TY - JOUR T1 - Altered expression of miR-181a and miR-146a does not change the expression of surface NCRs in human NK cells. AN - 1863698278; 28145491 AB - MicroRNAs (miRNAs) play an important role in regulating gene expression and immune responses. Of interest, miR-181a and miR-146a are key players in regulating immune responses and are among the most abundant miRNAs expressed in NK cells. Bioinformatically, we predicted miR-181a to regulate the expression of the natural cytotoxicity receptor NCR2 by seeded interaction with the 3'-untranslated region (3'-UTR). Whereas, miR-146a expression was not significantly different (P = 0.7361), miR-181a expression was, on average 10-fold lower in NK cells from breast cancer patients compared to normal subjects; P < 0.0001. Surface expression of NCR2 was detected in NK cells from breast cancer patients (P = 0.0384). While cytokine receptor-induced NK cell activation triggered overexpression of miR-146a when stimulated with IL-2 (P = 0.0039), IL-15 (P = 0.0078), and IL-12/IL-18 (P = 0.0072), expression of miR-181a was not affected. Overexpression or knockdown of miR-181a or miR-146a in primary cultured human NK cells did not affect the level of expression of any of the three NCRs; NCR1, NCR2 or NCR3 or NK cell cytotoxicity. Expression of miR-181a and miR-146a did not correlate to the expression of the NCRs in NK cells from breast cancer patients or cytokine-stimulated NK cells from healthy subjects. JF - Scientific reports AU - Rady, Mona AU - Watzl, Carsten AU - Claus, Maren AU - Khorshid, Ola AU - Mahran, Laila AU - Abou-Aisha, Khaled AD - Microbiology and Immunology Department, German University in Cairo (GUC), New Cairo, Egypt. ; Immunology Department, Leibniz Research Center for Working Environment and Human Factors (IfADo), Dortmund, Germany. ; Medical Oncology Department, National Cancer Institute (NCI), Cairo, Egypt. ; Pharmacology and Toxicology Department, German University in Cairo (GUC), New Cairo, Egypt. Y1 - 2017/02/01/ PY - 2017 DA - 2017 Feb 01 SP - 41381 VL - 7 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1863698278?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Altered+expression+of+miR-181a+and+miR-146a+does+not+change+the+expression+of+surface+NCRs+in+human+NK+cells.&rft.au=Rady%2C+Mona%3BWatzl%2C+Carsten%3BClaus%2C+Maren%3BKhorshid%2C+Ola%3BMahran%2C+Laila%3BAbou-Aisha%2C+Khaled&rft.aulast=Rady&rft.aufirst=Mona&rft.date=2017-02-01&rft.volume=7&rft.issue=&rft.spage=41381&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep41381 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-02-01 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1038/srep41381 ER - TY - JOUR T1 - Veterans' Location in Health Professional Shortage Areas: Implications for Access to Care and Workforce Supply AN - 1862136670 AB - Objective To describe the distribution of Veterans in areas of the United States where there are potentially inadequate supplies of health professionals, and to explore opportunities suggested by this distribution for fostering health workforce flexibility. Data Sources County-level data from the 2015-2016 Health Resources and Services Administration's (HRSA's) Area Health Resources Files (AHRF) were used to estimate Veteran populations in HRSA-designated health professional shortage areas (HPSAs). This information was then linked to 2015 VA health facility information from the Department of Veterans Affairs. Study Design Potential Veteran populations living in Shortage Area Counties with no VHA facilities were estimated, and the composition of these populations was explored by Census division and state. Principal Findings Nationwide, approximately 24 percent of all Veterans and 23 percent of Veterans enrolled in VHA health care live in Shortage Area Counties. These estimates mask considerable variation across states. Conclusions An examination of Veterans residing in Shortage Area Counties suggests extensive maldistribution of health services across the United States and the continued need to find ways to improve health care access for all Veterans. Effective avenues for doing so may include increasing health workforce flexibility through expansion of nurse practitioner scopes of practice. JF - Health Services Research AU - Doyle, Jamie Mihoko AU - Streeter, Robin A AD - Office of Extramural Research, Office of the Director, National Institutes of Health, Bethesda, MD; National Center for Health Workforce Analysis, Health Resources and Services Administration, Rockville, MD ; National Center for Health Workforce Analysis, Health Resources and Services Administration, Rockville, MD ; Office of Extramural Research, Office of the Director, National Institutes of Health, Bethesda, MD; National Center for Health Workforce Analysis, Health Resources and Services Administration, Rockville, MD Y1 - 2017/02// PY - 2017 DA - Feb 2017 SP - 459 EP - 480 CY - Chicago PB - Wiley Subscription Services, Inc. VL - 52 IS - S1 SN - 0017-9124 KW - Medical Sciences KW - Veterans KW - Labour force KW - Composition KW - Service provision KW - Flexibility KW - Census KW - Health services KW - Occupational health and safety KW - Health professionals KW - United States--US UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1862136670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Services+Research&rft.atitle=Veterans%27+Location+in+Health+Professional+Shortage+Areas%3A+Implications+for+Access+to+Care+and+Workforce+Supply&rft.au=Doyle%2C+Jamie+Mihoko%3BStreeter%2C+Robin+A&rft.aulast=Doyle&rft.aufirst=Jamie&rft.date=2017-02-01&rft.volume=52&rft.issue=S1&rft.spage=459&rft.isbn=&rft.btitle=&rft.title=Health+Services+Research&rft.issn=00179124&rft_id=info:doi/10.1111%2F1475-6773.12633 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © Health Research and Educational Trust N1 - Last updated - 2017-01-27 N1 - SubjectsTermNotLitGenreText - United States--US DO - http://dx.doi.org/10.1111/1475-6773.12633 ER - TY - JOUR T1 - Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: Scientific Underpinnings and Research Recommendations. AN - 1859715278; 27517672 AB - The current single-chemical-as-carcinogen risk assessment paradigm might underestimate or miss the cumulative effects of exposure to chemical mixtures, as highlighted in recent work from the Halifax Project. This is particularly important for chemical exposures in the low-dose range that may be affecting crucial cancer hallmark mechanisms that serve to enable carcinogenesis. Could ongoing low-dose exposures to a mixture of commonly encountered environmental chemicals produce effects in concert that lead to carcinogenesis? A workshop held at the NIEHS in August 2015 evaluated the scientific support for the low-dose mixture hypothesis of carcinogenesis and developed a research agenda. Here we describe the science that supports this novel theory, identify knowledge gaps, recommend future methodologies, and explore preventative risk assessment and policy decision-making that incorporates cancer biology, environmental health science, translational toxicology, and clinical epidemiology. The theoretical merits of the low-dose carcinogenesis hypothesis are well founded with clear biological relevance, and therefore, the premise warrants further investigation. Expert recommendations include the need for better insights into the ways in which noncarcinogenic constituents might combine to uniquely affect the process of cellular transformation (in vitro) and environmental carcinogenesis (in vivo), including investigations of the role of key defense mechanisms in maintaining transformed cells in a dormant state. The scientific community will need to acknowledge limitations of animal-based models in predicting human responses; evaluate biological events leading to carcinogenesis both spatially and temporally; examine the overlap between measurable cancer hallmarks and characteristics of carcinogens; incorporate epigenetic biomarkers, in silico modelling, high-performance computing and high-resolution imaging, microbiome, metabolomics, and transcriptomics into future research efforts; and build molecular annotations of network perturbations. The restructuring of many existing regulatory frameworks will require adequate testing of relevant environmental mixtures to build a critical mass of evidence on which to base policy decisions. Citation: Miller MF, Goodson WH III, Manjili MH, Kleinstreuer N, Bisson WH, Lowe L. 2017. Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: scientific underpinnings and research recommendations. Environ Health Perspect 125:163-169; http://dx.doi.org/10.1289/EHP411. JF - Environmental health perspectives AU - Miller, Mark F AU - Goodson, William H AU - Manjili, Masoud H AU - Kleinstreuer, Nicole AU - Bisson, William H AU - Lowe, Leroy AD - National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 163 EP - 169 VL - 125 IS - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859715278?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Low-Dose+Mixture+Hypothesis+of+Carcinogenesis+Workshop%3A+Scientific+Underpinnings+and+Research+Recommendations.&rft.au=Miller%2C+Mark+F%3BGoodson%2C+William+H%3BManjili%2C+Masoud+H%3BKleinstreuer%2C+Nicole%3BBisson%2C+William+H%3BLowe%2C+Leroy&rft.aulast=Miller&rft.aufirst=Mark&rft.date=2017-02-01&rft.volume=125&rft.issue=2&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2FEHP411 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-12 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1289/EHP411 ER - TY - JOUR T1 - Accuracy and agreement of PIRADSv2 for prostate cancer mpMRI: A multireader study AN - 1859498030; PQ0004014291 AB - Purpose Multiparametric MRI (mpMRI) improves the detection of clinically significant prostate cancer, but is limited by interobserver variation. The second version of theProstate Imaging Reporting and Data System (PIRADSv2) was recently proposed as a standard for interpreting mpMRI. To assess the performance and interobserver agreement of PIRADSv2 we performed a multi-reader study with five radiologists of varying experience. Materials and Methods Five radiologists (n=2 prostate dedicated, n=3 general body) blinded to clinicopathologic results detected and scored lesions on prostate mpMRI using PIRADSv2. The endorectal coil 3 Tesla MRI included T2W, diffusion-weighted imaging (apparent diffusion coefficient, b2000), and dynamic contrast enhancement. Thirty-four consecutive patients were included. Results were correlated with radical prostatectomy whole-mount histopathology produced with patient-specific three-dimensional molds. An index lesion was defined on pathology as the lesion with highest Gleason score or largest volume if equivalent grades. Average sensitivity and positive predictive values (PPVs) for all lesions and index lesions were determined using generalized estimating equations. Interobserver agreement was evaluated using index of specific agreement. Results Average sensitivity was 91% for detecting index lesions and 63% for all lesions across all readers. PPV was 85% for PIRADS greater than or equal to 3 and 90% for PIRADS greater than or equal to 4. Specialists performed better only for PIRADS greater than or equal to 4 with sensitivity 90% versus 79% (P=0.01) for index lesions. Index of specific agreement among readers was 93% for the detection of index lesions, 74% for the detection of all lesions, and 85% for scoring index lesions, and 58% for scoring all lesions. Conclusion By using PIRADSv2, general body radiologists and prostate specialists can detect high-grade index prostate cancer lesions with high sensitivity and agreement. Level of Evidence: 1 J. Magn. Reson. Imaging 2017; 45:579-585. JF - Journal of Magnetic Resonance Imaging AU - Greer, Matthew D AU - Brown, Anna M AU - Shih, Joanna H AU - Summers, Ronald M AU - Marko, Jamie AU - Law, Yan Mee AU - Sankineni, Sandeep AU - George, Arvin K AU - Merino, Maria J AU - Pinto, Peter A AU - Choyke, Peter L AU - Turkbey, Baris AD - Molecular Imaging Program, NCI, NIH, Bethesda, Maryland, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 579 EP - 585 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 45 IS - 2 SN - 1053-1807, 1053-1807 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859498030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Magnetic+Resonance+Imaging&rft.atitle=Accuracy+and+agreement+of+PIRADSv2+for+prostate+cancer+mpMRI%3A+A+multireader+study&rft.au=Greer%2C+Matthew+D%3BBrown%2C+Anna+M%3BShih%2C+Joanna+H%3BSummers%2C+Ronald+M%3BMarko%2C+Jamie%3BLaw%2C+Yan+Mee%3BSankineni%2C+Sandeep%3BGeorge%2C+Arvin+K%3BMerino%2C+Maria+J%3BPinto%2C+Peter+A%3BChoyke%2C+Peter+L%3BTurkbey%2C+Baris&rft.aulast=Greer&rft.aufirst=Matthew&rft.date=2017-02-01&rft.volume=45&rft.issue=2&rft.spage=579&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance+Imaging&rft.issn=10531807&rft_id=info:doi/10.1002%2Fjmri.25372 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/jmri.25372 ER - TY - JOUR T1 - Undernutrition as independent predictor of early mortality in elderly cancer patients AN - 1859484149; PQ0004015752 AB - Objectives The aim of this study was to evaluate the 1-y survival of elderly patients with cancer and the association between undernutrition and mortality. Methods This was a cohort study with elderly patients ages greater than or equal to 65 y admitted between September and October 2014. A nutritionist performed a Mini Nutritional Assessment-Short Form (MNA-SF) assessment during 48 h of hospital admission and collected data about potential confounding variables (comorbidities, stage of cancer, treatment in the previous 3 mo, and reason for hospitalization). Vital status was determined from the medical records or public records office. Overall survival was estimated using the Kaplan-Meier method. Cox regression was performed to estimate unadjusted hazard ratios. Variables with P < 0.20 by univariate analysis were selected for multivariate analysis. P < 0.05 was considered statistically significant. Results Of the 136 patients (mean age, 73.1 y; 52.2% men), 29.4%, 41.2%, and 29.4% were classified as normal, at risk for undernutrition, and undernutrition, respectively, according to the MNA-SF. The mortality rate was 31.6% after 12 mo. One-year mortality was higher among the undernourished patients, followed by patients at risk for undernutrition. After adjustment for confounding variables, the multivariate regression Cox model showed that being undernourished according to the MNA-SF increased the risk for death at 1 y (hazard ratio, 5.59; 95% confidence interval, 1.8-17.3; P < 0.001). Conclusion The results showed that the MNA-SF can be a useful tool in identifying elderly patients at higher risk for 1-y mortality. JF - Nutrition AU - Martucci, Renata B AU - Barbosa, Mariana V AU - D'Almeida, Cristiane A AU - Rodrigues, Viviane D AU - Bergmann, Anke AU - de Pinho, Nivaldo B AU - Thuler, Luiz Claudio S AD - Nutrition and Dietetic Service, Cancer Hospital Unit I, National Cancer Institute Jose Alencar Gomes da Silva, Rio de Janeiro, Brazil Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 65 EP - 70 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 34 SN - 0899-9007, 0899-9007 KW - Toxicology Abstracts KW - Cancer KW - Aging KW - Survival KW - Nutrition assessment KW - Undernutrition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859484149?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition&rft.atitle=Undernutrition+as+independent+predictor+of+early+mortality+in+elderly+cancer+patients&rft.au=Martucci%2C+Renata+B%3BBarbosa%2C+Mariana+V%3BD%27Almeida%2C+Cristiane+A%3BRodrigues%2C+Viviane+D%3BBergmann%2C+Anke%3Bde+Pinho%2C+Nivaldo+B%3BThuler%2C+Luiz+Claudio+S&rft.aulast=Martucci&rft.aufirst=Renata&rft.date=2017-02-01&rft.volume=34&rft.issue=&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Nutrition&rft.issn=08999007&rft_id=info:doi/10.1016%2Fj.nut.2016.09.011 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Number of references - 21 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1016/j.nut.2016.09.011 ER - TY - JOUR T1 - CYP3A5 Mediates Effects of Cocaine on Human Neocorticogenesis: Studies using an In Vitro 3D Self-Organized hPSC Model with a Single Cortex-Like Unit. AN - 1858107709; 27534267 AB - Because of unavoidable confounding variables in the direct study of human subjects, it has been difficult to unravel the effects of prenatal cocaine exposure on the human fetal brain, as well as the cellular and biochemical mechanisms involved. Here, we propose a novel approach using a human pluripotent stem cell (hPSC)-based 3D neocortical organoid model. This model retains essential features of human neocortical development by encompassing a single self-organized neocortical structure, without including an animal-derived gelatinous matrix. We reported previously that prenatal cocaine exposure to rats during the most active period of neural progenitor proliferation induces cytoarchitectural changes in the embryonic neocortex. We also identified a role of CYP450 and consequent oxidative ER stress signaling in these effects. However, because of differences between humans and rodents in neocorticogenesis and brain CYP metabolism, translation of the research findings from the rodent model to human brain development is uncertain. Using hPSC 3D neocortical organoids, we demonstrate that the effects of cocaine are mediated through CYP3A5-induced generation of reactive oxygen species, inhibition of neocortical progenitor cell proliferation, induction of premature neuronal differentiation, and interruption of neural tissue development. Furthermore, knockdown of CYP3A5 reversed these cocaine-induced pathological phenotypes, suggesting CYP3A5 as a therapeutic target to mitigate the deleterious neurodevelopmental effects of prenatal cocaine exposure in humans. Moreover, 3D organoid methodology provides an innovative platform for identifying adverse effects of abused psychostimulants and pharmaceutical agents, and can be adapted for use in neurodevelopmental disorders with genetic etiologies. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Lee, Chun-Ting AU - Chen, Jia AU - Kindberg, Abigail A AU - Bendriem, Raphael M AU - Spivak, Charles E AU - Williams, Melanie P AU - Richie, Christopher T AU - Handreck, Annelie AU - Mallon, Barbara S AU - Lupica, Carl R AU - Lin, Da-Ting AU - Harvey, Brandon K AU - Mash, Deborah C AU - Freed, William J AD - Intramural Research Program (IRP), National Institute on Drug Abuse, National Institutes of Health (NIH), Baltimore, MD, USA. ; Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany. ; NIH Stem Cell Unit, IRP, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA. ; Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 774 EP - 784 VL - 42 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1858107709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=CYP3A5+Mediates+Effects+of+Cocaine+on+Human+Neocorticogenesis%3A+Studies+using+an+In+Vitro+3D+Self-Organized+hPSC+Model+with+a+Single+Cortex-Like+Unit.&rft.au=Lee%2C+Chun-Ting%3BChen%2C+Jia%3BKindberg%2C+Abigail+A%3BBendriem%2C+Raphael+M%3BSpivak%2C+Charles+E%3BWilliams%2C+Melanie+P%3BRichie%2C+Christopher+T%3BHandreck%2C+Annelie%3BMallon%2C+Barbara+S%3BLupica%2C+Carl+R%3BLin%2C+Da-Ting%3BHarvey%2C+Brandon+K%3BMash%2C+Deborah+C%3BFreed%2C+William+J&rft.aulast=Lee&rft.aufirst=Chun-Ting&rft.date=2017-02-01&rft.volume=42&rft.issue=3&rft.spage=774&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=1740-634X&rft_id=info:doi/10.1038%2Fnpp.2016.156 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/npp.2016.156 ER - TY - JOUR T1 - CTDP-32476: A Promising Agonist Therapy for Treatment of Cocaine Addiction. AN - 1858106672; 27534265 AB - Agonist-replacement therapies have been successfully used for treatment of opiate and nicotine addiction, but not for cocaine addiction. One of the major obstacles is the cocaine-like addictive potential of the agonists themselves. We report here an atypical dopamine (DA) transporter (DAT) inhibitor, CTDP-32476, that may have translational potential for treating cocaine addiction. In vitro ligand-binding assays suggest that CTDP-32476 is a potent and selective DAT inhibitor and a competitive inhibitor of cocaine binding to the DAT. Systemic administration of CTDP-32476 alone produced a slow-onset, long-lasting increase in extracellular nucleus accumbens DA, locomotion, and brain-stimulation reward. Drug-naive rats did not self-administer CTDP-32476. In a substitution test, cocaine self-administration rats displayed a progressive reduction in CTDP-32476 self-administration with an extinction pattern of drug-taking behavior, suggesting significantly lower addictive potential than cocaine. Pretreatment with CTDP-32476 inhibited cocaine self-administration, cocaine-associated cue-induced relapse to drug seeking, and cocaine-enhanced extracellular DA in the nucleus accumbens. These findings suggest that CTDP-32476 is a unique DAT inhibitor that not only could satisfy 'drug hunger' through its slow-onset long-lasting DAT inhibitor action, but also render subsequent administration of cocaine ineffectual-thus constituting a novel and unique compound with translational potential as an agonist therapy for treatment of cocaine addiction. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Xi, Zheng-Xiong AU - Song, Rui AU - Li, Xia AU - Lu, Guan-Yi AU - Peng, Xiao-Qing AU - He, Yi AU - Bi, Guo-Hua AU - Sheng, Siyuan Peter AU - Yang, Hong-Ju AU - Zhang, Haiying AU - Li, Jin AU - Froimowitz, Mark AU - Gardner, Eliot L AD - Neuropsychopharmacology Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA. ; State Key Laboratory of Toxicology and Medical Countermeasures and Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China. ; Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA. ; Department of Behavioral Health, Saint Elizabeth's Hospital, Washington, DC, USA. ; Massachusetts College of Pharmacy and Health Sciences, Boston, MA, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 682 EP - 694 VL - 42 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1858106672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=CTDP-32476%3A+A+Promising+Agonist+Therapy+for+Treatment+of+Cocaine+Addiction.&rft.au=Xi%2C+Zheng-Xiong%3BSong%2C+Rui%3BLi%2C+Xia%3BLu%2C+Guan-Yi%3BPeng%2C+Xiao-Qing%3BHe%2C+Yi%3BBi%2C+Guo-Hua%3BSheng%2C+Siyuan+Peter%3BYang%2C+Hong-Ju%3BZhang%2C+Haiying%3BLi%2C+Jin%3BFroimowitz%2C+Mark%3BGardner%2C+Eliot+L&rft.aulast=Xi&rft.aufirst=Zheng-Xiong&rft.date=2017-02-01&rft.volume=42&rft.issue=3&rft.spage=682&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=1740-634X&rft_id=info:doi/10.1038%2Fnpp.2016.155 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/npp.2016.155 ER - TY - JOUR T1 - Sample size calculations for prevalent cohort designs AN - 1856453265 AB - Cross-sectional prevalent cohort design has drawn considerable interests in the studies of association between risk factors and time-to-event outcome. The sampling scheme in such design gives rise to length-biased data that require specialized analysis strategy but can improve study efficiency. The power and sample size calculation methods are however lacking for studies with prevalent cohort design, and using the formula developed for traditional survival data may overestimate sample size. We derive the sample size formulas that are appropriate for the design of cross-sectional prevalent cohort studies, under the assumptions of exponentially distributed event time and uniform follow-up for cross-sectional prevalent cohort design. We perform numerical and simulation studies to compare the sample size requirements for achieving the same power between prevalent cohort and incident cohort designs. We also use a large prospective prevalent cohort study to demonstrate the procedure. Using rigorous designs and proper analysis tools, the prospective prevalent cohort design can be more efficient than the incident cohort design with the same total sample sizes and study durations. JF - Statistical Methods in Medical Research AU - Liu, Hao AU - Shen, Yu AU - Ning, Jing AU - Qin, Jing AD - Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, USA ; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA ; Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA ; Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, USA Y1 - 2017/02// PY - 2017 DA - Feb 2017 SP - 280 EP - 291 CY - London PB - Sage Publications Ltd. VL - 26 IS - 1 SN - 0962-2802 KW - Medical Sciences KW - incident cohort design KW - length-biased data KW - prevalent cohort design KW - sample size determination KW - survival data KW - Power KW - Cohort analysis KW - Uniforms KW - Risk factors KW - Sampling KW - Simulation KW - Bias UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856453265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistical+Methods+in+Medical+Research&rft.atitle=Sample+size+calculations+for+prevalent+cohort+designs&rft.au=Liu%2C+Hao%3BShen%2C+Yu%3BNing%2C+Jing%3BQin%2C+Jing&rft.aulast=Liu&rft.aufirst=Hao&rft.date=2017-02-01&rft.volume=26&rft.issue=1&rft.spage=280&rft.isbn=&rft.btitle=&rft.title=Statistical+Methods+in+Medical+Research&rft.issn=09622802&rft_id=info:doi/10.1177%2F0962280214544730 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © The Author(s) 2014 N1 - Last updated - 2017-01-16 DO - http://dx.doi.org/10.1177/0962280214544730 ER - TY - JOUR T1 - Characterization of three human cell line models for high-throughput neuronal cytotoxicity screening AN - 1855077795; PQ0003949716 AB - More than 75 000 man-made chemicals contaminate the environment; many of these have not been tested for toxicities. These chemicals demand quantitative high-throughput screening assays to assess them for causative roles in neurotoxicities, including Parkinson's disease and other neurodegenerative disorders. To facilitate high throughput screening for cytotoxicity to neurons, three human neuronal cellular models were compared: SH-SY5Y neuroblastoma cells, LUHMES conditionally-immortalized dopaminergic neurons, and Neural Stem Cells (NSC) derived from human fetal brain. These three cell lines were evaluated for rapidity and degree of differentiation, and sensitivity to 32 known or candidate neurotoxicants. First, expression of neural differentiation genes was assayed during a 7-day differentiation period. Of the three cell lines, LUHMES showed the highest gene expression of neuronal markers after differentiation. Both in the undifferentiated state and after 7days of neuronal differentiation, LUHMES cells exhibited greater cytotoxic sensitivity to most of 32 suspected or known neurotoxicants than SH-SY5Y or NSCs. LUHMES cells were also unique in being more susceptible to several compounds in the differentiating state than in the undifferentiated state; including known neurotoxicants colchicine, methyl-mercury (II), and vincristine. Gene expression results suggest that differentiating LUHMES cells may be susceptible to apoptosis because they express low levels of anti-apoptotic genes BCL2 and BIRC5/survivin, whereas SH-SY5Y cells may be resistant to apoptosis because they express high levels of BCL2, BIRC5/survivin, and BIRC3 genes. Thus, LUHMES cells exhibited favorable characteristics for neuro-cytotoxicity screening: rapid differentiation into neurons that exhibit high level expression neuronal marker genes, and marked sensitivity of LUHMES cells to known neurotoxicants. Three human neuronal cell lines were evaluated as high throughput screening models for neuronal cytotoxicity: SH-SY5Y neuroblastoma cells, LUHMES conditionally-immortalized dopaminergic neurons, and Neural Stem Cells. After 7 days of differentiation, LUHMES expressed the highest levels of neuronal markers. Differentiated LUHMES cells exhibited greater cytotoxic sensitivity to most of 32 suspected or known neurotoxicants than differentiated SH-SY5Y or NSCs, and greater cytotoxic sensitivity to 11 compounds compared to undifferentiated LUHMES cells. JF - Journal of Applied Toxicology AU - Tong, Zhi-Bin AU - Hogberg, Helena AU - Kuo, David AU - Sakamuru, Srilatha AU - Xia, Menghang AU - Smirnova, Lena AU - Hartung, Thomas AU - Gerhold, David AD - National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 167 EP - 180 PB - Wiley Subscription Services, Inc., 1105 N Market St Wilmington DE 19801 VL - 37 IS - 2 SN - 0260-437X, 0260-437X KW - CSA Neurosciences Abstracts; Environment Abstracts; Toxicology Abstracts KW - Apoptosis KW - survivin KW - Parkinson's disease KW - Brain KW - Vincristine KW - Cell culture KW - Fetuses KW - Neurodegenerative diseases KW - Differentiation KW - Cytotoxicity KW - Movement disorders KW - Dopamine KW - Neurons KW - Neurotoxicity KW - Neuroblastoma cells KW - high-throughput screening KW - Colchicine KW - Neural stem cells KW - X 24310:Pharmaceuticals KW - N3 11028:Neuropharmacology & toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855077795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Applied+Toxicology&rft.atitle=Characterization+of+three+human+cell+line+models+for+high-throughput+neuronal+cytotoxicity+screening&rft.au=Tong%2C+Zhi-Bin%3BHogberg%2C+Helena%3BKuo%2C+David%3BSakamuru%2C+Srilatha%3BXia%2C+Menghang%3BSmirnova%2C+Lena%3BHartung%2C+Thomas%3BGerhold%2C+David&rft.aulast=Tong&rft.aufirst=Zhi-Bin&rft.date=2017-02-01&rft.volume=37&rft.issue=2&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Journal+of+Applied+Toxicology&rft.issn=0260437X&rft_id=info:doi/10.1002%2Fjat.3334 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Apoptosis; survivin; Parkinson's disease; Brain; Vincristine; Cell culture; Fetuses; Differentiation; Neurodegenerative diseases; Cytotoxicity; Dopamine; Movement disorders; Neurons; Neurotoxicity; Neuroblastoma cells; Colchicine; high-throughput screening; Neural stem cells DO - http://dx.doi.org/10.1002/jat.3334 ER - TY - JOUR T1 - Association between high risk human papillomavirus infection and co-infection with Candida spp. and Trichomonas vaginalis in women with cervical premalignant and malignant lesions. AN - 1851290265; 27992790 AB - Human papillomavirus (HPV) is the necessary cause of cervical cancer. Cervico-vaginal infection with pathogens like Chlamydia is a likely cofactor. The interactions between HPV, Trichomonas vaginalis (TV) and Candida spp. are less understood, though inflammation induced by these pathogens has been demonstrated to facilitate oncogenesis. Our study aimed to evaluate the association between Candida spp. and TV co-infection with HPV in cervical oncogenesis. Women with normal cervix who were high-risk HPV-negative (N=104) and HPV-positive (N=105); women with CIN 1 (N=106) and CIN 2/CIN 3 (N=62) were recruited from a community based cervical cancer screening program. Cervical cancer patients (N=106) were recruited from a tertiary care oncology clinic. High-risk HPV was detected by Hybrid Capture II technique; Candida spp. and TV were detected by culturing the high vaginal swabs followed by microscopic examination in all. The disease status was established by histopathology in all the women. HPV-positive women had significantly higher risk of having precursor lesions (of any grade) and cancer compared to HPV-negative women. Candida spp. or TV infection did not alter the risk of low grade or high grade lesions among HPV- positive women. HPV positive women co-infected with TV had higher risk of cervical cancer but not those co-infected with Candida spp. The higher risk of cancer observed in the women co-infected with HPV and TV without any enhanced risk of CIN 3 suggests secondary infection of the malignant growth by TV rather than any causal role. Co-infection with Candida spp. and/or TV infection did not increase the carcinogenic effect of HPV on cervix. Copyright © 2016 Elsevier B.V. All rights reserved. JF - Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology AU - Ghosh, Ishita AU - Muwonge, Richard AU - Mittal, Srabani AU - Banerjee, Dipanwita AU - Kundu, Pratip AU - Mandal, Ranajit AU - Biswas, Jaydip AU - Basu, Partha AD - Chittaranjan National Cancer Institute, Kolkata, West Bengal, India. ; Screening Group, Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France. ; Screening Group, Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France. Electronic address: BasuP@iarc.fr. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 43 EP - 48 VL - 87 KW - Trichomonas vaginalis KW - Cervical intraepithelial neoplasia KW - Candida KW - Human papillomavirus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851290265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+virology+%3A+the+official+publication+of+the+Pan+American+Society+for+Clinical+Virology&rft.atitle=Association+between+high+risk+human+papillomavirus+infection+and+co-infection+with+Candida+spp.+and+Trichomonas+vaginalis+in+women+with+cervical+premalignant+and+malignant+lesions.&rft.au=Ghosh%2C+Ishita%3BMuwonge%2C+Richard%3BMittal%2C+Srabani%3BBanerjee%2C+Dipanwita%3BKundu%2C+Pratip%3BMandal%2C+Ranajit%3BBiswas%2C+Jaydip%3BBasu%2C+Partha&rft.aulast=Ghosh&rft.aufirst=Ishita&rft.date=2017-02-01&rft.volume=87&rft.issue=&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+virology+%3A+the+official+publication+of+the+Pan+American+Society+for+Clinical+Virology&rft.issn=1873-5967&rft_id=info:doi/10.1016%2Fj.jcv.2016.12.007 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-19 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1016/j.jcv.2016.12.007 ER - TY - JOUR T1 - Estimating population exposure to ambient polycyclic aromatic hydrocarbon in the United States - Part I: Model development and evaluation. AN - 1851288211; 27988136 AB - PAHs (polycyclic aromatic hydrocarbons) in the environment are of significant concern due to their negative impact on human health. PAH measurements at the air toxics monitoring network stations alone are not sufficient to provide a complete picture of ambient PAH levels or to allow accurate assessment of public exposure in the United States. In this study, speciation profiles for PAHs were prepared using data assembled from existing emission profile data bases, and the Sparse Matrix Operator Kernel Emissions (SMOKE) model was used to generate the gridded national emissions of 16 priority PAHs in the US. The estimated emissions were applied to simulate ambient concentration of PAHs for January, April, July and October 2011, using a modified Community Multiscale Air Quality (CMAQ) model (v5.0.1) that treats the gas and particle phase partitioning of PAHs and their reactions in the gas phase and on particle surface. Predicted daily PAH concentrations at 61 air toxics monitoring sites generally agreed with observations, and averaging the predictions over a month reduced the overall error. The best model performance was obtained at rural sites, with an average mean fractional bias (MFB) of -0.03 and mean fractional error (MFE) of 0.70. Concentrations at suburban and urban sites were underestimated with overall MFB=-0.57 and MFE=0.89. Predicted PAH concentrations were highest in January with better model performance (MFB=0.12, MFE=0.69; including all sites), and lowest in July with worse model performance (MFB=-0.90, MFE=1.08). Including heterogeneous reactions of several PAHs with O3 on particle surface reduced the over-prediction bias in winter, although significant uncertainties were expected due to relative simple treatment of the heterogeneous reactions in the current model. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Environment international AU - Zhang, Jie AU - Li, Jingyi AU - Wang, Peng AU - Chen, Gang AU - Mendola, Pauline AU - Sherman, Seth AU - Ying, Qi AD - Zachary Depart of Civil Engineering, Texas A&M University, College Station, TX 77845, United States. ; Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD 20852, United States. ; The Emmes Corporation, Rockville, MD 20850, United States. ; Zachary Depart of Civil Engineering, Texas A&M University, College Station, TX 77845, United States. Electronic address: qying@civil.tamu.edu. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 263 EP - 274 VL - 99 KW - United States KW - Model performance KW - CMAQ KW - Speciation profiles KW - Exposure KW - SMOKE KW - PAH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851288211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environment+international&rft.atitle=Estimating+population+exposure+to+ambient+polycyclic+aromatic+hydrocarbon+in+the+United+States+-+Part+I%3A+Model+development+and+evaluation.&rft.au=Zhang%2C+Jie%3BLi%2C+Jingyi%3BWang%2C+Peng%3BChen%2C+Gang%3BMendola%2C+Pauline%3BSherman%2C+Seth%3BYing%2C+Qi&rft.aulast=Zhang&rft.aufirst=Jie&rft.date=2017-02-01&rft.volume=99&rft.issue=&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Environment+international&rft.issn=1873-6750&rft_id=info:doi/10.1016%2Fj.envint.2016.12.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-18 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1016/j.envint.2016.12.002 ER - TY - JOUR T1 - Harnessing molecular motors for nanoscale pulldown in live cells. AN - 1847889681; 27932498 AB - Protein-protein interactions (PPIs) regulate assembly of macromolecular complexes, yet remain challenging to study within the native cytoplasm where they normally exert their biological effect. Here we miniaturize the concept of affinity pulldown, a gold-standard in vitro PPI interrogation technique, to perform nanoscale pulldowns (NanoSPDs) within living cells. NanoSPD hijacks the normal process of intracellular trafficking by myosin motors to forcibly pull fluorescently tagged protein complexes along filopodial actin filaments. Using dual-color total internal reflection fluorescence microscopy, we demonstrate complex formation by showing that bait and prey molecules are simultaneously trafficked and actively concentrated into a nanoscopic volume at the tips of filopodia. The resulting molecular traffic jams at filopodial tips amplify fluorescence intensities and allow PPIs to be interrogated using standard epifluorescence microscopy. A rigorous quantification framework and software tool are provided to statistically evaluate NanoSPD data sets. We demonstrate the capabilities of NanoSPD for a range of nuclear and cytoplasmic PPIs implicated in human deafness, in addition to dissecting these interactions using domain mapping and mutagenesis experiments. The NanoSPD methodology is extensible for use with other fluorescent molecules, in addition to proteins, and the platform can be easily scaled for high-throughput applications. © 2017 Bird, Barzik, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). JF - Molecular biology of the cell AU - Bird, Jonathan E AU - Barzik, Melanie AU - Drummond, Meghan C AU - Sutton, Daniel C AU - Goodman, Spencer M AU - Morozko, Eva L AU - Cole, Stacey M AU - Boukhvalova, Alexandra K AU - Skidmore, Jennifer AU - Syam, Diana AU - Wilson, Elizabeth A AU - Fitzgerald, Tracy AU - Rehman, Atteeq U AU - Martin, Donna M AU - Boger, Erich T AU - Belyantseva, Inna A AU - Friedman, Thomas B AD - Laboratory of Molecular Genetics, National Institutes of Health, Bethesda, MD 20814 jonathan.bird@nih.gov. ; Laboratory of Molecular Genetics, National Institutes of Health, Bethesda, MD 20814. ; Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109. ; Mouse Auditory Testing Core Facility, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20814. Y1 - 2017/02/01/ PY - 2017 DA - 2017 Feb 01 SP - 463 EP - 475 VL - 28 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1847889681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+biology+of+the+cell&rft.atitle=Harnessing+molecular+motors+for+nanoscale+pulldown+in+live+cells.&rft.au=Bird%2C+Jonathan+E%3BBarzik%2C+Melanie%3BDrummond%2C+Meghan+C%3BSutton%2C+Daniel+C%3BGoodman%2C+Spencer+M%3BMorozko%2C+Eva+L%3BCole%2C+Stacey+M%3BBoukhvalova%2C+Alexandra+K%3BSkidmore%2C+Jennifer%3BSyam%2C+Diana%3BWilson%2C+Elizabeth+A%3BFitzgerald%2C+Tracy%3BRehman%2C+Atteeq+U%3BMartin%2C+Donna+M%3BBoger%2C+Erich+T%3BBelyantseva%2C+Inna+A%3BFriedman%2C+Thomas+B&rft.aulast=Bird&rft.aufirst=Jonathan&rft.date=2017-02-01&rft.volume=28&rft.issue=3&rft.spage=463&rft.isbn=&rft.btitle=&rft.title=Molecular+biology+of+the+cell&rft.issn=1939-4586&rft_id=info:doi/10.1091%2Fmbc.E16-08-0583 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-09 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1091/mbc.E16-08-0583 ER - TY - JOUR T1 - Sonic hedgehog pathway activation increases mitochondrial abundance and activity in hippocampal neurons. AN - 1847889279; 27932496 AB - Mitochondria are essential organelles whose biogenesis, structure, and function are regulated by many signaling pathways. We present evidence that, in hippocampal neurons, activation of the Sonic hedgehog (Shh) signaling pathway affects multiple aspects of mitochondria. Mitochondrial mass was increased significantly in neurons treated with Shh. Using biochemical and fluorescence imaging analyses, we show that Shh signaling activity reduces mitochondrial fission and promotes mitochondrial elongation, at least in part, via suppression of the mitochondrial fission protein dynamin-like GTPase Drp1. Mitochondria from Shh-treated neurons were more electron-dense, as revealed by electron microscopy, and had higher membrane potential and respiratory activity. We further show that Shh protects neurons against a variety of stresses, including the mitochondrial poison rotenone, amyloid β-peptide, hydrogen peroxide, and high levels of glutamate. Collectively our data suggest a link between Shh pathway activity and the physiological properties of mitochondria in hippocampal neurons. © 2017 Yao et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). JF - Molecular biology of the cell AU - Yao, Pamela J AU - Manor, Uri AU - Petralia, Ronald S AU - Brose, Rebecca D AU - Wu, Ryan T Y AU - Ott, Carolyn AU - Wang, Ya-Xian AU - Charnoff, Ari AU - Lippincott-Schwartz, Jennifer AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224. ; Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. ; Advanced Imaging Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892. Y1 - 2017/02/01/ PY - 2017 DA - 2017 Feb 01 SP - 387 EP - 395 VL - 28 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1847889279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+biology+of+the+cell&rft.atitle=Sonic+hedgehog+pathway+activation+increases+mitochondrial+abundance+and+activity+in+hippocampal+neurons.&rft.au=Yao%2C+Pamela+J%3BManor%2C+Uri%3BPetralia%2C+Ronald+S%3BBrose%2C+Rebecca+D%3BWu%2C+Ryan+T+Y%3BOtt%2C+Carolyn%3BWang%2C+Ya-Xian%3BCharnoff%2C+Ari%3BLippincott-Schwartz%2C+Jennifer%3BMattson%2C+Mark+P&rft.aulast=Yao&rft.aufirst=Pamela&rft.date=2017-02-01&rft.volume=28&rft.issue=3&rft.spage=387&rft.isbn=&rft.btitle=&rft.title=Molecular+biology+of+the+cell&rft.issn=1939-4586&rft_id=info:doi/10.1091%2Fmbc.E16-07-0553 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-09 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1091/mbc.E16-07-0553 ER - TY - JOUR T1 - Effect of anxiety on behavioural pattern separation in humans AN - 1845245991 AB - Behavioural pattern separation (BPS), the ability to distinguish among similar stimuli based on subtle physical differences, has been used to study the mechanism underlying stimulus generalisation. Fear overgeneralisation is often observed in individuals with posttraumatic stress disorder and other anxiety disorders. However, the relationship between anxiety and BPS remains unclear. The purpose of this study was to determine the effect of anxiety (threat of shock) on BPS, which was assessed across separate encoding and retrieval sessions. Images were encoded/retrieved during blocks of threat or safety in a 2 × 2 factorial design. During retrieval, participants indicated whether images were new, old, or altered. Better accuracy was observed for altered images encoded during periods of threat compared to safety, but only if those images were also retrieved during periods of safety. These results suggest that overgeneralisation in anxiety may be due to altered pattern separation. JF - Cognition & Emotion AU - Balderston, Nicholas L AU - Mathur, Ambika AU - Adu-Brimpong, Joel AU - Hale, Elizabeth A AU - Ernst, Monique AU - Grillon, Christian AD - Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA ; Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA Y1 - 2017/02// PY - 2017 DA - Feb 2017 SP - 238 EP - 248 CY - Hove PB - Taylor & Francis Ltd. VL - 31 IS - 2 SN - 0269-9931 KW - Psychology KW - Pattern separation KW - threat of shock KW - anxiety KW - startle KW - generalisation KW - Retrieval KW - Fear KW - Accuracy KW - Stimulus KW - Anxiety disorders KW - Encoding KW - Posttraumatic stress disorder KW - Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1845245991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cognition+%26+Emotion&rft.atitle=Effect+of+anxiety+on+behavioural+pattern+separation+in+humans&rft.au=Balderston%2C+Nicholas+L%3BMathur%2C+Ambika%3BAdu-Brimpong%2C+Joel%3BHale%2C+Elizabeth+A%3BErnst%2C+Monique%3BGrillon%2C+Christian&rft.aulast=Balderston&rft.aufirst=Nicholas&rft.date=2017-02-01&rft.volume=31&rft.issue=2&rft.spage=238&rft.isbn=&rft.btitle=&rft.title=Cognition+%26+Emotion&rft.issn=02699931&rft_id=info:doi/10.1080%2F02699931.2015.1096235 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 USC. 105, no copyright protection is available for such works under US Law. N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1080/02699931.2015.1096235 ER - TY - JOUR T1 - Identification of Human Anti-HIV gp160 Monoclonal Antibodies That Make Effective Immunotoxins. AN - 1841137569; 27852851 AB - The envelope (Env) glycoprotein of HIV is the only intact viral protein expressed on the surface of both virions and infected cells. Env is the target of neutralizing antibodies (Abs) and has been the subject of intense study in efforts to produce HIV vaccines. Therapeutic anti-Env Abs can also exert antiviral effects via Fc-mediated effector mechanisms or as cytotoxic immunoconjugates, such as immunotoxins (ITs). In the course of screening monoclonal antibodies (MAbs) for their ability to deliver cytotoxic agents to infected or Env-transfected cells, we noted disparities in their functional activities. Different MAbs showed diverse functions that did not correlate with each other. For example, MAbs against the external loop region of gp41 made the most effective ITs against infected cells but did not neutralize virus and bound only moderately to the same cells that they killed so effectively when they were used in ITs. There were also differences in IT-mediated killing among transfected and infected cell lines that were unrelated to the binding of the MAb to the target cells. Our studies of a well-characterized antigen demonstrate that MAbs against different epitopes have different functional activities and that the binding of one MAb can influence the interaction of other MAbs that bind elsewhere on the antigen. These results have implications for the use of MAbs and ITs to kill HIV-infected cells and eradicate persistent reservoirs of HIV infection. There is increased interest in using antibodies to treat and cure HIV infection. Antibodies can neutralize free virus and kill cells already carrying the virus. The virus envelope (Env) is the only HIV protein expressed on the surfaces of virions and infected cells. In this study, we examined a panel of human anti-Env antibodies for their ability to deliver cell-killing toxins to HIV-infected cells and to perform other antiviral functions. The ability of an antibody to make an effective immunotoxin could not be predicted from its other functional characteristics, such as its neutralizing activity. Anti-HIV immunotoxins could be used to eliminate virus reservoirs that persist despite effective antiretroviral therapy. Copyright © 2017 American Society for Microbiology. JF - Journal of virology AU - Pincus, Seth H AU - Song, Kejing AU - Maresh, Grace A AU - Hamer, Dean H AU - Dimitrov, Dimiter S AU - Chen, Weizao AU - Zhang, Mei-Yun AU - Ghetie, Victor F AU - Chan-Hui, Po-Ying AU - Robinson, James E AU - Vitetta, Ellen S AD - Research Institute for Children, Children's Hospital, New Orleans, Louisiana, USA spincu@lsuhsc.edu. ; Research Institute for Children, Children's Hospital, New Orleans, Louisiana, USA. ; Laboratory of Biochemistry, Center for Cancer Research, NCI, Bethesda, Maryland, USA. ; Cancer and Inflammation Program, Center for Cancer Research, NCI, Frederick, Maryland, USA. ; Departments of Immunology and Microbiology, UT Southwestern Medical Center, Dallas, Texas, USA. ; Theraclone Sciences, Seattle, Washington, USA. ; Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana, USA. Y1 - 2017/02/01/ PY - 2017 DA - 2017 Feb 01 VL - 91 IS - 3 KW - epitope KW - gp160 KW - HIV envelope KW - immunotoxin KW - monoclonal antibody UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841137569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Identification+of+Human+Anti-HIV+gp160+Monoclonal+Antibodies+That+Make+Effective+Immunotoxins.&rft.au=Pincus%2C+Seth+H%3BSong%2C+Kejing%3BMaresh%2C+Grace+A%3BHamer%2C+Dean+H%3BDimitrov%2C+Dimiter+S%3BChen%2C+Weizao%3BZhang%2C+Mei-Yun%3BGhetie%2C+Victor+F%3BChan-Hui%2C+Po-Ying%3BRobinson%2C+James+E%3BVitetta%2C+Ellen+S&rft.aulast=Pincus&rft.aufirst=Seth&rft.date=2017-02-01&rft.volume=91&rft.issue=3&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=1098-5514&rft_id=info:doi/10.1128%2FJVI.01955-16 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-17 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1128/JVI.01955-16 ER - TY - JOUR T1 - Type and frequency of MUTYH variants in Italian patients with suspected MAP: a retrospective multicenter study. AN - 1839108531; 27829682 AB - To determine prevalence, spectrum and genotype-phenotype correlations of MUTYH variants in Italian patients with suspected MAP (MUTYH-associated polyposis), a retrospective analysis was conducted to identify patients who had undergone MUTYH genetic testing from September 2002 to February 2014. Results of genetic testing and patient clinical characteristics were collected (gender, number of polyps, age at polyp diagnosis, presence of colorectal cancer (CRC) and/or other cancers, family data). The presence of large rearrangements of the MUTYH gene was evaluated by Multiplex Ligation-dependent Probe Amplification analysis. In all, 299 patients with colorectal neoplasia were evaluated: 61.2% were males, the median age at polyps or cancer diagnosis was 50 years (16-80 years), 65.2% had <100 polyps and 51.8% had CRC. A total of 36 different MUTYH variants were identified: 13 (36.1%) were classified as pathogenetic, whereas 23 (63.9%) were variants of unknown significance (VUS). Two pathogenetic variants were observed in 78 patients (26.1%). A large homozygous deletion of exon 15 was found in one patient (<1.0%). MAP patients were younger than those with negative MUTYH testing at polyps diagnosis (P<0.0001) and at first cancer diagnosis (P=0.007). MAP patients carrying the p.Glu480del variant presented with a younger age at polyp diagnosis as compared to patients carrying p.Gly396Asp and p.Tyr179Cys variants. A high heterogeneity of MUTYH variants and a high rate of VUS were identified in a cohort of Italian patients with suspected MAP. Genotype-phenotype analysis suggests that the p.Glu480del variant is associated with a severe phenotype. JF - Journal of human genetics AU - Ricci, Maria Teresa AU - Miccoli, Sara AU - Turchetti, Daniela AU - Bondavalli, Davide AU - Viel, Alessandra AU - Quaia, Michele AU - Giacomini, Elisa AU - Gismondi, Viviana AU - Sanchez-Mete, Lupe AU - Stigliano, Vittoria AU - Martayan, Aline AU - Mazzei, Filomena AU - Bignami, Margherita AU - Bonelli, Luigina AU - Varesco, Liliana AD - Unit of Hereditary Cancer, IRCCS AOU San Martino-IST, Genoa, Italy. ; Research Center on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. ; Funcional Onco-genomics and Genetics, CRO Aviano National Cancer Institute, Aviano (PN), Italy. ; Division of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute-IRCCS, Rome, Italy. ; Clinical Pathology Unit, Regina Elena National Cancer Institute-IRCCS, Rome, Italy. ; Unit of Experimental and Computational Carcinogenesis, Istituto Superiore di Sanità, Rome, Italy. ; Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genoa, Italy. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 309 EP - 315 VL - 62 IS - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839108531?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+human+genetics&rft.atitle=Type+and+frequency+of+MUTYH+variants+in+Italian+patients+with+suspected+MAP%3A+a+retrospective+multicenter+study.&rft.au=Ricci%2C+Maria+Teresa%3BMiccoli%2C+Sara%3BTurchetti%2C+Daniela%3BBondavalli%2C+Davide%3BViel%2C+Alessandra%3BQuaia%2C+Michele%3BGiacomini%2C+Elisa%3BGismondi%2C+Viviana%3BSanchez-Mete%2C+Lupe%3BStigliano%2C+Vittoria%3BMartayan%2C+Aline%3BMazzei%2C+Filomena%3BBignami%2C+Margherita%3BBonelli%2C+Luigina%3BVaresco%2C+Liliana&rft.aulast=Ricci&rft.aufirst=Maria&rft.date=2017-02-01&rft.volume=62&rft.issue=2&rft.spage=309&rft.isbn=&rft.btitle=&rft.title=Journal+of+human+genetics&rft.issn=1435-232X&rft_id=info:doi/10.1038%2Fjhg.2016.132 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-10 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1038/jhg.2016.132 ER - TY - JOUR T1 - Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats. AN - 1835672048; 27658484 AB - 3,4-Methylenedioxy-N-methylcathinone (methylone) is a new psychoactive substance and the β-keto analog of 3,4-methylenedioxy-N-methylamphetamine (MDMA). It is well established that MDMA metabolism produces bioactive metabolites. Here we tested the hypothesis that methylone metabolism in rats can form bioactive metabolites. First, we examined the pharmacokinetics (PKs) of methylone and its metabolites after subcutaneous (sc) methylone administration (3, 6, 12 mg/kg) to male rats fitted with intravenous (iv) catheters for repeated blood sampling. Plasma specimens were assayed by liquid chromatography tandem mass spectrometry to quantify methylone and its phase I metabolites: 3,4-methylenedioxycathinone (MDC), 3,4-dihydroxy-N-methylcathinone (HHMC), and 4-hydroxy-3-methoxy-N-methylcathinone (HMMC). The biological activity of methylone and its metabolites was then compared using in vitro transporter assays and in vivo microdialysis in rat nucleus accumbens. For the PK study, we found that methylone and MDC peaked early (Tmax=15-45 min) and were short lived (t1/2=60-90 min), while HHMC and HMMC peaked later (Tmax=60-120 min) and persisted (t1/2=120-180 min). Area-under-the-curve values for methylone and MDC were greater than dose-proportional, suggesting non-linear accumulation. Methylone produced significant locomotor activation, which was correlated with plasma methylone, MDC, and HHMC concentrations. Methylone, MDC, and HHMC were substrate-type releasers at monoamine transporters as determined in vitro, but only methylone and MDC (1, 3 mg/kg, iv) produced significant elevations in brain extracellular dopamine and 5-HT in vivo. Our findings demonstrate that methylone is extensively metabolized in rats, but MDC is the only centrally active metabolite that could contribute to overall effects of the drug in vivo. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Elmore, Joshua S AU - Dillon-Carter, Ora AU - Partilla, John S AU - Ellefsen, Kayla N AU - Concheiro, Marta AU - Suzuki, Masaki AU - Rice, Kenner C AU - Huestis, Marilyn A AU - Baumann, Michael H AD - Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA. ; Chemistry & Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA. ; Drug Design and Synthesis Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 649 EP - 660 VL - 42 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835672048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Pharmacokinetic+Profiles+and+Pharmacodynamic+Effects+for+Methylone+and+Its+Metabolites+in+Rats.&rft.au=Elmore%2C+Joshua+S%3BDillon-Carter%2C+Ora%3BPartilla%2C+John+S%3BEllefsen%2C+Kayla+N%3BConcheiro%2C+Marta%3BSuzuki%2C+Masaki%3BRice%2C+Kenner+C%3BHuestis%2C+Marilyn+A%3BBaumann%2C+Michael+H&rft.aulast=Elmore&rft.aufirst=Joshua&rft.date=2017-02-01&rft.volume=42&rft.issue=3&rft.spage=649&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=1740-634X&rft_id=info:doi/10.1038%2Fnpp.2016.213 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/npp.2016.213 ER - TY - JOUR T1 - Stem cell-derived models to improve mechanistic understanding and prediction of human drug-induced liver injury. AN - 1835515348; 27775817 AB - Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Efforts at improving predictability of drug-induced tissue injury in humans include using stem cell technology to generate human cells for screening for adverse effects of drugs in humans. The advent of induced pluripotent stem cells means that it may ultimately be possible to develop personalized toxicology to determine interindividual susceptibility to adverse drug reactions. However, the complexity of idiosyncratic drug-induced liver injury means that no current single-cell model, whether of primary liver tissue origin, from liver cell lines, or derived from stem cells, adequately emulates what is believed to occur during human drug-induced liver injury. Nevertheless, a single-cell model of a human hepatocyte which emulates key features of a hepatocyte is likely to be valuable in assessing potential chemical risk; furthermore, understanding how to generate a relevant hepatocyte will also be critical to efforts to build complex multicellular models of the liver. Currently, hepatocyte-like cells differentiated from stem cells still fall short of recapitulating the full mature hepatocellular phenotype. Therefore, we convened a number of experts from the areas of preclinical and clinical hepatotoxicity and safety assessment, from industry, academia, and regulatory bodies, to specifically explore the application of stem cells in hepatotoxicity safety assessment and to make recommendations for the way forward. In this short review, we particularly discuss the importance of benchmarking stem cell-derived hepatocyte-like cells to their terminally differentiated human counterparts using defined phenotyping, to make sure the cells are relevant and comparable between labs, and outline why this process is essential before the cells are introduced into chemical safety assessment. (Hepatology 2017;65:710-721). © 2016 by the American Association for the Study of Liver Diseases. JF - Hepatology (Baltimore, Md.) AU - Goldring, Christopher AU - Antoine, Daniel J AU - Bonner, Frank AU - Crozier, Jonathan AU - Denning, Chris AU - Fontana, Robert J AU - Hanley, Neil A AU - Hay, David C AU - Ingelman-Sundberg, Magnus AU - Juhila, Satu AU - Kitteringham, Neil AU - Silva-Lima, Beatriz AU - Norris, Alan AU - Pridgeon, Chris AU - Ross, James A AU - Young, Rowena Sison AU - Tagle, Danilo AU - Tornesi, Belen AU - van de Water, Bob AU - Weaver, Richard J AU - Zhang, Fang AU - Park, B Kevin AD - MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK. ; Stem Cells for Safer Medicines, London, UK. ; European Partnership for Alternative Approaches to Animal Testing, Brussels, Belgium. ; Department of Stem Cell Biology, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK. ; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI. ; Centre for Endocrinology & Diabetes, University of Manchester, and Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. ; MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK. ; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. ; R&D, In Vitro Biology, Orion Pharma, Espoo, Finland. ; Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal. ; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD. ; Abbvie Global Pharmaceutical Research and Development, North Chicago, IL. ; Faculty of Science, Leiden Academic Centre for Drug Research, Gorlaeus Laboratories, University of Leiden, Leiden, The Netherlands. ; Institut de Recherches Internationales Servier, Suresnes, France. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 710 EP - 721 VL - 65 IS - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835515348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Stem+cell-derived+models+to+improve+mechanistic+understanding+and+prediction+of+human+drug-induced+liver+injury.&rft.au=Goldring%2C+Christopher%3BAntoine%2C+Daniel+J%3BBonner%2C+Frank%3BCrozier%2C+Jonathan%3BDenning%2C+Chris%3BFontana%2C+Robert+J%3BHanley%2C+Neil+A%3BHay%2C+David+C%3BIngelman-Sundberg%2C+Magnus%3BJuhila%2C+Satu%3BKitteringham%2C+Neil%3BSilva-Lima%2C+Beatriz%3BNorris%2C+Alan%3BPridgeon%2C+Chris%3BRoss%2C+James+A%3BYoung%2C+Rowena+Sison%3BTagle%2C+Danilo%3BTornesi%2C+Belen%3Bvan+de+Water%2C+Bob%3BWeaver%2C+Richard+J%3BZhang%2C+Fang%3BPark%2C+B+Kevin&rft.aulast=Goldring&rft.aufirst=Christopher&rft.date=2017-02-01&rft.volume=65&rft.issue=2&rft.spage=710&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=1527-3350&rft_id=info:doi/10.1002%2Fhep.28886 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-24 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1002/hep.28886 ER - TY - JOUR T1 - Modulation of serotonin transporter function by kappa-opioid receptor ligands. AN - 1835447202; 27743931 AB - Kappa opioid receptor (KOR) agonists produce dysphoria and psychotomimesis. While KOR agonists produce pro-depressant-like effects, KOR antagonists produce anti-depressant-like effects in rodent models. The cellular mechanisms and downstream effector(s) by which KOR ligands produce these effects are not clear. KOR agonists modulate serotonin (5-HT) transmission in the brain regions implicated in mood and motivation regulation. Presynaptic serotonin transporter (SERT) activity is critical in the modulation of synaptic 5-HT and, subsequently, in mood disorders. Detailing the molecular events of KOR-linked SERT regulation is important for examining the postulated role of this protein in mood disorders. In this study, we used heterologous expression systems and native tissue preparations to determine the cellular signaling cascades linked to KOR-mediated SERT regulation. KOR agonists U69,593 and U50,488 produced a time and concentration dependent KOR antagonist-reversible decrease in SERT function. KOR-mediated functional down-regulation of SERT is sensitive to CaMKII and Akt inhibition. The U69,593-evoked decrease in SERT activity is associated with a decreased transport Vmax, reduced SERT cell surface expression, and increased SERT phosphorylation. Furthermore, KOR activation enhanced SERT internalization and decreased SERT delivery to the membrane. These data demonstrate that KOR activation decreases 5-HT uptake by altering SERT trafficking mechanisms and phosphorylation status to reduce the functional availability of surface SERT. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Neuropharmacology AU - Sundaramurthy, Santhanalakshmi AU - Annamalai, Balasubramaniam AU - Samuvel, Devadoss J AU - Shippenberg, Toni S AU - Jayanthi, Lankupalle D AU - Ramamoorthy, Sammanda AD - Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA. ; Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA. ; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA. ; Integrative Neuroscience Section, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA. ; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address: sammanda.ramamoorthy@vcuhealth.org. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 281 EP - 292 VL - 113 KW - Phosphorylation KW - Serotonin transporter KW - Kappa opioid receptor KW - Clearance KW - Serotonin KW - Trafficking UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835447202?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=Modulation+of+serotonin+transporter+function+by+kappa-opioid+receptor+ligands.&rft.au=Sundaramurthy%2C+Santhanalakshmi%3BAnnamalai%2C+Balasubramaniam%3BSamuvel%2C+Devadoss+J%3BShippenberg%2C+Toni+S%3BJayanthi%2C+Lankupalle+D%3BRamamoorthy%2C+Sammanda&rft.aulast=Sundaramurthy&rft.aufirst=Santhanalakshmi&rft.date=2017-02-01&rft.volume=113&rft.issue=&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=1873-7064&rft_id=info:doi/10.1016%2Fj.neuropharm.2016.10.011 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.neuropharm.2016.10.011 ER - TY - JOUR T1 - Design and In Vivo Characterization of Immunoconjugates Targeting HIV gp160. AN - 1834994363; 27795412 AB - The envelope (Env) glycoprotein of HIV is expressed on the surface of productively infected cells and can be used as a target for cytotoxic immunoconjugates (ICs), in which cell-killing moieties, including toxins, drugs, or radionuclides, are chemically or genetically linked to monoclonal antibodies (MAbs) or other targeting ligands. Such ICs could be used to eliminate persistent reservoirs of HIV infection. We have found that MAbs which bind to the external loop of gp41, e.g., MAb 7B2, make highly effective ICs, particularly when used in combination with soluble CD4. We evaluated the toxicity, immunogenicity, and efficacy of the ICs targeted with 7B2 in mice and in simian-human immunodeficiency virus-infected macaques. In the macaques, we tested immunotoxins (ITs), consisting of protein toxins bound to the targeting agent. ITs were well tolerated and initially efficacious but were ultimately limited by their immunogenicity. In an effort to decrease immunogenicity, we tested different toxic moieties, including recombinant toxins, cytotoxic drugs, and tubulin inhibitors. ICs containing deglycosylated ricin A chain prepared from ricin toxin extracted from castor beans were the most effective in killing HIV-infected cells. Having identified immunogenicity as a major concern, we show that conjugation of IT to polyethylene glycol limits immunogenicity. These studies demonstrate that cytotoxic ICs can target virus-infected cells in vivo but also highlight potential problems to be addressed. It is not yet possible to cure HIV infection. Even after years of fully effective antiviral therapy, a persistent reservoir of virus-infected cells remains. Here we propose that a targeted conjugate consisting of an anti-HIV antibody bound to a toxic moiety could function to kill the HIV-infected cells that constitute this reservoir. We tested this approach in HIV-infected cells grown in the lab and in animal infections. Our studies demonstrated that these immunoconjugates are effective both in vitro and in test animals. In particular, ITs constructed with the deglycosylated A chain prepared from native ricin were the most effective in killing cells, but their utility was blunted because they provoked immune reactions that interfered with the therapeutic effects. We then demonstrated that coating of the ITs with polyethylene glycol minimized the immunogenicity, as has been demonstrated with other protein therapies. Copyright © 2017 American Society for Microbiology. JF - Journal of virology AU - Pincus, Seth H AU - Song, Kejing AU - Maresh, Grace A AU - Frank, Anderson AU - Worthylake, David AU - Chung, Hye-Kyung AU - Polacino, Patricia AU - Hamer, Dean H AU - Coyne, Cody P AU - Rosenblum, Michael G AU - Marks, John W AU - Chen, Gang AU - Weiss, Deborah AU - Ghetie, Victor AU - Vitetta, Ellen S AU - Robinson, James E AU - Hu, Shiu-Lok AD - Research Institute for Children, Children's Hospital, New Orleans, Louisiana, USA spincu@lsuhsc.edu. ; Research Institute for Children, Children's Hospital, New Orleans, Louisiana, USA. ; Department of Pediatrics and Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA. ; Advanced Biosciences Laboratories, Inc., Rockville, Maryland, USA. ; Washington National Primate Research Center, University of Washington, Seattle, Washington, USA. ; Laboratory of Biochemistry, Center for Cancer Research, NCI, Bethesda, Maryland, USA. ; Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA. ; Department of Experimental Therapeutics, M. D. Anderson Cancer Center, Houston, Texas, USA. ; Concortis Biosystems, San Diego, California, USA. ; Departments of Immunology and Microbiology, UT Southwestern Medical Center, Dallas, Texas, USA. ; Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana, USA. Y1 - 2017/02/01/ PY - 2017 DA - 2017 Feb 01 VL - 91 IS - 3 KW - immunoglobulins KW - human immunodeficiency virus KW - antibody drug conjugate KW - monoclonal antibodies KW - immunotoxins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1834994363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Design+and+In+Vivo+Characterization+of+Immunoconjugates+Targeting+HIV+gp160.&rft.au=Pincus%2C+Seth+H%3BSong%2C+Kejing%3BMaresh%2C+Grace+A%3BFrank%2C+Anderson%3BWorthylake%2C+David%3BChung%2C+Hye-Kyung%3BPolacino%2C+Patricia%3BHamer%2C+Dean+H%3BCoyne%2C+Cody+P%3BRosenblum%2C+Michael+G%3BMarks%2C+John+W%3BChen%2C+Gang%3BWeiss%2C+Deborah%3BGhetie%2C+Victor%3BVitetta%2C+Ellen+S%3BRobinson%2C+James+E%3BHu%2C+Shiu-Lok&rft.aulast=Pincus&rft.aufirst=Seth&rft.date=2017-02-01&rft.volume=91&rft.issue=3&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=1098-5514&rft_id=info:doi/10.1128%2FJVI.01360-16 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-31 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1128/JVI.01360-16 ER - TY - JOUR T1 - Evaluating the Impact of the U.S. National Toxicology Program: A Case Study on Hexavalent Chromium. AN - 1826741944; 27483499 AB - Evaluating the impact of federally funded research with a broad, methodical, and objective approach is important to ensure that public funds advance the mission of federal agencies. We aimed to develop a methodical approach that would yield a broad assessment of National Toxicology Program's (NTP's) effectiveness across multiple sectors and demonstrate the utility of the approach through a case study. A conceptual model was developed with defined activities, outputs (products), and outcomes (proximal, intermediate, distal) and applied retrospectively to NTP's research on hexavalent chromium (CrVI). Proximal outcomes were measured by counting views of and requests for NTP's products by external stakeholders. Intermediate outcomes were measured by bibliometric analysis. Distal outcomes were assessed through Web and LexisNexis searches for documents related to legislation or regulation changes. The approach identified awareness of NTP's work on CrVI by external stakeholders (proximal outcome) and citations of NTP's research in scientific publications, reports, congressional testimonies, and legal and policy documents (intermediate outcome). NTP's research was key to the nation's first-ever drinking water standard for CrVI adopted by California in 2014 (distal outcome). By applying this approach to a case study, the utility and limitations of the approach were identified, including challenges to evaluating the outcomes of a research program. This study identified a broad and objective approach for assessing NTP's effectiveness, including methodological needs for more thorough and efficient impact assessments in the future. Citation: Xie Y, Holmgren S, Andrews DMK, Wolfe MS. 2017. Evaluating the impact of the U.S. National Toxicology Program: a case study on hexavalent chromium. Environ Health Perspect 125:181-188; http://dx.doi.org/10.1289/EHP21. JF - Environmental health perspectives AU - Xie, Yun AU - Holmgren, Stephanie AU - Andrews, Danica M K AU - Wolfe, Mary S AD - Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 181 EP - 188 VL - 125 IS - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826741944?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Evaluating+the+Impact+of+the+U.S.+National+Toxicology+Program%3A+A+Case+Study+on+Hexavalent+Chromium.&rft.au=Xie%2C+Yun%3BHolmgren%2C+Stephanie%3BAndrews%2C+Danica+M+K%3BWolfe%2C+Mary+S&rft.aulast=Xie&rft.aufirst=Yun&rft.date=2016-03-01&rft.volume=44&rft.issue=1&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Law%2C+Medicine+%26+Ethics&rft.issn=10731105&rft_id=info:doi/10.1177%2F1073110516644211 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-02 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1289/EHP21 ER - TY - JOUR T1 - Using natural products to promote caspase-8-dependent cancer cell death. AN - 1826702537; 27286684 AB - The selective killing of cancer cells without toxicity to normal nontransformed cells is an idealized goal of cancer therapy. Thus, there has been much interest in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a protein that appears to selectively kill cancer cells. TRAIL has been reported to trigger apoptosis and under some circumstances, an alternate death signaling pathway termed necroptosis. The relative importance of necroptosis for cell death induction in vivo is under intensive investigation. Nonetheless, many cancer cells (particularly those freshly isolated from cancer patients) are highly resistant to TRAIL-mediated cell death. Therefore, there is an underlying interest in identifying agents that can be combined with TRAIL to improve its efficacy. There are numerous reports in which combination of TRAIL with standard antineoplastic drugs has resulted in enhanced cancer cell death in vitro. However, many of these chemotherapeutic drugs are nonspecific and associated with adverse effects, which raise serious concerns for cancer therapy in patients. By contrast, natural products have been shown to be safer and efficacious alternatives. Recently, a number of studies have suggested that certain natural products when combined with TRAIL can enhance cancer cell death. In this review, we highlight molecular pathways that might be targeted by various natural products to promote cell death, and focus on our recent work with withanolides as TRAIL sensitizers. Finally, we will suggest synergistic approaches for combining active withanolides with various forms of immunotherapy to promote cancer cell death and an effective antitumor immune response. JF - Cancer immunology, immunotherapy : CII AU - Tewary, Poonam AU - Gunatilaka, A A Leslie AU - Sayers, Thomas J AD - Cancer and Inflammation Program, National Cancer Institute, Frederick, Frederick, MD, 21702, USA. tewaryp@mail.nih.gov. ; Natural Products Center, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ, USA. ; Cancer and Inflammation Program, National Cancer Institute, Frederick, Frederick, MD, 21702, USA. sayerst@mail.nih.gov. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 223 EP - 231 VL - 66 IS - 2 KW - TRAIL KW - Poly (I:C) KW - Apoptosis KW - PIVAC15 KW - Necroptosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826702537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+immunology%2C+immunotherapy+%3A+CII&rft.atitle=Using+natural+products+to+promote+caspase-8-dependent+cancer+cell+death.