCE; SOLID TUMORS; DOUBLE-BLIND; LUNG-CANCER; SURVIVAL;
PROGRESSION; SORAFENIB
AB Background: The US FDA and the EMA have approved seven agents for the treatment of renal cell carcinoma, primarily based on differences in progression-free survival (PFS). Because PFS is an arbitrary endpoint we hypothesized that an analysis would demonstrate the growth rate of tumors remained constant at the time of RECIST-defined disease progression.
Methods: We previously estimated the growth (g) and regression (d) rates and the stability of g using data from the Phase III trial comparing sunitinib and interferon.
Results: Sufficient data were available and rate constants statistically valid in 321 of 374 patients randomized to sunitinib. Median d was 0.0052 days(-1); in 53 patients no tumor growth was recorded. Median g was 0.00082 days(-1) and was stable for a median of 275 days on therapy, remaining stable beyond 300, 600 and 900 days in 122, 65 and 27 patients, respectively. A possible increase in g while receiving sunitinib could be discerned in only 18 of 321 patients. Given a median g of 0.00082 days 21 the estimated median time to a second progression were sunitinib continued past RECIST-defined progression was 7.3 months. At 100, 200, and 300 days after starting therapy, an estimated 47%, 27%, and 13% of tumor remains sunitinib sensitive and could explain a RECIST-defined response to a new TKI.
Conclusion: Prolonged stability of g with sunitinib suggests continued sunitinib beyond RECIST-defined progression may provide a beneficial outcome. Randomized trials in patients whose disease has "progressed" on sunitinib are needed to test this hypothesis.
C1 [Burotto, Mauricio; Wilkerson, Julia; Stein, Wilfred; Bates, Susan; Fojo, Tito] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Stein, Wilfred] Hebrew Univ Jerusalem, Jerusalem, Israel.
[Motzer, Robert] Mem Sloan Kettering Canc Ctr, New York, NY USA.
RP Burotto, M (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM mauricio.burottopichun@nih.gov
OI Wilkerson, Julia/0000-0002-6965-0867
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 26
TC 6
Z9 6
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 5
PY 2014
VL 9
IS 5
AR e96316
DI 10.1371/journal.pone.0096316
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI1ZV
UT WOS:000336656000063
PM 24796484
ER
PT J
AU Keleshian, VL
Kellom, M
Kim, HW
Taha, AY
Cheon, Y
Igarashi, M
Rapoport, SI
Rao, JS
AF Keleshian, Vasken L.
Kellom, Matthew
Kim, Hyung-Wook
Taha, Ameer Y.
Cheon, Yewon
Igarashi, Miki
Rapoport, Stanley I.
Rao, Jagadeesh S.
TI Neuropathological Responses to Chronic NMDA in Rats Are Worsened by
Dietary n-3 PUFA Deprivation but Are Not Ameliorated by Fish Oil
Supplementation
SO PLOS ONE
LA English
DT Article
ID POLYUNSATURATED FATTY-ACIDS; ALPHA-LINOLENIC ACID; FRONTAL-CORTEX;
DOCOSAHEXAENOIC ACID; ARACHIDONIC-ACID; DOUBLE-BLIND; UNANESTHETIZED
RATS; BRAIN; LIVER; METABOLISM
AB Background: Dietary long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation may be beneficial for chronic brain illnesses, but the issue is not agreed on. We examined effects of dietary n-3 PUFA deprivation or supplementation, compared with an n-3 PUFA adequate diet (containing alpha-linolenic acid [18: 3 n-3] but not docosahexaenoic acid [DHA, 22: 6n-3]), on brain markers of lipid metabolism and excitotoxicity, in rats treated chronically with NMDA or saline.
Methods: Male rats after weaning were maintained on one of three diets for 15 weeks. After 12 weeks, each diet group was injected i.p. daily with saline (1 ml/kg) or a subconvulsive dose of NMDA (25 mg/kg) for 3 additional weeks. Then, brain fatty acid concentrations and various markers of excitotoxicity and fatty acid metabolism were measured.
Results: Compared to the diet-adequate group, brain DHA concentration was reduced, while n-6 docosapentaenoic acid (DPA, 22: 5n-6) concentration was increased in the n-3 deficient group; arachidonic acid (AA, 20: 4n-6) concentration was unchanged. These concentrations were unaffected by fish oil supplementation. Chronic NMDA increased brain cPLA(2) activity in each of the three groups, but n-3 PUFA deprivation or fish oil did not change cPLA(2) activity or protein compared with the adequate group. sPLA(2) expression was unchanged in the three conditions, whereas iPLA(2) expression was reduced by deprivation but not changed by supplementation. BDNF protein was reduced by NMDA in N-3 PUFA deficient rats, but protein levels of IL-1 beta, NGF, and GFAP did not differ between groups.
Conclusions: N-3 PUFA deprivation significantly worsened several pathological NMDA-induced changes produced in diet adequate rats, whereas n-3 PUFA supplementation did not affect NMDA induced changes. Supplementation may not be critical for this measured neuropathology once the diet has an adequate n-3 PUFA content.
C1 [Keleshian, Vasken L.] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA.
[Kellom, Matthew] Arizona State Univ, Sch Earth & Space Explorat, Phoenix, AZ USA.
[Kim, Hyung-Wook] Sejong Univ, Coll Life Sci, Seoul, South Korea.
[Taha, Ameer Y.; Cheon, Yewon; Rapoport, Stanley I.; Rao, Jagadeesh S.] NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA.
RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA.
EM jrao@mail.nih.gov
FU Office of Dietary Supplementation awarded [OD-09-085]; intramural
program of National Institute on Aging, NIH
FX This research was supported by a grant from the Office of Dietary
Supplementation awarded to J.S. Rao (Grant #OD-09-085) and the
intramural program of National Institute on Aging, NIH. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 49
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U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 5
PY 2014
VL 9
IS 5
AR e95318
DI 10.1371/journal.pone.0095318
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI1ZV
UT WOS:000336656000017
PM 24798187
ER
PT J
AU Jjingo, D
Conley, AB
Wang, JR
Marino-Ramirez, L
Lunyak, VV
Jordan, IK
AF Jjingo, Daudi
Conley, Andrew B.
Wang, Jianrong
Marino-Ramirez, Leonardo
Lunyak, Victoria V.
Jordan, I. King
TI Mammalian-wide interspersed repeat (MIR)-derived enhancers and the
regulation of human gene expression
SO MOBILE DNA
LA English
DT Article
ID PROTEIN-DNA INTERACTIONS; TRANSPOSABLE ELEMENTS; TRANSCRIPTION FACTOR;
HUMAN GENOME; BINDING-SITES; STEM-CELLS; K562 CELLS; C-JUN; DATABASE;
EVOLUTION
AB Background: Mammalian-wide interspersed repeats (MIRs) are the most ancient family of transposable elements (TEs) in the human genome. The deep conservation of MIRs initially suggested the possibility that they had been exapted to play functional roles for their host genomes. MIRs also happen to be the only TEs whose presence in-and-around human genes is positively correlated to tissue-specific gene expression. Similar associations of enhancer prevalence within genes and tissue-specific expression, along with MIRs' previous implication as providing regulatory sequences, suggested a possible link between MIRs and enhancers.
Results: To test the possibility that MIRs contribute functional enhancers to the human genome, we evaluated the relationship between MIRs and human tissue-specific enhancers in terms of genomic location, chromatin environment, regulatory function, and mechanistic attributes. This analysis revealed MIRs to be highly concentrated in enhancers of the K562 and HeLa human cell-types. Significantly more enhancers were found to be linked to MIRs than would be expected by chance, and putative MIR-derived enhancers are characterized by a chromatin environment highly similar to that of canonical enhancers. MIR-derived enhancers show strong associations with gene expression levels, tissue-specific gene expression and tissue-specific cellular functions, including a number of biological processes related to erythropoiesis. MIR-derived enhancers were found to be a rich source of transcription factor binding sites, underscoring one possible mechanistic route for the element sequences co-option as enhancers. There is also tentative evidence to suggest that MIR-enhancer function is related to the transcriptional activity of non-coding RNAs.
Conclusions: Taken together, these data reveal enhancers to be an important cis-regulatory platform from which MIRs can exercise a regulatory function in the human genome and help to resolve a long-standing conundrum as to the reason for MIRs' deep evolutionary conservation.
C1 [Jjingo, Daudi; Conley, Andrew B.; Wang, Jianrong] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
[Marino-Ramirez, Leonardo] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Marino-Ramirez, Leonardo; Lunyak, Victoria V.; Jordan, I. King] PanAmer Bioinformat Inst, Santa Marta, Magdalena, Colombia.
[Lunyak, Victoria V.] Buck Inst Res Aging, Novato, CA USA.
RP Jordan, IK (reprint author), Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
EM king.jordan@biology.gatech.edu
OI Marino-Ramirez, Leonardo/0000-0002-5716-8512
FU Fulbright foundation; School of Biology, Georgia Institute of
Technology; Alfred P Sloan Research Fellowship in Computational and
Evolutionary Molecular Biology [BR-4839]; Intramural Research Program of
the NIH, NLM, NCBI; NIH [R21 AG043921]
FX This work was supported in part by the Fulbright foundation through a
PhD scholarship to DJ, the School of Biology, Georgia Institute of
Technology (to IKJ, DJ, ABC, and JW), an Alfred P Sloan Research
Fellowship in Computational and Evolutionary Molecular Biology (BR-4839)
to IKJ, and NIH R21 AG043921 to WL. This research was supported in part
by the Intramural Research Program of the NIH, NLM, NCBI. No funding
bodies played any role in the design, collection, analysis, and
interpretation of the data or the writing and submission of the
manuscript. The authors would like to acknowledge members of the Jordan
laboratory for helpful discussions. The authors are also grateful to the
ENCODE consortium for making their data freely accessible and
acknowledge the use of data generated by the ENCODE institutions and
groups below: Broad Institute and Massachusetts General Hospital-Harvard
Medical School/Bernstein Laboratory (histone modifications data).
Stanford University/Michael Snyder laboratory, Yale University/Mark
Gerstein and Sherman Weissman laboratories, University of Southern
California/ Peggy Farnham Laboratory and Harvard University/Kevin Struhl
Laboratory (transcription-factor binding data) and University of
Washington/Sandstrom laboratory (expression data).
NR 73
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U1 2
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1759-8753
J9 MOBILE DNA-UK
JI Mob. DNA
PD MAY 5
PY 2014
VL 5
AR 14
DI 10.1186/1759-8753-5-14
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA AH4BL
UT WOS:000336070400001
PM 25018785
ER
PT J
AU Guerard, F
Lee, YS
Brechbiel, MW
AF Guerard, Francois
Lee, Yong-Sok
Brechbiel, Martin W.
TI Rational Design, Synthesis, and Evaluation of Tetrahydroxamic Acid
Chelators for Stable Complexation of Zirconium( IV)
SO CHEMISTRY-A EUROPEAN JOURNAL
LA English
DT Article
DE chelates; imaging agents; ligand design; quantum chemistry; zirconium
ID P-ISOTHIOCYANATOBENZYL-DESFERRIOXAMINE; POSITRON-EMITTING RADIONUCLIDES;
MONOCLONAL-ANTIBODIES; BIFUNCTIONAL CHELATE; EMISSION-TOMOGRAPHY;
HYDROXAMIC ACIDS; PET; CHEMISTRY; ZR-89; CHALLENGES
AB Metals of interest for biomedical applications often need to be complexed and associated in a stable manner with a targeting agent before use. Whereas the fundamentals of most transition-metal complexation processes have been thoroughly studied, the complexation of Zr-IV has been somewhat neglected. This metal has received growing attention in recent years, especially in nuclear medicine, with the use of Zr-89, which a (+)-emitter with near ideal characteristics for cancer imaging. However, the best chelating agent known for this radionuclide is the trishydroxamate desferrioxamineB (DFB), the Zr-IV complex of which exhibits suboptimal stability, resulting in the progressive release of Zr-89 in vivo. Based on a recent report demonstrating the higher thermodynamic stability of the tetrahydroxamate complexes of Zr-IV compared with the trishydroxamate complexes analogues to DFB, we designed a series of tetrahydroxamic acids of varying geometries for improved complexation of this metal. Three macrocycles differing in their cavity size (28 to 36-membered rings) were synthesized by using a ring-closing metathesis strategy, as well as their acyclic analogues. A solution study with Zr-89 showed the complexation to be more effective with increasing cavity size. Evaluation of the kinetic inertness of these new complexes in ethylenediaminetetraacetic acid (EDTA) solution showed significantly improved stabilities of the larger chelates compared with Zr-89-DFB, whereas the smaller complexes suffered from insufficient stabilities. These results were rationalized by a quantum chemical study. The lower stability of the smaller chelates was attributed to ring strain, whereas the better stability of the larger cyclic complexes was explained by the macrocyclic effect and by the structural rigidity. Overall, these new chelating agents open new perspectives for the safe and efficient use of Zr-89 in nuclear imaging, with the best chelators providing dramatically improved stabilities compared with the reference DFB.
C1 [Guerard, Francois; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Yong-Sok] NIH, Ctr Mol Modeling, Div Computat Biosci, Bethesda, MD 20892 USA.
RP Guerard, F (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM francois.guerard@univ-nantes.fr
OI Guerard, Francois/0000-0001-9795-2785
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Center for Information Technology
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research and the Center for
Information Technology. The quantum chemical study utilized PC/LINUX
clusters at the Center for Molecular Modeling of the NIH
(http://cit.nih.gov). The authors are grateful to Dr. L. P. Szajek at
the PET department for providing 89Zr.
NR 30
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U1 4
U2 35
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 0947-6539
EI 1521-3765
J9 CHEM-EUR J
JI Chem.-Eur. J.
PD MAY 5
PY 2014
VL 20
IS 19
BP 5584
EP 5591
DI 10.1002/chem.201304115
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA AG1SS
UT WOS:000335197000011
PM 24740517
ER
PT J
AU Pindolia, DK
Garcia, AJ
Huang, ZJ
Fik, T
Smith, DL
Tatem, AJ
AF Pindolia, Deepa K.
Garcia, Andres J.
Huang, Zhuojie
Fik, Timothy
Smith, David L.
Tatem, Andrew J.
TI Quantifying cross-border movements and migrations for guiding the
strategic planning of malaria control and elimination
SO MALARIA JOURNAL
LA English
DT Article
ID PLASMODIUM-FALCIPARUM; TRANSMISSION; RISK; AFRICA; SWAZILAND; ZANZIBAR;
TRAVEL; ENDEMICITY; PATTERNS; SYSTEM
AB Background: Identifying human and malaria parasite movements is important for control planning across all transmission intensities. Imported infections can reintroduce infections into areas previously free of infection, maintain 'hotspots' of transmission and import drug resistant strains, challenging national control programmes at a variety of temporal and spatial scales. Recent analyses based on mobile phone usage data have provided valuable insights into population and likely parasite movements within countries, but these data are restricted to sub-national analyses, leaving important cross-border movements neglected.