&rft.au=Tewary%2C+Poonam%3BGunatilaka%2C+A+A+Leslie%3BSayers%2C+Thomas+J&rft.aulast=Tewary&rft.aufirst=Poonam&rft.date=2017-02-01&rft.volume=66&rft.issue=2&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Cancer+immunology%2C+immunotherapy+%3A+CII&rft.issn=1432-0851&rft_id=info:doi/10.1007%2Fs00262-016-1855-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-11 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1007/s00262-016-1855-0 ER - TY - JOUR T1 - Male Breast Cancer Incidence and Mortality Risk in the Japanese Atomic Bomb Survivors - Differences in Excess Relative and Absolute Risk from Female Breast Cancer. AN - 1826698125; 27286002 AB - There are well-known associations of ionizing radiation with female breast cancer, and emerging evidence also for male breast cancer. In the United Kingdom, female breast cancer following occupational radiation exposure is among that set of cancers eligible for state compensation and consideration is currently being given to an extension to include male breast cancer. We compare radiation-associated excess relative and absolute risks of male and female breast cancers. Breast cancer incidence and mortality data in the Japanese atomic-bomb survivors were analyzed using relative and absolute risk models via Poisson regression. We observed significant (p ≤ 0.01) dose-related excess risk for male breast cancer incidence and mortality. For incidence and mortality data, there are elevations by factors of approximately 15 and 5, respectively, of relative risk for male compared with female breast cancer incidence, the former borderline significant (p = 0.050). In contrast, for incidence and mortality data, there are elevations by factors of approximately 20 and 10, respectively, of female absolute risk compared with male, both statistically significant (p < 0.001). There are no indications of differences between the sexes in age/time-since-exposure/age-at-exposure modifications to the relative or absolute excess risk. The probability of causation of male breast cancer following radiation exposure exceeds by at least a factor of 5 that of many other malignancies. There is evidence of much higher radiation-associated relative risk for male than for female breast cancer, although absolute excess risks for males are much less than for females. However, the small number of male cases and deaths suggests a degree of caution in interpretation of this finding. Citation: Little MP, McElvenny DM. 2017. Male breast cancer incidence and mortality risk in the Japanese atomic bomb survivors - differences in excess relative and absolute risk from female breast cancer. Environ Health Perspect 125:223-229; http://dx.doi.org/10.1289/EHP151. JF - Environmental health perspectives AU - Little, Mark P AU - McElvenny, Damien M AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 223 EP - 229 VL - 125 IS - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826698125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Male+Breast+Cancer+Incidence+and+Mortality+Risk+in+the+Japanese+Atomic+Bomb+Survivors+-+Differences+in+Excess+Relative+and+Absolute+Risk+from+Female+Breast+Cancer.&rft.au=Little%2C+Mark+P%3BMcElvenny%2C+Damien+M&rft.aulast=Little&rft.aufirst=Mark&rft.date=2017-02-01&rft.volume=125&rft.issue=2&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2FEHP151 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-10 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1289/EHP151 ER - TY - JOUR T1 - Spectral biomarkers for chemoprevention of colonic neoplasia: a placebo-controlled double-blinded trial with aspirin. AN - 1826648599; 26503631 AB - A major impediment to translating chemoprevention to clinical practice has been lack of intermediate biomarkers. We previously reported that rectal interrogation with low-coherence enhanced backscattering spectroscopy (LEBS) detected microarchitectural manifestations of field carcinogenesis. We now wanted to ascertain if reversion of two LEBS markers spectral slope (SPEC) and fractal dimension (FRAC) could serve as a marker for chemopreventive efficacy. We conducted a multicentre, prospective, randomised, double-blind placebo-controlled, clinical trial in subjects with a history of colonic neoplasia who manifested altered SPEC/FRAC in histologically normal colonic mucosa. Subjects (n=79) were randomised to 325 mg aspirin or placebo. The primary endpoint changed in FRAC and SPEC spectral markers after 3 months. Mucosal levels of prostaglandin E2 (PGE2) and UDP-glucuronosyltransferase (UGT)1A6 genotypes were planned secondary endpoints. At 3 months, the aspirin group manifested alterations in SPEC (48.9%, p=0.055) and FRAC (55.4%, p=0.200) with the direction towards non-neoplastic status. As a measure of aspirin's pharmacological efficacy, we assessed changes in rectal PGE2 levels and noted that it correlated with SPEC and FRAC alterations (R=-0.55, p=0.01 and R=0.57, p=0.009, respectively) whereas there was no significant correlation in placebo specimens. While UGT1A6 subgroup analysis did not achieve statistical significance, the changes in SPEC and FRAC to a less neoplastic direction occurred only in the variant consonant with epidemiological evidence of chemoprevention. We provide the first proof of concept, albeit somewhat underpowered, that spectral markers reversion mirrors antineoplastic efficacy providing a potential modality for titration of agent type/dose to optimise chemopreventive strategies in clinical practice. NCT00468910. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/. JF - Gut AU - Roy, Hemant K AU - Turzhitsky, Vladimir AU - Wali, Ramesh AU - Radosevich, Andrew J AU - Jovanovic, Borko AU - Della'Zanna, Gary AU - Umar, Asad AU - Rubin, David T AU - Goldberg, Michael J AU - Bianchi, Laura AU - De La Cruz, Mart AU - Bogojevic, Andrej AU - Helenowski, Irene B AU - Rodriguez, Luz AU - Chatterton, Robert AU - Skripkauskas, Silvia AU - Page, Katherine AU - Weber, Christopher R AU - Huang, Xiaoke AU - Richmond, Ellen AU - Bergan, Raymond C AU - Backman, Vadim AD - Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA. ; Department of Biomedical Engineering, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA. ; Department of Preventive Medicine, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA. ; Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA. ; Department of Medicine, The University of Chicago Medical Center, Chicago, Illinois, USA. ; Department of Medicine, NorthShore University Health Systems, Evanston, Illinois, USA. ; Department of Obstetrics and Gynecology, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA. ; Department of Medicine, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA. ; Department of Pathology, The University of Chicago Medical Center, Chicago, Illinois, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 285 EP - 292 VL - 66 IS - 2 KW - COLORECTAL NEOPLASIA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826648599?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gut&rft.atitle=Spectral+biomarkers+for+chemoprevention+of+colonic+neoplasia%3A+a+placebo-controlled+double-blinded+trial+with+aspirin.&rft.au=Roy%2C+Hemant+K%3BTurzhitsky%2C+Vladimir%3BWali%2C+Ramesh%3BRadosevich%2C+Andrew+J%3BJovanovic%2C+Borko%3BDella%27Zanna%2C+Gary%3BUmar%2C+Asad%3BRubin%2C+David+T%3BGoldberg%2C+Michael+J%3BBianchi%2C+Laura%3BDe+La+Cruz%2C+Mart%3BBogojevic%2C+Andrej%3BHelenowski%2C+Irene+B%3BRodriguez%2C+Luz%3BChatterton%2C+Robert%3BSkripkauskas%2C+Silvia%3BPage%2C+Katherine%3BWeber%2C+Christopher+R%3BHuang%2C+Xiaoke%3BRichmond%2C+Ellen%3BBergan%2C+Raymond+C%3BBackman%2C+Vadim&rft.aulast=Roy&rft.aufirst=Hemant&rft.date=2017-02-01&rft.volume=66&rft.issue=2&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Gut&rft.issn=1468-3288&rft_id=info:doi/10.1136%2Fgutjnl-2015-309996 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2015-10-27 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1136/gutjnl-2015-309996 ER - TY - JOUR T1 - Evaluation of divided attention psychophysical task performance and effects on pupil sizes following smoked, vaporized and oral cannabis administration. AN - 1863220785; 28138971 AB - Establishing science-based driving per se blood Δ9 -tetrahydrocannabinol (THC) limits is challenging, in part because of prolonged THC detection in chronic, frequent users. Therefore, documenting observable signs of impairment is important for driving under the influence of drugs. We evaluated frequent and occasional cannabis smokers' performance on the modified Romberg balance, one leg stand (OLS), and walk and turn (WAT) tasks, and pupil size effects following controlled placebo (0.001% THC), smoked, vaporized and oral (6.9% [~50.4 mg] THC) cannabis administration. Significant effects following inhaled doses were not observed due to delayed tasks administration 1.5 and 3.5 h post-dose, but significant impairment was observed after oral dosing (blood THC concentrations peaked 1.5-3.5 h post-dose). Occasional smokers' odds of exhibiting ≥2 clues on the OLS or WAT following oral dosing were 6.4 (95% CI 2.3-18.4) times higher than after placebo, with THC and 11-hydroxy-THC blood concentrations individually producing odds ratios of 1.3 (1.1-1.5) and 1.5 (1.3-1.8) for impairment in these tasks, respectively. Pupil sizes after oral dosing under the direct lighting condition were significantly larger than after placebo by mean (SE, 95% CI) 0.4 (0.1, 0.2-0.6) mm at 1.5 h and 0.5 (0.2, 0.2-0.8) mm at 3.5 h among all participants. Oral cannabis administration impaired occasional cannabis users' performance on the OLS and WAT tasks compared to placebo, supporting other reports showing these tasks are sensitive to cannabis-related impairment. Occasional smokers' impairment was related to blood THC and 11-hydroxy-THC concentrations. These are important public health policy findings as consumption of edible cannabis products increases. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. JF - Journal of applied toxicology : JAT AU - Newmeyer, Matthew N AU - Swortwood, Madeleine J AU - Taylor, Megan E AU - Abulseoud, Osama A AU - Woodward, Thomas H AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse National Institutes of Health, Baltimore, MD, USA. ; Maryland Drug Recognition Expert Coordinator, Maryland State Police, Pikesville, MD, USA. Y1 - 2017/01/31/ PY - 2017 DA - 2017 Jan 31 KW - cannabis KW - pupil size KW - modified Romberg balance KW - walk and turn KW - edibles KW - performance KW - one leg stand KW - Drug Evaluation and Classification Program UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1863220785?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+applied+toxicology+%3A+JAT&rft.atitle=Evaluation+of+divided+attention+psychophysical+task+performance+and+effects+on+pupil+sizes+following+smoked%2C+vaporized+and+oral+cannabis+administration.&rft.au=Newmeyer%2C+Matthew+N%3BSwortwood%2C+Madeleine+J%3BTaylor%2C+Megan+E%3BAbulseoud%2C+Osama+A%3BWoodward%2C+Thomas+H%3BHuestis%2C+Marilyn+A&rft.aulast=Newmeyer&rft.aufirst=Matthew&rft.date=2017-01-31&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+applied+toxicology+%3A+JAT&rft.issn=1099-1263&rft_id=info:doi/10.1002%2Fjat.3440 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-31 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1002/jat.3440 ER - TY - JOUR T1 - The Human Longevity Gene Homolog INDY and Interleukin-6 Interact in Hepatic Lipid Metabolism. AN - 1862947196; 28133767 AB - Reduced expression of the Indy ('I am Not Dead, Yet') gene in lower organisms promotes longevity in a manner akin to caloric restriction. Deletion of the mammalian homolog of Indy (mIndy, Slc13a5) encoding for a plasma membrane associated citrate transporter expressed highly in the liver, protects mice from high-fat diet and aging-induced obesity and hepatic fat accumulation through a mechanism resembling caloric restriction. We aimed to study a possible role of mIndy in human hepatic fat metabolism. In obese, insulin resistant patients with NAFLD, hepatic mIndy expression was increased and mIndy expression was also independently associated with hepatic steatosis. In non-human primates, a two year high fat, high sucrose diet increased hepatic mIndy expression. Liver microarray analysis showed that high mIndy expression was associated with pathways involved in hepatic lipid metabolism and immunological processes. Interleukin-6 (IL-6) was identified as a regulator of mIndy by binding to its cognate receptor. Studies in human primary hepatocytes confirmed that IL-6 markedly induced mIndy transcription via the IL-6-receptor (IL-6R) and activation of the transcription factor Stat3 and a putative start site of the human mIndy promoter was determined. Activation of the IL-6-Stat3 pathway stimulated mIndy expression, enhanced cytoplasmic citrate influx and augmented hepatic lipogenesis in vivo. In contrast, deletion of mIndy completely prevented the stimulating effect of IL-6 on citrate uptake and reduced hepatic lipogenesis. These data show that mIndy is increased in liver of obese humans and non-human primates with NALFD. Moreover, our data identify mIndy as a target gene of IL-6 and determine novel functions of IL-6 via mINDY. Targeting human mINDY may have therapeutic potential in obese patients with NAFLD. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases. JF - Hepatology (Baltimore, Md.) AU - von Loeffelholz, Christian AU - Lieske, Stefanie AU - Neuschäfer-Rube, Frank AU - Willmes, Diana M AU - Raschzok, Nathanael AU - Sauer, Igor M AU - König, Jörg AU - Fromm, Martin AU - Horn, Paul AU - Chatzigeorgiou, Antonis AU - Pathe-Neuschäfer-Rube, Andrea AU - Jordan, Jens AU - Pfeiffer, Andreas F H AU - Mingrone, Geltrude AU - Bornstein, Stefan R AU - Stroehle, Peter AU - Harms, Christoph AU - Wunderlich, F Thomas AU - Helfand, Stephen L AU - Bernier, Michel AU - de Cabo, Rafael AU - Shulman, Gerald I AU - Chavakis, Triantafyllos AU - Püschel, Gerhard P AU - Birkenfeld, Andreas L AD - Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Friedrich Schiller University, and Department of Anesthesiology and Intensive Care, Jena University Hospital, Jena, 01774, Germany. ; Section of Metabolic Vascular Medicine, Medical Clinic III, Dresden University School of Medicine, Paul Langerhans Institute Dresden (PLID), TU Dresden, 01307, Germany. ; Lehrstuhl für Biochemie der Ernährung, Universität Potsdam, Potsdam, 14558, Germany. ; General, Visceral, and Transplantation Surgery, Charité - University School of Medicine, Berlin, 10117, Germany. ; Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität, Erlangen-Nürnberg, 91054, Germany. ; Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, University Clinic Dresden, TUD, Germany. ; Institute for Clinical Pharmacology, Hannover Medical School, 30625, Hannover, Germany. ; Department of Endocrinology, Diabetes and Nutrition, Charité - University School of Medicine, Berlin, 10117, Germany. ; Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King's College London, London, SE1 8WA, UK. ; Max Planck Institute for Metabolism Research, Excellence cluster on cellular stress responses in aging associated diseases (CECAD), Cologne, 5093, Germany. ; Department of Experimental Neurology, Charité-Universitätsmedizin Berlin, Center for Stroke Research, Charitéplatz 1, 10117, Berlin, Germany. ; Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, 02912, USA. ; Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA. ; Department of Internal Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, 06520, USA. Y1 - 2017/01/30/ PY - 2017 DA - 2017 Jan 30 KW - NAFLD KW - Liver KW - IL-6 KW - Insulin Resistance KW - Indy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1862947196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=The+Human+Longevity+Gene+Homolog+INDY+and+Interleukin-6+Interact+in+Hepatic+Lipid+Metabolism.&rft.au=von+Loeffelholz%2C+Christian%3BLieske%2C+Stefanie%3BNeusch%C3%A4fer-Rube%2C+Frank%3BWillmes%2C+Diana+M%3BRaschzok%2C+Nathanael%3BSauer%2C+Igor+M%3BK%C3%B6nig%2C+J%C3%B6rg%3BFromm%2C+Martin%3BHorn%2C+Paul%3BChatzigeorgiou%2C+Antonis%3BPathe-Neusch%C3%A4fer-Rube%2C+Andrea%3BJordan%2C+Jens%3BPfeiffer%2C+Andreas+F+H%3BMingrone%2C+Geltrude%3BBornstein%2C+Stefan+R%3BStroehle%2C+Peter%3BHarms%2C+Christoph%3BWunderlich%2C+F+Thomas%3BHelfand%2C+Stephen+L%3BBernier%2C+Michel%3Bde+Cabo%2C+Rafael%3BShulman%2C+Gerald+I%3BChavakis%2C+Triantafyllos%3BP%C3%BCschel%2C+Gerhard+P%3BBirkenfeld%2C+Andreas+L&rft.aulast=von+Loeffelholz&rft.aufirst=Christian&rft.date=2017-01-30&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=1527-3350&rft_id=info:doi/10.1002%2Fhep.29089 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-30 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1002/hep.29089 ER - TY - JOUR T1 - Associations among personal care product use patterns and exogenous hormone use in the NIEHS Sister Study. AN - 1861861964; 28120835 AB - It is hypothesized that certain chemicals in personal care products may alter the risk of adverse health outcomes. The primary aim of this study was to use a data-centered approach to classify complex patterns of exposure to personal care products and to understand how these patterns vary according to use of exogenous hormone exposures, oral contraceptives (OCs) and post-menopausal hormone therapy (HT). The NIEHS Sister Study is a prospective cohort study of 50,884 US women. Limiting the sample to non-Hispanic blacks and whites (N=47,019), latent class analysis (LCA) was used to identify groups of individuals with similar patterns of personal care product use based on responses to 48 survey questions. Personal care products were categorized into three product types (beauty, hair, and skincare products) and separate latent classes were constructed for each type. Adjusted prevalence differences (PD) were calculated to estimate the association between exogenous hormone use, as measured by ever/never OC or HT use, and patterns of personal care product use. LCA reduced data dimensionality by grouping of individuals with similar patterns of personal care product use into mutually exclusive latent classes (three latent classes for beauty product use, three for hair, and four for skin care. There were strong differences in personal care usage by race, particularly for haircare products. For both blacks and whites, exogenous hormone exposures were associated with higher levels of product use, especially beauty and skincare products. Relative to individual product use questions, latent class variables capture complex patterns of personal care product usage. These patterns differed by race and were associated with ever OC and HT use. Future studies should consider personal care product exposures with other exogenous exposures when modeling health risks.Journal of Exposure Science and Environmental Epidemiology advance online publication, 25 January 2017; doi:10.1038/jes.2016.82. JF - Journal of exposure science & environmental epidemiology AU - Taylor, Kyla W AU - Baird, Donna D AU - Herring, Amy H AU - Engel, Lawrence S AU - Nichols, Hazel B AU - Sandler, Dale P AU - Troester, Melissa A AD - Office of Health Assessment and Translation, National Toxicology Program, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina 27709 USA. ; Epidemiology Department, National Institute of Environmental Health Sciences, Chapel Hill, North Carolina, USA. ; Biostatistics Deptartment, University of North Carolina, Chapel Hill, North Carolina, USA. ; Epidemiology Deptartment, University of North Carolina, Chapel Hill, North Carolina, USA. Y1 - 2017/01/25/ PY - 2017 DA - 2017 Jan 25 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861861964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+exposure+science+%26+environmental+epidemiology&rft.atitle=Associations+among+personal+care+product+use+patterns+and+exogenous+hormone+use+in+the+NIEHS+Sister+Study.&rft.au=Taylor%2C+Kyla+W%3BBaird%2C+Donna+D%3BHerring%2C+Amy+H%3BEngel%2C+Lawrence+S%3BNichols%2C+Hazel+B%3BSandler%2C+Dale+P%3BTroester%2C+Melissa+A&rft.aulast=Taylor&rft.aufirst=Kyla&rft.date=2017-01-25&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+exposure+science+%26+environmental+epidemiology&rft.issn=1559-064X&rft_id=info:doi/10.1038%2Fjes.2016.82 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-25 N1 - Date revised - 2017-01-27 N1 - Last updated - 2017-01-28 DO - http://dx.doi.org/10.1038/jes.2016.82 ER - TY - JOUR T1 - Engineering Phototheranostic Nanoscale Metal-Organic Frameworks for Multimodal Imaging-Guided Cancer Therapy. AN - 1854106990; 28032505 AB - Many photoresponsive dyes have been utilized as imaging and photodynamic/photothermal therapy agents. Indocyanine green (ICG) is the only near-infrared region (NIR) organic dye for clinical applications approved by the United States Food and Drug Administration; however, the clinical application of ICG is limited by its poor aqueous solubility, low cancer specificity, and low sensitivity in cancer theranostics. To overcome these issues, a multifunctional nanoplatform based on hyaluronic acid (HA) and ICG-engineered metal-organic framework MIL-100(Fe) nanoparticles (MOF@HA@ICG NPs) was successfully developed for imaging-guided, anticancer photothermal therapy (PTT). The synthesized NPs showed a high loading content of ICG (40%), strong NIR absorbance, and photostability. The in vitro and in vivo imaging showed that the MOF@HA@ICG NPs exhibited greater cellular uptake in CD44-positive MCF-7 cells and enhanced tumor accumulation in xenograft tumors due to their targeting capability, compared to MOF@ICG NPs (non-HA-targeted) and free ICG. The in vitro photothermal toxicity and in vivo PTT treatments demonstrated that MOF@HA@ICG NPs could effectively inhibit the growth of MCF-7 cells/xenograft tumors. These results suggest that MOF@HA@ICG NPs could be served as a new promising theranostic nanoplatform for improved anticancer PTT through cancer-specific and image-guided drug delivery. JF - ACS applied materials & interfaces AU - Cai, Wen AU - Gao, Haiyan AU - Chu, Chengchao AU - Wang, Xiaoyong AU - Wang, Junqing AU - Zhang, Pengfei AU - Lin, Gan AU - Li, Wengang AU - Liu, Gang AU - Chen, Xiaoyuan AD - Institute of Medical Engineering, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center , Xi'an, Shaanxi 710061, China. ; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University , Xiamen, Fujian 361102, China. ; Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) , Bethesda, Maryland 20892, United States. Y1 - 2017/01/25/ PY - 2017 DA - 2017 Jan 25 SP - 2040 EP - 2051 VL - 9 IS - 3 KW - photothermal therapy KW - bioimaging KW - metal−organic frameworks (MOFs) KW - indocyanine green KW - theranostic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1854106990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ACS+applied+materials+%26+interfaces&rft.atitle=Engineering+Phototheranostic+Nanoscale+Metal-Organic+Frameworks+for+Multimodal+Imaging-Guided+Cancer+Therapy.&rft.au=Cai%2C+Wen%3BGao%2C+Haiyan%3BChu%2C+Chengchao%3BWang%2C+Xiaoyong%3BWang%2C+Junqing%3BZhang%2C+Pengfei%3BLin%2C+Gan%3BLi%2C+Wengang%3BLiu%2C+Gang%3BChen%2C+Xiaoyuan&rft.aulast=Cai&rft.aufirst=Wen&rft.date=2017-01-25&rft.volume=9&rft.issue=3&rft.spage=2040&rft.isbn=&rft.btitle=&rft.title=ACS+applied+materials+%26+interfaces&rft.issn=1944-8252&rft_id=info:doi/10.1021%2Facsami.6b11579 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-29 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1021/acsami.6b11579 ER - TY - JOUR T1 - Mechanisms and Barriers in Cancer Nanomedicine: Addressing Challenges, Looking for Solutions. AN - 1857376725; 28068099 AB - Remarkable progress has recently been made in the synthesis and characterization of engineered nanoparticles for imaging and treatment of cancers, resulting in several promising candidates in clinical trials. Despite these advances, clinical applications of nanoparticle-based therapeutic/imaging agents remain limited by biological, immunological, and translational barriers. In order to overcome the existing status quo in drug delivery, there is a need for open and frank discussion in the nanomedicine community on what is needed to make qualitative leaps toward translation. In this Nano Focus, we present the main discussion topics and conclusions from a recent workshop: "Mechanisms and Barriers in Nanomedicine". The focus of this informal meeting was on biological, toxicological, immunological, and translational aspects of nanomedicine and approaches to move the field forward productively. We believe that these topics reflect the most important issues in cancer nanomedicine. JF - ACS nano AU - Anchordoquy, Thomas J AU - Barenholz, Yechezkel AU - Boraschi, Diana AU - Chorny, Michael AU - Decuzzi, Paolo AU - Dobrovolskaia, Marina A AU - Farhangrazi, Z Shadi AU - Farrell, Dorothy AU - Gabizon, Alberto AU - Ghandehari, Hamidreza AU - Godin, Biana AU - La-Beck, Ninh M AU - Ljubimova, Julia AU - Moghimi, S Moein AU - Pagliaro, Len AU - Park, Ji-Ho AU - Peer, Dan AU - Ruoslahti, Erkki AU - Serkova, Natalie J AU - Simberg, Dmitri AD - Laboratory of Membrane and Liposome Research, IMRIC, The Hebrew University-Hadassah Medical School , Jerusalem 91120, Israel. ; Institute of Protein Biochemistry, National Research Council , 80131 Napoli, Italy. ; Department of Pediatrics, Perelman School of Medicine and the Children's Hospital of Philadelphia , Philadelphia, Pennsylvania 19104, United States. ; Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia , 16163 Genoa, Italy. ; Nanotechnology Characterization Lab, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research , Frederick, Maryland 21702, United States. ; Biotrends International, Denver Technological Center , Greenwood Village, Colorado 80111, United States. ; Office of Cancer Nanotechnology Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892, United States. ; Oncology Institute, Shaare Zedek Medical Center, and Hebrew University-School of Medicine , Jerusalem 9103102, Israel. ; Departments of Pharmaceutics, Pharmaceutical Chemistry and of Bioengineering, University of Utah , Salt Lake City, Utah 84112, United States. ; Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States. ; Departments of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Sciences Center , Abilene, Texas 79601, United States. ; Nanomedicine Research Center, Departments of Neurosurgery and of Biomedical Sciences, Comprehensive Cancer Center, Cedars-Sinai Medical Center , Los Angeles, California 90048, United States. ; School of Medicine, Pharmacy and Health, Durham University , Queen's Campus, Stockton-On-Tees TS17 6BH, United Kingdom. ; Siva Therapeutics Inc., Austin, Texas 78759, United States. ; Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology , Daejeon 34141, Republic of Korea. ; Departments of Cell Research and Immunology and of Materials Sciences and Engineering, Tel Aviv University , Tel Aviv 69978, Israel. ; Sanford Burnham Prebys Medical Discovery Institute , La Jolla, California 92037, United States. Y1 - 2017/01/24/ PY - 2017 DA - 2017 Jan 24 SP - 12 EP - 18 VL - 11 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1857376725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ACS+nano&rft.atitle=Mechanisms+and+Barriers+in+Cancer+Nanomedicine%3A+Addressing+Challenges%2C+Looking+for+Solutions.&rft.au=Anchordoquy%2C+Thomas+J%3BBarenholz%2C+Yechezkel%3BBoraschi%2C+Diana%3BChorny%2C+Michael%3BDecuzzi%2C+Paolo%3BDobrovolskaia%2C+Marina+A%3BFarhangrazi%2C+Z+Shadi%3BFarrell%2C+Dorothy%3BGabizon%2C+Alberto%3BGhandehari%2C+Hamidreza%3BGodin%2C+Biana%3BLa-Beck%2C+Ninh+M%3BLjubimova%2C+Julia%3BMoghimi%2C+S+Moein%3BPagliaro%2C+Len%3BPark%2C+Ji-Ho%3BPeer%2C+Dan%3BRuoslahti%2C+Erkki%3BSerkova%2C+Natalie+J%3BSimberg%2C+Dmitri&rft.aulast=Anchordoquy&rft.aufirst=Thomas&rft.date=2017-01-24&rft.volume=11&rft.issue=1&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=ACS+nano&rft.issn=1936-086X&rft_id=info:doi/10.1021%2Facsnano.6b08244 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-09 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1021/acsnano.6b08244 ER - TY - JOUR T1 - Glucose-Responsive Sequential Generation of Hydrogen Peroxide and Nitric Oxide for Synergistic Cancer Starving-Like/Gas Therapy. AN - 1852658839; 27936311 AB - Glucose is a key energy supplier and nutrient for tumor growth. Herein, inspired by the glucose oxidase (GOx)-assisted conversion of glucose into gluconic acid and toxic H2 O2 , a novel treatment paradigm of starving-like therapy is developed for significant tumor-killing effects, more effective than conventional starving therapy by only cutting off the energy supply. Furthermore, the generated acidic H2 O2 can oxidize l-Arginine (l-Arg) into NO for enhanced gas therapy. By using hollow mesoporous organosilica nanoparticle (HMON) as a biocompatible/biodegradable nanocarrier for the co-delivery of GOx and l-Arg, a novel glucose-responsive nanomedicine (l-Arg-HMON-GOx) has been for the first time constructed for synergistic cancer starving-like/gas therapy without the need of external excitation, which yields a remarkable H2 O2 -NO cooperative anticancer effect with minimal adverse effect. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. JF - Angewandte Chemie (International ed. in English) AU - Fan, Wenpei AU - Lu, Nan AU - Huang, Peng AU - Liu, Yi AU - Yang, Zhen AU - Wang, Sheng AU - Yu, Guocan AU - Liu, Yijing AU - Hu, Junkai AU - He, Qianjun AU - Qu, Junle AU - Wang, Tianfu AU - Chen, Xiaoyuan AD - Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, Shenzhen, 518060, China. ; Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, 20892, USA. ; Department of Chemistry & Biochemistry, University of Maryland, College Park, MD, 20742, USA. ; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China. Y1 - 2017/01/24/ PY - 2017 DA - 2017 Jan 24 SP - 1229 EP - 1233 VL - 56 IS - 5 KW - ultrasound imaging KW - nitric oxide KW - hydrogen peroxide KW - mesoporous nanomaterials KW - synergistic therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852658839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Angewandte+Chemie+%28International+ed.+in+English%29&rft.atitle=Glucose-Responsive+Sequential+Generation+of+Hydrogen+Peroxide+and+Nitric+Oxide+for+Synergistic+Cancer+Starving-Like%2FGas+Therapy.&rft.au=Fan%2C+Wenpei%3BLu%2C+Nan%3BHuang%2C+Peng%3BLiu%2C+Yi%3BYang%2C+Zhen%3BWang%2C+Sheng%3BYu%2C+Guocan%3BLiu%2C+Yijing%3BHu%2C+Junkai%3BHe%2C+Qianjun%3BQu%2C+Junle%3BWang%2C+Tianfu%3BChen%2C+Xiaoyuan&rft.aulast=Fan&rft.aufirst=Wenpei&rft.date=2017-01-24&rft.volume=56&rft.issue=5&rft.spage=1229&rft.isbn=&rft.btitle=&rft.title=Angewandte+Chemie+%28International+ed.+in+English%29&rft.issn=1521-3773&rft_id=info:doi/10.1002%2Fanie.201610682 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-09 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1002/anie.201610682 ER - TY - JOUR T1 - Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior. AN - 1861613100; 28114294 AB - Afferent inputs to the ventral tegmental area (VTA) control reward-related behaviors through regulation of dopamine neuron activity. The nucleus accumbens (NAc) provides one of the most prominent projections to the VTA; however, recent studies have provided conflicting evidence regarding the function of these inhibitory inputs. Using optogenetics, cell-specific ablation, whole cell patch-clamp and immuno-electron microscopy, we found that NAc inputs synapsed directly onto dopamine neurons, preferentially activating GABAB receptors. GABAergic inputs from the NAc and local VTA GABA neurons were differentially modulated and activated separate receptor populations in dopamine neurons. Genetic deletion of GABAB receptors from dopamine neurons in adult mice did not affect general or morphine-induced locomotor activity, but markedly increased cocaine-induced locomotion. Collectively, our findings demonstrate notable selectivity in the inhibitory architecture of the VTA and suggest that long-range GABAergic inputs to dopamine neurons fundamentally regulate behavioral responses to cocaine. JF - Nature neuroscience AU - Edwards, Nicholas J AU - Tejeda, Hugo A AU - Pignatelli, Marco AU - Zhang, Shiliang AU - McDevitt, Ross A AU - Wu, Jocelyn AU - Bass, Caroline E AU - Bettler, Bernhard AU - Morales, Marisela AU - Bonci, Antonello AD - Intramural Research Program, National Institute on Drug Abuse, US National Institutes of Health, Baltimore, Maryland, USA. ; Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, New York, USA. ; Department of Biomedicine, Pharmazentrum, University of Basel, Basel, Switzerland. Y1 - 2017/01/23/ PY - 2017 DA - 2017 Jan 23 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861613100?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+neuroscience&rft.atitle=Circuit+specificity+in+the+inhibitory+architecture+of+the+VTA+regulates+cocaine-induced+behavior.&rft.au=Edwards%2C+Nicholas+J%3BTejeda%2C+Hugo+A%3BPignatelli%2C+Marco%3BZhang%2C+Shiliang%3BMcDevitt%2C+Ross+A%3BWu%2C+Jocelyn%3BBass%2C+Caroline+E%3BBettler%2C+Bernhard%3BMorales%2C+Marisela%3BBonci%2C+Antonello&rft.aulast=Edwards&rft.aufirst=Nicholas&rft.date=2017-01-23&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Nature+neuroscience&rft.issn=1546-1726&rft_id=info:doi/10.1038%2Fnn.4482 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-23 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1038/nn.4482 ER - TY - JOUR T1 - In Silico Prediction of Physicochemical Properties of Environmental Chemicals Using Molecular Fingerprints and Machine Learning. AN - 1852780265; 28006899 AB - There are little available toxicity data on the vast majority of chemicals in commerce. High-throughput screening (HTS) studies, such as those being carried out by the U.S. Environmental Protection Agency (EPA) ToxCast program in partnership with the federal Tox21 research program, can generate biological data to inform models for predicting potential toxicity. However, physicochemical properties are also needed to model environmental fate and transport, as well as exposure potential. The purpose of the present study was to generate an open-source quantitative structure-property relationship (QSPR) workflow to predict a variety of physicochemical properties that would have cross-platform compatibility to integrate into existing cheminformatics workflows. In this effort, decades-old experimental property data sets available within the EPA EPI Suite were reanalyzed using modern cheminformatics workflows to develop updated QSPR models capable of supplying computationally efficient, open, and transparent HTS property predictions in support of environmental modeling efforts. Models were built using updated EPI Suite data sets for the prediction of six physicochemical properties: octanol-water partition coefficient (logP), water solubility (logS), boiling point (BP), melting point (MP), vapor pressure (logVP), and bioconcentration factor (logBCF). The coefficient of determination (R2) between the estimated values and experimental data for the six predicted properties ranged from 0.826 (MP) to 0.965 (BP), with model performance for five of the six properties exceeding those from the original EPI Suite models. The newly derived models can be employed for rapid estimation of physicochemical properties within an open-source HTS workflow to inform fate and toxicity prediction models of environmental chemicals. JF - Journal of chemical information and modeling AU - Zang, Qingda AU - Mansouri, Kamel AU - Williams, Antony J AU - Judson, Richard S AU - Allen, David G AU - Casey, Warren M AU - Kleinstreuer, Nicole C AD - Integrated Laboratory Systems, Inc. , Research Triangle Park, North Carolina 27709, United States. ; National Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27711, United States. ; National Toxicology Program, National Institute of Environmental Health Sciences , Research Triangle Park, North Carolina 27709, United States. Y1 - 2017/01/23/ PY - 2017 DA - 2017 Jan 23 SP - 36 EP - 49 VL - 57 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852780265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chemical+information+and+modeling&rft.atitle=In+Silico+Prediction+of+Physicochemical+Properties+of+Environmental+Chemicals+Using+Molecular+Fingerprints+and+Machine+Learning.&rft.au=Zang%2C+Qingda%3BMansouri%2C+Kamel%3BWilliams%2C+Antony+J%3BJudson%2C+Richard+S%3BAllen%2C+David+G%3BCasey%2C+Warren+M%3BKleinstreuer%2C+Nicole+C&rft.aulast=Zang&rft.aufirst=Qingda&rft.date=2017-01-23&rft.volume=57&rft.issue=1&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Journal+of+chemical+information+and+modeling&rft.issn=1549-960X&rft_id=info:doi/10.1021%2Facs.jcim.6b00625 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-23 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1021/acs.jcim.6b00625 ER - TY - JOUR T1 - Effects of perfluorinated chemicals on thyroid function, markers of ovarian reserve, and natural fertility. AN - 1861594042; 28111093 AB - Perfluorinated chemicals (PFCs) can act as endocrine-disrupting chemicals, but there has been limited study of their effects on ovarian reserve or fecundability. 99 women, 30-44 years old, without infertility were followed until pregnancy. Initially, serum was evaluated for Antimullerian hormone (AMH), thyroid hormones: thyroid stimulating hormone (TSH), thyroxine (T4), free thyroxine (fT4), and triiodothyronine (T3), and PFCs: perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS). Bivariate analyses assessed the relationship between thyroid hormones, AMH, and PFCs. Fecundability ratios (FR) were determined for each PFC using a discrete time-varying Cox model and a day-specific probability model. PFC levels were positively correlated with each other (r 0.24 to 0.90), but there was no correlation with TSH (r 0.02 to 0.15) or AMH (r -0.01 to -0.15). FR point estimates for each PFC were neither strong nor statistically significant. Although increased exposure to PFCs correlates with thyroid hormone levels, there is no significant association with fecundability or ovarian reserve. Copyright © 2017 Elsevier Inc. All rights reserved. JF - Reproductive toxicology (Elmsford, N.Y.) AU - Crawford, Natalie M AU - Fenton, Suzanne E AU - Strynar, Mark AU - Hines, Erin P AU - Pritchard, David A AU - Steiner, Anne Z AD - Department of Obstetrics and Gynecology, University of North Carolina, 4001 Old Campus Building, CB 7570, Chapel Hill, NC 27599, USA. Electronic address: nmcraw@gmail.com. ; Division of the National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. ; The National Exposure Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC 27709, USA. ; National Center for Environmental Assessment, United States Environmental Protection Agency, Research Triangle Park, NC 27709, USA. ; Department of Biostatistics, University of North Carolina, 3101 McGavran-Greenberg Hall, CB 7420, Chapel Hill, NC 27599, USA. ; Department of Obstetrics and Gynecology, University of North Carolina, 4001 Old Campus Building, CB 7570, Chapel Hill, NC 27599, USA. Electronic address: anne_steiner@med.unc.edu. Y1 - 2017/01/19/ PY - 2017 DA - 2017 Jan 19 KW - fecundability KW - perfluorinated chemicals KW - ovarian reserve KW - thyroid hormones KW - endocrine disrupting chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861594042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.atitle=Effects+of+perfluorinated+chemicals+on+thyroid+function%2C+markers+of+ovarian+reserve%2C+and+natural+fertility.&rft.au=Crawford%2C+Natalie+M%3BFenton%2C+Suzanne+E%3BStrynar%2C+Mark%3BHines%2C+Erin+P%3BPritchard%2C+David+A%3BSteiner%2C+Anne+Z&rft.aulast=Crawford&rft.aufirst=Natalie&rft.date=2017-01-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=1873-1708&rft_id=info:doi/10.1016%2Fj.reprotox.2017.01.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-23 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1016/j.reprotox.2017.01.006 ER - TY - JOUR T1 - Cholinergic signaling in myelination. AN - 1861576527; 28101995 AB - There is a long history of research on acetylcholine (ACh) function in myelinating glia, but a resurgence of interest recently as a result of the therapeutic potential of manipulating ACh signaling to promote remyelination, and the broader interest in neurotransmitter signaling in activity-dependent myelination. Myelinating glia express all the major types of muscarinic and nicotinic ACh receptors at different stages of development, and acetylcholinesterase and butyrylcholinesterase are highly expressed in white matter. This review traces the history of research on ACh signaling in Schwann cells, oligodendrocytes, and in the myelin sheath, and summarizes current knowledge on the intracellular signaling and functional consequences of ACh signaling in myelinating glia. Implications of ACh in diseases, such as Alzheimer's disease, multiple sclerosis, and white matter toxicity caused by pesticides are considered, together with an outline of major questions for future research. GLIA 2017. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. JF - Glia AU - Fields, R Douglas AU - Dutta, Dipankar J AU - Belgrad, Jillian AU - Robnett, Maya AD - Nervous System Development and Plasticity Section, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, Maryland. Y1 - 2017/01/19/ PY - 2017 DA - 2017 Jan 19 KW - acetylcholine (ACh) KW - muscarinic receptors KW - acetylcholinesterase (AChE) KW - nicotinic receptors KW - organophosphates KW - butyrylcholinesterase (BChE) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861576527?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Glia&rft.atitle=Cholinergic+signaling+in+myelination.&rft.au=Fields%2C+R+Douglas%3BDutta%2C+Dipankar+J%3BBelgrad%2C+Jillian%3BRobnett%2C+Maya&rft.aulast=Fields&rft.aufirst=R&rft.date=2017-01-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Glia&rft.issn=1098-1136&rft_id=info:doi/10.1002%2Fglia.23101 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-19 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1002/glia.23101 ER - TY - JOUR T1 - Neurochemical and metabolic effects of acute and chronic alcohol in the human brain: Studies with positron emission tomography. AN - 1861587896; 28108358 AB - The use of Positron emission tomography (PET) to study the effects of acute and chronic alcohol on the human brain has enhanced our understanding of the mechanisms underlying alcohol's rewarding effects, the neuroadaptations from chronic exposure that contribute to tolerance and withdrawal, and the changes in fronto-striatal circuits that lead to loss of control and enhanced motivation to drink that characterize alcohol use disorders (AUD). These include studies showing that alcohol's reinforcing effects may result not only from its enhancement of dopaminergic, GABAergic and opioid signaling but also from its caloric properties. Studies in those suffering from an AUD have revealed significant alterations in dopamine (DA), GABA, cannabinoids, opioid and serotonin neurotransmission and in brain energy utilization (glucose and acetate metabolism) that are likely to contribute to compulsive alcohol taking, dysphoria/depression, and to alcohol-associated neurotoxicity. Studies have also evaluated the effects of abstinence on recovery of brain metabolism and neurotransmitter function and the potential value of some of these measures to predict clinical outcomes. Finally, PET studies have started to provide insights about the neuronal mechanisms by which certain genes contribute to the vulnerability to AUD. These findings have helped identify new strategies for prevention and treatment of AUD. Published by Elsevier Ltd. JF - Neuropharmacology AU - Volkow, Nora D AU - Wiers, Corinde E AU - Shokri-Kojori, Ehsan AU - Tomasi, Dardo AU - Wang, Gene-Jack AU - Baler, Ruben AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD 20892, United States; National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD 20892, United States. Electronic address: nvolkow@nida.nih.gov. ; National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD 20892, United States. ; National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD 20892, United States. Y1 - 2017/01/18/ PY - 2017 DA - 2017 Jan 18 KW - Dopamine D2 receptors KW - Frontal activity KW - Alcoholism KW - Brain metabolism KW - Brain imaging KW - Striatum UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861587896?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=Neurochemical+and+metabolic+effects+of+acute+and+chronic+alcohol+in+the+human+brain%3A+Studies+with+positron+emission+tomography.&rft.au=Volkow%2C+Nora+D%3BWiers%2C+Corinde+E%3BShokri-Kojori%2C+Ehsan%3BTomasi%2C+Dardo%3BWang%2C+Gene-Jack%3BBaler%2C+Ruben&rft.aulast=Volkow&rft.aufirst=Nora&rft.date=2017-01-18&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=1873-7064&rft_id=info:doi/10.1016%2Fj.neuropharm.2017.01.012 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-21 N1 - Date revised - 2017-01-31 N1 - Last updated - 2017-01-31 DO - http://dx.doi.org/10.1016/j.neuropharm.2017.01.012 ER - TY - JOUR T1 - Hydrogen sulfide reduces RAGE toxicity through inhibition of its dimer formation. AN - 1861587344; 28108276 AB - RAGE is important in the development of neurodegenerative diseases. The present study was designed to investigate the effect of hydrogen sulfide (H2S, an endogenous gaseous mediator) on the cytotoxicity caused by RAGE activation during the chronic oxidative stress. Aβ1-42 decreased cell viability and induced cell senescence in SH-SY5Y cells. Treatment with advanced glycation end products (AGEs) induced cell injury in HEK293 cells stably expressing RAGE (HEK293-RAGE) and stimulated inflammatory responses in SH-SY5Y cells. Pretreatment of SH-SY5Y cells with an H2S donor, NaHS, significantly attenuated the above harmful effects caused by Aβ1-42 or AGEs. Western blotting analysis shows that oxidative stress enhanced RAGE protein expression which was attenuated by either NaHS or over-expression of cystathionine β-synthase (CBS), a critical enzyme for producing H2S in brain cells. Both Western blots and split GFP complementation analysis demonstrate that NaHS reduced H2O2-enhanced RAGE dimerization. Immunofluorescence analysis shows that H2O2 up-regulated the membrane expression of wild-type RAGE. However, H2O2-enhanced expression of the RAGE harboring C259S/C310S double mutation (DM-RAGE) was observed in the endoplasmic reticulum. Treatment with NaHS attenuated the effects of H2O2 on the protein expression of WT-RAGE, but not that of DM-RAGE. Cycloheximide chase and ubiquitination assays show that NaHS reduced the half-life of WT-RAGE to a similar level of DM-RAGE. S-sulfhydration assay with the tag-switch technique demonstrate that H2S may directly S-sulfhydrate the C259/C301 residues. Our data suggest that H2S reduces RAGE dimer formation and impairs its membrane stability. The lowered plasma membrane abundance of RAGE therefore helps to protect cells against various RAGE mediated pathological effects. Copyright © 2017 Elsevier Inc. All rights reserved. JF - Free radical biology & medicine AU - Zhou, Hong AU - Ding, Lei AU - Wu, Zhiyuan AU - Cao, Xu AU - Zhang, Qichun AU - Lin, Li AU - Bian, Jin-Song AD - Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600 Singapore, Singapore. ; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600 Singapore, Singapore; Life Science Institute, National University of Singapore, Singapore. ; Laboratory of Cardiovascular Sciences, National Institute on Aging, Baltimore, MD 21224, USA. ; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600 Singapore, Singapore; Life Science Institute, National University of Singapore, Singapore. Electronic address: phcbjs@nus.edu.sg. Y1 - 2017/01/18/ PY - 2017 DA - 2017 Jan 18 SP - 262 EP - 271 VL - 104 KW - Pharmacology KW - Free radicals KW - Aging KW - Hydrogen sulfide KW - Neurodegeneration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861587344?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Hydrogen+sulfide+reduces+RAGE+toxicity+through+inhibition+of+its+dimer+formation.&rft.au=Zhou%2C+Hong%3BDing%2C+Lei%3BWu%2C+Zhiyuan%3BCao%2C+Xu%3BZhang%2C+Qichun%3BLin%2C+Li%3BBian%2C+Jin-Song&rft.aulast=Zhou&rft.aufirst=Hong&rft.date=2017-01-18&rft.volume=104&rft.issue=&rft.spage=262&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=1873-4596&rft_id=info:doi/10.1016%2Fj.freeradbiomed.2017.01.026 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-21 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1016/j.freeradbiomed.2017.01.026 ER - TY - JOUR T1 - Clinical and pathological characteristics of HIV- and HHV8- negative Castleman disease. AN - 1861575370; 28100459 AB - Castleman disease (CD) comprises three poorly-understood lymphoproliferative variants that share several common histopathological features. Unicentric CD (UCD) is localized to a single region of lymph nodes. Multicentric CD (MCD) manifests with systemic inflammatory symptoms and organ dysfunction due to cytokine dysregulation, and involves multiple lymph node regions. Human herpes virus-8 causes MCD (HHV-8-associated MCD) in immunocompromised individuals, such as HIV infected patients. However, greater than 50% MCD cases are HIV and HHV-8 negative, defined as idiopathic (iMCD). The clinical and biological behavior of CD remain poorly elucidated. In this study, we analyzed the clinicopathologic features of 74 patients (43 UCD and 31 iMCD) and therapeutic response of 96 patients (43 UCD and 53 iMCD) in HIV/HHV8-negative CD compared with 51 HIV/HHV8-positive patients. Systemic inflammatory symptoms and elevated inflammatory factors were more common in iMCD patients than UCD patients. Abnormal bone marrow features were more frequent in iMCD (77.0%) than UCD (45%); the most frequent was plasmacytosis, which was seen in 3-30.4% of marrow cells. In the lymph nodes, higher numbers of CD3+ lymphocytes (median, 58.88±20.57) and lower frequency of CD19+/CD5+ (median, 5.88±6.52) were observed in iMCD patients compared to UCD (median CD3+ cells, 43.19±17.37; median CD19+/CD5+ cells, 17.37±15.80). Complete surgical resection is better option for patients with UCD. Siltuximab had greater proportion of complete responses and longer progression-free survival (PFS) for iMCD than rituximab. Centricity, histopathological type, and anemia significantly impacted PFS. This study reveals CD a heterogeneous group of diseases with differential immunophenotypic profiling and treatment response. Copyright © 2017 American Society of Hematology. JF - Blood AU - Yu, Li AU - Tu, Meifeng AU - Cortes, Jorge AU - Xu-Monette, Zijun Y AU - Miranda, Roberto N AU - Zhang, Jun AU - Orlowski, Robert Z AU - Neelapu, Sattva AU - Boddu, Prajwal C AU - Akosile, Mary A AU - Uldrick, Thomas S AU - Yarchoan, Robert AU - Medeiros, L Jeffrey AU - Li, Yong AU - Fajgenbaum, David C AU - Young, Ken H AD - Department of Hematology, The Second Affiliate Hospital of Nanchang University, China. ; 3Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China. ; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States. ; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States. ; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, United States. ; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States. ; HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD, United States. ; Department of Cancer Biology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, United States. ; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. ; Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX, United States khyoung@mdanderson.org. Y1 - 2017/01/18/ PY - 2017 DA - 2017 Jan 18 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861575370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Clinical+and+pathological+characteristics+of+HIV-+and+HHV8-+negative+Castleman+disease.&rft.au=Yu%2C+Li%3BTu%2C+Meifeng%3BCortes%2C+Jorge%3BXu-Monette%2C+Zijun+Y%3BMiranda%2C+Roberto+N%3BZhang%2C+Jun%3BOrlowski%2C+Robert+Z%3BNeelapu%2C+Sattva%3BBoddu%2C+Prajwal+C%3BAkosile%2C+Mary+A%3BUldrick%2C+Thomas+S%3BYarchoan%2C+Robert%3BMedeiros%2C+L+Jeffrey%3BLi%2C+Yong%3BFajgenbaum%2C+David+C%3BYoung%2C+Ken+H&rft.aulast=Yu&rft.aufirst=Li&rft.date=2017-01-18&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=1528-0020&rft_id=info:doi/10.1182%2Fblood-2016-11-748855 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-19 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1182/blood-2016-11-748855 ER - TY - JOUR T1 - Amphiphilic-Polymer-Guided Plasmonic Assemblies and Their Biomedical Applications. AN - 1861568860; 28095685 AB - Plasmonic nanostructures with unique physical and biological properties have attracted increased attention for potential biomedical applications. Polymers grafted on metal nanoparticle surface can be used as assembly regulating molecules to guide nanoparticles organize into ordered or hierarchical structures in solution, within condensed phases, or at interfaces. In this Topical Review, we will highlight recent efforts on self-assembly of gold nanoparticles coated with polymer brushes. How and what kind of polymer graft can be used to adjust nanoparticle interactions, to dictate interparticle orientation, and to determine assembled nanostructures will be discussed. Furthermore, the Topical Review will shed light on the physicochemical properties, including self-assembly behavior and kinetics, tunable localized surface plasmon resonance effect, enhanced surface enhanced Raman scattering, and other optical and thermal properties. The potential of self-assembled nanostructures for applications in different fields, especially in biomedicine, will also be elaborated. JF - Bioconjugate chemistry AU - Song, Jibin AU - Niu, Gang AU - Chen, Xiaoyuan AD - Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health , Bethesda, Maryland 20892, United States. Y1 - 2017/01/18/ PY - 2017 DA - 2017 Jan 18 SP - 105 EP - 114 VL - 28 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861568860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioconjugate+chemistry&rft.atitle=Amphiphilic-Polymer-Guided+Plasmonic+Assemblies+and+Their+Biomedical+Applications.&rft.au=Song%2C+Jibin%3BNiu%2C+Gang%3BChen%2C+Xiaoyuan&rft.aulast=Song&rft.aufirst=Jibin&rft.date=2017-01-18&rft.volume=28&rft.issue=1&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+chemistry&rft.issn=1520-4812&rft_id=info:doi/10.1021%2Facs.bioconjchem.6b00521 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-18 N1 - Date revised - 2017-01-27 N1 - Last updated - 2017-01-28 DO - http://dx.doi.org/10.1021/acs.bioconjchem.6b00521 ER - TY - JOUR T1 - Association of Osteopontin Gene Polymorphisms with Colorectal Cancer. AN - 1861572517; 28095066 AB - We investigated the association of the Osteopontin (OPN) (rs9138 and rs1126616) polymorphisms with colorectal cancer (CRC). One hundred CRC patients and 112 healthy individuals were subjected to OPN (rs9138 and rs1126616) genotyping and measurement of OPN protein plasma level. The C allele of OPN rs1126616 and the CC haplotype were significantly higher in CRC patient (p = 0.036, 0.003, respectively). In females, the C allele of OPN rs9318 (A/C) polymorphism was significantly associated with increased CRC risk (p = 0.036). The plasma OPN level >104.35 ng/mL was significantly associated with CRC. Our findings suggest a significant role played by OPN (rs9138 and rs1126616) in colorectal carcinogenesis. JF - Cancer investigation AU - Kamal, Asmaa AU - Darwish, Rania Kamal AU - Saad, Samar AU - Salama, Mohamed AU - El-Baradie, Tarek S AU - Mahmoud, Heba G M AU - Elshiwy, Yasmine AD - a Department of Clinical & Chemical Pathology, Faculty of Medicine , Cairo University , Cairo , Egypt. ; b Department of Surgical Oncology, National Cancer Institute , Cairo Univeristy , Cairo , Egypt. Y1 - 2017/01/17/ PY - 2017 DA - 2017 Jan 17 SP - 1 EP - 7 KW - OPN rs9138 KW - OPN rs1126616 KW - Gene polymorphism KW - Osteopontin KW - Colorectal cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861572517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+investigation&rft.atitle=Association+of+Osteopontin+Gene+Polymorphisms+with+Colorectal+Cancer.&rft.au=Kamal%2C+Asmaa%3BDarwish%2C+Rania+Kamal%3BSaad%2C+Samar%3BSalama%2C+Mohamed%3BEl-Baradie%2C+Tarek+S%3BMahmoud%2C+Heba+G+M%3BElshiwy%2C+Yasmine&rft.aulast=Kamal&rft.aufirst=Asmaa&rft.date=2017-01-17&rft.volume=&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Cancer+investigation&rft.issn=1532-4192&rft_id=info:doi/10.1080%2F07357907.2016.1247454 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-17 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1080/07357907.2016.1247454 ER - TY - JOUR T1 - A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity. AN - 1861562993; 28096355 AB - The self-assembly of α-synuclein is closely associated with Parkinson's disease and related syndromes. We show that squalamine, a natural product with known anticancer and antiviral activity, dramatically affects α-synuclein aggregation in vitro and in vivo. We elucidate the mechanism of action of squalamine by investigating its interaction with lipid vesicles, which are known to stimulate nucleation, and find that this compound displaces α-synuclein from the surfaces of such vesicles, thereby blocking the first steps in its aggregation process. We also show that squalamine almost completely suppresses the toxicity of α-synuclein oligomers in human neuroblastoma cells by inhibiting their interactions with lipid membranes. We further examine the effects of squalamine in a Caenorhabditis elegans strain overexpressing α-synuclein, observing a dramatic reduction of α-synuclein aggregation and an almost complete elimination of muscle paralysis. These findings suggest that squalamine could be a means of therapeutic intervention in Parkinson's disease and related conditions. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Perni, Michele AU - Galvagnion, Céline AU - Maltsev, Alexander AU - Meisl, Georg AU - Müller, Martin B D AU - Challa, Pavan K AU - Kirkegaard, Julius B AU - Flagmeier, Patrick AU - Cohen, Samuel I A AU - Cascella, Roberta AU - Chen, Serene W AU - Limboker, Ryan AU - Sormanni, Pietro AU - Heller, Gabriella T AU - Aprile, Francesco A AU - Cremades, Nunilo AU - Cecchi, Cristina AU - Chiti, Fabrizio AU - Nollen, Ellen A A AU - Knowles, Tuomas P J AU - Vendruscolo, Michele AU - Bax, Adriaan AU - Zasloff, Michael AU - Dobson, Christopher M AD - Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom. ; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. ; Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge CB3 0WA, United Kingdom. ; Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence 50134, Italy. ; Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit BIFI-IQFR (CSIC), University of Zaragoza, 50018 Zaragoza, Spain. ; University Medical Centre Groningen, European Research Institute for the Biology of Aging, University of Groningen, Groningen 9713 AV, The Netherlands. ; Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom; mv245@cam.ac.uk bax@nih.gov maz5@georgetown.edu cmd44@cam.ac.uk. ; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; mv245@cam.ac.uk bax@nih.gov maz5@georgetown.edu cmd44@cam.ac.uk. ; MedStar-Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, DC 20010 mv245@cam.ac.uk bax@nih.gov maz5@georgetown.edu cmd44@cam.ac.uk. Y1 - 2017/01/17/ PY - 2017 DA - 2017 Jan 17 KW - Parkinson’s disease KW - amyloid formation KW - toxic oligomers KW - drug development KW - protein aggregation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861562993?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=A+natural+product+inhibits+the+initiation+of+%CE%B1-synuclein+aggregation+and+suppresses+its+toxicity.&rft.au=Perni%2C+Michele%3BGalvagnion%2C+C%C3%A9line%3BMaltsev%2C+Alexander%3BMeisl%2C+Georg%3BM%C3%BCller%2C+Martin+B+D%3BChalla%2C+Pavan+K%3BKirkegaard%2C+Julius+B%3BFlagmeier%2C+Patrick%3BCohen%2C+Samuel+I+A%3BCascella%2C+Roberta%3BChen%2C+Serene+W%3BLimboker%2C+Ryan%3BSormanni%2C+Pietro%3BHeller%2C+Gabriella+T%3BAprile%2C+Francesco+A%3BCremades%2C+Nunilo%3BCecchi%2C+Cristina%3BChiti%2C+Fabrizio%3BNollen%2C+Ellen+A+A%3BKnowles%2C+Tuomas+P+J%3BVendruscolo%2C+Michele%3BBax%2C+Adriaan%3BZasloff%2C+Michael%3BDobson%2C+Christopher+M&rft.aulast=Perni&rft.aufirst=Michele&rft.date=2017-01-17&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=1091-6490&rft_id=info:doi/10.1073%2Fpnas.1610586114 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-18 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1073/pnas.1610586114 ER - TY - JOUR T1 - Unconventional oil and gas development and risk of childhood leukemia: Assessing the evidence. AN - 1835678718; 27783932 AB - The widespread distribution of unconventional oil and gas (UO&G) wells and other facilities in the United States potentially exposes millions of people to air and water pollutants, including known or suspected carcinogens. Childhood leukemia is a particular concern because of the disease severity, vulnerable population, and short disease latency. A comprehensive review of carcinogens and leukemogens associated with UO&G development is not available and could inform future exposure monitoring studies and human health assessments. The objective of this analysis was to assess the evidence of carcinogenicity of water contaminants and air pollutants related to UO&G development. We obtained a list of 1177 chemicals in hydraulic fracturing fluids and wastewater from the U.S. Environmental Protection Agency and constructed a list of 143 UO&G-related air pollutants through a review of scientific papers published through 2015 using PubMed and ProQuest databases. We assessed carcinogenicity and evidence of increased risk for leukemia/lymphoma of these chemicals using International Agency for Research on Cancer (IARC) monographs. The majority of compounds (>80%) were not evaluated by IARC and therefore could not be reviewed. Of the 111 potential water contaminants and 29 potential air pollutants evaluated by IARC (119 unique compounds), 49 water and 20 air pollutants were known, probable, or possible human carcinogens (55 unique compounds). A total of 17 water and 11 air pollutants (20 unique compounds) had evidence of increased risk for leukemia/lymphoma, including benzene, 1,3-butadiene, cadmium, diesel exhaust, and several polycyclic aromatic hydrocarbons. Though information on the carcinogenicity of compounds associated with UO&G development was limited, our assessment identified 20 known or suspected carcinogens that could be measured in future studies to advance exposure and risk assessments of cancer-causing agents. Our findings support the need for investigation into the relationship between UO&G development and risk of cancer in general and childhood leukemia in particular. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved. JF - The Science of the total environment AU - Elliott, Elise G AU - Trinh, Pauline AU - Ma, Xiaomei AU - Leaderer, Brian P AU - Ward, Mary H AU - Deziel, Nicole C AD - Yale School of Public Health, Yale University, 60 College St., New Haven, CT 06520, USA. ; National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, MD 20850, USA. ; Yale School of Public Health, Yale University, 60 College St., New Haven, CT 06520, USA.. Electronic address: nicole.deziel@yale.edu. Y1 - 2017/01/15/ PY - 2017 DA - 2017 Jan 15 SP - 138 EP - 147 VL - 576 KW - Air pollution KW - Water contamination KW - Carcinogens KW - Shale KW - Wastewater KW - Hydraulic fracturing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835678718?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Science+of+the+total+environment&rft.atitle=Unconventional+oil+and+gas+development+and+risk+of+childhood+leukemia%3A+Assessing+the+evidence.&rft.au=Elliott%2C+Elise+G%3BTrinh%2C+Pauline%3BMa%2C+Xiaomei%3BLeaderer%2C+Brian+P%3BWard%2C+Mary+H%3BDeziel%2C+Nicole+C&rft.aulast=Elliott&rft.aufirst=Elise&rft.date=2017-01-15&rft.volume=576&rft.issue=&rft.spage=138&rft.isbn=&rft.btitle=&rft.title=The+Science+of+the+total+environment&rft.issn=1879-1026&rft_id=info:doi/10.1016%2Fj.scitotenv.2016.10.072 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.scitotenv.2016.10.072 ER - TY - JOUR T1 - Effect of ginseng extract on the TGF-β1 signaling pathway in CCl4-induced liver fibrosis in rats. AN - 1861512564; 28086769 AB - Liver diseases are major global health problems. Ginseng extract has antioxidant, immune-modulatory and anti-inflammatory activities. This study investigated the effect of ginseng extract on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Male Wistar rats were divided into four groups: control group, ginseng group, CCl4 group and CCl4 + ginseng group. Liver injury was induced by the intraperitoneal (I.P) injection of 3 ml/kg CCl4 (30% in olive oil) weekly for 8 weeks. The control group was I.P injected with olive oil. The expression of genes encoding transforming growth factor beta (TGF-β), type I TGF-β receptor (TβR-1), type II TGF-β receptor (TβR-II), mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad4, matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor matrix metalloproteinase-1 (TIMP-1), Collagen 1a2 (Col1a2), Collagen 3a1 (Col3a1), interleukin-8 (IL-8) and interleukin -10 (IL-10) were measured by real-time PCR. Treatment with ginseng extract decreased hepatic fat deposition and lowered hepatic reticular fiber accumulation compared with the CCl4 group. The CCl4 group showed a significant increase in hepatotoxicity biomarkers and up-regulation of the expression of genes encoding TGF-β, TβR-I, TβR-II, MMP2, MMP9, Smad-2,-3, -4, and IL-8 compared with the control group. However, CCl4 administration resulted in the significant down-regulation of IL-10 mRNA expression compared with the control group. Interestingly, ginseng extract supplementation completely reversed the biochemical markers of hepatotoxicity and the gene expression alterations induced by CCl4. ginseng extract had an anti-fibrosis effect via the regulation of the TGF-β1/Smad signaling pathway in the CCl4-induced liver fibrosis model. The major target was the inhibition of the expression of TGF-β1, Smad2, and Smad3. JF - BMC complementary and alternative medicine AU - Hafez, Mohamed M AU - Hamed, Sherifa S AU - El-Khadragy, Manal F AU - Hassan, Zeinab K AU - Al Rejaie, Salim S AU - Sayed-Ahmed, Mohamed M AU - Al-Harbi, Naif O AU - Al-Hosaini, Khalid A AU - Al-Harbi, Mohamed M AU - Alhoshani, Ali R AU - Al-Shabanah, Othman A AU - Alsharari, Shakir Dekhal AD - Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia. ; Department of Zoology, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia. ; National Cancer Institute, Virology and Immunology Unit, Cancer Biology Department, Cairo University, Cairo, Egypt. ; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia. shabanah@ksu.edu.sa. Y1 - 2017/01/13/ PY - 2017 DA - 2017 Jan 13 SP - 45 VL - 17 IS - 1 KW - Interleukin-8 KW - 0 KW - Plant Extracts KW - Receptors, Transforming Growth Factor beta KW - Smad Proteins KW - Transforming Growth Factor beta1 KW - Interleukin-10 KW - 130068-27-8 KW - Carbon Tetrachloride KW - CL2T97X0V0 KW - TGF-beta type I receptor KW - EC 2.7.1.11 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Gene expression KW - Carbon tetrachloride KW - Ginseng extract KW - Real time PCR KW - Smad Proteins -- genetics KW - Receptors, Transforming Growth Factor beta -- genetics KW - Animals KW - Protein-Serine-Threonine Kinases -- metabolism KW - Humans KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Protein-Serine-Threonine Kinases -- genetics KW - Carbon Tetrachloride -- adverse effects KW - Rats KW - Smad Proteins -- metabolism KW - Interleukin-10 -- metabolism KW - Signal Transduction -- drug effects KW - Rats, Wistar KW - Interleukin-8 -- genetics KW - Interleukin-10 -- genetics KW - Interleukin-8 -- metabolism KW - Male KW - Liver Cirrhosis -- chemically induced KW - Panax -- chemistry KW - Transforming Growth Factor beta1 -- metabolism KW - Liver Cirrhosis -- drug therapy KW - Liver Cirrhosis -- metabolism KW - Transforming Growth Factor beta1 -- genetics KW - Liver Cirrhosis -- genetics KW - Plant Extracts -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861512564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+complementary+and+alternative+medicine&rft.atitle=Effect+of+ginseng+extract+on+the+TGF-%CE%B21+signaling+pathway+in+CCl4-induced+liver+fibrosis+in+rats.&rft.au=Hafez%2C+Mohamed+M%3BHamed%2C+Sherifa+S%3BEl-Khadragy%2C+Manal+F%3BHassan%2C+Zeinab+K%3BAl+Rejaie%2C+Salim+S%3BSayed-Ahmed%2C+Mohamed+M%3BAl-Harbi%2C+Naif+O%3BAl-Hosaini%2C+Khalid+A%3BAl-Harbi%2C+Mohamed+M%3BAlhoshani%2C+Ali+R%3BAl-Shabanah%2C+Othman+A%3BAlsharari%2C+Shakir+Dekhal&rft.aulast=Hafez&rft.aufirst=Mohamed&rft.date=2017-01-13&rft.volume=17&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=BMC+complementary+and+alternative+medicine&rft.issn=1472-6882&rft_id=info:doi/10.1186%2Fs12906-016-1507-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-25 N1 - Date created - 2017-01-14 N1 - Date revised - 2017-01-27 N1 - Last updated - 2017-01-28 DO - http://dx.doi.org/10.1186/s12906-016-1507-0 ER - TY - JOUR T1 - Vibrio cholerae Cholix toxin-induced HepG2 cell death is enhanced by tumor necrosis factor-alpha through ROS and intracellular signal-regulated kinases. AN - 1861495899; 28087840 AB - Cholix toxin (Cholix) from Vibrio cholerae is a potent virulence factor exhibiting ADP-ribosyltransferase activity on eukaryotic elongation factor 2 (eEF2) of host cells, resulting in inhibition of protein synthesis. Administration of Cholix or its homologue Pseudomonas exotoxin A (PEA) to mice causes lethal hepatocyte damage. In this study, we demonstrate cytotoxicity of Cholix on immortalized human hepatocytes in the presence of tumor necrosis factor α (TNF-α), which has been reported to play a fatal role in PEA administered to mice. Compared to incubating HepG2 cells with Cholix alone, co-treatment with TNF-α and Cholix (TNF-α/Cholix) significantly enhanced activation of caspases, cytochrome c release from mitochondria into cytoplasm, and poly-ADP-ribose polymerase (PARP) cleavage, while incubation with TNF-α alone or co-treatment with TNF-α/χαταλyτιχαλlψ inactive Cholix did not. In the early stage of cell death, Cholix increased phosphorylation of mitogen-activated protein kinases (e.g., p38, ERK, JNK) and Akt, which was not affected by TNF-α alone. MAPK inhibitors (SP600125, SB20852, U0126) suppressed PARP cleavage induced by TNF-α/Cholix. Protein kinase inhibitor Go6976 suppressed JNK phosphorylation and PARP cleavage by TNF-α/Cholix. In contrast, PKC activator PMA in the absence of TNF-α promoted Cholix-induced PARP cleavage. Reactive oxygen species (ROS) inhibitor, N-acetyl cysteine (NAC), suppressed TNF-α/Χhoλιξ-induced JNK and ERK phosphorylation, resulting in inhibition of PARP cleavage. These data suggest that ROS and JNK pathways are important mediators of TNF-α/Cholix-induced HepG2 cell death. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Ogura, Kohei AU - Terasaki, Yasuhiro AU - Miyoshi-Akiyama, Tohru AU - Terasaki, Mika AU - Moss, Joel AU - Noda, Masatoshi AU - Yahiro, Kinnosuke AD - Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan. ; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan. ; Pathogenic Microbe Laboratory, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. ; Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1590, USA. ; Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan; yahirok@faculty.chiba-u.jp. Y1 - 2017/01/13/ PY - 2017 DA - 2017 Jan 13 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861495899?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Vibrio+cholerae+Cholix+toxin-induced+HepG2+cell+death+is+enhanced+by+tumor+necrosis+factor-alpha+through+ROS+and+intracellular+signal-regulated+kinases.&rft.au=Ogura%2C+Kohei%3BTerasaki%2C+Yasuhiro%3BMiyoshi-Akiyama%2C+Tohru%3BTerasaki%2C+Mika%3BMoss%2C+Joel%3BNoda%2C+Masatoshi%3BYahiro%2C+Kinnosuke&rft.aulast=Ogura&rft.aufirst=Kohei&rft.date=2017-01-13&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=1096-0929&rft_id=info:doi/10.1093%2Ftoxsci%2Fkfx009 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-14 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1093/toxsci/kfx009 ER - TY - JOUR T1 - Neutrophil elastase cleavage of the gC1q domain impairs the EMILIN1-α4β1 integrin interaction, cell adhesion and anti-proliferative activity. AN - 1857753264; 28074935 AB - The extracellular matrix glycoprotein EMILIN1 exerts a wide range of functions mainly associated with its gC1q domain. Besides providing functional significance for adhesion and migration, the direct interaction between α4β1 integrin and EMILIN1-gC1q regulates cell proliferation, transducing net anti-proliferative effects. We have previously demonstrated that EMILIN1 degradation by neutrophil elastase (NE) is a specific mechanism leading to the loss of functions disabling its regulatory properties. In this study we further analysed the proteolytic activity of NE, MMP-3, MMP-9, and MT1-MMP on EMILIN1 and found that MMP-3 and MT1-MMP partially cleaved EMILIN1 but without affecting the functional properties associated with the gC1q domain, whereas NE was able to fully impair the interaction of gC1q with the α4β1 integrin by cleaving this domain outside of the E933 integrin binding site. By a site direct mutagenesis approach we mapped the bond between S913 and R914 residues and selected the NE-resistant R914W mutant still able to interact with the α4β1 integrin after NE treatment. Functional studies showed that NE impaired the EMILIN1-α4β1 integrin interaction by cleaving the gC1q domain in a region crucial for its proper structural conformation, paving the way to better understand NE effects on EMILIN1-cell interaction in pathological context. JF - Scientific reports AU - Maiorani, Orlando AU - Pivetta, Eliana AU - Capuano, Alessandra AU - Modica, Teresa Maria Elisa AU - Wassermann, Bruna AU - Bucciotti, Francesco AU - Colombatti, Alfonso AU - Doliana, Roberto AU - Spessotto, Paola AD - Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, Aviano 33081, Italy. Y1 - 2017/01/11/ PY - 2017 DA - 2017 Jan 11 SP - 39974 VL - 7 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1857753264?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Neutrophil+elastase+cleavage+of+the+gC1q+domain+impairs+the+EMILIN1-%CE%B14%CE%B21+integrin+interaction%2C+cell+adhesion+and+anti-proliferative+activity.&rft.au=Maiorani%2C+Orlando%3BPivetta%2C+Eliana%3BCapuano%2C+Alessandra%3BModica%2C+Teresa+Maria+Elisa%3BWassermann%2C+Bruna%3BBucciotti%2C+Francesco%3BColombatti%2C+Alfonso%3BDoliana%2C+Roberto%3BSpessotto%2C+Paola&rft.aulast=Maiorani&rft.aufirst=Orlando&rft.date=2017-01-11&rft.volume=7&rft.issue=&rft.spage=39974&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep39974 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-11 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1038/srep39974 ER - TY - JOUR T1 - Cost evaluation of irinotecan-related toxicities associated with the UGT1A1*28 patient genotype. AN - 1857751914; 28074472 AB - The adoption of a pre-emptive UGT1A1*28 genotyping to increase irinotecan safety in clinical practice is still limited. This is the first actual study of costs associated to the management of irinotecan-related toxicity, and their association with UGT1A1*28 genotype. A retrospective analysis of the cost of toxicity management was conducted on 243 metastatic colorectal cancer patients enrolled in a clinical trial and treated with standard of care FOLFIRI. The mean predicted cost per patient was higher for *28/*28 (4,886€), versus *1/*1 (812€), (regression coefficient 1.79, 95%CI=1.31-2.28; P<0.001) and for *1/*28 (1,119€) versus *1/*1 (regression coefficient 0.32, 95%CI=0.04-0.60; P=0.024). This is consistent with a different grade 4 toxicity profile among the three genotypes, and a higher frequency of costly interventions like hospitalization among patients with the *28 allele. A differential toxicity management cost by *28 genotype is herein demonstrated, representing a first step towards a demonstration of the test clinical utility. This article is protected by copyright. All rights reserved. © 2017 American Society for Clinical Pharmacology and Therapeutics. JF - Clinical pharmacology and therapeutics AU - Roncato, R AU - Cecchin, E AU - Montico, M AU - De Mattia, E AU - Giodini, L AU - Buonadonna, A AU - Solfrini, V AU - Innocenti, F AU - Toffoli, G AD - Experimental and Clinical Pharmacology, Centro Di Riferimento Oncologico- National Cancer Institute, 2-33081, Aviano, Italy. ; Medical Oncology Unit B, Centro Di Riferimento Oncologico- National Cancer Institute, 2-33081, Aviano, Italy. ; Sanitary Direction, Centro Di Riferimento Oncologico- National Cancer Institute, 2-33081, Aviano, Italy. ; Eshelman School of Pharmacy, Center for Pharmacogenomics and Individualized Therapy, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. Y1 - 2017/01/11/ PY - 2017 DA - 2017 Jan 11 KW - direct medical costs KW - irinotecan KW - cost of toxicity management KW - UGT1A1*28 KW - pharmacogenetics KW - colorectal cancer KW - Italy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1857751914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Journal+of+Epidemiology&rft.atitle=Circulatory+disease+mortality+in+the+Massachusetts+tuberculosis+fluoroscopy+cohort+study&rft.au=Little%2C+Mark+P%3BZablotska%2C+Lydia+B%3BBrenner%2C+Alina+V%3BLipshultz%2C+Steven+E&rft.aulast=Little&rft.aufirst=Mark&rft.date=2016-03-01&rft.volume=31&rft.issue=3&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Epidemiology&rft.issn=03932990&rft_id=info:doi/10.1007%2Fs10654-015-0075-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/cpt.615 ER - TY - JOUR T1 - Mammary extracellular matrix directs differentiation of testicular and embryonic stem cells to form functional mammary glands in vivo. AN - 1857374964; 28071703 AB - Previously, we demonstrated the ability of the normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem cells (ESCs) to adopt a mammary epithelial cell (MEC) fate. These studies relied upon the interaction of transplanted normal MECs with non-mammary cells within the mammary fat-pads of recipient mice that had their endogenous epithelium removed. Here, we tested whether acellular mammary extracellular matrix (mECM) preparations are sufficient to direct differentiation of testicular-derived cells and ESCs to form functional mammary epithelial trees in vivo. We found that mECMs isolated from adult mice and rats were sufficient to redirect testicular derived cells to produce normal mammary epithelial trees within epithelial divested mouse mammary fat-pads. Conversely, ECMs isolated from omental fat and lung did not redirect testicular cells to a MEC fate, indicating the necessity of tissue specific components of the mECM. mECM preparations also completely inhibited teratoma formation from ESC inoculations. Further, a phenotypically normal ductal outgrowth resulted from a single inoculation of ESCs and mECM. To the best of our knowledge, this is the first demonstration of a tissue specific ECM driving differentiation of cells to form a functional tissue in vivo. JF - Scientific reports AU - Bruno, Robert D AU - Fleming, Jodie M AU - George, Andrea L AU - Boulanger, Corinne A AU - Schedin, Pepper AU - Smith, Gilbert H AD - School of Medical Diagnostic &Translational Sciences, College of Health Sciences, Old Dominion University, Norfolk, VA 23529, USA. ; Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, NC, 27707, USA. ; Mammary Stem Cell Biology Section, Basic Research Laboratory, CCR, NCI/NIH, Bethesda MD, 20892, USA. ; Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Y1 - 2017/01/10/ PY - 2017 DA - 2017 Jan 10 SP - 40196 VL - 7 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1857374964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Mammary+extracellular+matrix+directs+differentiation+of+testicular+and+embryonic+stem+cells+to+form+functional+mammary+glands+in+vivo.&rft.au=Bruno%2C+Robert+D%3BFleming%2C+Jodie+M%3BGeorge%2C+Andrea+L%3BBoulanger%2C+Corinne+A%3BSchedin%2C+Pepper%3BSmith%2C+Gilbert+H&rft.aulast=Bruno&rft.aufirst=Robert&rft.date=2017-01-10&rft.volume=7&rft.issue=&rft.spage=40196&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep40196 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-10 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1038/srep40196 ER - TY - JOUR T1 - Oxidized nucleotide insertion by pol β confounds ligation during base excision repair. AN - 1856864860; 28067232 AB - Oxidative stress in cells can lead to accumulation of reactive oxygen species and oxidation of DNA precursors. Oxidized purine nucleotides can be inserted into DNA during replication and repair. The main pathway for correcting oxidized bases in DNA is base excision repair (BER), and in vertebrates DNA polymerase β (pol β) provides gap filling and tailoring functions. Here we report that the DNA ligation step of BER is compromised after pol β insertion of oxidized purine nucleotides into the BER intermediate in vitro. These results suggest the possibility that BER mediated toxic strand breaks are produced in cells under oxidative stress conditions. We observe enhanced cytotoxicity in oxidizing-agent treated pol β expressing mouse fibroblasts, suggesting formation of DNA strand breaks under these treatment conditions. Increased cytotoxicity following MTH1 knockout or treatment with MTH1 inhibitor suggests the oxidation of precursor nucleotides. JF - Nature communications AU - Çağlayan, Melike AU - Horton, Julie K AU - Dai, Da-Peng AU - Stefanick, Donna F AU - Wilson, Samuel H AD - Genome Integrity and Structural Biology Laboratory, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2017/01/09/ PY - 2017 DA - 2017 Jan 09 SP - 14045 VL - 8 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856864860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+communications&rft.atitle=Oxidized+nucleotide+insertion+by+pol+%CE%B2+confounds+ligation+during+base+excision+repair.&rft.au=%C3%87a%C4%9Flayan%2C+Melike%3BHorton%2C+Julie+K%3BDai%2C+Da-Peng%3BStefanick%2C+Donna+F%3BWilson%2C+Samuel+H&rft.aulast=%C3%87a%C4%9Flayan&rft.aufirst=Melike&rft.date=2017-01-09&rft.volume=8&rft.issue=&rft.spage=14045&rft.isbn=&rft.btitle=&rft.title=Nature+communications&rft.issn=2041-1723&rft_id=info:doi/10.1038%2Fncomms14045 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/ncomms14045 ER - TY - JOUR T1 - Proteomic Analysis of Primary Human Airway Epithelial Cells Exposed to the Respiratory Toxicant Diacetyl. AN - 1852676393; 27966365 AB - Occupational exposures to the diketone flavoring agent, diacetyl, have been associated with bronchiolitis obliterans, a rare condition of airway fibrosis. Model studies in rodents have suggested that the airway epithelium is a major site of diacetyl toxicity, but the effects of diacetyl exposure upon the human airway epithelium are poorly characterized. Here we performed quantitative LC-MS/MS-based proteomics to study the effects of repeated diacetyl vapor exposures on 3D organotypic cultures of human primary tracheobronchial epithelial cells. Using a label-free approach, we quantified approximately 3400 proteins and 5700 phosphopeptides in cell lysates across four independent donors. Altered expression of proteins and phosphopeptides were suggestive of loss of cilia and increased squamous differentiation in diacetyl-exposed cells. These phenomena were confirmed by immunofluorescence staining of culture cross sections. Hyperphosphorylation and cross-linking of basal cell keratins were also observed in diacetyl-treated cells, and we used parallel reaction monitoring to confidently localize and quantify previously uncharacterized sites of phosphorylation in keratin 6. Collectively, these data identify numerous molecular changes in the epithelium that may be important to the pathogenesis of flavoring-induced bronchiolitis obliterans. More generally, this study highlights the utility of quantitative proteomics for the study of in vitro models of airway injury and disease. JF - Journal of proteome research AU - Foster, Matthew W AU - Gwinn, William M AU - Kelly, Francine L AU - Brass, David M AU - Valente, Ashlee M AU - Moseley, M Arthur AU - Thompson, J Will AU - Morgan, Daniel L AU - Palmer, Scott M AD - National Institute of Environmental Health Sciences , Research Triangle Park, North Carolina 27709, United States. Y1 - 2017/01/09/ PY - 2017 DA - 2017 Jan 09 KW - squamous metaplasia KW - repetin KW - butter flavoring KW - RSPH4A KW - TGM1 KW - butanedione KW - BO KW - cornified envelope KW - PRM KW - pentanedione UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852676393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+proteome+research&rft.atitle=Proteomic+Analysis+of+Primary+Human+Airway+Epithelial+Cells+Exposed+to+the+Respiratory+Toxicant+Diacetyl.&rft.au=Foster%2C+Matthew+W%3BGwinn%2C+William+M%3BKelly%2C+Francine+L%3BBrass%2C+David+M%3BValente%2C+Ashlee+M%3BMoseley%2C+M+Arthur%3BThompson%2C+J+Will%3BMorgan%2C+Daniel+L%3BPalmer%2C+Scott+M&rft.aulast=Foster&rft.aufirst=Matthew&rft.date=2017-01-09&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+proteome+research&rft.issn=1535-3907&rft_id=info:doi/10.1021%2Facs.jproteome.6b00672 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.jproteome.6b00672 ER - TY - JOUR T1 - Renal Toxicities of Novel Agents Used for Treatment of Multiple Myeloma. AN - 1856594646; 27654928 AB - Survival for patients with multiple myeloma has significantly improved in the last decade in large part due to the development of proteasome inhibitors and immunomodulatory drugs. These next generation agents with novel mechanisms of action as well as targeted therapies are being used both in the preclinical and clinical settings for patients with myeloma. These agents include monoclonal antibodies, deacetylase inhibitors, kinase inhibitors, agents affecting various signaling pathways, immune check point inhibitors, and other targeted therapies. In some cases, off target effects of these therapies can lead to unanticipated effects on the kidney that can range from electrolyte disorders to AKI. In this review, we discuss the nephrotoxicities of novel agents currently in practice as well as in development for the treatment of myeloma. Copyright © 2016 by the American Society of Nephrology. JF - Clinical journal of the American Society of Nephrology : CJASN AU - Wanchoo, Rimda AU - Abudayyeh, Ala AU - Doshi, Mona AU - Edeani, Amaka AU - Glezerman, Ilya G AU - Monga, Divya AU - Rosner, Mitchell AU - Jhaveri, Kenar D AD - Division of Nephrology, Hofstra Northwell School of Medicine, Great Neck, New York. ; Division of Internal Medicine, Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, Texas. ; Division of Nephrology, Wayne State University School of Medicine, Detroit, Michigan. ; Kidney Diseases Branch, National Institute of Diabetes, Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland. ; Department of Medicine, Renal Service, Memorial Sloan Kettering Cancer Center and Department of Medicine, Weill Cornell Medical Center, New York, New York. ; Nephrology Division, University of Mississippi Medical Center, Jackson, Mississippi; and. ; Division of Nephrology, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia. ; Division of Nephrology, Hofstra Northwell School of Medicine, Great Neck, New York; kjhaveri@northwell.edu. Y1 - 2017/01/06/ PY - 2017 DA - 2017 Jan 06 SP - 176 EP - 189 VL - 12 IS - 1 KW - Proteasome Inhibitors KW - multiple myeloma KW - Coal Tar KW - electrolytes KW - humans KW - chronic kidney disease KW - Antibodies, Monoclonal KW - drug nephrotoxicity KW - Acute Kidney Injury KW - acute renal failure KW - Water-Electrolyte Imbalance KW - kidney KW - cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856594646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+journal+of+the+American+Society+of+Nephrology+%3A+CJASN&rft.atitle=Renal+Toxicities+of+Novel+Agents+Used+for+Treatment+of+Multiple+Myeloma.&rft.au=Wanchoo%2C+Rimda%3BAbudayyeh%2C+Ala%3BDoshi%2C+Mona%3BEdeani%2C+Amaka%3BGlezerman%2C+Ilya+G%3BMonga%2C+Divya%3BRosner%2C+Mitchell%3BJhaveri%2C+Kenar+D&rft.aulast=Wanchoo&rft.aufirst=Rimda&rft.date=2017-01-06&rft.volume=12&rft.issue=1&rft.spage=176&rft.isbn=&rft.btitle=&rft.title=Clinical+journal+of+the+American+Society+of+Nephrology+%3A+CJASN&rft.issn=1555-905X&rft_id=info:doi/10.2215%2FCJN.06100616 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-22 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.2215/CJN.06100616 ER - TY - JOUR T1 - Don't Worry, Be Happy: Endocannabinoids and Cannabis at the Intersection of Stress and Reward. AN - 1856593194; 27618739 AB - Cannabis enables and enhances the subjective sense of well-being by stimulating the endocannabinoid system (ECS), which plays a key role in modulating the response to stress, reward, and their interactions. However, over time, repeated activation of the ECS by cannabis can trigger neuroadaptations that may impair the sensitivity to stress and reward. This effect, in vulnerable individuals, can lead to addiction and other adverse consequences. The recent shift toward legalization of medical or recreational cannabis has renewed interest in investigating the physiological role of the ECS as well as the potential health effects, both adverse and beneficial, of cannabis. Here we review our current understanding of the ECS and its complex physiological roles. We discuss the implications of this understanding vis-á-vis the ECS's modulation of stress and reward and its relevance to mental disorders in which these processes are disrupted (i.e., addiction, depression, posttraumatic stress disorder, schizophrenia), along with the therapeutic potential of strategies to manipulate the ECS for these conditions. JF - Annual review of pharmacology and toxicology AU - Volkow, Nora D AU - Hampson, Aidan J AU - Baler, Ruben D AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland 20892; email: nvolkow@nida.nih.gov. Y1 - 2017/01/06/ PY - 2017 DA - 2017 Jan 06 SP - 285 EP - 308 VL - 57 KW - endocannabinoids KW - cannabis KW - reward KW - THC KW - stress KW - marijuana UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856593194?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+pharmacology+and+toxicology&rft.atitle=Don%27t+Worry%2C+Be+Happy%3A+Endocannabinoids+and+Cannabis+at+the+Intersection+of+Stress+and+Reward.&rft.au=Volkow%2C+Nora+D%3BHampson%2C+Aidan+J%3BBaler%2C+Ruben+D&rft.aulast=Volkow&rft.aufirst=Nora&rft.date=2017-01-06&rft.volume=57&rft.issue=&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+pharmacology+and+toxicology&rft.issn=1545-4304&rft_id=info:doi/10.1146%2Fannurev-pharmtox-010716-104615 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-13 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1146/annurev-pharmtox-010716-104615 ER - TY - JOUR T1 - CNS Target Identification and Validation: Avoiding the Valley of Death or Naive Optimism? AN - 1856593185; 27575715 AB - There are many challenges along the path to the approval of new drugs to treat CNS disorders, one of the greatest areas of unmet medical need with a large societal burden and health-care impact. Unfortunately, over the past two decades, few CNS drug approvals have succeeded, leading many pharmaceutical companies to deprioritize this therapeutic area. The reasons for the failures in CNS drug discovery are likely to be multifactorial. However, selecting the most biologically plausible molecular targets that are relevant to the disorder is a critical first step to improve the probability of success. In this review, we outline previous methods for identifying and validating novel targets for CNS drug discovery, and, cognizant of previous failures, we discuss potential new strategies that may improve the probability of success of developing novel treatments for CNS disorders. JF - Annual review of pharmacology and toxicology AU - Hutson, P H AU - Clark, J A AU - Cross, A J AD - Neurobiology, CNS Discovery, Teva Pharmaceuticals, West Chester, Pennsylvania 19380; email: peter.hutson@tevapharm.com. ; Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland 20892; email: Janet.Clark@nih.gov. ; Neuroscience Innovative Medicines, AstraZeneca, Cambridge, Massachusetts 01239; email: alan.cross@azneuro.com. Y1 - 2017/01/06/ PY - 2017 DA - 2017 Jan 06 SP - 171 EP - 187 VL - 57 KW - drug development KW - psychiatry KW - neurology KW - drug discovery KW - translational research UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856593185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+pharmacology+and+toxicology&rft.atitle=CNS+Target+Identification+and+Validation%3A+Avoiding+the+Valley+of+Death+or+Naive+Optimism%3F&rft.au=Hutson%2C+P+H%3BClark%2C+J+A%3BCross%2C+A+J&rft.aulast=Hutson&rft.aufirst=P&rft.date=2017-01-06&rft.volume=57&rft.issue=&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+pharmacology+and+toxicology&rft.issn=1545-4304&rft_id=info:doi/10.1146%2Fannurev-pharmtox-010716-104624 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-30 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1146/annurev-pharmtox-010716-104624 ER - TY - JOUR T1 - Harnessing Big Data for Systems Pharmacology. AN - 1836728054; 27814027 AB - Systems pharmacology aims to holistically understand mechanisms of drug actions to support drug discovery and clinical practice. Systems pharmacology modeling (SPM) is data driven. It integrates an exponentially growing amount of data at multiple scales (genetic, molecular, cellular, organismal, and environmental). The goal of SPM is to develop mechanistic or predictive multiscale models that are interpretable and actionable. The current explosions in genomics and other omics data, as well as the tremendous advances in big data technologies, have already enabled biologists to generate novel hypotheses and gain new knowledge through computational models of genome-wide, heterogeneous, and dynamic data sets. More work is needed to interpret and predict a drug response phenotype, which is dependent on many known and unknown factors. To gain a comprehensive understanding of drug actions, SPM requires close collaborations between domain experts from diverse fields and integration of heterogeneous models from biophysics, mathematics, statistics, machine learning, and semantic webs. This creates challenges in model management, model integration, model translation, and knowledge integration. In this review, we discuss several emergent issues in SPM and potential solutions using big data technology and analytics. The concurrent development of high-throughput techniques, cloud computing, data science, and the semantic web will likely allow SPM to be findable, accessible, interoperable, reusable, reliable, interpretable, and actionable. JF - Annual review of pharmacology and toxicology AU - Xie, Lei AU - Draizen, Eli J AU - Bourne, Philip E AD - Department of Computer Science, Hunter College, The City University of New York, New York, NY 10065; email: lei.xie@hunter.cuny.edu. ; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894; email: philip.bourne@nih.gov. Y1 - 2017/01/06/ PY - 2017 DA - 2017 Jan 06 SP - 245 EP - 262 VL - 57 KW - data science KW - systems pharmacology modeling KW - NIH Commons KW - systems biology KW - computational modeling KW - machine learning KW - cloud computing KW - semantic web UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836728054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+pharmacology+and+toxicology&rft.atitle=Harnessing+Big+Data+for+Systems+Pharmacology.&rft.au=Xie%2C+Lei%3BDraizen%2C+Eli+J%3BBourne%2C+Philip+E&rft.aulast=Xie&rft.aufirst=Lei&rft.date=2017-01-06&rft.volume=57&rft.issue=&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+pharmacology+and+toxicology&rft.issn=1545-4304&rft_id=info:doi/10.1146%2Fannurev-pharmtox-010716-104659 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1146/annurev-pharmtox-010716-104659 ER - TY - JOUR T1 - Introduction to the Theme "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology". AN - 1835420354; 27732830 AB - Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme for a number of articles in this volume. These include ones that review the development and use of new experimental tools and approaches (e.g., nanobodies and techniques to explore protein-protein interactions), new types of therapeutics (e.g., aptamers and antisense oligonucleotides), and systems pharmacology, which assembles (big) data derived from omics studies together with information regarding drugs and patients. The application of these new methods and therapeutic approaches has the potential to have a major impact on basic and clinical research in pharmacology and toxicology as well as on patient care. JF - Annual review of pharmacology and toxicology AU - Insel, Paul A AU - Amara, Susan G AU - Blaschke, Terrence F AU - Meyer, Urs A AD - Department of Pharmacology, University of California, San Diego, La Jolla, California 92093. ; National Institute of Mental Health, Bethesda, Maryland 20892. ; Department of Medicine, Stanford University School of Medicine, Stanford, California 94305. ; Biozentrum, University of Basel, CH-4056 Basel, Switzerland. Y1 - 2017/01/06/ PY - 2017 DA - 2017 Jan 06 SP - 13 EP - 17 VL - 57 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835420354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+pharmacology+and+toxicology&rft.atitle=Introduction+to+the+Theme+%22New+Methods+and+Novel+Therapeutic+Approaches+in+Pharmacology+and+Toxicology%22.&rft.au=Insel%2C+Paul+A%3BAmara%2C+Susan+G%3BBlaschke%2C+Terrence+F%3BMeyer%2C+Urs+A&rft.aulast=Insel&rft.aufirst=Paul&rft.date=2017-01-06&rft.volume=57&rft.issue=&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+pharmacology+and+toxicology&rft.issn=1545-4304&rft_id=info:doi/10.1146%2Fannurev-pharmtox-091616-023708 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1146/annurev-pharmtox-091616-023708 ER - TY - JOUR T1 - Type-dependent association between risk of cervical intraepithelial neoplasia and viral load of oncogenic human papillomavirus types other than types 16 and 18. AN - 1855788136; 28052328 AB - Studies of the clinical relevance of human papillomavirus (HPV) DNA load have focused mainly on HPV16 and HPV18. Data on other oncogenic types are rare. Study subjects were women enrolled in the atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) triage study who had ≥1 of 11 non-HPV16/18 oncogenic types detected during a 2-year follow-up at 6-month intervals. Viral load measurements were performed on the first type-specific HPV-positive specimens. The association of cervical intraepithelial neoplasia grades 2-3 (CIN2/3) with type-specific HPV DNA load was assessed with discrete-time Cox regression. Overall, the increase in the cumulative risk of CIN2/3 per 1 unit increase in log10 -transformed viral load was statistically significant for four types within species 9 including HPV31 (adjusted hazard ratio [HR adjusted ] = 1.32: 95% confidence interval [CI], 1.14-1.52), HPV35 (HR adjusted  = 1.47; 95% CI, 1.23-1.76), HPV52 (HR adjusted  = 1.14; 95% CI, 1.01-1.30) and HPV58 (HR adjusted  = 1.49; 95% CI, 1.23-1.82). The association was marginally significant for HPV33 (species 9) and HPV45 (species 7) and was not appreciable for other types. The per 1 log10 -unit increase in viral load of a group of species 9 non-HPV16 oncogenic types was statistically significantly associated with risk of CIN2/3 for women with a cytologic diagnosis of within normal limits, ASC-US, or LSIL at the first HPV-positive visit but not for those with high-grade SIL. Findings suggest that the viral load-associated risk of CIN2/3 is type-dependent, and mainly restricted to the species of HPV types related to HPV16, which shares this association. © 2017 UICC. JF - International journal of cancer AU - Fu Xi, Long AU - Schiffman, Mark AU - Ke, Yang AU - Hughes, James P AU - Galloway, Denise A AU - He, Zhonghu AU - Hulbert, Ayaka AU - Winer, Rachel L AU - Koutsky, Laura A AU - Kiviat, Nancy B AD - Department of Pathology, School of Medicine, University of Washington, Seattle, WA. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD. ; Key Laboratory of Carcinogenesis and Translational Research, Peking University School of Oncology, Beijing, People's Republic of China. ; Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, WA. ; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA. ; Department of Epidemiology, University of Washington, Seattle, WA. Y1 - 2017/01/04/ PY - 2017 DA - 2017 Jan 04 KW - risk association KW - human papillomavirus KW - cervical intraepithelial neoplasia KW - viral load UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855788136?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Type-dependent+association+between+risk+of+cervical+intraepithelial+neoplasia+and+viral+load+of+oncogenic+human+papillomavirus+types+other+than+types+16+and+18.&rft.au=Fu+Xi%2C+Long%3BSchiffman%2C+Mark%3BKe%2C+Yang%3BHughes%2C+James+P%3BGalloway%2C+Denise+A%3BHe%2C+Zhonghu%3BHulbert%2C+Ayaka%3BWiner%2C+Rachel+L%3BKoutsky%2C+Laura+A%3BKiviat%2C+Nancy+B&rft.aulast=Fu+Xi&rft.aufirst=Long&rft.date=2017-01-04&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=1097-0215&rft_id=info:doi/10.1002%2Fijc.30594 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-04 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1002/ijc.30594 ER - TY - JOUR T1 - Cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis. AN - 1855331799; 28051126 AB - Cytochrome P450-2E1 (CYP2E1) increases oxidative stress. High hepatic cholesterol causes non-alcoholic steatohepatitis (NASH) and fibrosis. Thus, we aimed to study the role of CYP2E1 in promoting liver fibrosis by high cholesterol-containing fast-food (FF). Male wild-type (WT) and Cyp2e1-null mice were fed standard chow or FF for 2, 12, and 24 weeks. Various parameters of liver fibrosis and potential mechanisms such as oxidative and endoplasmic reticulum (ER) stress, inflammation, and insulin resistance (IR) were studied. Indirect calorimetry was also used to determine metabolic parameters. Liver histology showed that only WT fed FF (WT-FF) developed NASH and fibrosis. Hepatic levels of fibrosis protein markers were significantly increased in WT-FF. The nitroxidative stress marker iNOS, but not CYP2E1, was significantly elevated only in FF-fed WT. Serum endotoxin, TLR-4 levels, and inflammatory markers were highest in WT-FF. FAS, PPAR-α, PPAR-γ, and CB1-R were markedly altered in WT-FF. Electron microscopy and immunoblot analyses showed significantly higher levels of ER stress in FF-fed WT. Indirect calorimetry showed that Cyp2e1-null-mice fed FF exhibited consistently higher total energy expenditure (TEE) than their corresponding WT. These results demonstrate that CYP2E1 is important in fast food-mediated liver fibrosis by promoting nitroxidative and ER stress, endotoxemia, inflammation, IR, and low TEE. JF - Scientific reports AU - Abdelmegeed, Mohamed A AU - Choi, Youngshim AU - Godlewski, Grzegorz AU - Ha, Seung-Kwon AU - Banerjee, Atrayee AU - Jang, Sehwan AU - Song, Byoung-Joon AD - Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA. ; Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20982, USA. Y1 - 2017/01/04/ PY - 2017 DA - 2017 Jan 04 SP - 39764 VL - 7 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855331799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Cytochrome+P450-2E1+promotes+fast+food-mediated+hepatic+fibrosis.&rft.au=Abdelmegeed%2C+Mohamed+A%3BChoi%2C+Youngshim%3BGodlewski%2C+Grzegorz%3BHa%2C+Seung-Kwon%3BBanerjee%2C+Atrayee%3BJang%2C+Sehwan%3BSong%2C+Byoung-Joon&rft.aulast=Abdelmegeed&rft.aufirst=Mohamed&rft.date=2017-01-04&rft.volume=7&rft.issue=&rft.spage=39764&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep39764 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep39764 ER - TY - JOUR T1 - Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity. AN - 1855066304; 28045021 AB - The cannabinoid CB2 receptor (CB2R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed and widely used to target CB2R, their selectivity, molecular mode of action and pharmacokinetic properties have been poorly characterized. Here we report the most extensive characterization of the molecular pharmacology of the most widely used CB2R ligands to date. In a collaborative effort between multiple academic and industry laboratories, we identify marked differences in the ability of certain agonists to activate distinct signalling pathways and to cause off-target effects. We reach a consensus that HU910, HU308 and JWH133 are the recommended selective CB2R agonists to study the role of CB2R in biological and disease processes. We believe that our unique approach would be highly suitable for the characterization of other therapeutic targets in drug discovery research. JF - Nature communications AU - Soethoudt, Marjolein AU - Grether, Uwe AU - Fingerle, Jürgen AU - Grim, Travis W AU - Fezza, Filomena AU - de Petrocellis, Luciano AU - Ullmer, Christoph AU - Rothenhäusler, Benno AU - Perret, Camille AU - van Gils, Noortje AU - Finlay, David AU - MacDonald, Christa AU - Chicca, Andrea AU - Gens, Marianela Dalghi AU - Stuart, Jordyn AU - de Vries, Henk AU - Mastrangelo, Nicolina AU - Xia, Lizi AU - Alachouzos, Georgios AU - Baggelaar, Marc P AU - Martella, Andrea AU - Mock, Elliot D AU - Deng, Hui AU - Heitman, Laura H AU - Connor, Mark AU - Di Marzo, Vincenzo AU - Gertsch, Jürg AU - Lichtman, Aron H AU - Maccarrone, Mauro AU - Pacher, Pal AU - Glass, Michelle AU - van der Stelt, Mario AD - Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden 2333 CC, The Netherlands. ; Roche Innovation Center Basel, F. Hoffman-La Roche Ltd., Grenzachterstrasse 124, Basel 4070, Switzerland. ; Department of Biochemistry, NMI, University Tübingen, Markwiesenstrasse 55, Reutlingen 72770, Germany. ; Department of Pharmacology and Toxicology, 1220 East Broad Street, PO Box 980613, Richmond, Virginia 23298-0613, USA. ; Department of Experimental Medicine and Surgery, Tor Vergata University of Rome, Via Montpellier 1, Rome 00133, Italy. ; Endocannabinoid Research Group, Institute of Biomolecular Chemistry, C.N.R., Via Campi Flegrei 34, Comprensorio Olivetti, Pozzuoli 80078, Italy. ; Department of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, Leiden 2333 CC, The Netherlands. ; Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park road, Grafton, Auckland 1023, New Zealand. ; Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, Bern CH-3012, Switzerland. ; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, North Ryde, New South Wales 2109, Australia. ; Department of Medicine, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, Rome 00128, Italy. ; European Center for Brain Research/IRCCS Santa Lucia Foundation, via del Fosso del Fiorano 65, Rome 00143, Italy. ; Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute of Health/NIAAA, 5625 Fishers Lane, Rockville, Maryland 20852, USA. Y1 - 2017/01/03/ PY - 2017 DA - 2017 Jan 03 SP - 13958 VL - 8 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855066304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+communications&rft.atitle=Cannabinoid+CB2+receptor+ligand+profiling+reveals+biased+signalling+and+off-target+activity.&rft.au=Soethoudt%2C+Marjolein%3BGrether%2C+Uwe%3BFingerle%2C+J%C3%BCrgen%3BGrim%2C+Travis+W%3BFezza%2C+Filomena%3Bde+Petrocellis%2C+Luciano%3BUllmer%2C+Christoph%3BRothenh%C3%A4usler%2C+Benno%3BPerret%2C+Camille%3Bvan+Gils%2C+Noortje%3BFinlay%2C+David%3BMacDonald%2C+Christa%3BChicca%2C+Andrea%3BGens%2C+Marianela+Dalghi%3BStuart%2C+Jordyn%3Bde+Vries%2C+Henk%3BMastrangelo%2C+Nicolina%3BXia%2C+Lizi%3BAlachouzos%2C+Georgios%3BBaggelaar%2C+Marc+P%3BMartella%2C+Andrea%3BMock%2C+Elliot+D%3BDeng%2C+Hui%3BHeitman%2C+Laura+H%3BConnor%2C+Mark%3BDi+Marzo%2C+Vincenzo%3BGertsch%2C+J%C3%BCrg%3BLichtman%2C+Aron+H%3BMaccarrone%2C+Mauro%3BPacher%2C+Pal%3BGlass%2C+Michelle%3Bvan+der+Stelt%2C+Mario&rft.aulast=Soethoudt&rft.aufirst=Marjolein&rft.date=2017-01-03&rft.volume=8&rft.issue=&rft.spage=13958&rft.isbn=&rft.btitle=&rft.title=Nature+communications&rft.issn=2041-1723&rft_id=info:doi/10.1038%2Fncomms13958 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/ncomms13958 ER - TY - JOUR T1 - Profiling the Serum Albumin Cys34 Adductome of Solid Fuel Users in Xuanwei and Fuyuan, China. AN - 1852658684; 27936627 AB - Xuanwei and Fuyuan counties in China have the highest lung cancer rates in the world due to household air pollution from combustion of smoky coal for cooking and heating. To discover potential biomarkers of indoor combustion products, we profiled adducts at the Cys34 locus of human serum albumin (HSA) in 29 nonsmoking Xuanwei and Fuyuan females who used smoky coal, smokeless coal, or wood and 10 local controls who used electricity or gas fuel. Our untargeted "adductomics" method detected 50 tryptic peptides of HSA, containing Cys34 and prominent post-translational modifications. Putative adducts included Cys34 oxidation products, mixed disulfides, rearrangements, and truncations. The most significant differences in adduct levels across fuel types were observed for S-glutathione (S-GSH) and S-γ-glutamylcysteine (S-γ-GluCys), both of which were present at lower levels in subjects exposed to combustion products than in controls. After adjustment for age and personal measurements of airborne benzo(a)pyrene, the largest reductions in levels of S-GSH and S-γ-GluCys relative to controls were observed for users of smoky coal, compared to users of smokeless coal and wood. These results point to possible depletion of GSH, an essential antioxidant, and its precursor γ-GluCys in nonsmoking females exposed to indoor-combustion products in Xuanwei and Fuyuan, China. JF - Environmental science & technology AU - Lu, Sixin S AU - Grigoryan, Hasmik AU - Edmands, William M B AU - Hu, Wei AU - Iavarone, Anthony T AU - Hubbard, Alan AU - Rothman, Nathaniel AU - Vermeulen, Roel AU - Lan, Qing AU - Rappaport, Stephen M AD - Department of Nutritional Sciences and Toxicology, College of Natural Resources, University of California , Berkeley, California 94720, United States. ; Division of Environmental Health Sciences, School of Public Health, University of California , Berkeley, California 94720, United States. ; Department of Health and Human Service, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Rockville, Maryland 20850, United States. ; California Institute for Quantitative Biosciences, University of California , Berkeley, California 94720, United States. ; Division of Biostatistics, School of Public Health, University of California , Berkeley, California 94720, United States. ; Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University , 3508 TD Utrecht, The Netherlands. Y1 - 2017/01/03/ PY - 2017 DA - 2017 Jan 03 SP - 46 EP - 57 VL - 51 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852658684?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+science+%26+technology&rft.atitle=Profiling+the+Serum+Albumin+Cys34+Adductome+of+Solid+Fuel+Users+in+Xuanwei+and+Fuyuan%2C+China.&rft.au=Lu%2C+Sixin+S%3BGrigoryan%2C+Hasmik%3BEdmands%2C+William+M+B%3BHu%2C+Wei%3BIavarone%2C+Anthony+T%3BHubbard%2C+Alan%3BRothman%2C+Nathaniel%3BVermeulen%2C+Roel%3BLan%2C+Qing%3BRappaport%2C+Stephen+M&rft.aulast=Lu&rft.aufirst=Sixin&rft.date=2017-01-03&rft.volume=51&rft.issue=1&rft.spage=46&rft.isbn=&rft.btitle=&rft.title=Environmental+science+%26+technology&rft.issn=1520-5851&rft_id=info:doi/10.1021%2Facs.est.6b03955 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.est.6b03955 ER - TY - JOUR T1 - An inducible ER-Golgi tether facilitates ceramide transport to alleviate lipotoxicity. AN - 1852786764; 28011845 AB - Ceramides are key intermediates in sphingolipid biosynthesis and potent signaling molecules. However, excess ceramide is toxic, causing growth arrest and apoptosis. In this study, we identify a novel mechanism by which cells prevent the toxic accumulation of ceramides; they facilitate nonvesicular ceramide transfer from the endoplasmic reticulum (ER) to the Golgi complex, where ceramides are converted to complex sphingolipids. We find that the yeast protein Nvj2p promotes the nonvesicular transfer of ceramides from the ER to the Golgi complex. The protein is a tether that generates close contacts between these compartments and may directly transport ceramide. Nvj2p normally resides at contacts between the ER and other organelles, but during ER stress, it relocalizes to and increases ER-Golgi contacts. ER-Golgi contacts fail to form during ER stress in cells lacking Nvj2p. Our findings demonstrate that cells regulate ER-Golgi contacts in response to stress and reveal that nonvesicular ceramide transfer out of the ER prevents the buildup of toxic amounts of ceramides. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. JF - The Journal of cell biology AU - Liu, Li-Ka AU - Choudhary, Vineet AU - Toulmay, Alexandre AU - Prinz, William A AD - Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. ; Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 toulmayal@niddk.nih.gov prinzw@helix.nih.gov. Y1 - 2017/01/02/ PY - 2017 DA - 2017 Jan 02 SP - 131 EP - 147 VL - 216 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852786764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+cell+biology&rft.atitle=An+inducible+ER-Golgi+tether+facilitates+ceramide+transport+to+alleviate+lipotoxicity.&rft.au=Liu%2C+Li-Ka%3BChoudhary%2C+Vineet%3BToulmay%2C+Alexandre%3BPrinz%2C+William+A&rft.aulast=Liu&rft.aufirst=Li-Ka&rft.date=2017-01-02&rft.volume=216&rft.issue=1&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+cell+biology&rft.issn=1540-8140&rft_id=info:doi/10.1083%2Fjcb.201606059 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-24 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1083/jcb.201606059 ER - TY - JOUR T1 - Caught between two proteins: a mycobacterial inhibitor challenges the mold AN - 1863210602; PQ0003986939 AB - Elucidating the target or mechanism of action of potential drugs in the discovery pipeline is an integral component of most programs. For antibacterial compounds, generation of resistant mutants followed by whole genome sequencing has often been successful in uncovering the proteins involved in regulating compound activation, uptake, efflux and importantly, target processes. When this process succeeds, we are quick to declare a target. In a study reported by Sing and Dhar et al. (in press), the combination of resistant mutant generation, whole genome sequencing and recombineering to identify the target of a Mycobacterium tuberculosis growth inhibitor, pointed to a mechanism involving a scaffolding protein, Wag31, involved in polar elongation of mycobacterial cells. Time-lapse microscopy and electron microscopy confirmed the view that this inhibitor resulted in interruption of nascent cell wall biosynthesis. However, co-expression as well as regulated titration of the putative Wag31 target demonstrated that the wild-type allele was dominant and showed no synergy with the inhibitor. The most plausible explanation from their results was that this inhibitor interfered with the interaction of Wag31 with one of its interacting partners in the elongation complex. JF - Molecular Microbiology AU - Boshoff, Helena I AD - Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, 20892-3206, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 2 EP - 6 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 103 IS - 1 SN - 0950-382X, 0950-382X KW - Microbiology Abstracts B: Bacteriology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1863210602?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Caught+between+two+proteins%3A+a+mycobacterial+inhibitor+challenges+the+mold&rft.au=Boshoff%2C+Helena+I&rft.aulast=Boshoff&rft.aufirst=Helena&rft.date=2017-01-01&rft.volume=103&rft.issue=1&rft.spage=2&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fmmi.13570 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1111/mmi.13570 ER - TY - JOUR T1 - Neuronal Cell Death and Degeneration through Increased Nitroxidative Stress and Tau Phosphorylation in HIV-1 Transgenic Rats. AN - 1861587464; 28107387 AB - The underlying mechanisms for increased neurodegeneration and neurocognitive deficits in HIV-infected people are unclear. Therefore, this study was aimed to investigate the mechanisms of increased neurodegeneration in 5-month old male HIV-1 Transgenic (Tg) rats compared to the age- and gender-matched wild-type (WT) by evaluating histological changes and biochemical parameters of the key proteins involved in the cell death signaling and apoptosis. Histological and immunohistochemical analyses revealed decreased neuronal cells with elevated astrogliosis in HIV-1 Tg rats compared to WT. Mechanistic studies revealed that increased levels of nitroxidative stress marker proteins such as NADPH-oxidase, cytochrome P450-2E1 (CYP2E1), inducible nitric oxide synthase (iNOS), the stress-activated mitogen-activated protein kinases such as JNK and p38K, activated cell-cycle dependent CDK5, hypoxia-inducible protein-1α, nitrated proteins, hyperphosphorylated tau, and amyloid plaques in HIV-Tg rats were consistently observed in HIV-1 Tg rats. Confocal microscopy and cell viability analyses showed that treatment with an antioxidant N-acetylcysteine or a specific inhibitor of iNOS 1400W significantly prevented the increased apoptosis of neuro-2A cells by HIV-1 Tat or gp120 protein, demonstrating the causal role of HIV-1 mediated nitroxidative stress and protein nitration in promoting neuronal cell death. Immunoprecipitation and immunoblot analysis confirmed nitration of Hsp90, evaluated as an example of nitrated proteins, suggesting possible involvement of nitrated proteins in neuronal damage. Further, activated p-JNK directly binds tau and phosphorylates multiple amino acids, suggesting an important role of p-JNK in tau hyperphosphorylation and tauopathy. These changes were accompanied with elevated levels of many apoptosis-related proteins Bax and cleaved (activated) caspase-3 as well as proinflammatory cytokines including TNF-α, IL-6 and MCP-1. Collectively, these results indicate that raised nitroxidative stress accompanied by elevated inflammation, cell death signaling pathway including activated p-JNK, C-terminal C99 amyloid fragment formation and tau hyperphosphorylation are responsible for increased apoptosis of neuronal cells and neurodegeneration in 5-month old HIV-Tg rats. JF - PloS one AU - Cho, Young-Eun AU - Lee, Myoung-Hwa AU - Song, Byoung-Joon AD - Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, United States of America. ; Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, United States of America. Y1 - 2017 PY - 2017 DA - 2017 SP - 1 VL - 12 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861587464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PloS+one&rft.atitle=Neuronal+Cell+Death+and+Degeneration+through+Increased+Nitroxidative+Stress+and+Tau+Phosphorylation+in+HIV-1+Transgenic+Rats.&rft.au=Cho%2C+Young-Eun%3BLee%2C+Myoung-Hwa%3BSong%2C+Byoung-Joon&rft.aulast=Cho&rft.aufirst=Young-Eun&rft.date=2017-01-01&rft.volume=12&rft.issue=1&rft.spage=e0169945&rft.isbn=&rft.btitle=&rft.title=PloS+one&rft.issn=1932-6203&rft_id=info:doi/10.1371%2Fjournal.pone.0169945 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-20 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1371/journal.pone.0169945 ER - TY - JOUR T1 - Tetrabromobisphenol A activates the hepatic interferon pathway in rats AN - 1859502039; PQ0004015269 AB - Tetrabromobisphenol A (TBBPA) is a widely used flame retardant in printed circuit boards, paper, and textiles. In a two-year study, TBBPA showed evidence of uterine tumors in female Wistar-Han rats and liver and colon tumors in B6C3F1 mice. In order to gain further insight into early gene and pathway changes leading to cancer, we exposed female Wistar Han rats to TBBPA at 0, 25, 250, or 1000mg/kg (oral gavage in corn oil, 5/week) for 13 weeks. Because at the end of the TBBPA exposure period, there were no treatment-related effects on body weights, liver or uterus lesions, and liver and uterine organ weights were within 10% of controls, only the high dose animals were analyzed. Analysis of the hepatic and uterine transcriptomes showed TBBPA-induced changes primarily in the liver (1000mg/kg), with 159 transcripts corresponding to 132 genes differentially expressed compared to controls (FDR=0.05). Pathway analysis showed activation of interferon (IFN) and metabolic networks. TBBPA induced few molecular changes in the uterus. Activation of the interferon pathway in the liver occurred after 13-weeks of TBBPA exposure, and with longer term TBBPA exposure this may lead to immunomodulatory changes that contribute to carcinogenic processes. JF - Toxicology Letters AU - Dunnick, J K AU - Morgan, D L AU - Elmore, SA AU - Gerrish, K AU - Pandiri, A AU - Ton, T V AU - Shockley, K R AU - Merrick, BA AD - Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 32 EP - 41 PB - Elsevier B.V., Elsevier House, Brookvale Plaza East Park Shannon, Co. Clare Ireland VL - 266 SN - 0378-4274, 0378-4274 KW - Toxicology Abstracts KW - Tetrabromobisphenol A KW - Toxicogenomics KW - Microarray KW - Interferon response transcripts KW - Pathway analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859502039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=Tetrabromobisphenol+A+activates+the+hepatic+interferon+pathway+in+rats&rft.au=Dunnick%2C+J+K%3BMorgan%2C+D+L%3BElmore%2C+SA%3BGerrish%2C+K%3BPandiri%2C+A%3BTon%2C+T+V%3BShockley%2C+K+R%3BMerrick%2C+BA&rft.aulast=Dunnick&rft.aufirst=J&rft.date=2017-01-01&rft.volume=266&rft.issue=&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&rft_id=info:doi/10.1016%2Fj.toxlet.2016.11.019 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1016/j.toxlet.2016.11.019 ER - TY - JOUR T1 - Skin microbiome before development of atopic dermatitis: Early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year AN - 1859501011; PQ0004015398 AB - Background Disease flares of established atopic dermatitis (AD) are generally associated with a low-diversity skin microbiota and Staphylococcus aureus dominance. The temporal transition of the skin microbiome between early infancy and the dysbiosis of established AD is unknown. Methods We randomly selected 50 children from the Cork Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE) longitudinal birth cohort for microbiome sampling at 3 points in the first 6 months of life at 4 skin sites relevant to AD: the antecubital and popliteal fossae, nasal tip, and cheek. We identified 10 infants with AD and compared them with 10 randomly selected control infants with no AD. We performed bacterial 16S ribosomal RNA sequencing and analysis directly from clinical samples. Results Bacterial community structures and diversity shifted over time, suggesting that age strongly affects the skin microbiome in infants. Unlike established AD, these patients with infantile AD did not have noticeably dysbiotic communities before or with disease and were not colonized by S aureus. In comparing patients and control subjects, infants who had affected skin at month 12 had statistically significant differences in bacterial communities on the antecubital fossa at month 2 compared with infants who were unaffected at month 12. In particular, commensal staphylococci were significantly less abundant in infants affected at month 12, suggesting that this genus might protect against the later development of AD. Conclusions This study suggests that 12-month-old infants with AD were not colonized with S aureus before having AD. Additional studies are needed to confirm whether colonization with commensal staphylococci modulates skin immunity and attenuates development of AD. JF - Journal of Allergy and Clinical Immunology AU - Kennedy, Elizabeth A AU - Connolly, Jennifer AU - Hourihane, Jonathan O'B AU - Fallon, Padraic G AU - McLean, WHIrwin AU - Murray, Deirdre AU - Jo, Jay-Hyun AU - Segre, Julia A AU - Kong, Heidi H AU - Irvine, Alan D AD - Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 166 EP - 172 PB - Elsevier Science Ltd., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 139 IS - 1 SN - 0091-6749, 0091-6749 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Staphylococcus aureus KW - atopic dermatitis KW - skin KW - microbiome KW - longitudinal birth cohort KW - 16S sequencing KW - AD Atopic dermatitis KW - Af Antecubital fossa KW - AMOVA Analysis of molecular variance KW - BASELINE Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints KW - FLG Filaggrin KW - Nt Nasal tip KW - OTU Operational taxonomic unit KW - Pf Popliteal fossa UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859501011?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Allergy+and+Clinical+Immunology&rft.atitle=Skin+microbiome+before+development+of+atopic+dermatitis%3A+Early+colonization+with+commensal+staphylococci+at+2+months+is+associated+with+a+lower+risk+of+atopic+dermatitis+at+1+year&rft.au=Kennedy%2C+Elizabeth+A%3BConnolly%2C+Jennifer%3BHourihane%2C+Jonathan+O%27B%3BFallon%2C+Padraic+G%3BMcLean%2C+WHIrwin%3BMurray%2C+Deirdre%3BJo%2C+Jay-Hyun%3BSegre%2C+Julia+A%3BKong%2C+Heidi+H%3BIrvine%2C+Alan+D&rft.aulast=Kennedy&rft.aufirst=Elizabeth&rft.date=2017-01-01&rft.volume=139&rft.issue=1&rft.spage=166&rft.isbn=&rft.btitle=&rft.title=Journal+of+Allergy+and+Clinical+Immunology&rft.issn=00916749&rft_id=info:doi/10.1016%2Fj.jaci.2016.07.029 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Number of references - 43 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1016/j.jaci.2016.07.029 ER - TY - JOUR T1 - Optimal high b-value for diffusion weighted MRI in diagnosing high risk prostate cancers in the peripheral zone AN - 1859499069; PQ0003966527 AB - Purpose To retrospectively determine the optimal b-value(s) of diffusion-weighted imaging (DWI) associated with intermediate-high risk cancer in the peripheral zone (PZ) of the prostate. Materials and Methods Forty-two consecutive patients underwent multi b-value (16 evenly spaced b-values between 0 and 2000 s/mm super(2)) DWI along with multi-parametric MRI (MP-MRI) of the prostate at 3 Tesla followed by trans-rectal ultrasound/MRI fusion guided targeted biopsy of suspicious lesions detected at MP-MRI. Computed DWI images up to a simulated b-value of 4000 s/mm super(2) were also obtained using a pair of b-values (b = 133 and 400 or 667 or 933 s/mm super(2)) from the multi b-value DWI. The contrast ratio of average intensity of the targeted lesions and the background PZ was determined. Receiver operator characteristic curves and the area under the curve (AUCs) were obtained for separating patients eligible for active surveillance with low risk prostate cancers from intermediate-high risk prostate cancers as per the cancer of the prostate risk assessment (CAPRA) scoring system. Results The AUC first increased then decreased with the increase in b-values reaching maximum at b = 1600 s/mm super(2) (0.74) with no statistically significant different AUC of DWI with b-values 1067-2000 s/mm super(2). The AUC of computed DWI increased then decreased with the increase in b-values reaching a maximum of 0.75 around b = 2000 s/mm super(2). There was no statistically significant difference between the AUC of optimal acquired DWI and either of optimal computed DWI. Conclusion The optimal b-value for acquired DWI in differentiating intermediate-high from low risk prostate cancers in the PZ is b = 1600 s/mm super(2). The computed DWI has similar performance as that of acquired DWI with the optimal performance around b = 2000 s/mm super(2). Level of Evidence: 4 J. Magn. Reson. Imaging 2017; 45:125-131. JF - Journal of Magnetic Resonance Imaging AU - Agarwal, Harsh K AU - Mertan, Francesca V AU - Sankineni, Sandeep AU - Bernardo, Marcelino AU - Senegas, Julien AU - Keupp, Jochen AU - Daar, Dagane AU - Merino, Maria AU - Wood, Bradford J AU - Pinto, Peter A AU - Choyke, Peter L AU - Turkbey, Baris AD - Molecular Imaging Program, NCI, NIH, Bethesda, Maryland, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 125 EP - 131 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 45 IS - 1 SN - 1053-1807, 1053-1807 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859499069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Magnetic+Resonance+Imaging&rft.atitle=Optimal+high+b-value+for+diffusion+weighted+MRI+in+diagnosing+high+risk+prostate+cancers+in+the+peripheral+zone&rft.au=Agarwal%2C+Harsh+K%3BMertan%2C+Francesca+V%3BSankineni%2C+Sandeep%3BBernardo%2C+Marcelino%3BSenegas%2C+Julien%3BKeupp%2C+Jochen%3BDaar%2C+Dagane%3BMerino%2C+Maria%3BWood%2C+Bradford+J%3BPinto%2C+Peter+A%3BChoyke%2C+Peter+L%3BTurkbey%2C+Baris&rft.aulast=Agarwal&rft.aufirst=Harsh&rft.date=2017-01-01&rft.volume=45&rft.issue=1&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance+Imaging&rft.issn=10531807&rft_id=info:doi/10.1002%2Fjmri.25353 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/jmri.25353 ER - TY - JOUR T1 - Quadruple-Negative GIST Is a Sentinel for Unrecognized Neurofibromatosis Type 1 Syndrome AN - 1859496720; PQ0004016226 AB - Purpose: The majority of gastrointestinal stromal tumors (GIST) are driven by KIT, PDGFRA, or, less commonly, BRAF mutations, and SDH gene inactivation is involved in a limited fraction of gastric lesions. However, about 10% of GISTs are devoid of any of such alterations and are poorly responsive to standard treatments. This study aims to shed light on the molecular drivers of quadruple-negative GISTs.Experimental Design: Twenty-two sporadic quadruple-negative GISTs with no prior association with Neurofibromatosis Type 1 syndrome were molecularly profiled for a panel of genes belonging to tyrosine kinase pathways or previously implicated in GISTs. For comparison purposes, 24 GISTs carrying KIT, PDGFRA, or SDH gene mutations were also analyzed. Molecular findings were correlated to clinicopathologic features.Results: Most quadruple-negative GISTs featured intestinal localization, with a female predilection. About 60% (13/22) of quadruple-negative tumors carried NF1 pathogenic mutations, often associated with biallelic inactivation. The analysis of normal tissues, available in 11 cases, indicated the constitutional nature of the NF1 mutation in 7 of 11 cases, unveiling an unrecognized Neurofibromatosis Type 1 syndromic condition. Multifocality and a multinodular pattern of growth were common findings in NF1-mutated quadruple-negative GISTs.Conclusions: NF1 gene mutations are frequent in quadruple-negative GISTs and are often constitutional, indicating that a significant fraction of patients with apparently sporadic quadruple-negative GISTs are affected by unrecognized Neurofibromatosis Type 1 syndrome. Hence, a diagnosis of quadruple-negative GIST, especially if multifocal or with a multinodular growth pattern and a nongastric location, should alert the clinician to a possible Neurofibromatosis Type 1 syndromic condition. Clin Cancer Res; 23(1); 273-82. [copy2016 AACR. JF - Clinical Cancer Research AU - Gasparotto, Daniela AU - Rossi, Sabrina AU - Polano, Maurizio AU - Tamborini, Elena AU - Lorenzetto, Erica AU - Sbaraglia, Marta AU - Mondello, Alessia AU - Massani, Marco AU - Lamon, Stefano AU - Bracci, Raffaella AU - Mandolesi, Alessandra AU - Frate, Elisabetta AU - Stanzial, Franco AU - Agaj, Jerin AU - Mazzoleni, Guido AU - Pilotti, Silvana AU - Gronchi, Alessandro AU - Dei Tos, Angelo Paolo AU - Maestro, Roberta AD - Experimental Oncology 1, CRO Aviano National Cancer Institute, Aviano, Italy, maestro@cro.it Y1 - 2017/01/01/ PY - 2017 DA - 2017 Jan 01 SP - 273 EP - 282 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 23 IS - 1 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859496720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Quadruple-Negative+GIST+Is+a+Sentinel+for+Unrecognized+Neurofibromatosis+Type+1+Syndrome&rft.au=Gasparotto%2C+Daniela%3BRossi%2C+Sabrina%3BPolano%2C+Maurizio%3BTamborini%2C+Elena%3BLorenzetto%2C+Erica%3BSbaraglia%2C+Marta%3BMondello%2C+Alessia%3BMassani%2C+Marco%3BLamon%2C+Stefano%3BBracci%2C+Raffaella%3BMandolesi%2C+Alessandra%3BFrate%2C+Elisabetta%3BStanzial%2C+Franco%3BAgaj%2C+Jerin%3BMazzoleni%2C+Guido%3BPilotti%2C+Silvana%3BGronchi%2C+Alessandro%3BDei+Tos%2C+Angelo+Paolo%3BMaestro%2C+Roberta&rft.aulast=Gasparotto&rft.aufirst=Daniela&rft.date=2017-01-01&rft.volume=23&rft.issue=1&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0152 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0152 ER - TY - JOUR T1 - Epigenome-Wide Tumor DNA Methylation Profiling Identifies Novel Prognostic Biomarkers of Metastatic-Lethal Progression in Men Diagnosed with Clinically Localized Prostate Cancer AN - 1859496177; PQ0004016230 AB - Purpose: Aside from Gleason sum, few factors accurately identify the subset of prostate cancer patients at high risk for metastatic progression. We hypothesized that epigenetic alterations could distinguish prostate tumors with life-threatening potential.Experimental Design: Epigenome-wide DNA methylation profiling was performed in surgically resected primary tumor tissues from a population-based (n = 430) and a replication (n = 80) cohort of prostate cancer patients followed prospectively for at least 5 years. Metastasis was confirmed by positive bone scan, MRI, CT, or biopsy, and death certificates confirmed cause of death. AUC, partial AUC (pAUC, 95% specificity), and P value criteria were used to select differentially methylated CpG sites that robustly stratify patients with metastatic-lethal from nonrecurrent tumors, and which were complementary to Gleason sum.Results: Forty-two CpG biomarkers stratified patients with metastatic-lethal versus nonrecurrent prostate cancer in the discovery cohort, and eight of these CpGs replicated in the validation cohort based on a significant (P < 0.05) AUC (range, 0.66-0.75) or pAUC (range, 0.007-0.009). The biomarkers that improved discrimination of patients with metastatic-lethal prostate cancer include CpGs in five genes (ALKBH5, ATP11A, FHAD1, KLHL8, and PI15) and three intergenic regions. In the validation dataset, the AUC for Gleason sum alone (0.82) significantly increased with the addition of four individual CpGs (range, 0.86-0.89; all P <0.05).Conclusions: Eight differentially methylated CpGs that distinguish patients with metastatic-lethal from nonrecurrent tumors were validated. These novel epigenetic biomarkers warrant further investigation as they may improve prognostic classification of patients with clinically localized prostate cancer and provide new insights on tumor aggressiveness. Clin Cancer Res; 23(1); 311-9. [copy2016 AACR. JF - Clinical Cancer Research AU - Zhao, Shanshan AU - Geybels, Milan S AU - Leonardson, Amy AU - Rubicz, Rohina AU - Kolb, Suzanne AU - Yan, Qingxiang AU - Klotzle, Brandy AU - Bibikova, Marina AU - Hurtado-Coll, Antonio AU - Troyer, Dean AU - Lance, Raymond AU - Lin, Daniel W AU - Wright, Jonathan L AU - Ostrander, Elaine A AU - Fan, Jian-Bing AU - Feng, Ziding AU - Stanford, Janet L AD - National Institute of Environmental Health Sciences, Biostatistics and Computational Biology Branch, Research Triangle Park, Durham, North Carolina, jstanfor@fredhutch.org Y1 - 2017/01/01/ PY - 2017 DA - 2017 Jan 01 SP - 311 EP - 319 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 23 IS - 1 SN - 1078-0432, 1078-0432 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859496177?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Epigenome-Wide+Tumor+DNA+Methylation+Profiling+Identifies+Novel+Prognostic+Biomarkers+of+Metastatic-Lethal+Progression+in+Men+Diagnosed+with+Clinically+Localized+Prostate+Cancer&rft.au=Zhao%2C+Shanshan%3BGeybels%2C+Milan+S%3BLeonardson%2C+Amy%3BRubicz%2C+Rohina%3BKolb%2C+Suzanne%3BYan%2C+Qingxiang%3BKlotzle%2C+Brandy%3BBibikova%2C+Marina%3BHurtado-Coll%2C+Antonio%3BTroyer%2C+Dean%3BLance%2C+Raymond%3BLin%2C+Daniel+W%3BWright%2C+Jonathan+L%3BOstrander%2C+Elaine+A%3BFan%2C+Jian-Bing%3BFeng%2C+Ziding%3BStanford%2C+Janet+L&rft.aulast=Zhao&rft.aufirst=Shanshan&rft.date=2017-01-01&rft.volume=23&rft.issue=1&rft.spage=311&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0549 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0549 ER - TY - JOUR T1 - ISMRM Raw data format: A proposed standard for MRI raw datasets AN - 1859496027; PQ0003987633 AB - Purpose This work proposes the ISMRM Raw Data format as a common MR raw data format, which promotes algorithm and data sharing. Methods A file format consisting of a flexible header and tagged frames of k-space data was designed. Application Programming Interfaces were implemented in C/C++, MATLAB, and Python. Converters for Bruker, General Electric, Philips, and Siemens proprietary file formats were implemented in C++. Raw data were collected using magnetic resonance imaging scanners from four vendors, converted to ISMRM Raw Data format, and reconstructed using software implemented in three programming languages (C++, MATLAB, Python). Results Images were obtained by reconstructing the raw data from all vendors. The source code, raw data, and images comprising this work are shared online, serving as an example of an image reconstruction project following a paradigm of reproducible research. Conclusion The proposed raw data format solves a practical problem for the magnetic resonance imaging community. It may serve as a foundation for reproducible research and collaborations. The ISMRM Raw Data format is a completely open and community-driven format, and the scientific community is invited (including commercial vendors) to participate either as users or developers. Magn Reson Med 77:411-421, 2017. JF - Magnetic Resonance in Medicine AU - Inati, Souheil J AU - Naegele, Joseph D AU - Zwart, Nicholas R AU - Roopchansingh, Vinai AU - Lizak, Martin J AU - Hansen, David C AU - Liu, Chia-Ying AU - Atkinson, David AU - Kellman, Peter AU - Kozerke, Sebastian AU - Xue, Hui AU - Campbell-Washburn, Adrienne E AU - Soerensen, Thomas S AU - Hansen, Michael S AD - National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 411 EP - 421 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 77 IS - 1 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859496027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=ISMRM+Raw+data+format%3A+A+proposed+standard+for+MRI+raw+datasets&rft.au=Inati%2C+Souheil+J%3BNaegele%2C+Joseph+D%3BZwart%2C+Nicholas+R%3BRoopchansingh%2C+Vinai%3BLizak%2C+Martin+J%3BHansen%2C+David+C%3BLiu%2C+Chia-Ying%3BAtkinson%2C+David%3BKellman%2C+Peter%3BKozerke%2C+Sebastian%3BXue%2C+Hui%3BCampbell-Washburn%2C+Adrienne+E%3BSoerensen%2C+Thomas+S%3BHansen%2C+Michael+S&rft.aulast=Inati&rft.aufirst=Souheil&rft.date=2017-01-01&rft.volume=77&rft.issue=1&rft.spage=411&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.26089 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/mrm.26089 ER - TY - JOUR T1 - Phase II Study of Alemtuzumab (CAMPATH-1) in Patients with HTLV-1-Associated Adult T-cell Leukemia/lymphoma AN - 1859495761; PQ0004016195 AB - Purpose: Therapeutic regimens for adult T-cell leukemia/lymphoma (ATL) are limited with unsatisfactory results, thereby warranting development of novel therapies. This study investigated antitumor activity and toxicity of alemtuzumab with regard to response, duration of response, progression-free survival, and overall survival in patients with human T-cell lymphotropic virus-1 (HTLV-1)-associated ATL.Experimental Design: Twenty-nine patients with chronic, acute, and lymphomatous types of ATL were enrolled in a single-institution, nonrandomized, open-label phase II trial wherein patients received intravenous alemtuzumab 30 mg three times weekly for a maximum of 12 weeks.Results: Twenty-nine patients were evaluable for response and toxicity. The overall objective response was 15 of 29 patients [95% confidence interval (CI), 32.5%-70.6%]. The 15 patients who responded manifested a median time to response of 1.1 months. Median response duration was 1.4 months for the whole group and 14.5 months among responders. Median progression-free survival was 2.0 months. Median overall survival was 5.9 months. The most common adverse events were 2 with vasovagal episodes (7%) and 3 with hypotensive episodes (10%), leukopenia (41%) grade 3 and (17%) grade 4, lymphocytopenia (59%) grade 3, neutropenia (31%) grade 3, anemia (24%), and thrombocytopenia (10%). All patients developed cytomegalovirus antigenemia (CMV). Three were symptomatic and all responded to antiviral therapy. Grade 3 or 4 infections were reported in 4 (14%) of patients.Conclusions: Alemtuzumab induced responses in patients with acute HTLV-1-associated ATL with acceptable toxicity, but with short duration of responses. These studies support inclusion of alemtuzumab in novel multidrug therapies for ATL. Clin Cancer Res; 23(1); 35-42. [copy2016 AACR. JF - Clinical Cancer Research AU - Sharma, Kamal AU - Janik, John E AU - O'Mahony, Deirdre AU - Stewart, Donn AU - Pittaluga, Stefania AU - Stetler-Stevenson, Maryalice AU - Jaffe, Elaine S AU - Raffeld, Mark AU - Fleisher, Thomas A AU - Lee, Cathryn C AU - Steinberg, Seth M AU - Waldmann, Thomas A AU - Morris, John C AD - Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, tawald@helix.nih.gov Y1 - 2017/01/01/ PY - 2017 DA - 2017 Jan 01 SP - 35 EP - 42 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 23 IS - 1 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859495761?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Phase+II+Study+of+Alemtuzumab+%28CAMPATH-1%29+in+Patients+with+HTLV-1-Associated+Adult+T-cell+Leukemia%2Flymphoma&rft.au=Sharma%2C+Kamal%3BJanik%2C+John+E%3BO%27Mahony%2C+Deirdre%3BStewart%2C+Donn%3BPittaluga%2C+Stefania%3BStetler-Stevenson%2C+Maryalice%3BJaffe%2C+Elaine+S%3BRaffeld%2C+Mark%3BFleisher%2C+Thomas+A%3BLee%2C+Cathryn+C%3BSteinberg%2C+Seth+M%3BWaldmann%2C+Thomas+A%3BMorris%2C+John+C&rft.aulast=Sharma&rft.aufirst=Kamal&rft.date=2017-01-01&rft.volume=23&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-1022 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-1022 ER - TY - JOUR T1 - Endometriosis diagnosis and staging by operating surgeon and expert review using multiple diagnostic tools: an inter-rater agreement study AN - 1859487784; PQ0003986525 AB - Objective To determine agreement on endometriosis diagnosis between real-time laparoscopy and subsequent expert review of digital images, operative reports, magnetic resonance imaging (MRI), and histopathology, viewed sequentially. Design Inter-rater agreement study. Setting Five urban surgical centres. Population Women, aged 18-44 years, who underwent a laparoscopy regardless of clinical indication. A random sample of 105 women with and 43 women without a postoperative endometriosis diagnosis was obtained from the ENDO study. Methods Laparoscopies were diagnosed, digitally recorded, and reassessed. Main outcome measures Inter-observer agreement of endometriosis diagnosis and staging according to the revised American Society for Reproductive Medicine criteria. Prevalence and bias-adjusted kappa values ( Kappa ) were calculated for diagnosis, and weighted Kappa values were calculated for staging. Results Surgeons and expert reviewers had substantial agreement on diagnosis and staging after viewing digital images (n = 148; mean Kappa = 0.67, range 0.61-0.69; mean Kappa = 0.64, range 0.53-0.78, respectively) and after additionally viewing operative reports (n = 148; mean Kappa = 0.88, range 0.85-0.89; mean Kappa = 0.85, range 0.84-0.86, respectively). Although additionally viewing MRI findings (n = 36) did not greatly impact agreement, agreement substantially decreased after viewing histological findings (n = 67), with expert reviewers changing their assessment from a positive to a negative diagnosis in up to 20% of cases. Conclusion Although these findings suggest that misclassification bias in the diagnosis or staging of endometriosis via visualised disease is minimal, they should alert gynaecologists who review operative images in order to make decisions on endometriosis treatment that operative reports/drawings and histopathology, but not necessarily MRI, will improve their ability to make sound judgments. JF - BJOG AU - Schliep, K C AU - Chen, Z AU - Stanford, J B AU - Xie, Y AU - Mumford, S L AU - Hammoud, A O AU - Boiman Johnstone, E AU - Dorais, J K AU - Varner, M W AU - Buck Louis, GM AU - Peterson, C M AD - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, Maryland, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 220 EP - 229 PB - Wiley Subscription Services, Inc., 1105 N Market St Wilmington DE 19801 VL - 124 IS - 2 SN - 1470-0328, 1470-0328 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859487784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BJOG&rft.atitle=Endometriosis+diagnosis+and+staging+by+operating+surgeon+and+expert+review+using+multiple+diagnostic+tools%3A+an+inter-rater+agreement+study&rft.au=Schliep%2C+K+C%3BChen%2C+Z%3BStanford%2C+J+B%3BXie%2C+Y%3BMumford%2C+S+L%3BHammoud%2C+A+O%3BBoiman+Johnstone%2C+E%3BDorais%2C+J+K%3BVarner%2C+M+W%3BBuck+Louis%2C+GM%3BPeterson%2C+C+M&rft.aulast=Schliep&rft.aufirst=K&rft.date=2017-01-01&rft.volume=124&rft.issue=2&rft.spage=220&rft.isbn=&rft.btitle=&rft.title=BJOG&rft.issn=14700328&rft_id=info:doi/10.1111%2F1471-0528.13711 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1111/1471-0528.13711 ER - TY - JOUR T1 - Characterization of aqueous formulations of tetra- and pentavalent forms of vanadium in support of test article selection in toxicology studies AN - 1859487637; PQ0004018525 AB - Tetravalent (V super(IV)) and pentavalent (V super(V)) forms of vanadium were selected for testing by the National Toxicology Program via drinking water exposure due to potential human exposure. To aid in the test article selection, drinking water formulations (125-2000 mg/L) of vanadyl sulfate (V super(IV)), sodium orthovanadate, and sodium metavanadate (V super(V)) were characterized by ultraviolet/visible (UV/VIS) spectroscopy, mass spectrometry (MS), or super(51)V nuclear magnetic resonance (NMR) spectroscopy. Aqueous formulations of orthovanadate, metavanadate, and vanadyl sulfate in general were basic, neutral, and acidic, respectively. Changes in vanadium speciation were investigated by adjusting formulation pH to acidic, neutral, or basic. There was no visible difference in UV/VIS spectra of pentavalent forms. NMR and MS analyses showed that the predominant oxidovanadate species in both ortho- and metavanadate formulations at basic and acidic pH, respectively, were the monomer and decamer, while, a mixture of oxidovanadates were present at neutral pH. Oxidovanadate species were not observed in vanadyl sulfate formulations at acidic pH but were observed at basic pH suggesting conversion of V super(IV) to V super(V). These data suggest that formulations of both ortho- and metavanadate form similar oxidovanadate species in acidic, neutral and basic pH and exist mainly in the V super(V) form while vanadyl sulfate exists mainly as V super(IV) in acidic pH. Therefore, the formulation stability overtime was investigated only for sodium metavanadate and vanadyl sulfate. Drinking water formulations (50 and 2000 mg/L) of metavanadate (~pH 7) and vanadyl sulfate (~pH 3.5) were greater than or equal to 92 % of target concentration up to 42 days at ~5 degree C and ambient temperature demonstrating the utility in toxicology studies. JF - Environmental Science and Pollution Research International AU - Mutlu, Esra AU - Cristy, Tim AU - Graves, Steven W AU - Hooth, Michelle J AU - Waidyanatha, Suramya AD - Division of the National Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233, Mail Drop K2-07, Research Triangle Park, NC, 27709, USA, waidyanathas@niehs.nih.gov Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 405 EP - 416 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 24 IS - 1 SN - 0944-1344, 0944-1344 KW - Pollution Abstracts; Ecology Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859487637?