Methods: National census data were used to analyse and model cross-border migration and movement, using East Africa as an example. 'Hotspots' of origin-specific immigrants from neighbouring countries were identified for Kenya, Tanzania and Uganda. Populations of origin-specific migrants were compared to distance from origin country borders and population size at destination, and regression models were developed to quantify and compare differences in migration patterns. Migration data were then combined with existing spatially-referenced malaria data to compare the relative propensity for cross-border malaria movement in the region.
Results: The spatial patterns and processes for immigration were different between each origin and destination country pair. Hotspots of immigration, for example, were concentrated close to origin country borders for most immigrants to Tanzania, but for Kenya, a similar pattern was only seen for Tanzanian and Ugandan immigrants. Regression model fits also differed between specific migrant groups, with some migration patterns more dependent on population size at destination and distance travelled than others. With these differences between immigration patterns and processes, and heterogeneous transmission risk in East Africa and the surrounding region, propensities to import malaria infections also likely show substantial variations.
Conclusion: This was a first attempt to quantify and model cross-border movements relevant to malaria transmission and control. With national census available worldwide, this approach can be translated to construct a cross-border human and malaria movement evidence base for other malaria endemic countries. The outcomes of this study will feed into wider efforts to quantify and model human and malaria movements in endemic regions to facilitate improved intervention planning, resource allocation and collaborative policy decisions.
C1 [Pindolia, Deepa K.; Garcia, Andres J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA.
[Pindolia, Deepa K.; Garcia, Andres J.; Fik, Timothy] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Pindolia, Deepa K.] Clinton Hlth Access Initiat, Boston, MA USA.
[Huang, Zhuojie] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Huang, Zhuojie] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
[Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Smith, David L.; Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
RP Pindolia, DK (reprint author), Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA.
EM dpindolia@gmail.com
RI Emchi, Karma/Q-1952-2016; Smith, David/L-8850-2013
OI Smith, David/0000-0003-4367-3849
FU Emerging Pathogens Institute; University of Florida; RAPIDD program of
the Science and Technology Directorate; Department of Homeland Security;
Fogarty International Center; National Institutes of Health; NIH/NIAID
[U19AI089674]; Bloomberg Family Foundation
FX The authors acknowledge the Spatial Epidemiology Unit at the Department
of Public Health Research, KEMRI-Wellcome Trust in Kenya, for data
acquisition support and thank Victor Alegana, Abdisalan Noor and Robert
Snow for their contributions during the data compilation and
conceptualization stages of this manuscript. AJT & DLS acknowledge
funding support from the Emerging Pathogens Institute, University of
Florida, the RAPIDD program of the Science and Technology Directorate,
Department of Homeland Security, and the Fogarty International Center,
National Institutes of Health, and are also supported by grants from
NIH/NIAID (U19AI089674) and the Bill and Melinda Gates Foundation
(#49446 and #1032350). DLS acknowledges funding support from Bloomberg
Family Foundation. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript. This paper forms part of the output of the WorldPop
population mapping project (www.worldpop.org.uk), Flowminder
(www.flowminder.org) and the human mobility mapping project
(www.thummp.org).
NR 48
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U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD MAY 3
PY 2014
VL 13
AR 169
DI 10.1186/1475-2875-13-169
PG 11
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA AL2IJ
UT WOS:000338948900001
PM 24886389
ER
PT J
AU Golubic, R
Martin, KR
Ekelund, U
Hardy, R
Kuh, D
Wareham, N
Cooper, R
Brage, S
AF Golubic, Rajna
Martin, Kathryn R.
Ekelund, Ulf
Hardy, Rebecca
Kuh, Diana
Wareham, Nicholas
Cooper, Rachel
Brage, Soren
CA NSHD Sci Team
Data Collection Team
TI Levels of physical activity among a nationally representative sample of
people in early old age: results of objective and self-reported
assessments
SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY
LA English
DT Article
DE Physical activity; Sedentary behaviour; Physical activity questionnaire;
Combined sensing; Birth cohort; Old age
ID ACTIVITY ENERGY-EXPENDITURE; CORONARY-HEART-DISEASE; BRITISH BIRTH
COHORT; ALL-CAUSE MORTALITY; ACTIVITY QUESTIONNAIRE; POSTMENOPAUSAL
WOMEN; ACTIVITY PATTERNS; PAID EMPLOYMENT; ADULTS; HEALTH
AB Background: Detailed assessment of physical activity (PA) in older adults is required to comprehensively describe habitual PA-levels in this growing population segment. Current evidence of population PA-levels is predominantly based on self-report.
Methods: We examined PA and sedentary behaviour in a nationally representative sample of British people aged 60-64, using individually-calibrated combined heart-rate and movement sensing and a validated questionnaire (EPAQ2), and the socio-demographic and behavioural factors that may explain between-individual variation in PA.
Results: Between 2006-2010, 2224 participants completed EPAQ2 capturing the past year's activity in four domains (leisure, work, transportation and domestic life) and 1787 participants provided 2-5 days of combined-sensing data. According to objective estimates, median(IQR) physical activity energy expenditure (PAEE) was 33.5 (25.3-42.2) and 35.5 (26.6-47.3) kJ/kg/day for women and men, respectively. Median (IQR) time spent in moderate-to-vigorous PA (MVPA; >3MET), light-intensity PA (1.5-3 MET) and sedentary (<1.5 MET) was 26.0 (12.3-48.1) min/day, 5.4 (4.2-6.7) h/day and 18.0 (16.6-19.4) h/day, respectively, in women; and 41.0 (18.8-73.0) min/day, 5.2 (4.0-6.5) h/day and 17.9 (16.3-19.4) h/day in men. PAEE and time spent in MVPA were lower and sedentary time was greater in obese individuals, those with poor health, and those with lower educational attainment (women only). Questionnaire-derived PAEE and MVPA tended to have similar patterns of variation across socio-demographic strata. In the whole sample, domestic PA had the greatest relative contribution to total questionnaire-derived PAEE (58%), whereas occupational PA was the main driver among employed participants (54%). Only 2.2% of participants achieved an average of >30 min MVPA per day combined with >60 min strength-training per week.
Conclusions: The use of both self-report and objective monitoring to assess PA in early old age provides important information on the domains of PA, PAEE and time spent at different intensity levels. Our findings suggest PA levels are generally low and observed patterns of variation indicate specific subgroups who might benefit from targeted interventions to increase PA.
C1 [Golubic, Rajna; Ekelund, Ulf; Wareham, Nicholas; Brage, Soren] Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit,Addenbrookes Hosp, Cambridge CB2 0QQ, England.
[Martin, Kathryn R.; Hardy, Rebecca; Kuh, Diana; Cooper, Rachel] UCL, Unit Lifelong Hlth & Ageing, MRC, London WC1B 5JU, England.
[Martin, Kathryn R.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Martin, Kathryn R.] Univ Aberdeen, Inst Appl Hlth Sci, Sch Med & Dent, Aberdeen AB25 2ZD, Scotland.
[Ekelund, Ulf] Norwegian Sch Sport Sci, Dept Sport Med, N-0806 Oslo, Norway.
RP Golubic, R (reprint author), Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit,Addenbrookes Hosp, Box 285,Hills Rd, Cambridge CB2 0QQ, England.
EM rajna.golubic@mrc-epid.cam.ac.uk
OI Cooper, Rachel/0000-0003-3370-5720
FU MRC programme [MC_UU_12015/3, MC_UU_12019/1]; Intramural Research
Program of the National Institute on Aging, NIH; Gates Cambridge Trust;
St. John's College Cambridge; School of Clinical Medicine, University of
Cambridge
FX This work was supported by the MRC programme codes MC_UU_12015/3 and
MC_UU_12019/1, and in part by the Intramural Research Program of the
National Institute on Aging, NIH. Rajna Golubic is financially supported
by a scholarship from the Gates Cambridge Trust, Benefactors'
Scholarship from St. John's College Cambridge and Raymond and Beverly
Sackler Studentship from the School of Clinical Medicine, University of
Cambridge.
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PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5868
J9 INT J BEHAV NUTR PHY
JI Int. J. Behav. Nutr. Phys. Act.
PD MAY 3
PY 2014
VL 11
AR 58
DI 10.1186/1479-5868-11-58
PG 17
WC Nutrition & Dietetics; Physiology
SC Nutrition & Dietetics; Physiology
GA AI3KX
UT WOS:000336761300001
PM 24885497
ER
PT J
AU Weiss, DJ
Bhatt, S
Mappin, B
Van Boeckel, TP
Smith, DL
Hay, SI
Gething, PW
AF Weiss, Daniel J.
Bhatt, Samir
Mappin, Bonnie
Van Boeckel, Thomas P.
Smith, David L.
Hay, Simon I.
Gething, Peter W.
TI Air temperature suitability for Plasmodium falciparum malaria
transmission in Africa 2000-2012: a high-resolution spatiotemporal
prediction
SO MALARIA JOURNAL
LA English
DT Article
DE Temperature suitability; Plasmodium falciparum; Africa
ID SUB-SAHARAN AFRICA; ANOPHELES-GAMBIAE; SATELLITE IMAGERY; AQUATIC
STAGES; CLIMATE; MODEL; RISK; EVAPOTRANSPIRATION; POPULATIONS; CULICIDAE
AB Background: Temperature suitability for malaria transmission is a useful predictor variable for spatial models of malaria infection prevalence. Existing continental or global models, however, are synoptic in nature and so do not characterize inter-annual variability in seasonal patterns of temperature suitability, reducing their utility for predicting malaria risk.
Methods: A malaria Temperature Suitability Index (TSI) was created by first modeling minimum and maximum air temperature with an eight-day temporal resolution from gap-filled MODerate Resolution Imaging Spectroradiometer (MODIS) daytime and night-time Land Surface Temperature (LST) datasets. An improved version of an existing biological model for malaria temperature suitability was then applied to the resulting temperature information for a 13-year data series. The mechanism underlying this biological model is simulation of emergent mosquito cohorts on a two-hour time-step and tracking of each cohort throughout its life to quantify the impact air temperature has on both mosquito survival and sporozoite development.
Results: The results of this research consist of 154 monthly raster surfaces that characterize spatiotemporal patterns in TSI across Africa from April 2000 through December 2012 at a 1 km spatial resolution. Generalized TSI patterns were as expected, with consistently high values in equatorial rain forests, seasonally variable values in tropical savannas (wet and dry) and montane areas, and low values in arid, subtropical regions. Comparisons with synoptic approaches demonstrated the additional information available within the dynamic TSI dataset that is lost in equivalent synoptic products derived from long-term monthly averages.
Conclusions: The dynamic TSI dataset presented here provides a new product with far richer spatial and temporal information than any other presently available for Africa. As spatiotemporal malaria modeling endeavors evolve, dynamic predictor variables such as the malaria temperature suitability data developed here will be essential for the rational assessment of changing patterns of malaria risk.
C1 [Weiss, Daniel J.; Bhatt, Samir; Mappin, Bonnie; Hay, Simon I.; Gething, Peter W.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
[Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, Baltimore, MD USA.
[Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Van Boeckel, Thomas P.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Smith, David L.; Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Weiss, DJ (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Tinbergen Bldg,S Parks Rd, Oxford OX1 3PS, England.
EM daniel.weiss@zoo.ox.ac.uk
RI Hay, Simon/F-8967-2015; Smith, David/L-8850-2013;
OI Gething, Peter/0000-0001-6759-5449; Hay, Simon/0000-0002-0611-7272;
Smith, David/0000-0003-4367-3849; Mappin, Bonnie/0000-0002-1205-719X
FU Bill and Melinda Gates Foundation [OPP1068048]; NIH/NIAID [U19AI089674];
Bloomberg Family Foundation; Senior Research Fellowship from the
Wellcome Trust [095066]; RAPIDD program of the Science & Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health
FX We thank David Benz for his assistance in handling the MODIS data and
Ursula Dalrymple for proof reading this manuscript. PWG is a Medical
Research Council Career Development Fellow (# K00669X) and receives
support from the Bill and Melinda Gates Foundation (# OPP1068048) that
also supports DJW, SB and BJM. DLS acknowledges funding from NIH/NIAID
(U19AI089674) and the Bloomberg Family Foundation. SIH is funded by a
Senior Research Fellowship from the Wellcome Trust (# 095066) and
acknowledges funding support from the RAPIDD program of the Science &
Technology Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health.
NR 45
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U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD MAY 3
PY 2014
VL 13
AR 171
DI 10.1186/1475-2875-13-171
PG 11
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA AI4DL
UT WOS:000336815700001
PM 24886586
ER
PT J
AU Jahrling, PB
Tomori, O
AF Jahrling, Peter B.
Tomori, Owale
TI Variola virus archives: a new century, a new approach
SO LANCET
LA English
DT Editorial Material
C1 [Jahrling, Peter B.] NIAID, NIH, Ft Detrick, MD 21702 USA.
[Tomori, Owale] Redeemers Univ, Redemption City, Ogin State, Nigeria.
RP Jahrling, PB (reprint author), NIAID, NIH, Ft Detrick, MD 21702 USA.
EM jahrlingp@niaid.nih.gov
NR 9
TC 2
Z9 2
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD MAY 3
PY 2014
VL 383
IS 9928
BP 1525
EP 1526
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AG5YO
UT WOS:000335495400005
PM 24792843
ER
PT J
AU Carafoli, E
Klee, CB
Lennarz, W
AF Carafoli, Ernesto
Klee, Claude B.
Lennarz, William
TI Malcolm Daniel Lane
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Biographical-Item
C1 [Carafoli, Ernesto] Univ Padua, Dipartimento Chim Biol, Padua, Italy.
[Klee, Claude B.] NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
[Lennarz, William] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA.
RP Carafoli, E (reprint author), Univ Padua, Dipartimento Chim Biol, Padua, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD MAY 2
PY 2014
VL 447
IS 2
BP 223
EP 223
DI 10.1016/j.bbrc.2014.04.094
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AI0BJ
UT WOS:000336510900001
ER
PT J
AU Oboti, L
Perez-Gomez, A
Keller, M
Jacobi, E
Birnbaumer, L
Leinders-Zufall, T
Zufall, F
Chamero, P
AF Oboti, Livio
Perez-Gomez, Anabel
Keller, Matthieu
Jacobi, Eric
Birnbaumer, Lutz
Leinders-Zufall, Trese
Zufall, Frank
Chamero, Pablo
TI A wide range of pheromone-stimulated sexual and reproductive behaviors
in female mice depend on G protein Gao
SO BMC BIOLOGY
LA English
DT Article
DE Bruce effect; Estrus induction; Gao signaling; Lordosis; Mate
recognition; Puberty acceleration; Reproduction
ID ACCESSORY OLFACTORY-BULB; MALE-MOUSE URINE; VOMERONASAL RECEPTOR
NEURONS; G-ALPHA-O; AGGRESSIVE-BEHAVIOR; SENSORY NEURONS; SYNTHETIC
ANALOGS; MULTIGENE FAMILY; MUTANT MICE; ORGAN
AB Background: Optimal reproductive fitness is essential for the biological success and survival of species. The vomeronasal organ is strongly implicated in the display of sexual and reproductive behaviors in female mice, yet the roles that apical and basal vomeronasal neuron populations play in controlling these gender-specific behaviors remain largely unclear.