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Science+and+Pollution+Research+International&rft.atitle=Characterization+of+aqueous+formulations+of+tetra-+and+pentavalent+forms+of+vanadium+in+support+of+test+article+selection+in+toxicology+studies&rft.au=Mutlu%2C+Esra%3BCristy%2C+Tim%3BGraves%2C+Steven+W%3BHooth%2C+Michelle+J%3BWaidyanatha%2C+Suramya&rft.aulast=Mutlu&rft.aufirst=Esra&rft.date=2017-01-01&rft.volume=24&rft.issue=1&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=Environmental+Science+and+Pollution+Research+International&rft.issn=09441344&rft_id=info:doi/10.1007%2Fs11356-016-7803-x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Number of references - 57 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1007/s11356-016-7803-x ER - TY - JOUR T1 - Trends in published meta-analyses in cancer research, 2008-2013 AN - 1859483147; PQ0004019499 AB - In order to capture trends in the contribution of epidemiology to cancer research, we describe an online meta-analysis database resource for cancer clinical and population research and illustrate trends and descriptive detail of cancer meta-analyses from 2008 through 2013. A total of 4,686 cancer meta-analyses met our inclusion criteria. During this 6-year period, a fivefold increase was observed in the yearly number of meta-analyses. Fifty-six percent of meta-analyses concerned observational studies, mostly of cancer risk, more than half of which were genetic studies. The major cancer sites were breast, colorectal, and digestive. This online database for Cancer Genomics and Epidemiology Navigator will be continuously updated to allow investigators to quickly navigate the meta-analyses emerging from cancer epidemiology studies and cancer clinical trials. JF - Cancer Causes & Control AU - Qadir, Ximena V AU - Clyne, Mindy AU - Lam, Tram Kim AU - Khoury, Muin J AU - Schully, Sheri D AD - Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, 6100 Executive Boulevard, Suite 2B03, Bethesda, MD, USA, schullys@mail.nih.gov Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 5 EP - 12 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 28 IS - 1 SN - 0957-5243, 0957-5243 KW - Toxicology Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859483147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Trends+in+published+meta-analyses+in+cancer+research%2C+2008-2013&rft.au=Qadir%2C+Ximena+V%3BClyne%2C+Mindy%3BLam%2C+Tram+Kim%3BKhoury%2C+Muin+J%3BSchully%2C+Sheri+D&rft.aulast=Qadir&rft.aufirst=Ximena&rft.date=2017-01-01&rft.volume=28&rft.issue=1&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/10.1007%2Fs10552-016-0830-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Number of references - 14 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1007/s10552-016-0830-6 ER - TY - JOUR T1 - An epigenome-wide study of body mass index and DNA methylation in blood using participants from the Sister Study cohort AN - 1859481620; PQ0003999300 AB - Background/ Objectives: The relationship between obesity and chronic disease risk is well-established; the underlying biological mechanisms driving this risk increase may include obesity-related epigenetic modifications. To explore this hypothesis, we conducted a genome-wide analysis of DNA methylation and body mass index (BMI) using data from a subset of women in the Sister Study.Subjects/ Methods: The Sister Study is a cohort of 50 884 US women who had a sister with breast cancer but were free of breast cancer themselves at enrollment. Study participants completed examinations which included measurements of height and weight, and provided blood samples. Blood DNA methylation data generated with the Illumina Infinium HumanMethylation27 BeadChip array covering 27,589 CpG sites was available for 871 women from a prior study of breast cancer and DNA methylation. To identify differentially methylated CpG sites associated with BMI, we analyzed this methylation data using robust linear regression with adjustment for age and case status. For those CpGs passing the false discovery rate significance level, we examined the association in a replication set comprised of a non-overlapping group of 187 women from the Sister Study who had DNA methylation data generated using the Infinium HumanMethylation450 BeadChip array. Analysis of this expanded 450 K array identified additional BMI-associated sites which were investigated with targeted pyrosequencing. Results: Four CpG sites reached genome-wide significance (false discovery rate (FDR) q<0.05) in the discovery set and associations for all four were significant at strict Bonferroni correction in the replication set. An additional 23 sites passed FDR in the replication set and five were replicated by pyrosequencing in the discovery set. Several of the genes identified including ANGPT4, RORC, SOCS3, FSD2, XYLT1, ABCG1, STK39, ASB2 and CRHR2 have been linked to obesity and obesity-related chronic diseases. Conclusions: Our findings support the hypothesis that obesity-related epigenetic differences are detectable in blood and may be related to risk of chronic disease. JF - International Journal of Obesity AU - Wilson, L E AU - Harlid, S AU - Xu, Z AU - Sandler, D P AU - Taylor, J A AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 194 EP - 199 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 41 IS - 1 SN - 0307-0565, 0307-0565 KW - Biochemistry Abstracts 2: Nucleic Acids; Health & Safety Science Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859481620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Obesity&rft.atitle=An+epigenome-wide+study+of+body+mass+index+and+DNA+methylation+in+blood+using+participants+from+the+Sister+Study+cohort&rft.au=Wilson%2C+L+E%3BHarlid%2C+S%3BXu%2C+Z%3BSandler%2C+D+P%3BTaylor%2C+J+A&rft.aulast=Wilson&rft.aufirst=L&rft.date=2017-01-01&rft.volume=41&rft.issue=1&rft.spage=194&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Obesity&rft.issn=03070565&rft_id=info:doi/10.1038%2Fijo.2016.184 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1038/ijo.2016.184 ER - TY - JOUR T1 - Disease Centered Around Calcified Taenia solium Granuloma AN - 1859479823; PQ0004008865 AB - Taenia solium (the pork tapeworm) is present in most developing countries, where it is a frequent cause of seizures and other neurological disease. Parasitic larvae invade the human brain, establish, and eventually resolve, leaving a calcified scar. While these lesions are common in endemic regions, and most of these are clinically silent, a proportion of individuals with calcified cysticerci develop seizures from these lesions, and 30-65% of these cases are associated with perilesional edema (PE), likely due to host inflammation. This manuscript summarizes the importance, characteristics, natural history, and potential prevention and treatments of symptomatic calcified neurocysticercosis (NCC). JF - Trends in Parasitology AU - Nash, Theodore E AU - Bustos, Javier A AU - Garcia, Hector H AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 65 EP - 73 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 33 IS - 1 SN - 1471-4922, 1471-4922 KW - ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - neurocysticercosis KW - calcified granuloma KW - perilesional edema KW - epilepsy KW - seizures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859479823?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Parasitology&rft.atitle=Disease+Centered+Around+Calcified+Taenia+solium+Granuloma&rft.au=Nash%2C+Theodore+E%3BBustos%2C+Javier+A%3BGarcia%2C+Hector+H&rft.aulast=Nash&rft.aufirst=Theodore&rft.date=2017-01-01&rft.volume=33&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Trends+in+Parasitology&rft.issn=14714922&rft_id=info:doi/10.1016%2Fj.pt.2016.09.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1016/j.pt.2016.09.003 ER - TY - JOUR T1 - Impact of parental obesity on neonatal markers of inflammation and immune response AN - 1859479412; PQ0003999303 AB - Background/ Objectives: Maternal obesity may influence neonatal and childhood morbidities through increased inflammation and/or altered immune response. Less is known about paternal obesity. We hypothesized that excessive parental weight contributes to elevated inflammation and altered immunoglobulin (Ig) profiles in neonates.Subjects/ Methods: In the Upstate KIDS Study maternal pre-pregnancy body mass index (BMI) was obtained from vital records and paternal BMI from maternal report. Biomarkers were measured from newborn dried blood spots (DBS) among neonates whose parents provided consent. Inflammatory scores were calculated by assigning one point for each of five pro-inflammatory biomarkers above the median and one point for an anti-inflammatory cytokine below the median. Linear regression models and generalized estimating equations were used to estimate mean differences ( beta ) and 95% confidence intervals (CI) in the inflammatory score and Ig levels by parental overweight/obesity status compared with normal weight. Results: Among 2974 pregnancies, 51% were complicated by excessive maternal weight (BMI>25), 73% by excessive paternal weight and 28% by excessive gestational weight gain. Maternal BMI categories of overweight (BMI 25.0-29.9) and obese class II/III (BMI greater than or equal to 35) were associated with increased neonatal inflammation scores ( beta =0.12, 95% CI: 0.02, 0.21; P=0.02 and beta =0.13, CI: -0.002, 0.26; P=0.05, respectively) but no increase was observed in the obese class I group (BMI 30-34.9). Mothers with class I and class II/III obesity had newborns with increased IgM levels ( beta =0.11, CI: 0.04, 0.17; P=0.001 and beta =0.12, CI: 0.05, 0.19); P<0.001, respectively). Paternal groups of overweight, obese class I and obese class II/III had decreased neonatal IgM levels ( beta =-0.08, CI: -0.13,-0.03, P=0.001; beta =-0.07, CI: -0.13, -0.01, P=0.029 and beta =-0.11, CI:-0.19,-0.04, P=0.003, respectively). Conclusions: Excessive maternal weight was generally associated with increased inflammation and IgM supporting previous observations of maternal obesity and immune dysregulation in offspring. The role of paternal obesity requires further study. JF - International Journal of Obesity AU - Broadney, M M AU - Chahal, N AU - Michels, K A AU - McLain, A C AU - Ghassabian, A AU - Lawrence, D A AU - Yeung, E H AD - Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA; Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 30 EP - 37 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 41 IS - 1 SN - 0307-0565, 0307-0565 KW - Health & Safety Science Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859479412?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Obesity&rft.atitle=Impact+of+parental+obesity+on+neonatal+markers+of+inflammation+and+immune+response&rft.au=Broadney%2C+M+M%3BChahal%2C+N%3BMichels%2C+K+A%3BMcLain%2C+A+C%3BGhassabian%2C+A%3BLawrence%2C+D+A%3BYeung%2C+E+H&rft.aulast=Broadney&rft.aufirst=M&rft.date=2017-01-01&rft.volume=41&rft.issue=1&rft.spage=30&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Obesity&rft.issn=03070565&rft_id=info:doi/10.1038%2Fijo.2016.187 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1038/ijo.2016.187 ER - TY - JOUR T1 - A longitudinal study of serum insulin and insulin resistance as predictors of weight and body fat gain in African American and Caucasian children AN - 1859479258; PQ0003999283 AB - Background: The influence of insulin and insulin resistance (IR) on children's weight and fat gain is unclear. Objective: To evaluate insulin and IR as predictors of weight and body fat gain in children at high risk for adult obesity. We hypothesized that baseline IR would be positively associated with follow-up body mass index (BMI) and fat mass.Subjects/ Methods: Two hundred and forty-nine healthy African American and Caucasian children aged 6-12 years at high risk for adult obesity because of early-onset childhood overweight and/or parental overweight were followed for up to 15 years with repeated BMI and fat mass measurements. We examined baseline serum insulin and homeostasis model of assessment-IR (HOMA-IR) as predictors of follow-up BMI Z-score and fat mass by dual-energy X-ray absorptiometry in mixed model longitudinal analyses accounting for baseline body composition, pubertal stage, sociodemographic factors and follow-up interval. Results: At baseline, 39% were obese (BMI[egs]95th percentile for age/sex). Data from 1335 annual visits were examined. Children were followed for an average of 7.2 plus or minus 4.3 years, with a maximum follow-up of 15 years. After accounting for covariates, neither baseline insulin nor HOMA-IR was significantly associated with follow-up BMI (Ps>0.26), BMIz score (Ps>0.22), fat mass (Ps>0.78) or fat mass percentage (Ps>0.71). In all models, baseline BMI (P<0.0001), body fat mass (P<0.0001) and percentage of fat (P<0.001) were strong positive predictors for change in BMI and fat mass. In models restricted to children without obesity at baseline, some but not all models had significant interaction terms between body adiposity and insulinemia/HOMA-IR that suggested less gain in mass among those with greater insulin or IR. The opposite was found in some models restricted to children with obesity at baseline. Conclusions: In middle childhood, BMI and fat mass, but not insulin or IR, are strong predictors of children's gains in BMI and fat mass during adolescence. JF - International Journal of Obesity AU - Sedaka, N M AU - Olsen, C H AU - Yannai, L E AU - Stutzman, W E AU - Krause, A J AU - Sherafat-Kazemzadeh, R AU - Condarco, T A AU - Brady, S M AU - Demidowich, A P AU - Reynolds, J C AU - Yanovski, S Z AU - Hubbard, V S AU - Yanovski, J A AD - Section on Growth and Obesity (SGO), Program in Developmental Endocrinology and Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 61 EP - 70 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 41 IS - 1 SN - 0307-0565, 0307-0565 KW - Health & Safety Science Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859479258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Obesity&rft.atitle=A+longitudinal+study+of+serum+insulin+and+insulin+resistance+as+predictors+of+weight+and+body+fat+gain+in+African+American+and+Caucasian+children&rft.au=Sedaka%2C+N+M%3BOlsen%2C+C+H%3BYannai%2C+L+E%3BStutzman%2C+W+E%3BKrause%2C+A+J%3BSherafat-Kazemzadeh%2C+R%3BCondarco%2C+T+A%3BBrady%2C+S+M%3BDemidowich%2C+A+P%3BReynolds%2C+J+C%3BYanovski%2C+S+Z%3BHubbard%2C+V+S%3BYanovski%2C+J+A&rft.aulast=Sedaka&rft.aufirst=N&rft.date=2017-01-01&rft.volume=41&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Obesity&rft.issn=03070565&rft_id=info:doi/10.1038%2Fijo.2016.145 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1038/ijo.2016.145 ER - TY - JOUR T1 - Association of N-Methyl-D-Aspartate receptor 2B Subunit (GRIN2B) polymorphism with earlier age at onset of withdrawal symptoms in Indian alcohol dependent subjects AN - 1859473537 AB - The associations of GRIN2B polymorphism (rs1806201) with alcohol withdrawal and related clinical parameters in alcohol dependent subjects were investigated. Cases were assessed using a semi-structured clinical pro forma for alcohol abuse and a questionnaire for family history of alcohol dependence and psychiatric disorders after obtaining informed consent. The study included alcohol dependent male cases (n = 220, age at onset of alcohol withdrawal symptoms = 32.4 ± 8.8 y) recruited at the Center for Addiction Medicine, National Institute of Mental Health and Neurosciences, Bangalore, India. The controls comprised of healthy unrelated males (n = 183) who were ethnically matched and selected randomly. The polymorphism rs1806201 was analyzed by polymerase chain reaction and restriction fragment length polymorphism. The presence of T allele at this locus was significantly associated with lower age at onset of alcohol withdrawal symptoms (p = .005) among the cases. Mean age at onset of alcohol withdrawal symptoms in subjects who were T carriers was 31.4 ± 8.5 y (n = 160) and non-T carriers was 35.2 ± 9.0 y (n = 60). The SNP rs1806201 in GRIN2B may play an important role in genetic susceptibility to earlier age of withdrawal in alcohol dependent patients. JF - Journal of Addictive Diseases AU - Paul, Pradip, MSc AU - Dahale, Ajit, MD AU - Kishore, Brij, MD AU - Chand, Prabhat, MD AU - Benegal, Vivek, MD AU - Jain, Sanjeev, MD AU - Murthy, Pratima, MD AU - Purushottam, Meera, PhD AD - Molecular Genetics Laboratory, Neurobiology Research Centre, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India ; Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India ; Mid-West Area Mental Health Service, North Western Mental Health, Melbourne Health, Victoria, Australia ; Center for Addiction Medicine, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India ; Molecular Genetics Laboratory, Neurobiology Research Centre, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India Y1 - 2017///Jan/Mar PY - 2017 DA - Jan/Mar 2017 SP - 48 EP - 52 CY - Binghamton PB - Taylor & Francis Ltd. VL - 36 IS - 1 SN - 1055-0887 KW - Drug Abuse And Alcoholism KW - Alcohol dependence KW - withdrawal KW - glutamate KW - N-Methyl-D-Aspartate receptor (GRIN2B) KW - polymorphism KW - rs1806201 KW - Men KW - Symptoms KW - Neurosciences KW - Susceptibility KW - Psychiatric disorders KW - Genetic family histories KW - Addiction KW - Informed consent KW - Genetic susceptibility KW - Age of onset KW - Questionnaires KW - Parameters KW - Chemical analysis KW - Withdrawal symptoms KW - Alcohol abuse KW - Mental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859473537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Addictive+Diseases&rft.atitle=Association+of+N-Methyl-D-Aspartate+receptor+2B+Subunit+%28GRIN2B%29+polymorphism+with+earlier+age+at+onset+of+withdrawal+symptoms+in+Indian+alcohol+dependent+subjects&rft.au=Paul%2C+Pradip%2C+MSc%3BDahale%2C+Ajit%2C+MD%3BKishore%2C+Brij%2C+MD%3BChand%2C+Prabhat%2C+MD%3BBenegal%2C+Vivek%2C+MD%3BJain%2C+Sanjeev%2C+MD%3BMurthy%2C+Pratima%2C+MD%3BPurushottam%2C+Meera%2C+PhD&rft.aulast=Paul&rft.aufirst=Pradip&rft.date=2017-01-01&rft.volume=36&rft.issue=1&rft.spage=48&rft.isbn=&rft.btitle=&rft.title=Journal+of+Addictive+Diseases&rft.issn=10550887&rft_id=info:doi/10.1080%2F10550887.2016.1140434 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © 2017 Taylor & Francis Group, LLC N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1080/10550887.2016.1140434 ER - TY - JOUR T1 - Patient's lung cancer diagnosis as a cue for relatives' smoking cessation: evaluating the constructs of the teachable moment AN - 1858560688 AB - Background To understand whether patient-reported experiences with lung cancer may create teachable moments (TM) for their relatives as evidenced by shifts in their risk perceptions, affective response, and self-image and in turn, motivation to quit smoking. Methods Patients at a comprehensive cancer center (n=152) completed a survey within 6 months of lung cancer diagnosis to assess their cancer-related symptoms and openness and enumerated relatives who were smokers. Relative smokers (n=218) then completed a survey assessing their risk perceptions, affective response, and self-image as a smoker related to the patient's diagnosis (TM mechanisms), and their motivation to quit smoking. Cross-sectional mediation and moderation analyses were conducted to explore the links between patient-reported experiences, and relatives' TM mechanisms, and motivation to quit smoking. Results Relative-reported affect was a significant mediator of the association between patient-reported symptoms and relative smoker's desire to quit. Relatives' self-image was a significant moderator of the association between patient-reported symptoms and relative smoker's desire to quit, such that patients' reported symptoms were associated with relatives' desire to quit only when the relative smoker reported a generally positive self-image as a smoker. No evidence was found for moderated mediation. However, the link between symptoms and negative affect was moderated by perceptions of risk. Conclusion Whether smokers experience a family member's lung cancer as a TM is influenced by multiple interrelated cognitive and affective factors that warrant further exploration. Clearer understanding of these factors could inform how to re-invigorate and sustain this motivation to promote concrete actions toward smoking cessation. Copyright © 2015 John Wiley & Sons, Ltd. JF - Psycho-Oncology AU - McBride, Colleen M AU - Blocklin, Michelle AU - Lipkus, Isaac M AU - Klein, William M P AU - Brandon, Thomas H AD - Department of Behavioral Sciences and Health Education, Emory Rollins School of Public Health, Atlanta, GA, USA ; Abt Associates, Boston, MA, USA ; Duke University, Durham, NC, USA ; National Cancer Institute, Rockville, MD, USA; National Institutes of Health, Bethesda, MD, USA ; Tobacco Research and Intervention Program, Moffitt Cancer Center, Tampa, FL, USA ; Department of Behavioral Sciences and Health Education, Emory Rollins School of Public Health, Atlanta, GA, USA Y1 - 2017/01// PY - 2017 DA - Jan 2017 SP - 88 EP - 95 CY - Chichester PB - Wiley Subscription Services, Inc. VL - 26 IS - 1 SN - 1057-9249 KW - Medical Sciences--Psychiatry And Neurology KW - Smokers KW - Risk perception KW - Smoking KW - Negative affect KW - Motivation KW - Relatives KW - Openness KW - Cessation KW - Perceptions KW - Lung cancer KW - Risk assessment KW - Affective responses KW - Mediation KW - Negative affectivity KW - Surveys KW - Selfimage KW - Desire KW - Diagnosis KW - Moderation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1858560688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psycho-Oncology&rft.atitle=Patient%27s+lung+cancer+diagnosis+as+a+cue+for+relatives%27+smoking+cessation%3A+evaluating+the+constructs+of+the+teachable+moment&rft.au=McBride%2C+Colleen+M%3BBlocklin%2C+Michelle%3BLipkus%2C+Isaac+M%3BKlein%2C+William+M+P%3BBrandon%2C+Thomas+H&rft.aulast=McBride&rft.aufirst=Colleen&rft.date=2017-01-01&rft.volume=26&rft.issue=1&rft.spage=88&rft.isbn=&rft.btitle=&rft.title=Psycho-Oncology&rft.issn=10579249&rft_id=info:doi/10.1002%2Fpon.4011 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2017 John Wiley & Sons, Ltd. N1 - Last updated - 2017-01-16 DO - http://dx.doi.org/10.1002/pon.4011 ER - TY - JOUR T1 - Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape. AN - 1858109610; 28076415 AB - A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing antibodies and identifies a set of mutations in the gp120 C terminus that exposes the membrane-proximal external region of gp41, with potential utility in HIV vaccine design. JF - PLoS pathogens AU - Wibmer, Constantinos Kurt AU - Gorman, Jason AU - Ozorowski, Gabriel AU - Bhiman, Jinal N AU - Sheward, Daniel J AU - Elliott, Debra H AU - Rouelle, Julie AU - Smira, Ashley AU - Joyce, M Gordon AU - Ndabambi, Nonkululeko AU - Druz, Aliaksandr AU - Asokan, Mangai AU - Burton, Dennis R AU - Connors, Mark AU - Abdool Karim, Salim S AU - Mascola, John R AU - Robinson, James E AU - Ward, Andrew B AU - Williamson, Carolyn AU - Kwong, Peter D AU - Morris, Lynn AU - Moore, Penny L AD - Centre for HIV and STIs, National Institute for Communicable Diseases (NICD), of the National Health Laboratory Service (NHLS), Johannesburg, South Africa. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America. ; Department of Integrative Structural and Computational Biology, CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California, United States of America. ; Institute of Infectious Disease and Molecular Medicine (IDM) and Division of Medical Virology, University of Cape Town and NHLS, Cape Town, South Africa. ; Department of Pediatrics, Tulane University Medical Center, New Orleans, Louisiana, United States of America. ; Department of Immunology and Microbial Science, CHAVI-ID and IAVI Neutralizing Antibody Centre, The Scripps Research Institute, La Jolla, California, United States of America. ; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America. ; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 1 VL - 13 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1858109610?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PLoS+pathogens&rft.atitle=Structure+and+Recognition+of+a+Novel+HIV-1+gp120-gp41+Interface+Antibody+that+Caused+MPER+Exposure+through+Viral+Escape.&rft.au=Wibmer%2C+Constantinos+Kurt%3BGorman%2C+Jason%3BOzorowski%2C+Gabriel%3BBhiman%2C+Jinal+N%3BSheward%2C+Daniel+J%3BElliott%2C+Debra+H%3BRouelle%2C+Julie%3BSmira%2C+Ashley%3BJoyce%2C+M+Gordon%3BNdabambi%2C+Nonkululeko%3BDruz%2C+Aliaksandr%3BAsokan%2C+Mangai%3BBurton%2C+Dennis+R%3BConnors%2C+Mark%3BAbdool+Karim%2C+Salim+S%3BMascola%2C+John+R%3BRobinson%2C+James+E%3BWard%2C+Andrew+B%3BWilliamson%2C+Carolyn%3BKwong%2C+Peter+D%3BMorris%2C+Lynn%3BMoore%2C+Penny+L&rft.aulast=Wibmer&rft.aufirst=Constantinos&rft.date=2017-01-01&rft.volume=13&rft.issue=1&rft.spage=e1006074&rft.isbn=&rft.btitle=&rft.title=PLoS+pathogens&rft.issn=1553-7374&rft_id=info:doi/10.1371%2Fjournal.ppat.1006074 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-11 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1371/journal.ppat.1006074 ER - TY - JOUR T1 - Neuroserpin Attenuates H2O2-Induced Oxidative Stress in Hippocampal Neurons via AKT and BCL-2 Signaling Pathways. AN - 1856868286; 27510267 AB - Oxidative stress plays a critical role in neuronal injury and is associated with various neurological diseases. Here, we explored the potential protective effect of neuroserpin against oxidative stress in primary cultured hippocampal neurons. Our results show that neuroserpin inhibits H2O2-induced neurotoxicity in hippocampal cultures as measured by WST, LDH release, and TUNEL assays. We found that neuroserpin enhanced the activation of AKT in cultures subjected to oxidative stress and that the AKT inhibitor Ly294002 blocked this neuroprotective effect. Neuroserpin increased the expression of the anti-apoptotic protein BCL-2 and blocked the activation of caspase-3. Neuroserpin did not increase the level of neuroprotection over levels seen in neurons transduced with a BCL-2 expression vector, and an inhibitor of Trk receptors, K252a, did not block neuroserpin's effect. Taken together, our study demonstrates that neuroserpin protects against oxidative stress-induced dysfunction and death of primary cultured hippocampal neurons through the AKT-BCL-2 signaling pathway through a mechanism that does not involve the Trk receptors and leads to inhibition of caspase-3 activation. JF - Journal of molecular neuroscience : MN AU - Cheng, Yong AU - Loh, Y Peng AU - Birch, Nigel P AD - Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA. ; School of Biological Sciences, Centre for Brain Research and Brain Research New Zealand, Rangahau Roro Aotearoa, University of Auckland, 3a Symonds Street 92019, Auckland, 1142, New Zealand. n.birch@auckland.ac.nz. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 123 EP - 131 VL - 61 IS - 1 KW - Hippocampal neurons KW - Reactive oxygen species KW - Protease inhibitor KW - Oxidative stress KW - Neuroprotection UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856868286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+neuroscience+%3A+MN&rft.atitle=Neuroserpin+Attenuates+H2O2-Induced+Oxidative+Stress+in+Hippocampal+Neurons+via+AKT+and+BCL-2+Signaling+Pathways.&rft.au=Cheng%2C+Yong%3BLoh%2C+Y+Peng%3BBirch%2C+Nigel+P&rft.aulast=Cheng&rft.aufirst=Yong&rft.date=2017-01-01&rft.volume=61&rft.issue=1&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+neuroscience+%3A+MN&rft.issn=1559-1166&rft_id=info:doi/10.1007%2Fs12031-016-0807-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s12031-016-0807-7 ER - TY - JOUR T1 - Variability in measures of health and health behavior among emerging adults 1 year after high school according to college status AN - 1856379130 AB - Objective: To examine changes in health behaviors among US emerging adults 1 year after high school. Participants: The national sample of participants (N = 1,927), including those attending 4-year college/university (n = 884), 2-year colleges/technical schools (n = 588), and no college (n = 455), participated in annual spring surveys 2013-2014. Methods: Health behaviors were assessed the last year of high school and first year of college; differences by college status controlling for previous-year values were estimated using regression analyses. Results: Relative to 4-year college attendees, those attending technical school/community college were less likely to binge drink (odds ratio [OR] = 0.57, confidence interval [CI] = 0.38-0.86) but more likely to speed (OR = 1.26, CI = 1.0-2.84), consume sodas (OR = 1.57, CI = 1.0-2.47), and report lower family satisfaction (p < .01), with marginally more physical and depressive symptoms. College nonattendees reported more DWI (driving while intoxicated; OR = 1.60, CI = 1.05-2.47), soda drinking (OR = 2.51, CI = 1.76-3.59), oversleeping (OR = 4.78, CI = 3.65-8.63), and less family satisfaction (p < .04). Conclusions: Health risk behaviors among emerging adults varied by college status. JF - Journal of American College Health AU - Simons-Morton, Bruce, EdD, MPH AU - Haynie, Denise, PhD, MPH AU - O'Brien, Fearghal, PhD AU - Lipsky, Leah, PhD AU - Bible, Joe, PhD AU - Liu, Danping, PhD AD - Health Behavior Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA ; Biostatistics and Bioinformatics Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA ; Health Behavior Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA Y1 - 2017/01// PY - 2017 DA - Jan 2017 SP - 58 EP - 66 CY - Washington PB - Taylor & Francis Ltd. VL - 65 IS - 1 SN - 0744-8481 KW - Education--Higher Education KW - College health KW - college students KW - diet KW - driving KW - exercise KW - mental health KW - physical health KW - substance use KW - Confidence intervals KW - Adults KW - First year KW - Health behaviour KW - Depression KW - Behavioural changes KW - Family satisfaction KW - Physical symptoms KW - Carbonated beverages KW - Risk behaviour KW - Variability UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856379130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+American+College+Health&rft.atitle=Variability+in+measures+of+health+and+health+behavior+among+emerging+adults+1+year+after+high+school+according+to+college+status&rft.au=Simons-Morton%2C+Bruce%2C+EdD%2C+MPH%3BHaynie%2C+Denise%2C+PhD%2C+MPH%3BO%27Brien%2C+Fearghal%2C+PhD%3BLipsky%2C+Leah%2C+PhD%3BBible%2C+Joe%2C+PhD%3BLiu%2C+Danping%2C+PhD&rft.aulast=Simons-Morton&rft.aufirst=Bruce&rft.date=2017-01-01&rft.volume=65&rft.issue=1&rft.spage=58&rft.isbn=&rft.btitle=&rft.title=Journal+of+American+College+Health&rft.issn=07448481&rft_id=info:doi/10.1080%2F07448481.2016.1238384 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - This article not subject to US copyright law N1 - Last updated - 2017-01-08 DO - http://dx.doi.org/10.1080/07448481.2016.1238384 ER - TY - JOUR T1 - Developmental Relations Among Behavioral Inhibition, Anxiety, and Attention Biases to Threat and Positive Information AN - 1855652820 AB - This study examined relations between behavioral inhibition (BI) assessed in toddlerhood (n = 268) and attention biases (AB) to threat and positive faces and maternal-reported anxiety assessed when children were 5- and 7-year-old. Results revealed that BI predicted anxiety at age 7 in children with AB toward threat, away from positive, or with no bias, at age 7; BI did not predict anxiety for children displaying AB away from threat or toward positive. Five-year AB did not moderate the link between BI and 7-year anxiety. No direct association between AB and BI or anxiety was detected; moreover, children did not show stable AB across development. These findings extend our understanding of the developmental links among BI, AB, and anxiety. JF - Child Development AU - White, Lauren K AU - Degnan, Kathryn A AU - Henderson, Heather A AU - Perez-Edgar, Koraly AU - Walker, Olga L AU - Shechner, Tomer AU - Leibenluft, Ellen AU - Bar-Haim, Yair AU - Pine, Daniel S AU - Fox, Nathan A AD - Children's Hospital of Philadelphia ; Catholic University ; University of Waterloo ; The Pennsylvania State University ; University of Maryland, College Park ; University of Haifa ; National Institute of Mental Health ; Tel Aviv University ; Children's Hospital of Philadelphia Y1 - 2017///Jan/Feb PY - 2017 DA - Jan/Feb 2017 SP - 141 EP - 155 CY - Ann Arbor PB - Wiley Subscription Services, Inc. VL - 88 IS - 1 SN - 0009-3920 KW - Psychology KW - Attentional bias KW - Anxiety KW - Children KW - Inhibition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855652820?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=Developmental+Relations+Among+Behavioral+Inhibition%2C+Anxiety%2C+and+Attention+Biases+to+Threat+and+Positive+Information&rft.au=White%2C+Lauren+K%3BDegnan%2C+Kathryn+A%3BHenderson%2C+Heather+A%3BPerez-Edgar%2C+Koraly%3BWalker%2C+Olga+L%3BShechner%2C+Tomer%3BLeibenluft%2C+Ellen%3BBar-Haim%2C+Yair%3BPine%2C+Daniel+S%3BFox%2C+Nathan+A&rft.aulast=White&rft.aufirst=Lauren&rft.date=2017-01-01&rft.volume=88&rft.issue=1&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/10.1111%2Fcdev.12696 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Child Development © 2017 The Society for Research in Child Development, Inc. N1 - Last updated - 2017-01-06 DO - http://dx.doi.org/10.1111/cdev.12696 ER - TY - JOUR T1 - Face Detection and the Development of Own-Species Bias in Infant Macaques AN - 1854601982 AB - In visually complex environments, numerous items compete for attention. Infants may exhibit attentional efficiency--privileged detection, attention capture, and holding--for face-like stimuli. However, it remains unknown when these biases develop and what role, if any, experience plays in this emerging skill. Here, nursery-reared infant macaques' (Macaca mulatta;n = 10) attention to faces in 10-item arrays of nonfaces was measured using eye tracking. With limited face experience, 3-week-old monkeys were more likely to detect faces and looked longer at faces compared to nonfaces, suggesting a robust face detection system. By 3 months, after peer exposure, infants looked faster to conspecific faces but not heterospecific faces, suggesting an own-species bias in face attention capture, consistent with perceptual attunement. JF - Child Development AU - Simpson, Elizabeth A AU - Jakobsen, Krisztina V AU - Damon, Fabrice AU - Suomi, Stephen J AU - Ferrari, Pier F AU - Paukner, Annika AD - University of Miami ; James Madison University ; Université Grenoble Alpes ; National Institutes of Health ; Università di Parma ; University of Miami Y1 - 2017///Jan/Feb PY - 2017 DA - Jan/Feb 2017 SP - 103 EP - 113 CY - Ann Arbor PB - Wiley Subscription Services, Inc. VL - 88 IS - 1 SN - 0009-3920 KW - Psychology KW - Detection KW - Tracking KW - Eye tracking KW - Infants KW - Holding KW - Bias KW - Attention KW - Monkeys UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1854601982?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=Face+Detection+and+the+Development+of+Own-Species+Bias+in+Infant+Macaques&rft.au=Simpson%2C+Elizabeth+A%3BJakobsen%2C+Krisztina+V%3BDamon%2C+Fabrice%3BSuomi%2C+Stephen+J%3BFerrari%2C+Pier+F%3BPaukner%2C+Annika&rft.aulast=Simpson&rft.aufirst=Elizabeth&rft.date=2017-01-01&rft.volume=88&rft.issue=1&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/10.1111%2Fcdev.12565 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Child Development © 2017 The Society for Research in Child Development, Inc. N1 - Last updated - 2017-01-06 DO - http://dx.doi.org/10.1111/cdev.12565 ER - TY - JOUR T1 - Sensory Processing in Rhesus Monkeys: Developmental Continuity, Prenatal Treatment, and Genetic Influences AN - 1854601976 AB - Neonatal sensory processing (tactile and vestibular function) was tested in 78 rhesus macaques from two experiments. At ages 4-5 years, striatal dopamine D2 receptor binding was examined using positron emission tomography. At ages 5-7 years, adult sensory processing was assessed. Findings were: (a) prenatal stress exposure yielded less optimal neonatal sensory processing; (b) animals carrying the short rh5-HTTLPR allele had less optimal neonatal sensory scores than monkeys homozygous for the long allele; (c) neonatal sensory processing was significantly related to striatal D2 receptor binding for carriers of the short allele, but not for animals homozygous for the long allele; and (d) there was moderate developmental continuity in sensory processing from the neonatal period to adulthood. JF - Child Development AU - Schneider, Mary L AU - Moore, Colleen F AU - Adkins, Miriam AU - Barr, Christina S AU - Larson, Julie A AU - Resch, Leslie M AU - Roberts, Andrew AD - Department of Kinesiology, University of Wisconsin-Madison; Harlow Center for Biological Psychology, University of Wisconsin-Madison; Department of Psychology, University of Wisconsin-Madison ; Department of Psychology, University of Wisconsin-Madison; Department of Psychology, Montana State University-Bozeman ; Department of Kinesiology, University of Wisconsin-Madison ; National Institutes of Health ; Department of Kinesiology, University of Wisconsin-Madison; Harlow Center for Biological Psychology, University of Wisconsin-Madison ; Minnesota State University-Mankato ; Department of Kinesiology, University of Wisconsin-Madison; Harlow Center for Biological Psychology, University of Wisconsin-Madison; Department of Psychology, University of Wisconsin-Madison Y1 - 2017///Jan/Feb PY - 2017 DA - Jan/Feb 2017 SP - 183 EP - 197 CY - Ann Arbor PB - Wiley Subscription Services, Inc. VL - 88 IS - 1 SN - 0009-3920 KW - Psychology KW - Dopamine KW - Genetic factors KW - Alleles KW - Sensory processes KW - Adulthood KW - Emission KW - Tomography KW - Fetal exposure KW - Animals KW - Positron emission tomography KW - Antenatal KW - Monkeys UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1854601976?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=Sensory+Processing+in+Rhesus+Monkeys%3A+Developmental+Continuity%2C+Prenatal+Treatment%2C+and+Genetic+Influences&rft.au=Schneider%2C+Mary+L%3BMoore%2C+Colleen+F%3BAdkins%2C+Miriam%3BBarr%2C+Christina+S%3BLarson%2C+Julie+A%3BResch%2C+Leslie+M%3BRoberts%2C+Andrew&rft.aulast=Schneider&rft.aufirst=Mary&rft.date=2017-01-01&rft.volume=88&rft.issue=1&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/10.1111%2Fcdev.12572 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Child Development © 2017 The Society for Research in Child Development, Inc. N1 - Last updated - 2017-01-06 DO - http://dx.doi.org/10.1111/cdev.12572 ER - TY - JOUR T1 - The histopathological evaluation of drug-induced liver injury. AN - 1852677738; 27960237 AB - Drug-induced liver injury (DILI) presents unique challenges to the pathologist. It is not only an uncommon reason for liver biopsy, but the pathology of DILI is spread across the entire spectrum of hepatic injury patterns. It is important for the pathologist to suspect DILI when the histological changes are unusual or out of synchronicity with the patient's history. A systematic evaluation approach will yield the most information. It begins with the characterization of the general pattern of injury which, for most cases, will be found in a handful of necroinflammatory and cholestatic patterns. A careful assessment of the severity of injury across the various anatomic compartments will provide information on the probable natural history of the injury. Correlation of liver injury with the patient's medication history and clinical findings will help to narrow the differential diagnosis, particularly when it is recognized that most drugs have a limited range of histological findings and vary in their propensity to cause injury. This review provides an overview of the assessment of the liver biopsy and its use to confirm or exclude particular drugs as contributing to the patient's liver injury. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. JF - Histopathology AU - Kleiner, David E AD - Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 81 EP - 93 VL - 70 IS - 1 KW - cholestasis KW - acute hepatitis KW - acute liver failure KW - hepatic necrosis KW - hepatotoxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852677738?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Histopathology&rft.atitle=The+histopathological+evaluation+of+drug-induced+liver+injury.&rft.au=Kleiner%2C+David+E&rft.aulast=Kleiner&rft.aufirst=David&rft.date=2017-01-01&rft.volume=70&rft.issue=1&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Histopathology&rft.issn=1365-2559&rft_id=info:doi/10.1111%2Fhis.13082 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-13 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/his.13082 ER - TY - JOUR T1 - Azathioprine and 6-Mercaptopurine-induced Liver Injury: Clinical Features and Outcomes. AN - 1852656862; 27648552 AB - The objective of the study was to define the clinical, biochemical, and histologic features of liver injury from thiopurines. Azathioprine (Aza) and 6-mercaptopurine (6-MP) can cause liver injury, but no large series exist. Clinical and laboratory data and 6-month outcomes of patients with thiopurine hepatotoxicity from the Drug-Induced Liver Injury Network Prospective Study were analyzed. Twenty-two patients were identified, 12 due to Aza and 10 due to 6-MP, with a median age of 55 years; the majority were female (68%). Inflammatory bowel disease was the indication in 55%, and the median thiopurine dose was 150 (range, 25 to 300) mg daily. The median latency to onset was 75 (range, 3 to 2584) days. Injury first arose after a dose escalation in 59% of patients, the median latency after dose increase being 44 (range, 3 to 254) days. At onset, the median alanine aminotransferase level was 210 U/L, alkaline phosphatase was 151 U/L, and bilirubin was 7.4 mg/dL (peak, 13.4 mg/dL). There were no major differences between Aza and 6-MP cases, but anicteric cases typically had nonspecific symptoms and a hepatocellular pattern of enzyme elevations, whereas icteric cases experienced cholestatic hepatitis with modest enzyme elevations in a mixed pattern. One patient with preexisting cirrhosis required liver transplantation; all others resolved clinically. One patient still had moderate alkaline phosphatase elevations 2 years after onset. Nearly three-quarters of patients with thiopurine-induced liver injury present with self-limited, cholestatic hepatitis, typically within 3 months of starting or a dose increase. The prognosis is favorable except in patients with preexisting cirrhosis. JF - Journal of clinical gastroenterology AU - Björnsson, Einar S AU - Gu, Jiezhun AU - Kleiner, David E AU - Chalasani, Naga AU - Hayashi, Paul H AU - Hoofnagle, Jay H AU - DILIN Investigators AD - *Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institutes of Health, Bethesda, MD †The Faculty of Medicine, University of Iceland ‡National University Hospital of Iceland, Reykjavik, Iceland §Duke Clinical Research Institute, Durham, NC ∥Laboratory of Pathology, National Cancer Institute, National Institutes of Health ¶Indiana University School of Medicine, Indianapolis, IN #University of North Carolina, Chapel Hill, NC. ; DILIN Investigators Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 63 EP - 69 VL - 51 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852656862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+gastroenterology&rft.atitle=Azathioprine+and+6-Mercaptopurine-induced+Liver+Injury%3A+Clinical+Features+and+Outcomes.&rft.au=Bj%C3%B6rnsson%2C+Einar+S%3BGu%2C+Jiezhun%3BKleiner%2C+David+E%3BChalasani%2C+Naga%3BHayashi%2C+Paul+H%3BHoofnagle%2C+Jay+H%3BDILIN+Investigators&rft.aulast=Bj%C3%B6rnsson&rft.aufirst=Einar&rft.date=2017-01-01&rft.volume=51&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+gastroenterology&rft.issn=1539-2031&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Mechanism of O2 diffusion and reduction in FeFe hydrogenases. AN - 1851299047; 27995927 AB - FeFe hydrogenases are the most efficient H2-producing enzymes. However, inactivation by O2 remains an obstacle that prevents them being used in many biotechnological devices. Here, we combine electrochemistry, site-directed mutagenesis, molecular dynamics and quantum chemical calculations to uncover the molecular mechanism of O2 diffusion within the enzyme and its reactions at the active site. We propose that the partial reversibility of the reaction with O2 results from the four-electron reduction of O2 to water. The third electron/proton transfer step is the bottleneck for water production, competing with formation of a highly reactive OH radical and hydroxylated cysteine. The rapid delivery of electrons and protons to the active site is therefore crucial to prevent the accumulation of these aggressive species during prolonged O2 exposure. These findings should provide important clues for the design of hydrogenase mutants with increased resistance to oxidative damage. JF - Nature chemistry AU - Kubas, Adam AU - Orain, Christophe AU - De Sancho, David AU - Saujet, Laure AU - Sensi, Matteo AU - Gauquelin, Charles AU - Meynial-Salles, Isabelle AU - Soucaille, Philippe AU - Bottin, Hervé AU - Baffert, Carole AU - Fourmond, Vincent AU - Best, Robert B AU - Blumberger, Jochen AU - Léger, Christophe AD - Department of Physics and Astronomy, University College London, Gower Street, London WC1E 6BT, UK. ; Aix Marseille Univ, CNRS, Laboratoire de Bioénergétique et Ingénierie des Protéines, Institut de Microbiologie de la Méditerranée, Marseille, France. ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Institut de Biologie et de Technologies de Saclay IBITECS, SB2SM, F-91191 Gif sur Yvette, France. ; Université de Toulouse, INSA, UPS, INP, LISBP, INRA:UMR792, CNRS:UMR 5504, 135 avenue de Rangueil, Toulouse 31077 Cedex 04, France. ; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 88 EP - 95 VL - 9 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851299047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+chemistry&rft.atitle=Mechanism+of+O2+diffusion+and+reduction+in+FeFe+hydrogenases.&rft.au=Kubas%2C+Adam%3BOrain%2C+Christophe%3BDe+Sancho%2C+David%3BSaujet%2C+Laure%3BSensi%2C+Matteo%3BGauquelin%2C+Charles%3BMeynial-Salles%2C+Isabelle%3BSoucaille%2C+Philippe%3BBottin%2C+Herv%C3%A9%3BBaffert%2C+Carole%3BFourmond%2C+Vincent%3BBest%2C+Robert+B%3BBlumberger%2C+Jochen%3BL%C3%A9ger%2C+Christophe&rft.aulast=Kubas&rft.aufirst=Adam&rft.date=2017-01-01&rft.volume=9&rft.issue=1&rft.spage=88&rft.isbn=&rft.btitle=&rft.title=Nature+chemistry&rft.issn=1755-4349&rft_id=info:doi/10.1038%2Fnchem.2592 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/nchem.2592 ER - TY - JOUR T1 - High pesticide exposure events and DNA methylation among pesticide applicators in the agricultural health study. AN - 1851297150; 27996157 AB - Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects. We evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina. DNA was extracted from whole blood from male AHS pesticide applicators (n = 695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant's lifetime. Pyrosequencing was used to quantify DNAm in CDH1, GSTp1, and MGMT promoters, and in the repetitive element, LINE-1. Linear and robust regression analyses evaluated adjusted associations between HPEE and DNAm. Ever having an HPEE (n = 142; 24%) was associated with elevated DNAm in the GSTp1 promoter at CpG7 (chr11:67,351,134; P 59 years and those with plasma folate levels ≤16.56 ng/mL (p-interaction 59 years and reduced LINE-1 DNAm (P = 0.05) among applicators with ≤16.56 ng/mL plasma folate. Non-specific HPEEs may contribute to increased DNAm in GSTp1, and in some groups, reduced DNAm in MGMT and LINE-1. The impacts of these alterations on disease development are unclear, but elevated GSTp1 promoter DNAm and subsequent gene inactivation has been consistently associated with prostate cancer. Environ. Mol. Mutagen. 58:19-29, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. JF - Environmental and molecular mutagenesis AU - Rusiecki, Jennifer A AU - Beane Freeman, Laura E AU - Bonner, Matthew R AU - Alexander, Melannie AU - Chen, Ligong AU - Andreotti, Gabriella AU - Barry, Kathryn H AU - Moore, Lee E AU - Byun, Hyang-Min AU - Kamel, Freya AU - Alavanja, Michael AU - Hoppin, Jane A AU - Baccarelli, Andrea AD - Department of Preventive Medicine, Uniformed Services University, Bethesda, Maryland. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland. ; Department of Epidemiology and Environmental Health, State University of New York, Buffalo, New York. ; Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom. ; Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina. ; Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina. ; Harvard School of Public Health, Harvard University, Boston, Massachusetts. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 19 EP - 29 VL - 58 IS - 1 KW - exposure KW - Agricultural Health Study KW - epigenetics KW - DNA methylation KW - pesticides UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851297150?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=High+pesticide+exposure+events+and+DNA+methylation+among+pesticide+applicators+in+the+agricultural+health+study.&rft.au=Rusiecki%2C+Jennifer+A%3BBeane+Freeman%2C+Laura+E%3BBonner%2C+Matthew+R%3BAlexander%2C+Melannie%3BChen%2C+Ligong%3BAndreotti%2C+Gabriella%3BBarry%2C+Kathryn+H%3BMoore%2C+Lee+E%3BByun%2C+Hyang-Min%3BKamel%2C+Freya%3BAlavanja%2C+Michael%3BHoppin%2C+Jane+A%3BBaccarelli%2C+Andrea&rft.aulast=Rusiecki&rft.aufirst=Jennifer&rft.date=2017-01-01&rft.volume=58&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=1098-2280&rft_id=info:doi/10.1002%2Fem.22067 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-20 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1002/em.22067 ER - TY - JOUR T1 - Pharmacokinetics of lenalidomide during high cut-off dialysis in a patient with multiple myeloma and renal failure. AN - 1851294783; 27988790 AB - High cut-off dialysis, increasingly used in multiple myeloma patients, is susceptible to influence anticancer drug elimination. We report about lenalidomide disposition in a patient on high cut-off dialysis for renal failure secondary to myeloma cast nephropathy. The patient received a higher dosage of lenalidomide (5 mg b.i.d.), owing to concerns about a potential decrease in lenalidomide exposure during dialysis sessions. A set of blood samples was taken in order to develop a pharmacokinetic model accounting for lenalidomide concentrations in this setting. According to our model, the area under the curve was 3273 µg h/L, i.e., 60% higher than expected under usual dosage (25 mg q.d.) with normal renal function. Despite this, the patient did not develop major hematological toxicity. Lenalidomide doses of 5 mg b.i.d. led to high exposure in a patient with renal failure undergoing high cut-off dialysis. Yet, the dosage of 5 mg q.d. recommended in conventional dialysis would probably be adequate in such patients. JF - Cancer chemotherapy and pharmacology AU - Dao, Kim AU - Lu, Yimin AU - Peer, Cody J AU - Figg, William D AU - Stadelmann, Raphael AU - Burnier, Michel AU - Buclin, Thierry AU - Kissling, Sebastien AD - Division of Clinical Pharmacology, Biomedicine, Department of Laboratories, CHUV, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 17, 1011, Lausanne, Switzerland. kim.dao@chuv.ch. ; Service of Nephrology, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. ; Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. ; Division of Hematology, Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. ; Division of Clinical Pharmacology, Biomedicine, Department of Laboratories, CHUV, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 17, 1011, Lausanne, Switzerland. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 215 EP - 218 VL - 79 IS - 1 KW - High cut-off membrane KW - Lenalidomide KW - High-flux dialysis KW - Pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851294783?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Pharmacokinetics+of+lenalidomide+during+high+cut-off+dialysis+in+a+patient+with+multiple+myeloma+and+renal+failure.&rft.au=Dao%2C+Kim%3BLu%2C+Yimin%3BPeer%2C+Cody+J%3BFigg%2C+William+D%3BStadelmann%2C+Raphael%3BBurnier%2C+Michel%3BBuclin%2C+Thierry%3BKissling%2C+Sebastien&rft.aulast=Dao&rft.aufirst=Kim&rft.date=2017-01-01&rft.volume=79&rft.issue=1&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=1432-0843&rft_id=info:doi/10.1007%2Fs00280-016-3219-z LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s00280-016-3219-z ER - TY - JOUR T1 - Ponatinib Induces a Persistent Molecular Response and Graft-versus-Host Disease/Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia with a T315I Mutation following Early Relapse after Allogeneic Transplant. AN - 1851272957; 27618144 AB - We describe the case of a patient with a Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with dasatinib plus steroids as the first-line therapy who achieved a molecular complete remission and then underwent a matched, unrelated donor allogeneic transplant. Five months after the transplant, he experienced a disease relapse with an T315I mutation, which was resistant to salvage chemotherapy. Once the details of the T315I mutation were acquired, we initiated ponatinib treatment at a standard dosage and observed a rapid decrease of minimal residual disease (MRD) at molecular assessment. The bone marrow evaluation after 2, 3, 6, 10 and 13 months was negative for MRD. After starting ponatinib, the patient experienced a skin graft-versus-host disease (GVHD), whereas no occurrence of GVHD was observed after transplant, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect, but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib was well tolerated but a thyroid dysfunction mimicking a cardiovascular toxicity was observed and solved with hormonal substitutive treatment. © 2016 S. Karger AG, Basel. JF - Chemotherapy AU - Renzi, Daniela AU - Marchesi, Francesco AU - De Angelis, Gottardo AU - Elia, Loredana AU - Salvatorelli, Emanuela AU - Gumenyuk, Svitlana AU - Palombi, Francesca AU - Pisani, Francesco AU - Romano, Atelda AU - Spadea, Antonio AU - Papa, Elena AU - Canfora, Marco AU - Arcese, William AU - Mengarelli, Andrea AU - Rome Transplant Network AD - Hematology and Stem Cell Transplant Unit, Regina Elena National Cancer Institute, Rome, Italy. ; Rome Transplant Network Y1 - 2017 PY - 2017 DA - 2017 SP - 58 EP - 61 VL - 62 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851272957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemotherapy&rft.atitle=Ponatinib+Induces+a+Persistent+Molecular+Response+and+Graft-versus-Host+Disease%2FGraft-versus-Leukemia+Effect+in+a+Patient+with+Philadelphia-Positive+Acute+Lymphoblastic+Leukemia+with+a+T315I+Mutation+following+Early+Relapse+after+Allogeneic+Transplant.&rft.au=Renzi%2C+Daniela%3BMarchesi%2C+Francesco%3BDe+Angelis%2C+Gottardo%3BElia%2C+Loredana%3BSalvatorelli%2C+Emanuela%3BGumenyuk%2C+Svitlana%3BPalombi%2C+Francesca%3BPisani%2C+Francesco%3BRomano%2C+Atelda%3BSpadea%2C+Antonio%3BPapa%2C+Elena%3BCanfora%2C+Marco%3BArcese%2C+William%3BMengarelli%2C+Andrea%3BRome+Transplant+Network&rft.aulast=Renzi&rft.aufirst=Daniela&rft.date=2017-01-01&rft.volume=62&rft.issue=1&rft.spage=58&rft.isbn=&rft.btitle=&rft.title=Chemotherapy&rft.issn=1421-9794&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - RRx-001: a systemically non-toxic M2-to-M1 macrophage stimulating and prosensitizing agent in Phase II clinical trials. AN - 1847895497; 27935336 AB - According to Hanahan and Weinberg, cancer manifests as six essential physiologic hallmarks: (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) invasion and metastasis. As a facilitator of these traits as well as immunosuppression and chemoresistance, the presence of tumor-associated macrophages (TAMs) may serve as the seventh hallmark of cancer. Anticancer agents that successfully reprogram TAMs to target rather than support tumor cells may hold the key to better therapeutic outcomes. Areas covered: This article summarizes the characteristics of the macrophage-stimulating agent RRx-001, a molecular iconoclast, sourced from the aerospace industry, with a particular emphasis on the cell-to-cell transfer mechanism of action (RBCs to TAMs) underlying its antitumor activity as well as its chemo and radioprotective properties, consolidated from various preclinical and clinical studies. Expert opinion: RRx-001 is macrophage-stimulating agent with the potential to synergize with chemotherapy, radiotherapy and immunotherapy while simultaneously protecting normal tissues from their cytotoxic effects. Given the promising indications of activity in multiple tumor types and these normal tissue protective properties, RRx-001 may be used to treat a broad spectrum of malignancies, if it is approved in the future. JF - Expert opinion on investigational drugs AU - Oronsky, Bryan AU - Paulmurugan, Ramasamy AU - Foygel, Kira AU - Scicinski, Jan AU - Knox, Susan J AU - Peehl, Donna AU - Zhao, Hongjuan AU - Ning, Shoucheng AU - Cabrales, Pedro AU - Summers, Thomas A AU - Reid, Tony R AU - Fitch, William L AU - Kim, Michelle M AU - Trepel, Jane B AU - Lee, Min-Jung AU - Kesari, Santosh AU - Abrouk, Nacer D AU - Day, Regina M AU - Oronsky, Arnold AU - Ray, Carolyn M AU - Carterg, Corey A AD - a EpicentRx (no department). ; b Department of Radiology , Stanford University , Palo Alto , CA , USA. ; c Department of Radiation Oncology , Stanford University , Palo Alto , CA , USA. ; d Department of Urology , Stanford University , Palo Alto , CA , USA. ; f Department of Bioengineering , University of California at San Diego (UCSD ) , La Jolla , CA , USA. ; g Murtha Cancer Center , Walter Reed National Military Medical Center ; Bethesda , MD , USA. ; h Moores Cancer Center , University of California at San Diego (UCSD) , CA , USA. ; e Department of Anesthesia , Stanford University , Palo Alto , CA , USA. ; k Innovexe. ; i National Cancer Institute , National Institutes of Health , Bethesda , MD , USA. ; j John Wayne Cancer Institute, Providence Saint John's Health Center , CA , USA. ; l Department of pharmacology , Uniformed Services University , Bethesda , MD , USA. ; m InterWest Partners. ; n Cancer Center, St. Francis Hospital , Hartford , CT , USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 109 EP - 119 VL - 26 IS - 1 KW - RRx-001 KW - cancer stem cells KW - cancer therapy KW - Tumor associated macrophages UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1847895497?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+investigational+drugs&rft.atitle=RRx-001%3A+a+systemically+non-toxic+M2-to-M1+macrophage+stimulating+and+prosensitizing+agent+in+Phase+II+clinical+trials.&rft.au=Oronsky%2C+Bryan%3BPaulmurugan%2C+Ramasamy%3BFoygel%2C+Kira%3BScicinski%2C+Jan%3BKnox%2C+Susan+J%3BPeehl%2C+Donna%3BZhao%2C+Hongjuan%3BNing%2C+Shoucheng%3BCabrales%2C+Pedro%3BSummers%2C+Thomas+A%3BReid%2C+Tony+R%3BFitch%2C+William+L%3BKim%2C+Michelle+M%3BTrepel%2C+Jane+B%3BLee%2C+Min-Jung%3BKesari%2C+Santosh%3BAbrouk%2C+Nacer+D%3BDay%2C+Regina+M%3BOronsky%2C+Arnold%3BRay%2C+Carolyn+M%3BCarterg%2C+Corey+A&rft.aulast=Oronsky&rft.aufirst=Bryan&rft.date=2017-01-01&rft.volume=26&rft.issue=1&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+investigational+drugs&rft.issn=1744-7658&rft_id=info:doi/10.1080%2F13543784.2017.1268600 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1080/13543784.2017.1268600 ER - TY - JOUR T1 - Phase I clinical and pharmacokinetic study of S-1 plus oral leucovorin in patients with metastatic colorectal cancer. AN - 1847893675; 27933371 AB - S-1 has shown a response rate of 35% in chemonaïve patients with metastatic colorectal cancer (mCRC). Leucovorin enhances the antitumor activity of 5-fluorouracil, and concurrent oral administration of S-1 and leucovorin may represent a more active treatment option for mCRC. S-1 (35 mg/m2) and leucovorin (25 mg/body) were orally administered twice daily to chemonaïve patients with mCRC. Predefined dose (schedule)-limiting toxicities (DLTs) during the first course and treatment continuity during the first two courses were evaluated during three periods of treatment with S-1 plus leucovorin (level 0, 2 weeks; level 1, 3 weeks; and level 2, 4 weeks), each followed by a 2-week rest. The pharmacokinetics (PK) of S-1 and leucovorin were studied on days 1 and 14 of the first course. Fifteen patients were enrolled. All three patients had DLTs at level 2, and this level was considered the maximum tolerated schedule. Level 0 was designated as the recommended schedule based on the incidences of DLTs and treatment continuity. The main toxic effects were gastrointestinal, such as diarrhea and stomatitis. There was no grade 4 adverse event or treatment-related death. The overall response rate was 67% (95% confidence interval, 38-88%). The PK profiles of S-1 plus leucovorin were similar to those in previous studies. The recommended schedule was 2 weeks of S-1 plus leucovorin followed by a 2-week rest. The increased response and gastrointestinal toxicities of S-1 plus leucovorin as compared with S-1 monotherapy suggest that co-administration of leucovorin enhanced the activity of S-1. JF - Cancer chemotherapy and pharmacology AU - Yoshino, Takayuki AU - Hyodo, Ichinosuke AU - Nishina, Tomohiro AU - Narahara, Hiroyuki AU - Sugimoto, Naotoshi AU - Yoshisue, Kunihiro AU - Boku, Narikazu AD - Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. tyoshino@east.ncc.go.jp. ; Division of Gastroenterology, University of Tsukuba, Tsukuba, Japan. ; Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. ; Division of Clinical Research Center, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan. ; Department of Clinical Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. ; Pharmacokinetics Research Laboratories, Tsukuba Research Center, Taiho Pharmaceutical Co., Ltd, Tsukuba, Japan. ; Department of Gastrointestinal Oncology, National Cancer Institute Hospital, Tokyo, Japan. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 107 EP - 116 VL - 79 IS - 1 KW - Colorectal cancer KW - Leucovorin KW - S-1 KW - Pharmacokinetics KW - Recommended schedule KW - Phase I study UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1847893675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Phase+I+clinical+and+pharmacokinetic+study+of+S-1+plus+oral+leucovorin+in+patients+with+metastatic+colorectal+cancer.&rft.au=Yoshino%2C+Takayuki%3BHyodo%2C+Ichinosuke%3BNishina%2C+Tomohiro%3BNarahara%2C+Hiroyuki%3BSugimoto%2C+Naotoshi%3BYoshisue%2C+Kunihiro%3BBoku%2C+Narikazu&rft.aulast=Yoshino&rft.aufirst=Takayuki&rft.date=2017-01-01&rft.volume=79&rft.issue=1&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=1432-0843&rft_id=info:doi/10.1007%2Fs00280-016-3212-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s00280-016-3212-6 ER - TY - JOUR T1 - Computational Tools for Allosteric Drug Discovery: Site Identification and Focus Library Design. AN - 1845831980; 27914066 AB - Allostery is an intrinsic phenomenon of biological macromolecules involving regulation and/or signal transduction induced by a ligand binding to an allosteric site distinct from a molecule's active site. Allosteric drugs are currently receiving increased attention in drug discovery because drugs that target allosteric sites can provide important advantages over the corresponding orthosteric drugs including specific subtype selectivity within receptor families. Consequently, targeting allosteric sites, instead of orthosteric sites, can reduce drug-related side effects and toxicity. On the down side, allosteric drug discovery can be more challenging than traditional orthosteric drug discovery due to difficulties associated with determining the locations of allosteric sites and designing drugs based on these sites and the need for the allosteric effects to propagate through the structure, reach the ligand binding site and elicit a conformational change. In this study, we present computational tools ranging from the identification of potential allosteric sites to the design of "allosteric-like" modulator libraries. These tools may be particularly useful for allosteric drug discovery. JF - Methods in molecular biology (Clifton, N.J.) AU - Huang, Wenkang AU - Nussinov, Ruth AU - Zhang, Jian AD - Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai JiaoTong University School of Medicine (SJTU-SM), Shanghai, 200025, China. ; Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, National Cancer Institute, Frederick, MD, 21702, USA. NussinoR@helix.nih.gov. ; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai JiaoTong University School of Medicine (SJTU-SM), Shanghai, 200025, China. jian.zhang@sjtu.edu.cn. Y1 - 2017 PY - 2017 DA - 2017 SP - 439 EP - 446 VL - 1529 KW - Allosteric drug discovery KW - Allosteric drug design KW - Allostery KW - Allosteric site KW - Allosteric modulator UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1845831980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Computational+Tools+for+Allosteric+Drug+Discovery%3A+Site+Identification+and+Focus+Library+Design.&rft.au=Huang%2C+Wenkang%3BNussinov%2C+Ruth%3BZhang%2C+Jian&rft.aulast=Huang&rft.aufirst=Wenkang&rft.date=2017-01-01&rft.volume=1529&rft.issue=&rft.spage=439&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=1940-6029&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Predictive Comprehensive Geriatric Assessment in elderly prostate cancer patients: the prospective observational scoop trial results. AN - 1845255749; 27579728 AB - The Comprehensive Geriatric Assessment (CGA) represents the future of the geriatric oncology to reduce toxicities and treatment-related hospitalization in the elderly. Most patients receiving docetaxel for metastatic castration-resistant prostate cancer are in their seventies or older. We explored the efficacy of the CGA in predicting chemotherapy feasibility and response to docetaxel in a cohort of 24 patients aged at least 70. This was an observational, prospective study involving 24 patients who were 70 years of age or older and about to start chemotherapy with docetaxel for metastatic castration-resistant prostate cancer; we performed a CGA including five domains and divided our patients into 'healthy' and 'frail'; the relations between general condition and (i) early chemotherapy discontinuation and (ii) response to docetaxel were explored. We found a statistically significant relationship between frailty assessed by CGA and early docetaxel discontinuation; we also found an association between frailty and response to chemotherapy, but this did not reach statistical significance. A geriatric assessment before starting chemotherapy may help clinicians to recognize frail patients, and hence to reduce toxicities and early treatment discontinuation. Further analyses are required to simplify the CGA tools and to facilitate its incorporation into routine clinical practice. JF - Anti-cancer drugs AU - Della Pepa, Chiara AU - Cavaliere, Carla AU - Rossetti, Sabrina AU - Di Napoli, Marilena AU - Cecere, Sabrina C AU - Crispo, Anna AU - De Sangro, Carlo AU - Rossi, Emanuela AU - Turitto, Dino AU - Germano, Domenico AU - Iovane, Gelsomina AU - Berretta, Massimiliano AU - D'Aniello, Carmine AU - Pisconti, Salvatore AU - Maiorino, Luigi AU - Daniele, Bruno AU - Gridelli, Cesare AU - Pignata, Sandro AU - Facchini, Gaetano AD - aDivision of Medical Oncology, Department of Uro-Gynaecological Oncology 'Istituto Nazionale Tumori' 'Fondazione G. Pascale'-IRCCS bUnit of Epidemiology, 'Istituto Nazionale Tumori' 'Fondazione G. Pascale' - IRCCS cDivision of Medical Oncology, 'San Gennaro dei Poveri' Hospital, Naples dDepartment of Onco-Ematology and Medical Oncology, S.G. Moscati Hospital of Taranto, Taranto eDivision of Medical Oncology, 'San Giuseppe Moscati' Hospital, Avellino fDivision of Medical Oncology, 'Gaetano Rummo' Hospital, Benevento gDepartment of Medical Oncology, National Cancer Institute, Aviano, Italy. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 104 EP - 109 VL - 28 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1845255749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-cancer+drugs&rft.atitle=Predictive+Comprehensive+Geriatric+Assessment+in+elderly+prostate+cancer+patients%3A+the+prospective+observational+scoop+trial+results.&rft.au=Della+Pepa%2C+Chiara%3BCavaliere%2C+Carla%3BRossetti%2C+Sabrina%3BDi+Napoli%2C+Marilena%3BCecere%2C+Sabrina+C%3BCrispo%2C+Anna%3BDe+Sangro%2C+Carlo%3BRossi%2C+Emanuela%3BTuritto%2C+Dino%3BGermano%2C+Domenico%3BIovane%2C+Gelsomina%3BBerretta%2C+Massimiliano%3BD%27Aniello%2C+Carmine%3BPisconti%2C+Salvatore%3BMaiorino%2C+Luigi%3BDaniele%2C+Bruno%3BGridelli%2C+Cesare%3BPignata%2C+Sandro%3BFacchini%2C+Gaetano&rft.aulast=Della+Pepa&rft.aufirst=Chiara&rft.date=2017-01-01&rft.volume=28&rft.issue=1&rft.spage=104&rft.isbn=&rft.btitle=&rft.title=Anti-cancer+drugs&rft.issn=1473-5741&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-31 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Chemotherapy-related leukopenia as a biomarker predicting survival outcomes in locally advanced cervical cancer. AN - 1844354140; 27888705 AB - To investigate the impact of hematologic toxicity and leukopenia in locally advanced cervical cancer patients undergoing neoadjuvant chemotherapy (NACT). Data of consecutive patients undergoing platinum-based NACT followed by surgery were retrospectively searched in order to evaluate the impact of chemotherapy-related toxicity on survival outcomes. Toxicity was graded per the Common Terminology Criteria for Adverse Events (CTCAEv.4.03). Survival outcomes were evaluated using Kaplan-Meir and Cox hazard models. Overall, 126 patients were included. Among those, 94 (74.6%) patients experienced grade2+ hematologic toxicity; while, grade2+ non-hematologic toxicity occurred in 11 (8.7%) patients. After a median follow-up of 37.1 (inter-quartile range, 12-57.5) months, 21 (16.6%) patients experienced recurrence. Via multivariate analysis, no factor was independently associated with disease-free survival; while a trend toward worse prognosis was observed for patients experiencing grade2+ leukopenia at cycle-3 (HR:3.13 (95%CI: 0.94, 10.3); p=0.06). Similarly, grade2+ leukopenia (HR:9.98 (95%CI: 1.14, 86.6); p=0.03), lymph-node positivity (HR:14.6 (95%CI:1.0, 214.4); p=0.05) and vaginal involvement (HR:5.81 (95%CI:1.43, 23.6); p=0.01) impacted on overall survival, at multivariate analysis. Magnitude of leukopenia correlated with survival (p<0.001). Although, our data have to be confirmed by prospective investigations, the present study shows an association between the occurrence of leukopenia and survival outcomes. NACT-related immunosuppression might reduce the response against the tumor, thus promoting cancer progression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. JF - European journal of obstetrics, gynecology, and reproductive biology AU - Bogani, Giorgio AU - Sabatucci, Ilaria AU - Maltese, Giuseppa AU - Lecce, Francesca AU - Signorelli, Mauro AU - Martinelli, Fabio AU - Chiappa, Valentina AU - Indini, Alice AU - Leone Roberti Maggiore, Umberto AU - Borghi, Chiara AU - Fucà, Giovanni AU - Ditto, Antonino AU - Raspagliesi, Francesco AU - Lorusso, Domenica AD - Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy. Electronic address: giorgiobogani@yahoo.it. ; Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy. ; Academic Unit of Obstetrics and Gynecology, IRCCS AOU San-Martino-IST, Genoa, Italy. ; Department of Morphology, Surgery and Experimental Medicine, Ferrara, Italy. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 41 EP - 45 VL - 208 KW - Neoadjuvant chemotherapy KW - Cervical cancer KW - Survival KW - Leukopenia UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844354140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+obstetrics%2C+gynecology%2C+and+reproductive+biology&rft.atitle=Chemotherapy-related+leukopenia+as+a+biomarker+predicting+survival+outcomes+in+locally+advanced+cervical+cancer.&rft.au=Bogani%2C+Giorgio%3BSabatucci%2C+Ilaria%3BMaltese%2C+Giuseppa%3BLecce%2C+Francesca%3BSignorelli%2C+Mauro%3BMartinelli%2C+Fabio%3BChiappa%2C+Valentina%3BIndini%2C+Alice%3BLeone+Roberti+Maggiore%2C+Umberto%3BBorghi%2C+Chiara%3BFuc%C3%A0%2C+Giovanni%3BDitto%2C+Antonino%3BRaspagliesi%2C+Francesco%3BLorusso%2C+Domenica&rft.aulast=Bogani&rft.aufirst=Giorgio&rft.date=2017-01-01&rft.volume=208&rft.issue=&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=European+journal+of+obstetrics%2C+gynecology%2C+and+reproductive+biology&rft.issn=1872-7654&rft_id=info:doi/10.1016%2Fj.ejogrb.2016.11.017 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ejogrb.2016.11.017 ER - TY - JOUR T1 - Low dose assessment of the carcinogenicity of furan in male F344/N Nctr rats in a 2-year gavage study. AN - 1842600255; 27871980 AB - Furan is a volatile organic chemical that is a contaminant in many common foods. Furan is hepatocarcinogenic in mice and rats; however, the risk to humans from dietary exposure to furan cannot be estimated accurately because the lowest tested dose of furan in a 2-year bioassay in rats gave nearly a 100% incidence of cholangiocarcinoma. To provide bioassay data that can be used in preparing risk assessments, the carcinogenicity of furan was determined in male F344/N Nctr rats administered 0, 0.02, 0.044, 0.092, 0.2, 0.44, 0.92, and 2 mg furan/kg body weight (BW) by gavage 5 days/week for 2 years. Exposure to furan was associated with the development of malignant mesothelioma on membranes surrounding the epididymis and on the testicular tunics, with the increase being significant at 2 mg furan/kg BW. There was also a dose-related increase in the incidence of mononuclear cell leukemia, with the increase in incidence being significant at 0.092, 0.2, 0.92, and 2 mg furan/kg BW. Dose-related non-neoplastic liver lesions included cholangiofibrosis, mixed cell foci, basophilic foci, biliary tract hyperplasia, oval cell hyperplasia, regenerative hyperplasia, and cytoplasmic vacuolization. The most sensitive non-neoplastic lesion was cholangiofibrosis, the frequency of which increased significantly at 0.2 mg furan/kg BW. Published by Elsevier Ltd. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Von Tungeln, Linda S AU - Walker, Nigel J AU - Olson, Greg R AU - Mendoza, Maria C B AU - Felton, Robert P AU - Thorn, Brett T AU - Marques, M Matilde AU - Pogribny, Igor P AU - Doerge, Daniel R AU - Beland, Frederick A AD - Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States. ; Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, United States. ; Toxicologic Pathology Associates, Jefferson, AR 72079, United States. ; Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, Jefferson, AR 72079, United States. ; Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal. ; Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States. Electronic address: frederick.beland@fda.hhs.gov. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 170 EP - 181 VL - 99 KW - Rats KW - Cholangiocarcinoma KW - Cholangiofibrosis KW - Furan KW - Tumorigenicity KW - Bioassay UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1842600255?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Low+dose+assessment+of+the+carcinogenicity+of+furan+in+male+F344%2FN+Nctr+rats+in+a+2-year+gavage+study.