Results: To dissect the neural pathways underlying these functions, we genetically inactivated the basal vomeronasal organ layer using conditional, cell-specific ablation of the G protein Gao. Female mice mutant for Gao show severe alterations in sexual and reproductive behaviors, timing of puberty onset, and estrous cycle. These mutant mice are insensitive to reproductive facilitation stimulated by male pheromones that accelerate puberty and induce ovulation. Gao-mutant females exhibit a striking reduction in sexual receptivity or lordosis behavior to males, but gender discrimination seems to be intact. These mice also show a loss in male scent preference, which requires a learned association for volatile olfactory signals with other nonvolatile ownership signals that are contained in the high molecular weight fraction of male urine. Thus, Gao impacts on both instinctive and learned social responses to pheromones.
Conclusions: These results highlight that sensory neurons of the Gao-expressing vomeronasal subsystem, together with the receptors they express and the molecular cues they detect, control a wide range of fundamental mating and reproductive behaviors in female mice.
C1 [Oboti, Livio; Perez-Gomez, Anabel; Jacobi, Eric; Leinders-Zufall, Trese; Zufall, Frank; Chamero, Pablo] Univ Saarland, Dept Physiol, Sch Med, D-66421 Homburg, Germany.
[Keller, Matthieu] Univ Tours, Lab Physiol Reprod & Comportments, CNRS, UMR 7247,INRA, F-37380 Nouzilly, France.
[Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA.
RP Zufall, F (reprint author), Univ Saarland, Dept Physiol, Sch Med, D-66421 Homburg, Germany.
EM frank.zufall@uks.eu; pablo.chamero@uks.eu
RI Perez-Gomez, Anabel/B-1888-2015; Oboti, Livio/P-5876-2015;
Leinders-Zufall, Trese/B-4103-2009;
OI Perez-Gomez, Anabel/0000-0001-9477-731X; Oboti,
Livio/0000-0001-7197-568X; Leinders-Zufall, Trese/0000-0002-0678-362X;
Chamero, Pablo/0000-0002-4305-1073; Keller, Matthieu/0000-0002-5445-7431
FU Deutsche Forschungsgemeinschaft [CH 920/2-1, SFB 894/A17, SFB 894/A16];
Intramural Research Program of the NIH [Z01 ES-101643]; Volkswagen
Foundation; French Agence Nationale de la Recherche (Pherosex grant);
DFG-funded International Graduate Program [GK1326]
FX We thank Peter Mombaerts and Ulrich Boehm for supplying OMP-Cre mice and
eR26-tGFP reporter mice, respectively, and Martina Pyrski for help with
genotyping. This work was supported by grants from the Deutsche
Forschungsgemeinschaft to PC (CH 920/2-1), FZ (SFB 894/A17) and TL-Z
(SFB 894/A16), the Intramural Research Program of the NIH to LB (Project
Z01 ES-101643), Volkswagen Foundation to TL-Z and the French Agence
Nationale de la Recherche (Pherosex grant) to MK. EJ was supported by
the DFG-funded International Graduate Program GK1326. TL-Z is a
Lichtenberg Professor of the Volkswagen Foundation.
NR 69
TC 17
Z9 17
U1 2
U2 24
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7007
J9 BMC BIOL
JI BMC Biol.
PD MAY 2
PY 2014
VL 12
AR 31
DI 10.1186/1741-7007-12-31
PG 17
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AI4CI
UT WOS:000336812800001
PM 24886577
ER
PT J
AU Timsit, YE
Negishi, M
AF Timsit, Yoav E.
Negishi, Masahiko
TI Coordinated Regulation of Nuclear Receptor CAR by CCRP/DNAJC7, HSP70 and
the Ubiquitin-Proteasome System
SO PLOS ONE
LA English
DT Article
ID CONSTITUTIVE ACTIVE/ANDROSTANE RECEPTOR; HEAT-SHOCK PROTEINS; HEPG2
CELLS; MOUSE-LIVER; ANDROSTANE RECEPTOR; SYNERGISTIC ACTIVATION;
MOLECULAR CHAPERONES; PRIMARY HEPATOCYTES; GENE-TRANSCRIPTION;
ESTROGEN-RECEPTOR
AB The constitutive active/androstane receptor (CAR) plays an important role as a coordinate transcription factor in the regulation of various hepatic metabolic pathways for chemicals such as drugs, glucose, fatty acids, bilirubin, and bile acids. Currently, it is known that in its inactive state, CAR is retained in the cytoplasm in a protein complex with HSP90 and the tetratricopeptide repeat protein cytosoplasmic CAR retention protein (CCRP). Upon activation by phenobarbital (PB) or the PB-like inducer 1,4-bis[2-(3,5-dichloropyridyloxy)]-benzene (TCPOBOP), CAR translocates into the nucleus. We have identified two new components to the cytoplasmic regulation of CAR: ubiquitin-dependent degradation of CCRP and protein-protein interaction with HSP70. Treatment with the proteasome inhibitor MG132 (5 mu M) causes CAR to accumulate in the cytoplasm of transfected HepG2 cells. In the presence of MG132, TCPOBOP increases CCRP ubiquitination in HepG2 cells co-expressing CAR, while CAR ubiquitination was not detected. MG132 treatment of HepG2 also attenuated of TCPOBOP-induced CAR transcriptional activation on reporter constructs which contain CAR-binding DNA elements derived from the human CYP2B6 gene. The elevation of cytoplasmic CAR protein with MG132 correlated with an increase of HSP70, and to a lesser extent HSP60. Both CCRP and CAR were found to interact with endogenous HSP70 in HepG2 cells by immunoprecipitation analysis. Induction of HSP70 levels by heat shock also increased cytoplasmic CAR levels, similar to the effect of MG132. Lastly, heat shock attenuated TCPOBOP-induced CAR transcriptional activation, also similar to the effect of MG132. Collectively, these data suggest that ubiquitin-proteasomal regulation of CCRP and HSP70 are important contributors to the regulation of cytoplasmic CAR levels, and hence the ability of CAR to respond to PB or PB-like inducers.
C1 [Timsit, Yoav E.; Negishi, Masahiko] Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
RP Negishi, M (reprint author), Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
EM negishi@niehs.nih.gov
FU NIH [Z01ES1005-01]
FX NIH Intramural Reseach program:: Z01ES1005-01. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 56
TC 5
Z9 5
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 2
PY 2014
VL 9
IS 5
AR e96092
DI 10.1371/journal.pone.0096092
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI1ZS
UT WOS:000336655700056
PM 24789201
ER
PT J
AU Marshall, KE
Offerdahl, DK
Speare, JO
Dorward, DW
Hasenkrug, A
Carmody, AB
Baron, GS
AF Marshall, Karen E.
Offerdahl, Danielle K.
Speare, Jonathan O.
Dorward, David W.
Hasenkrug, Aaron
Carmody, Aaron B.
Baron, Gerald S.
TI Glycosylphosphatidylinositol Anchoring Directs the Assembly of Sup35NM
Protein into Non-fibrillar, Membrane-bound Aggregates
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Amyloid; Electron Microscopy (EM); Glycosylphosphatidylinositol Anchors;
Prions; Protein Aggregation; Protein Misfolding; Protein Self-assembly
ID SCRAPIE PRION PROTEIN; STRAUSSLER-SCHEINKER DISEASE; YEAST PRION;
IN-VIVO; ALZHEIMERS-DISEASE; AMYLOID DEPOSITS; SACCHAROMYCES-CEREVISIAE;
NEUROBLASTOMA-CELLS; ELECTRON-MICROSCOPY; BETA-AMYLOIDOSIS
AB Background: Sup35NM is a soluble protein that when misfolded forms amyloid fibril aggregates. Results: When tethered to membranes via a lipid anchor, Sup35NM aggregates adopt a non-fibrillar, membrane-bound structure. Conclusion: Lipid anchor-directed membrane association prevents assembly into fibrils. Significance: This may explain differences between prion diseases compared with related protein aggregation diseases because only prion diseases involve aggregation of a lipid-anchored protein.
In prion-infected hosts, PrPSc usually accumulates as non-fibrillar, membrane-bound aggregates. Glycosylphosphatidylinositol (GPI) anchor-directed membrane association appears to be an important factor controlling the biophysical properties of PrPSc aggregates. To determine whether GPI anchoring can similarly modulate the assembly of other amyloid-forming proteins, neuronal cell lines were generated that expressed a GPI-anchored form of a model amyloidogenic protein, the NM domain of the yeast prion protein Sup35 (Sup35(GPI)). We recently reported that GPI anchoring facilitated the induction of Sup35(GPI) prions in this system. Here, we report the ultrastructural characterization of self-propagating Sup35(GPI) aggregates of either spontaneous or induced origin. Like membrane-bound PrPSc, Sup35(GPI) aggregates resisted release from cells treated with phosphatidylinositol-specific phospholipase C. Sup35(GPI) aggregates of spontaneous origin were detergent-insoluble, protease-resistant, and self-propagating, in a manner similar to that reported for recombinant Sup35NM amyloid fibrils and induced Sup35(GPI) aggregates. However, GPI-anchored Sup35 aggregates were not stained with amyloid-binding dyes, such as Thioflavin T. This was consistent with ultrastructural analyses, which showed that the aggregates corresponded to dense cell surface accumulations of membrane vesicle-like structures and were not fibrillar. Together, these results showed that GPI anchoring directs the assembly of Sup35NM into non-fibrillar, membrane-bound aggregates that resemble PrPSc, raising the possibility that GPI anchor-dependent modulation of protein aggregation might occur with other amyloidogenic proteins. This may contribute to differences in pathogenesis and pathology between prion diseases, which uniquely involve aggregation of a GPI-anchored protein, versus other protein misfolding diseases.
C1 [Marshall, Karen E.; Offerdahl, Danielle K.; Speare, Jonathan O.; Dorward, David W.; Hasenkrug, Aaron; Carmody, Aaron B.; Baron, Gerald S.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Baron, GS (reprint author), 903 S 4th St, Hamilton, MT 59840 USA.
EM gbaron@niaid.nih.gov
FU National Institutes of Health, NIAID, Intramural Research Program
FX This work was supported, in whole or in part, by the National Institutes
of Health, NIAID, Intramural Research Program.
NR 89
TC 3
Z9 3
U1 1
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 2
PY 2014
VL 289
IS 18
BP 12245
EP 12263
DI 10.1074/jbc.M114.556639
PG 19
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AG7ER
UT WOS:000335581400006
PM 24627481
ER
PT J
AU Yu, SL
Levi, L
Casadesus, G
Kunos, G
Noy, N
AF Yu, Shuiliang
Levi, Liraz
Casadesus, Gemma
Kunos, George
Noy, Noa
TI Fatty Acid-binding Protein 5 (FABP5) Regulates Cognitive Function Both
by Decreasing Anandamide Levels and by Activating the Nuclear Receptor
Peroxisome Proliferatoractivated Receptor beta/delta(PPAR beta/delta) in
the Brain
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Arachidonic Acid; Endocannabinoids; Lipids; Lipid-binding Protein;
Peroxisome Proliferator-activated Receptor (PPAR)
ID RETINOIC ACID; ENDOCANNABINOID SYSTEM; CANNABINOID RECEPTOR; HIPPOCAMPAL
NEUROGENESIS; SIGNAL-TRANSDUCTION; INSULIN-RESISTANCE; MEMORY; ALPHA;
MICE; CB1
AB Background: FABP5 shuttles ligands to the nuclear receptor PPAR/ and enhances degradation of the endocannabinoid anandamide. Results: Brain level of anandamide is high and PPAR/ activation is low in FABP5-null mice. These mice display impaired learning and memory. Conclusion: FABP5 regulates learning and memory by two distinct mechanisms. Significance: The data suggest that FABP5 may be a novel target for therapy of cognitive dysfunction.
Endocannabinoids modulate multiple behaviors, including learning and memory. We show that the endocannabinoid anandamide (AEA) can alter neuronal cell function both through its established role in activation of the G-protein-coupled receptor CB1, and by serving as a precursor for a potent agonist of the nuclear receptor PPAR/, in turn up-regulating multiple cognition-associated genes. We show further that the fatty acid-binding protein FABP5 controls both of these functions in vivo. FABP5 both promotes the hydrolysis of AEA into arachidonic acid and thus reduces brain endocannabinoid levels, and directly shuttles arachidonic acid to the nucleus where it delivers it to PPAR/, enabling its activation. In accordance, ablation of FABP5 in mice results in excess accumulation of AEA, abolishes PPAR/ activation in the brain, and markedly impairs hippocampus-based learning and memory. The data indicate that, by controlling anandamide disposition and activities, FABP5 plays a key role in regulating hippocampal cognitive function.
C1 [Yu, Shuiliang; Levi, Liraz; Noy, Noa] Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA.
[Casadesus, Gemma] Case Western Reserve Univ, Dept Neurosci, Sch Med, Cleveland, OH 44106 USA.
[Noy, Noa] Case Western Reserve Univ, Dept Nutr, Sch Med, Cleveland, OH 44106 USA.
[Kunos, George] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
RP Noy, N (reprint author), Case Western Reserve Univ, Dept Pharmacol, Sch Med, 10900 Euclid Ave W333, Cleveland, OH 44106 USA.
EM noa.noy@case.edu
FU National Institutes of Health [R01 DK060684]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant R01 DK060684 (to N. N.).
NR 54
TC 21
Z9 21
U1 0
U2 10
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 2
PY 2014
VL 289
IS 18
BP 12748
EP 12758
DI 10.1074/jbc.M114.559062
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AG7ER
UT WOS:000335581400045
PM 24644281
ER
PT J
AU Hartman, KG
Vitolo, MI
Pierce, AD
Fox, JM
Shapiro, P
Martin, SS
Wilder, PT
Weber, DJ
AF Hartman, Kira G.
Vitolo, Michele I.
Pierce, Adam D.
Fox, Jennifer M.
Shapiro, Paul
Martin, Stuart S.
Wilder, Paul T.
Weber, David J.
TI Complex Formation between S100B Protein and the p90 Ribosomal S6 Kinase
( RSK) in Malignant Melanoma Is Calcium-dependent and Inhibits
Extracellular Signalregulated Kinase ( ERK)-mediated Phosphorylation of
RSK
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Calcium; Calcium Binding Proteins; Cancer; ERK; MAP Kinases (MAPKs);
Melanoma; RSK; S100 Proteins
ID MAGNETIC-RESONANCE-SPECTROSCOPY; GLYCATION END-PRODUCTS; BINDING
PROTEIN; WILD-TYPE; P53; S100B(BETA-BETA); ACTIVATION; RECEPTOR; CANCER;
FAMILY
AB Background: S100B is overexpressed in malignant melanoma and contributes to cancer progression. Results: The S100B-RSK complex was found to be Ca2+-dependent, block phosphorylation of RSK at Thr-573, and sequester RSK to the cytosol. Conclusion: The Ca2+-dependent S100B-RSK complex provides a new link between the MAPK and Ca2+ signaling pathways. Significance: S100B inhibitors may restore normal MAPK and Ca2+ signaling in malignant melanoma.
S100B is a prognostic marker for malignant melanoma. Increasing S100B levels are predictive of advancing disease stage, increased recurrence, and low overall survival in malignant melanoma patients. Using S100B overexpression and shRNA(S100B) knockdown studies in melanoma cell lines, elevated S100B was found to enhance cell viability and modulate MAPK signaling by binding directly to the p90 ribosomal S6 kinase (RSK). S100B-RSK complex formation was shown to be Ca2+-dependent and to block ERK-dependent phosphorylation of RSK, at Thr-573, in its C-terminal kinase domain. Additionally, the overexpression of S100B sequesters RSK into the cytosol and prevents it from acting on nuclear targets. Thus, elevated S100B contributes to abnormal ERK/RSK signaling and increased cell survival in malignant melanoma.
C1 [Pierce, Adam D.; Wilder, Paul T.; Weber, David J.] Univ Maryland, Dept Biochem & Mol Biol, Sch Med, Baltimore, MD 21201 USA.
[Hartman, Kira G.; Fox, Jennifer M.; Martin, Stuart S.; Weber, David J.] Univ Maryland, Program Mol Med, Grad Program Life Sci, Baltimore, MD 21201 USA.
[Vitolo, Michele I.; Martin, Stuart S.; Wilder, Paul T.] Univ Maryland, Dept Physiol, Sch Med, Baltimore, MD 21201 USA.
[Pierce, Adam D.; Weber, David J.] Univ Maryland, Ctr Biomol Therapeut, Sch Med, Baltimore, MD 21201 USA.
[Shapiro, Paul] Univ Maryland, Dept Pharmaceut Sci, Sch Pharm, Baltimore, MD 21201 USA.
[Vitolo, Michele I.; Shapiro, Paul; Martin, Stuart S.; Wilder, Paul T.; Weber, David J.] Univ Maryland, Baltimore, MD 21201 USA.
[Vitolo, Michele I.; Shapiro, Paul; Martin, Stuart S.; Wilder, Paul T.; Weber, David J.] Stewart Greenebaum NCI Canc Ctr, Baltimore, MD 21201 USA.
[Fox, Jennifer M.] Univ Maryland, Ctr Stem Cell Biol & Regenerat Med, Dept Pediat, Sch Med, Baltimore, MD 21201 USA.
RP Wilder, PT (reprint author), Dept Biochem & Mol Biol, 108 N Greene St, Baltimore, MD 21201 USA.
EM pwild001@umaryland.edu; dweber@som.umaryland.edu
FU National Institutes of Health [GM58888, CA107331, CA166576]
FX This works was supported, in whole or in part, by National Institutes of
Health grants GM58888 and CA107331 (to D.J.W.) and CA166576 (to M.I.V.).
NR 64
TC 9
Z9 9
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 2
PY 2014
VL 289
IS 18
BP 12886
EP 12895
DI 10.1074/jbc.M114.561613
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AG7ER
UT WOS:000335581400057
PM 24627490
ER
PT J
AU Kamnaksh, A
Budde, MD
Kovesdi, E
Long, JB
Frank, JA
Agoston, DV
AF Kamnaksh, Alaa
Budde, Matthew D.
Kovesdi, Erzsebet
Long, Joseph B.
Frank, Joseph A.
Agoston, Denes V.
TI Diffusion Tensor Imaging Reveals Acute Subcortical Changes after Mild
Blast-Induced Traumatic Brain Injury
SO SCIENTIFIC REPORTS
LA English
DT Article
ID LONG-TERM CONSEQUENCES; AXONAL INJURY; MILITARY; CONCUSSION; BIOMARKERS;
VETERANS; COMBAT; MODEL; RATS; MRI
AB Mild blast-induced traumatic brain injury (mbTBI) poses special diagnostic challenges due to its overlapping symptomatology with other neuropsychiatric conditions and the lack of objective outcome measures. Diffusion tensor imaging (DTI) can potentially provide clinically relevant information toward a differential diagnosis. In this study, we aimed to determine if single and repeated (5 total; administered on consecutive days) mild blast overpressure exposure results in detectable structural changes in the brain, especially in the hippocampus. Fixed rat brains were analyzed by ex vivo DTI at 2 h and 42 days after blast (or sham) exposure(s). An anatomy-based region of interest analysis revealed significant interactions in axial and radial diffusivity in a number of subcortical structures at 2 h only. Differences between single-and multiple-injured rats were largely in the thalamus but not the hippocampus. Our findings demonstrate the value and the limitations of DTI in providing a better understanding of mbTBI pathobiology.
C1 [Kamnaksh, Alaa; Agoston, Denes V.] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA.
[Kamnaksh, Alaa] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Budde, Matthew D.; Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
[Kovesdi, Erzsebet] US Dept Vet Affairs, Vet Affairs Cent Off, Washington, DC 20420 USA.
[Long, Joseph B.] Walter Reed Army Inst Res, Ctr Mil Psychiat & Neurosci, Blast Induced Neurotrauma Branch, Silver Spring, MD 20910 USA.
RP Agoston, DV (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM denes.agoston@usuhs.edu
FU Center for Neuroscience and Regenerative Medicine [G1703F]
FX We thank the Neurotrauma Team at the Walter Reed Army Institute of
Research for their technical help during the exposures, along with Eric
Gold and Lindsay Janes for assistance with the MRI experiments. This
work was supported by the Center for Neuroscience and Regenerative
Medicine grant number G1703F.
NR 59
TC 6
Z9 7
U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAY 2
PY 2014
VL 4
AR 4809
DI 10.1038/srep04809
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1ZZ
UT WOS:000335216000001
PM 24786839
ER
PT J
AU Zakirova, NF
Karpenko, IL
Prokofjeva, MM
Vanpouille, C
Prassolov, VS
Shipitsyn, AV
Kochetkov, SN
AF Zakirova, N. F.
Karpenko, I. L.
Prokofjeva, M. M.
Vanpouille, C.
Prassolov, V. S.
Shipitsyn, A. V.
Kochetkov, S. N.
TI Acyclovir phosphoramidates as potential anti-HIV drugs
SO RUSSIAN CHEMICAL BULLETIN
LA English
DT Article
DE acyclovir; phosphoramidates; human immunodeficiency virus
ID DERIVATIVES; TECHNOLOGY
AB A number of phosphoramidate derivatives of acyclovir (ACV) were obtained. These compounds revealed themselves as latent forms of acyclovir monophosphate (ACV-MP). The optimized route to the title phosphoramidates involves the synthesis of intermediate phosphorodichloridates followed by their treatment with various amines. The compounds obtained showed moderate antiviral activity both in vitro in a controlled system of secure screening for anti-HIV agents and in a tissue system enabling ex vivo determination of the efficiency of the drug and its effect on HIV replication in two weeks.
C1 [Zakirova, N. F.; Karpenko, I. L.; Prokofjeva, M. M.; Prassolov, V. S.; Shipitsyn, A. V.; Kochetkov, S. N.] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 119991, Russia.
[Vanpouille, C.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Shipitsyn, AV (reprint author), Russian Acad Sci, VA Engelhardt Mol Biol Inst, 32 Ul Vavilova, Moscow 119991, Russia.
EM chip@email.ru
RI Karpenko, Inna/F-5879-2015
OI Karpenko, Inna/0000-0001-9849-0447
FU Russian Foundation for Basic Research [13-04-00829-a, 12-04-00581-a];
Presidium of the Russian Academy of Sciences (Program "Molecular and
Cell Biology")
FX This work was financially supported by the Russian Foundation for Basic
Research (Project Nos 13-04-00829-a and 12-04-00581-a) and the Presidium
of the Russian Academy of Sciences (Program "Molecular and Cell
Biology").
NR 13
TC 1
Z9 1
U1 0
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1066-5285
EI 1573-9171
J9 RUSS CHEM B+
JI Russ. Chem. Bull.
PD MAY
PY 2014
VL 63
IS 5
BP 1192
EP 1196
PG 5
WC Chemistry, Multidisciplinary
SC Chemistry
GA CC1ZD
UT WOS:000350143000025
ER
PT J
AU Song, HK
Preiss, LR
Maslen, CL
Kroner, B
Devereux, RB
Roman, MJ
Holmes, KW
Tolunay, HE
Desvigne-Nickens, P
Asch, FM
Milewski, RK
Bavaria, J
LeMaire, SA
AF Song, Howard K.
Preiss, Liliana R.
Maslen, Cheryl L.
Kroner, Barbara
Devereux, Richard B.
Roman, Mary J.
Holmes, Kathryn W.
Tolunay, H. Eser
Desvigne-Nickens, Patrice
Asch, Federico M.
Milewski, Rita K.
Bavaria, Joseph
LeMaire, Scott A.
CA GenTAC Consortium
TI Valve-Sparing Aortic Root Replacement in Patients with Marfan Syndrome
Enrolled in the National Registry of Genetically Triggered Thoracic
Aortic Aneurysms and Cardiovascular Conditions
SO JOURNAL OF HEART VALVE DISEASE
LA English
DT Article
ID ASCENDING AORTA; SURGERY; INCOMPETENCE; EXPERIENCE; OPERATIONS; GENE
AB Background and aim of the study: The long-term outcomes of aortic valve-sparing (AVS) root replacement in Marfan syndrome (MFS) patients remain uncertain. The study aim was to determine the utilization and outcomes of AVS root replacement in MFS patients enrolled in the Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC).
Methods: At the time of this analysis, 788 patients with MFS were enrolled in the GenTAC Registry, of whom 288 had undergone aortic root replacement. Patients who had undergone AVS procedures were compared to those who had undergone aortic valve replacement (AVR).
Results: AVS root replacement was performed in 43.5% of MFS patients, and the frequency of AVS was increased over the past five years. AVS patients were younger at the time of surgery (31.0 versus 36.3 years, p = 0.006) and more likely to have had elective rather than emergency surgery compared to AVR patients, in whom aortic valve dysfunction and aortic dissection was the more likely primary indication for surgery. After a mean follow up of 6.2 +/- 3.6 years, none of the 87 AVS patients had required reoperation; in contrast, after a mean follow up of 10.5 +/- 7.6 years, 11.5% of AVR patients required aortic root reoperation. Aortic valve function has been durable, with 95.8% of AVS patients having aortic insufficiency that was graded as mild or less.
Conclusion: AVS root replacement is performed commonly among the MFS population, and the durability of the aortic repair and aortic valve function have been excellent to date. These results justify a continued use of the procedure in an elective setting. The GenTAC Registry will be a useful resource to assess the long-term durability of AVS root replacement in the future.
C1 [Song, Howard K.] OHSU, Div Cardiothorac Surg, Portland, OR 97239 USA.
[Preiss, Liliana R.; Kroner, Barbara] Oregon Hlth & Sci Univ, Div Cardiovasc Med, Portland, OR 97239 USA.
[Maslen, Cheryl L.] Oregon Hlth & Sci Univ, Div Pediat Cardiol, Portland, OR 97239 USA.
[Devereux, Richard B.; Roman, Mary J.] Res Triangle Inst Int, Bethesda, MD USA.
[Holmes, Kathryn W.] Weill Cornell Med Coll, Div Cardiol, New York, NY USA.
[Tolunay, H. Eser; Desvigne-Nickens, Patrice] NHLBI, Bethesda, MD 20892 USA.
[Asch, Federico M.] MedStar Washington Hosp Ctr, Div Cardiol, Washington, DC USA.
[Milewski, Rita K.; Bavaria, Joseph] Univ Penn, Med Ctr, Div Cardiothorac Surg, Philadelphia, PA 19104 USA.
[LeMaire, Scott A.] Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77030 USA.
RP Song, HK (reprint author), OHSU, Div Cardiothorac Surg, Mail Code L353,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM songh@ohsu.edu
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Department of Health and Human Services [HHSN268200648199C,
HHSN268201000048C]; National Institute of Arthritis and Musculoskeletal
and Skin Diseases; Oregon Clinical and Translational Research Institute
(Portland, OR); National Center for Research Resources (Bethesda, MD)
[UL1 RR024140]; Weill Cornell Medical College Clinical Translational
Science Center (New York, NY) [UL1RR024996]
FX The GenTAC Registry has been supported in full by Federal funds from the
National Heart, Lung, and Blood Institute, National Institutes of
Health, Department of Health and Human Services, under Contract Numbers
HHSN268200648199C and HHSN268201000048C. Additional support was provided
by the National Institute of Arthritis and Musculoskeletal and Skin
Diseases, the Oregon Clinical and Translational Research Institute
(Portland, OR), grant UL1 RR024140 from the National Center for Research
Resources (Bethesda, MD), and by the Weill Cornell Medical College
Clinical Translational Science Center (New York, NY), grant UL1RR024996.
Stephen N. Palmer PhD, ELS contributed to the editing of the manuscript.
NR 28
TC 2
Z9 2
U1 0
U2 3
PU I C R PUBLISHERS
PI NORTHWOOD
PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET,
ENGLAND
SN 0966-8519
J9 J HEART VALVE DIS
JI J. Heart Valve Dis.
PD MAY
PY 2014
VL 23
IS 3
BP 292
EP 298
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CB4BJ
UT WOS:000349572900005
PM 25296451
ER
PT J
AU Saketkoo, LA
Mittoo, S
Huscher, D
Khanna, D
Dellaripa, PF
Distler, O
Flaherty, KR
Frankel, S
Oddis, CV
Denton, CP
Fischer, A
Kowal-Bielecka, OM
LeSage, D
Merkel, PA
Phillips, K
Pittrow, D
Swigris, J
Antoniou, K
Baughman, RP
Castelino, FV
Christmann, RB
Christopher-Stine, L
Collard, HR
Cottin, V
Danoff, S
Highland, KB
Hummers, L
Shah, AA
Kim, DS
Lynch, DA
Miller, FW
Proudman, SM
Richeldi, L
Ryu, JH
Sandorfi, N
Sarver, C
Wells, AU
Strand, V
Matteson, EL
Brown, KK
Seibold, JR
AF Saketkoo, Lesley Ann
Mittoo, Shikha
Huscher, Doerte
Khanna, Dinesh
Dellaripa, Paul F.
Distler, Oliver
Flaherty, Kevin R.
Frankel, Sid
Oddis, Chester V.
Denton, Christopher P.
Fischer, Aryeh
Kowal-Bielecka, Otylia M.
LeSage, Daphne
Merkel, Peter A.
Phillips, Kristine
Pittrow, David
Swigris, Jeffrey
Antoniou, Katerina
Baughman, Robert P.
Castelino, Flavia V.
Christmann, Romy B.
Christopher-Stine, Lisa
Collard, Harold R.
Cottin, Vincent
Danoff, Sonye
Highland, Kristin B.
Hummers, Laura
Shah, Ami A.
Kim, Dong Soon
Lynch, David A.
Miller, Frederick W.
Proudman, Susanna M.
Richeldi, Luca
Ryu, Jay H.
Sandorfi, Nora
Sarver, Catherine
Wells, Athol U.
Strand, Vibeke
Matteson, Eric L.
Brown, Kevin K.
Seibold, James R.
TI Connective tissue disease related interstitial lung diseases and
idiopathic pulmonary fibrosis: provisional core sets of domains and
instruments for use in clinical trials
SO THORAX
LA English
DT Article
ID GEORGES RESPIRATORY QUESTIONNAIRE; QUALITY-OF-LIFE; SYSTEMIC-SCLEROSIS;
SCLERODERMA LUNG; END-POINT; VALIDITY; IPF; MORTALITY; COUGH;
CYCLOPHOSPHAMIDE
AB Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities.
Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF).
Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed.
Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.
C1 [Saketkoo, Lesley Ann] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA.
[Mittoo, Shikha] Univ Toronto, Toronto, ON, Canada.
[Huscher, Doerte] German Rheumatism Res Ctr, Berlin, Germany.
[Huscher, Doerte] Charite, D-13353 Berlin, Germany.
[Khanna, Dinesh; Flaherty, Kevin R.; Phillips, Kristine] Univ Michigan, Ann Arbor, MI 48109 USA.
[Dellaripa, Paul F.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Distler, Oliver] Univ Zurich Hosp, CH-8091 Zurich, Switzerland.
[Frankel, Sid] Univ Manitoba, Winnipeg, MB R3T 2N2, Canada.
[Oddis, Chester V.] Univ Pittsburgh, Pittsburgh, PA USA.
[Denton, Christopher P.] Royal Free Hosp, London NW3 2QG, England.
[Fischer, Aryeh; Swigris, Jeffrey; Lynch, David A.; Brown, Kevin K.] Natl Jewish Hlth, Denver, CO USA.
[Kowal-Bielecka, Otylia M.] Med Univ Bialystok, Bialystok, Poland.
[LeSage, Daphne] Patient Res Partner, Off Publ Hlth, New Orleans, LA USA.
[Merkel, Peter A.; Sandorfi, Nora] Univ Penn, Philadelphia, PA 19104 USA.
[Pittrow, David] Univ Dresden, Dresden, Germany.
[Antoniou, Katerina] Univ Crete, Iraklion, Greece.
[Baughman, Robert P.] Univ Cincinnati, Cincinnati, OH USA.
[Castelino, Flavia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Christmann, Romy B.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Christopher-Stine, Lisa; Danoff, Sonye; Hummers, Laura; Shah, Ami A.] Johns Hopkins Univ, Baltimore, MD USA.
[Collard, Harold R.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Cottin, Vincent] Univ Lyon 1, F-69365 Lyon, France.
[Highland, Kristin B.] Cleveland Clin, Cleveland, OH 44106 USA.
[Kim, Dong Soon] Univ Ulsan, Asan Med Ctr, Ulsan 680749, South Korea.
[Miller, Frederick W.] NIEHS, NIH, Bethesda, MD USA.
[Proudman, Susanna M.] Univ Adelaide, Adelaide, SA, Australia.
[Richeldi, Luca] Univ Southampton, Resp Biomed Res Unit, Southampton SO9 5NH, Hants, England.
[Ryu, Jay H.; Matteson, Eric L.] Mayo Clin, Coll Med, Rochester, MN USA.
[Sarver, Catherine] Patient Res Partner, Bethesda, MD USA.
[Wells, Athol U.] Royal Brompton Hosp, London SW3 6LY, England.
[Wells, Athol U.] Natl Heart & Lung Inst, London, England.
[Strand, Vibeke] Stanford Univ, Palo Alto, CA 94304 USA.
[Seibold, James R.] Scleroderma Res Consultants LLC, Avon, CT USA.
RP Saketkoo, LA (reprint author), Louisiana State Univ, Hlth Sci Ctr New Orleans, LSU Scleroderma & Sarcoidosis Patient, Dept Med,Sect Rheumatol, 1542 Tulane Ave, New Orleans, LA 70112 USA.
EM ctd.ild@gmail.com
RI Keen, Kevin/D-5628-2013; Mittoo, Shikha/C-4616-2015; Baddini Martinez,
Jose/E-3098-2012; Riemekasten, Gabriela/B-5019-2017; Kairalla,
Ronaldo/D-5736-2014;
OI Keen, Kevin/0000-0001-5695-0505; Kairalla, Ronaldo/0000-0001-7194-0479;
Porter, Joanna/0000-0002-7307-169X; Miller,
Frederick/0000-0003-2831-9593; Dixon, William/0000-0001-5881-4857
FU intramural division of the National Institute of Environmental Health
Sciences, National Institutes of Health; Brigham and Women's Hospital;
Charite Hospital-Berlin; German Rheumatism Research Centre; Ira J Fine
Discovery Fund; Jonathan and Lisa Rye Scleroderma Research Foundation;
Louisiana State University Health Sciences Center-New Orleans; Mayo
Clinic-Rochester; National Jewish Hospital Denver; Louisiana State
Office of Public Health-New Orleans; OMERACT (Outcome Measures in
Rheumatology); Scleroderma Foundation; Sibley Hospital Foundation; Sonia
Roth AARC Foundation; Abbott Laboratories Canada; Actelion;
Boehringer-Ingelheim Pharmaceuticals; Celgene; Intermune; Sigma Tau;
UCB; United Therapeutics
FX Non-profit support: These studies were supported in part by the
intramural division of the National Institute of Environmental Health
Sciences, National Institutes of Health; and the following non-profit
organisations: Brigham and Women's Hospital, Charite Hospital-Berlin,
German Rheumatism Research Centre, Ira J Fine Discovery Fund, Jonathan
and Lisa Rye Scleroderma Research Foundation, Louisiana State University
Health Sciences Center-New Orleans, Mayo Clinic-Rochester, National
Jewish Hospital Denver, Louisiana State Office of Public Health-New
Orleans, OMERACT (Outcome Measures in Rheumatology), Scleroderma
Foundation, Sibley Hospital Foundation, and Sonia Roth AARC Foundation.
Commercial Interest Support: Abbott Laboratories Canada, Actelion,
Boehringer-Ingelheim Pharmaceuticals, Celgene, Intermune, Sigma Tau, UCB
and United Therapeutics.
NR 41
TC 28
Z9 29
U1 2
U2 13
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0040-6376
EI 1468-3296
J9 THORAX
JI Thorax
PD MAY
PY 2014
VL 69
IS 5
BP 428
EP 436
DI 10.1136/thoraxjnl-2013-204202
PG 9
WC Respiratory System
SC Respiratory System
GA AY5ZW
UT WOS:000347648600009
PM 24368713
ER
PT J
AU Bilic, E
Grkovic, L
Pulanic, D
Seiwerth, RS
Bilic, E
Nemet, D
Pavletic, SZ
AF Bilic, E.
Grkovic, L.
Pulanic, D.
Seiwerth, R. Serventi
Bilic, E.
Nemet, D.
Pavletic, S. Z.
TI Small fiber neuropathy in patients with chronic graft-versus-host
disease after allogeneic hematopoietic stem cell transplantation:
preliminary results of a prospective study
SO JOURNAL OF NEUROLOGY
LA English
DT Meeting Abstract
CT Joint Congress of European Neurology
CY MAY 31-JUN 03, 2014
CL Istanbul, TURKEY
SP European Federat Neurol Soc
C1 [Bilic, E.] Univ Zagreb, Sch Med, Clin Hosp Ctr Zagreb, Dept Neurol, Zagreb 41001, Croatia.
[Grkovic, L.; Pulanic, D.; Seiwerth, R. Serventi; Nemet, D.] Univ Zagreb, Sch Med, Clin Hosp Ctr Zagreb, Dept Hematol, Zagreb 41001, Croatia.
[Bilic, E.] Univ Zagreb, Sch Med, Clin Hosp Ctr Zagreb, Dept Pediat Hematol & Oncol, Zagreb 41001, Croatia.
[Pavletic, S. Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
EI 1432-1459
J9 J NEUROL
JI J. Neurol.
PD MAY
PY 2014
VL 261
SU 1
MA PP1251
BP S312
EP S312
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AY6KA
UT WOS:000347674001044
ER
PT J
AU Vural, A
Johnson, J
Singleton, A
Temucin, CM
AF Vural, A.
Johnson, J.
Singleton, A.
Temucin, C. M.
TI Adult-onset case of Brown-Vialetto-Van-Laere syndrome with SLC52A3
mutation
SO JOURNAL OF NEUROLOGY
LA English
DT Meeting Abstract
CT Joint Congress of European Neurology
CY MAY 31-JUN 03, 2014
CL Istanbul, TURKEY
SP European Federat Neurol Soc
C1 [Vural, A.] Besni Govt Hosp, Dept Neurol, Adiyaman, Turkey.
[Johnson, J.; Singleton, A.] Natl Inst Ageing, Neurogenet Lab, NIH, Bethesda, MD USA.
[Temucin, C. M.] Hacettepe Univ, Fac Med, Dept Neurol, TR-06100 Ankara, Turkey.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
EI 1432-1459
J9 J NEUROL
JI J. Neurol.
PD MAY
PY 2014
VL 261
SU 1
MA PP4091
BP S426
EP S426
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AY6KA
UT WOS:000347674001320
ER
PT J
AU Warnke, C
von Geldern, G
Markwerth, P
Dehmel, T
Hoepner, R
Gold, R
Pawlita, M
Kumpfel, T
Maurer, M
Stangel, M
Wegner, F
Hohlfeld, R
Straeten, V
Limmroth, V
Weber, T
Hermsen, D
Kleinschnitz, C
Hartung, HP
Wattjes, MP
Svenningson, A
Major, E
Olsson, T
Kieseier, BC
Adams, O
AF Warnke, C.
von Geldern, G.
Markwerth, P.
Dehmel, T.
Hoepner, R.
Gold, R.
Pawlita, M.
Kuempfel, T.
Maeurer, M.
Stangel, M.
Wegner, F.
Hohlfeld, R.
Straeten, V.
Limmroth, V.
Weber, T.
Hermsen, D.
Kleinschnitz, C.
Hartung, H. -P.
Wattjes, M. P.
Svenningson, A.
Major, E.
Olsson, T.
Kieseier, B. C.
Adams, O.
TI The CSF JCV antibody index for diagnosis of natalizumab-associated PML
SO JOURNAL OF NEUROLOGY
LA English
DT Meeting Abstract
CT Joint Congress of European Neurology
CY MAY 31-JUN 03, 2014
CL Istanbul, TURKEY
SP European Federat Neurol Soc
C1 [Warnke, C.; Markwerth, P.; Dehmel, T.; Hermsen, D.; Hartung, H. -P.; Kieseier, B. C.; Adams, O.] Univ Dusseldorf, Dusseldorf, Germany.
[von Geldern, G.; Major, E.] NINDS, Bethesda, MD 20892 USA.
[Hoepner, R.; Gold, R.] Ruhr Univ Bochum, St Josef Hosp, Bochum, Germany.
[Pawlita, M.] German Canc Res Ctr, Heidelberg, Germany.
[Kuempfel, T.; Hohlfeld, R.] Univ Munich, Munich, Germany.
[Maeurer, M.] Caritas Hosp, Bad Mergentheim, Germany.
[Stangel, M.; Wegner, F.] Hannover Med Sch MHH, Hannover, Germany.
[Straeten, V.] Johannes Wesling Hosp Minden, Minden, Germany.
[Limmroth, V.] Merheim Hosp, Cologne, Germany.
[Weber, T.] Marienhospital, Hamburg, Germany.
[Kleinschnitz, C.] Univ Wurzburg, D-97070 Wurzburg, Germany.
[Wattjes, M. P.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
[Svenningson, A.] Umea Univ Hosp, S-90185 Umea, Sweden.
[Olsson, T.] Karolinska Inst, Stockholm, Sweden.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
EI 1432-1459
J9 J NEUROL
JI J. Neurol.
PD MAY
PY 2014
VL 261
SU 1
MA OS2124
BP S44
EP S45
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AY6KA
UT WOS:000347674000117
ER
PT J
AU Gipson, C
Brown, P
AF Gipson, Chester
Brown, Patricia
TI A word from USDA and OLAW
SO LAB ANIMAL
LA English
DT Editorial Material
C1 [Gipson, Chester] USDA, APHIS, AC, Washington, DC 20250 USA.
[Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD USA.
RP Gipson, C (reprint author), USDA, APHIS, AC, Washington, DC 20250 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
EI 1548-4475
J9 LAB ANIMAL
JI Lab Anim.
PD MAY
PY 2014
VL 43
IS 5
BP 159
EP 159
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA AZ2ZC
UT WOS:000348096700014
PM 24751846
ER
PT J
AU Urquidez-Romero, R
Esparza-Romero, J
Chaudhari, LS
Begay, RC
Giraldo, M
Ravussin, E
Knowler, WC
Hanson, RL
Bennett, PH
Schulz, LO
Valencia, ME
AF Urquidez-Romero, Rene
Esparza-Romero, Julian
Chaudhari, Lisa S.
Begay, R. Cruz
Giraldo, Mario
Ravussin, Eric
Knowler, William C.
Hanson, Robert L.
Bennett, Peter H.
Schulz, Leslie O.
Valencia, Mauro E.
TI Study Design of the Maycoba Project: Obesity and Diabetes in Mexican
Pimas
SO AMERICAN JOURNAL OF HEALTH BEHAVIOR
LA English
DT Article
DE type 2 diabetes; prevalence; environmental changes; Pima Indians
ID DAILY ENERGY-EXPENDITURE; DOUBLY LABELED WATER; ENZYMATIC DETERMINATION;
PHYSICAL-ACTIVITY; AMERICAN-INDIANS; LIFE-STYLE; ASSOCIATION;
CHOLESTEROL; PREVALENCE; IDENTIFICATION
AB Objective: To focus on the rationale and methods of the Maycoba Project. Methods: Study population included Mexican Pima Indians (MPI) and Blancos aged >= 20-years, living in the village of Maycoba and surrounding area. Surveys in 1995 and 2010 included a medical history, biochemical and anthropometric measurements. Additionally, socioeconomic, physical activity, and dietary interviews were conducted. The 2010 study incorporated investigations on type 2 diabetes (T2D) and obesity-associated genetic alleles and human-environment changes. Results: The study results are limited to demographic data and description of the eligible and examined sample. Conclusions: This study may yield important information on T2D and obesity etiology in a traditional population exposed to environmental changes.
C1 [Urquidez-Romero, Rene] Univ Autonoma Ciudad Juarez, Dept Ciencias Salud, Inst Ciencias Biomed, Ciudad Juarez, Chihuahua, Mexico.
[Esparza-Romero, Julian; Valencia, Mauro E.] Ctr Invest Alimentac & Desarrollo, Dept Nutr Publ & Salud, Ac Hermosillo, Sonora, Mexico.
[Chaudhari, Lisa S.; Begay, R. Cruz; Schulz, Leslie O.] No Arizona Univ, Coll Hlth & Human Serv, Flagstaff, AZ 86011 USA.
[Giraldo, Mario] Calif State Univ Northridge, Dept Geog, Northridge, CA 91330 USA.
[Ravussin, Eric] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
[Knowler, William C.; Hanson, Robert L.; Bennett, Peter H.] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
RP Valencia, ME (reprint author), Ctr Invest Alimentac & Desarrollo, Dept Nutr Publ & Salud, Ac Hermosillo, Sonora, Mexico.
EM mauro@ciad.mx
FU NIDDK NIH HHS [R01 DK082568, 1R01DK082568-01A1, P30 DK072476]
NR 38
TC 2
Z9 2
U1 0
U2 6
PU PNG PUBLICATIONS
PI OAK RIDGE
PA 2205-K OAK RIDGE RD, #115, OAK RIDGE, NC 27310 USA
SN 1945-7359
J9 AM J HEALTH BEHAV
JI Am. J. Health Behav.