&rft.au=Von+Tungeln%2C+Linda+S%3BWalker%2C+Nigel+J%3BOlson%2C+Greg+R%3BMendoza%2C+Maria+C+B%3BFelton%2C+Robert+P%3BThorn%2C+Brett+T%3BMarques%2C+M+Matilde%3BPogribny%2C+Igor+P%3BDoerge%2C+Daniel+R%3BBeland%2C+Frederick+A&rft.aulast=Von+Tungeln&rft.aufirst=Linda&rft.date=2017-01-01&rft.volume=99&rft.issue=&rft.spage=170&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=1873-6351&rft_id=info:doi/10.1016%2Fj.fct.2016.11.015 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.fct.2016.11.015 ER - TY - JOUR T1 - Breakthrough Cancer Pain: Preliminary Data of The Italian Oncologic Pain Multisetting Multicentric Survey (IOPS-MS). AN - 1842599471; 27873235 AB - An ongoing national multicenter survey [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] is evaluating the characteristics of breakthrough cancer pain (BTP) in different clinical settings. Preliminary data from the first 1500 cancer patients with BTP enrolled in this study are presented here. Thirty-two clinical centers are involved in the survey. A diagnosis of BTP was performed by a standard algorithm. Epidemiological data, Karnofsky index, stage of disease, presence and sites of metastases, ongoing oncologic treatment, and characteristics of background pain and BTP and their treatments were recorded. Background pain and BTP intensity were measured. Patients were also questioned about BTP predictability, BTP onset (≤10 or >10 min), BTP duration, background and BTP medications and their doses, time to meaningful pain relief after BTP medication, and satisfaction with BTP medication. The occurrence of adverse reactions was also assessed, as well as mucosal toxicity. Background pain was well controlled with opioid treatment (numerical rating scale 3.0 ± 1.1). Patients reported 2.5 ± 1.6 BTP episodes/day with a mean intensity of 7.5 ± 1.4 and duration of 43 ± 40 min; 977 patients (65.1%) reported non-predictable BTP, and 1076 patients (71.7%) reported a rapid onset of BTP (≤10 min). Higher patient satisfaction was reported by patients treated with fast onset opioids. These preliminary data underline that the standard algorithm used is a valid tool for a proper diagnosis of BTP in cancer patients. Moreover, rapid relief of pain is crucial for patients' satisfaction. The final IOPS-MS data are necessary to understand relationships between BTP characteristics and other clinical variables in oncologic patients. Molteni Farmaceutici, Italy. JF - Advances in therapy AU - Mercadante, Sebastiano AU - Marchetti, Paolo AU - Cuomo, Arturo AU - Caraceni, Augusto AU - Mediati, Rocco Domenico AU - Mammucari, Massimo AU - Natoli, Silvia AU - Lazzari, Marzia AU - Dauri, Mario AU - Airoldi, Mario AU - Azzarello, Giuseppe AU - Bandera, Mauro AU - Blasi, Livio AU - Cartenì, Giacomo AU - Chiurazzi, Bruno AU - Costanzo, Benedetta Veruska Pierpaola AU - Degiovanni, Daniela AU - Fusco, Flavio AU - Guardamagna, Vittorio AU - Iaffaioli, Vincenzo AU - Liguori, Simeone AU - Lorusso, Vito AU - Mameli, Sergio AU - Mattioli, Rodolfo AU - Mazzei, Teresita AU - Melotti, Rita Maria AU - Menardo, Valentino AU - Miotti, Danilo AU - Moroso, Stefano AU - De Santis, Stefano AU - Orsetti, Remo AU - Papa, Alfonso AU - Ricci, Sergio AU - Sabato, Alessandro Fabrizio AU - Scelzi, Elvira AU - Sofia, Michele AU - Tonini, Giuseppe AU - Aielli, Federica AU - Valle, Alessandro AU - IOPS MS study group AD - Anesthesia and Intensive Care and Pain Relief and Supportive Care, La Maddalena Cancer Center, Via San Lorenzo 312, 90146, Palermo, Italy. terapiadeldolore@lamaddalenanet.it. ; Molecular and Clinical Medicine, Medical Oncology, La Sapienza University of Rome, Rome, Italy. ; Anesthesiology, Resuscitation, and Pain Therapy Department, National Cancer Institute, IRCCS Foundation Pascale, Naples, Italy. ; Palliative Care, Pain Therapy and Rehabilitation, National Cancer Institute IRCCS Foundation, Milan, Italy. ; Palliative Care and Pain Therapy Unit, Careggi Hospital, Florence, Italy. ; Primary Care Unit, ASL RM1, Rome, Italy. ; Department of Clinical Science and Translational Medicine, University of Rome Tor Vergata, Rome, Italy. ; 2nd Medical Oncology Division, Città della Salute e della Scienza Hospital of Turin, Turin, Italy. ; Medical Specialties Department, Oncology and Oncologic Hematology, ASL 13 Mirano, Venice, Italy. ; Medical Oncology Unit, Ospedale di Circolo e Fondazione Macchi Hospital, Varese, Italy. ; Medical Oncology Unit, ARNAS Ospedale Civico, Di Cristina, Benfratelli, Palermo, Italy. ; Medical Oncology, A.O.R.N. Cardarelli, Naples, Italy. ; Palliative Care Unit, SAMO ONLUS, Catania, Italy. ; Palliative Care Unit, ASLAL, Casale Monferrato, Italy. ; Palliative Care Unit, Department of Primary and Community Care, ASL3 Genovese, Genoa, Italy. ; Palliative Care and Pain Therapy Unit, European Oncology Institute IRCCS, Milan, Italy. ; Abdominal Medical Oncology, National Cancer Institute, IRCCS Foundation Pascale, Naples, Italy. ; Palliative Care and Pain Therapy Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy. ; Medical Oncology Unit, National Cancer Research Centre "Giovanni Paolo II", Bari, Italy. ; Pain Therapy Unit, "A. Businco" Hospital, ASL 8, Cagliari, Italy. ; Medical Oncology Unit, S. Croce Hospital, Fano, Pesaro, Italy. ; Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy. ; Department of Medicine and Surgery Sciences, University of Bologna, Bologna, Italy. ; Pain Therapy, S. Croce e Carle, Hospital Cuneo, Cuneo, Italy. ; Palliative Care Unit, Salvatore Maugeri-IRCCS Foundation, Pavia, Italy. ; Medical Oncology, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy. ; Palliative Care and Oncologic Pain Service, S. Camillo-Forlanini Hospital, Rome, Italy. ; Pain Medicine Unit, S. Camillo-Forlanini Hospital, Rome, Italy. ; Pain Relief, A.O. Dei Colli, Monaldi Hospital, Naples, Italy. ; Division of Medical Oncology, Department of Oncology, S. Chiara University Hospital, Pisa, Italy. ; Medical Oncology, Castelfranco Veneto Hospital, Treviso, Italy. ; Department of Palliative Care with Hospice and Pain Therapy Unit, "G.Salvini" Hospital, Garbagnate Milanese, Milan, Italy. ; Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy. ; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. ; Palliative Care, FARO Foundation, Turin, Italy. ; IOPS MS study group Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 120 EP - 135 VL - 34 IS - 1 KW - Pain assessment KW - Rapid-onset opioid KW - Breakthrough pain KW - Cancer pain UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1842599471?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+therapy&rft.atitle=Breakthrough+Cancer+Pain%3A+Preliminary+Data+of+The+Italian+Oncologic+Pain+Multisetting+Multicentric+Survey+%28IOPS-MS%29.&rft.au=Mercadante%2C+Sebastiano%3BMarchetti%2C+Paolo%3BCuomo%2C+Arturo%3BCaraceni%2C+Augusto%3BMediati%2C+Rocco+Domenico%3BMammucari%2C+Massimo%3BNatoli%2C+Silvia%3BLazzari%2C+Marzia%3BDauri%2C+Mario%3BAiroldi%2C+Mario%3BAzzarello%2C+Giuseppe%3BBandera%2C+Mauro%3BBlasi%2C+Livio%3BCarten%C3%AC%2C+Giacomo%3BChiurazzi%2C+Bruno%3BCostanzo%2C+Benedetta+Veruska+Pierpaola%3BDegiovanni%2C+Daniela%3BFusco%2C+Flavio%3BGuardamagna%2C+Vittorio%3BIaffaioli%2C+Vincenzo%3BLiguori%2C+Simeone%3BLorusso%2C+Vito%3BMameli%2C+Sergio%3BMattioli%2C+Rodolfo%3BMazzei%2C+Teresita%3BMelotti%2C+Rita+Maria%3BMenardo%2C+Valentino%3BMiotti%2C+Danilo%3BMoroso%2C+Stefano%3BDe+Santis%2C+Stefano%3BOrsetti%2C+Remo%3BPapa%2C+Alfonso%3BRicci%2C+Sergio%3BSabato%2C+Alessandro+Fabrizio%3BScelzi%2C+Elvira%3BSofia%2C+Michele%3BTonini%2C+Giuseppe%3BAielli%2C+Federica%3BValle%2C+Alessandro%3BIOPS+MS+study+group&rft.aulast=Mercadante&rft.aufirst=Sebastiano&rft.date=2017-01-01&rft.volume=34&rft.issue=1&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Advances+in+therapy&rft.issn=1865-8652&rft_id=info:doi/10.1007%2Fs12325-016-0440-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-22 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1007/s12325-016-0440-4 ER - TY - JOUR T1 - Avoiding phagocytosis-related artifact in myeloid derived suppressor cell T-lymphocyte suppression assays. AN - 1841797780; 27856191 AB - Myeloid-derived suppressor cells (MDSCs) have garnered much attention in recent years as a potential target for altering the immunosuppressive tumor microenvironment in a variety of solid tumor types. The ability to accurately assess the immunosuppressive capacity of MDSCs is fundamental to the development of therapeutic approaches aimed at disabling these immunosuppressive functions. In this article we provide evidence that the use of CD3/28 coated microbeads leads to artefactual T-lymphocyte suppression due to sequestration of beads by MDSCs isolated from the spleens of wild-type mice bearing subcutaneous syngeneic, carcinogen-induced oral cavity carcinomas. Mechanisms of this finding may include early MDSC death and acquisition of phagocytic capacity. These artefactual findings were avoided by eliminating the use of microbeads and instead using plate bound CD3/28 antibody as the T-lymphocyte stimulus. We propose model-specific validation of microbead-based MDSC assays, or use of an alternative stimulation approach such as plate bound CD3/28 antibodies. Copyright © 2016 Elsevier B.V. All rights reserved. JF - Journal of immunological methods AU - Davis, Ruth J AU - Silvin, Christopher AU - Allen, Clint T AD - Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United States. ; Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United States; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD, United States. Electronic address: clint.allen@nih.gov. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 12 EP - 18 VL - 440 KW - MDSC KW - Artifact KW - Myeloid-derived suppressor cells KW - T-cell suppression assay KW - Phagocytosis KW - CD3/28 microbeads UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841797780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunological+methods&rft.atitle=Avoiding+phagocytosis-related+artifact+in+myeloid+derived+suppressor+cell+T-lymphocyte+suppression+assays.&rft.au=Davis%2C+Ruth+J%3BSilvin%2C+Christopher%3BAllen%2C+Clint+T&rft.aulast=Davis&rft.aufirst=Ruth&rft.date=2017-01-01&rft.volume=440&rft.issue=&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunological+methods&rft.issn=1872-7905&rft_id=info:doi/10.1016%2Fj.jim.2016.11.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jim.2016.11.006 ER - TY - JOUR T1 - Liver injury from herbal and dietary supplements. AN - 1841795830; 27677775 AB - Herbal and dietary supplements (HDS) are used increasingly both in the United States and worldwide, and HDS-induced liver injury in the United States has increased proportionally. Current challenges in the diagnosis and management of HDS-induced liver injury were the focus of a 2-day research symposium sponsored by the American Association for the Study of Liver Disease and the National Institutes of Health. HDS-induced liver injury now accounts for 20% of cases of hepatotoxicity in the United States based on research data. The major implicated agents include anabolic steroids, green tea extract, and multi-ingredient nutritional supplements. Anabolic steroids marketed as bodybuilding supplements typically induce a prolonged cholestatic but ultimately self-limiting liver injury that has a distinctive serum biochemical as well as histological phenotype. Green tea extract and many other products, in contrast, tend to cause an acute hepatitis-like injury. Currently, however, the majority of cases of HDS-associated liver injury are due to multi-ingredient nutritional supplements, and the component responsible for the toxicity is usually unknown or can only be suspected. HDS-induced liver injury presents many clinical and research challenges in diagnosis, identification of the responsible constituents, treatment, and prevention. Also important are improvements in regulatory oversight of nonprescription products to guarantee their constituents and ensure purity and safety. The confident identification of injurious ingredients within HDS will require strategic alignments among clinicians, chemists, and toxicologists. The ultimate goal should be to prohibit or more closely regulate potentially injurious ingredients and thus promote public safety. (Hepatology 2017;65:363-373). © 2016 by the American Association for the Study of Liver Diseases. JF - Hepatology (Baltimore, Md.) AU - Navarro, Victor J AU - Khan, Ikhlas AU - Björnsson, Einar AU - Seeff, Leonard B AU - Serrano, Jose AU - Hoofnagle, Jay H AD - Division of Hepatology, Einstein Healthcare Network, Philadelphia, PA. ; Department of Pharmacognosy, School of Pharmacy, University of Mississippi, Jackson, MS. ; National University Hospital of Iceland and Faculty of Medicine, University of Iceland, Reykjavik, Iceland. ; Liver Disease Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 363 EP - 373 VL - 65 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841795830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Liver+injury+from+herbal+and+dietary+supplements.&rft.au=Navarro%2C+Victor+J%3BKhan%2C+Ikhlas%3BBj%C3%B6rnsson%2C+Einar%3BSeeff%2C+Leonard+B%3BSerrano%2C+Jose%3BHoofnagle%2C+Jay+H&rft.aulast=Navarro&rft.aufirst=Victor&rft.date=2017-01-01&rft.volume=65&rft.issue=1&rft.spage=363&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=1527-3350&rft_id=info:doi/10.1002%2Fhep.28813 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-28 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/hep.28813 ER - TY - JOUR T1 - Psychological health in long-term cancer survivorship: an Italian survey on depression and anxiety AN - 1837058569 AB - Since long-term survivorship is now a reality for an increasingly number of people with a history of cancer, understanding their psychological health can inform health care policy as well as help supporting individual patients. This study was aimed to describe depression and anxiety (i.e. two of the most common psychological symptoms reported in oncology) in a sample of Italian long-term cancer survivors (LTCSs) defined as people who have been free from cancer and cancer treatments for at least five years. Four hundred and four Italian adult LTCSs completed a battery of questionnaires including the Zung Self-rating Depression Scale and the State Anxiety sub-scale of the State-Trait Anxiety Inventory respectively for depression and anxiety assessment. 16.5% of the sample displayed mild depression, 11.1% moderate depression, and 7.1% severe depression. depression was negatively associated with education (p = .017), perceived social support as provided by the family (p = .028), and perceived social support provided by friends (p = .008), and it was positively associated with occupational status (p = .023), presence of health issues (p = .010), and anxiety (p < .001). 8.7 and 15.8% of the sample were respectively possible and probable cases of anxiety. Anxiety was negatively associated with occupational status (p = .038) and it was positively associated with depression (p < .001). These data support ongoing assessment and monitoring of depression and anxiety in LTCSs, and stimulate the development and testing of psychological interventions for such individuals. In addition, they encourage further study on the psychological health of this specific population. JF - Psychology, Health & Medicine AU - Muzzatti, Barbara AU - Giovannini, Lorena AU - Romito, Francesca AU - Cormio, Claudia AU - Barberio, Daniela AU - Abate, Valentina AU - De Falco, Francesco AU - Annunziata, Maria Antonietta AD - Centro di Riferimento Oncologico - National Cancer Institute, Aviano, Italy ; Istituto Tumori "G. Paolo II" - National Cancer Institute, Bari, Italy ; Istituto Tumori "G. Pascale" - National Cancer Institute, Napoli, Italy ; Centro di Riferimento Oncologico - National Cancer Institute, Aviano, Italy Y1 - 2017/01// PY - 2017 DA - Jan 2017 SP - 12 EP - 18 CY - Abingdon PB - Taylor & Francis Ltd. VL - 22 IS - 1 SN - 1354-8506 KW - Psychology KW - Anxiety KW - cancer survivorship KW - depression KW - oncology KW - psychological health KW - Health care KW - Friends KW - Anxiety-Depression KW - Mental health KW - Psychological wellbeing KW - Survivors KW - Oncology KW - Occupational status KW - Genetic family histories KW - Perceived social support KW - Questionnaires KW - Psychological development KW - Psychological problems KW - Trait anxiety KW - Cancer KW - Social support UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837058569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychology%2C+Health+%26+Medicine&rft.atitle=Psychological+health+in+long-term+cancer+survivorship%3A+an+Italian+survey+on+depression+and+anxiety&rft.au=Muzzatti%2C+Barbara%3BGiovannini%2C+Lorena%3BRomito%2C+Francesca%3BCormio%2C+Claudia%3BBarberio%2C+Daniela%3BAbate%2C+Valentina%3BDe+Falco%2C+Francesco%3BAnnunziata%2C+Maria+Antonietta&rft.aulast=Muzzatti&rft.aufirst=Barbara&rft.date=2017-01-01&rft.volume=22&rft.issue=1&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Psychology%2C+Health+%26+Medicine&rft.issn=13548506&rft_id=info:doi/10.1080%2F13548506.2016.1164874 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © 2016 Informa UK Limited, trading as Taylor & Francis Group N1 - Last updated - 2016-11-08 DO - http://dx.doi.org/10.1080/13548506.2016.1164874 ER - TY - JOUR T1 - A Brief Overview of the STP 35th Annual Symposium on the Basis and Relevance of Variation in Toxicologic Responses. AN - 1836736439; 27815490 AB - The title of the 2016 Society of Toxicologic Pathology (STP) Symposium was the "Basis and Relevance of Variation in Toxicologic Responses." Many factors may contribute to variation in toxicologic responses and can confound results, complicate interpretation of data, interfere with reproducibility, and make extrapolation to humans problematic. This brief overview summarizes speaker presentations from each session which describes important factors that may impact the interpretation of nonclinical discovery and developmental toxicity studies. In addition, summaries of the Continuing Education (CE) courses and other educational events that occurred during the Symposium are highlighted. JF - Toxicologic pathology AU - Irizarry, Armando R AU - Gropp, Kathryn E AU - Dixon, Darlene AD - 1 Eli Lilly & Company, Indianapolis, Indiana, USA. ; 2 Pfizer Inc., Groton, Connecticut, USA. ; 3 National Institute of Environmental Health Sciences and the National Toxicology Program, National Institutes of Health (NIH), U.S. Department of Health and Human Services (HHS), Research Triangle Park, North Carolina, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 52 EP - 56 VL - 45 IS - 1 KW - Toxicologic Pathology KW - clinical pathology KW - variation KW - nonclinical toxicity studies KW - toxicology KW - toxicologic responses KW - annual symposium UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836736439?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=A+Brief+Overview+of+the+STP+35th+Annual+Symposium+on+the+Basis+and+Relevance+of+Variation+in+Toxicologic+Responses.&rft.au=Irizarry%2C+Armando+R%3BGropp%2C+Kathryn+E%3BDixon%2C+Darlene&rft.aulast=Irizarry&rft.aufirst=Armando&rft.date=2017-01-01&rft.volume=45&rft.issue=1&rft.spage=52&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=1533-1601&rft_id=info:doi/10.1177%2F0192623316675765 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1177/0192623316675765 ER - TY - JOUR T1 - The Association of Arsenic Exposure and Metabolism With Type 1 and Type 2 Diabetes in Youth: The SEARCH Case-Control Study. AN - 1836733204; 27810988 AB - Little is known about arsenic and diabetes in youth. We examined the association of arsenic with type 1 and type 2 diabetes in the SEARCH for Diabetes in Youth Case-Control (SEARCH-CC) study. Because one-carbon metabolism can influence arsenic metabolism, we also evaluated the potential interaction of folate and vitamin B12 with arsenic metabolism on the odds of diabetes. Six hundred eighty-eight participants <22 years of age (429 with type 1 diabetes, 85 with type 2 diabetes, and 174 control participants) were evaluated. Arsenic species (inorganic arsenic [iAs], monomethylated arsenic [MMA], dimethylated arsenic [DMA]), and one-carbon metabolism biomarkers (folate and vitamin B12) were measured in plasma. We used the sum of iAs, MMA, and DMA (∑As) and the individual species as biomarkers of arsenic concentrations and the relative proportions of the species over their sum (iAs%, MMA%, DMA%) as biomarkers of arsenic metabolism. Median ∑As, iAs%, MMA%, and DMA% were 83.1 ng/L, 63.4%, 10.3%, and 25.2%, respectively. ∑As was not associated with either type of diabetes. The fully adjusted odds ratios (95% CI), rescaled to compare a difference in levels corresponding to the interquartile range of iAs%, MMA%, and DMA%, were 0.68 (0.50-0.91), 1.33 (1.02-1.74), and 1.28 (1.01-1.63), respectively, for type 1 diabetes and 0.82 (0.48-1.39), 1.09 (0.65-1.82), and 1.17 (0.77-1.77), respectively, for type 2 diabetes. In interaction analysis, the odds ratio of type 1 diabetes by MMA% was 1.80 (1.25-2.58) and 0.98 (0.70-1.38) for participants with plasma folate levels above and below the median (P for interaction = 0.02), respectively. Low iAs% versus high MMA% and DMA% was associated with a higher odds of type 1 diabetes, with a potential interaction by folate levels. These data support further research on the role of arsenic metabolism in type 1 diabetes, including the interplay with one-carbon metabolism biomarkers. © 2017 by the American Diabetes Association. JF - Diabetes care AU - Grau-Pérez, Maria AU - Kuo, Chin-Chi AU - Spratlen, Miranda AU - Thayer, Kristina A AU - Mendez, Michelle A AU - Hamman, Richard F AU - Dabelea, Dana AU - Adgate, John L AU - Knowler, William C AU - Bell, Ronny A AU - Miller, Frederick W AU - Liese, Angela D AU - Zhang, Chongben AU - Douillet, Christelle AU - Drobná, Zuzana AU - Mayer-Davis, Elizabeth J AU - Styblo, Miroslav AU - Navas-Acien, Ana AD - Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD mgraupe1@jhu.edu anavasa1@jhu.edu. ; Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. ; Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC. ; Department of Nutrition, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC. ; Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO. ; Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado Denver, Aurora, CO. ; Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ. ; Wake Forest School of Medicine, Winston-Salem, NC. ; National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD. ; Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 46 EP - 53 VL - 40 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836733204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diabetes+care&rft.atitle=The+Association+of+Arsenic+Exposure+and+Metabolism+With+Type+1+and+Type+2+Diabetes+in+Youth%3A+The+SEARCH+Case-Control+Study.&rft.au=Grau-P%C3%A9rez%2C+Maria%3BKuo%2C+Chin-Chi%3BSpratlen%2C+Miranda%3BThayer%2C+Kristina+A%3BMendez%2C+Michelle+A%3BHamman%2C+Richard+F%3BDabelea%2C+Dana%3BAdgate%2C+John+L%3BKnowler%2C+William+C%3BBell%2C+Ronny+A%3BMiller%2C+Frederick+W%3BLiese%2C+Angela+D%3BZhang%2C+Chongben%3BDouillet%2C+Christelle%3BDrobn%C3%A1%2C+Zuzana%3BMayer-Davis%2C+Elizabeth+J%3BStyblo%2C+Miroslav%3BNavas-Acien%2C+Ana&rft.aulast=Grau-P%C3%A9rez&rft.aufirst=Maria&rft.date=2017-01-01&rft.volume=40&rft.issue=1&rft.spage=46&rft.isbn=&rft.btitle=&rft.title=Diabetes+care&rft.issn=1935-5548&rft_id=info:doi/10.2337%2Fdc16-0810 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.2337/dc16-0810 ER - TY - JOUR T1 - Experimental and Study Design Considerations for Uncovering Oncometabolites. AN - 1836732291; 27807829 AB - Metabolomics as a field has gained attention due to its potential for biomarker discovery, namely because it directly reflects disease phenotype and is the downstream effect of posttranslational modifications. The field provides a "top-down," integrated view of biochemistry in complex organisms, as opposed to the traditional "bottom-up" approach that aims to analyze networks of interactions between genes, proteins and metabolites. It also allows for the detection of thousands of endogenous metabolites in various clinical biospecimens in a high-throughput manner, including tissue and biofluids such as blood and urine. Of note, because biological fluid samples can be collected relatively easily, the time-dependent fluctuations of metabolites can be readily studied in detail.In this chapter, we aim to provide an overview of (1) analytical methods that are currently employed in the field, and (2) study design concepts that should be considered prior to conducting high-throughput metabolomics studies. While widely applicable, the concepts presented here are namely applicable to high-throughput untargeted studies that aim to search for metabolite biomarkers that are associated with a particular human disease. JF - Methods in molecular biology (Clifton, N.J.) AU - Haznadar, Majda AU - Mathé, Ewy A AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA. ; Biomedical Informatics Department, College of Medicine, Ohio State University, Columbus, OH, 43210, USA. Ewy.Mathe@osumc.edu. Y1 - 2017 PY - 2017 DA - 2017 SP - 37 EP - 47 VL - 1513 KW - Biomarker discovery KW - Oncometabolites KW - Analytical techniques KW - Mass spectrometry KW - Metabolomics KW - Study design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836732291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Experimental+and+Study+Design+Considerations+for+Uncovering+Oncometabolites.&rft.au=Haznadar%2C+Majda%3BMath%C3%A9%2C+Ewy+A&rft.aulast=Haznadar&rft.aufirst=Majda&rft.date=2017-01-01&rft.volume=1513&rft.issue=&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=1940-6029&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Proteomic analysis of acetaminophen-induced hepatotoxicity and identification of heme oxygenase 1 as a potential plasma biomarker of liver injury. AN - 1835689316; 27634590 AB - Overdose of acetaminophen (APAP) is a major cause of acute liver failure. This study was aimed to identify pathways related to hepatotoxicity and potential biomarkers of liver injury. Rats were treated with low (100 mg/kg) and high (1250 mg/kg) doses of APAP, and liver tissues at 6 and 24 h post-treatment were analyzed using a proteomic approach of 16O/18O labeling and 2D-LC-MS/MS. Molecular pathways evolved progressively from scattered and less significant perturbations to more focused and significant alterations in a dose- and time-dependent manner upon APAP treatment. Imbalanced expression of hemeoxygenase 1 (HMOX1) and biliverdin reductase A (BLVRA) was associated with hepatotoxicity. Protein abundance changes of a total of 31 proteins were uniquely correlated to liver damage, among which a dramatic increase of HMOX1 levels in plasma was observed. Liver injury-associated significant elevation of plasma HMOX1 was further validated in mice treated with APAP. This study unveiled molecular changes associated with APAP-induced liver toxicity at the pathway levels and identified HMOX1 as a potential plasma biomarker of liver injury. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. JF - Proteomics. Clinical applications AU - Gao, Yuan AU - Cao, Zhijun AU - Yang, Xi AU - Abdelmegeed, Mohamed A AU - Sun, Jinchun AU - Chen, Si AU - Beger, Richard D AU - Davis, Kelly AU - Salminen, William F AU - Song, Byoung-Joon AU - Mendrick, Donna L AU - Yu, Li-Rong AD - Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA. ; Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. ; Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA. ; Toxicologic Pathology Associates, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 VL - 11 IS - 1-2 KW - Heme oxygenase 1 (HMOX1) KW - Hepatotoxicity KW - Acetaminophen KW - MS UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835689316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteomics.+Clinical+applications&rft.atitle=Proteomic+analysis+of+acetaminophen-induced+hepatotoxicity+and+identification+of+heme+oxygenase+1+as+a+potential+plasma+biomarker+of+liver+injury.&rft.au=Gao%2C+Yuan%3BCao%2C+Zhijun%3BYang%2C+Xi%3BAbdelmegeed%2C+Mohamed+A%3BSun%2C+Jinchun%3BChen%2C+Si%3BBeger%2C+Richard+D%3BDavis%2C+Kelly%3BSalminen%2C+William+F%3BSong%2C+Byoung-Joon%3BMendrick%2C+Donna+L%3BYu%2C+Li-Rong&rft.aulast=Gao&rft.aufirst=Yuan&rft.date=2017-01-01&rft.volume=11&rft.issue=1-2&rft.spage=360&rft.isbn=&rft.btitle=&rft.title=Addiction+biology&rft.issn=1369-1600&rft_id=info:doi/10.1111%2Fadb.12206 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/prca.201600123 ER - TY - JOUR T1 - FutureTox III: Bridges for Translation. AN - 1835685355; 27780885 AB - Future Tox III, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in November 2015. Building upon Future Tox I and II, Future Tox III was focused on developing the high throughput risk assessment paradigm and taking the science of in vitro data and in silico models forward to explore the question-what progress is being made to address challenges in implementing the emerging big-data toolbox for risk assessment and regulatory decision-making. This article reports on the outcome of the workshop including 2 examples of where advancements in predictive toxicology approaches are being applied within Federal agencies, where opportunities remain within the exposome and AOP domains, and how collectively the toxicology community across multiple sectors can continue to bridge the translation from historical approaches to Tox21 implementation relative to risk assessment and regulatory decision-making. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Juberg, Daland R AU - Knudsen, Thomas B AU - Sander, Miriam AU - Beck, Nancy B AU - Faustman, Elaine M AU - Mendrick, Donna L AU - Fowle, John R AU - Hartung, Thomas AU - Tice, Raymond R AU - Lemazurier, Emmanuel AU - Becker, Richard A AU - Fitzpatrick, Suzanne Compton AU - Daston, George P AU - Harrill, Alison AU - Hines, Ronald N AU - Keller, Douglas A AU - Lipscomb, John C AU - Watson, David AU - Bahadori, Tina AU - Crofton, Kevin M AD - Dow AgroSciences, Indianapolis, Indiana; drjuberg@dow.com. ; US Environmental Protection Agency, Research Triangle Park, North Carolina. ; Page One Editorial Services, Boulder, Colorado. ; American Chemistry Council, Washington, The District of Columbia. ; University of Washington, Seattle, Washington. ; US Food and Drug Administration, Silver Spring, Maryland. ; Science to Inform, LLC, Pittsboro, North Carolina. ; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. ; National Toxicology Program/National Institute of Environmental Health Sciences, Durham, North Carolina. ; INERIS-Chronic Risk Division, Verneeuil-en-Halatte, France. ; US Food and Drug Administration, College Park, Maryland. ; Procter & Gamble Company, Cincinnati, Ohio. ; University of Arkansas for Medical Sciences, Little Rock, Arkansas. ; Sanofi, Bridgewater, New Jersey. ; US Environmental Protection Agency, Cincinnati, Ohio. ; Lhasa Limited, Leeds, United Kingdom. ; US Environmental Protection Agency, Washington, The District of Columbia. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 22 EP - 31 VL - 155 IS - 1 KW - predictive toxicology KW - testing alternatives. KW - in vitro and alternatives KW - regulatory/policy KW - risk assessment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835685355?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=FutureTox+III%3A+Bridges+for+Translation.&rft.au=Juberg%2C+Daland+R%3BKnudsen%2C+Thomas+B%3BSander%2C+Miriam%3BBeck%2C+Nancy+B%3BFaustman%2C+Elaine+M%3BMendrick%2C+Donna+L%3BFowle%2C+John+R%3BHartung%2C+Thomas%3BTice%2C+Raymond+R%3BLemazurier%2C+Emmanuel%3BBecker%2C+Richard+A%3BFitzpatrick%2C+Suzanne+Compton%3BDaston%2C+George+P%3BHarrill%2C+Alison%3BHines%2C+Ronald+N%3BKeller%2C+Douglas+A%3BLipscomb%2C+John+C%3BWatson%2C+David%3BBahadori%2C+Tina%3BCrofton%2C+Kevin+M&rft.aulast=Juberg&rft.aufirst=Daland&rft.date=2017-01-01&rft.volume=155&rft.issue=1&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=1096-0929&rft_id=info:doi/10.1093%2Ftoxsci%2Fkfw194 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/toxsci/kfw194 ER - TY - JOUR T1 - An Interaction between Arsenic-Induced Epigenetic Modification and Inflammatory Promotion in a Skin Equivalent during Arsenic Carcinogenesis. AN - 1835519759; 27592797 AB - Animal studies have shown that chemical carcinogenesis consists of a three-stage process: initiation, promotion, and progression. However, because of the lack of a suitable tissue model, the molecular mechanisms of cell-cell interactions involved in those processes remain unclear. We have established a human intraepidermal carcinoma skin equivalent with organotypic culture-consisting of keratinocytes, fibroblasts, and peripheral blood mononuclear cells - induced by arsenic treatment. This SE shows the pathognomonic characteristics of arsenic-induced Bowen's disease, including acanthosis, dysplasia, and dyskeratosis. Using this SE model, we showed that arsenic initiated SUV39H2-mediated epigenetic modification of E2F1, which induced centrosome amplification in keratinocytes in 2 days; this, however, led to caspase-8-mediated apoptosis in 10 days. In parallel, arsenic stimulated tumor necrosis factor-α release mainly from peripheral blood mononuclear cells. Tumor necrosis factor-α triggered anti-apoptotic signals via FLIP-associated caspase-8 inactivation in arsenic-treated keratinocytes, which in turn contributed to cell survival and aneuploidy. The interaction between arsenic-induced epigenetic modification and inflammatory promotion resulted in the development of the pathognomonic features of arsenic-induced Bowen's disease in this model. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved. JF - The Journal of investigative dermatology AU - Liao, Wei-Ting AU - Lu, Jian-He AU - Lee, Chih-Hung AU - Lan, Cheng-Che E AU - Chang, Jan-Gowth AU - Chai, Chee-Yin AU - Yu, Hsin-Su AD - Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan. ; Graduate Institute of Medical Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan. ; Department of Dermatology, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan. ; Department of Dermatology, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. ; College of Medicine, China Medical University, Taichung 404, Taiwan. ; Department of Pathology, Kaohsiung Medical University and Hospital, Kaohsiung 807, Taiwan. ; Department of Dermatology, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan 350, Taiwan. Electronic address: dermyu@nhri.org.tw. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 187 EP - 196 VL - 137 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835519759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=An+Interaction+between+Arsenic-Induced+Epigenetic+Modification+and+Inflammatory+Promotion+in+a+Skin+Equivalent+during+Arsenic+Carcinogenesis.&rft.au=Liao%2C+Wei-Ting%3BLu%2C+Jian-He%3BLee%2C+Chih-Hung%3BLan%2C+Cheng-Che+E%3BChang%2C+Jan-Gowth%3BChai%2C+Chee-Yin%3BYu%2C+Hsin-Su&rft.aulast=Liao&rft.aufirst=Wei-Ting&rft.date=2017-01-01&rft.volume=137&rft.issue=1&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=1523-1747&rft_id=info:doi/10.1016%2Fj.jid.2016.08.017 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jid.2016.08.017 ER - TY - JOUR T1 - Oculocutaneous albinism type 1: link between mutations, tyrosinase conformational stability, and enzymatic activity. AN - 1835514661; 27775880 AB - Oculocutaneous albinism type 1 (OCA1) is an autosomal recessive disorder caused by mutations in the tyrosinase gene. Two subtypes of OCA1 have been described: severe OCA1A with complete absence of tyrosinase activity and less severe OCA1B with residual tyrosinase activity. Here, we characterize the recombinant human tyrosinase intramelanosomal domain and mutant variants, which mimic genetic changes in both subtypes of OCA1 patients. Proteins were prepared using site-directed mutagenesis, expressed in insect larvae, purified by chromatography, and characterized by enzymatic activities, tryptophan fluorescence, and Gibbs free energy changes. The OCA1A mutants showed very low protein expression and protein yield and are enzymatically inactive. Mutants mimicking OCA1B were biochemically similar to the wild type, but exhibited lower specific activities and protein stabilities. The results are consistent with clinical data, which indicates that OCA1A mutations inactivate tyrosinase and result in severe phenotype, while OCA1B mutations partially inactivate tyrosinase and result in OCA1B albinism. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. JF - Pigment cell & melanoma research AU - Dolinska, Monika B AU - Kus, Nicole J AU - Farney, S Katie AU - Wingfield, Paul T AU - Brooks, Brian P AU - Sergeev, Yuri V AD - National Eye Institute, National Institutes of Health, Bethesda, MD, USA. ; National Institute of Artritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 41 EP - 52 VL - 30 IS - 1 KW - protein stability KW - genetic mutations KW - protein unfolding KW - protein structure KW - oculocutaneous albinism KW - tyrosinase KW - protein purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835514661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pigment+cell+%26+melanoma+research&rft.atitle=Oculocutaneous+albinism+type+1%3A+link+between+mutations%2C+tyrosinase+conformational+stability%2C+and+enzymatic+activity.&rft.au=Dolinska%2C+Monika+B%3BKus%2C+Nicole+J%3BFarney%2C+S+Katie%3BWingfield%2C+Paul+T%3BBrooks%2C+Brian+P%3BSergeev%2C+Yuri+V&rft.aulast=Dolinska&rft.aufirst=Monika&rft.date=2017-01-01&rft.volume=30&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Pigment+cell+%26+melanoma+research&rft.issn=1755-148X&rft_id=info:doi/10.1111%2Fpcmr.12546 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-24 N1 - Date revised - 2017-01-31 N1 - Last updated - 2017-01-31 DO - http://dx.doi.org/10.1111/pcmr.12546 ER - TY - JOUR T1 - Serum polybrominated diphenyl ether (PBDE) concentrations in relation to biomarkers of oxidative stress and inflammation: The National Health and Nutrition Examination Survey 2003-2004. AN - 1835450348; 27750136 AB - Exposure to polybrominated diphenyl ethers (PBDEs) has been associated with various adverse health outcomes related to liver, neural and endocrine systems. Some of these may be the result of PBDE-induced oxidative stress or inflammation, but these associations have been explored minimally in humans. In the present study we examined the relationship between PBDE concentrations and biomarkers of oxidative stress and inflammation measured in blood samples among a representative US sample from the National Health and Nutrition Examination Survey. Oxidative stress biomarkers showed no significant associations with PBDEs in adjusted regression models. For inflammation biomarkers, we observed small but statistically significant positive associations between BDE-153 and alkaline phosphatase (percent change with an interquartile range [IQR] increase in BDE-153=0.82, 95% confidence interval [CI]=0.01, 1.65) and absolute neutrophil count (percent change with IQR increase in BDE-153=0.53%, 95% CI=0.03, 1.04). Associations with other PBDE congeners and inflammation markers were generally positive but did not reach statistical significance. These results are consistent with human research of oxidative stress and inflammation in response to PBDE congeners and mixtures, and support previous reports of inflammation in response to PBDE treatment in animal and in vitro studies. More detailed toxicological and epidemiologic research in humans is needed to confirm the present results, and to determine the potential clinical and public health significance of these findings. Published by Elsevier B.V. JF - The Science of the total environment AU - Yuan, Ye AU - Meeker, John D AU - Ferguson, Kelly K AD - Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA. ; Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA. ; Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA; Epidemiology Branch, National Institute of Environmental Health Sciences, USA. Electronic address: kelly.ferguson2@nih.gov. Y1 - 2017/01/01/ PY - 2017 DA - 2017 Jan 01 SP - 400 EP - 405 VL - 575 KW - Blood biomarkers KW - Reactive oxygen species KW - Flame retardants KW - National Health and Nutrition Examination Survey KW - C-reactive protein UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835450348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Science+of+the+total+environment&rft.atitle=Serum+polybrominated+diphenyl+ether+%28PBDE%29+concentrations+in+relation+to+biomarkers+of+oxidative+stress+and+inflammation%3A+The+National+Health+and+Nutrition+Examination+Survey+2003-2004.&rft.au=Yuan%2C+Ye%3BMeeker%2C+John+D%3BFerguson%2C+Kelly+K&rft.aulast=Yuan&rft.aufirst=Ye&rft.date=2017-01-01&rft.volume=575&rft.issue=&rft.spage=400&rft.isbn=&rft.btitle=&rft.title=The+Science+of+the+total+environment&rft.issn=1879-1026&rft_id=info:doi/10.1016%2Fj.scitotenv.2016.10.028 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.scitotenv.2016.10.028 ER - TY - JOUR T1 - Safety and Efficacy of Atorvastatin in Human Immunodeficiency Virus-infected Children, Adolescents and Young Adults With Hyperlipidemia. AN - 1835443990; 27749649 AB - Human immunodeficiency virus (HIV)-infected children receiving antiretroviral therapy (ART) have increased prevalence of hyperlipidemia and risk factors for cardiovascular disease. No studies have investigated the efficacy and safety of statins in this population. HIV-infected youth 10 to <24 years of age on stable ART with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL for ≥6 months initiated atorvastatin 10 mg once daily. Atorvastatin was increased to 20 mg if LDL-C efficacy criteria (LDL-C < 110 mg/dL or decreased ≥30% from baseline) were not met at week 4. Primary outcomes were safety and efficacy. Twenty-eight youth initiated atorvastatin; 7 were 10-15 years and 21 were 15-24 years. Mean baseline LDL-C was 161 mg/dL (standard deviation 19 mg/dL). Efficacy criteria were met at week 4 by 17 of 27 (63%) participants. Atorvastatin was increased to 20 mg in 10 participants. Mean LDL-C decreased from baseline by 30% (90% confidence interval: 26%, 35%) at week 4, 28% (90% confidence interval: 23%, 33%) at week 24 and 26% (90% confidence interval: 20%, 33%) at week 48. LDL-C was less than 110 mg/dL in 44% at week 4, 42% at week 12 and 46% at weeks 24 and 48. Total cholesterol, non high-density lipoprotein (non-HDL)-C and apolipoprotein B decreased significantly, but IL-6 and high-sensitivity C-reactive protein did not. Two participants in the younger age group discontinued study for toxicities possibly related to atorvastatin. Atorvastatin lowered total cholesterol, LDL-C, non HDL-C and apolipoprotein B in HIV-infected youth with ART-associated hyperlipidemia. Atorvastatin could be considered for HIV-infected children with hyperlipidemia, but safety monitoring is important particularly in younger children. JF - The Pediatric infectious disease journal AU - Melvin, Ann J AU - Montepiedra, Grace AU - Aaron, Lisa AU - Meyer, William A AU - Spiegel, Hans M AU - Borkowsky, William AU - Abzug, Mark J AU - Best, Brookie M AU - Crain, Marilyn J AU - Borum, Peggy R AU - Graham, Bobbie AU - Anthony, Patricia AU - Shin, Katherine AU - Siberry, George K AU - P1063 Study Team AD - From the *Division of Pediatric Infectious Disease, Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, Washington; †Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts; ‡Quest Diagnostics, Baltimore, Maryland; §HJF-DAIDS, a Division of The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Contractor to National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; ¶Department of Pediatrics, New York University School of Medicine, New York City, New York; ‖Department of Pediatrics (Infectious Diseases), University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado; **UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences and School of Medicine, University of California San Diego, San Diego, California; ††Department of Pediatrics and Microbiology, University of Alabama at Birmingham Pediatric Infectious Diseases, Birmingham, Alabama; ‡‡Department of Food Science and Human Nutrition, University of Florida, Gainesville, Florida; §§Frontier Science Inc., Buffalo, New York; ¶¶University of Southern California Maternal Child Adolescent Virology Research Lab, Los Angeles, California; ‖‖Pharmaceutical Affairs Branch Division of AIDS, NIAID, NIH, Bethesda, Maryland; and ***Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. ; P1063 Study Team Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 53 EP - 60 VL - 36 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835443990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Pediatric+infectious+disease+journal&rft.atitle=Safety+and+Efficacy+of+Atorvastatin+in+Human+Immunodeficiency+Virus-infected+Children%2C+Adolescents+and+Young+Adults+With+Hyperlipidemia.&rft.au=Melvin%2C+Ann+J%3BMontepiedra%2C+Grace%3BAaron%2C+Lisa%3BMeyer%2C+William+A%3BSpiegel%2C+Hans+M%3BBorkowsky%2C+William%3BAbzug%2C+Mark+J%3BBest%2C+Brookie+M%3BCrain%2C+Marilyn+J%3BBorum%2C+Peggy+R%3BGraham%2C+Bobbie%3BAnthony%2C+Patricia%3BShin%2C+Katherine%3BSiberry%2C+George+K%3BP1063+Study+Team&rft.aulast=Melvin&rft.aufirst=Ann&rft.date=2017-01-01&rft.volume=36&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=The+Pediatric+infectious+disease+journal&rft.issn=1532-0987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - The Second Pediatric Blood and Marrow Transplant Consortium International Consensus Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Defining the Unique Late Effects of Children Undergoing Hematopoietic Cell Transplantation for Immune Deficiencies, Inherited Marrow Failure Disorders, and Hemoglobinopathies. AN - 1835411720; 27737772 AB - An international consensus conference sponsored by the Pediatric Blood and Marrow Transplant consortium entitled "Late Effects Screening and Recommendations Following Allogeneic Hematopoietic Cell Transplant for Immune Deficiency and Nonmalignant Hematologic Disease" was held in Minneapolis, Minnesota on May 10, 2016 and May 11, 2016. The purpose of the conference was to address the unmet need for greater understanding of and the screening for long-term complications in the growing population of survivors of transplantation for nonmalignant disorders. The conference focused on transplantation for hemoglobinopathy, immune deficiency, and inherited bone marrow syndromes. A multidisciplinary group of experts in the disease areas and transplantation late effects presented the current state of understanding of how the underlying disease, pretransplantation therapies, and transplantation-related factors uniquely interact to influence the development of late toxicities. Recommendations were put forth by the group for the late effects screening of survivors of transplantation for these nonmalignant disorders. The findings and recommendations that came from this conference will be presented in a series of 6 additional manuscripts in the upcoming months. In this manuscript, we explore the need for screening practices specific to the survivors of transplantation for nonmalignant diseases and the methodologic challenges associated with the study of these patients. Copyright © 2017 The American Society for Blood and Marrow Transplantation. All rights reserved. JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation AU - Dietz, Andrew C AU - Duncan, Christine N AU - Alter, Blanche P AU - Bresters, Dorine AU - Cowan, Morton J AU - Notarangelo, Luigi AU - Rosenberg, Philip S AU - Shenoy, Shalini AU - Skinner, Roderick AU - Walters, Mark C AU - Wagner, John AU - Baker, K Scott AU - Pulsipher, Michael A AD - Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California. ; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts. ; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. ; Willem-Alexander Children's Hospital, SCT Unit, Leiden University Medical Center, Leiden, The Netherlands. ; University of California San Francisco, Department of Pediatrics, Allergy, Immunology, and Blood and Marrow Transplant Division, San Francisco, California. ; Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. ; Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. ; St. Louis Children's Hospital, Washington University, St. Louis, Missouri. ; Great North Children's Hospital and Northern Institute of Cancer Research, Newcastle upon Tyne, United Kingdom. ; UCSF Benioff Children's Hospital Oakland, Oakland, California. ; Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota. ; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. ; Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California. Electronic address: mpulsipher@chla.usc.edu. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 24 EP - 29 VL - 23 IS - 1 KW - Late effects KW - Immune deficiencies KW - Hemoglobinopathies KW - Marrow failure disorders KW - Pediatric allogeneic bone marrow transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835411720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.atitle=The+Second+Pediatric+Blood+and+Marrow+Transplant+Consortium+International+Consensus+Conference+on+Late+Effects+after+Pediatric+Hematopoietic+Cell+Transplantation%3A+Defining+the+Unique+Late+Effects+of+Children+Undergoing+Hematopoietic+Cell+Transplantation+for+Immune+Deficiencies%2C+Inherited+Marrow+Failure+Disorders%2C+and+Hemoglobinopathies.&rft.au=Dietz%2C+Andrew+C%3BDuncan%2C+Christine+N%3BAlter%2C+Blanche+P%3BBresters%2C+Dorine%3BCowan%2C+Morton+J%3BNotarangelo%2C+Luigi%3BRosenberg%2C+Philip+S%3BShenoy%2C+Shalini%3BSkinner%2C+Roderick%3BWalters%2C+Mark+C%3BWagner%2C+John%3BBaker%2C+K+Scott%3BPulsipher%2C+Michael+A&rft.aulast=Dietz&rft.aufirst=Andrew&rft.date=2017-01-01&rft.volume=23&rft.issue=1&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.issn=1523-6536&rft_id=info:doi/10.1016%2Fj.bbmt.2016.10.004 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-14 N1 - Date revised - 2017-01-30 N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1016/j.bbmt.2016.10.004 ER - TY - JOUR T1 - Polycyclic aromatic hydrocarbons and postmenopausal breast cancer: An evaluation of effect measure modification by body mass index and weight change. AN - 1835409894; 27741445 AB - Polycyclic aromatic hydrocarbons (PAHs) have been linked to breast cancer in many, but not all, previous studies. PAHs are lipophilic and stored in fat tissue, which we hypothesized may result in constant low-dose exposure to these carcinogens. No previous studies have evaluated whether obesity modifies associations between multiple measures of PAHs and breast cancer incidence. This population-based study included 1,006 postmenopausal women with first primary in situ or invasive breast cancer and 990 age-frequency matched controls. To evaluate effect modification by obesity (adult body mass index (BMI, kg/m2) and weight change) on multiple PAH measures (the biomarker PAH-DNA adducts, and long-term sources active cigarette smoking, living with a smoking spouse, grilled/smoked meat intake, residential synthetic log burning, and vehicular traffic), interaction contrast ratios (ICRs) for the additive scale, and ratio of odds ratios (RORs) with log-likelihood ratio tests (LRT) for the multiplicative scale, were determined using unconditional logistic regression. BMI modified the PAH-DNA adduct and postmenopausal breast cancer association on the additive (ICR: 0.49; 95% CI: 0.01, 0.96) and multiplicative (ROR: 1.56; 95% CI: 0.91, 2.68) scales. The odds ratio for detectable vs. non-detectable adducts was increased among women with BMI ≥25 (OR=1.34; 95% CI: 0.94, 1.92), but not in those with BMI <25 (OR=0.86; 95% CI: 0.57, 1.28) (LRT p=0.1). For most other PAH measures, the pattern of modification by BMI/weight gain was similar, but estimates were imprecise. The association between PAH-DNA adducts and breast cancer incidence may be elevated among overweight/obese women. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Environmental research AU - Niehoff, Nicole AU - White, Alexandra J AU - McCullough, Lauren E AU - Steck, Susan E AU - Beyea, Jan AU - Mordukhovich, Irina AU - Shen, Jing AU - Neugut, Alfred I AU - Conway, Kathleen AU - Santella, Regina M AU - Gammon, Marilie D AD - Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA. Electronic address: nicolen@live.unc.edu. ; Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. ; Department of Epidemiology, Emory University, Atlanta, GA, USA. ; Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USA. ; Department of Consulting in the Public Interest (CIPI), Lambertville, NJ, USA. ; Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA. ; Department of Environmental Health Sciences, Columbia University, New York, NY, USA. ; Department of Epidemiology, Columbia University, New York, NY, USA; Departments of Medicine, Columbia University, New York, NY, USA. ; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 17 EP - 25 VL - 152 KW - Obesity KW - Polycyclic aromatic hydrocarbons KW - Weight gain KW - Adducts KW - Breast cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835409894?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+research&rft.atitle=Polycyclic+aromatic+hydrocarbons+and+postmenopausal+breast+cancer%3A+An+evaluation+of+effect+measure+modification+by+body+mass+index+and+weight+change.&rft.au=Niehoff%2C+Nicole%3BWhite%2C+Alexandra+J%3BMcCullough%2C+Lauren+E%3BSteck%2C+Susan+E%3BBeyea%2C+Jan%3BMordukhovich%2C+Irina%3BShen%2C+Jing%3BNeugut%2C+Alfred+I%3BConway%2C+Kathleen%3BSantella%2C+Regina+M%3BGammon%2C+Marilie+D&rft.aulast=Niehoff&rft.aufirst=Nicole&rft.date=2017-01-01&rft.volume=152&rft.issue=&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=Environmental+research&rft.issn=1096-0953&rft_id=info:doi/10.1016%2Fj.envres.2016.09.022 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.envres.2016.09.022 ER - TY - JOUR T1 - A Two-Gene Prognostic Classifier for Early-Stage Lung Squamous Cell Carcinoma in Multiple Large-Scale and Geographically Diverse Cohorts. AN - 1835399000; 27613525 AB - There are no validated molecular methods that prospectively identify patients with surgically resected lung squamous cell carcinoma (SCC) at high risk for recurrence. By focusing on the expression of genes with known functions in development of lung SCC and prognosis, we sought to develop a robust prognostic classifier of early-stage lung SCC. The expression of 253 genes selected by literature search was evaluated in microarrays from 107 stage I/II tumors. Associations with survival were evaluated by Cox regression and Kaplan-Meier survival analyses in two independent cohorts of 121 and 91 patients with SCC, respectively. A classifier score based on multivariable Cox regression was derived and examined in six additional publicly available data sets of stage I/II lung SCC expression profiles (n = 358). The prognostic value of this classifier was evaluated in meta-analysis of patients with stage I/II (n = 479) and stage I (n = 326) lung SCC. Dual specificity phosphatase 6 gene (DUSP6) and actinin alpha 4 gene (ACTN4) were associated with prognostic outcome in two independent patient cohorts. Their expression values were utilized to develop a classifier that identified patients with stage I/II lung SCC at high risk for recurrence (hazard ratio [HR] = 4.7, p = 0.018) or cancer-specific mortality (HR = 3.5, p = 0.016). This classifier also identified patients at high risk for recurrence (HR = 2.7, p = 0.008) or death (HR = 2.2, p = 0.001) in publicly available data sets of stage I/II and in meta-analysis of stage I patients. We have established and validated a prognostic classifier to inform clinical management of patients with lung SCC after surgical resection. Published by Elsevier Inc. JF - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer AU - Noro, Rintaro AU - Ishigame, Teruhide AU - Walsh, Naomi AU - Shiraishi, Kouya AU - Robles, Ana I AU - Ryan, Bríd M AU - Schetter, Aaron J AU - Bowman, Elise D AU - Welsh, Judith A AU - Seike, Masahiro AU - Gemma, Akihiko AU - Skaug, Vidar AU - Mollerup, Steen AU - Haugen, Aage AU - Yokota, Jun AU - Kohno, Takashi AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute Center for Cancer Research, National Institutes of Health, Bethesda, Maryland. ; Laboratory of Human Carcinogenesis, National Cancer Institute Center for Cancer Research, National Institutes of Health, Bethesda, Maryland; Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland. ; Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan. ; Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. ; Department of Chemical and Biological Working Environment, National Institute of Occupational Health, Oslo, Norway. ; Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer, Barcelona, Spain. ; Laboratory of Human Carcinogenesis, National Cancer Institute Center for Cancer Research, National Institutes of Health, Bethesda, Maryland. Electronic address: curtis_harris@nih.gov. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 65 EP - 76 VL - 12 IS - 1 KW - Gene expression KW - Microarray KW - Biomarker KW - Prognostic classifier KW - Lung squamous cell carcinoma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835399000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+thoracic+oncology+%3A+official+publication+of+the+International+Association+for+the+Study+of+Lung+Cancer&rft.atitle=A+Two-Gene+Prognostic+Classifier+for+Early-Stage+Lung+Squamous+Cell+Carcinoma+in+Multiple+Large-Scale+and+Geographically+Diverse+Cohorts.&rft.au=Noro%2C+Rintaro%3BIshigame%2C+Teruhide%3BWalsh%2C+Naomi%3BShiraishi%2C+Kouya%3BRobles%2C+Ana+I%3BRyan%2C+Br%C3%ADd+M%3BSchetter%2C+Aaron+J%3BBowman%2C+Elise+D%3BWelsh%2C+Judith+A%3BSeike%2C+Masahiro%3BGemma%2C+Akihiko%3BSkaug%2C+Vidar%3BMollerup%2C+Steen%3BHaugen%2C+Aage%3BYokota%2C+Jun%3BKohno%2C+Takashi%3BHarris%2C+Curtis+C&rft.aulast=Noro&rft.aufirst=Rintaro&rft.date=2017-01-01&rft.volume=12&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Journal+of+thoracic+oncology+%3A+official+publication+of+the+International+Association+for+the+Study+of+Lung+Cancer&rft.issn=1556-1380&rft_id=info:doi/10.1016%2Fj.jtho.2016.08.141 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jtho.2016.08.141 ER - TY - JOUR T1 - Drug interactions in HIV treatment: complementary & alternative medicines and over-the-counter products. AN - 1835397569; 27715369 AB - Use of complementary and alternative medicines (CAMs) and over-the-counter (OTC) medications are very common among HIV-infected patients. These products can cause clinically significant drug-drug interactions (DDIs) with antiretroviral (ARV) medications, thereby increasing risk for negative outcomes such as toxicity or loss of virologic control. Areas covered: This article provides an updated review of the different mechanisms by which CAM and OTC products are implicated in DDIs with ARV medications. Expert commentary: Much of the literature published to date involves studies of CAMs interacting with older ARV agents via the cytochrome P450 (CYP450) system. However, the HIV treatment and prevention arsenal is continually evolving. Furthermore, our elucidation of the role of non-CYP450 mediated DDIs with ARV medications is greatly increasing. Therefore, clinicians are well served to understand the various mechanisms and extent by which new ARV therapies may be involved in drug interactions with CAMs and OTC medications. JF - Expert review of clinical pharmacology AU - Brooks, Kristina M AU - George, Jomy M AU - Kumar, Parag AD - a Clinical Pharmacokinetics Research Unit, Clinical Center Pharmacy Department , National Institutes of Health , Bethesda , MD , USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 59 EP - 79 VL - 10 IS - 1 KW - herbals KW - Antiretrovirals KW - drug interactions KW - over-the-counter (OTC) KW - HIV KW - pharmacokinetics KW - supplements KW - complementary and alternative medicines (CAMs) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835397569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+review+of+clinical+pharmacology&rft.atitle=Drug+interactions+in+HIV+treatment%3A+complementary+%26amp%3B+alternative+medicines+and+over-the-counter+products.&rft.au=Brooks%2C+Kristina+M%3BGeorge%2C+Jomy+M%3BKumar%2C+Parag&rft.aulast=Brooks&rft.aufirst=Kristina&rft.date=2017-01-01&rft.volume=10&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Expert+review+of+clinical+pharmacology&rft.issn=1751-2441&rft_id=info:doi/10.1080%2F17512433.2017.1246180 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1080/17512433.2017.1246180 ER - TY - JOUR T1 - A phase II trial of valproic acid in patients with advanced, radioiodine-resistant thyroid cancers of follicular cell origin. AN - 1826715975; 27392538 AB - Valproic acid (VA) is a histone deacetylase (HDAC) inhibitor that has antiproliferative effects on several types of cancer, including thyroid cancer. In addition, VA has been reported to upregulate the sodium-iodine symporter in thyroid cancer cells and increases radioiodine uptake in preclinical studies. The aim of this study was to assess the antiproliferative effects of VA and to evaluate if VA can increase the radioiodine uptake in patients with advanced, radioiodine-negative thyroid cancer. An open-label Simon two-stage phase II trial. Valproic acid was administered orally, and doses were adjusted to maintain serum trough levels between 50 and 100 mg/l for 10 weeks, followed by injections of recombinant human thyroid-stimulating hormone and a radioiodine uptake scan. Anatomical imaging studies were performed at week 16 to assess tumour response and radioiodine therapy in patients with increased radioiodine uptake. Thirteen patients with a median age of 66 years (50-78 years) were enrolled and evaluated. Seven patients had papillary thyroid cancer (PTC), two had follicular variant PTC, two had follicular thyroid cancer, and two had Hürthle cell carcinoma. None of the 10 patients who completed the 10-week treatment had increased radioiodine uptake at their tumour sites. Three patients were taken off the study prior to the 10-week radioiodine uptake scan: one with grade-3 hepatic toxicity, one with disease progression and one for noncompliance. Four of 13 patients had decreased stimulated serum thyroglobulin with VA treatment. None of the patients had complete or partial responses based on Response Evaluation Criteria in Solid Tumors (RECIST), and six patients had disease progression. Valproic acid does not increase radioiodine uptake and does not have anticancer activity in patients with advanced, radioiodine-negative thyroid cancer of follicular cell origin. © 2016 John Wiley & Sons Ltd. JF - Clinical endocrinology AU - Nilubol, Naris AU - Merkel, Roxanne AU - Yang, Lily AU - Patel, Dhaval AU - Reynolds, James C AU - Sadowski, Samira M AU - Neychev, Vladimir AU - Kebebew, Electron AD - Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ; Nuclear Medicine Department, Clinical Research Center, National Institutes of Health, Bethesda, MD, USA. ; Thoracic and Endocrine Surgery, University Hospitals of Geneva, Geneva, Switzerland. ; Department of Surgery, University Multiprofile Hospital for Active Treatment 'Alexandrovska', Medical University, Sofia, Bulgaria. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 128 EP - 133 VL - 86 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826715975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+endocrinology&rft.atitle=A+phase+II+trial+of+valproic+acid+in+patients+with+advanced%2C+radioiodine-resistant+thyroid+cancers+of+follicular+cell+origin.&rft.au=Nilubol%2C+Naris%3BMerkel%2C+Roxanne%3BYang%2C+Lily%3BPatel%2C+Dhaval%3BReynolds%2C+James+C%3BSadowski%2C+Samira+M%3BNeychev%2C+Vladimir%3BKebebew%2C+Electron&rft.aulast=Nilubol&rft.aufirst=Naris&rft.date=2017-01-01&rft.volume=86&rft.issue=1&rft.spage=128&rft.isbn=&rft.btitle=&rft.title=Clinical+endocrinology&rft.issn=1365-2265&rft_id=info:doi/10.1111%2Fcen.13154 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-08 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/cen.13154 ER - TY - JOUR T1 - Features of Autoimmune Hepatitis in Patients With Drug-induced Liver Injury. AN - 1826699152; 27311619 AB - Drug-induced liver injury (DILI) has features similar to those of other liver diseases including autoimmune hepatitis (AIH). We aimed to characterize the clinical and autoimmune features of liver injury caused by nitrofurantoin, minocycline, methyldopa, or hydralazine. We analyzed data from 88 cases of DILI attributed to nitrofurantoin, minocycline, methyldopa, or hydralazine included in the Drug-Induced Liver Injury Network prospective study from 2004 through 2014. Sera were collected from patients at baseline and follow-up examination and tested for levels of immunoglobulin G (IgG), antibodies to nuclear antigen (ANA), smooth muscle (SMA), and soluble liver antigen (SLA). An autoimmune score was derived on the basis of increases in levels of IgG, ANA, SMA, and SLA (assigned values of 0, 1+, or 2+). AIH-associated HLA-DRB1*03:01 and HLA-DRB1*04:01 allele frequencies were compared with those of the general population (controls). Of the 88 cases, 80 were women (91%), 74% had hepatocellular injury, and 25% had severe injury. At the onset of DILI, 39% of cases had increased levels of IgG, 72% had increased levels of ANA, 60% had increased levels of SMA, and none had increases in SLA. A phenotype of autoimmunity (autoimmune score ≥2) was observed in 82% of cases attributed to nitrofurantoin and 73% of cases attributed to minocycline (73%) but only 55% of cases attributed to methyldopa and 43% of cases attributed to hydralazine (P = .16 for nitrofurantoin and minocycline vs methyldopa and hydralazine). We observed a decrease in numbers of serum samples positive for ANA (P = .01) or SMA (P < .001) and in autoimmune scores (P < .001) between DILI onset and follow-up. Similar percentages of patients with DILI had HLA-DRB1*03:01 (15%) and HLA-DRB1*04:01 (9%) as controls (12% and 9%, respectively). In analysis of data from the DILIN prospective study, we found that most cases of DILI attributed to nitrofurantoin or minocycline and about half of cases that were due to methyldopa and hydralazine have a phenotype of autoimmunity similar to AIH. These features decrease with recovery of the injury and are not associated with the typical HLA alleles found in patients with idiopathic AIH. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved. JF - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association AU - de Boer, Ynto S AU - Kosinski, Andrzej S AU - Urban, Thomas J AU - Zhao, Zhen AU - Long, Nanye AU - Chalasani, Naga AU - Kleiner, David E AU - Hoofnagle, Jay H AU - Drug-Induced Liver Injury Network AD - Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: y.deboer@vumc.nl. ; Duke Clinical Research Institute, Durham, North Carolina. ; Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina, Chapel Hill, North Carolina. ; Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland. ; Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana. ; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. ; Liver Disease Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. Electronic address: hoofnaglej@extra.niddk.nih.gov. ; Drug-Induced Liver Injury Network Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 103 EP - 112.e2 VL - 15 IS - 1 KW - Immune Response KW - Immunoglobulin KW - Database Analysis KW - Toxicity KW - Hepatotoxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826699152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+gastroenterology+and+hepatology+%3A+the+official+clinical+practice+journal+of+the+American+Gastroenterological+Association&rft.atitle=Features+of+Autoimmune+Hepatitis+in+Patients+With+Drug-induced+Liver+Injury.&rft.au=de+Boer%2C+Ynto+S%3BKosinski%2C+Andrzej+S%3BUrban%2C+Thomas+J%3BZhao%2C+Zhen%3BLong%2C+Nanye%3BChalasani%2C+Naga%3BKleiner%2C+David+E%3BHoofnagle%2C+Jay+H%3BDrug-Induced+Liver%C2%A0Injury%C2%A0Network&rft.aulast=de+Boer&rft.aufirst=Ynto&rft.date=2017-01-01&rft.volume=15&rft.issue=1&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Clinical+gastroenterology+and+hepatology+%3A+the+official+clinical+practice+journal+of+the+American+Gastroenterological+Association&rft.issn=1542-7714&rft_id=info:doi/10.1016%2Fj.cgh.2016.05.043 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.cgh.2016.05.043 ER - TY - JOUR T1 - Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases. AN - 1826679270; 27143693 AB - As regulators of bioenergetics in the cell and the primary source of endogenous reactive oxygen species (ROS), dysfunctional mitochondria have been implicated for decades in the process of aging and age-related diseases. Mitochondrial DNA (mtDNA) is replicated and repaired by nuclear-encoded mtDNA polymerase γ (Pol γ) and several other associated proteins, which compose the mtDNA replication machinery. Here, we review evidence that errors caused by this replication machinery and failure to repair these mtDNA errors results in mtDNA mutations. Clonal expansion of mtDNA mutations results in mitochondrial dysfunction, such as decreased electron transport chain (ETC) enzyme activity and impaired cellular respiration. We address the literature that mitochondrial dysfunction, in conjunction with altered mitochondrial dynamics, is a major driving force behind aging and age-related diseases. Additionally, interventions to improve mitochondrial function and attenuate the symptoms of aging are examined. Published by Elsevier B.V. JF - Ageing research reviews AU - DeBalsi, Karen L AU - Hoff, Kirsten E AU - Copeland, William C AD - Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. ; Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Electronic address: copelan1@niehs.nih.gov. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 89 EP - 104 VL - 33 KW - POLG KW - Mitochondrial DNA mutations KW - Aging KW - Age-related diseases KW - MtDNA replication KW - DNA polymerase gamma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826679270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ageing+research+reviews&rft.atitle=Role+of+the+mitochondrial+DNA+replication+machinery+in+mitochondrial+DNA+mutagenesis%2C+aging+and+age-related+diseases.&rft.au=DeBalsi%2C+Karen+L%3BHoff%2C+Kirsten+E%3BCopeland%2C+William+C&rft.aulast=DeBalsi&rft.aufirst=Karen&rft.date=2017-01-01&rft.volume=33&rft.issue=&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Ageing+research+reviews&rft.issn=1872-9649&rft_id=info:doi/10.1016%2Fj.arr.2016.04.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.arr.2016.04.006 ER - TY - JOUR T1 - Dibenzo[def,p]chrysene transplacental carcinogenesis in wild-type, Cyp1b1 knockout, and CYP1B1 humanized mice. AN - 1826660414; 26990437 AB - The cytochrome P450 (CYP) 1 family is active toward numerous environmental pollutants, including polycyclic aromatic hydrocarbons (PAHs). Utilizing a mouse model, null for Cyp1b1 and expressing human CYP1B1, we tested the hypothesis that hCYP1B1 is important for dibenzo[def,p]chrysene (DBC) transplacental carcinogenesis. Wild-type mCyp1b1, transgenic hCYP1B1 (mCyp1b1 null background), and mCyp1b1 null mice were assessed. Each litter had an equal number of siblings with Ahrb-1/d and Ahrd/d alleles. Pregnant mice were dosed (gavage) on gestation day 17 with 6.5 or 12 mg/kg of DBC or corn oil. At 10 months of age, mortality, general health, lymphoid disease and lung tumor incidence, and multiplicity were assessed. hCYP1B1 genotype did not impact lung tumor multiplicity, but tended to enhance incidence compared to Cyp1b1 wild-type mice (P = 0.07). As with Cyp1b1 in wild-type mice, constitutive hCYP1B1 protein is non-detectable in liver but was induced with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Wild-type mice were 59% more likely to succumb to T-cell Acute Lymphoblastic Leukemia (T-ALL). Unlike an earlier examination of the Ahr genotype in this model (Yu et al., Cancer Res, 2006;66:755-762), but in agreement with a more recent study (Shorey et al., Toxicol Appl Pharmacol, 2013;270:60-69), this genotype was not associated with lung tumor incidence, multiplicity, or mortality. Sex was not significant with respect to lung tumor incidence or mortality but males exhibited significantly greater multiplicity. Lung tumor incidence was greater in mCyp1b1 nulls compared to wild-type mice. To our knowledge, this is the first application of a humanized mouse model in transplacental carcinogenesis. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. JF - Molecular carcinogenesis AU - Madeen, Erin P AU - Löhr, Christiane V AU - You, Hannah AU - Siddens, Lisbeth K AU - Krueger, Sharon K AU - Dashwood, Roderick H AU - Gonzalez, Frank J AU - Baird, William M AU - Ho, Emily AU - Bramer, Lisa AU - Waters, Katrina M AU - Williams, David E AD - Department of Molecular and Environmental Toxicology, Oregon State University, Corvallis, Oregon. ; Cancer Prevention and Intervention Program, Linus Pauling Institute, Oregon State University, Corvallis, Oregon. ; Center for Epigenetics and Disease Prevention, M.D. Anderson Cancer Center, Houston, Texas. ; Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. ; Superfund Research Program, Oregon State University, Corvallis, Oregon. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 163 EP - 171 VL - 56 IS - 1 KW - transplacental cancer KW - PAH carcinogenesis KW - cytochrome P450 1B1 KW - CYP1B1 humanized mice UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826660414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Dibenzo%5Bdef%2Cp%5Dchrysene+transplacental+carcinogenesis+in+wild-type%2C+Cyp1b1+knockout%2C+and+CYP1B1+humanized+mice.&rft.au=Madeen%2C+Erin+P%3BL%C3%B6hr%2C+Christiane+V%3BYou%2C+Hannah%3BSiddens%2C+Lisbeth+K%3BKrueger%2C+Sharon+K%3BDashwood%2C+Roderick+H%3BGonzalez%2C+Frank+J%3BBaird%2C+William+M%3BHo%2C+Emily%3BBramer%2C+Lisa%3BWaters%2C+Katrina+M%3BWilliams%2C+David+E&rft.aulast=Madeen&rft.aufirst=Erin&rft.date=2017-01-01&rft.volume=56&rft.issue=1&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=1098-2744&rft_id=info:doi/10.1002%2Fmc.22480 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-03-18 N1 - Date revised - 2017-01-27 N1 - Last updated - 2017-01-28 DO - http://dx.doi.org/10.1002/mc.22480 ER - TY - JOUR T1 - The landscape of new drugs in lymphoma. AN - 1854107024; 28031560 AB - The landscape of drugs for the treatment of lymphoma has become crowded in light of the plethora of new agents, necessitating the efficient prioritization of drugs for expedited development. The number of drugs available, and the fact that many can be given for an extended period of time, has resulted in the emergence of new challenges; these include determining the optimal duration of therapy, and the need to balance costs, benefits, and the risk of late-onset toxicities. Moreover, with the increase in the number of available investigational drugs, the number of possible combinations is becoming overwhelming, which necessitates prioritization plans for the selective development of novel combination regimens. In this Review, we describe the most-promising agents in clinical development for the treatment of lymphoma, and provide expert opinion on new strategies that might enable more streamlined drug development. We also address new approaches for patient selection and for incorporating new end points into clinical trials. JF - Nature reviews. Clinical oncology AU - Younes, Anas AU - Ansell, Stephen AU - Fowler, Nathan AU - Wilson, Wyndham AU - de Vos, Sven AU - Seymour, John AU - Advani, Ranjana AU - Forero, Andres AU - Morschhauser, Franck AU - Kersten, Marie Jose AU - Tobinai, Kensei AU - Zinzani, Pier Luigi AU - Zucca, Emanuele AU - Abramson, Jeremy AU - Vose, Julie AD - Lymphoma Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA. ; Division of Haematology, Mayo Clinic, 200 1st St Sw, Rochester, Minnesota 55905, USA. ; Department of Lymphoma and Myeloma, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. ; Lymphoid Malignancies Branch, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA. ; Department of Medicine, Ronald Reagan UCLA Medical Center, Santa Monica, California 90404, USA. ; Department of Haematology, Peter MacCallum Cancer Centre, A'Beckett Street, East Melbourne, Victoria 8006, Australia. ; Division of Oncology, Stanford University Cancer Center, 875 Blake Wilbur Drive, Stanford, California 94305, USA. ; Division of Haematology and Oncology, University of Alabama School of Medicine, 1720 2nd Avenue South, NP2540, Birmingham, Alabama 35294-3300, USA. ; Department of Haematology, Hôpital Claude Huriez, F-59037 Lille, France. ; Department of Haematology, Academic Medical Center and LYMMCARE, Amsterdam, Netherlands. ; Haematology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. ; Institute of Haematology "L. e A. Seràgnoli," University of Bologna, Via Massarenti, 9-40138 Bologna, Italy. ; Oncology Institute of Southern Switzerland, Ospedale San Giovanni, 6500 Bellinzona, Switzerland. ; Massachusetts General Hospital Cancer Center, Yawkey Center for Outpatient Care, Mailstop: Yawkey 9A, 32 Fruit Street, Boston, Massachusetts 02114, USA. ; UNMC Oncology/Haematology Division, 987680 Nebraska Medical Center, Omaha, Nebraska 681980-7680, USA. Y1 - 2016/12/29/ PY - 2016 DA - 2016 Dec 29 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1854107024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+reviews.