PD MAY
PY 2014
VL 38
IS 3
BP 370
EP 378
DI 10.5993/AJHB.38.3.6
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AS1JB
UT WOS:000344036300006
PM 24636033
ER
PT J
AU Logan, J
Kim, SW
Pareto, D
Telang, F
Wang, GJ
Fowler, JS
Biegon, A
AF Logan, Jean
Kim, Sung Won
Pareto, Deborah
Telang, Frank
Wang, Gene-Jack
Fowler, Joanna S.
Biegon, Anat
TI Kinetic Analysis of [C-11]Vorozole Binding in the Human Brain with
Positron Emission Tomography
SO MOLECULAR IMAGING
LA English
DT Article
ID MONOAMINE-OXIDASE-A; IN-VIVO; AROMATASE INHIBITOR; PET; BOLUS;
CYTOCHROME-P450; INFUSION; SMOKING; POTENT; RAT
AB Using positron emission tomography, we investigated the kinetics of [C-11]vorozole ([C-11]VOR), a radiotracer for the enzyme aromatase that catalyzes the last step in estrogen biosynthesis. Six subjects were scanned under baseline conditions followed by retest 2 weeks later. The retest was followed by a blocking study with 2.5 mg of the aromatase inhibitor letrozole. The binding potential (BPNDA) was estimated from a Lassen plot using the total tissue distribution volume (V-T) for baseline and blocked. BPNDA for the thalamus was found to be 15 times higher than that for the cerebellum. From the letrozole studies, we found that [C-11]VOR exhibits a slow binding compartment (small k(4)) that has a nonspecific and a blockable component. Because of the sensitivity of V-T to variations in k(4), a common value was used for the four highest binding regions. We also considered the tissue uptake to plasma ratio for 60 to 90 minutes as an outcome measure. Using the ratio method, the difference between the highest and lowest was 2.4 compared to 3.5 for the V-T. The ratio method underestimates the high regions but is less variable and may be more suitable for patient studies. Because of its kinetics and distribution, this tracer is not a candidate for a bolus infusion or reference tissue methods.
C1 [Logan, Jean] Brookhaven Natl Lab, Dept Biosci, Upton, NY 11973 USA.
NIAAA, Bethesda, MD USA.
Hosp Valle De Hebron, Magnet Resonance Unit, Barcelona, Spain.
CIBER BBN, Zaragoza, Spain.
Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA.
SUNY Stony Brook, Sch Med, Dept Neurol, Stony Brook, NY 11794 USA.
RP Logan, J (reprint author), Brookhaven Natl Lab, Dept Biosci, Upton, NY 11973 USA.
EM jean.logan@nyumc.org
FU [1R21EB012707]
FX Financial disclosure of authors: This study was supported by grant
1R21EB012707 (Anat Biegon PI).
NR 41
TC 0
Z9 0
U1 1
U2 2
PU B C DECKER INC
PI HAMILTON
PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA
SN 1535-3508
EI 1536-0121
J9 MOL IMAGING
JI Mol. Imaging
PD MAY
PY 2014
VL 13
IS 3
DI 10.2310/7290.2014.00004
PG 12
WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical
Imaging
SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical
Imaging
GA AS4AF
UT WOS:000344215300003
ER
PT J
AU Farrell, MM
La Porta, M
Gallagher, A
Vinson, C
Bernal, SB
AF Farrell, Margaret M.
La Porta, Madeline
Gallagher, Alissa
Vinson, Cynthia
Bernal, Sarah Bruce
TI Research to Reality: Moving Evidence Into Practice Through an Online
Community of Practice
SO PREVENTING CHRONIC DISEASE
LA English
DT Article
ID CANCER CONTROL; PARTNERSHIP; TRANSLATION; HEALTH
AB How can a community of practice help further the practical application of cancer control research? In 2011, the National Cancer Institute (NCI) launched an online community of practice, Research to Reality (R2R). R2R aims to infuse evidence-based strategies into communities by engaging researchers and practitioners in a joint approach to research dissemination. To measure community growth and engagement, NCI measures data across 3 program domains: content, interaction, and activity. NCI uses Web analytics, usability testing, and content analyses to manage and evaluate R2R. As of December 2013, R2R had more than 1,700 registered members. More than 500 researchers and practitioners register for the monthly cyber-seminars, and 40% return each month. R2R hosts more than 15,500 page views and 5,000 site visits in an average month. This article describes the process of convening this online community and quantifies our experiences to date.
C1 [Farrell, Margaret M.; La Porta, Madeline; Gallagher, Alissa; Vinson, Cynthia] NCI, Bethesda, MD 20892 USA.
[Bernal, Sarah Bruce] ICF Int, Fairfax, VA USA.
RP Farrell, MM (reprint author), NCI, 9609 Med Ctr Dr,Room 4E444, Bethesda, MD 20892 USA.
EM farrellm@mail.nih.gov
NR 20
TC 1
Z9 1
U1 1
U2 10
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1545-1151
J9 PREV CHRONIC DIS
JI Prev. Chronic Dis.
PD MAY
PY 2014
VL 11
AR 130272
DI 10.5888/pcd11.130272
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AR3XH
UT WOS:000343522000008
ER
PT J
AU Wells, SA
Santoro, M
AF Wells, Samuel A., Jr.
Santoro, Massimo
TI Update: The Status of Clinical Trials With Kinase Inhibitors in Thyroid
Cancer
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID PHASE-II TRIAL; CHRONIC MYELOID-LEUKEMIA; LYMPH-NODE METASTASES;
PPAR-GAMMA AGONIST; ACQUIRED-RESISTANCE; COLORECTAL-CANCER;
UNITED-STATES; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; RET/PTC
REARRANGEMENTS; PROGRESSIVE MEDULLARY
AB Context: Thyroid cancer is usually cured by timely thyroidectomy; however, the treatment of patients with advanced disease is challenging because their tumors are mostly unresponsive to conventional therapies. Recently, the malignancy has attracted much interest for two reasons: the dramatic increase in its incidence over the last three decades, and the discovery of the genetic mutations or chromosomal rearrangements causing most histological types of thyroid cancer.
Objective: This update reviews the molecular genetics of thyroid cancer and the clinical trials evaluating kinase inhibitors (KIs) in patients with locally advanced or metastatic disease. The update also reviews studies in other malignancies, which have identified mechanisms of efficacy, and also resistance, to specific KIs. This information has been critical both to the development of effective second-generation drugs and to the design of combinatorial therapeutic regimens. Finally, the update addresses the major challenges facing clinicians who seek to develop more effective therapy for patients with thyroid cancer.
Results: PubMed was searched from January 2000 to November 2013 using the following terms: thyroid cancer, treatment of thyroid cancer, clinical trials in thyroid cancer, small molecule therapeutics, kinase inhibitors, and next generation sequencing.
Conclusions: A new era in cancer therapy has emerged based on the introduction of KIs for the treatment of patients with liquid and solid organ malignancies. Patients with thyroid cancer have benefited from this advance and will continue to do so with the development of drugs having greater specificity and with the implementation of clinical trials of combined therapeutics to overcome drug resistance.
C1 [Wells, Samuel A., Jr.] NCI, Canc Genet Branch, Bethesda, MD 20892 USA.
[Santoro, Massimo] Univ Naples Federico II, Dipartimento Med Mol & Biotecnol Med, I-80131 Naples, Italy.
RP Wells, SA (reprint author), NCI, Canc Genet Branch, Bldg 37,Room 1-1A106,Convent Dr, Bethesda, MD 20892 USA.
EM wellss@mail.nih.gov
FU AstraZeneca PLC; Roche
FX S.A.W. has nothing to declare. M.S. has received research support from
AstraZeneca PLC, and Roche. He has also participated in a collaborative
study with Ariad Pharmaceuticals, Inc.
NR 141
TC 16
Z9 16
U1 0
U2 3
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAY
PY 2014
VL 99
IS 5
BP 1543
EP 1555
DI 10.1210/jc.2013-2622
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AP8PB
UT WOS:000342339800034
PM 24423326
ER
PT J
AU Sklavos, MM
Giri, N
Stratton, P
Alter, BP
Pinto, LA
AF Sklavos, Martha M.
Giri, Neelam
Stratton, Pamela
Alter, Blanche P.
Pinto, Ligia A.
TI Anti-Mullerian Hormone Deficiency in Females With Fanconi Anemia
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID PRIMARY OVARIAN INSUFFICIENCY; MENSTRUAL-CYCLE; RESERVE; CANCER;
PREGNANCY; FAILURE; MARKER; COHORT; RISK; AMH
AB Context: In females with Fanconi anemia (FA), infertility is often accompanied by diminished ovarian reserve and hypergonadotropic amenorrhea before the age of 30 years, suggesting primary ovarian insufficiency (POI). POI is typically diagnosed only after perimenopausal symptoms are observed.
Objective: The objective of the study was to assess whether serum anti-Mullerian hormone (AMH) levels can serve as a cycle-independent marker for the diagnosis of POI in patients with FA.
Design and Setting: This observational study used the National Cancer Institute's inherited bone marrow failure syndrome cohort at the National Institutes of Health Clinical Center.
Participants: The study included 22 females with FA, 20 unaffected female relatives of patients with FA, and 21 unrelated healthy females under 41 years of age.
Main Outcome Measure: Serum AMH, a marker of ovarian reserve, was measured in all participants.
Results: Females with FA had very low AMH levels (median 0.05 ng/mL; range 0-2.32 ng/mL; P < .01) when compared with unaffected relatives (median 2.10 ng/mL; range 0.04-4.73 ng/mL) and unrelated healthy females (median 1.92 ng/mL; range 0.31-6.64 ng/mL). All patients with FA older than 25 years of age were diagnosed with POI and had undetectable AMH levels.
Conclusions: AMH deficiency appears to be a shared trait across this heterogeneous FA cohort. Substantially reduced AMH levels in females with FA suggest a primary ovarian defect associated with reduced fertility. Measurement of AMH at the time of FA diagnosis and subsequent monitoring of AMH levels at regular intervals may be useful for the timely management of complications related to POI such as subfertility/infertility, osteoporosis, and menopausal symptoms.
C1 [Sklavos, Martha M.; Pinto, Ligia A.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Human Papillomavirus Immunol Lab, Frederick, MD 21702 USA.
[Giri, Neelam; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Giri, Neelam; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD 20814 USA.
RP Pinto, LA (reprint author), Leidos Biomed Res Inc, Human Papillomavirus Immunol Lab, Bldg 469,Room 111,1050 Boyles St, Frederick, MD 21702 USA.
EM pintol@mail.nih.gov
FU Fanconi Anemia Research Fund; Intramural Research Program of the
National Institutes of Health and the National Cancer Institute; Westat,
Inc. [N02CP-91026, N02-CP-11019, HHSN261200655001C]; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]
FX This work was supported in part by a research grant from Fanconi Anemia
Research Fund(fanconi.org) (to N.G.); the Intramural Research Program of
the National Institutes of Health and the National Cancer Institute (to
B.P.A. and N.G.); and by contracts N02CP-91026, N02-CP-11019, and
HHSN261200655001C with Westat, Inc. This project has been funded in
whole or in part with federal funds from the National Cancer Institute,
National Institutes of Health, under Contract HHSN261200800001E.
NR 31
TC 4
Z9 4
U1 1
U2 4
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAY
PY 2014
VL 99
IS 5
BP 1608
EP 1614
DI 10.1210/jc.2013-3559
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AP8PB
UT WOS:000342339800042
PM 24438373
ER
PT J
AU Bible, KC
Suman, VJ
Molina, JR
Smallridge, RC
Maples, WJ
Menefee, ME
Rubin, J
Karlin, N
Sideras, K
Morris, JC
Mclver, B
Hay, I
Fatourechi, V
Burton, JK
Webster, KP
Bieber, C
Traynor, AM
Flynn, PJ
Goh, BC
Isham, CR
Harris, P
Erlichman, C
AF Bible, Keith C.
Suman, Vera J.
Molina, Julian R.
Smallridge, Robert C.
Maples, William J.
Menefee, Michael E.
Rubin, Joseph
Karlin, Nina
Sideras, Kostandinos
Morris, John C., III
Mclver, Bryan
Hay, Ian
Fatourechi, Vahab
Burton, Jill K.
Webster, Kevin P.
Bieber, Carolyn
Traynor, Anne M.
Flynn, Patrick J.
Goh, Boon Cher
Isham, Crescent R.
Harris, Pamela
Erlichman, Charles
CA Endocrine Malignancies Disease Ori
Mayo Clinic Cancer Ctr
Mayo Phase 2 Consortium
TI A Multicenter Phase 2 Trial of Pazopanib in Metastatic and Progressive
Medullary Thyroid Carcinoma: MC057H
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ALTERNATING COMBINATION; CANCER; EFFICACY; SORAFENIB; SUNITINIB
AB Context: Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-alpha and -beta; and c-Kit. We previously reported a tumor response rate of 49% in patients with advanced differentiated thyroid cancer and 0% in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC).
Objective, Design, Setting, Patients, Intervention, and Outcome Measures: Having noted preclinical activity of pazopanib in MTC, patients with advanced MTC who had disease progression within the preceding 6 months were accrued to this multiinstitutional phase II clinical trial to assess tumor response rate (by Response Evaluation Criteria In Solid Tumors criteria) and safety of pazopanib given orally once daily at 800 mg until disease progression or intolerability.
Results: From September 22, 2008, to December 11, 2011, 35 individuals (80% males, median age 60 y) were enrolled. All patients have been followed up until treatment discontinuation or for a minimum of four cycles. Eight patients (23%) are still on the study treatment. The median number of therapy cycles was eight. Five patients attained partial Response Evaluation Criteria In Solid Tumors responses (14.3%; 90% confidence interval 5.8%-27.7%), with a median progression-free survival and overall survival of 9.4 and 19.9 months, respectively. Side effects included treatment-requiring (new) hypertension (33%), fatigue (14%), diarrhea (9%), and abnormal liver tests (6%); 3 of 35 patients (8.6%) discontinued therapy due to adverse events. There was one death of a study patient after withdrawal from the trial deemed potentially treatment related.
Conclusions: Pazopanib has promising clinical activity in metastatic MTC with overall manageable toxicities.
C1 [Bible, Keith C.; Molina, Julian R.; Rubin, Joseph; Sideras, Kostandinos; Burton, Jill K.; Webster, Kevin P.; Isham, Crescent R.; Erlichman, Charles] Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA.
[Suman, Vera J.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
[Morris, John C., III; Mclver, Bryan; Hay, Ian; Fatourechi, Vahab] Mayo Clin, Div Endocrinol, Rochester, MN 55905 USA.
[Smallridge, Robert C.] Mayo Clin Florida, Div Endocrinol, Jacksonville, FL 32224 USA.
[Maples, William J.; Menefee, Michael E.; Bieber, Carolyn] Mayo Clin Florida, Div Med Oncol, Jacksonville, FL 32224 USA.
[Karlin, Nina] Mayo Clin Arizona, Div Med Oncol, Scottsdale, AZ 85259 USA.