+Clinical+oncology&rft.atitle=The+landscape+of+new+drugs+in+lymphoma.&rft.au=Younes%2C+Anas%3BAnsell%2C+Stephen%3BFowler%2C+Nathan%3BWilson%2C+Wyndham%3Bde+Vos%2C+Sven%3BSeymour%2C+John%3BAdvani%2C+Ranjana%3BForero%2C+Andres%3BMorschhauser%2C+Franck%3BKersten%2C+Marie+Jose%3BTobinai%2C+Kensei%3BZinzani%2C+Pier+Luigi%3BZucca%2C+Emanuele%3BAbramson%2C+Jeremy%3BVose%2C+Julie&rft.aulast=Younes&rft.aufirst=Anas&rft.date=2016-12-29&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Nature+reviews.+Clinical+oncology&rft.issn=1759-4782&rft_id=info:doi/10.1038%2Fnrclinonc.2016.205 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-29 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1038/nrclinonc.2016.205 ER - TY - JOUR T1 - Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas. AN - 1854104478; 28029918 AB - Background Effective medical therapies are lacking for the treatment of neurofibromatosis type 1-related plexiform neurofibromas, which are characterized by elevated RAS-mitogen-activated protein kinase (MAPK) signaling. Methods We conducted a phase 1 trial of selumetinib (AZD6244 or ARRY-142886), an oral selective inhibitor of MAPK kinase (MEK) 1 and 2, in children who had neurofibromatosis type 1 and inoperable plexiform neurofibromas to determine the maximum tolerated dose and to evaluate plasma pharmacokinetics. Selumetinib was administered twice daily at a dose of 20 to 30 mg per square meter of body-surface area on a continuous dosing schedule (in 28-day cycles). We also tested selumetinib using a mouse model of neurofibromatosis type 1-related neurofibroma. Response to treatment (i.e., an increase or decrease from baseline in the volume of plexiform neurofibromas) was monitored by using volumetric magnetic resonance imaging analysis to measure the change in size of the plexiform neurofibroma. Results A total of 24 children (median age, 10.9 years; range, 3.0 to 18.5) with a median tumor volume of 1205 ml (range, 29 to 8744) received selumetinib. Patients were able to receive selumetinib on a long-term basis; the median number of cycles was 30 (range, 6 to 56). The maximum tolerated dose was 25 mg per square meter (approximately 60% of the recommended adult dose). The most common toxic effects associated with selumetinib included acneiform rash, gastrointestinal effects, and asymptomatic creatine kinase elevation. The results of pharmacokinetic evaluations of selumetinib among the children in this trial were similar to those published for adults. Treatment with selumetinib resulted in confirmed partial responses (tumor volume decreases from baseline of ≥20%) in 17 of the 24 children (71%) and decreases from baseline in neurofibroma volume in 12 of 18 mice (67%). Disease progression (tumor volume increase from baseline of ≥20%) has not been observed to date. Anecdotal evidence of decreases in tumor-related pain, disfigurement, and functional impairment was observed. Conclusions Our early-phase data suggested that children with neurofibromatosis type 1 and inoperable plexiform neurofibromas benefited from long-term dose-adjusted treatment with selumetinib without having excess toxic effects. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01362803 .). JF - The New England journal of medicine AU - Dombi, Eva AU - Baldwin, Andrea AU - Marcus, Leigh J AU - Fisher, Michael J AU - Weiss, Brian AU - Kim, AeRang AU - Whitcomb, Patricia AU - Martin, Staci AU - Aschbacher-Smith, Lindsey E AU - Rizvi, Tilat A AU - Wu, Jianqiang AU - Ershler, Rachel AU - Wolters, Pamela AU - Therrien, Janet AU - Glod, John AU - Belasco, Jean B AU - Schorry, Elizabeth AU - Brofferio, Alessandra AU - Starosta, Amy J AU - Gillespie, Andrea AU - Doyle, Austin L AU - Ratner, Nancy AU - Widemann, Brigitte C AD - From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.). Y1 - 2016/12/29/ PY - 2016 DA - 2016 Dec 29 SP - 2550 EP - 2560 VL - 375 IS - 26 KW - AZD 6244 KW - 0 KW - Benzimidazoles KW - Protein Kinase Inhibitors KW - Mitogen-Activated Protein Kinase Kinases KW - EC 2.7.12.2 KW - Abridged Index Medicus KW - Index Medicus KW - Magnetic Resonance Imaging KW - Animals KW - Humans KW - Disease Progression KW - Disease Models, Animal KW - Mice KW - Child KW - Adolescent KW - Male KW - Female KW - Child, Preschool KW - Neurofibromatosis 1 -- drug therapy KW - Protein Kinase Inhibitors -- adverse effects KW - Neurofibroma, Plexiform -- drug therapy KW - Benzimidazoles -- adverse effects KW - Benzimidazoles -- administration & dosage KW - Protein Kinase Inhibitors -- administration & dosage KW - Protein Kinase Inhibitors -- pharmacokinetics KW - Mitogen-Activated Protein Kinase Kinases -- antagonists & inhibitors KW - Benzimidazoles -- pharmacokinetics KW - Neurofibroma, Plexiform -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1854104478?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Activity+of+Selumetinib+in+Neurofibromatosis+Type+1-Related+Plexiform+Neurofibromas.&rft.au=Dombi%2C+Eva%3BBaldwin%2C+Andrea%3BMarcus%2C+Leigh+J%3BFisher%2C+Michael+J%3BWeiss%2C+Brian%3BKim%2C+AeRang%3BWhitcomb%2C+Patricia%3BMartin%2C+Staci%3BAschbacher-Smith%2C+Lindsey+E%3BRizvi%2C+Tilat+A%3BWu%2C+Jianqiang%3BErshler%2C+Rachel%3BWolters%2C+Pamela%3BTherrien%2C+Janet%3BGlod%2C+John%3BBelasco%2C+Jean+B%3BSchorry%2C+Elizabeth%3BBrofferio%2C+Alessandra%3BStarosta%2C+Amy+J%3BGillespie%2C+Andrea%3BDoyle%2C+Austin+L%3BRatner%2C+Nancy%3BWidemann%2C+Brigitte+C&rft.aulast=Dombi&rft.aufirst=Eva&rft.date=2016-12-29&rft.volume=375&rft.issue=26&rft.spage=2550&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=1533-4406&rft_id=info:doi/10.1056%2FNEJMoa1605943 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-10 N1 - Date created - 2016-12-28 N1 - Date revised - 2017-01-14 N1 - Genetic sequence - NCT01362803; ClinicalTrials.gov N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1056/NEJMoa1605943 ER - TY - JOUR T1 - Exome sequencing provides additional evidence for the involvement of ARHGAP29 in Mendelian orofacial clefting and extends the phenotypic spectrum to isolated cleft palate. AN - 1853741387; 28029220 AB - Recent advances in genomics methodologies, in particular the availability of next-generation sequencing approaches have made it possible to identify risk loci throughout the genome, in particular the exome. In the current study, we present findings from an exome study conducted in five affected individuals of a multiplex family with cleft palate only. The GEnome MINIng (GEMINI) pipeline was used to functionally annotate the single nucleotide polymorphisms, insertions and deletions. Filtering methods were applied to identify variants that are clinically relevant and present in affected individuals at minor allele frequencies (≤1%) in the 1000 Genomes Project single nucleotide polymorphism database, Exome Aggregation Consortium, and Exome Variant Server databases. The bioinformatics tool Systems Tool for Craniofacial Expression-Based Gene Discovery was used to prioritize cleft candidates in our list of variants, and Sanger sequencing was used to validate the presence of identified variants in affected and unaffected relatives. Our analyses approach narrowed the candidates down to the novel missense variant in ARHGAP29 (GenBank: NM_004815.3, NP_004806.3;c.1654T>C [p.Ser552Pro]. A functional assay in zebrafish embryos showed that the encoded protein lacks the activity possessed by its wild-type counterpart, and migration assays revealed that keratinocytes transfected with wild-type ARHGAP29 migrated faster than counterparts transfected with the p.Ser552Pro ARHGAP29 variant or empty vector (control). These findings reveal ARHGAP29 to be a regulatory protein essential for proper development of the face, identifies an amino acid that is key for this, and provides a potential new diagnostic tool.Birth Defects Research (Part A) 00:000-000, 2016.© 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. JF - Birth defects research. Part A, Clinical and molecular teratology AU - Liu, Huan AU - Busch, Tamara AU - Eliason, Steven AU - Anand, Deepti AU - Bullard, Steven AU - Gowans, Lord J J AU - Nidey, Nichole AU - Petrin, Aline AU - Augustine-Akpan, Eno-Abasi AU - Saadi, Irfan AU - Dunnwald, Martine AU - Lachke, Salil A AU - Zhu, Ying AU - Adeyemo, Adebowale AU - Amendt, Brad AU - Roscioli, Tony AU - Cornell, Robert AU - Murray, Jeffrey AU - Butali, Azeez AD - Department of Anatomy and Cell Biology, Iowa City, Iowa. ; Department of Pediatrics, University of Iowa, Iowa City, Iowa. ; Department of Biological Sciences, University of Delaware, Newark, Deleware. ; Department of Internal Medicine, University of Iowa, Iowa City, Iowa. ; Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, Iowa. ; Department of Anatomy and Cell Biology, University of Kansas Medical Center Kansas City, Kansas. ; Newcastle GOLD Service, Hunter Genetics, Waratah, NSW, Australia. ; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland. ; Department of Medical Genetics, Sydney Children's Hospital, Sydney, Australia. Y1 - 2016/12/28/ PY - 2016 DA - 2016 Dec 28 KW - exome KW - cleft palate KW - missense mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1853741387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Birth+defects+research.+Part+A%2C+Clinical+and+molecular+teratology&rft.atitle=Exome+sequencing+provides+additional+evidence+for+the+involvement+of+ARHGAP29+in+Mendelian+orofacial+clefting+and+extends+the+phenotypic+spectrum+to+isolated+cleft+palate.&rft.au=Liu%2C+Huan%3BBusch%2C+Tamara%3BEliason%2C+Steven%3BAnand%2C+Deepti%3BBullard%2C+Steven%3BGowans%2C+Lord+J+J%3BNidey%2C+Nichole%3BPetrin%2C+Aline%3BAugustine-Akpan%2C+Eno-Abasi%3BSaadi%2C+Irfan%3BDunnwald%2C+Martine%3BLachke%2C+Salil+A%3BZhu%2C+Ying%3BAdeyemo%2C+Adebowale%3BAmendt%2C+Brad%3BRoscioli%2C+Tony%3BCornell%2C+Robert%3BMurray%2C+Jeffrey%3BButali%2C+Azeez&rft.aulast=Liu&rft.aufirst=Huan&rft.date=2016-12-28&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Birth+defects+research.+Part+A%2C+Clinical+and+molecular+teratology&rft.issn=1542-0760&rft_id=info:doi/10.1002%2Fbdra.23596 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-28 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/bdra.23596 ER - TY - JOUR T1 - Implementing Pharmacogenomics in Europe: Design and Implementation Strategy of the Ubiquitous Pharmacogenomics Consortium. AN - 1853745274; 28027596 AB - Despite scientific and clinical advances in the field of pharmacogenomics (PGx), application into routine care remains limited. Opportunely, several implementation studies and programmes have been initiated over recent years. This article presents an overview of these studies and identifies current research gaps. Importantly, one such gap is the undetermined collective clinical utility of implementing a panel of PGx-markers into routine care, because the evidence base is currently limited to specific, individual drug-gene pairs. The Ubiquitous Pharmacogenomics Consortium (U-PGx), which has been funded by the European Commission's Horizon-2020 programme, aims to address this unmet need. In a prospective, block-randomized, controlled clinical study (PREPARE), pre-emptive genotyping of a panel of clinically relevant PGx-markers, for which guidelines are available, will be implemented across healthcare institutions in seven European countries. The impact on patient outcomes and cost-effectiveness will be investigated. The program is unique in its multi-center, multi-gene, multi-drug, multi-ethnic, and multi-healthcare system approach. This article is protected by copyright. All rights reserved. © 2016 American Society for Clinical Pharmacology and Therapeutics. JF - Clinical pharmacology and therapeutics AU - van der Wouden, Cathelijne H AU - Cambon-Thomsen, Anne AU - Cecchin, Erika AU - Cheung, Ka-Chun AU - Lucía Dávila-Fajardo, Cristina AU - Deneer, Vera H AU - Dolžan, Vita AU - Ingelman-Sundberg, Magnus AU - Jönsson, Siv AU - Karlsson, Mats O AU - Kriek, Marjolein AU - Mitropoulou, Christina AU - Patrinos, George P AU - Pirmohamed, Munir AU - Samwald, Matthias AU - Schaeffeler, Elke AU - Schwab, Matthias AU - Steinberger, Daniela AU - Stingl, Julia AU - Sunder-Plassmann, Gere AU - Toffoli, Giuseppe AU - Turner, Richard M AU - van Rhenen, Mandy H AU - Swen, Jesse J AU - Guchelaar, Henk-Jan AU - Ubiquitous Pharmacogenomics Consortium AD - Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands. ; UMR Inserm U1027 and Université de Toulouse III Paul Sabatier, Toulouse, France. ; Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy. ; Royal Dutch Pharmacists Association (KNMP), The Hague, The Netherlands. ; Department of Clinical Pharmacy, Granada University Hospital, Institute for Biomedical Research, Granada, Spain. ; Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, The Netherlands. ; Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia. ; Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden. ; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. ; Center for Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. ; The Golden Helix Foundation, London, United Kingdom. ; University of Patras, School of Health Sciences, Department of Pharmacy, University Campus, Rion, Patras, Greece. ; Department of Molecular & Clinical Pharmacology, Royal Liverpool University Hospital and University of Liverpool, Liverpool, United Kingdom. ; Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria. ; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany and University of Tübingen, Tübingen, Germany. ; bio.logis Center for Human Genetics, Frankfurt am Main, Germany. ; Research Division, Federal Institute for Drugs and Medical Devices, Bonn, Germany. ; Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. ; Ubiquitous Pharmacogenomics Consortium Y1 - 2016/12/27/ PY - 2016 DA - 2016 Dec 27 KW - Pre-emptive KW - Clinical Trial KW - Pharmacogenomics KW - Adverse Drug Reactions KW - Genotyping KW - Next-Generation Sequencing KW - Clinical Implementation KW - Pharmacogenetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1853745274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+pharmacology+and+therapeutics&rft.atitle=Implementing+Pharmacogenomics+in+Europe%3A+Design+and+Implementation+Strategy+of+the+Ubiquitous+Pharmacogenomics+Consortium.&rft.au=van+der+Wouden%2C+Cathelijne+H%3BCambon-Thomsen%2C+Anne%3BCecchin%2C+Erika%3BCheung%2C+Ka-Chun%3BLuc%C3%ADa+D%C3%A1vila-Fajardo%2C+Cristina%3BDeneer%2C+Vera+H%3BDol%C5%BEan%2C+Vita%3BIngelman-Sundberg%2C+Magnus%3BJ%C3%B6nsson%2C+Siv%3BKarlsson%2C+Mats+O%3BKriek%2C+Marjolein%3BMitropoulou%2C+Christina%3BPatrinos%2C+George+P%3BPirmohamed%2C+Munir%3BSamwald%2C+Matthias%3BSchaeffeler%2C+Elke%3BSchwab%2C+Matthias%3BSteinberger%2C+Daniela%3BStingl%2C+Julia%3BSunder-Plassmann%2C+Gere%3BToffoli%2C+Giuseppe%3BTurner%2C+Richard+M%3Bvan+Rhenen%2C+Mandy+H%3BSwen%2C+Jesse+J%3BGuchelaar%2C+Henk-Jan%3BUbiquitous+Pharmacogenomics+Consortium&rft.aulast=van+der+Wouden&rft.aufirst=Cathelijne&rft.date=2016-12-27&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Clinical+pharmacology+and+therapeutics&rft.issn=1532-6535&rft_id=info:doi/10.1002%2Fcpt.602 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/cpt.602 ER - TY - JOUR T1 - Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations. AN - 1853363032; 28025329 AB - To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P < 5 × 10-8), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases. Comparison of the overall associations with published results in Western populations revealed that the majority of these findings were distinct, underscoring the importance of distinct contributing factors for smoking and non-smoking lung cancer. Our results extend the catalogue of regions associated with lung adenocarcinoma in non-smoking Asian women and highlight the importance of how the germline could inform risk for specific tumour mutation patterns, which could have important translational implications. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US. JF - Human molecular genetics AU - Seow, Wei Jie AU - Matsuo, Keitaro AU - Hsiung, Chao Agnes AU - Shiraishi, Kouya AU - Song, Minsun AU - Kim, Hee Nam AU - Wong, Maria Pik AU - Hong, Yun-Chul AU - Hosgood, H Dean AU - Wang, Zhaoming AU - Chang, I-Shou AU - Wang, Jiu-Cun AU - Chatterjee, Nilanjan AU - Tucker, Margaret AU - Wei, Hu AU - Mitsudomi, Tetsuya AU - Zheng, Wei AU - Kim, Jin Hee AU - Zhou, Baosen AU - Caporaso, Neil E AU - Albanes, Demetrius AU - Shin, Min-Ho AU - Chung, Lap Ping AU - An, She-Juan AU - Wang, Ping AU - Zheng, Hong AU - Yatabe, Yasushi AU - Zhang, Xu-Chao AU - Kim, Young Tae AU - Shu, Xiao-Ou AU - Kim, Young-Chul AU - Bassig, Bryan A AU - Chang, Jiang AU - Ho, James Chung Man AU - Ji, Bu-Tian AU - Kubo, Michiaki AU - Daigo, Yataro AU - Ito, Hidemi AU - Momozawa, Yukihide AU - Ashikawa, Kyota AU - Kamatani, Yoichiro AU - Honda, Takayuki AU - Sakamoto, Hiromi AU - Kunitoh, Hideo AU - Tsuta, Koji AU - Watanabe, Shun-Ichi AU - Nokihara, Hiroshi AU - Miyagi, Yohei AU - Nakayama, Haruhiko AU - Matsumoto, Shingo AU - Tsuboi, Masahiro AU - Goto, Koichi AU - Yin, Zhihua AU - Shi, Jianxin AU - Takahashi, Atsushi AU - Goto, Akiteru AU - Minamiya, Yoshihiro AU - Shimizu, Kimihiro AU - Tanaka, Kazumi AU - Wu, Tangchun AU - Wei, Fusheng AU - Wong, Jason Y Y AU - Matsuda, Fumihiko AU - Su, Jian AU - Kim, Yeul Hong AU - Oh, In-Jae AU - Song, Fengju AU - Lee, Victor Ho Fun AU - Su, Wu-Chou AU - Chen, Yuh-Min AU - Chang, Gee-Chen AU - Chen, Kuan-Yu AU - Huang, Ming-Shyan AU - Yang, Pan-Chyr AU - Lin, Hsien-Chih AU - Xiang, Yong-Bing AU - Seow, Adeline AU - Park, Jae Yong AU - Kweon, Sun-Seog AU - Chen, Chien-Jen AU - Li, Haixin AU - Gao, Yu-Tang AU - Wu, Chen AU - Qian, Biyun AU - Lu, Daru AU - Liu, Jianjun AU - Jeon, Hyo-Sung AU - Hsiao, Chin-Fu AU - Sung, Jae Sook AU - Tsai, Ying-Huang AU - Jung, Yoo Jin AU - Guo, Huan AU - Hu, Zhibin AU - Wang, Wen-Chang AU - Chung, Charles C AU - Lawrence, Charles AU - Burdett, Laurie AU - Yeager, Meredith AU - Jacobs, Kevin B AU - Hutchinson, Amy AU - Berndt, Sonja I AU - He, Xingzhou AU - Wu, Wei AU - Wang, Junwen AU - Li, Yuqing AU - Choi, Jin Eun AU - Park, Kyong Hwa AU - Sung, Sook Whan AU - Liu, Li AU - Kang, Chang Hyun AU - Hu, Lingmin AU - Chen, Chung-Hsing AU - Yang, Tsung-Ying AU - Xu, Jun AU - Guan, Peng AU - Tan, Wen AU - Wang, Chih-Liang AU - Sihoe, Alan Dart Loon AU - Chen, Ying AU - Choi, Yi Young AU - Hung, Jen-Yu AU - Kim, Jun Suk AU - Yoon, Ho-Il AU - Cai, Qiuyin AU - Lin, Chien-Chung AU - Park, In Kyu AU - Xu, Ping AU - Dong, Jing AU - Kim, Christopher AU - He, Qincheng AU - Perng, Reury-Perng AU - Chen, Chih-Yi AU - Vermeulen, Roel AU - Wu, Junjie AU - Lim, Wei-Yen AU - Chen, Kun-Chieh AU - Chan, John K C AU - Chu, Minjie AU - Li, Yao-Jen AU - Li, Jihua AU - Chen, Hongyan AU - Yu, Chong-Jen AU - Jin, Li AU - Lo, Yen-Li AU - Chen, Ying-Hsiang AU - Fraumeni, Joseph F AU - Liu, Jie AU - Yamaji, Taiki AU - Yang, Yang AU - Hicks, Belynda AU - Wyatt, Kathleen AU - Li, Shengchao A AU - Dai, Juncheng AU - Ma, Hongxia AU - Jin, Guangfu AU - Song, Bao AU - Wang, Zhehai AU - Cheng, Sensen AU - Li, Xuelian AU - Ren, Yangwu AU - Cui, Ping AU - Iwasaki, Motoki AU - Shimazu, Taichi AU - Tsugane, Shoichiro AU - Zhu, Junjie AU - Jiang, Gening AU - Fei, Ke AU - Wu, Guoping AU - Chien, Li-Hsin AU - Chen, Hui-Ling AU - Su, Yu-Chun AU - Tsai, Fang-Yu AU - Chen, Yi-Song AU - Yu, Jinming AU - Stevens, Victoria L AU - Laird-Offringa, Ite A AU - Marconett, Crystal N AU - Lin, Dongxin AU - Chen, Kexin AU - Wu, Yi-Long AU - Landi, Maria Teresa AU - Shen, Hongbing AU - Rothman, Nathaniel AU - Kohno, Takashi AU - Chanock, Stephen J AU - Lan, Qing AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA ephswj@nus.edu.sg. ; Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. ; Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan. ; Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. ; Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea. ; Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong. ; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. ; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA. ; National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan. ; Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, People's Republic of China. ; Division of Thoracic Surgery, Kinki University School of Medicine, Sayama, Japan. ; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. ; Department of Integrative Bioscience & Biotechnology, Sejong University, Seoul, Republic of Korea. ; Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People's Republic of China. ; Guangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China. ; Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China. ; Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China. ; Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Central Hospital, Nagoya, Japan. ; Department of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. ; Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Hwasun-eup, Republic of Korea. ; Department of Etiology & Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. ; Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong. ; Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan. ; Center for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Division of Epidemiology & Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. ; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. ; Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan. ; Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan. ; Department of Pathology, National Cancer Center Hospital, Tokyo, Japan. ; Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan. ; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. ; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Kanagawa, Japan. ; Department of Thoracic Surgery, Kanagawa Cancer Center, Kanagawa, Japan. ; Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center, Chiba, Japan. ; Department of Thoracic Surgery, National Cancer Center Hospital East, Chiba, Japan. ; Department of Thoracic Oncology, National Cancer Center Hospital East, Japan. ; Department of Cellular and Organ Pathology. ; Department of Thoracic Surgery, Graduate School of Medicine, Akita University, Akita City, Japan. ; Department of Integrative Center of General Surgery, Gunma University Hospital, Gunma, Japan. ; Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. ; China National Environmental Monitoring Center, Beijing, People's Republic of China. ; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. ; Department of Internal Medicine, Division of Oncology/Hematology, College of Medicine, Korea University Anam Hospital, Seoul, Republic of Korea. ; Department of Clinical Oncology, The University of Hong Kong, Queen Mary Hospital, Hong Kong. ; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. ; Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. ; School of Medicine, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan. ; Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. ; Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. ; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. ; Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People's Republic of China. ; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore. ; Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea. ; Genomic Research Center, Academia Sinica, Taipei, Taiwan. ; Department of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. ; Cancer Research Center, Kyungpook National University Medical Center, Daegu, Republic of Korea. ; Division of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan. ; Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China. ; The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. ; Westat, Rockville, MD, USA. ; Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China. ; Department of Health Sciences Research. ; Cancer Prevention Institute of California, Fremont, CA, USA. ; Department of Thoracic and Cardiovascular Surgery, Seoul St Mary's Hospital, The Catholic University of Korea, Republic of Korea. ; Department of Oncology, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan, People's Republic of China. ; Ministry of Education Key Laboratory of Modern Toxicology. ; Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. ; School of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. ; Department of Pulmonary and Critical Care, Chang Gung Memorial Hospital, Taoyuan, Taiwan. ; Department of Surgery, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. ; Division of Medical Oncology, Department of Internal Medicine, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea. ; Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. ; Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, People's Republic of China. ; Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan. ; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. ; Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands. ; Agency for Integrated Care, Singapore. ; Department of Pathology, Queen Elizabeth Hospital, Hong Kong, People's Republic of China. ; Qujing Center for Diseases Control and Prevention, Qujing, People's Republic of China. ; Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, People's Republic of China. ; Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan. ; Shanghai Pulmonary Hospital, Shanghai, People's Republic of China. ; Laboratory Services, American Cancer Society, Atlanta, GA, USA. ; Department of Surgery, Department of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Y1 - 2016/12/26/ PY - 2016 DA - 2016 Dec 26 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1853363032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=Association+between+GWAS-identified+lung+adenocarcinoma+susceptibility+loci+and+EGFR+mutations+in+never-smoking+Asian+women%2C+and+comparison+with+findings+from+Western+populations.&rft.au=Seow%2C+Wei+Jie%3BMatsuo%2C+Keitaro%3BHsiung%2C+Chao+Agnes%3BShiraishi%2C+Kouya%3BSong%2C+Minsun%3BKim%2C+Hee+Nam%3BWong%2C+Maria+Pik%3BHong%2C+Yun-Chul%3BHosgood%2C+H+Dean%3BWang%2C+Zhaoming%3BChang%2C+I-Shou%3BWang%2C+Jiu-Cun%3BChatterjee%2C+Nilanjan%3BTucker%2C+Margaret%3BWei%2C+Hu%3BMitsudomi%2C+Tetsuya%3BZheng%2C+Wei%3BKim%2C+Jin+Hee%3BZhou%2C+Baosen%3BCaporaso%2C+Neil+E%3BAlbanes%2C+Demetrius%3BShin%2C+Min-Ho%3BChung%2C+Lap+Ping%3BAn%2C+She-Juan%3BWang%2C+Ping%3BZheng%2C+Hong%3BYatabe%2C+Yasushi%3BZhang%2C+Xu-Chao%3BKim%2C+Young+Tae%3BShu%2C+Xiao-Ou%3BKim%2C+Young-Chul%3BBassig%2C+Bryan+A%3BChang%2C+Jiang%3BHo%2C+James+Chung+Man%3BJi%2C+Bu-Tian%3BKubo%2C+Michiaki%3BDaigo%2C+Yataro%3BIto%2C+Hidemi%3BMomozawa%2C+Yukihide%3BAshikawa%2C+Kyota%3BKamatani%2C+Yoichiro%3BHonda%2C+Takayuki%3BSakamoto%2C+Hiromi%3BKunitoh%2C+Hideo%3BTsuta%2C+Koji%3BWatanabe%2C+Shun-Ichi%3BNokihara%2C+Hiroshi%3BMiyagi%2C+Yohei%3BNakayama%2C+Haruhiko%3BMatsumoto%2C+Shingo%3BTsuboi%2C+Masahiro%3BGoto%2C+Koichi%3BYin%2C+Zhihua%3BShi%2C+Jianxin%3BTakahashi%2C+Atsushi%3BGoto%2C+Akiteru%3BMinamiya%2C+Yoshihiro%3BShimizu%2C+Kimihiro%3BTanaka%2C+Kazumi%3BWu%2C+Tangchun%3BWei%2C+Fusheng%3BWong%2C+Jason+Y+Y%3BMatsuda%2C+Fumihiko%3BSu%2C+Jian%3BKim%2C+Yeul+Hong%3BOh%2C+In-Jae%3BSong%2C+Fengju%3BLee%2C+Victor+Ho+Fun%3BSu%2C+Wu-Chou%3BChen%2C+Yuh-Min%3BChang%2C+Gee-Chen%3BChen%2C+Kuan-Yu%3BHuang%2C+Ming-Shyan%3BYang%2C+Pan-Chyr%3BLin%2C+Hsien-Chih%3BXiang%2C+Yong-Bing%3BSeow%2C+Adeline%3BPark%2C+Jae+Yong%3BKweon%2C+Sun-Seog%3BChen%2C+Chien-Jen%3BLi%2C+Haixin%3BGao%2C+Yu-Tang%3BWu%2C+Chen%3BQian%2C+Biyun%3BLu%2C+Daru%3BLiu%2C+Jianjun%3BJeon%2C+Hyo-Sung%3BHsiao%2C+Chin-Fu%3BSung%2C+Jae+Sook%3BTsai%2C+Ying-Huang%3BJung%2C+Yoo+Jin%3BGuo%2C+Huan%3BHu%2C+Zhibin%3BWang%2C+Wen-Chang%3BChung%2C+Charles+C%3BLawrence%2C+Charles%3BBurdett%2C+Laurie%3BYeager%2C+Meredith%3BJacobs%2C+Kevin+B%3BHutchinson%2C+Amy%3BBerndt%2C+Sonja+I%3BHe%2C+Xingzhou%3BWu%2C+Wei%3BWang%2C+Junwen%3BLi%2C+Yuqing%3BChoi%2C+Jin+Eun%3BPark%2C+Kyong+Hwa%3BSung%2C+Sook+Whan%3BLiu%2C+Li%3BKang%2C+Chang+Hyun%3BHu%2C+Lingmin%3BChen%2C+Chung-Hsing%3BYang%2C+Tsung-Ying%3BXu%2C+Jun%3BGuan%2C+Peng%3BTan%2C+Wen%3BWang%2C+Chih-Liang%3BSihoe%2C+Alan+Dart+Loon%3BChen%2C+Ying%3BChoi%2C+Yi+Young%3BHung%2C+Jen-Yu%3BKim%2C+Jun+Suk%3BYoon%2C+Ho-Il%3BCai%2C+Qiuyin%3BLin%2C+Chien-Chung%3BPark%2C+In+Kyu%3BXu%2C+Ping%3BDong%2C+Jing%3BKim%2C+Christopher%3BHe%2C+Qincheng%3BPerng%2C+Reury-Perng%3BChen%2C+Chih-Yi%3BVermeulen%2C+Roel%3BWu%2C+Junjie%3BLim%2C+Wei-Yen%3BChen%2C+Kun-Chieh%3BChan%2C+John+K+C%3BChu%2C+Minjie%3BLi%2C+Yao-Jen%3BLi%2C+Jihua%3BChen%2C+Hongyan%3BYu%2C+Chong-Jen%3BJin%2C+Li%3BLo%2C+Yen-Li%3BChen%2C+Ying-Hsiang%3BFraumeni%2C+Joseph+F%3BLiu%2C+Jie%3BYamaji%2C+Taiki%3BYang%2C+Yang%3BHicks%2C+Belynda%3BWyatt%2C+Kathleen%3BLi%2C+Shengchao+A%3BDai%2C+Juncheng%3BMa%2C+Hongxia%3BJin%2C+Guangfu%3BSong%2C+Bao%3BWang%2C+Zhehai%3BCheng%2C+Sensen%3BLi%2C+Xuelian%3BRen%2C+Yangwu%3BCui%2C+Ping%3BIwasaki%2C+Motoki%3BShimazu%2C+Taichi%3BTsugane%2C+Shoichiro%3BZhu%2C+Junjie%3BJiang%2C+Gening%3BFei%2C+Ke%3BWu%2C+Guoping%3BChien%2C+Li-Hsin%3BChen%2C+Hui-Ling%3BSu%2C+Yu-Chun%3BTsai%2C+Fang-Yu%3BChen%2C+Yi-Song%3BYu%2C+Jinming%3BStevens%2C+Victoria+L%3BLaird-Offringa%2C+Ite+A%3BMarconett%2C+Crystal+N%3BLin%2C+Dongxin%3BChen%2C+Kexin%3BWu%2C+Yi-Long%3BLandi%2C+Maria+Teresa%3BShen%2C+Hongbing%3BRothman%2C+Nathaniel%3BKohno%2C+Takashi%3BChanock%2C+Stephen+J%3BLan%2C+Qing&rft.aulast=Seow&rft.aufirst=Wei&rft.date=2016-12-26&rft.volume=&rft.issue=&rft.spage=e20&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/10.1093%2Fnar%2Fgkv907 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-27 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1093/hmg/ddw414 ER - TY - JOUR T1 - Production and quality control assessment of a GLP-grade immunotoxin, D2C7-(scdsFv)-PE38KDEL, for a phase I/II clinical trial. AN - 1859755533; 28013405 AB - D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel recombinant Pseudomonas exotoxin A-based immunotoxin (IT), targeting both wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins overexpressed in glioblastomas. Initial pre-clinical testing demonstrated the anti-tumor efficacy of D2C7-IT against orthotopic glioblastoma xenograft models expressing EGFRwt, EGFRvIII, or both EGFRwt and EGFRvIII. A good laboratory practice (GLP) manufacturing process was developed to produce sufficient material for a phase I/II clinical trial. D2C7-IT was expressed under the control of the T7 promoter in Escherichia coli BLR (λ DE3). D2C7-IT was produced by a 10-L batch fermentation process and was then purified from inclusion bodies using anion exchange, size exclusion, and an endotoxin removal process that achieved a yield of over 300 mg of purified protein. The final vialed batch of D2C7-IT for clinical testing was at a concentration of 0.12 ± 0.1 mg/mL, the pH was at 7.4 ± 0.4, and endotoxin levels were below the detection limit of 10 EU/mL (1.26 EU/mL). The stability of the vialed D2C7-IT has been monitored over a period of 42 months through protein concentration, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing, size exclusion chromatography, cytotoxicity, sterility, and pH measurements. The vialed D2C7-IT is currently being tested in a phase I/II clinical trial by intratumoral convection-enhanced delivery for 72 h in patients with recurrent glioblastoma (NCT02303678, D2C7 for Adult Patients with Recurrent Malignant Glioma; clinicaltrials.gov ). JF - Applied microbiology and biotechnology AU - Chandramohan, Vidyalakshmi AU - Pegram, Charles N AU - Piao, Hailan AU - Szafranski, Scott E AU - Kuan, Chien-Tsun AU - Pastan, Ira H AU - Bigner, Darell D AD - Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC, USA. vidyalakshmi.chandramohan@duke.edu. ; Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC, USA. ; Center for Cancer Research, National Cancer Institute, Building 37, Room 5106, Bethesda, MD, 20892, USA. Y1 - 2016/12/24/ PY - 2016 DA - 2016 Dec 24 KW - Recombinant immunotoxin KW - Malignant glioma KW - Epidermal growth factor receptor KW - Mutant EGFR variant III KW - Good laboratory practice UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859755533?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+microbiology+and+biotechnology&rft.atitle=Production+and+quality+control+assessment+of+a+GLP-grade+immunotoxin%2C+D2C7-%28scdsFv%29-PE38KDEL%2C+for+a+phase+I%2FII+clinical+trial.&rft.au=Chandramohan%2C+Vidyalakshmi%3BPegram%2C+Charles+N%3BPiao%2C+Hailan%3BSzafranski%2C+Scott+E%3BKuan%2C+Chien-Tsun%3BPastan%2C+Ira+H%3BBigner%2C+Darell+D&rft.aulast=Chandramohan&rft.aufirst=Vidyalakshmi&rft.date=2016-12-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Applied+microbiology+and+biotechnology&rft.issn=1432-0614&rft_id=info:doi/10.1007%2Fs00253-016-8063-x LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s00253-016-8063-x ER - TY - JOUR T1 - TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice. AN - 1852786578; 28012173 AB - Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the brain-derived neurotrophic factor (BDNF)/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine-induced status epilepticus (SE). The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3-selective inhibitor Pyr3. Video and electroencephalography (EEG) recording of pilocarpine-induced seizures were performed. We found that genetic ablation of TRPC3 channels reduces behavioral manifestations of seizures and the root-mean-square (RMS) power of SE, indicating a significant contribution of TRPC3 channels to pilocarpine-induced SE. Furthermore, the reduction in SE in TRPC3KO mice is caused by a selective attenuation of pilocarpine-induced theta activity, which dominates both the preictal phase and SE phase. Pyr3 also caused a reduction in the overall RMS power of pilocarpine-induced SE and a selective reduction in the theta activity during SE. Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anticonvulsive drugs. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy. JF - Epilepsia AU - Phelan, Kevin D AU - Shwe, U Thaung AU - Cozart, Michael A AU - Wu, Hong AU - Mock, Matthew M AU - Abramowitz, Joel AU - Birnbaumer, Lutz AU - Zheng, Fang AD - Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A. ; Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A. ; Neurobiology Laboratory, National Institute of Environmental Health Sciences, Durham, North Carolina, U.S.A. Y1 - 2016/12/24/ PY - 2016 DA - 2016 Dec 24 KW - Beta rhythm KW - Transient receptor potential channels KW - Seizures KW - Electroencephalography KW - Spectral analysis KW - Gamma rhythm UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852786578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsia&rft.atitle=TRPC3+channels+play+a+critical+role+in+the+theta+component+of+pilocarpine-induced+status+epilepticus+in+mice.&rft.au=Phelan%2C+Kevin+D%3BShwe%2C+U+Thaung%3BCozart%2C+Michael+A%3BWu%2C+Hong%3BMock%2C+Matthew+M%3BAbramowitz%2C+Joel%3BBirnbaumer%2C+Lutz%3BZheng%2C+Fang&rft.aulast=Phelan&rft.aufirst=Kevin&rft.date=2016-12-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Epilepsia&rft.issn=1528-1167&rft_id=info:doi/10.1111%2Fepi.13648 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/epi.13648 ER - TY - JOUR T1 - Modulation of cell death in human colorectal and breast cancer cells through a manganese chelate by involving GSH with intracellular p53 status. AN - 1852786717; 28012015 AB - Chemotherapy is central to current treatment modality especially for advanced and metastatic colorectal and breast cancers. Targeting the key molecular events of the neoplastic cells may open a possibility to treat cancer. Although some improvements in understanding of colorectal and breast cancer treatment have been recorded, the involvement of glutathione (GSH) and dependency of p53 status on the modulation of GSH-mediated treatment efficacy have been largely overlooked. Herein, we tried to decipher the underlying mechanism of the action of Mn-N-(2-hydroxyacetophenone) glycinate (MnNG) against differential p53 status bearing Hct116, MCF-7, and MDA-MB-468 cells on the backdrop of intracellular GSH level and reveal the role of p53 status in modulating GSH-dependant abrogation of MnNG-induced apoptosis in these cancer cells. Present study discloses that MnNG targets specifically wild-type-p53 expressing Hct116 and MCF-7 cells by significantly depleting both cytosolic, mitochondrial GSH, and modulating nuclear GSH through Glutathione reductase and Glutamate-cysteine ligase depletion that may in turn induce p53-mediated intrinsic apoptosis in them. Thus GSH addition abrogates p53-mediated apoptosis in wild-type-p53 expressing cells. GSH addition also overrides MnNG-induced modulation of phase II detoxifying parameters in them. However, GSH addition partially replenishes the down-regulated or modulated GSH pool in cytosol, mitochondria, and nucleus, and relatively abrogates MnNG-induced intrinsic apoptosis in p53-mutated MDA-MB-468 cells. On the contrary, although MnNG induces significant cell death in p53-null Hct116 cells, GSH addition fails to negate MnNG-induced cell death. Thus p53 status with intracellular GSH is critical for the modulation of MnNG-induced apoptosis. JF - Molecular and cellular biochemistry AU - Banerjee, Kaushik AU - Das, Satyajit AU - Majumder, Saikat AU - Majumdar, Subrata AU - Biswas, Jaydip AU - Choudhuri, Soumitra Kumar AD - Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700 026, India. ; Division of Molecular Medicine, Bose Institute, Kolkata, India. ; Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700 026, India. soumitra01@yahoo.com. Y1 - 2016/12/23/ PY - 2016 DA - 2016 Dec 23 KW - p53 KW - Apoptosis KW - Glutathione KW - Schiff-based manganese complex KW - Colorectal and breast cancer KW - Phase II detoxifying enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852786717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biochemistry&rft.atitle=Modulation+of+cell+death+in+human+colorectal+and+breast+cancer+cells+through+a+manganese+chelate+by+involving+GSH+with+intracellular+p53+status.&rft.au=Banerjee%2C+Kaushik%3BDas%2C+Satyajit%3BMajumder%2C+Saikat%3BMajumdar%2C+Subrata%3BBiswas%2C+Jaydip%3BChoudhuri%2C+Soumitra+Kumar&rft.aulast=Banerjee&rft.aufirst=Kaushik&rft.date=2016-12-23&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biochemistry&rft.issn=1573-4919&rft_id=info:doi/10.1007%2Fs11010-016-2896-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s11010-016-2896-6 ER - TY - JOUR T1 - Rare copy number variants in a population-based investigation of hypoplastic right heart syndrome. AN - 1852784515; 28009100 AB - Hypoplastic right heart syndrome (HRHS) is a rare congenital defect characterized by underdevelopment of the right heart structures commonly accompanied by an atrial septal defect. Familial HRHS reports suggest genetic factor involvement. We examined the role of copy number variants (CNVs) in HRHS. We genotyped 32 HRHS cases identified from all New York State live births (1998-2005) using Illumina HumanOmni2.5 microarrays. CNVs were called with PennCNV and prioritized if they were ≥20 Kb, contained ≥10 SNPs and had minimal overlap with CNVs from in-house controls, the Database of Genomic Variants, HapMap3, and Childrens Hospital of Philadelphia database. We identified 28 CNVs in 17 cases; several encompassed genes important for right heart development. One case had a 2p16-2p23 duplication spanning LBH, a limb and heart development transcription factor. Lbh mis-expression results in right ventricular hypoplasia and pulmonary valve defects. This duplication also encompassed SOS1, a factor associated with pulmonary valve stenosis in Noonan syndrome. Sos1-/- mice display thin and poorly trabeculated ventricles. In another case, we identified a 1.5 Mb deletion associated with Williams-Beuren syndrome, a disorder that includes valvular malformations. A third case had a 24 Kb deletion upstream of the TGFβ ligand ITGB8. Embryos genetically null for Itgb8, and its intracellular interactant Band 4.1B, display lethal cardiac phenotypes. To our knowledge, this is the first study of CNVs in HRHS. We identified several rare CNVs that overlap genes related to right ventricular wall and valve development, suggesting that genetics plays a role in HRHS and providing clues for further investigation. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. JF - Birth defects research. Part A, Clinical and molecular teratology AU - Dimopoulos, Aggeliki AU - Sicko, Robert J AU - Kay, Denise M AU - Rigler, Shannon L AU - Druschel, Charlotte M AU - Caggana, Michele AU - Browne, Marilyn L AU - Fan, Ruzong AU - Romitti, Paul A AU - Brody, Lawrence C AU - Mills, James L AD - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. ; Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York. ; Congenital Malformations Registry, New York State Department of Health, Albany, New York. ; Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, Iowa. ; Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 2016/12/23/ PY - 2016 DA - 2016 Dec 23 KW - hypoplastic right ventricle KW - LBH KW - hypoplastic right heart KW - ITGB8 KW - SOS1 KW - copy number variants KW - PRRX2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852784515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Birth+defects+research.+Part+A%2C+Clinical+and+molecular+teratology&rft.atitle=Rare+copy+number+variants+in+a+population-based+investigation+of+hypoplastic+right+heart+syndrome.&rft.au=Dimopoulos%2C+Aggeliki%3BSicko%2C+Robert+J%3BKay%2C+Denise+M%3BRigler%2C+Shannon+L%3BDruschel%2C+Charlotte+M%3BCaggana%2C+Michele%3BBrowne%2C+Marilyn+L%3BFan%2C+Ruzong%3BRomitti%2C+Paul+A%3BBrody%2C+Lawrence+C%3BMills%2C+James+L&rft.aulast=Dimopoulos&rft.aufirst=Aggeliki&rft.date=2016-12-23&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Birth+defects+research.+Part+A%2C+Clinical+and+molecular+teratology&rft.issn=1542-0760&rft_id=info:doi/10.1002%2Fbdra.23586 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/bdra.23586 ER - TY - JOUR T1 - Prediction of hERG Liability - Using SVM Classification, Bootstrapping and Jackknifing. AN - 1851297998; 28000393 AB - Drug-induced QT prolongation leads to life-threatening cardiotoxicity, mostly through blockage of the human ether-à-go-go-related gene (hERG) encoded potassium ion (K+ ) channels. The hERG channel is one of the most important antitargets to be addressed in the early stage of drug discovery process, in order to avoid more costly failures in the development phase. Using a thallium flux assay, 4,323 molecules were screened for hERG channel inhibition in a quantitative high throughput screening (qHTS) format. Here, we present support vector classification (SVC) models of hERG channel inhibition with the averaged area under the receiver operator characteristics curve (AUC-ROC) of 0.93 for the tested compounds. Both Jackknifing and bootstrapping have been employed to rebalance the heavily biased training datasets, and the impact of these two under-sampling rebalance methods on the performance of the predictive models is discussed. Our results indicated that the rebalancing techniques did not enhance the predictive power of the resulting models; instead, adoption of optimal cutoffs could restore the desirable balance of sensitivity and specificity of the binary classifiers. In an external validation set of 66 drug molecules, the SVC model exhibited an AUC-ROC of 0.86, further demonstrating the utility of this modeling approach to predict hERG liabilities. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. JF - Molecular informatics AU - Sun, Hongmao AU - Huang, Ruili AU - Xia, Menghang AU - Shahane, Sampada AU - Southall, Noel AU - Wang, Yuhong AD - National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2016/12/21/ PY - 2016 DA - 2016 Dec 21 KW - bootstrap KW - ROC KW - support vector classification KW - hERG KW - jackknife KW - rebalance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851297998?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+informatics&rft.atitle=Prediction+of+hERG+Liability+-+Using+SVM+Classification%2C+Bootstrapping+and+Jackknifing.&rft.au=Sun%2C+Hongmao%3BHuang%2C+Ruili%3BXia%2C+Menghang%3BShahane%2C+Sampada%3BSouthall%2C+Noel%3BWang%2C+Yuhong&rft.aulast=Sun&rft.aufirst=Hongmao&rft.date=2016-12-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Molecular+informatics&rft.issn=1868-1751&rft_id=info:doi/10.1002%2Fminf.201600126 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/minf.201600126 ER - TY - JOUR T1 - Peroxisome proliferator-activated receptor-β/δ inhibits human neuroblastoma cell tumorigenesis by inducing p53- and SOX2-mediated cell differentiation. AN - 1851298646; 27996177 AB - Neuroblastoma is a common childhood cancer typically treated by inducing differentiation with retinoic acid (RA). Peroxisome proliferator-activated receptor-β/δ, (PPARβ/δ) is known to promote terminal differentiation of many cell types. In the present study, PPARβ/δ was over-expressed in three human neuroblastoma cell lines, NGP, SK-N-BE(2), and IMR-32, that exhibit high, medium, and low sensitivity, respectively, to retinoic acid-induced differentiation to determine if PPARβ/δ and retinoic acid receptors (RARs) could be jointly targeted to increase the efficacy of treatment. All-trans-RA (atRA) decreased expression of SRY (sex determining region Y)-box 2 (SOX2), a stem cell regulator and marker of de-differentiation, in NGP and SK-N-BE(2) cells with inactive or mutant tumor suppressor p53, respectively. However, atRA did not suppress SOX2 expression in IMR-32 cells carrying wild-type p53. Over-expression and/or ligand activation of PPARβ/δ reduced the average volume and weight of ectopic tumor xenografts from NGP, SK-N-BE(2), or IMR-32 cells compared to controls. Compared with that found with atRA, PPARβ/δ suppressed SOX2 expression in NGP and SK-N-BE(2) cells and ectopic xenografts, and was also effective in suppressing SOX2 expression in IMR-32 cells that exhibit higher p53 expression compared to the former cell lines. Combined, these observations demonstrate that activating or over-expressing PPARβ/δ induces cell differentiation through p53- and SOX2-dependent signaling pathways in neuroblastoma cells and tumors. This suggests that combinatorial activation of both RARα and PPARβ/δ may be suitable as an alternative therapeutic approach for RA-resistant neuroblastoma patients. Published [2016]. This article is a U.S. Government work and is in the public domain in the USA. JF - Molecular carcinogenesis AU - Yao, Pei-Li AU - Chen, Liping AU - Dobrzański, Tomasz P AU - Zhu, Bokai AU - Kang, Boo-Hyon AU - Müller, Rolf AU - Gonzalez, Frank J AU - Peters, Jeffrey M AD - Department of Veterinary and Biomedical Sciences and The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania. ; Non-clinical Research Institute, Chemon, Jeil-Ri, Yangji-Myeon, Cheoin-Gu, Yongin-Si, Gyeonggi-Do, Korea. ; Institute of Molecular Biology and Tumor Research, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany. ; Laboratory of Metabolism, National Cancer Institute, Bethesda, Maryland. Y1 - 2016/12/20/ PY - 2016 DA - 2016 Dec 20 KW - p53 KW - peroxisome proliferator-activated receptor-β/δ KW - SOX2 KW - neuroblastoma KW - retinoid acid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851298646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Peroxisome+proliferator-activated+receptor-%CE%B2%2F%CE%B4+inhibits+human+neuroblastoma+cell+tumorigenesis+by+inducing+p53-+and+SOX2-mediated+cell+differentiation.&rft.au=Yao%2C+Pei-Li%3BChen%2C+Liping%3BDobrza%C5%84ski%2C+Tomasz+P%3BZhu%2C+Bokai%3BKang%2C+Boo-Hyon%3BM%C3%BCller%2C+Rolf%3BGonzalez%2C+Frank+J%3BPeters%2C+Jeffrey+M&rft.aulast=Yao&rft.aufirst=Pei-Li&rft.date=2016-12-20&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=1098-2744&rft_id=info:doi/10.1002%2Fmc.22607 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-20 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1002/mc.22607 ER - TY - JOUR T1 - Safety and Preclinical Efficacy of Aerosol Pioglitazone on Lung Adenoma Prevention in A/J Mice. AN - 1851302065; 27993834 AB - Pioglitazone is a PPARγ agonist commonly prescribed for the clinical treatment of diabetes. We sought to expand its use to lung cancer prevention in a benzo[a]pyrene (B[a]P) mouse model with direct lung delivery via inhalation. Initially, we conducted inhalational toxicity experiments with 0, 15, 50, 150, and 450 μg/kg body weight/day pioglitazone in 40 A/J mice. We examined the animals for any physical toxicity and bronchoalveolar lavage fluids for inflammatory and cytotoxicity markers. Doses up to and including 450 μg/kg bw/d failed to demonstrate toxicity with aerosol pioglitazone. For chemoprevention experiments, A/J mice were randomized to treatment groups of inhaled doses of 0, 50, 150, or 450 μg/kg bw/d pioglitazone 1 or 8 weeks after the last dose of B[a]P. For the early treatment group, we found up to 32% decrease in lung adenoma formation with 450 μg/kg bw/d pioglitazone. We repeated the treatments in a second late-stage experiment and found up to 44% decreases in lung adenoma formation in doses of pioglitazone of 150 and 450 μg/kg bw/day. Both the early- and the late-stage experiments demonstrated biologically relevant and statistically significant decreases in adenoma formation. We conclude that aerosol pioglitazone is well-tolerated in the A/J mouse model and a promising chemoprevention agent for the lower respiratory tract. Cancer Prev Res; 10(2); 1-9. ©2016 AACR. ©2016 American Association for Cancer Research. JF - Cancer prevention research (Philadelphia, Pa.) AU - Seabloom, Donna E AU - Galbraith, Arthur R AU - Haynes, Anna M AU - Antonides, Jennifer D AU - Wuertz, Beverly R AU - Miller, Wendy A AU - Miller, Kimberly A AU - Steele, Vernon E AU - Suen, Chen S AU - O'Sullivan, M Gerard AU - Ondrey, Frank G AD - AeroCore Inhalation Testing, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota. ; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. ; Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota. ; Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland. ; Comparative Pathology, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. ; AeroCore Inhalation Testing, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota. ondre002@umn.edu. Y1 - 2016/12/19/ PY - 2016 DA - 2016 Dec 19 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851302065?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+prevention+research+%28Philadelphia%2C+Pa.%29&rft.atitle=Safety+and+Preclinical+Efficacy+of+Aerosol+Pioglitazone+on+Lung+Adenoma+Prevention+in+A%2FJ+Mice.&rft.au=Seabloom%2C+Donna+E%3BGalbraith%2C+Arthur+R%3BHaynes%2C+Anna+M%3BAntonides%2C+Jennifer+D%3BWuertz%2C+Beverly+R%3BMiller%2C+Wendy+A%3BMiller%2C+Kimberly+A%3BSteele%2C+Vernon+E%3BSuen%2C+Chen+S%3BO%27Sullivan%2C+M+Gerard%3BOndrey%2C+Frank+G&rft.aulast=Seabloom&rft.aufirst=Donna&rft.date=2016-12-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Cancer+prevention+research+%28Philadelphia%2C+Pa.%29&rft.issn=1940-6215&rft_id=info:doi/10.1158%2F1940-6207.CAPR-16-0174 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-20 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1158/1940-6207.CAPR-16-0174 ER - TY - JOUR T1 - Split hand/foot malformation genetics supports the chromosome 7 copy segregation mechanism for human limb development AN - 1846406312; PQ0003860101 AB - Genetic aberrations of several unlinked loci cause human congenital split hand/foot malformation (SHFM) development. Mutations of the DLX5 (distal-less) transcription factor-encoding gene in chromosome 7 cause SHFM through haploinsufficiency, but the vast majority of cases result from heterozygous chromosomal aberrations of the region without mutating the DLX5 gene. To resolve this paradox, we invoke a chromosomal epigenetic mechanism for limb development. It is composed of a monochromatid gene expression phenomenon that we discovered in two fission yeasts with the selective chromosome copy segregation phenomenon that we discovered in mouse cells. Accordingly, one daughter cell inherits both expressed DLX5 copies while the other daughter inherits both epigenetically silenced ones from a single deterministic cell of the developing limb. Thus, differentiated daughter cells after further proliferation will correspondingly produce proximal/distal-limb tissues. Published results of a Chr. 7 translocation with a centromere-proximal breakpoint situated over 41 million bases away from the DLX locus, centromeric and DLX5-region inversions have satisfied key genetic and developmental biology predictions of the mechanism. Further genetic tests of the mechanism are proposed. We propose that the DNA double helical structure itself causes the development of sister cells' gene regulation asymmetry. We also argue against the conventionally invoked morphogen model of development.This article is part of the themed issue 'Provocative questions in left-right asymmetry'. JF - Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences AU - Klar, Amar JS AD - Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, Center for Cancer Research, National Institutes of Health, , Building 539, Room 154, Frederick, MD 21702-1201, USA, klara@mail.nih.gov Y1 - 2016/12/19/ PY - 2016 DA - 2016 Dec 19 SP - 20150415 PB - Royal Society of London, 6 Carlton House Terrace London SW1Y 5AG United Kingdom VL - 371 IS - 1710 SN - 0962-8436, 0962-8436 KW - Ecology Abstracts KW - limb development KW - human split hand/foot malformation KW - selective chromatid segregation mechanism KW - selective DNA strand segregation mechanism KW - asymmetric cell division mechanism KW - DNA chirality-based developmental mechanism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846406312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Philosophical+Transactions+of+the+Royal+Society+of+London%2C+Series+B%3A+Biological+Sciences&rft.atitle=Split+hand%2Ffoot+malformation+genetics+supports+the+chromosome+7+copy+segregation+mechanism+for+human+limb+development&rft.au=Klar%2C+Amar+JS&rft.aulast=Klar&rft.aufirst=Amar&rft.date=2016-12-19&rft.volume=371&rft.issue=1710&rft.spage=20150415&rft.isbn=&rft.btitle=&rft.title=Philosophical+Transactions+of+the+Royal+Society+of+London%2C+Series+B%3A+Biological+Sciences&rft.issn=09628436&rft_id=info:doi/10.1098%2Frstb.2015.0415 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-07 DO - http://dx.doi.org/10.1098/rstb.2015.0415 ER - TY - JOUR T1 - Inhibitors of Acetylcholinesterase Derived from 7-Methoxytacrine and Their Effects on the Choline Transporter CHT1. AN - 1851294782; 27988521 AB - Reversible acetylcholinesterase inhibitors are used in Alzheimer disease therapy. However, tacrine and its derivatives have severe side effects. Derivatives of the tacrine analogue 7-methoxytacrine (MEOTA) are less toxic. We evaluated new derivatives of 7-MEOTA (2 homodimers linked by 2 C4-C5 chains and 5 N-alkylated C4-C8 side chain derivatives) in vitro, using the rat hippocampal choline transporter CHT1. Some derivatives were effective inhibitors of rat acetylcholinesterase and comparable with 7-MEOTA. All derivatives were able to inhibit CHT1, probably via quaternary ammonium, and this interaction could be involved in the enhancement of their detrimental side effects and/or in the attenuation of their promising effects. Under conditions of disrupted lipid rafts, the unfavorable effects of some derivatives were weakened. Only tacrine was probably able to stereospecifically interact with the naturally occurring amyloid-β isoform and to simultaneously stimulate CHT1. Some derivatives, when coincubated with amyloid β, did not influence CHT1. All derivatives also increased the fluidity of the cortical membranes. The N-alkylated derivative of 7-MEOTA bearing from C4 side chains appears to be the most promising compound and should be evaluated in future in vivo research. © 2016 S. Karger AG, Basel. JF - Dementia and geriatric cognitive disorders AU - Kristofikova, Zdenka AU - Ricny, Jan AU - Soukup, Ondrej AU - Korabecny, Jan AU - Nepovimova, Eugenie AU - Kuca, Kamil AU - Ripova, Daniela AD - Alzheimer Disease Center, National Institute of Mental Health, Klecany, Czech Republic. Y1 - 2016/12/17/ PY - 2016 DA - 2016 Dec 17 SP - 45 EP - 58 VL - 43 IS - 1-2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851294782?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Dementia+and+geriatric+cognitive+disorders&rft.atitle=Inhibitors+of+Acetylcholinesterase+Derived+from+7-Methoxytacrine+and+Their+Effects+on+the+Choline+Transporter+CHT1.&rft.au=Kristofikova%2C+Zdenka%3BRicny%2C+Jan%3BSoukup%2C+Ondrej%3BKorabecny%2C+Jan%3BNepovimova%2C+Eugenie%3BKuca%2C+Kamil%3BRipova%2C+Daniela&rft.aulast=Kristofikova&rft.aufirst=Zdenka&rft.date=2016-12-17&rft.volume=43&rft.issue=1-2&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Dementia+and+geriatric+cognitive+disorders&rft.issn=1421-9824&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Risks of Serious Toxicities from Intermittent versus Continuous Androgen Deprivation Therapy for Advanced Prostate Cancer Patients: A Population-based Study. AN - 1851297756; 27993663 AB - Randomized trials have reported that intermittent androgen deprivation therapy (IADT) for patients with advanced prostate cancer (PCa) may improve sexual and physical functioning compared to continuous ADT (CADT) without compromising survival. It is unknown whether IADT alters the risk of serious toxicities associated with CADT. We conducted a population-based cohort study of 9,772 men aged 66 or older diagnosed with advanced PCa from 2002-2011 treated with ADT. We classified men as receiving IADT if they had at least one 90-day gap between the completion of an ADT therapeutic duration and the start of the following one, and had doctor visits or PSA testing during the gap. Outcomes included acute myocardial infarction (AMI), stroke, heart failure (HF), type-2-diabetes, and fracture. We used Cox-proportional hazard models to estimate hazard ratios (HRs) for the comparative risk between IADT and CADT of serious toxicities. A total of 2,113 (22%), 769 (9%), and 899 (9%) men had a new cardiovascular event, diabetes, or fracture, respectively, within 5 years of starting ADT. Compared to the CADT group, the IADT group showed lower risk of serious cardiovascular events (HR= 0.64, 95% confidence interval [CI]=0.53-0.77, p<0.0001), particularly in reducing the risk of HF (HR=0.62, 95% CI=0.49-0.78, p<0.0001) and fracture (HR=0.52, 95%CI= 0.38, 0.70, p<0.0001). IADT was associated with lower risk of HF and fracture compared to CADT, raising toxicity concerns for CADT relative to IADT and suggesting that IADT may represent a safer therapeutic choice in elderly men with advanced PCa. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved. JF - The Journal of urology AU - Tsai, Huei-Ting AU - Pfeiffer, Ruth M AU - Philips, George K AU - Barac, Ana AU - Fu, Alex Z AU - Penson, David F AU - Zhou, Yingjun AU - Potosky, Arnold L AD - Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington D.C., USA. ; National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. ; Department of Medicine, Georgetown University Medical Center, Georgetown University, Washington D.C., USA. ; Division of Cardiology, MedStar Washington Hospital Center, Washington DC, United States. ; Department of Urologic Surgery, Vanderbilt University Medical Center. Y1 - 2016/12/16/ PY - 2016 DA - 2016 Dec 16 KW - comparative risk KW - intermittent androgen deprivation therapy KW - advanced prostate cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851297756?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Panitumumab+in+combination+with+gemcitabine+and+oxaliplatin+does+not+prolong+survival+in+wild-type+KRAS+advanced+biliary+tract+cancer%3A+A+randomized+phase+2+trial+%28Vecti-BIL+study%29.&rft.au=Leone%2C+Francesco%3BMarino%2C+Donatella%3BCereda%2C+Stefano%3BFilippi%2C+Roberto%3BBelli%2C+Carmen%3BSpadi%2C+Rosella%3BNasti%2C+Guglielmo%3BMontano%2C+Massimo%3BAmatu%2C+Alessio%3BAprile%2C+Giuseppe%3BCagnazzo%2C+Celeste%3BFasola%2C+Gianpiero%3BSiena%2C+Salvatore%3BCiuffreda%2C+Libero%3BReni%2C+Michele%3BAglietta%2C+Massimo&rft.aulast=Leone&rft.aufirst=Francesco&rft.date=2016-02-15&rft.volume=122&rft.issue=4&rft.spage=574&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=1097-0142&rft_id=info:doi/10.1002%2Fcncr.29778 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.juro.2016.12.022 ER - TY - JOUR T1 - mTOR Inhibition Mitigates Enhanced mRNA Translation Associated with the Metastatic Phenotype of Osteosarcoma Cells In Vivo AN - 1859483732; PQ0003994022 AB - Purpose: To successfully metastasize, tumor cells must respond appropriately to biological stressors encountered during metastatic progression. We sought to test the hypothesis that enhanced efficiency of mRNA translation during periods of metastatic stress is required for metastatic competence of osteosarcoma and that this metastasis-specific adaptation is amenable to therapeutic intervention.Experimental Design: We employ novel reporter and proteomic systems that enable tracking of mRNA translation efficiency and output in metastatic osteosarcoma cells as they colonize the lungs. We test the potential to target mRNA translation as an antimetastatic therapeutic strategy through pharmacokinetic studies and preclinical assessment of the prototypic mTOR inhibitor, rapamycin, across multiple models of metastasis.Results: Metastatic osteosarcoma cells translate mRNA more efficiently than nonmetastatic cells during critical stressful periods of metastatic colonization of the lung. Rapamycin inhibits translational output during periods of metastatic stress, mitigates lung colonization, and prolongs survival. mTOR-inhibiting exposures of rapamycin are achievable in mice using treatment schedules that correspond to human doses well below the MTDs defined in human patients, and as such are very likely to be tolerated over long exposures alone and in combination with other agents.Conclusions: Metastatic competence of osteosarcoma cells is dependent on efficient mRNA translation during stressful periods of metastatic progression, and the mTOR inhibitor, rapamycin, can mitigate this translation and inhibit metastasis in vivo. Our data suggest that mTOR pathway inhibitors should be reconsidered in the clinic using rationally designed dosing schedules and clinical metrics related to metastatic progression. Clin Cancer Res; 22(24); 6129-41. [copy2016 AACR. JF - Clinical Cancer Research AU - Morrow, James J AU - Mendoza, Arnulfo AU - Koyen, Allyson AU - Lizardo, Michael M AU - Ren, Ling AU - Waybright, Timothy J AU - Hansen, Ryan J AU - Gustafson, Daniel L AU - Zhou, Ming AU - Fan, Timothy M AU - Scacheri, Peter C AU - Khanna, Chand AD - Pediatric Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, ckhanna@ethosvet.com Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 6129 EP - 6141 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 24 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859483732?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=mTOR+Inhibition+Mitigates+Enhanced+mRNA+Translation+Associated+with+the+Metastatic+Phenotype+of+Osteosarcoma+Cells+In+Vivo&rft.au=Morrow%2C+James+J%3BMendoza%2C+Arnulfo%3BKoyen%2C+Allyson%3BLizardo%2C+Michael+M%3BRen%2C+Ling%3BWaybright%2C+Timothy+J%3BHansen%2C+Ryan+J%3BGustafson%2C+Daniel+L%3BZhou%2C+Ming%3BFan%2C+Timothy+M%3BScacheri%2C+Peter+C%3BKhanna%2C+Chand&rft.aulast=Morrow&rft.aufirst=James&rft.date=2016-12-15&rft.volume=22&rft.issue=24&rft.spage=6129&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0326 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0326 ER - TY - JOUR T1 - Endothelial Nitric Oxide Synthase Traffic Inducer (NOSTRIN) is a Negative Regulator of Disease Aggressiveness in Pancreatic Cancer AN - 1859482293; PQ0003994008 AB - Purpose: Pancreatic ductal adenocarcinoma (PDAC) is refractory to available treatments. Delineating critical pathways, responsible for disease aggressiveness and therapeutic resistance, may identify effective therapeutic targets. We aimed to identify key pathways contributing to disease aggressiveness by comparing gene expression profiles of tumors from early-stage PDAC cases with extremely poor survival ( less than or equal to 7 months) and those surviving 2 years or more following surgical resection.Experimental Design: Gene expression profiling was performed in tumors in a test cohort of PDAC (N = 50), which included short ( less than or equal to 7 months, N = 11) and long surviving ( greater than or equal to 2 years, N = 14) patients, using affymetrix GeneChip Human 1.0 ST array. Key genes associated with disease aggressiveness were identified, using Cox regression, Kaplan-Meier, and pathway analyses with validations in independent cohorts for mechanistic and functional analyses.Results: Gene expression profiling identified 1,820 differentially expressed genes between short and long survival groups with inflammatory gene network ranking first. Lower expression of endothelial nitric oxide synthase traffic inducer (NOSTRIN) was associated with worst survival indicating its potential inhibitory role in disease progression. NOSTRIN overexpression suppressed migration and invasion of pancreatic cancer cells and enhanced sensitivity to chemotherapeutic drug gemcitabine. NOSTRIN inhibited production of nitric oxide (NO) by suppressing the activation of endothelial nitric oxide synthase (eNOS). Furthermore, miR-221, bound to the 3'UTR of NOSTRIN and suppressed its expression, and an increased miR-221 expression associated with poor survival in PDAC.Conclusions: Our findings showed that NOSTRIN is a potential negative regulator of disease aggressiveness, which may be targeted for designing improved treatment strategy in PDAC. Clin Cancer Res; 22(24); 5992-6001. [copy2016 AACR. JF - Clinical Cancer Research AU - Wang, Jian AU - Yang, Shouhui AU - He, Peijun AU - Schetter, Aaron J AU - Gaedcke, Jochen AU - Ghadimi, BMichael AU - Ried, Thomas AU - Yfantis, Harris G AU - Lee, Dong H AU - Gaida, Matthias M AU - Hanna, Nader AU - Alexander, HRichard AU - Hussain, SPerwez AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, NCI, Bethesda, Maryland, hussainp@mail.nih.gov Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 5992 EP - 6001 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 24 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859482293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Endothelial+Nitric+Oxide+Synthase+Traffic+Inducer+%28NOSTRIN%29+is+a+Negative+Regulator+of+Disease+Aggressiveness+in+Pancreatic+Cancer&rft.au=Wang%2C+Jian%3BYang%2C+Shouhui%3BHe%2C+Peijun%3BSchetter%2C+Aaron+J%3BGaedcke%2C+Jochen%3BGhadimi%2C+BMichael%3BRied%2C+Thomas%3BYfantis%2C+Harris+G%3BLee%2C+Dong+H%3BGaida%2C+Matthias+M%3BHanna%2C+Nader%3BAlexander%2C+HRichard%3BHussain%2C+SPerwez&rft.aulast=Wang&rft.aufirst=Jian&rft.date=2016-12-15&rft.volume=22&rft.issue=24&rft.spage=5992&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0511 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0511 ER - TY - JOUR T1 - Targeting Estrogen Receptor Signaling with Fulvestrant Enhances Immune and Chemotherapy-Mediated Cytotoxicity of Human Lung Cancer AN - 1859481189; PQ0003994028 AB - Purpose: The conversion of tumor cells from an epithelial to a mesenchymal-like phenotype, via a process designated as the epithelial-mesenchymal transition (EMT), is known to mediate tumor resistance to a variety of cell death inducers, including cytotoxic effector immune cells. The goal of this study was to identify and potentially repurpose FDA-approved compounds capable of reducing mesenchymal features of human lung carcinoma cells, which could be used in combination with immunotherapies or chemotherapeutic strategies to improve clinical responses.Experimental Design: In the current report, we have utilized a quantitative high-throughput screening (qHTS) of a pharmaceutical collection of more than 2,000 compounds to identify clinically approved drugs capable of augmenting the sensitivity of mesenchymal-like, lung cancer cells to immune- and chemotherapy-mediated lysis, both in vitro and in vivo.Results: The estrogen receptor antagonist fulvestrant was shown to reduce mesenchymal features of lung carcinoma cells, resulting in tumor sensitization to the cytotoxic effect of antigen-specific T cells, natural killer (NK) effector cells, and chemotherapy both in vivo and in vitro.Conclusions: To our knowledge, this is the first report defining a potential role for estrogenic signaling in promoting tumor resistance to immune-mediated cytotoxicity and chemotherapy in lung cancer. Our data demonstrate a robust association between the acquisition of mesenchymal attributes, therapeutic resistance of lung carcinoma cells, and the expression of estrogen receptor 1 (ESR1), supporting further investigations on the role of estrogen signaling in lung cancer progression via the induction of EMT. Clin Cancer Res; 22(24); 6204-16. [copy2016 AACR. JF - Clinical Cancer Research AU - Hamilton, Duane H AU - Griner, Lesley Mathews AU - Keller, Jonathan M AU - Hu, Xin AU - Southall, Noel AU - Marugan, Juan AU - David, Justin M AU - Ferrer, Marc AU - Palena, Claudia AD - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, palenac@mail.nih.gov Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 6204 EP - 6216 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 24 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859481189?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Targeting+Estrogen+Receptor+Signaling+with+Fulvestrant+Enhances+Immune+and+Chemotherapy-Mediated+Cytotoxicity+of+Human+Lung+Cancer&rft.au=Hamilton%2C+Duane+H%3BGriner%2C+Lesley+Mathews%3BKeller%2C+Jonathan+M%3BHu%2C+Xin%3BSouthall%2C+Noel%3BMarugan%2C+Juan%3BDavid%2C+Justin+M%3BFerrer%2C+Marc%3BPalena%2C+Claudia&rft.aulast=Hamilton&rft.aufirst=Duane&rft.date=2016-12-15&rft.volume=22&rft.issue=24&rft.spage=6204&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-3059 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-3059 ER - TY - JOUR T1 - Minimally Toxic Dose of Lipopolysaccharide and α-Synuclein Oligomer Elicit Synergistic Dopaminergic Neurodegeneration: Role and Mechanism of Microglial NOX2 Activation. AN - 1852685149; 27975175 AB - The aim of this study is to investigate the role and mechanism of microglial NOX2 activation in minimally toxic dose of LPS and Syn-elicited synergistic dopaminergic neurodegeneration. NOX2+/+ and NOX2-/- mice and multiple primary cultures were treated with LPS and/or Syn in vivo and in vitro. Neuronal function and morphology were evaluated by uptake of related neurotransmitter and immunostaining with specific antibody. Levels of superoxide, intracellular reactive oxygen species, mRNA and protein of relevant molecules, and dopamine were detected. LPS and Syn synergistically induce selective and progressive dopaminergic neurodegeneration. Microglia are functionally and morphologically activated, contributing to synergistic dopaminergic neurotoxicity elicited by LPS and Syn. NOX2-/- mice are more resistant to synergistic neurotoxicity than NOX2+/+mice in vivo and in vitro, and NOX2 inhibitor protects against synergistic neurotoxicity through decreasing microglial superoxide production, illustrating a critical role of microglial NOX2. Microglial NOX2 is activated by LPS and Syn as mRNA and protein levels of NOX2 subunits P47and gp91 are enhanced. Molecules relevant to microglial NOX2 activation include PKC-σ, P38, ERK1/2, JNK, and NF-КBP50 as their mRNA and protein levels are elevated after treatment with LPS and Syn. Combination of exogenous and endogenous environmental factors with minimally toxic dose synergistically propagates dopaminergic neurodegeneration through activating microglial NOX2 and relevant signaling molecules, casting a new light for PD pathogenesis. JF - Molecular neurobiology AU - Zhang, Wei AU - Gao, Jun-Hua AU - Yan, Zhao-Fen AU - Huang, Xi-Yan AU - Guo, Peng AU - Sun, Li AU - Liu, Zhuo AU - Hu, Yang AU - Zuo, Li-Jun AU - Yu, Shu-Yang AU - Cao, Chen-Jie AU - Wang, Xiao-Min AU - Hong, Jau-Shyong AD - Department of Geriatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China. ttyyzw@163.com. ; Department of Neurology, Beijing Tiantian Hospital, Capital Medical University, Beijing, 100050, China. ; Department of Geriatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China. ; Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing, 100069, China. ; Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, Durham, NC, 27709, USA. Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 KW - Parkinson disease KW - Microglial activation KW - Synergistic KW - Dopaminergic neurodegeneration KW - α-Synuclein oligomer KW - Lipopolysaccharide KW - Environmental factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852685149?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+neurobiology&rft.atitle=Minimally+Toxic+Dose+of+Lipopolysaccharide+and+%CE%B1-Synuclein+Oligomer+Elicit+Synergistic+Dopaminergic+Neurodegeneration%3A+Role+and+Mechanism+of+Microglial+NOX2+Activation.