[Traynor, Anne M.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53705 USA.
[Flynn, Patrick J.] Minnesota Oncol Hematol, Minneapolis, MN 55407 USA.
[Goh, Boon Cher] Natl Univ Singapore Hosp, Singapore 119228, Singapore.
[Harris, Pamela] Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Bible, KC (reprint author), Div Med Oncol, 200 First St SW, Rochester, MN 55901 USA.
EM bible.keith@mayo.edu
FU National Cancer Institute [CA15083, CM62205]
FX This work was supported by National Cancer Institute Grants CA15083 and
CM62205.
NR 15
TC 23
Z9 24
U1 0
U2 2
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAY
PY 2014
VL 99
IS 5
BP 1687
EP 1693
DI 10.1210/jc.2013-3713
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AP8PB
UT WOS:000342339800051
PM 24606083
ER
PT J
AU Billings, LK
Jablonski, KA
Ackerman, RJ
Taylor, A
Fanelli, RR
McAteer, JB
Guiducci, C
Delahanty, LM
Dabelea, D
Kahn, SE
Franks, PW
Hanson, RL
Maruthur, NM
Shuldiner, AR
Mayer-Davis, EJ
Knowler, WC
Florez, JC
AF Billings, Liana K.
Jablonski, Kathleen A.
Ackerman, Rachel J.
Taylor, Andrew
Fanelli, Rebecca R.
McAteer, Jarred B.
Guiducci, Candace
Delahanty, Linda M.
Dabelea, Dana
Kahn, Steven E.
Franks, Paul W.
Hanson, Robert L.
Maruthur, Nisa M.
Shuldiner, Alan R.
Mayer-Davis, Elizabeth J.
Knowler, William C.
Florez, Jose C.
CA Diab Prevention Program Res Grp
TI The Influence of Rare Genetic Variation in SLC30A8 on Diabetes Incidence
and beta-Cell Function
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ZINC TRANSPORTER ZNT8; PREVENTION PROGRAM; INSULIN-SECRETION;
LIFE-STYLE; BASE-LINE; GLUCOSE; ASSOCIATION; INTERVENTION; METFORMIN;
VARIANTS
AB Context/Objective: The variant rs13266634 in SLC30A8, encoding a beta-cell-specific zinc transporter, is associated with type 2 diabetes. We aimed to identify other variants in SLC30A8 that increase diabetes risk and impair beta-cell function, and test whether zinc intake modifies this risk.
Design/Outcome: We sequenced exons in SLC30A8 in 380 Diabetes Prevention Program (DPP) participants and identified 44 novel variants, which were genotyped in 3445 DPP participants and tested for association with diabetes incidence and measures of insulin secretion and processing. We examined individual common variants and used gene burden tests to test 39 rare variants in aggregate.
Results: We detected a near-nominal association between a rare-variant genotype risk score and diabetes risk. Five common variants were associated with the oral disposition index. Various methods aggregating rare variants demonstrated associations with changes in oral disposition index and insulinogenic index during year 1 of follow-up. We did not find a clear interaction of zinc intake with genotype on diabetes incidence.
Conclusions: Individual common and an aggregate of rare genetic variation in SLC30A8 are associated with measures of beta-cell function in the DPP. Exploring rare variation may complement ongoing efforts to uncover the genetic influences that underlie complex diseases.
C1 [Billings, Liana K.; Ackerman, Rachel J.; Taylor, Andrew; Fanelli, Rebecca R.; McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.
[Billings, Liana K.; Delahanty, Linda M.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Billings, Liana K.; Delahanty, Linda M.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Billings, Liana K.] NorthShore Univ HealthSyst, Dept Med, Evanston, IL 60201 USA.
[Billings, Liana K.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA.
[Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA.
[Taylor, Andrew; McAteer, Jarred B.; Guiducci, Candace; Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Dabelea, Dana] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Denver, CO 80045 USA.
[Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA.
Univ Washington, Seattle, WA 98108 USA.
[Franks, Paul W.] Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, SE-20041 Malmo, Sweden.
[Hanson, Robert L.; Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ 85014 USA.
[Maruthur, Nisa M.] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Dept Med, Baltimore, MD 21205 USA.
[Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA.
[Mayer-Davis, Elizabeth J.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA.
RP Florez, JC (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,Simches Res Bldg CPZN 5-250, Boston, MA 02114 USA.
EM dppmail@biostat.bsc.gwu.edu
FU National Institutes of Health (NIH)/National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) [R01 DK072041]; NIH/NIDDK at the
DPP Data Coordinating Center in George Washington University [U01
DK048489]; NIH Office of Dietary Supplements; NRSA Institutional
Training Grant [T32 DK007028-35]; Endocrine Society's Lilly Scholar's
Award; NIH Loan Repayment Award; NIDDK [1 L30 DK089944-01]; Doris Duke
Charitable Foundation; NorthShore Auxiliary Research Scholar Award;
Department of Veterans Affairs; NIDDK of the NIH; NIDDK; Indian Health
Service; Office of Research on Minority Health; National Institute of
Child Health and Human Development; National Institute on Aging; Centers
for Disease Control and Prevention; Office of Research on Women's
Health; American Diabetes Association
FX This work was supported by National Institutes of Health (NIH)/National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant
R01 DK072041 to J.C.F., K.A.J., and A.R.S. and a subcontract from
NIH/NIDDK U01 DK048489 at the DPP Data Coordinating Center in George
Washington University to J.C.F., facilitated by a targeted grant from
the NIH Office of Dietary Supplements. During the course of this study,
L.K.B. was supported by NRSA Institutional Training Grant T32
DK007028-35 to the Massachusetts General Hospital, the Endocrine
Society's Lilly Scholar's Award, NIH Loan Repayment Award, NIDDK 1 L30
DK089944-01, Harvard Catalyst, a Distinguished Clinical Scientist Award
to David Altshuler from the Doris Duke Charitable Foundation, and the
NorthShore Auxiliary Research Scholar Award. S.E.K. is supported in part
by the Department of Veterans Affairs.; The NIDDK of the NIH provided
funding to the clinical centers and the Coordinating Center for the
design and conduct of the study and collection, management, analysis,
and interpretation of the data. The Southwestern American Indian Centers
were supported directly by the NIDDK and the Indian Health Service. The
General Clinical Research Center Program, National Center for Research
Resources, supported data collection at many of the clinical centers.
Funding for data collection and participant support was also provided by
the Office of Research on Minority Health, the National Institute of
Child Health and Human Development, the National Institute on Aging, the
Centers for Disease Control and Prevention, the Office of Research on
Women's Health, the Department of Veterans Affairs, and the American
Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided
medication. This research was also supported, in part, by the intramural
research program of the NIDDK. LifeScan Inc, Health O Meter, Hoechst
Marion Roussel, Inc, Merck-Medco Managed Care, Inc, Merck and Co, Nike
Sports Marketing, Slim Fast Foods Co, and Quaker Oats Co donated
materials, equipment, or medicines for concomitant conditions. McKesson
BioServices Corp, Matthews Media Group, Inc, and the Henry M. Jackson
Foundation provided support services under subcontract with the
Coordinating Center. The opinions expressed are those of the
investigators and do not necessarily reflect the views of the Indian
Health Service or other funding agencies. A complete list of centers,
investigators, and staff can be found in the Supplemental Appendix.
NR 19
TC 6
Z9 6
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAY
PY 2014
VL 99
IS 5
BP E926
EP E930
DI 10.1210/jc.2013-2378
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AP8PB
UT WOS:000342339800025
PM 24471563
ER
PT J
AU Bram, Z
Xekouki, P
Louiset, E
Keil, MF
Avgeropoulos, D
Giatzakis, C
Nesterova, M
Sinaii, N
Hofland, LJ
Cherqaoui, R
Lefebvre, H
Stratakis, CA
AF Bram, Zakariae
Xekouki, Paraskevi
Louiset, Estelle
Keil, Meg F.
Avgeropoulos, Dimitrios
Giatzakis, Christoforos
Nesterova, Maria
Sinaii, Ninet
Hofland, Leo J.
Cherqaoui, Rabia
Lefebvre, Herve
Stratakis, Constantine A.
TI Does Somatostatin Have a Role in the Regulation of Cortisol Secretion in
Primary Pigmented Nodular Adrenocortical Disease (PPNAD)? A Clinical and
in Vitro Investigation
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID GASTRIC-INHIBITORY POLYPEPTIDE; CUSHINGS-SYNDROME; RECEPTOR SUBTYPES;
CARNEY COMPLEX; GLUCOCORTICOID-RECEPTOR; NEUROENDOCRINE TUMORS;
MEDICAL-TREATMENT; GENE-EXPRESSION; ADRENAL-TUMORS; DEXAMETHASONE
AB Context: Somatostatin (SST) receptors (SSTRs) are expressed in a number of tissues, including the adrenal cortex, but their role in cortisol secretion has not been well characterized.
Objectives: The objective of the study was to investigate the expression of SSTRs in the adrenal cortex and cultured adrenocortical cells from primary pigmented nodular adrenocortical disease (PPNAD) tissues and to test the effect of a single injection of 100 mu g of the SST analog octreotide on cortisol secretion in patients with PPNAD.
Setting and Design: The study was conducted at an academic research laboratory and clinical research center. Expression of SSTRs was examined in 26 PPNAD tissues and the immortalized PPNAD cell line CAR47. Ten subjects with PPNAD underwent a randomized, single-blind, crossover study of their cortisol secretion every 30 minutes over 12 hours (6:00 PM to 6:00 AM) before and after the midnight administration of octreotide 100 mu g sc.
Methods: SSTRs expression was investigated by quantitative PCR and immunohistochemistry. The CAR47 and primary cell lines were studied in vitro. The data of the 10 patients were analyzed before and after the administration of octreotide.
Results: All SSTRs, especially SSTR1-3, were expressed in PPNAD at significantly higher levels than in normal adrenal. SST was found to differentially regulate expression of its own receptors in the CAR47 cell line. However, the administration of octreotide to patients with PPNAD did not significantly affect cortisol secretion.
Conclusions: SSTRs are overexpressed in PPNAD tissues in comparison with normal adrenal cortex. Octreotide did not exert any significant effect on cortisol secretion in a short clinical pilot study in a small number of patients with PPNAD, but long-acting SST analogs targeting multiple SSTRs may be worth investigating in this condition.
C1 [Bram, Zakariae; Louiset, Estelle; Lefebvre, Herve] Univ Rouen, Inst Res & Innovat Biomed, Lab Neuronal & Neuroendocrine Differentiat & Comm, INSERM U982, F-76821 Rouen, France.
[Xekouki, Paraskevi; Avgeropoulos, Dimitrios; Giatzakis, Christoforos; Nesterova, Maria; Cherqaoui, Rabia; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Sect Endocrinol & Genet, Bethesda, MD 20892 USA.
[Keil, Meg F.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Pediat Endocrinol Inter Inst Training Program, NIH, Bethesda, MD 20892 USA.
[Sinaii, Ninet] NICHHD, NIH, Ctr Clin, Bethesda, MD 20892 USA.
NIH, Bethesda, MD 20892 USA.
[Hofland, Leo J.] Erasmus MC, NL-3015 GE Rotterdam, Netherlands.
[Lefebvre, Herve] Univ Hosp Rouen, Inst Res & Innovat Biomed, Dept Endocrinol, F-76031 Rouen, France.
RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bldg 10,CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU National Institutes of Health Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; Agence Nationale de la Recherche and Societe Francaise
d'Endocrinologie
FX This work was supported by the National Institutes of Health Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development. Z.B. was the recipient of grants
from Agence Nationale de la Recherche and Societe Francaise
d'Endocrinologie.
NR 36
TC 1
Z9 1
U1 0
U2 2
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAY
PY 2014
VL 99
IS 5
BP E891
EP E901
DI 10.1210/jc.2013-2657
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AP8PB
UT WOS:000342339800021
PM 24512486
ER
PT J
AU Nicolaides, NC
Roberts, ML
Kino, T
Braatvedt, G
Hurt, DE
Katsantoni, E
Sertedaki, A
Chrousos, GP
Charmandari, E
AF Nicolaides, Nicolas C.
Roberts, Michael L.
Kino, Tomoshige
Braatvedt, Geoffrey
Hurt, Darrell E.
Katsantoni, Eleni
Sertedaki, Amalia
Chrousos, George P.
Charmandari, Evangelia
TI A Novel Point Mutation of the Human Glucocorticoid Receptor Gene Causes
Primary Generalized Glucocorticoid Resistance Through Impaired
Interaction With the LXXLL Motif of the p160 Coactivators: Dissociation
of the Transactivating and Transreppressive Activities
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID LIGAND-BINDING DOMAIN; STRESS-RESPONSE; DISEASE; GR
AB Context: Primary generalized glucocorticoid resistance is a rare genetic disorder characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. The molecular basis of the condition has been ascribed to inactivating mutations in the human glucocorticoid receptor (hGR) gene.
Objective: The objective of the study was to present three new cases caused by a novel mutation in the hGR gene and to delineate the molecular mechanisms through which the mutant receptor impairs glucocorticoid signal transduction.
Design and Results: The index case (father) and his two daughters presented with increased urinary free cortisol excretion and resistance of the hypothalamic-pituitary-adrenal axis to dexamethasone suppression in the absence of clinical manifestations suggestive of Cushing syndrome. All subjects harbored a novel, heterozygous, point mutation (T -> G) at nucleotide position 1724 of the hGR gene, which resulted in substitution of valine by glycine at amino acid 575 of the receptor. Compared with the wild-type receptor, the hGR alpha V575G demonstrated a significant (33%) reduction in its ability to transactivate the mouse mammary tumor virus promoter in response to dexamethasone, a 50% decrease in its affinity for the ligand, and a 2.5-fold delay in nuclear translocation. Although it did not exert a dominant negative effect on the wild-type receptor and preserved its ability to bind to DNA, hGR alpha V575G displayed significantly enhanced (similar to 80%) ability to transrepress the nuclear factor-kappa B signaling pathway. Finally, the mutant receptor hGR alpha V575G demonstrated impaired interaction with the LXXLL motif of the glucocorticoid receptor-interacting protein 1 coactivator in vitro and in computer-based structural simulation via its defective activation function-2 (AF-2) domain.
Conclusions: The natural mutant receptor hGR alpha V575G causes primary generalized glucocorticoid resistance by affecting multiple steps in the glucocorticoid signaling cascade, including the affinity for the ligand, the time required for nuclear translocation, and the interaction with the glucocorticoid-interacting protein-1 coactivator.
C1 [Nicolaides, Nicolas C.; Roberts, Michael L.; Sertedaki, Amalia; Chrousos, George P.; Charmandari, Evangelia] Univ Athens, Sch Med, Aghia Sophia Childrens Hosp, Dept Pediat 1,Div Endocrinol Metab & Diabet, Athens 11527, Greece.
[Nicolaides, Nicolas C.; Roberts, Michael L.; Sertedaki, Amalia; Chrousos, George P.; Charmandari, Evangelia] Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Endocrinol & Metab, Athens 11527, Greece.
[Katsantoni, Eleni] Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Hematol, Athens 11527, Greece.