&rft.au=Zhang%2C+Wei%3BGao%2C+Jun-Hua%3BYan%2C+Zhao-Fen%3BHuang%2C+Xi-Yan%3BGuo%2C+Peng%3BSun%2C+Li%3BLiu%2C+Zhuo%3BHu%2C+Yang%3BZuo%2C+Li-Jun%3BYu%2C+Shu-Yang%3BCao%2C+Chen-Jie%3BWang%2C+Xiao-Min%3BHong%2C+Jau-Shyong&rft.aulast=Zhang&rft.aufirst=Wei&rft.date=2016-12-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Molecular+neurobiology&rft.issn=1559-1182&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Effect of Selumetinib and MK-2206 vs Oxaliplatin and Fluorouracil in Patients With Metastatic Pancreatic Cancer After Prior Therapy: SWOG S1115 Study Randomized Clinical Trial. AN - 1852682595; 27978579 AB - KRAS mutations are common in pancreatic cancer, but directly targeting the KRAS protein has thus far been unsuccessful. The aim of this trial was to block the MEK and PI3K/AKT pathways downstream of the KRAS protein as an alternate treatment strategy to slow cancer growth and prolong survival. This was the first cooperative group trial to evaluate this strategy using molecularly targeted oral combination therapy for the treatment of chemotherapy-refractory pancreatic cancer. To compare selumetinib and MK-2206 vs modified FOLFOX (mFOLFOX) in patients with metastatic pancreatic cancer for whom gemcitabine-based therapy had failed. SWOG S1115 was a randomized phase 2 clinical trial. Between September 2012 and May 2014, 137 patients with metastatic pancreatic adenocarcinoma for whom gemcitabine-based chemotherapy had failed were randomized to selumetinib plus MK-2206 or mFOLFOX. Patients were randomized in a 1:1 fashion and stratified according to duration of prior systemic therapy and presence of liver metastases. Patients received selumetinib 100 mg orally per day plus MK-2206 135 mg orally once per week or mFOLFOX (oxaliplatin, 85 mg/m2 intravenous, and fluorouracil, 2400 mg/m2 intravenous infusion over 46-48 hours) on days 1 and 15 of a 28-day cycle. The primary end point of the study was overall survival. Secondary objectives included evaluating toxic effects, objective tumor response, and progression-free survival. There were 58 patients in the selumetinib plus MK-2206 (experimental) arm (60% male; median [range] age, 69 [54-88] years) and 62 patients in the mFOLFOX arm (35% male; median [range] age, 65 [34-82] years). In the experimental arm, median overall survival was shorter (3.9 vs 6.7 months; HR, 1.37; 95% CI, 0.90-2.08; P = .15), as was median progression-free survival (1.9 vs 2.0 months; HR, 1.61; 95% CI, 1.07-2.43; P = .02). One vs 5 patients had a partial response and 12 vs 14 patients had stable disease in the experimental arm vs mFOLFOX arm. Grade 3 or higher toxic effects were observed in 39 patients treated with selumetinib and MK-2206 vs 23 patients treated with mFOLFOX. More patients in the experimental arm discontinued therapy due to adverse events (13 vs 7 patients). Dual targeting of the MEK and PI3K/AKT pathways downstream of KRAS by selumetinib plus MK-2206 did not improve overall survival in patients with metastatic pancreatic adenocarcinoma for whom gemcitabine-based chemotherapy had failed. This was the first randomized prospective evaluation of mFOLFOX in the US population that showed comparable results to CONKO-003 and PANCREOX. clinicaltrials.gov: NCT01658943. JF - JAMA oncology AU - Chung, Vincent AU - McDonough, Shannon AU - Philip, Philip A AU - Cardin, Dana AU - Wang-Gillam, Andrea AU - Hui, Laifong AU - Tejani, Mohamedtaki A AU - Seery, Tara E AU - Dy, Irene A AU - Al Baghdadi, Tareq AU - Hendifar, Andrew E AU - Doyle, L Austin AU - Lowy, Andrew M AU - Guthrie, Katherine A AU - Blanke, Charles D AU - Hochster, Howard S AD - City of Hope National Medical Center, Duarte, California. ; SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington. ; Karmanos Cancer Institute, Wayne State University, Detroit, Michigan. ; Vanderbilt University Medical Center, Nashville, Tennessee. ; Washington University in St Louis, St Louis, Missouri. ; Kaiser Permanente NCORP, Sacramento, California. ; University of Rochester, Rochester, New York. ; University of California, Irvine, Orange. ; Crossroads Cancer Center/Heartland NCORP, Effingham, Illinois. ; St Joseph Mercy Hospital/Michigan CRC NCORP, Ann Arbor. ; Cedars-Sinai Medical Center, Los Angeles, California. ; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland. ; University of California, San Diego, La Jolla. ; SWOG Group Chair's Office/Knight Cancer Institute, Oregon Health and Science University, Portland. ; Yale Cancer Center, New Haven, Connecticut. Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852682595?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA+oncology&rft.atitle=Effect+of+Selumetinib+and+MK-2206+vs+Oxaliplatin+and+Fluorouracil+in+Patients+With+Metastatic+Pancreatic+Cancer+After+Prior+Therapy%3A+SWOG+S1115+Study+Randomized+Clinical+Trial.&rft.au=Chung%2C+Vincent%3BMcDonough%2C+Shannon%3BPhilip%2C+Philip+A%3BCardin%2C+Dana%3BWang-Gillam%2C+Andrea%3BHui%2C+Laifong%3BTejani%2C+Mohamedtaki+A%3BSeery%2C+Tara+E%3BDy%2C+Irene+A%3BAl+Baghdadi%2C+Tareq%3BHendifar%2C+Andrew+E%3BDoyle%2C+L+Austin%3BLowy%2C+Andrew+M%3BGuthrie%2C+Katherine+A%3BBlanke%2C+Charles+D%3BHochster%2C+Howard+S&rft.aulast=Chung&rft.aufirst=Vincent&rft.date=2016-12-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=JAMA+oncology&rft.issn=2374-2445&rft_id=info:doi/10.1001%2Fjamaoncol.2016.5383 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1001/jamaoncol.2016.5383 ER - TY - JOUR T1 - Rev1 is a base excision repair enzyme with 5'-deoxyribose phosphate lyase activity. AN - 1852657660; 27683219 AB - Rev1 is a member of the Y-family of DNA polymerases and is known for its deoxycytidyl transferase activity that incorporates dCMP into DNA and its ability to function as a scaffold factor for other Y-family polymerases in translesion bypass events. Rev1 also is involved in mutagenic processes during somatic hypermutation of immunoglobulin genes. In light of the mutation pattern consistent with dCMP insertion observed earlier in mouse fibroblast cells treated with a base excision repair-inducing agent, we questioned whether Rev1 could also be involved in base excision repair (BER). Here, we uncovered a weak 5'-deoxyribose phosphate (5'-dRP) lyase activity in mouse Rev1 and demonstrated the enzyme can mediate BER in vitro The full-length Rev1 protein and its catalytic core domain are similar in their ability to support BER in vitro The dRP lyase activity in both of these proteins was confirmed by NaBH4 reduction of the Schiff base intermediate and kinetics studies. Limited proteolysis, mass spectrometry and deletion analysis localized the dRP lyase active site to the C-terminal segment of Rev1's catalytic core domain. These results suggest that Rev1 could serve as a backup polymerase in BER and could potentially contribute to AID-initiated antibody diversification through this activity. Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US. JF - Nucleic acids research AU - Prasad, Rajendra AU - Poltoratsky, Vladimir AU - Hou, Esther W AU - Wilson, Samuel H AD - Genome Integrity and Structural Biology Laboratory, National Institutes of Health, NIEHS, 111 T.W. Alexander Drive, PO Box 12233, MD F3-01, Research Triangle Park, NC 27709, USA. ; Genome Integrity and Structural Biology Laboratory, National Institutes of Health, NIEHS, 111 T.W. Alexander Drive, PO Box 12233, MD F3-01, Research Triangle Park, NC 27709, USA wilson5@niehs.nih.gov. Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 10824 EP - 10833 VL - 44 IS - 22 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852657660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Rev1+is+a+base+excision+repair+enzyme+with+5%27-deoxyribose+phosphate+lyase+activity.&rft.au=Prasad%2C+Rajendra%3BPoltoratsky%2C+Vladimir%3BHou%2C+Esther+W%3BWilson%2C+Samuel+H&rft.aulast=Prasad&rft.aufirst=Rajendra&rft.date=2016-12-15&rft.volume=44&rft.issue=22&rft.spage=10824&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Antagonism of BST-2/Tetherin Is a Conserved Function of the Env Glycoprotein of Primary HIV-2 Isolates. AN - 1844608543; 27681141 AB - Although HIV-2 does not encode a vpu gene, the ability to antagonize bone marrow stromal antigen 2 (BST-2) is conserved in some HIV-2 isolates, where it is controlled by the Env glycoprotein. We previously reported that a single-amino-acid difference between the laboratory-adapted ROD10 and ROD14 Envs controlled the enhancement of virus release (referred to here as Vpu-like) activity. Here, we investigated how conserved the Vpu-like activity is in primary HIV-2 isolates. We found that half of the 34 tested primary HIV-2 Env isolates obtained from 7 different patients enhanced virus release. Interestingly, most HIV-2 patients harbored a mixed population of viruses containing or lacking Vpu-like activity. Vpu-like activity and Envelope functionality varied significantly among Env isolates; however, there was no direct correlation between these two functions, suggesting they evolved independently. In comparing the Env sequences from one HIV-2 patient, we found that similar to the ROD10/ROD14 Envs, a single-amino-acid change (T568I) in the ectodomain of the TM subunit was sufficient to confer Vpu-like activity to an inactive Env variant. Surprisingly, however, absence of Vpu-like activity was not correlated with absence of BST-2 interaction. Taken together, our data suggest that maintaining the ability to antagonize BST-2 is of functional relevance not only to HIV-1 but also to HIV-2 as well. Our data show that as with Vpu, binding of HIV-2 Env to BST-2 is important but not sufficient for antagonism. Finally, as observed previously, the Vpu-like activity in HIV-2 Env can be controlled by single-residue changes in the TM subunit. Lentiviruses such as HIV-1 and HIV-2 encode accessory proteins whose function is to overcome host restriction mechanisms. Vpu is a well-studied HIV-1 accessory protein that enhances virus release by antagonizing the host restriction factor BST-2. HIV-2 does not encode a vpu gene. Instead, the HIV-2 Env glycoprotein was found to antagonize BST-2 in some isolates. Here, we cloned multiple Env sequences from 7 HIV-2-infected patients and found that about half were able to antagonize BST-2. Importantly, most HIV-2 patients harbored a mixed population of viruses containing or lacking the ability to antagonize BST-2. In fact, in comparing Env sequences from one patient combined with site-directed mutagenesis, we were able to restore BST-2 antagonism to an inactive Env protein by a single-amino-acid change. Our data suggest that targeting BST-2 by HIV-2 Env is a dynamic process that can be regulated by simple changes in the Env sequence. Copyright © 2016, American Society for Microbiology. All Rights Reserved. JF - Journal of virology AU - Chen, Chia-Yen AU - Shingai, Masashi AU - Welbourn, Sarah AU - Martin, Malcolm A AU - Borrego, Pedro AU - Taveira, Nuno AU - Strebel, Klaus AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA. ; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal. ; Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA kstrebel@nih.gov. Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 11062 EP - 11074 VL - 90 IS - 24 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844608543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Antagonism+of+BST-2%2FTetherin+Is+a+Conserved+Function+of+the+Env+Glycoprotein+of+Primary+HIV-2+Isolates.&rft.au=Chen%2C+Chia-Yen%3BShingai%2C+Masashi%3BWelbourn%2C+Sarah%3BMartin%2C+Malcolm+A%3BBorrego%2C+Pedro%3BTaveira%2C+Nuno%3BStrebel%2C+Klaus&rft.aulast=Chen&rft.aufirst=Chia-Yen&rft.date=2016-12-15&rft.volume=90&rft.issue=24&rft.spage=11062&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=1098-5514&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - The complementary and divergent roles of uncoupling proteins 1 and 3 in thermoregulation. AN - 1841793417; 27647490 AB - Both uncoupling protein 1 (UCP1) and UCP3 are important for mammalian thermoregulation. UCP1 and UCP3 in brown adipose tissue mediate early and late phases of sympathomimetic thermogenesis, respectively. Lipopolysaccharide thermogenesis requires skeletal muscle UCP3 but not UCP1. Acute noradrenaline-induced hyperthermia requires UCP1 but not UCP3. Loss of both UCP1 and UCP3 accelerate the loss of body temperature compared to UCP1KO alone during acute cold exposure. Uncoupling protein 1 (UCP1) is the established mediator of brown adipose tissue-dependent thermogenesis. In contrast, the role of UCP3, expressed in both skeletal muscle and brown adipose tissue, in thermoregulatory physiology is less well understood. Here, we show that mice lacking UCP3 (UCP3KO) have impaired sympathomimetic (methamphetamine) and completely abrogated lipopolysaccharide (LPS) thermogenesis, but a normal response to noradrenaline. By comparison, UCP1 knockout (UCP1KO) mice exhibit blunted methamphetamine and fully inhibited noradrenaline thermogenesis, but an increased febrile response to LPS. We further establish that mice lacking both UCP1 and 3 (UCPDK) fail to show methamphetamine-induced hyperthermia, and have a markedly accelerated loss of body temperature and survival after cold exposure compared to UCP1KO mice. Finally, we show that skeletal muscle-specific human UCP3 expression is able to significantly rescue LPS, but not sympathomimetic thermogenesis blunted in UCP3KO mice. These studies identify UCP3 as an important mediator of physiological thermogenesis and support a renewed focus on targeting UCP3 in metabolic physiology. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society. JF - The Journal of physiology AU - Riley, Christopher L AU - Dao, Christine AU - Kenaston, M Alexander AU - Muto, Luigina AU - Kohno, Shohei AU - Nowinski, Sara M AU - Solmonson, Ashley D AU - Pfeiffer, Matthew AU - Sack, Michael N AU - Lu, Zhongping AU - Fiermonte, Giuseppe AU - Sprague, Jon E AU - Mills, Edward M AD - Department of Molecular Biosciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX, 78712, USA. ; Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX, 78712, USA. ; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Cosenza, Italy. ; Department of Biochemistry, The University of Utah, Salt Lake City, UT, 84112, USA. ; National Heart, Lung, and Blood Institute, Laboratory of Mitochondrial Biology and Metabolism, NIH, Bethesda, MD, 20892, USA. ; Cardiovascular and Pulmonary Branch and the Department of Biochemistry and Molecular Medicine, George Washington University, and the Veterans Affairs Medical Center, Washington, DC, 20422, 20052, USA. ; Department of Biosciences, Biotechnologies, and Biopharmaceutics and Center of Excellence in Comparative Genomics, University of Bari, 70125, Bari, Italy. ; The Ohio Attorney General's Center for the Future of Forensic Science, Bowling Green State University, Bowling Green, OH, 43403, USA. Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 7455 EP - 7464 VL - 594 IS - 24 KW - uncoupling protein KW - brown adipose tissue KW - LPS KW - sympathomimetic KW - skeletal muscle KW - methamphetamine KW - thermogenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841793417?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+physiology&rft.atitle=The+complementary+and+divergent+roles+of+uncoupling+proteins+1+and+3+in+thermoregulation.&rft.au=Riley%2C+Christopher+L%3BDao%2C+Christine%3BKenaston%2C+M+Alexander%3BMuto%2C+Luigina%3BKohno%2C+Shohei%3BNowinski%2C+Sara+M%3BSolmonson%2C+Ashley+D%3BPfeiffer%2C+Matthew%3BSack%2C+Michael+N%3BLu%2C+Zhongping%3BFiermonte%2C+Giuseppe%3BSprague%2C+Jon+E%3BMills%2C+Edward+M&rft.aulast=Riley&rft.aufirst=Christopher&rft.date=2016-12-15&rft.volume=594&rft.issue=24&rft.spage=7455&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+physiology&rft.issn=1469-7793&rft_id=info:doi/10.1113%2FJP272971 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1113/JP272971 ER - TY - JOUR T1 - PRMT5 is essential for the maintenance of chondrogenic progenitor cells in the limb bud. AN - 1839127850; 27827819 AB - During embryonic development, undifferentiated progenitor cells balance the generation of additional progenitor cells with differentiation. Within the developing limb, cartilage cells differentiate from mesodermal progenitors in an ordered process that results in the specification of the correct number of appropriately sized skeletal elements. The internal pathways by which these cells maintain an undifferentiated state while preserving their capacity to differentiate is unknown. Here, we report that the arginine methyltransferase PRMT5 has a crucial role in maintaining progenitor cells. Mouse embryonic buds lacking PRMT5 have severely truncated bones with wispy digits lacking joints. This novel phenotype is caused by widespread cell death that includes mesodermal progenitor cells that have begun to precociously differentiate into cartilage cells. We propose that PRMT5 maintains progenitor cells through its regulation of Bmp4 Intriguingly, adult and embryonic stem cells also require PRMT5 for maintaining pluripotency, suggesting that similar mechanisms might regulate lineage-restricted progenitor cells during organogenesis. © 2016. Published by The Company of Biologists Ltd. JF - Development (Cambridge, England) AU - Norrie, Jacqueline L AU - Li, Qiang AU - Co, Swanie AU - Huang, Bau-Lin AU - Ding, Ding AU - Uy, Jann C AU - Ji, Zhicheng AU - Mackem, Susan AU - Bedford, Mark T AU - Galli, Antonella AU - Ji, Hongkai AU - Vokes, Steven A AD - Department of Molecular Biosciences, University of Texas at Austin, 2500 Speedway Stop A4800, Austin, TX 78712, USA. ; Cancer and Developmental Biology Laboratory, CCR, NCI, Frederick, MD 21702, USA. ; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room E3638, Baltimore, MD 21205, USA. ; Department of Epigenetics & Molecular Carcinogenesis, M.D. Anderson Cancer Center, 1808 Park Road 1C (P.O. Box 389), Smithville, TX 78957, USA. ; Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. ; Department of Molecular Biosciences, University of Texas at Austin, 2500 Speedway Stop A4800, Austin, TX 78712, USA svokes@austin.utexas.edu. Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 4608 EP - 4619 VL - 143 IS - 24 KW - BMP4 KW - Progenitor cells KW - Limb development KW - PRMT5 KW - SOX9 KW - Chondrogenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839127850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=PRMT5+is+essential+for+the+maintenance+of+chondrogenic+progenitor+cells+in+the+limb+bud.&rft.au=Norrie%2C+Jacqueline+L%3BLi%2C+Qiang%3BCo%2C+Swanie%3BHuang%2C+Bau-Lin%3BDing%2C+Ding%3BUy%2C+Jann+C%3BJi%2C+Zhicheng%3BMackem%2C+Susan%3BBedford%2C+Mark+T%3BGalli%2C+Antonella%3BJi%2C+Hongkai%3BVokes%2C+Steven+A&rft.aulast=Norrie&rft.aufirst=Jacqueline&rft.date=2016-12-15&rft.volume=143&rft.issue=24&rft.spage=4608&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=1477-9129&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-09 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 ER - TY - JOUR T1 - Differential modulation of FXR activity by chlorophacinone and ivermectin analogs. AN - 1835538159; 27773686 AB - Chemicals that alter normal function of farnesoid X receptor (FXR) have been shown to affect the homeostasis of bile acids, glucose, and lipids. Several structural classes of environmental chemicals and drugs that modulated FXR transactivation were previously identified by quantitative high-throughput screening (qHTS) of the Tox21 10K chemical collection. In the present study, we validated the FXR antagonist activity of selected structural classes, including avermectin anthelmintics, dihydropyridine calcium channel blockers, 1,3-indandione rodenticides, and pyrethroid pesticides, using in vitro assay and quantitative structural-activity relationship (QSAR) analysis approaches. (Z)-Guggulsterone, chlorophacinone, ivermectin, and their analogs were profiled for their ability to alter CDCA-mediated FXR binding using a panel of 154 coregulator motifs and to induce or inhibit transactivation and coactivator recruitment activities of constitutive androstane receptor (CAR), liver X receptor alpha (LXRα), or pregnane X receptor (PXR). Our results showed that chlorophacinone and ivermectin had distinct modes of action (MOA) in modulating FXR-coregulator interactions and compound selectivity against the four aforementioned functionally-relevant nuclear receptors. These findings collectively provide mechanistic insights regarding compound activities against FXR and possible explanations for in vivo toxicological observations of chlorophacinone, ivermectin, and their analogs. Published by Elsevier Inc. JF - Toxicology and applied pharmacology AU - Hsu, Chia-Wen AU - Hsieh, Jui-Hua AU - Huang, Ruili AU - Pijnenburg, Dirk AU - Khuc, Thai AU - Hamm, Jon AU - Zhao, Jinghua AU - Lynch, Caitlin AU - van Beuningen, Rinie AU - Chang, Xiaoqing AU - Houtman, René AU - Xia, Menghang AD - NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA. ; National Toxicology Program, National Institutes of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. ; PamGene International B.V., Wolvenhoek 10, 5211 HH 's-Hertogenbosch, The Netherlands. ; Integrated Laboratory System, Inc., Morrisville, NC, USA. ; NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA. Electronic address: mxia@mail.nih.gov. Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 138 EP - 148 VL - 313 KW - Farnesoid X receptor KW - Nuclear receptor KW - Ivermetin KW - Diphacinone KW - Tox21 KW - Chlorophacinone KW - Moxidectin UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835538159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Differential+modulation+of+FXR+activity+by+chlorophacinone+and+ivermectin+analogs.&rft.au=Hsu%2C+Chia-Wen%3BHsieh%2C+Jui-Hua%3BHuang%2C+Ruili%3BPijnenburg%2C+Dirk%3BKhuc%2C+Thai%3BHamm%2C+Jon%3BZhao%2C+Jinghua%3BLynch%2C+Caitlin%3Bvan+Beuningen%2C+Rinie%3BChang%2C+Xiaoqing%3BHoutman%2C+Ren%C3%A9%3BXia%2C+Menghang&rft.aulast=Hsu&rft.aufirst=Chia-Wen&rft.date=2016-12-15&rft.volume=313&rft.issue=&rft.spage=138&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=1096-0333&rft_id=info:doi/10.1016%2Fj.taap.2016.10.017 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.taap.2016.10.017 ER - TY - JOUR T1 - Dual-specific chimeric antigen receptor T cells and an indirect vaccine eradicate a variety of large solid tumors in an immunocompetent, self-antigen setting. AN - 1852679340; 27965307 AB - While adoptive transfer of T cells bearing a chimeric antigen receptor (CAR) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. We aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model. In this study, we generated dual-specific T cells expressing both a CAR specific for Her2 and a TCR specific for the melanocyte protein (gp100). We used a regimen of adoptive cell transfer incorporating vaccination (ACTIV), with recombinant vaccinia virus expressing gp100, to treat a range of tumors including orthotopic breast tumors and large liver tumors. ACTIV therapy induced durable complete remission of a variety of Her2+ tumors, some in excess of 150 mm2, in immunocompetent mice expressing Her2 in normal tissues, including the breast and brain. Vaccinia virus induced extensive proliferation of T cells, leading to massive infiltration of T cells into tumors. Durable tumor responses required the chemokine receptor CXCR3 and exogenous IL-2, but were independent of IFN-gamma. Mice were resistant to tumor rechallenge, indicating immune memory involving epitope spreading. Evidence of limited neurologic toxicity was observed, associated with infiltration of cerebellum by T cells, but was only transient. This study supports a view that it is possible to design a highly effective combination immunotherapy for solid cancers, with acceptable transient toxicity, even when the target antigen is also expressed in vital tissues. Copyright ©2016, American Association for Cancer Research. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Slaney, Clare Y AU - von Scheidt, Bianca AU - Davenport, Alexander J AU - Beavis, Paul AU - Westwood, Jennifer A AU - Mardiana, Sherly AU - Tscharke, David AU - Ellis, Sarah AU - Prince, H Miles AU - Trapani, Joseph A AU - Johnstone, Ricky W AU - Smyth, Mark J AU - Teng, Michele W L AU - Ali, Aesha AU - Yu, Zhiya AU - Rosenberg, Steven A AU - Restifo, Nicholas P AU - Neeson, Paul J AU - Darcy, Phillip K AU - Kershaw, Michael H AD - Research, Peter MacCallum Cancer Centre. ; Cancer Immuonology Program, Peter Mac Research. ; Cancer Immunology Program, Peter MacCallum Cancer Centre. ; Cancer Immunology Program, Peter MacCallum Cancer Center. ; John Curtin School of Medical Research, Australian National University. ; Histology, Peter MacCallum Cancer Centre. ; Department of Cancer Medicine, Peter MacCallum Cancer Centre. ; Gene Regulation Laboratory, Peter MacCallum Cancer Centre. ; Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute. ; Cancer Immunoregulation and Immunotherapy Laboratory, QIMR Berghofer Medical Research Institute. ; Cancer Immunology Program, Peter MacCallum Cancer Research Centre. ; Surgery Branch, Center for Cancer Research, National Institutes of Health, National Cancer Institute. ; Surgery Branch, National Cancer Institute. ; Cancer Immunology Research, Peter MacCallum Cancer Center. ; Cancer Immunology Program, Peter MacCallum Cancer Center michael.kershaw@petermac.org. Y1 - 2016/12/13/ PY - 2016 DA - 2016 Dec 13 SN - 1078-0432, 1078-0432 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852679340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Dual-specific+chimeric+antigen+receptor+T+cells+and+an+indirect+vaccine+eradicate+a+variety+of+large+solid+tumors+in+an+immunocompetent%2C+self-antigen+setting.&rft.au=Slaney%2C+Clare+Y%3Bvon+Scheidt%2C+Bianca%3BDavenport%2C+Alexander+J%3BBeavis%2C+Paul%3BWestwood%2C+Jennifer+A%3BMardiana%2C+Sherly%3BTscharke%2C+David%3BEllis%2C+Sarah%3BPrince%2C+H+Miles%3BTrapani%2C+Joseph+A%3BJohnstone%2C+Ricky+W%3BSmyth%2C+Mark+J%3BTeng%2C+Michele+W+L%3BAli%2C+Aesha%3BYu%2C+Zhiya%3BRosenberg%2C+Steven+A%3BRestifo%2C+Nicholas+P%3BNeeson%2C+Paul+J%3BDarcy%2C+Phillip+K%3BKershaw%2C+Michael+H&rft.aulast=Slaney&rft.aufirst=Clare&rft.date=2016-12-13&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Increased activity of TNAP compensates for reduced adenosine production and promotes ectopic calcification in the genetic disease ACDC. AN - 1852677322; 27965423 AB - ACDC (arterial calcification due to deficiency of CD73) is an autosomal recessive disease resulting from loss-of-function mutations in NT5E, which encodes CD73, a 5'-ectonucleotidase that converts extracellular adenosine monophosphate to adenosine. ACDC patients display progressive calcification of lower extremity arteries, causing limb ischemia. Tissue-nonspecific alkaline phosphatase (TNAP), which converts pyrophosphate (PPi) to inorganic phosphate (Pi), and extracellular purine metabolism play important roles in other inherited forms of vascular calcification. Compared to cells from healthy subjects, induced pluripotent stem cell-derived mesenchymal stromal cells (iMSCs) from ACDC patients displayed accelerated calcification and increased TNAP activity when cultured under conditions that promote osteogenesis. TNAP activity generated adenosine in iMSCs derived from ACDC patients but not in iMSCs from control subjects, which have CD73. In response to osteogenic stimulation, ACDC patient-derived iMSCs had decreased amounts of the TNAP substrate PPi, an inhibitor of extracellular matrix calcification, and exhibited increased activation of AKT, mechanistic target of rapamycin (mTOR), and the 70-kDa ribosomal protein S6 kinase (p70S6K), a pathway that promotes calcification. In vivo, teratomas derived from ACDC patient cells showed extensive calcification and increased TNAP activity. Treating mice bearing these teratomas with an A2b adenosine receptor agonist, the mTOR inhibitor rapamycin, or the bisphosphonate etidronate reduced calcification. These results show that an increase of TNAP activity in ACDC contributes to ectopic calcification by disrupting the extracellular balance of PPi and Pi and identify potential therapeutic targets for ACDC. Copyright © 2016, American Association for the Advancement of Science. JF - Science signaling AU - Jin, Hui AU - St Hilaire, Cynthia AU - Huang, Yuting AU - Yang, Dan AU - Dmitrieva, Natalia I AU - Negro, Alejandra AU - Schwartzbeck, Robin AU - Liu, Yangtengyu AU - Yu, Zhen AU - Walts, Avram AU - Davaine, Jean-Michel AU - Lee, Duck-Yeon AU - Donahue, Danielle AU - Hsu, Kevin S AU - Chen, Jessica AU - Cheng, Tao AU - Gahl, William AU - Chen, Guibin AU - Boehm, Manfred AD - Center for Molecular Medicine, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), 10 Center Drive, Bethesda, MD 20892, USA. ; Center for Molecular Medicine, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), 10 Center Drive, Bethesda, MD 20892, USA. boehmm@nhlbi.nih.gov chengb@nhlbi.nih.gov. Y1 - 2016/12/13/ PY - 2016 DA - 2016 Dec 13 SP - 1 VL - 9 IS - 458 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852677322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+signaling&rft.atitle=Increased+activity+of+TNAP+compensates+for+reduced+adenosine+production+and+promotes+ectopic+calcification+in+the+genetic+disease+ACDC.&rft.au=Jin%2C+Hui%3BSt+Hilaire%2C+Cynthia%3BHuang%2C+Yuting%3BYang%2C+Dan%3BDmitrieva%2C+Natalia+I%3BNegro%2C+Alejandra%3BSchwartzbeck%2C+Robin%3BLiu%2C+Yangtengyu%3BYu%2C+Zhen%3BWalts%2C+Avram%3BDavaine%2C+Jean-Michel%3BLee%2C+Duck-Yeon%3BDonahue%2C+Danielle%3BHsu%2C+Kevin+S%3BChen%2C+Jessica%3BCheng%2C+Tao%3BGahl%2C+William%3BChen%2C+Guibin%3BBoehm%2C+Manfred&rft.aulast=Jin&rft.aufirst=Hui&rft.date=2016-12-13&rft.volume=9&rft.issue=458&rft.spage=ra121&rft.isbn=&rft.btitle=&rft.title=Science+signaling&rft.issn=1937-9145&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Interactions between ethanol and cigarette smoke in a mouse lung carcinogenesis model. AN - 1839122371; 27840117 AB - Both ethanol and cigarette smoke are classified as human carcinogens. They can synergize, especially in tissues of the upper aerodigestive tract that are targeted by both agents. The main objective of the present study was to evaluate the individual and combined effects of ethanol and smoke in the respiratory tract, either following transplacental exposure and/or postnatal exposure. We designed two consecutive studies in mouse models by exposing Swiss H mice to oral ethanol and/or inhaled mainstream cigarette smoke for up to 4 months, at various prenatal and postnatal life stages. Clastogenic effects and histopathological alterations were evaluated after 4 and 8 months, respectively. Ethanol was per se devoid of clastogenic effects in mouse peripheral blood erythrocytes. However, especially in mice exposed both transplacentally throughout pregnancy and in the postnatal life, ethanol administration was associated not only with liver damage but also with pro-angiogenetic effects in the lung by stimulating the proliferation of blood vessels. In addition, these mice developed pulmonary emphysema, alveolar epithelial hyperplasias, microadenomas, and benign tumors. On the other hand, ethanol interfered in the lung carcinogenesis process resulting from the concomitant exposure of mice to smoke. In fact, ethanol significantly attenuated some smoke-related preneoplastic and neoplastic lesions in the respiratory tract, such as alveolar epithelial hyperplasia, microadenomas, and even malignant tumors. In addition, ethanol attenuated cigarette smoke clastogenicity. In conclusion, preclinical studies provide evidence that, in spite of its pulmonary toxicity, ethanol may mitigate some noxious effects of cigarette smoke in the respiratory tract. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. JF - Toxicology AU - Balansky, Roumen AU - Ganchev, Gancho AU - Iltcheva, Marietta AU - Nikolov, Manasi AU - La Maestra, S AU - Micale, Rosanna T AU - Steele, Vernon E AU - De Flora, Silvio AD - National Center of Oncology, Str. Plovdivsko pole 6, Sofia, 1756, Bulgaria; Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa, Italy. Electronic address: rubalansky@sbaloncology.bg. ; National Center of Oncology, Str. Plovdivsko pole 6, Sofia, 1756, Bulgaria. Electronic address: drganchoganchev@abv.bg. ; National Center of Oncology, Str. Plovdivsko pole 6, Sofia, 1756, Bulgaria. Electronic address: mariettailtcheva@yahoo.com. ; National Center of Oncology, Str. Plovdivsko pole 6, Sofia, 1756, Bulgaria. Electronic address: mdn@mail.bg. ; Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa, Italy. Electronic address: lamaestra78@yahoo.it. ; Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa, Italy. Electronic address: rosannamicale@yahoo.it. ; National Cancer Institute, Chemoprevention Agent Development Research Group, Division of Cancer Prevention,9609 Medical Center Drive, Bethesda, MD 20892, USA. Electronic address: steelev@mail.nih.gov. ; Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa, Italy. Electronic address: sdf@unige.it. Y1 - 2016/12/12/ PY - 2016 DA - 2016 Dec 12 SP - 54 EP - 62 VL - 373 KW - Lung tumors KW - Histopathological alterations KW - Cytogenetic damage KW - Cigarette smoke KW - Ethanol UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839122371?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Interactions+between+ethanol+and+cigarette+smoke+in+a+mouse+lung+carcinogenesis+model.&rft.au=Balansky%2C+Roumen%3BGanchev%2C+Gancho%3BIltcheva%2C+Marietta%3BNikolov%2C+Manasi%3BLa+Maestra%2C+S%3BMicale%2C+Rosanna+T%3BSteele%2C+Vernon+E%3BDe+Flora%2C+Silvio&rft.aulast=Balansky&rft.aufirst=Roumen&rft.date=2016-12-12&rft.volume=373&rft.issue=&rft.spage=54&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=1879-3185&rft_id=info:doi/10.1016%2Fj.tox.2016.11.008 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.tox.2016.11.008 ER - TY - JOUR T1 - The Cr-isotope signature of surface seawater - A global perspective AN - 1861076725; 786143-9 AB - This study presents chromium-isotope data (expressed as delta (super 53) Cr) and chromium concentrations (Cr) of surface seawater (0-2 m depth) from a variety of locations worldwide. In addition to samples from the open ocean (Arctic, Southern, Pacific, and Atlantic Oceans), samples were analysed from areas with more restricted water exchange rates (the Mediterranean Sea, Oresund, and Baltic Sea). The data indicate a heterogeneous distribution of delta (super 53) Cr in seawater with a total range from + 0.13 ppm to + 1.24 ppm. The data are in agreement with a previous study, which focused on depth profiles, suggesting that seawater heterogeneity in delta (super 53) Cr and Cr concentration can be explained using a single fractionation factor for Cr-reduction (epsilon = - 0.79 + or - 0.06 ppm 2SD). In basins with limited water exchange with the open ocean, however, local factors seem to control the Cr-isotope composition. JF - Chemical Geology AU - Paulukat, Cora AU - Gilleaudeau, Geoffrey J AU - Chernyavskiy, Pavel AU - Frei, Robert Y1 - 2016/12/09/ PY - 2016 DA - 2016 Dec 09 SP - 101 EP - 109 PB - Elsevier, Amsterdam VL - 444 SN - 0009-2541, 0009-2541 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861076725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefinprocess&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Geology&rft.atitle=The+Cr-isotope+signature+of+surface+seawater+-+A+global+perspective&rft.au=Paulukat%2C+Cora%3BGilleaudeau%2C+Geoffrey+J%3BChernyavskiy%2C+Pavel%3BFrei%2C+Robert&rft.aulast=Paulukat&rft.aufirst=Cora&rft.date=2016-12-09&rft.volume=444&rft.issue=&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Chemical+Geology&rft.issn=00092541&rft_id=info:doi/10.1016%2Fj.chemgeo.2016.10.004 L2 - http://www.sciencedirect.com/science/journal/00092541 LA - English DB - GeoRef N1 - Copyright - GeoRef in Process, Copyright 2017, American Geosciences Institute. After editing and indexing, this record will be added to Georef. Reference includes data from CAPCAS, Elsevier Scientific Publishers, Amsterdam, Netherlands N1 - Last updated - 2017-01-24 N1 - CODEN - CHGEAD DO - http://dx.doi.org/10.1016/j.chemgeo.2016.10.004 ER - TY - JOUR T1 - Peroxisome proliferator-activated receptor-β/δ modulates mast cell phenotype. AN - 1847892341; 27935639 AB - The peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) is known to have multiple anti-inflammatory effects, typically observed in endothelial cells, macrophages, T cells and B cells. Despite the fact that mast cells are important mediators of inflammation, to date, the role of PPARβ/δ in mast cells has not been examined. Hence, the present study examined the hypothesis that PPARβ/δ modulates mast cell phenotype. Bone-marrow-derived mast cells (BMMCs) and peritoneal mast cells from Pparβ/δ+/+ mice expressed higher levels of high-affinity IgE receptor (FcεRI) compared with Pparβ/δ-/- mice. BMMCs from Pparβ/δ+/+ mice also exhibited dense granules, associated with higher expression of enzymes and proteases compared with Pparβ/δ-/- mice. Resting BMMCs from Pparβ/δ+/+ mice secreted lower levels of inflammatory cytokines, associated with the altered activation of phospholipase Cγ1 and extracellular signal-regulated kinases compared with Pparβ/δ-/- mice. Moreover, the production of cytokines by mast cells induced by various stimuli was highly dependent on PPARβ/δ expression. This study demonstrates that PPARβ/δ is an important regulator of mast cell phenotype. © 2016 John Wiley & Sons Ltd. JF - Immunology AU - Yao, Pei-Li AU - Morales, Jose L AU - Gonzalez, Frank J AU - Peters, Jeffrey M AD - Department of Veterinary and Biomedical Sciences, The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA, USA. ; Laboratory of Metabolism, National Cancer Institute, Bethesda, MD, USA. Y1 - 2016/12/09/ PY - 2016 DA - 2016 Dec 09 KW - inflammation KW - peroxisome proliferator-activated receptor-β/δ KW - cytokine KW - bone marrow-derived mast cells UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1847892341?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunology&rft.atitle=Peroxisome+proliferator-activated+receptor-%CE%B2%2F%CE%B4+modulates+mast+cell+phenotype.&rft.au=Yao%2C+Pei-Li%3BMorales%2C+Jose+L%3BGonzalez%2C+Frank+J%3BPeters%2C+Jeffrey+M&rft.aulast=Yao&rft.aufirst=Pei-Li&rft.date=2016-12-09&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+proteome+research&rft.issn=1535-3907&rft_id=info:doi/10.1021%2Facs.jproteome.5b00957 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-09 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1111/imm.12699 ER - TY - JOUR T1 - Development and Validation of a Computational Model for Androgen Receptor Activity. AN - 1847891450; 27933809 AB - Testing thousands of chemicals to identify potential androgen receptor (AR) agonists or antagonists would cost millions of dollars and take decades to complete using current validated methods. High-throughput in vitro screening (HTS) and computational toxicology approaches can more rapidly and inexpensively identify potential androgen-active chemicals. We integrated 11 HTS ToxCast/Tox21 in vitro assays into a computational network model to distinguish true AR pathway activity from technology-specific assay interference. The in vitro HTS assays probed perturbations of the AR pathway at multiple points (receptor binding, coregulator recruitment, gene transcription, and protein production) and multiple cell types. Confirmatory in vitro antagonist assay data and cytotoxicity information were used as additional flags for potential nonspecific activity. Validating such alternative testing strategies requires high-quality reference data. We compiled 158 putative androgen-active and -inactive chemicals from a combination of international test method validation efforts and semiautomated systematic literature reviews. Detailed in vitro assay information and results were compiled into a single database using a standardized ontology. Reference chemical concentrations that activated or inhibited AR pathway activity were identified to establish a range of potencies with reproducible reference chemical results. Comparison with existing Tier 1 AR binding data from the U.S. EPA Endocrine Disruptor Screening Program revealed that the model identified binders at relevant test concentrations (<100 μM) and was more sensitive to antagonist activity. The AR pathway model based on the ToxCast/Tox21 assays had balanced accuracies of 95.2% for agonist (n = 29) and 97.5% for antagonist (n = 28) reference chemicals. Out of 1855 chemicals screened in the AR pathway model, 220 chemicals demonstrated AR agonist or antagonist activity and an additional 174 chemicals were predicted to have potential weak AR pathway activity. JF - Chemical research in toxicology AU - Kleinstreuer, Nicole C AU - Ceger, Patricia AU - Watt, Eric D AU - Martin, Matthew AU - Houck, Keith AU - Browne, Patience AU - Thomas, Russell S AU - Casey, Warren M AU - Dix, David J AU - Allen, David AU - Sakamuru, Srilatha AU - Xia, Menghang AU - Huang, Ruili AU - Judson, Richard AD - NIH/NIEHS/DNTP/The NTP Interagency Center for the Evaluation of Alternative Toxicological Methods , Research Triangle Park, North Carolina 27713, United States. ; Integrated Laboratory Systems, Inc. , Research Triangle Park, North Carolina 27560, United States. ; EPA/ORD/National Center for Computational Toxicology , Research Triangle Park, North Carolina 27711, United States. ; OECD Environment Directorate, Environment Health and Safety Division , Paris 75775, France. ; EPA/OCSPP/Office of Science Coordination and Policy , Washington, DC, 20460, United States. ; NIH/National Center for Advancing Translational Sciences , Bethesda, Maryland 20892, United States. Y1 - 2016/12/09/ PY - 2016 DA - 2016 Dec 09 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1847891450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Development+and+Validation+of+a+Computational+Model+for+Androgen+Receptor+Activity.&rft.au=Kleinstreuer%2C+Nicole+C%3BCeger%2C+Patricia%3BWatt%2C+Eric+D%3BMartin%2C+Matthew%3BHouck%2C+Keith%3BBrowne%2C+Patience%3BThomas%2C+Russell+S%3BCasey%2C+Warren+M%3BDix%2C+David+J%3BAllen%2C+David%3BSakamuru%2C+Srilatha%3BXia%2C+Menghang%3BHuang%2C+Ruili%3BJudson%2C+Richard&rft.aulast=Kleinstreuer&rft.aufirst=Nicole&rft.date=2016-12-09&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=1520-5010&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - HPV 16 E5 oncoprotein is expressed in early stage carcinogenesis and can be a target of immunotherapy. AN - 1847898485; 27929754 AB - HPV16 persistent infection is a well-known condition that precedes human cancer development. High risk HPV E5 proteins cooperate with E6/E7 oncogenes to promote hyper-proliferation of infected cells leading to possible cancer progression. Thus, presence of E5 viral transcripts could be a key marker of active infection and, in turn, a target of immunotherapy. Purpose of the study is to detect E5 transcripts in clinical samples and to explore the activity of novel anti-HPV16 E5 DNA vaccines. HPV transcripts were detected by PCR with specific primers encompassing the splice-donor sites of E5 transcript. For E5-based immunotherapies, 2 E5-based versions of DNA vaccines carrying whole E5 gene or a synthetic multiepitope gene were improved by fusion to sequence of PVX coat protein. These vaccines were challenged with a new luminescent animal model based on C3-Luc cell line. E5 transcripts were detected in clinical samples of women with HPV positive low-grade SIL, demonstrating the validity of our test. In C3 pre-clinical mouse model, vaccine candidates were able to induce a strong cellular immunity as indicated by ELISPOT assays. In addition, E5-CP vaccines elicited strong anti-tumor effects as showed by decreased tumor growth monitored by animal imaging. The tumor growth inhibition was comparable to those obtained with anti-E7 DNA vaccines. In conclusion, detection of E5 transcripts in clinical samples indicates that E5 is a possible target of immunotherapy. Data from pre-clinical model demonstrate that E5 genetic immunization is feasible, efficacious and could be utilized in clinical trials. JF - Human vaccines & immunotherapeutics AU - Paolini, Francesca AU - Curzio, Gianfranca AU - Cordeiro, Marcelo Nazario AU - Massa, Silvia AU - Mariani, Luciano AU - Pimpinelli, Fulvia AU - de Freitas, Antonio Carlos AU - Franconi, Rosella AU - Venuti, Aldo AD - a Regina Elena National Cancer Institute, HPV Unit , Rome , Italy. ; b Federal University of Pernambuco , Department of Genetics , LEMTE , Pernambuco , Brazil. ; c ENEA, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, C.R. Casaccia , Rome , Italy. ; d San Gallicano Dermatologic Institute , Rome , Italy. Y1 - 2016/12/08/ PY - 2016 DA - 2016 Dec 08 SP - 1 EP - 7 KW - immunotherapy KW - E5 KW - therapeutic vaccine KW - HPV transcripts KW - HPV KW - cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1847898485?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+vaccines+%26+immunotherapeutics&rft.atitle=HPV+16+E5+oncoprotein+is+expressed+in+early+stage+carcinogenesis+and+can+be+a+target+of+immunotherapy.&rft.au=Paolini%2C+Francesca%3BCurzio%2C+Gianfranca%3BCordeiro%2C+Marcelo+Nazario%3BMassa%2C+Silvia%3BMariani%2C+Luciano%3BPimpinelli%2C+Fulvia%3Bde+Freitas%2C+Antonio+Carlos%3BFranconi%2C+Rosella%3BVenuti%2C+Aldo&rft.aulast=Paolini&rft.aufirst=Francesca&rft.date=2016-12-08&rft.volume=&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Human+vaccines+%26+immunotherapeutics&rft.issn=2164-554X&rft_id=info:doi/10.1080%2F21645515.2017.1264777 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-08 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1080/21645515.2017.1264777 ER - TY - JOUR T1 - Activation induced deaminase mutational signature overlaps with CpG methylation sites in follicular lymphoma and other cancers. AN - 1846721880; 27924834 AB - Follicular lymphoma (FL) is an uncurable cancer characterized by progressive severity of relapses. We analyzed sequence context specificity of mutations in the B cells from a large cohort of FL patients. We revealed substantial excess of mutations within a novel hybrid nucleotide motif: the signature of somatic hypermutation (SHM) enzyme, Activation Induced Deaminase (AID), which overlaps the CpG methylation site. This finding implies that in FL the SHM machinery acts at genomic sites containing methylated cytosine. We identified the prevalence of this hybrid mutational signature in many other types of human cancer, suggesting that AID-mediated, CpG-methylation dependent mutagenesis is a common feature of tumorigenesis. JF - Scientific reports AU - Rogozin, Igor B AU - Lada, Artem G AU - Goncearenco, Alexander AU - Green, Michael R AU - De, Subhajyoti AU - Nudelman, German AU - Panchenko, Anna R AU - Koonin, Eugene V AU - Pavlov, Youri I AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. ; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA. ; Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA. ; Department of Neurology and Systems Biology Center, Icahn School of Medicine at Mount Sinai, New York, USA. Y1 - 2016/12/07/ PY - 2016 DA - 2016 Dec 07 SP - 38133 VL - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846721880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Activation+induced+deaminase+mutational+signature+overlaps+with+CpG+methylation+sites+in+follicular+lymphoma+and+other+cancers.&rft.au=Rogozin%2C+Igor+B%3BLada%2C+Artem+G%3BGoncearenco%2C+Alexander%3BGreen%2C+Michael+R%3BDe%2C+Subhajyoti%3BNudelman%2C+German%3BPanchenko%2C+Anna+R%3BKoonin%2C+Eugene+V%3BPavlov%2C+Youri+I&rft.aulast=Rogozin&rft.aufirst=Igor&rft.date=2016-12-07&rft.volume=6&rft.issue=&rft.spage=38133&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep38133 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep38133 ER - TY - JOUR T1 - Deletion of IQGAP1 promotes Helicobacter pylori-induced gastric dysplasia in mice and acquisition of cancer stem cell properties in vitro. AN - 1835407132; 27729612 AB - Helicobacter pylori infection is responsible for gastric carcinogenesis but host factors are also implicated. IQGAP1, a scaffolding protein of the adherens junctions interacting with E-cadherin, regulates cellular plasticity and proliferation. In mice, IQGAP1 deficiency leads to gastric hyperplasia. The aim of this study was to elucidate the consequences of IQGAP1 deletion on H. pylori-induced gastric carcinogenesis.Transgenic mice deleted for iqgap1 and WT littermates were infected with Helicobacter sp., and histopathological analyses of the gastric mucosa were performed. IQGAP1 and E-cadherin expression was evaluated in gastric tissues and in gastric epithelial cell lines in response to H. pylori infection. The consequences of IQGAP1 deletion on gastric epithelial cell behaviour and on the acquisition of cancer stem cell (CSC)-like properties were evaluated. After one year of infection, iqgap1+/- mice developed more preneoplastic lesions and up to 8 times more gastro-intestinal neoplasia (GIN) than WT littermates. H. pylori infection induced IQGAP1 and E-cadherin delocalization from cell-cell junctions. In vitro, knock-down of IQGAP1 favoured the acquisition of a mesenchymal phenotype and CSC-like properties induced by H. pylori infection.Our results indicate that alterations in IQGAP1 signalling promote the emergence of CSCs and gastric adenocarcinoma development in the context of an H. pylori infection. JF - Oncotarget AU - Bessède, Emilie AU - Molina, Silvia AU - Amador, Luis Acuña AU - Dubus, Pierre AU - Staedel, Cathy AU - Chambonnier, Lucie AU - Buissonnière, Alice AU - Sifré, Elodie AU - Giese, Alban AU - Bénéjat, Lucie AU - Rousseau, Benoît AU - Costet, Pierre AU - Sacks, David B AU - Mégraud, Francis AU - Varon, Christine AD - Bacteriology Laboratory, University of Bordeaux, Bordeaux, France. ; EA2406 Histologie et Pathologie Moléculaire des Tumeurs, University of Bordeaux, Bordeaux, France. ; 'RNA: Natural and Artificial Regulation' (ARNA) Laboratory, University of Bordeaux, Bordeaux, France. ; Service Commun des Animaleries, Animalerie A2, University of Bordeaux, Bordeaux, France. ; Service Commun des Animaleries, Animalerie Transgénique, University of Bordeaux, Bordeaux, France. ; Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/12/06/ PY - 2016 DA - 2016 Dec 06 SP - 80688 EP - 80699 VL - 7 IS - 49 KW - gastric cancer KW - CD44 KW - Zeb KW - EMT KW - E-cadherin UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835407132?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncotarget&rft.atitle=Deletion+of+IQGAP1+promotes+Helicobacter+pylori-induced+gastric+dysplasia+in+mice+and+acquisition+of+cancer+stem+cell+properties+in+vitro.&rft.au=Bess%C3%A8de%2C+Emilie%3BMolina%2C+Silvia%3BAmador%2C+Luis+Acu%C3%B1a%3BDubus%2C+Pierre%3BStaedel%2C+Cathy%3BChambonnier%2C+Lucie%3BBuissonni%C3%A8re%2C+Alice%3BSifr%C3%A9%2C+Elodie%3BGiese%2C+Alban%3BB%C3%A9n%C3%A9jat%2C+Lucie%3BRousseau%2C+Beno%C3%AEt%3BCostet%2C+Pierre%3BSacks%2C+David+B%3BM%C3%A9graud%2C+Francis%3BVaron%2C+Christine&rft.aulast=Bess%C3%A8de&rft.aufirst=Emilie&rft.date=2016-12-06&rft.volume=7&rft.issue=49&rft.spage=80688&rft.isbn=&rft.btitle=&rft.title=Oncotarget&rft.issn=1949-2553&rft_id=info:doi/10.18632%2Foncotarget.12486 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-12 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.18632/oncotarget.12486 ER - TY - JOUR T1 - Disease drivers of aging AN - 1855080217; PQ0003960484 AB - It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship-the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging. JF - Annals of the New York Academy of Sciences AU - Hodes, Richard J AU - Sierra, Felipe AU - Austad, Steven N AU - Epel, Elissa AU - Neigh, Gretchen N AU - Erlandson, Kristine M AU - Schafer, Marissa J AU - LeBrasseur, Nathan K AU - Wiley, Christopher AU - Campisi, Judith AU - Sehl, Mary E AU - Scalia, Rosario AU - Eguchi, Satoru AU - Kasinath, Balakuntalam S AU - Halter, Jeffrey B AU - Cohen, Harvey Jay AU - Demark-Wahnefried, Wendy AU - Ahles, Tim A AU - Barzilai, Nir AU - Hurria, Arti AU - Hunt, Peter W AD - National Institute on Aging, Bethesda, Maryland. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 45 EP - 68 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 1386 IS - 1 SN - 0077-8923, 0077-8923 KW - Immunology Abstracts; Environment Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855080217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Disease+drivers+of+aging&rft.au=Hodes%2C+Richard+J%3BSierra%2C+Felipe%3BAustad%2C+Steven+N%3BEpel%2C+Elissa%3BNeigh%2C+Gretchen+N%3BErlandson%2C+Kristine+M%3BSchafer%2C+Marissa+J%3BLeBrasseur%2C+Nathan+K%3BWiley%2C+Christopher%3BCampisi%2C+Judith%3BSehl%2C+Mary+E%3BScalia%2C+Rosario%3BEguchi%2C+Satoru%3BKasinath%2C+Balakuntalam+S%3BHalter%2C+Jeffrey+B%3BCohen%2C+Harvey+Jay%3BDemark-Wahnefried%2C+Wendy%3BAhles%2C+Tim+A%3BBarzilai%2C+Nir%3BHurria%2C+Arti%3BHunt%2C+Peter+W&rft.aulast=Hodes&rft.aufirst=Richard&rft.date=2016-12-01&rft.volume=1386&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fnyas.13299 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-04 DO - http://dx.doi.org/10.1111/nyas.13299 ER - TY - JOUR T1 - Reverse geroscience: how does exposure to early diseases accelerate the age-related decline in health? AN - 1855077200; PQ0003960483 AB - Aging is the major risk factor for both the development of chronic diseases and loss of functional capacity. Geroscience provides links among the biology of aging, the biology of disease, and the physiology of frailty, three fields where enormous progress has been made in the last few decades. While, previously, the focus was on the role of aging in susceptibility to disease and disability, the other side of this relationship, which is the contribution of disease to aging, has been less explored at the molecular/cellular level. Indeed, the role of childhood or early adulthood exposure to chronic disease and/or treatment on accelerating aging phenotypes is well known in epidemiology, but the biological basis is poorly understood. A recent summit co-organized by the National Institutes of Health GeroScience Interest Group and the New York Academy of Sciences explored these relationships, using three chronic diseases as examples: cancer, HIV/AIDS, and diabetes. The epidemiological literature clearly indicates that early exposure to any of these diseases and/or their treatments results in an acceleration of the appearance of aging phenotypes, including loss of functional capacity and accelerated appearance of clinical symptoms of aging-related diseases not obviously related to the earlier event. The discussions at the summit focused on the molecular and cellular relationships between each of these diseases and the recently defined molecular and cellular pillars of aging. Two major conclusions from the meeting include the desire to refine an operational definition of aging and to concomitantly develop biomarkers of aging, in order to move from chronological to physiological age. The discussion also opened a dialogue on the possibility of improving late-life outcomes in patients affected by chronic disease by including age-delaying modalities along with the standard care for the disease in question. JF - Annals of the New York Academy of Sciences AU - Kohanski, Ronald A AU - Deeks, Steven G AU - Gravekamp, Claudia AU - Halter, Jeffrey B AU - High, Kevin AU - Hurria, Arti AU - Fuldner, Rebecca AU - Green, Paige AU - Huebner, Robin AU - Macchiarini, Francesca AU - Sierra, Felipe AD - Division of Aging Biology, National Institute on Aging, NIH, Bethesda, Maryland. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 30 EP - 44 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 1386 IS - 1 SN - 0077-8923, 0077-8923 KW - Immunology Abstracts; Environment Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855077200?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Reverse+geroscience%3A+how+does+exposure+to+early+diseases+accelerate+the+age-related+decline+in+health%3F&rft.au=Kohanski%2C+Ronald+A%3BDeeks%2C+Steven+G%3BGravekamp%2C+Claudia%3BHalter%2C+Jeffrey+B%3BHigh%2C+Kevin%3BHurria%2C+Arti%3BFuldner%2C+Rebecca%3BGreen%2C+Paige%3BHuebner%2C+Robin%3BMacchiarini%2C+Francesca%3BSierra%2C+Felipe&rft.aulast=Kohanski&rft.aufirst=Ronald&rft.date=2016-12-01&rft.volume=1386&rft.issue=1&rft.spage=30&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fnyas.13297 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-04 DO - http://dx.doi.org/10.1111/nyas.13297 ER - TY - JOUR T1 - Cell lineage responses to photobiomodulation therapy AN - 1855074864; PQ0003962077 AB - Photobiomodulation (PBM) therapy has been noted to promote cell proliferation and growth in many different cell types shown both in vitro and in vivo. Currently, treatment regimens are used in the clinic for a variety of ailments, including wound healing. However, most protocols treat an anatomical site without considering individual cell types constituting the target tissues. This study investigates the maximal dose threshold for oral keratinocyte and fibroblast cell types treated with near-infrared laser therapy. We observed keratinocytes have increased sensitivity to laser irradiances (>0.047 W/cm super(2), 300 sec, 14.2 J/cm super(2)) compared to the fibroblast cells (>0.057 W/cm super(2), 300 sec, 15.1 J/cm super(2)) (p < 0.0001). Laser treatments were noted to generate increased reactive oxygen species (ROS) levels in keratinocytes compared to fibroblasts that appeared to inversely correlate with higher basal catalase expression. To validate these observations, melatonin was used to treat keratinocytes to induce catalase activity (p < 0.0001). Increased melatonin-induced catalase levels were noted to significantly improve keratinocyte survival to phototoxic laser doses. These observations suggest that clinical laser dosing should account for differential effects of lasers on individual cell types to improve safety and clinical efficacy of PBM therapy. Distinct effects of dose-dependent laser treatments on discrete cell lineages indicate that illumination of a treatment site must include careful attention to individual targets within this area. Variations in inherent lineage-dependent ubiquitous photoresponses could be attributed to presence or absence of specific photoreception molecules as well as biochemical mediators or neutralizers. A specific example outlined in this study is variable concentrations of ROS neutralizing agent, Catalase in epithelial versus fibroblasts. JF - Journal of Biophotonics AU - Engel, Karl W AU - Khan, Imran AU - Arany, Praveen R AD - Cell Regulation and Control Unit, National Institute of Dental and Craniofacial Research, National Institute of Health, 30 Convent Drive, Bethesda, MD 20814, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1148 EP - 1156 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 9 IS - 11-12 SN - 1864-063X, 1864-063X KW - Biotechnology and Bioengineering Abstracts KW - Cell lineage KW - I.R. radiation KW - Reactive oxygen species KW - Illumination KW - Wound healing KW - Lasers KW - Melatonin KW - Keratinocytes KW - Cell proliferation KW - Catalase KW - Fibroblasts KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855074864?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biophotonics&rft.atitle=Cell+lineage+responses+to+photobiomodulation+therapy&rft.au=Engel%2C+Karl+W%3BKhan%2C+Imran%3BArany%2C+Praveen+R&rft.aulast=Engel&rft.aufirst=Karl&rft.date=2016-12-01&rft.volume=9&rft.issue=11-12&rft.spage=1148&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biophotonics&rft.issn=1864063X&rft_id=info:doi/10.1002%2Fjbio.201600025 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Cell lineage; I.R. radiation; Illumination; Reactive oxygen species; Wound healing; Melatonin; Lasers; Keratinocytes; Cell proliferation; Catalase; Fibroblasts DO - http://dx.doi.org/10.1002/jbio.201600025 ER - TY - JOUR T1 - Winner's Curse Correction and Variable Thresholding Improve Performance of Polygenic Risk Modeling Based on Genome-Wide Association Study Summary-Level Data. AN - 1854618540; 28036406 AB - Recent heritability analyses have indicated that genome-wide association studies (GWAS) have the potential to improve genetic risk prediction for complex diseases based on polygenic risk score (PRS), a simple modelling technique that can be implemented using summary-level data from the discovery samples. We herein propose modifications to improve the performance of PRS. We introduce threshold-dependent winner's-curse adjustments for marginal association coefficients that are used to weight the single-nucleotide polymorphisms (SNPs) in PRS. Further, as a way to incorporate external functional/annotation knowledge that could identify subsets of SNPs highly enriched for associations, we propose variable thresholds for SNPs selection. We applied our methods to GWAS summary-level data of 14 complex diseases. Across all diseases, a simple winner's curse correction uniformly led to enhancement of performance of the models, whereas incorporation of functional SNPs was beneficial only for selected diseases. Compared to the standard PRS algorithm, the proposed methods in combination led to notable gain in efficiency (25-50% increase in the prediction R2) for 5 of 14 diseases. As an example, for GWAS of type 2 diabetes, winner's curse correction improved prediction R2 from 2.29% based on the standard PRS to 3.10% (P = 0.0017) and incorporating functional annotation data further improved R2 to 3.53% (P = 2×10-5). Our simulation studies illustrate why differential treatment of certain categories of functional SNPs, even when shown to be highly enriched for GWAS-heritability, does not lead to proportionate improvement in genetic risk-prediction because of non-uniform linkage disequilibrium structure. JF - PLoS genetics AU - Shi, Jianxin AU - Park, Ju-Hyun AU - Duan, Jubao AU - Berndt, Sonja T AU - Moy, Winton AU - Yu, Kai AU - Song, Lei AU - Wheeler, William AU - Hua, Xing AU - Silverman, Debra AU - Garcia-Closas, Montserrat AU - Hsiung, Chao Agnes AU - Figueroa, Jonine D AU - Cortessis, Victoria K AU - Malats, Núria AU - Karagas, Margaret R AU - Vineis, Paolo AU - Chang, I-Shou AU - Lin, Dongxin AU - Zhou, Baosen AU - Seow, Adeline AU - Matsuo, Keitaro AU - Hong, Yun-Chul AU - Caporaso, Neil E AU - Wolpin, Brian AU - Jacobs, Eric AU - Petersen, Gloria M AU - Klein, Alison P AU - Li, Donghui AU - Risch, Harvey AU - Sanders, Alan R AU - Hsu, Li AU - Schoen, Robert E AU - Brenner, Hermann AU - MGS (Molecular Genetics of Schizophrenia) GWAS Consortium AU - GECCO (The Genetics and Epidemiology of Colorectal Cancer Consortium) AU - GAME-ON/TRICL (Transdisciplinary Research in Cancer of the Lung) GWAS Consortium AU - PRACTICAL (PRostate cancer AssoCiation group To Investigate Cancer Associated aLterations) Consortium AU - PanScan Consortium AU - GAME-ON/ELLIPSE Consortium AU - Stolzenberg-Solomon, Rachael AU - Gejman, Pablo AU - Lan, Qing AU - Rothman, Nathaniel AU - Amundadottir, Laufey T AU - Landi, Maria Teresa AU - Levinson, Douglas F AU - Chanock, Stephen J AU - Chatterjee, Nilanjan AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America. ; Department of Statistics, Dongguk University, Seoul, Korea. ; Center for Psychiatric Genetics, Department of Psychiatry and Behavioral Sciences, North Shore University Health System Research Institute, University of Chicago Pritzker School of Medicine, Evanston, Illinois, United States of America. ; Dept. of Statistics, Northern Illinois University, DeKalb, Illinois, United States of America. ; Information Management Services, Inc., Rockville, Maryland, United States of America. ; Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan. ; Department of Preventive Medicine and Department of Obstetrics and Gynecology, USC Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America. ; Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. ; Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, United States of America. ; Human Genetics Foundation, Turin, Italy. ; National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan. ; Department of Etiology & Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. ; Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China. ; Saw Swee Hock School of Public Health, National University of Singapore, Singapore. ; Division of Molecular Medicine, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Japan. ; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America. ; Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America. ; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America. ; Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. ; Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America. ; Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, United States of America. ; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. ; Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America. ; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. ; MGS (Molecular Genetics of Schizophrenia) GWAS Consortium ; GECCO (The Genetics and Epidemiology of Colorectal Cancer Consortium) ; GAME-ON/TRICL (Transdisciplinary Research in Cancer of the Lung) GWAS Consortium ; PRACTICAL (PRostate cancer AssoCiation group To Investigate Cancer Associated aLterations) Consortium ; PanScan Consortium ; GAME-ON/ELLIPSE Consortium ; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, United States of America. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1 VL - 12 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1854618540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PLoS+genetics&rft.atitle=Winner%27s+Curse+Correction+and+Variable+Thresholding+Improve+Performance+of+Polygenic+Risk+Modeling+Based+on+Genome-Wide+Association+Study+Summary-Level+Data.&rft.au=Shi%2C+Jianxin%3BPark%2C+Ju-Hyun%3BDuan%2C+Jubao%3BBerndt%2C+Sonja+T%3BMoy%2C+Winton%3BYu%2C+Kai%3BSong%2C+Lei%3BWheeler%2C+William%3BHua%2C+Xing%3BSilverman%2C+Debra%3BGarcia-Closas%2C+Montserrat%3BHsiung%2C+Chao+Agnes%3BFigueroa%2C+Jonine+D%3BCortessis%2C+Victoria+K%3BMalats%2C+N%C3%BAria%3BKaragas%2C+Margaret+R%3BVineis%2C+Paolo%3BChang%2C+I-Shou%3BLin%2C+Dongxin%3BZhou%2C+Baosen%3BSeow%2C+Adeline%3BMatsuo%2C+Keitaro%3BHong%2C+Yun-Chul%3BCaporaso%2C+Neil+E%3BWolpin%2C+Brian%3BJacobs%2C+Eric%3BPetersen%2C+Gloria+M%3BKlein%2C+Alison+P%3BLi%2C+Donghui%3BRisch%2C+Harvey%3BSanders%2C+Alan+R%3BHsu%2C+Li%3BSchoen%2C+Robert+E%3BBrenner%2C+Hermann%3BMGS+%28Molecular+Genetics+of+Schizophrenia%29+GWAS+Consortium%3BGECCO+%28The+Genetics+and+Epidemiology+of+Colorectal+Cancer+Consortium%29%3BGAME-ON%2FTRICL+%28Transdisciplinary+Research+in+Cancer+of+the+Lung%29+GWAS+Consortium%3BPRACTICAL+%28PRostate+cancer+AssoCiation+group+To+Investigate+Cancer+Associated+aLterations%29+Consortium%3BPanScan+Consortium%3BGAME-ON%2FELLIPSE+Consortium%3BStolzenberg-Solomon%2C+Rachael%3BGejman%2C+Pablo%3BLan%2C+Qing%3BRothman%2C+Nathaniel%3BAmundadottir%2C+Laufey+T%3BLandi%2C+Maria+Teresa%3BLevinson%2C+Douglas+F%3BChanock%2C+Stephen+J%3BChatterjee%2C+Nilanjan&rft.aulast=Shi&rft.aufirst=Jianxin&rft.date=2016-12-01&rft.volume=12&rft.issue=12&rft.spage=e1006493&rft.isbn=&rft.btitle=&rft.title=PLoS+genetics&rft.issn=1553-7404&rft_id=info:doi/10.1371%2Fjournal.pgen.1006493 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-30 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1371/journal.pgen.1006493 ER - TY - JOUR T1 - Drug induced interstitial lung disease in oncology phase I trials. AN - 1854104420; 27685762 AB - Interstitial lung disease is a serious drug-related condition that can cause life threatening organ failure. The incidence and risk factors of drug-induced interstitial lung disease (DILD) are unknown in oncology phase I trials. This study analyzed clinical information from 8906 patients with malignancies who were enrolled in 470 phase I trials sponsored by the Cancer Therapy Evaluation Program, National Cancer Institute, from 1988 to 2014. Logistic and Cox statistical analyses were utilized to determine clinical differences between patients who developed DILD and patients who did not. In this study, the overall incidence rate of patients with pulmonary toxicity was 2.7%. The overall incidence rate for DILD was 0.77%, whereas for grade 3 or 4 DILD it was 0.31%. Median time to occurrence of DILD was 1.4 months. The Cox hazard analysis indicated smaller body surface area and a combination of thoracic radiation with investigational drug regimens were significant risk factors for time to occurrence of interstitial lung disease. Investigators should carefully monitor for DILD in oncology patients enrolled in phase I trials with identified risk factors. A 6-month observation period would be sufficient to detect the onset of most DILD in such patients. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. JF - Cancer science AU - Yonemori, Kan AU - Hirakawa, Akihiro AU - Kawachi, Asuka AU - Kinoshita, Fumie AU - Okuma, Hitomi AU - Nishikawa, Tadaaki AU - Tamura, Kenji AU - Fujiwara, Yasuhiro AU - Takebe, Naoko AD - Department of Breast and Medical Oncology, National Cancer Center Hospital, National Cancer Center, Tokyo, Japan. ; Biostatistics and Bioinformatics Section, Center for Advanced Medicine and Clinical Research, Graduate School of Medicine, Nagoya University, Nagoya, Japan. ; Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institute of Health, Rockville, Maryland, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1830 EP - 1836 VL - 107 IS - 12 KW - investigational new drug KW - Drug induced interstitial lung disease KW - oncology KW - phase I trial pulmonary toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1854104420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+science&rft.atitle=Drug+induced+interstitial+lung+disease+in+oncology+phase%C2%A0I+trials.&rft.au=Yonemori%2C+Kan%3BHirakawa%2C+Akihiro%3BKawachi%2C+Asuka%3BKinoshita%2C+Fumie%3BOkuma%2C+Hitomi%3BNishikawa%2C+Tadaaki%3BTamura%2C+Kenji%3BFujiwara%2C+Yasuhiro%3BTakebe%2C+Naoko&rft.aulast=Yonemori&rft.aufirst=Kan&rft.date=2016-12-01&rft.volume=107&rft.issue=12&rft.spage=1830&rft.isbn=&rft.btitle=&rft.title=Cancer+science&rft.issn=1349-7006&rft_id=info:doi/10.1111%2Fcas.13087 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/cas.13087 ER - TY - JOUR T1 - Beyond RCHOP: A Blueprint for Diffuse Large B Cell Lymphoma Research. AN - 1852692133; 27986884 AB - Diffuse large B cell lymphoma (DLBCL) comprises multiple molecular and biological subtypes, resulting in a broad range of clinical outcomes. With standard chemoimmunotherapy, there remains an unacceptably high treatment failure rate in certain DLBCL subsets: activated B cell (ABC) DLBCL, double-hit lymphoma defined by the dual translocation of MYC and BCL2, dual protein-expressing lymphomas defined by the overexpression of MYC and BCL2, and older patients and those with central nervous system involvement. The main research challenges for DLBCL are to accurately identify molecular subsets and to determine if specific chemotherapy platforms and targeted agents offer differential benefit. The ultimate goal should be to maximize initial cure rates to improve long-term survival while minimizing toxicity. In particular, a frontline trial should focus on biologically defined risk groups not likely to be cured with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP). An additional challenge is to develop effective and personalized strategies in the relapsed setting, for which there is no current standard other than autologous stem cell transplantation, which benefits a progressively smaller proportion of patients. Relapsed/refractory DLBCL is the ideal setting for testing novel agents and new biomarker tools and will require a national call for biopsies to optimize discovery in this setting. Accordingly, the development of tools with both prognostic and predictive utility and the individualized application of new therapies should be the main priorities. This report identifies clinical research priorities for critical areas of unmet need in this disease. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US. JF - Journal of the National Cancer Institute AU - Nowakowski, Grzegorz S AU - Blum, Kristie A AU - Kahl, Brad S AU - Friedberg, Jonathan W AU - Baizer, Lawrence AU - Little, Richard F AU - Maloney, David G AU - Sehn, Laurie H AU - Williams, Michael E AU - Wilson, Wyndham H AU - Leonard, John P AU - Smith, Sonali M AD - Department of Medicine, Mayo Clinic, Rochester, MN (GSN); Department of Internal Medicine, Ohio State University, Columbus, OH (KAB); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials (LB), Division of Cancer Treatment and Diagnosis (RFL), and Center for Cancer Research (WHW), National Cancer Institute, National Institute of Health, Bethesda, MD; Division of Oncology, University of Washington, Seattle WA (DGM); British Colombia Cancer Agency, Vancouver, BC (LHS); Department of Medicine, University of Virginia, Charlottesville, VA (MEW); Department of Medicine, Weil Cornell University, New York, NY (JPL); Department of Medicine, University of Chicago, Chicago, IL (SMS) nowakowski.grzegorz@mayo.edu. ; Department of Medicine, Mayo Clinic, Rochester, MN (GSN); Department of Internal Medicine, Ohio State University, Columbus, OH (KAB); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials (LB), Division of Cancer Treatment and Diagnosis (RFL), and Center for Cancer Research (WHW), National Cancer Institute, National Institute of Health, Bethesda, MD; Division of Oncology, University of Washington, Seattle WA (DGM); British Colombia Cancer Agency, Vancouver, BC (LHS); Department of Medicine, University of Virginia, Charlottesville, VA (MEW); Department of Medicine, Weil Cornell University, New York, NY (JPL); Department of Medicine, University of Chicago, Chicago, IL (SMS). Y1 - 2016/12// PY - 2016 DA - December 2016 VL - 108 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852692133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Beyond+RCHOP%3A+A+Blueprint+for+Diffuse+Large+B+Cell+Lymphoma+Research.