[Kino, Tomoshige] NIAID, Off Cyber Infrastructure & Computat Biol, NIH, Unit Mol Hormone Action, Bethesda, MD 20892 USA.
[Hurt, Darrell E.] NIAID, Off Cyber Infrastructure & Computat Biol, NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Braatvedt, Geoffrey] Univ Auckland, Dept Med, Auckland 1142, New Zealand.
RP Charmandari, E (reprint author), Univ Athens, Sch Med, Aghia Sophia Childrens Hosp, Dept Pediat 1,Div Endocrinol Metab & Diabet, Thivon & Papadiamantopoulou St, Athens 11527, Greece.
EM evangelia.charmandari@googlemail.com
RI Charmandari, Evangelia/B-6701-2011
FU European Union (European Social Fund); Greek national funds through the
Operational Program "Education and Lifelong Learning" of the National
Strategic Reference Framework, Research Funding Program, THALIS,
University of Athens, Athens, Greece; Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Bethesda, Maryland; National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, Maryland
FX This work was supported by the European Union (European Social Fund) and
Greek national funds through the Operational Program "Education and
Lifelong Learning" of the National Strategic Reference Framework,
Research Funding Program, THALIS, University of Athens, Athens, Greece;
the intramural program of the Eunice Kennedy Shriver National Institute
of Child Health and Human Development, National Institutes of Health,
Bethesda, Maryland 20892; and the National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
NR 19
TC 11
Z9 11
U1 0
U2 6
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAY
PY 2014
VL 99
IS 5
BP E902
EP E907
DI 10.1210/jc.2013-3005
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AP8PB
UT WOS:000342339800022
PM 24483153
ER
PT J
AU Roe, A
Hillman, J
Butts, S
Smith, M
Rader, D
Playford, M
Mehta, NN
Dokras, A
AF Roe, Andrea
Hillman, Jennifer
Butts, Samantha
Smith, Mathew
Rader, Daniel
Playford, Martin
Mehta, Nehal N.
Dokras, Anuja
TI Decreased Cholesterol Efflux Capacity and Atherogenic Lipid Profile in
Young Women With PCOS
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID POLYCYSTIC-OVARY-SYNDROME; HIGH-DENSITY-LIPOPROTEIN;
CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; PARTICLE-SIZE; RISK;
DYSLIPIDEMIA; HEART; MANAGEMENT; TRANSPORT
AB Context: Women with polycystic ovary syndrome (PCOS) have a high prevalence of cardiovascular disease (CVD) risk factors including dyslipidemia. Lipoproteins are heterogeneous, and measurement of serum lipids provides only the size of the pool and does not predict their function or composition. Recently, high-density lipoprotein cholesterol (HDL-C) function, as determined by cholesterol efflux capacity from macrophages, has been shown to be an independent predictor of subclinical CVD.
Objective: The aim of the study was to comprehensively evaluate lipoprotein profile including lipid particle size and number and cholesterol efflux capacity in PCOS to better define CVD risk.
Design and Setting: A case control study was performed at an academic PCOS center.
Patients: Women with PCOS (n = 124) and geographically matched controls (n = 67) were included in the study.
Main Outcome Measures: The primary outcome was to measure HDL-C efflux capacity by an ex vivo system involving the incubation of macrophages with apolipoprotein (Apo) B-depleted serum from subjects, and the secondary outcome was to measure lipid particle size and number using nuclear magnetic resonance spectroscopy.
Results: Women with PCOS had significantly higher body mass index and blood pressure but similar HDL-C and low-density lipoprotein cholesterol levels compared to controls. The mean ApoA1 levels were lower, and the ApoB/ApoA1 ratio was higher in PCOS subjects compared to controls (P < .01). There were no differences in ApoB levels. Women with PCOS had an 7% decrease in normalized cholesterol efflux capacity compared to controls (P < .003). Cholesterol efflux capacity in PCOS correlated with body mass index, ApoA1, HDL-C, and the presence of metabolic syndrome. In a multivariable regression model, PCOS was significantly associated with diminished cholesterol efflux. PCOS was also associated with an atherogenic profile including an increase in large very low-density lipoprotein particles, very low-density lipoprotein (VLDL) size, and small low-density lipoprotein cholesterol particles (P < .01).
Conclusions: Our novel findings of decreased cholesterol efflux and an atherogenic lipid particle number and size pattern in women with PCOS, independent of obesity, further substantiate the increased risk of CVD in this population.
C1 [Roe, Andrea; Hillman, Jennifer; Butts, Samantha; Smith, Mathew; Dokras, Anuja] Univ Penn, Dept Obstet & Gynecol, Div Reprod Endocrinol, Philadelphia, PA 19104 USA.
[Rader, Daniel] Univ Penn, Translat Res Ctr 11 125, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA.
[Playford, Martin; Mehta, Nehal N.] NHLBI, Sect Inflammat & Cardiometabol Dis, Bethesda, MD 20892 USA.
RP Dokras, A (reprint author), Univ Penn, Dept Obstet & Gynecol, Div Reprod Endocrinol, 3701 Market St,Suite 800, Philadelphia, PA 19104 USA.
EM adokras@obgyn.upenn.edu
FU National Institutes of Health [DK19525]; FOCUS medical student
fellowship awards at the University of Pennsylvania
FX This work was funded by National Institutes of Health Grant DK19525 to
the Diabetes Research Center RIA Biomarkers Core at the University of
Pennsylvania. A.R. and J.H. were recipients of FOCUS medical student
fellowship awards at the University of Pennsylvania.
NR 31
TC 15
Z9 15
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAY
PY 2014
VL 99
IS 5
BP E841
EP E847
DI 10.1210/jc.2013-3918
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AP8PB
UT WOS:000342339800012
PM 24512495
ER
PT J
AU Klenke, U
Taylor-Burds, C
Wray, S
AF Klenke, Ulrike
Taylor-Burds, Carol
Wray, Susan
TI Metabolic Influences on Reproduction: Adiponectin Attenuates GnRH
Neuronal Activity in Female Mice
SO ENDOCRINOLOGY
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; ENDOTHELIAL-CELLS; LHRH NEURONS;
PARAVENTRICULAR NUCLEUS; CALCIUM OSCILLATOR; HORMONE-1 NEURONS; EXPLANT
CULTURES; GENE-EXPRESSION; PITUITARY-GLAND; ENERGY-BALANCE
AB Metabolic dysfunctions are often linked to reproductive abnormalities. Adiponectin (ADP), a peripheral hormone secreted by white adipose tissue, is important in energy homeostasis and appetite regulation. GnRH neurons are integral components of the reproductive axis, controlling synthesis, and release of gonadotropins. This report examined whether ADP can directly act on GnRH neurons. Double-label immunofluorescence on brain sections from adult female revealed that a subpopulation of GnRH neurons express ADP receptor (AdipoR) 2. GnRH/AdipoR2+ cells were distributed throughout the forebrain. To determine the influence of ADP on GnRH neuronal activity and the signal transduction pathway of AdipoR2, GnRH neurons maintained in explants were assayed using whole-cell patch clamping and calcium imaging. This mouse model system circumvents the dispersed distribution of GnRH neurons within the forebrain, making analysis of large numbers of GnRH cells possible. Single-cell PCR analysis and immunocytochemistry confirmed the presence of AdipoR2 in GnRH neurons in explants. Functional analysis revealed 20% of the total GnRH population responded to ADP, exhibiting hyperpolarization or decreased calcium oscillations. Perturbation studies revealed that ADP activates AMP kinase via the protein kinase C zeta/liver kinase B1 pathway. The modulation of GnRH neuronal activity by ADP demonstrated in this report directly links energy balance to neurons controlling reproduction.
C1 [Klenke, Ulrike; Taylor-Burds, Carol; Wray, Susan] NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Wray, S (reprint author), 35 Lincoln Dr, Bethesda, MD 20892 USA.
EM wrays@ninds.nih.gov
OI wray, susan/0000-0001-7670-3915
FU Intramural Research Program of the National Institutes of Health,
National Institute of Neurological Disorder and Stroke [NS002824-23]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Neurological
Disorder and Stroke Grant NS002824-23.
NR 76
TC 8
Z9 8
U1 0
U2 6
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAY
PY 2014
VL 155
IS 5
BP 1851
EP 1863
DI 10.1210/en.2013-1677
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AP8PY
UT WOS:000342342200027
PM 24564393
ER
PT J
AU Valdiserri, R
Khalsa, J
Dan, C
Holmberg, S
Zibbell, J
Holtzman, D
Lubran, R
Compton, W
AF Valdiserri, Ronald
Khalsa, Jag
Dan, Corinna
Holmberg, Scott
Zibbell, Jon
Holtzman, Deborah
Lubran, Robert
Compton, Wilson
TI Confronting the Emerging Epidemic of HCV Infection Among Young Injection
Drug Users
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID HEPATITIS-C VIRUS; UNITED-STATES; USE DISORDERS; NEW-YORK; RISK; ABUSE;
ADOLESCENTS; HEALTH; ADULTS; HIV
AB Hepatitis C virus infection is a significant public health problem in the United States and an important cause of morbidity and mortality. Recent reports document HCV infection increases among young injection drug users in several US regions, associated with America's prescription opioid abuse epidemic. Incident HCV infection increases among young injectors who have recently transitioned from oral opioid abuse present an important public health challenge requiring a comprehensive, community-based response. We summarize recommendations from a 2013 Office of HIV/AIDS and Infectious Disease Policy convening of experts in epidemiology, behavioral science, drug prevention and treatment, and other research; community service providers; and federal, state, and local government representatives. Their observations highlight gaps in our surveillance, program, and research portfolios and advocate a syndemic approach to this emerging public health problem.
C1 [Valdiserri, Ronald; Dan, Corinna] US Dept HHS, Off HIV AIDS & Infect Dis Policy, Washington, DC 20201 USA.
[Khalsa, Jag; Compton, Wilson] NIDA, Bethesda, MD 20892 USA.
[Lubran, Robert] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA.
[Holmberg, Scott; Zibbell, Jon; Holtzman, Deborah] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Valdiserri, R (reprint author), US Dept HHS, 200 Independence Ave SW,Room 443-H, Washington, DC 20201 USA.
EM ron.valdiserri@hhs.gov
OI Lubran, Robert/0000-0003-1235-5207
NR 51
TC 28
Z9 28
U1 3
U2 7
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD MAY
PY 2014
VL 104
IS 5
BP 816
EP 821
DI 10.2105/AJPH.2013.301812
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AP0XU
UT WOS:000341790600022
PM 24625174
ER
PT J
AU Choi, CI
Yoon, SP
Choi, JM
Kim, SS
Lee, YD
Birnbaumer, L
Suh-Kim, H
AF Choi, Chan-Il
Yoon, Sang-Phil
Choi, Jung-Mi
Kim, Sung-Soo
Lee, Young-Don
Birnbaumer, Lutz
Suh-Kim, Haeyoung
TI Simultaneous deletion of floxed genes mediated by CaMKII alpha-Cre in
the brain and in male germ cells: application to conditional and
conventional disruption of Go alpha
SO EXPERIMENTAL AND MOLECULAR MEDICINE
LA English
DT Article
DE brain; Cre; CaMKII alpha; Gnao; testis
ID CALMODULIN KINASE-II; TRANSGENE EXPRESSION; MOUSE-BRAIN; MICE;
RECOMBINATION; MUTAGENESIS; DEFICIENT; ALLELES; CORTEX; TRKB
AB The Cre/LoxP system is a well-established approach to spatially and temporally control genetic inactivation. The calcium/calmodulin-dependent protein kinase II alpha subunit (CaMKII alpha) promoter limits expression to specific regions of the forebrain and thus has been utilized for the brain-specific inactivation of the genes. Here, we show that CaMKII alpha-Cre can be utilized for simultaneous inactivation of genes in the adult brain and in male germ cells. Double transgenic Rosa26(+/stop-lacZ)::CaMKII alpha-Cre(+/Cre) mice generated by crossing CaMKII alpha-Cre(+/Cre) mice with floxed ROSA26 lacZ reporter (Rosa26(+/stop-lacZ)) mice exhibited lacZ expression in the brain and testis. When these mice were mated to wild-type females, about 27% of the offspring were whole body blue by X-gal staining without inheriting the Cre transgene. These results indicate that recombination can occur in the germ cells of male Rosa26(+/stop-lacZ):: CaMKII alpha-Cre(+/Cre) mice. Similarly, when double transgenic Gnao(+/f)::CaMKII alpha-Cre(+/Cre) mice carrying a floxed Go-alpha gene (Gnao(f/f)) were backcrossed to wild-type females, approximately 22% of the offspring carried the disrupted allele (Gnao(Delta)) without inheriting the Cre transgene. The Gnao(Delta/Delta) mice closely resembled conventional Go-alpha knockout mice (Gnao(-/-)) with respect to impairment of their behavior. Thus, we conclude that CaMKII alpha-Cre mice afford recombination for both tissue-and time-controlled inactivation of floxed target genes in the brain and for their permanent disruption. This work also emphasizes that extra caution should be exercised in utilizing CaMKII alpha-Cre mice as breeding pairs.
C1 [Choi, Chan-Il; Yoon, Sang-Phil; Choi, Jung-Mi; Kim, Sung-Soo; Lee, Young-Don; Suh-Kim, Haeyoung] Ajou Univ, Sch Med, Dept Anat, Suwon 443721, South Korea.
[Choi, Chan-Il; Yoon, Sang-Phil; Choi, Jung-Mi; Suh-Kim, Haeyoung] Ajou Univ, Sch Med, Neurosci Grad Program, Suwon 443721, South Korea.
[Choi, Chan-Il; Yoon, Sang-Phil; Choi, Jung-Mi; Suh-Kim, Haeyoung] Ajou Univ, Sch Med, Div Cell Transformat & Restorat BK21, Suwon 443721, South Korea.
[Kim, Sung-Soo; Lee, Young-Don] Ajou Univ, Sch Med, Ctr Cell Death Regulating Biodrug, Suwon 443721, South Korea.
[Lee, Young-Don] Ajou Univ, Dept Mol Sci & Technol, Suwon 443721, South Korea.
[Birnbaumer, Lutz] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Suh-Kim, H (reprint author), Ajou Univ, Sch Med, Dept Anat, San 5 Wonchon Dong, Suwon 443721, South Korea.
EM hysuh@ajou.ac.kr
FU NIH, NIEHS [Z01-ES101643]; Korea Healthcare technology RD Project
[HI10C14110100, HI10C14110300]; Bio & Medical Technology Development
Program of the Korean National Research Foundation [NRF-2010-0020406]
FX This study was supported in part by the Intramural research Program of
the NIH, NIEHS (project Z01-ES101643 to LB); by the Korea Healthcare
technology R&D Project (HI10C14110100 to HS-K & HI10C14110300 to S-SK)
and the Bio & Medical Technology Development Program of the Korean
National Research Foundation (NRF-2010-0020406 to HS-K).
NR 33
TC 4
Z9 4
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1226-3613
EI 2092-6413
J9 EXP MOL MED
JI Exp. Mol. Med.
PD MAY
PY 2014
VL 46
AR e93
DI 10.1038/emm.2014.14
PG 8
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA AP7WY
UT WOS:000342290100001
PM 24787734
ER
EF