&rft.au=Nowakowski%2C+Grzegorz+S%3BBlum%2C+Kristie+A%3BKahl%2C+Brad+S%3BFriedberg%2C+Jonathan+W%3BBaizer%2C+Lawrence%3BLittle%2C+Richard+F%3BMaloney%2C+David+G%3BSehn%2C+Laurie+H%3BWilliams%2C+Michael+E%3BWilson%2C+Wyndham+H%3BLeonard%2C+John+P%3BSmith%2C+Sonali+M&rft.aulast=Nowakowski&rft.aufirst=Grzegorz&rft.date=2016-12-01&rft.volume=108&rft.issue=12&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=1460-2105&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Repeated measures analysis of associations between urinary bisphenol-A concentrations and biomarkers of inflammation and oxidative stress in pregnancy AN - 1850783340; PQ0003895727 AB - Bisphenol-A (BPA) exposure occurs commonly and may adversely impact pregnancy. Endocrine disruption is posited as the primary mechanism of action, but oxidative stress and inflammation pathways may also be important. We investigated associations between BPA exposure and oxidative stress and inflammation in 482 pregnant women. Participants were recruited early in pregnancy and provided urine and plasma at up to four visits. We measured total BPA and two biomarkers of oxidative stress (8-hydroxydeoxyguanosine and 8-isoprostane) in urine from each visit. Inflammation markers, including C-reactive protein and four cytokines were measured in plasma from the same time points. In adjusted models, an interquartile range increase in BPA was associated with significant increases in both oxidative stress biomarkers (5-9% increase). Additionally, we observed significantly higher IL-6 concentrations in association with an interquartile range increase in BPA (8.95% increase). These systemic changes consequent to BPA exposure may mediate adverse birth outcomes and/or fetal development. JF - Reproductive Toxicology AU - Ferguson, Kelly K AU - Cantonwine, David E AU - McElrath, Thomas F AU - Mukherjee, Bhramar AU - Meeker, John D AD - Epidemiology Branch, National Institute of Environmental Health Sciences, 111 TW Alexander Drive, Research Triangle Park, NC, USA Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 93 EP - 98 PB - Elsevier B.V., Box 882 New York NY 10159 United States VL - 66 SN - 0890-6238, 0890-6238 KW - Toxicology Abstracts KW - BPA Bisphenol-A KW - PPAR peroxisome proliferator activated receptor KW - 8-OHdG 8-hydroxydeoxyguanosine KW - CRP C-reactive protein KW - LOD limit of detection KW - BMI body mass index KW - IQR interquartile range KW - MEHP mono-2-ethylhexyl phthalate KW - MEHHP mono-2-ethyl-5-hydroxyhexyl phthalate KW - MEOHP mono-2-ethyl-5-oxohexyl phthalate KW - MECPP mono-2-ethyl-5-carboxypentyl phthalate KW - MBzP mono-benzyl phthalate KW - MBP mono-n-butyl phthalate KW - MiBP mono-iso-butyl phthalate KW - MEP mono-ethyl phthalate KW - MCPP mono-carboxypropyl phthalate KW - BPA KW - Oxidative stress KW - Inflammation KW - IL-6 KW - Pregnancy KW - Biomarkers KW - Longitudinal KW - Interleukin 6 KW - Endocrine disruptors KW - Development KW - biomarkers KW - Fetuses KW - Models KW - 8-Hydroxydeoxyguanosine KW - Bisphenol A KW - Birth KW - Urine KW - C-reactive protein KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1850783340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+Toxicology&rft.atitle=Repeated+measures+analysis+of+associations+between+urinary+bisphenol-A+concentrations+and+biomarkers+of+inflammation+and+oxidative+stress+in+pregnancy&rft.au=Ferguson%2C+Kelly+K%3BCantonwine%2C+David+E%3BMcElrath%2C+Thomas+F%3BMukherjee%2C+Bhramar%3BMeeker%2C+John+D&rft.aulast=Ferguson&rft.aufirst=Kelly&rft.date=2016-12-01&rft.volume=66&rft.issue=&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/10.1016%2Fj.reprotox.2016.10.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-21 N1 - SubjectsTermNotLitGenreText - Interleukin 6; Endocrine disruptors; Development; biomarkers; Fetuses; Inflammation; Pregnancy; Models; Birth; Bisphenol A; 8-Hydroxydeoxyguanosine; Oxidative stress; Urine; C-reactive protein DO - http://dx.doi.org/10.1016/j.reprotox.2016.10.002 ER - TY - JOUR T1 - Association Between Type-specific HPV Infections and hTERT DNA Methylation in Patients with Invasive Cervical Cancer AN - 1850781098; PQ0003898673 AB - Background: There exists limited information on the role of hTERT methylation, and its association with type-specific HPV infections in cervical cancer. Materials and Methods: Eighty-seven frozen samples were analyzed for type-specific HPV infection using a GP5 super(+)/GP6 super(+) PCR-RLB assay (RLB). hTERT DNA methylation analysis was performed using a newly developed PCR-RLB-hTERT. Results: Ninety-three percent of samples were HPV-positive and fifteen different types were detected. hTERT methylation analysis of region 1 revealed no methylation in 78.8% of the samples and partial methylation in 21.2%. In region two, 68.2% showed no methylation and 31.8% showed a pattern of partial methylation. An association between the alpha 9 and alpha 7 species with a pattern of no methylation of hTERT in the region 1 was established (p=0.02 and p=0.03, respectively). Conclusion: Differences in patterns of methylation of the hTERT core promoter [region 1 (nt -208 to -1) and region 2 (nt +1 to +104) relative to first ATG] are related to the HPV species present. JF - Cancer Genomics & Proteomics AU - Molano, Monica AU - Moreno-Acosta, Pablo AU - Morales, NicolAs AU - Burgos, Marcela AU - Buitrago, Lina AU - Gamboa, Oscar AU - Alvarez, Rayner AU - Garland, Suzanne M AU - Tabrizi, Sepehr N AU - Steenbergen, Renske DM AU - Mejia, Juan Carlos AD - Research Group in Cancer Biology, Research Branch, National Cancer Institute, Bogota, Colombia, pmoreno@cancer.gov.co Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 483 EP - 491 PB - International Institute of Anticancer Research, 1st km Kapandritiou-Kalamou Road Kapandriti Attiki 19014 Greece VL - 13 IS - 6 SN - 1109-6535, 1109-6535 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Oncogenes & Growth Factors Abstracts KW - DNA methylation KW - uterine cervical neoplasms KW - telomerase reverse transcriptase KW - papillomavirus infections KW - Promoters KW - Invasiveness KW - Cervical cancer KW - Papillomaviridae KW - proteomics KW - Infection KW - G 07880:Human Genetics KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1850781098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Genomics+%26+Proteomics&rft.atitle=Association+Between+Type-specific+HPV+Infections+and+hTERT+DNA+Methylation+in+Patients+with+Invasive+Cervical+Cancer&rft.au=Molano%2C+Monica%3BMoreno-Acosta%2C+Pablo%3BMorales%2C+NicolAs%3BBurgos%2C+Marcela%3BBuitrago%2C+Lina%3BGamboa%2C+Oscar%3BAlvarez%2C+Rayner%3BGarland%2C+Suzanne+M%3BTabrizi%2C+Sepehr+N%3BSteenbergen%2C+Renske+DM%3BMejia%2C+Juan+Carlos&rft.aulast=Molano&rft.aufirst=Monica&rft.date=2016-12-01&rft.volume=13&rft.issue=6&rft.spage=483&rft.isbn=&rft.btitle=&rft.title=Cancer+Genomics+%26+Proteomics&rft.issn=11096535&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-21 N1 - SubjectsTermNotLitGenreText - Promoters; Invasiveness; Cervical cancer; DNA methylation; proteomics; telomerase reverse transcriptase; Infection; Papillomaviridae ER - TY - JOUR T1 - Active follow-up versus passive linkage with cancer registries for case ascertainment in a cohort AN - 1850778382; PQ0003896823 AB - Background Ascertaining incident cancers is a critical component of cancer-focused epidemiologic cohorts and of cancer prevention trials. Potential methods: for cancer case ascertainment include active follow-up and passive linkage with state cancer registries. Here we compare the two approaches in a large cancer screening trial. Methods The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial enrolled 154,955 subjects at ten U.S. centers and followed them for all-cancer incidence. Cancers were ascertained by an active follow-up process involving annual questionnaires, retrieval of records and medical record abstracting to ascertain and confirm cancers. For a subset of centers, linkage with state cancer registries was also performed. We assessed the agreement of the two methods in ascertaining incident cancers from 1993 to 2009 in 80,083 subjects from six PLCO centers where cancers were ascertained both by active follow-up and through linkages with 14 state registries. Results The ratio (times 100) of confirmed cases ascertained by registry linkage compared to active follow-up was 96.4 (95% CI: 95.1-98.2). Of cancers ascertained by either method, 86.6% and 83.5% were identified by active follow-up and by registry linkage, respectively. Of cancers missed by active follow-up, 30% were after subjects were lost to follow-up and 16% were reported but could not be confirmed. Of cancers missed by the registries, 27% were not sent to the state registry of the subject's current address at the time of linkage. Conclusion Linkage with state registries identified a similar number of cancers as active follow-up and can be a cost-effective method to ascertain incident cancers in a large cohort. JF - Cancer Epidemiology AU - Pinsky, P F AU - Yu, K AU - Black, A AU - Huang, W Y AU - Prorok, P C AD - Division of Cancer Prevention, National Cancer Institute, United States Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 26 EP - 31 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 45 SN - 1877-7821, 1877-7821 KW - Toxicology Abstracts KW - Cancer registries KW - Linkage KW - Active-follow-up KW - Case ascertainment KW - Inventories KW - Ovarian cancer KW - medical records KW - Phospholipase C KW - Prostate KW - Cancer KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1850778382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Epidemiology&rft.atitle=Active+follow-up+versus+passive+linkage+with+cancer+registries+for+case+ascertainment+in+a+cohort&rft.au=Pinsky%2C+P+F%3BYu%2C+K%3BBlack%2C+A%3BHuang%2C+W+Y%3BProrok%2C+P+C&rft.aulast=Pinsky&rft.aufirst=P&rft.date=2016-12-01&rft.volume=45&rft.issue=&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology&rft.issn=18777821&rft_id=info:doi/10.1016%2Fj.canep.2016.09.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Number of references - 6 N1 - Last updated - 2016-12-21 N1 - SubjectsTermNotLitGenreText - Ovarian cancer; Inventories; medical records; Phospholipase C; Prostate; Cancer DO - http://dx.doi.org/10.1016/j.canep.2016.09.003 ER - TY - JOUR T1 - Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study. AN - 1846721957; 27923066 AB - Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We detected driver genes by testing whether the nonsynonymous mutation rate was significantly higher than the background mutation rate and replicated our findings in public datasets with 724 samples. We performed subclonality analysis for mutations based on mutant allele data and copy number alteration data. We also tested the association between mutation signatures and clinical outcomes, including distant metastasis, survival, and tumor grade. We identified and replicated two novel candidate driver genes, POU class 4 homeobox 2 (POU4F2) (mutated in 9 [8.9%] samples) and ZKSCAN1 (mutated in 6 [5.9%] samples), and characterized their major deleterious mutations. ZKSCAN1 was part of a mutually exclusive gene set that included the RTK/RAS/RAF pathway genes BRAF, EGFR, KRAS, MET, and NF1, indicating an important driver role for this gene. Moreover, we observed strong associations between methylation in specific genomic regions and somatic mutation patterns. In the tumor evolution analysis, four driver genes had a significantly lower fraction of subclonal mutations (FSM), including TP53 (p = 0.007), KEAP1 (p = 0.012), STK11 (p = 0.0076), and EGFR (p = 0.0078), suggesting a tumor initiation role for these genes. Subclonal mutations were significantly enriched in APOBEC-related signatures (p < 2.5×10-50). The total number of somatic mutations (p = 0.0039) and the fraction of transitions (p = 5.5×10-4) were associated with increased risk of distant metastasis. Our study's limitations include a small number of LUAD patients for subgroup analyses and a single-sample design for investigation of subclonality. These data provide a genomic characterization of LUAD pathogenesis and progression. The distinct clonal and subclonal mutation signatures suggest possible diverse carcinogenesis pathways for endogenous and exogenous exposures, and may serve as a foundation for more effective treatments for this lethal disease. LUAD's high heterogeneity emphasizes the need to further study this tumor type and to associate genomic findings with clinical outcomes. JF - PLoS medicine AU - Shi, Jianxin AU - Hua, Xing AU - Zhu, Bin AU - Ravichandran, Sarangan AU - Wang, Mingyi AU - Nguyen, Cu AU - Brodie, Seth A AU - Palleschi, Alessandro AU - Alloisio, Marco AU - Pariscenti, Gianluca AU - Jones, Kristine AU - Zhou, Weiyin AU - Bouk, Aaron J AU - Boland, Joseph AU - Hicks, Belynda AU - Risch, Adam AU - Bennett, Hunter AU - Luke, Brian T AU - Song, Lei AU - Duan, Jubao AU - Liu, Pengyuan AU - Kohno, Takashi AU - Chen, Qingrong AU - Meerzaman, Daoud AU - Marconett, Crystal AU - Laird-Offringa, Ite AU - Mills, Ian AU - Caporaso, Neil E AU - Gail, Mitchell H AU - Pesatori, Angela C AU - Consonni, Dario AU - Bertazzi, Pier Alberto AU - Chanock, Stephen J AU - Landi, Maria Teresa AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America. ; Advanced Biomedical Computing Center, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, Maryland, United States of America. ; Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, Maryland, United States of America. ; Division of Thoracic Surgery, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy. ; Division of Thoracic Surgery, Istituto Clinico Humanitas, Rozzano, Milan, Italy. ; Thoracic Surgery Unit, Community Hospital, Brescia, Italy. ; Information Management Services, Inc., Rockville, Maryland, United States of America. ; Center for Psychiatric Genetics, Department of Psychiatry and Behavioral Sciences, North Shore University Health System Research Institute, University of Chicago Pritzker School of Medicine, Evanston, Illinois, United States of America. ; Department of Physiology & Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America. ; Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan. ; Departments of Surgery and of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America. ; Prostate Cancer UK/Movember Centre of Excellence for Prostate Cancer Research, Centre for Cancer Research and Cell Biology, Queen's University, Belfast, United Kingdom. ; Epidemiology Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1 VL - 13 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846721957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PLoS+medicine&rft.atitle=Somatic+Genomics+and+Clinical+Features+of+Lung+Adenocarcinoma%3A+A+Retrospective+Study.&rft.au=Shi%2C+Jianxin%3BHua%2C+Xing%3BZhu%2C+Bin%3BRavichandran%2C+Sarangan%3BWang%2C+Mingyi%3BNguyen%2C+Cu%3BBrodie%2C+Seth+A%3BPalleschi%2C+Alessandro%3BAlloisio%2C+Marco%3BPariscenti%2C+Gianluca%3BJones%2C+Kristine%3BZhou%2C+Weiyin%3BBouk%2C+Aaron+J%3BBoland%2C+Joseph%3BHicks%2C+Belynda%3BRisch%2C+Adam%3BBennett%2C+Hunter%3BLuke%2C+Brian+T%3BSong%2C+Lei%3BDuan%2C+Jubao%3BLiu%2C+Pengyuan%3BKohno%2C+Takashi%3BChen%2C+Qingrong%3BMeerzaman%2C+Daoud%3BMarconett%2C+Crystal%3BLaird-Offringa%2C+Ite%3BMills%2C+Ian%3BCaporaso%2C+Neil+E%3BGail%2C+Mitchell+H%3BPesatori%2C+Angela+C%3BConsonni%2C+Dario%3BBertazzi%2C+Pier+Alberto%3BChanock%2C+Stephen+J%3BLandi%2C+Maria+Teresa&rft.aulast=Bae&rft.aufirst=Jisuk&rft.date=2016-02-01&rft.volume=543&rft.issue=&rft.spage=28&rft.isbn=&rft.btitle=&rft.title=The+Science+of+the+total+environment&rft.issn=1879-1026&rft_id=info:doi/10.1016%2Fj.scitotenv.2015.11.019 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-06 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1371/journal.pmed.1002162 ER - TY - JOUR T1 - Genetic diversity of Klebsiella pneumoniae isolates during an outbreak in a non-human primate research colony AN - 1846409917; PQ0003857925 AB - Background Klebsiella pneumoniae can be a serious pathogen in non-human primates, particularly Neotropical monkeys. Methods During a K. pneumoniae outbreak in an owl monkey research colony, 13 K. pneumoniae isolates were DNA fingerprinted by automated repetitive extragenic palindromic-polymerase chain reaction and the profiles compared to isolates obtained from other non-human primate species during the same time period and isolates from previous outbreaks. Results Eleven different types of K. pneumoniae were circulating in the owl monkey colony at the time of the outbreak. When comparing owl monkey isolates relatedness to previous colony outbreak isolates and squirrel monkey and capuchin monkey isolates, all were different. Conclusions These results agree with recent reports where K. pneumoniae nosocomial isolates in hospital settings can have high genetic diversity, and multiple strains can be circulating simultaneously. This potential genetic diversity should be considered when designing strategies for controlling K. pneumoniae outbreaks in captive non-human primate colonies. JF - Journal of Medical Primatology (Online) AU - Gozalo, Alfonso S AU - Elkins, William R AU - Lambert, Lynn E AU - Stock, Frida AU - Thomas, Marvin L AU - Woodward, Ruth A AD - Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 312 EP - 317 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 45 IS - 6 SN - 0047-2565, 0047-2565 KW - Microbiology Abstracts B: Bacteriology; CSA Neurosciences Abstracts KW - Saimiri KW - Colonies KW - DNA KW - Genetic diversity KW - Pathogens KW - Klebsiella pneumoniae KW - Hospitals KW - N3 11145:Methodology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846409917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Medical+Primatology+%28Online%29&rft.atitle=Genetic+diversity+of+Klebsiella+pneumoniae+isolates+during+an+outbreak+in+a+non-human+primate+research+colony&rft.au=Gozalo%2C+Alfonso+S%3BElkins%2C+William+R%3BLambert%2C+Lynn+E%3BStock%2C+Frida%3BThomas%2C+Marvin+L%3BWoodward%2C+Ruth+A&rft.aulast=Gozalo&rft.aufirst=Alfonso&rft.date=2016-12-01&rft.volume=45&rft.issue=6&rft.spage=312&rft.isbn=&rft.btitle=&rft.title=Journal+of+Medical+Primatology+%28Online%29&rft.issn=00472565&rft_id=info:doi/10.1111%2Fjmp.12229 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2017-02-01 N1 - SubjectsTermNotLitGenreText - Colonies; DNA; Genetic diversity; Pathogens; Hospitals; Saimiri; Klebsiella pneumoniae DO - http://dx.doi.org/10.1111/jmp.12229 ER - TY - JOUR T1 - Disposition of the Emerging Brominated Flame Retardant, 2-Ethylhexyl 2,3,4,5-Tetrabromobenzoate, in Female SD Rats and Male B6C3F1 Mice: Effects of Dose, Route, and Repeated Administration. AN - 1846365671; 27613714 AB - 2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB; MW 549.92 g/mol; CAS 183658-27-7) is a brominated component of flame retardant mixtures used as substitutes for some PBDEs. EH-TBB is added to various consumer products, including polyurethane foams, and has been detected in humans. The present study characterized the fate of EH-TBB in rodents. [14C]-labeled EH-TBB was absorbed, metabolized, and eliminated via the urine and feces following single administrations of 0.1-100 µmol/kg (∼0.05-55 mg/kg) or repeated administration (0.1 µmol/kg/day × 5-10 days) by gavage to female Hsd:Sprague DawleySD (SD) rats. Cumulative excretion via feces increased (39-60%) with dose (0.1-10 µmol/kg) with corresponding decreases in urinary excretion (54 to 37%) after 72 h. Delayed excretion of [14C]-radioactivity in urine and feces of a 100 µmol/kg oral dose was noted. Recovery was complete for all doses by 72 h. IV-injected rats excreted more of the 0.1 µmol/kg dose in urine and less in feces than did gavaged rats, indicating partial biliary elimination of systemically available compound. No tissue bioaccumulation was found for rats given 5 oral daily doses of EH-TBB. Parent molecule was not detected in urine whereas 2 metabolites, tetrabromobenzoic acid (TBBA), a TBBA-sulfate conjugate, and a TBBA-glycine conjugate were identified. EH-TBB and TBBA were identified in extracts from feces. Data from gavaged male B6C3F1/Tac mice indicated minimal sex- or species differences are likely for the disposition of EH-TBB. Approximately 85% of a 0.1 µmol/kg dose was absorbed from the gut. Overall absorption of EH-TBB is expected to be even greater at lower levels. Published by Oxford University Press on behalf of the Society of Toxicology 2016. This work is written by US Government employees and is in the public domain in the US. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Knudsen, Gabriel A AU - Sanders, J Michael AU - Birnbaum, Linda S AD - NCI Laboratory of Toxicology and Toxicokinetics, Research Triangle Park, North Carolina gabriel.knudsen@nih.gov. ; NCI Laboratory of Toxicology and Toxicokinetics, Research Triangle Park, North Carolina. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 392 EP - 402 VL - 154 IS - 2 KW - metabolism. KW - 2-Ethylhexyl 2,3,4,5-Tetrabromobenzoate KW - disposition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846365671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Disposition+of+the+Emerging+Brominated+Flame+Retardant%2C+2-Ethylhexyl+2%2C3%2C4%2C5-Tetrabromobenzoate%2C+in+Female+SD+Rats+and+Male+B6C3F1+Mice%3A+Effects+of+Dose%2C+Route%2C+and+Repeated+Administration.&rft.au=Knudsen%2C+Gabriel+A%3BSanders%2C+J+Michael%3BBirnbaum%2C+Linda+S&rft.aulast=Knudsen&rft.aufirst=Gabriel&rft.date=2016-12-01&rft.volume=154&rft.issue=2&rft.spage=392&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=1096-0929&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Novel TDP2-ubiquitin interactions and their importance for the repair of topoisomerase II-mediated DNA damage. AN - 1846024050; 27543075 AB - Tyrosyl DNA phosphodiesterase 2 (TDP2) is a multifunctional protein implicated in DNA repair, signal transduction and transcriptional regulation. In its DNA repair role, TDP2 safeguards genome integrity by hydrolyzing 5'-tyrosyl DNA adducts formed by abortive topoisomerase II (Top2) cleavage complexes to allow error-free repair of DNA double-strand breaks, thereby conferring cellular resistance against Top2 poisons. TDP2 consists of a C-terminal catalytic domain responsible for its phosphodiesterase activity, and a functionally uncharacterized N-terminal region. Here, we demonstrate that this N-terminal region contains a ubiquitin (Ub)-associated (UBA) domain capable of binding multiple forms of Ub with distinct modes of interactions and preference for either K48- or K63-linked polyUbs over monoUb. The structure of TDP2 UBA bound to monoUb shows a canonical mode of UBA-Ub interaction. However, the absence of the highly conserved MGF motif and the presence of a fourth α-helix make TDP2 UBA distinct from other known UBAs. Mutations in the TDP2 UBA-Ub binding interface do not affect nuclear import of TDP2, but severely compromise its ability to repair Top2-mediated DNA damage, thus establishing the importance of the TDP2 UBA-Ub interaction in DNA repair. The differential binding to multiple Ub forms could be important for responding to DNA damage signals under different contexts or to support the multi-functionality of TDP2. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. JF - Nucleic acids research AU - Rao, Timsi AU - Gao, Rui AU - Takada, Saeko AU - Al Abo, Muthana AU - Chen, Xiang AU - Walters, Kylie J AU - Pommier, Yves AU - Aihara, Hideki AD - Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA. ; Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. ; Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA. ; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA aihar001@umn.edu. Y1 - 2016/12/01/ PY - 2016 DA - 2016 Dec 01 SP - 10201 EP - 10215 VL - 44 IS - 21 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846024050?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Novel+TDP2-ubiquitin+interactions+and+their+importance+for+the+repair+of+topoisomerase+II-mediated+DNA+damage.&rft.au=Rao%2C+Timsi%3BGao%2C+Rui%3BTakada%2C+Saeko%3BAl+Abo%2C+Muthana%3BChen%2C+Xiang%3BWalters%2C+Kylie+J%3BPommier%2C+Yves%3BAihara%2C+Hideki&rft.aulast=Rao&rft.aufirst=Timsi&rft.date=2016-12-01&rft.volume=44&rft.issue=21&rft.spage=10201&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Stability of core language skill across the first decade of life in children at biological and social risk AN - 1845015267 AB - Background Command of language is a fundamental skill, a cornerstone of multiple cognitive and socioemotional aspects of development, and a necessary ingredient of successful adjustment and functioning in society. Little is known about the developmental stability of language in at-risk youth or which biological and social risk factors moderate stability. Methods This four-wave 10-year prospective longitudinal study evaluated stability of core language skill in 1,780 children in varying categories of biological and social risk in a multiage, multidomain, multimeasure, and multireporter framework. Results Structural equation modeling supported loadings of diverse age-appropriate measures of child language on single latent variables of core language skill at 15 and 25 months and 5 and 11 years, respectively. Core language skill was stable over the first decade of life; significant and comparable stability coefficients were obtained for children with diverse biological and social risks, including poor health, welfare status, teen motherhood, ethnicity, gender, birth order, and families that changed in income and maternal education over the study period; stability in language was strong even accounting for child nonverbal intelligence and social competence, maternal education and language, and the family home environment. Conclusions Core language skill varies in stability with age but is robustly stable in children regardless of multiple biological and social risk factors. JF - Journal of Child Psychology and Psychiatry AU - Bornstein, Marc H AU - Hahn, Chun-Shin AU - Putnick, Diane L AD - Child and Family Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Public Health Service, Bethesda, MD, USA ; Child and Family Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Public Health Service, Bethesda, MD, USA Y1 - 2016/12// PY - 2016 DA - Dec 2016 SP - 1434 EP - 1443 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 12 KW - Psychology KW - At risk KW - Intelligence KW - Birth order KW - Socioemotional aspects KW - Home environment KW - Risk factors KW - Ethnicity KW - Health status KW - Welfare KW - Social competence KW - Motherhood KW - Nonverbal intelligence KW - Adolescent motherhood KW - Childbirth UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1845015267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Stability+of+core+language+skill+across+the+first+decade+of+life+in+children+at+biological+and+social+risk&rft.au=Bornstein%2C+Marc+H%3BHahn%2C+Chun-Shin%3BPutnick%2C+Diane+L&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=2016-12-01&rft.volume=57&rft.issue=12&rft.spage=1434&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12632 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1111/jcpp.12632 ER - TY - JOUR T1 - Commentary: Mapping the young, resilient brain - reflections on Burt et al. (2016) AN - 1845015051 AB - The resilience of many children in the face of adversity has long been a research focus. The study by Burt et al. delineates the neuroanatomy of resilience, using in vivo magnetic resonance images acquired on 1,800 youth. They find that resilient youth had a larger right lateral prefrontal cortex compared to youth who either lacked resilience or did not experience adversity. The size of the right lateral prefrontal cortex was further associated with a likelihood of a maladaptive problem of alcohol use. These findings implicate high-order regulatory processes supported by the right lateral prefrontal cortex as pivotal in resilience. The study also sets the stage for exploring how neuroimaging data, combined with behavioral and genomic information might be used to assess treatment efficacy and identify children who need therapeutic interventions to boost their resilience. Read the full article at doi: 10.1111/jcpp.12552 JF - Journal of Child Psychology and Psychiatry AU - Shaw, Philip AD - Neurobehavioral Clinical Research Section, Social and Behavioral Research Branch, National Human Genome Research Institute and the National Institute of Mental Health, Bethesda, MD, USA ; Neurobehavioral Clinical Research Section, Social and Behavioral Research Branch, National Human Genome Research Institute and the National Institute of Mental Health, Bethesda, MD, USA Y1 - 2016/12// PY - 2016 DA - Dec 2016 SP - 1465 EP - 1466 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 12 KW - Psychology KW - Neuroimaging KW - Young people KW - Adversity KW - Brain KW - Neuroanatomy KW - Cortex KW - Efficacy KW - Mapping KW - Problem drinking KW - Resilience UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1845015051?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Commentary%3A+Mapping+the+young%2C+resilient+brain+-+reflections+on+Burt+et%26amp%3B%23xa0%3Bal.+%282016%29&rft.au=Shaw%2C+Philip&rft.aulast=Shaw&rft.aufirst=Philip&rft.date=2016-12-01&rft.volume=57&rft.issue=12&rft.spage=1465&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12613 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1111/jcpp.12613 ER - TY - JOUR T1 - The experience of electroconvulsive therapy and its impact on associated stigma: A meta-analysis AN - 1844719041 AB - Background: Despite its efficacy and safety, electroconvulsive therapy (ECT) is underutilized, in part due to stigma associated with the treatment. Aims: The aim of this study was to test the hypothesis that experiencing ECT has an impact on associated stigma, as measured by patient and family knowledge of and attitudes toward ECT. Methods: A comprehensive literature search was conducted using MEDLINE, EMBASE and PsycINFO. Studies with cross-sectional and/or longitudinal designs were identified. Studies were further categorized into subcategories based on participant type (patients or patient family members) and outcome domain (knowledge or attitudes). Effect size (Cohen's d ) was calculated for each study and then integrated into each subcategory (participant type by outcome domain) using a random effect model. Results: Eight studies were identified as being eligible for analysis. Two studies were cross-sectional, five were longitudinal and one incorporated both designs. Analysis of the longitudinal studies indicated that experiencing ECT both increased knowledge of and improved attitudes toward ECT in patients; in family members of patients, analysis showed significant positive change in knowledge of ECT, but no significant change in attitudes toward ECT. Conclusion: Experience with ECT may have a positive impact on knowledge of and attitudes toward ECT. However, the quality of evidence of included studies was low; further research is required in order to clarify the relationship and to identify information of use to individuals considering ECT as a treatment option. JF - The International Journal of Social Psychiatry AU - Aoki, Yuta AU - Yamaguchi, Sosei AU - Ando, Shuntaro AU - Sasaki, Natsuki AU - Bernick, Peter J AU - Akiyama, Tsuyoshi AD - The Child Study Center, New York University Langone Medical Center, New York, NY, USA; Department of Neuropsychiatry, The University of Tokyo, Tokyo, Japan ; Department of Psychiatric Rehabilitation, National Institute of Mental Health, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan ; Department of Neuropsychiatry, The University of Tokyo, Tokyo, Japan; Department of Psychiatry and Behavioral Science, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan ; Department of Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan ; Center for Health and Community Medicine and the Student Accessibility Office, Nagasaki University, Nagasaki, Japan ; Department of Neuropsychiatry, NTT Medical Center Tokyo, Tokyo, Japan ; The Child Study Center, New York University Langone Medical Center, New York, NY, USA; Department of Neuropsychiatry, The University of Tokyo, Tokyo, Japan Y1 - 2016/12// PY - 2016 DA - Dec 2016 SP - 708 EP - 718 CY - London PB - SAGE PUBLICATIONS, INC. VL - 62 IS - 8 SN - 0020-7640 KW - Medical Sciences--Psychiatry And Neurology KW - Attitude KW - electroconvulsive therapy KW - meta-analysis KW - stigma KW - systematic review KW - Electroconvulsive therapy KW - Studies KW - Attitudes KW - Patients KW - Stigma KW - Positive action KW - Analysis KW - Efficacy KW - Relatives KW - Safety KW - Stigmatization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844719041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+International+Journal+of+Social+Psychiatry&rft.atitle=The+experience+of+electroconvulsive+therapy+and+its+impact+on+associated+stigma%3A+A+meta-analysis&rft.au=Aoki%2C+Yuta%3BYamaguchi%2C+Sosei%3BAndo%2C+Shuntaro%3BSasaki%2C+Natsuki%3BBernick%2C+Peter+J%3BAkiyama%2C+Tsuyoshi&rft.aulast=Aoki&rft.aufirst=Yuta&rft.date=2016-12-01&rft.volume=62&rft.issue=8&rft.spage=708&rft.isbn=&rft.btitle=&rft.title=The+International+Journal+of+Social+Psychiatry&rft.issn=00207640&rft_id=info:doi/10.1177%2F0020764016675379 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © The Author(s) 2016 N1 - Last updated - 2017-01-29 DO - http://dx.doi.org/10.1177/0020764016675379 ER - TY - JOUR T1 - Update on Burkitt Lymphoma. AN - 1844354298; 27888884 AB - Because of its rarity and high curability, progress in advancing therapeutics in Burkitt lymphoma (BL) has been difficult. Over recent years, several new mutations that cooperate with MYC have been identified, and this has paved the way for testing novel agents in the disease. One of the challenges of most standard approaches typically used is severe treatment-related toxicity that often leads to discontinuation of therapy. To that point, there has been recent success developing intermediate intensity approaches that are well tolerated in all patient groups and maintain high cure rates in a multicenter setting. Published by Elsevier Inc. JF - Hematology/oncology clinics of North America AU - Dunleavy, Kieron AU - Little, Richard F AU - Wilson, Wyndham H AD - Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: dunleavk@mail.nih.gov. ; HIV and Stem Cell Therapeutics, Cancer Therapeutic Evaluation Program (CTEP), National Cancer Institute, Bethesda, MD 20892, USA. ; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1333 EP - 1343 VL - 30 IS - 6 KW - Risk-adapted KW - Endemic KW - CCND3 KW - Sporadic KW - Burkitt lymphoma KW - ID3 KW - TCF3 KW - MYC UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844354298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hematology%2Foncology+clinics+of+North+America&rft.atitle=Update+on+Burkitt+Lymphoma.&rft.au=Dunleavy%2C+Kieron%3BLittle%2C+Richard+F%3BWilson%2C+Wyndham+H&rft.aulast=Dunleavy&rft.aufirst=Kieron&rft.date=2016-12-01&rft.volume=30&rft.issue=6&rft.spage=1333&rft.isbn=&rft.btitle=&rft.title=Hematology%2Foncology+clinics+of+North+America&rft.issn=1558-1977&rft_id=info:doi/10.1016%2Fj.hoc.2016.07.009 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.hoc.2016.07.009 ER - TY - JOUR T1 - Anal human papillomavirus in HIV-uninfected men who have sex with men: incidence and clearance rates, duration of infection, and risk factors. AN - 1844352031; 27585942 AB - Little is known regarding the natural history of anal human papillomavirus (HPV) infection. We aimed to evaluate incidence and clearance rates, their risk factors, and duration of anal HPV infection in HIV-uninfected men who have sex with men (MSM). A longitudinal study was conducted. Anal samples were analysed using the Linear Array HPV Genotyping test. Incidence and clearance rates, and corresponding risk factors, were estimated using a two-state Markov model. Overall, 155 MSM (median age 33.4 years) attending the largest sexually transmitted infection (STI) centre in Rome, Italy, were followed for a median of 12.2 months (Q1-Q3: 7.0-18.1). Incidence and clearance rates for any HPV were 85.6 (95% CI: 58.4-125.4) and 35.6 (95% CI: 24.7-51.5) × 1000 person-months, respectively; the median duration of infection was 9.4 months (Q1-Q3: 7.5-12.1). Receptive anal sex emerged as the only risk factor for the acquisition of any HPV (Hazard Ratio, HR = 2.65, 95% CI: 1.16-6.06). The incidence rates for carcinogenic and non-carcinogenic types were 42.3 (95% CI: 29.2-61.4) and 29.2 (95% CI: 19.5-43.7) × 1000 person-months, respectively (p = 0.13); their clearance rates were 62.9 (95% CI: 45.1-87.7) and 65.7 (95% CI: 47.4-91.0) × 1000 person-months, respectively (p = 0.83). HPV16 showed the lowest clearance rate among carcinogenic types (59.7 × 1000 person-months), and a duration of infection of 16.8 months. In conclusion, a higher incidence rate was observed for carcinogenic compared to non-carcinogenic HPV types, although the difference was not significant. HPV16 emerged as the type with the longest duration of infection and the lowest clearance rate among carcinogenic types. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved. JF - Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases AU - Donà, M G AU - Vescio, M F AU - Latini, A AU - Giglio, A AU - Moretto, D AU - Frasca, M AU - Benevolo, M AU - Rollo, F AU - Colafigli, M AU - Cristaudo, A AU - Giuliani, M AD - STI/HIV Unit, UOC Dermatologia Infettiva e Allergologica, San Gallicano Dermatological Institute (IFO-IRCCS), Rome, Italy. Electronic address: mariagabriella.dona@ifo.gov.it. ; Infectious, Parasitic and Immunomediated Diseases Department, Istituto Superiore di Sanità, Rome, Italy. ; STI/HIV Unit, UOC Dermatologia Infettiva e Allergologica, San Gallicano Dermatological Institute (IFO-IRCCS), Rome, Italy. ; Microbiology and Clinical Pathology Department, San Gallicano Dermatological Institute (IFO-IRCCS), Rome, Italy. ; Pathology Department, Regina Elena National Cancer Institute (IFO-IRCCS), Rome, Italy. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1004.e1 EP - 1004.e7 VL - 22 IS - 12 KW - Men who have sex with men KW - Risk factors KW - Anal infection KW - HIV-negative KW - Incidence KW - Clearance KW - Markov KW - Human papillomavirus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844352031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+microbiology+and+infection+%3A+the+official+publication+of+the+European+Society+of+Clinical+Microbiology+and+Infectious+Diseases&rft.atitle=Anal+human+papillomavirus+in+HIV-uninfected+men+who+have+sex+with+men%3A+incidence+and+clearance+rates%2C+duration+of+infection%2C+and+risk+factors.&rft.au=Don%C3%A0%2C+M+G%3BVescio%2C+M+F%3BLatini%2C+A%3BGiglio%2C+A%3BMoretto%2C+D%3BFrasca%2C+M%3BBenevolo%2C+M%3BRollo%2C+F%3BColafigli%2C+M%3BCristaudo%2C+A%3BGiuliani%2C+M&rft.aulast=Don%C3%A0&rft.aufirst=M&rft.date=2016-12-01&rft.volume=22&rft.issue=12&rft.spage=1004.e1&rft.isbn=&rft.btitle=&rft.title=Clinical+microbiology+and+infection+%3A+the+official+publication+of+the+European+Society+of+Clinical+Microbiology+and+Infectious+Diseases&rft.issn=1469-0691&rft_id=info:doi/10.1016%2Fj.cmi.2016.08.011 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-30 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.cmi.2016.08.011 ER - TY - JOUR T1 - Identification of novel SNPs associated with risk and prognosis in patients with castration-resistant prostate cancer. AN - 1844021333; 27883295 AB - Metabolism and transport play major roles in life-long exposure to endogenous and exogenous carcinogens. We therefore explored associations between polymorphisms in absorption, distribution, metabolism and elimination genes and the risk and prognosis of castration-resistant prostate cancer (CRPC). A total of 634 genotypes were tested in 74 patients using the Affymetrix DMETv1.0 platform. No relation to risk was found. Three SNPs were associated with CRPC prognosis in Caucasians: ABCB11 rs7602171G>A (p = 0.003; n = 30; hazard ratio [HR]: 0.307), GSTP1 rs1799811C>T (p = 0.001; n = 38; HR: 0.254) and SLC5A6 rs1395 (p = 0.004; n = 35; HR: 3.15). Two other polymorphisms among Caucasians were associated with interesting trends: ABCB4 rs2302387C>T (p = 0.039) and ABCC5 rs939339A>G (p = 0.018). This exploratory study is the first to show that polymorphisms in several absorption, distribution, metabolism and elimination genes may be associated with CRPC prognosis. JF - Pharmacogenomics AU - Sissung, Tristan M AU - Deeken, John AU - Leibrand, Crystal R AU - Price, Douglas K AU - Ehrlich, Sheryl AU - Steinberg, Seth M AU - Liewehr, David J AU - Dahut, William AU - Figg, William D AD - Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, 9000 Rockville Pike, Building 10, Room 5A01, Bethesda, MD 20892, USA. ; Inova Comprehensive Cancer & Research Institute, Falls Church, VA 22042, USA. ; Molecular Pharmacology Program, National Cancer Institute, 9000 Rockville Pike, Building 10, Room 5A01, Bethesda, MD 20892, USA. ; Biostatistics & Data Management Section, Office of the Clinical Director, National Cancer Institute, NIH, Shady Grove, MD 20850, USA. ; Prostate Cancer Clinical Research Section, Genitourinary Malignancies Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1979 EP - 1986 VL - 17 IS - 18 KW - transport KW - metabolism KW - castration-resistant prostate cancer KW - genotype KW - survival KW - outcome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844021333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenomics&rft.atitle=Identification+of+novel+SNPs+associated+with+risk+and+prognosis+in+patients+with+castration-resistant+prostate+cancer.&rft.au=Sissung%2C+Tristan+M%3BDeeken%2C+John%3BLeibrand%2C+Crystal+R%3BPrice%2C+Douglas+K%3BEhrlich%2C+Sheryl%3BSteinberg%2C+Seth+M%3BLiewehr%2C+David+J%3BDahut%2C+William%3BFigg%2C+William+D&rft.aulast=Sissung&rft.aufirst=Tristan&rft.date=2016-12-01&rft.volume=17&rft.issue=18&rft.spage=1979&rft.isbn=&rft.btitle=&rft.title=Pharmacogenomics&rft.issn=1744-8042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study. AN - 1841794380; 27863194 AB - Purpose Kaposi's sarcoma (KS) is a multicentric tumor caused by Kaposi's sarcoma-associated herpesvirus. Unmet needs include therapies that are oral, anthracycline sparing, and deliverable in resource-limited settings. We evaluated pomalidomide, an oral immune modulatory agent, in patients with symptomatic KS. Methods The primary objectives were to assess tolerability, pharmacokinetics, and activity. Initial dosage level was 5 mg once per day for 21 days per 28-day cycle, with a de-escalated level of 3 mg if not tolerable, and aspirin 81 mg once per day thromboprophylaxis. HIV-infected patients required controlled viremia with either persistent KS despite 3 months of antiretroviral therapy (ART) or progressive KS despite 2 months of ART. Evaluations included tumor response and health-related quality of life (HRQL). Results Twenty-two patients were treated; 15 (68%) were HIV infected, 17 (77%) had advanced (T1) disease, and 19 (86%) previous KS therapy excluding ART. All were treated with 5 mg because no dose-limiting toxicities occurred. Over 156 cycles, the grade 3/4 adverse events possibly attributable to therapy were neutropenia (23 cycles, 10 patients), infection (1 cycle), and edema (1 cycle). Sixteen patients responded (73%; 95% CI, 50% to 89%): nine of 15 HIV-infected patients (60%; 95% CI, 32% to 84%) and all seven HIV-uninfected patients (100%; 95% CI, 59% to 100%). Median time to response was 4 weeks (range, 4 to 36 weeks). HRQL showed no impairment during therapy and improved satisfaction with appearance at end therapy ( P = .03). Significant increases in CD4+ and CD8+ cells were seen in patients with and without HIV, together with a transient increase in Kaposi's sarcoma-associated herpesvirus viral load at week 4 ( P = .05). Conclusion Pomalidomide is well tolerated and active in KS regardless of HIV status. Responses were rapid, with improved self-reported outcomes, and occurred in advanced and heavily pretreated disease. Correlative studies support, at least in part, an immunologic mechanism of activity. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Polizzotto, Mark N AU - Uldrick, Thomas S AU - Wyvill, Kathleen M AU - Aleman, Karen AU - Peer, Cody J AU - Bevans, Margaret AU - Sereti, Irini AU - Maldarelli, Frank AU - Whitby, Denise AU - Marshall, Vickie AU - Goncalves, Priscila H AU - Khetani, Vikram AU - Figg, William D AU - Steinberg, Seth M AU - Zeldis, Jerome B AU - Yarchoan, Robert AD - Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 4125 EP - 4131 VL - 34 IS - 34 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841794380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Pomalidomide+for+Symptomatic+Kaposi%27s+Sarcoma+in+People+With+and+Without+HIV+Infection%3A+A+Phase+I%2FII+Study.&rft.au=Polizzotto%2C+Mark+N%3BUldrick%2C+Thomas+S%3BWyvill%2C+Kathleen+M%3BAleman%2C+Karen%3BPeer%2C+Cody+J%3BBevans%2C+Margaret%3BSereti%2C+Irini%3BMaldarelli%2C+Frank%3BWhitby%2C+Denise%3BMarshall%2C+Vickie%3BGoncalves%2C+Priscila+H%3BKhetani%2C+Vikram%3BFigg%2C+William+D%3BSteinberg%2C+Seth+M%3BZeldis%2C+Jerome+B%3BYarchoan%2C+Robert&rft.aulast=Polizzotto&rft.aufirst=Mark&rft.date=2016-12-01&rft.volume=34&rft.issue=34&rft.spage=4125&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=1527-7755&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Mesothelin Immunotherapy for Cancer: Ready for Prime Time? AN - 1841794130; 27863199 AB - Mesothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. It is an attractive target for cancer immunotherapy because its normal expression is limited to mesothelial cells, which are dispensable. Several antibody-based therapeutic agents as well as vaccine and T-cell therapies directed at mesothelin are undergoing clinical evaluation. These include antimesothelin immunotoxins (SS1P, RG7787/LMB-100), chimeric antimesothelin antibody (amatuximab), mesothelin-directed antibody drug conjugates (anetumab ravtansine, DMOT4039A, BMS-986148), live attenuated Listeria monocytogenes-expressing mesothelin (CRS-207, JNJ-64041757), and chimeric antigen receptor T-cell therapies. Two antimesothelin agents are currently in multicenter clinical registration trials for malignant mesothelioma: amatuximab in the first-line setting and anetumab ravtansine as second-line therapy. Phase II randomized clinical trials of CRS-207 as a boosting agent and in combination with immune checkpoint inhibition for pancreatic cancer are nearing completion. These ongoing studies will define the utility of mesothelin immunotherapy for treating cancer. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Hassan, Raffit AU - Thomas, Anish AU - Alewine, Christine AU - Le, Dung T AU - Jaffee, Elizabeth M AU - Pastan, Ira AD - Raffit Hassan, Anish Thomas, Christine Alewine, and Ira Pastan, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda; and Dung T. Le and Elizabeth M. Jaffee, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 4171 EP - 4179 VL - 34 IS - 34 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841794130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Mesothelin+Immunotherapy+for+Cancer%3A+Ready+for+Prime+Time%3F&rft.au=Hassan%2C+Raffit%3BThomas%2C+Anish%3BAlewine%2C+Christine%3BLe%2C+Dung+T%3BJaffee%2C+Elizabeth+M%3BPastan%2C+Ira&rft.aulast=Hassan&rft.aufirst=Raffit&rft.date=2016-12-01&rft.volume=34&rft.issue=34&rft.spage=4171&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=1527-7755&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Predispositions to Lymphoma: A Practical Review for Genetic Counselors AN - 1841002335 AB - This review provides a synopsis for genetic counselors of the major concepts of lymphoma predisposition: genomic instability, immune deficiency, inappropriate lymphoproliferation, and chronic antigen stimulation. We discuss syndromes typifying each of these mechanisms. Importantly, our review of the genetic counseling literature reveals sparse discussion of genetically-based immune-mediated lymphoma predisposition, which we address in depth here. We aim to increase awareness among genetic counselors and colleagues in oncology about familial susceptibility and facilitate critical thinking about lymphoma risk assessment. Clinical application of this knowledge is aided by recommendations for collection of personal and family history to guide risk assessment and testing. Lastly, we include a special discussion of genetic counseling issues including perceptions of the context, nature, and magnitude of lymphoma risk, as well as coping with awareness of susceptibility to lymphoma. JF - Journal of Genetic Counseling AU - Similuk, Morgan AU - Rao, V Koneti AU - Churpek, Jane AU - Lenardo, Michael AD - National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA ; University of Chicago Medical Center, Chicago, IL, USA ; National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA Y1 - 2016/12// PY - 2016 DA - Dec 2016 SP - 1157 EP - 1170 CY - New York PB - Springer Science & Business Media VL - 25 IS - 6 SN - 1059-7700 KW - Psychology KW - Lymphoma KW - Heredity KW - Predisposition KW - Cancer KW - Mechanism KW - Genetic counseling KW - Risk assessment KW - Immunology KW - Susceptibility KW - Oncology KW - Stimulation KW - Counselling KW - Clinical assessment KW - Genetic family histories KW - Inappropriateness KW - Critical thinking KW - Clinical guidelines KW - Coping KW - Genetic counselling UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841002335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Journal+of+Genetic+Counseling&rft.atitle=Predispositions+to+Lymphoma%3A+A+Practical+Review+for+Genetic+Counselors&rft.au=Similuk%2C+Morgan%3BRao%2C+V+Koneti%3BChurpek%2C+Jane%3BLenardo%2C+Michael&rft.aulast=Similuk&rft.aufirst=Morgan&rft.date=2016-12-01&rft.volume=25&rft.issue=6&rft.spage=1157&rft.isbn=&rft.btitle=&rft.title=Journal+of+Genetic+Counseling&rft.issn=10597700&rft_id=info:doi/10.1007%2Fs10897-016-9979-0 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Journal of Genetic Counseling is a copyright of Springer, 2016. N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1007/s10897-016-9979-0 ER - TY - JOUR T1 - Respiratory toxicity and immunotoxicity evaluations of microparticle and nanoparticle C60 fullerene aggregates in mice and rats following nose-only inhalation for 13 weeks. AN - 1839740976; 27618498 AB - C60 fullerene (C60), or buckminsterfullerene, is a spherical arrangement of 60 carbon atoms, having a diameter of approximately 1 nm, and is produced naturally as a by-product of combustion. Due to its small size, C60 has attracted much attention for use in a variety of applications; however, insufficient information is available regarding its toxicological effects. The effects on respiratory toxicity and immunotoxicity of C60 aggregates (50 nm [nano-C60] and 1 μm [micro-C60] diameter) were examined in B6C3F1/N mice and Wistar Han rats after nose-only inhalation for 13 weeks. Exposure concentrations were selected to allow for data evaluations using both mass-based and particle surface area-based exposure metrics. Nano-C60 exposure levels selected were 0.5 and 2 mg/m3 (0.033 and 0.112 m2/m3), while micro-C60 exposures were 2, 15 and 30 mg/m3 (0.011, 0.084 and 0.167 m2/m3). There were no systemic effects on innate, cell-mediated, or humoral immune function. Pulmonary inflammatory responses (histiocytic infiltration, macrophage pigmentation, chronic inflammation) were concentration-dependent and corresponded to increases in monocyte chemoattractant protein (MCP)-1 (rats) and macrophage inflammatory protein (MIP)-1α (mice) in bronchoalveolar lavage (BAL) fluid. Lung overload may have contributed to the pulmonary inflammatory responses observed following nano-C60 exposure at 2 mg/m3 and micro-C60 exposure at 30 mg/m3. Phenotype shifts in cells recovered from the BAL were also observed in all C60-exposed rats, regardless of the level of exposure. Overall, more severe pulmonary effects were observed for nano-C60 than for micro-C60 for mass-based exposure comparisons. However, for surface-area-based exposures, more severe pulmonary effects were observed for micro-C60 than for nano-C60, highlighting the importance of dosimetry when evaluating toxicity between nano- and microparticles. JF - Nanotoxicology AU - Sayers, Brian C AU - Germolec, Dori R AU - Walker, Nigel J AU - Shipkowski, Kelly A AU - Stout, Matthew D AU - Cesta, Mark F AU - Roycroft, Joseph H AU - White, Kimber L AU - Baker, Gregory L AU - Dill, Jeffrey A AU - Smith, Matthew J AD - a Division of the National Toxicology Program , National Institute of Environmental Health Sciences , Research Triangle Park , NC , USA. ; b Department of Pharmacology and Toxicology , Virginia Commonwealth University , Richmond , VA , USA. ; c Battelle Toxicology Northwest , Richland , WA , USA , and. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1458 EP - 1468 VL - 10 IS - 10 KW - inhalation KW - Buckminsterfullerene KW - pulmonary inflammation KW - immunotoxicity KW - nanoparticles UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839740976?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nanotoxicology&rft.atitle=Respiratory+toxicity+and+immunotoxicity+evaluations+of+microparticle+and+nanoparticle+C60+fullerene+aggregates+in+mice+and+rats+following+nose-only+inhalation+for+13+weeks.&rft.au=Sayers%2C+Brian+C%3BGermolec%2C+Dori+R%3BWalker%2C+Nigel+J%3BShipkowski%2C+Kelly+A%3BStout%2C+Matthew+D%3BCesta%2C+Mark+F%3BRoycroft%2C+Joseph+H%3BWhite%2C+Kimber+L%3BBaker%2C+Gregory+L%3BDill%2C+Jeffrey+A%3BSmith%2C+Matthew+J&rft.aulast=Sayers&rft.aufirst=Brian&rft.date=2016-12-01&rft.volume=10&rft.issue=10&rft.spage=1458&rft.isbn=&rft.btitle=&rft.title=Nanotoxicology&rft.issn=1743-5404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-30 N1 - Date revised - 2017-01-30 N1 - Last updated - 2017-01-30 ER - TY - JOUR T1 - Phase I study of RO4929097 with bevacizumab in patients with recurrent malignant glioma. AN - 1839106459; 27826680 AB - Antiangiogenic therapies for malignant gliomas often result in transient response, and recurrent disease is characterized by adoption of invasive and hypoxic phenotype. The notch signaling pathway is activated in gliomas, and augments cell migration and hypoxic response. Here we report a clinical study of the combination of bevacizumab and RO4929097, an inhibitor of the notch signaling cascade. A phase I clinical trial was conducted through the Adult Brain Tumor Consortium in subjects with recurrent malignant glioma. Primary objectives were to assess safety and to define the maximum tolerated dose of RO4929097 in combination with bevacizumab. Secondary objectives were to determine overall survival, progression free survival, radiographic response, pharmacokinetic evaluation, and tissue biomarker analysis. Thirteen subjects were enrolled. Of the three subjects treated with the highest dose of RO4929097, one grade 3 toxicity and one grade 2 toxicity were observed. Definitive maximum tolerated dose of RO4929097 in combination with bevacizumab was not identified due to manufacturer's decision to halt drug production. 2 of 12 evaluable subjects demonstrated radiographic response; one subject experienced CR and the second PR. The median overall survival was 10.9 months with a median progression-free survival of 3.7 months. Two subjects remained free of disease progression at 6 months from treatment initiation. PK evaluation did not identify clinically significant drug-drug interactions. All analyzed tissue specimens revealed activation of notch signaling. Combination of RO4929097 and bevacizumab was well-tolerated. Given the compelling scientific rationale, additional studies of antiangiogenic and notch signaling inhibitors should be considered. JF - Journal of neuro-oncology AU - Pan, Edward AU - Supko, Jeffrey G AU - Kaley, Thomas J AU - Butowski, Nicholas A AU - Cloughesy, Timothy AU - Jung, Jinkyu AU - Desideri, Serena AU - Grossman, Stuart AU - Ye, Xiaobu AU - Park, Deric M AD - Department of Medicine, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, 75390, USA. Edward.Pan@UTSouthwestern.edu. ; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. ; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ; Department of Neurological Surgery, University of California, San Francisco, CA, USA. ; Department of Neurology, University of California, Los Angeles, CA, USA. ; Neuro-Oncology Branch, CCR, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. ; Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA. ; Neuro-Oncology Branch, CCR, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. deric.park@nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 571 EP - 579 VL - 130 IS - 3 KW - Gamma secretase KW - Notch KW - Glioma KW - Bevacizumab KW - Clinical trial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839106459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuro-oncology&rft.atitle=Phase+I+study+of+RO4929097+with+bevacizumab+in+patients+with+recurrent+malignant+glioma.&rft.au=Pan%2C+Edward%3BSupko%2C+Jeffrey+G%3BKaley%2C+Thomas+J%3BButowski%2C+Nicholas+A%3BCloughesy%2C+Timothy%3BJung%2C+Jinkyu%3BDesideri%2C+Serena%3BGrossman%2C+Stuart%3BYe%2C+Xiaobu%3BPark%2C+Deric+M&rft.aulast=Pan&rft.aufirst=Edward&rft.date=2016-12-01&rft.volume=130&rft.issue=3&rft.spage=571&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuro-oncology&rft.issn=1573-7373&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - HIV Transmission Risk Behavior in a Cohort of HIV-Infected Treatment-Naïve Men and Women in the United States AN - 1838984969 AB - Antiretroviral therapy (ART) can minimize HIV transmission. Prevention benefits may be compromised by barriers to virologic suppression, and by increased condomless sex among those initiating ART. We evaluated condomless sex in a cohort of HIVinfected US individuals poised to initiate ART in a clinical trial. We assessed partner and sex act type, condom use, and perception of infectiousness. Six percent of participants reported as not infectious; men who have sex with men were more likely to perceive high infectivity. Prevalence of condomless sex was 44 %; 74 % of those also reported homosexual acquisition of HIV. Predictors of increased risk of condomless sex included greater numbers of lifetime partners, recent stimulant drug use and an HIV-positive or unknown serostatus partner. In the context of serodifferent partners, lower perception of infectiousness was also associated with a higher risk of condomless sex. Results highlight opportunities for prevention education for HIV infected individuals at ART initiation. JF - AIDS and Behavior AU - Landovitz, Raphael J AU - Tran, Thuy Tien; T AU - Cohn, Susan E AU - Ofotokun, Ighovwhera AU - Godfrey, Catherine AU - Kuritzkes, Daniel R AU - Lennox, Jeffrey L AU - Currier, Judith S AU - Ribaudo, Heather J AD - Division of Infectious Diseases, UCLA Center for Clinical AIDS Research and Education, University of California, Los Angeles, Los Angeles, CA, USA ; Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, MA, USA ; Division of Infectious Diseases, Northwestern University School of Medicine, Chicago, IL, USA ; Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA ; Therapeutics Research Branch, Division of AIDS, National Institutes of Health, Bethesda, MD, USA ; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA ; Division of Infectious Diseases, UCLA Center for Clinical AIDS Research and Education, University of California, Los Angeles, Los Angeles, CA, USA Y1 - 2016/12// PY - 2016 DA - Dec 2016 SP - 2983 EP - 2995 CY - New York PB - Springer Science & Business Media VL - 20 IS - 12 SN - 1090-7165 KW - Psychology KW - Condom use KW - HIV transmission KW - ART-naïve KW - Behavior KW - Acquired Immune Deficiency Syndrome KW - Prevention KW - Drug Abuse KW - Homosexuality KW - Sexual Behavior KW - Treatment KW - Medications KW - Risk KW - 6126:acquired immune deficiency syndrome (AIDS) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1838984969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+and+Behavior&rft.atitle=HIV+Transmission+Risk+Behavior+in+a+Cohort+of+HIV-Infected+Treatment-Na%C3%AFve+Men+and+Women+in+the+United+States&rft.au=Landovitz%2C+Raphael+J%3BTran%2C+Thuy+Tien%3B+T%3BCohn%2C+Susan+E%3BOfotokun%2C+Ighovwhera%3BGodfrey%2C+Catherine%3BKuritzkes%2C+Daniel+R%3BLennox%2C+Jeffrey+L%3BCurrier%2C+Judith+S%3BRibaudo%2C+Heather+J&rft.aulast=Landovitz&rft.aufirst=Raphael&rft.date=2016-12-01&rft.volume=20&rft.issue=12&rft.spage=2983&rft.isbn=&rft.btitle=&rft.title=AIDS+and+Behavior&rft.issn=10907165&rft_id=info:doi/10.1007%2Fs10461-016-1365-2 LA - English DB - Social Services Abstracts N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2017-01-10 DO - http://dx.doi.org/10.1007/s10461-016-1365-2 ER - TY - JOUR T1 - A high-throughput functional genomics workflow based on CRISPR/Cas9-mediated targeted mutagenesis in zebrafish. AN - 1836734396; 27809318 AB - The zebrafish is a popular model organism for studying development and disease, and genetically modified zebrafish provide an essential tool for functional genomic studies. Numerous publications have demonstrated the efficacy of gene targeting in zebrafish using CRISPR/Cas9, and they have included descriptions of a variety of tools and methods for guide RNA synthesis and mutant identification. However, most of the published techniques are not readily scalable to increase throughput. We recently described a CRISPR/Cas9-based high-throughput mutagenesis and phenotyping pipeline in zebrafish. Here, we present a complete workflow for this pipeline, including target selection; cloning-free single-guide RNA (sgRNA) synthesis; microinjection; validation of the target-specific activity of the sgRNAs; founder screening to identify germline-transmitting mutations by fluorescence PCR; determination of the exact lesion by Sanger or next-generation sequencing (including software for analysis); and genotyping in the F1 or subsequent generations. Using these methods, sgRNAs can be evaluated in 3 d, zebrafish germline-transmitting mutations can be identified within 3 months and stable lines can be established within 6 months. Realistically, two researchers can target tens to hundreds of genes per year using this protocol. JF - Nature protocols AU - Varshney, Gaurav K AU - Carrington, Blake AU - Pei, Wuhong AU - Bishop, Kevin AU - Chen, Zelin AU - Fan, Chunxin AU - Xu, Lisha AU - Jones, Marypat AU - LaFave, Matthew C AU - Ledin, Johan AU - Sood, Raman AU - Burgess, Shawn M AD - Developmental Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. ; Zebrafish Core, Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. ; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Ministry of Education, Shanghai, China. ; Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. ; Department of Organismal Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 2357 EP - 2375 VL - 11 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836734396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+protocols&rft.atitle=A+high-throughput+functional+genomics+workflow+based+on+CRISPR%2FCas9-mediated+targeted+mutagenesis+in+zebrafish.&rft.au=Varshney%2C+Gaurav+K%3BCarrington%2C+Blake%3BPei%2C+Wuhong%3BBishop%2C+Kevin%3BChen%2C+Zelin%3BFan%2C+Chunxin%3BXu%2C+Lisha%3BJones%2C+Marypat%3BLaFave%2C+Matthew+C%3BLedin%2C+Johan%3BSood%2C+Raman%3BBurgess%2C+Shawn+M&rft.aulast=Varshney&rft.aufirst=Gaurav&rft.date=2016-12-01&rft.volume=11&rft.issue=12&rft.spage=2357&rft.isbn=&rft.btitle=&rft.title=Nature+protocols&rft.issn=1750-2799&rft_id=info:doi/10.1038%2Fnprot.2016.141 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/nprot.2016.141 ER - TY - JOUR T1 - Differential susceptibility to acetaminophen-induced liver injury in sub-strains of C57BL/6 mice: 6N versus 6J. AN - 1835540209; 27773698 AB - Mouse models of acetaminophen (APAP) hepatotoxicity are considered relevant for the human pathophysiology. The C57BL/6 strain is most popular because it is the background strain of gene knock-out mice. However, conflicting results in the literature may have been caused by sub-strain mismatches, e.g. C57BL/6J and C57BL/6N. This study was initiated to determine the mechanism behind the sub-strain susceptibility to APAP toxicity. C57BL/6N and C57BL/6J mice were dosed with 200 mg/kg APAP and sacrificed at different time points. C57BL/6N mice developed significantly more liver injury as measured by plasma ALT activities and histology. Although there was no difference in glutathione depletion or cytochrome P450 activity between groups, C57BL/6N had a higher glutathione disulfide-to-glutathione ratio and more APAP protein adducts. C57BL/6N showed more mitochondrial translocation of phospho-JNK and BAX, and more release of mitochondrial intermembrane proteins apoptosis-inducing factor (AIF), second mitochondria-derived activator of caspases (SMAC), which caused more DNA fragmentation. The increased mitochondrial dysfunction was confirmed in vitro as C57BL/6N hepatocytes had a more precipitous drop in JC-1 fluorescence after APAP exposure. C57BL/6N mice are more susceptible to APAP-induced hepatotoxicity, likely due to increased formation of APAP-protein adducts and a subsequent enhancement of mitochondrial dysfunction associated with aggravated nuclear DNA fragmentation. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Duan, Luqi AU - Davis, John S AU - Woolbright, Benjamin L AU - Du, Kuo AU - Cahkraborty, Mala AU - Weemhoff, James AU - Jaeschke, Hartmut AU - Bourdi, Mohammed AD - Department of Pharmacology, Toxicology & Therapeutics, Kansas City, KS, 66160, USA. Electronic address: lduan@kumc.edu. ; Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20850, USA. Electronic address: John.Davis@nih.gov. ; Department of Pharmacology, Toxicology & Therapeutics, Kansas City, KS, 66160, USA. Electronic address: bwoolbright@kmc.edu. ; Department of Pharmacology, Toxicology & Therapeutics, Kansas City, KS, 66160, USA. Electronic address: kdu@kumc.edu. ; Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20850, USA. Electronic address: mala.cahkraborty@nih.gov. ; Department of Pharmacology, Toxicology & Therapeutics, Kansas City, KS, 66160, USA. Electronic address: jweemhoff@kumc.edu. ; Department of Pharmacology, Toxicology & Therapeutics, Kansas City, KS, 66160, USA. Electronic address: hjaeschke@kumc.edu. ; Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20850, USA. Electronic address: mohammed.bourdi@nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 107 EP - 118 VL - 98 KW - DNA fragmentation KW - Protein adducts KW - C57BL/6 sub-strains KW - Acetaminophen hepatotoxicity KW - Mitochondrial dysfunction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835540209?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Differential+susceptibility+to+acetaminophen-induced+liver+injury+in%C2%A0sub-strains+of+C57BL%2F6+mice%3A+6N+versus+6J.&rft.au=Duan%2C+Luqi%3BDavis%2C+John+S%3BWoolbright%2C+Benjamin+L%3BDu%2C+Kuo%3BCahkraborty%2C+Mala%3BWeemhoff%2C+James%3BJaeschke%2C+Hartmut%3BBourdi%2C+Mohammed&rft.aulast=Duan&rft.aufirst=Luqi&rft.date=2016-12-01&rft.volume=98&rft.issue=&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=1873-6351&rft_id=info:doi/10.1016%2Fj.fct.2016.10.021 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.fct.2016.10.021 ER - TY - JOUR T1 - Dose-response assessment of the dermal toxicity of Virginia cedarwood oil in F344/N rats and B6C3F1/N mice. AN - 1835517347; 27769849 AB - Virginia cedarwood oil is widely used as a fragrance material in household and personal products and as a naturally derived pesticide alternative. Due to conflicting literature on dermal exposures in animals and humans, concern for safe levels of human exposure remains. The present study evaluated the toxicity of cedarwood oil applied dermally to F344/N rats and B6C3F1/N mice for 13 weeks. Groups of 10 male and female rats and mice received no treatment (untreated control) or were administered cedarwood oil in 95% aqueous ethanol dermally at concentrations ranging from 0% (vehicle control), 6.25%, 12.5%, 25%, 50%, and 100% (undiluted). Rats and mice developed extensive skin lesions at the site of application. Benchmark dose modeling (BMD) was performed for the significantly increased skin lesions observed in the rat, to provide perspective for risk assessment applications. Benchmark dose modeling levels (BMDL) of 0.65 to 2.1% and 1.2 to 4.4% (equivalent to 13 to 42 mg/kg and 24 to 48 mg/kg, respectively) cedarwood oil were calculated for the most sensitive endpoint of epidermal hyperplasia in female rats and chronic active inflammation in male rats, respectively. These BMDL levels coincide with reported use levels in cosmetics and pesticides, raising the concern for human exposure. Published by Elsevier Ltd. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Catlin, Natasha R AU - Herbert, Ron AU - Janardhan, Kyathanahalli AU - Hejtmancik, Milton R AU - Fomby, Laurene M AU - Vallant, Molly AU - Kissling, Grace E AU - DeVito, Michael J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Electronic address: natasha.catlin@nih.gov. ; National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. ; Integrated Laboratory Systems, Inc, Morrisville, NC 27560, USA. ; Battelle, Columbus, OH 43201, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 159 EP - 168 VL - 98 KW - Cedarwood oil KW - Skin KW - Benchmark dose UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835517347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Dose-response+assessment+of+the+dermal+toxicity+of+Virginia+cedarwood+oil+in+F344%2FN+rats+and+B6C3F1%2FN+mice.&rft.au=Catlin%2C+Natasha+R%3BHerbert%2C+Ron%3BJanardhan%2C+Kyathanahalli%3BHejtmancik%2C+Milton+R%3BFomby%2C+Laurene+M%3BVallant%2C+Molly%3BKissling%2C+Grace+E%3BDeVito%2C+Michael+J&rft.aulast=Catlin&rft.aufirst=Natasha&rft.date=2016-12-01&rft.volume=98&rft.issue=&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=1873-6351&rft_id=info:doi/10.1016%2Fj.fct.2016.10.016 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.fct.2016.10.016 ER - TY - JOUR T1 - Pharmacokinetics of Unboosted Atazanavir in Treatment-experienced HIV-infected Children, Adolescents and Young Adults. AN - 1835504152; 27583590 AB - HIV protease inhibitor use in pediatrics is challenging due to the poor palatability and/or toxicity of concomitant low-dose ritonavir. Atazanavir without ritonavir (unboosted) is not recommended for patients with prior virologic failure, a common problem for perinatally-infected adolescents. Atazanavir 400 mg once-daily provided suboptimal exposure. Higher unboosted doses or splitting the daily dose to twice-daily warrants investigation in this treatment-experienced population. JF - The Pediatric infectious disease journal AU - Cressey, Tim R AU - Hazra, Rohan AU - Wiznia, Andrew AU - Foca, Marc AU - Jean-Philippe, Patrick AU - Graham, Bobbie AU - King, Jennifer R AU - Britto, Paula AU - Carey, Vincent J AU - Acosta, Edward P AU - Yogev, Ram AU - IMPAACT P1058A Team AD - From the *Program for HIV Prevention and Treatment (IRD UMI 174), Faculty of Associated Medical Sciences, Department of Medical Technology, Chiang Mai University, Chiang Mai, Thailand; †Harvard T.H Chan School of Public Health, Boston, Massachusetts; ‡National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Maternal and Pediatric Infectious Disease Branch, Bethesda, Maryland; §Jacobi Medical Center, Bronx, New York; ¶Columbia University Medical Center, New York, New York; ‖HJF-DAIDS, a Division of The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Contractor to NIAID, NIH, DHHS, Bethesda, Maryland; **Frontier Science & Technology, Amherst, New York, New York; ††University of Alabama at Birmingham, Birmingham, Alabama; and ‡‡Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois. ; IMPAACT P1058A Team Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1333 EP - 1335 VL - 35 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835504152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Pediatric+infectious+disease+journal&rft.atitle=Pharmacokinetics+of+Unboosted+Atazanavir+in+Treatment-experienced+HIV-infected+Children%2C+Adolescents+and+Young+Adults.&rft.au=Cressey%2C+Tim+R%3BHazra%2C+Rohan%3BWiznia%2C+Andrew%3BFoca%2C+Marc%3BJean-Philippe%2C+Patrick%3BGraham%2C+Bobbie%3BKing%2C+Jennifer+R%3BBritto%2C+Paula%3BCarey%2C+Vincent+J%3BAcosta%2C+Edward+P%3BYogev%2C+Ram%3BIMPAACT+P1058A+Team&rft.aulast=Cressey&rft.aufirst=Tim&rft.date=2016-12-01&rft.volume=35&rft.issue=12&rft.spage=1333&rft.isbn=&rft.btitle=&rft.title=The+Pediatric+infectious+disease+journal&rft.issn=1532-0987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - RNA interference mediated downregulation of human telomerase reverse transcriptase (hTERT) in LN18 cells. AN - 1835491579; 27757712 AB - Human telomerase reverse transcriptase (hTERT) gene is a biomarker for the targeted therapy in various cancers. Presence of increased telomerase activity is a common feature of all cancers including glioblastoma. Both RNA and catalytic subunits of hTERT are the target sites for blocking its activity. The current study focuses on the expression of hTERT in glioblastoma and its regulation using two different novel siRNAs (small interfering RNA). Our patient data demonstrated increased expression of hTERT, which could be correlated with carcinogenesis in glioma. In vitro studies in siRNA transfected LN18 cells confirmed significant cell death (p < 0.05) as evidenced by MTT and trypan blue exclusion assay. These results were further supported by flow cytometry data, which showed significant increase in early and late apoptosis. The hTERT mRNA expression was effectively downregulated by 45 and 39 % with siRNA1 and siRNA2, respectively. These results were further confirmed by immunoblotting analysis (p < 0.05). Our results suggest that both the siRNAs effectively down regulated the expression of hTERT at mRNA and protein levels, thereby decreasing cell viability and proliferation rate. Hence siRNA mediated downregulation of hTERT could be a potential therapeutic avenue in glioblastoma. JF - Cytotechnology AU - Lavanya, Ch AU - Sibin, M K AU - Srinivas Bharath, M M AU - Manoj, M Jeru AU - Venkataswamy, Manjunatha M AU - Bhat, Dhananjaya I AU - Narasinga Rao, K V L AU - Chetan, G K AD - Department of Human Genetics, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India. ; Department of Neuro-chemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India. ; Department of Neurovirology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India. ; Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bangalore, India. ; Department of Human Genetics, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India. drchetangk@gmail.com. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 2311 EP - 2321 VL - 68 IS - 6 SN - 0920-9069, 0920-9069 KW - Glioblastoma KW - LN18 cell line KW - Apoptosis KW - Small interfering RNA KW - hTERT UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835491579?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotechnology&rft.atitle=RNA+interference+mediated+downregulation+of+human+telomerase+reverse+transcriptase+%28hTERT%29+in+LN18+cells.&rft.au=Lavanya%2C+Ch%3BSibin%2C+M+K%3BSrinivas+Bharath%2C+M+M%3BManoj%2C+M+Jeru%3BVenkataswamy%2C+Manjunatha+M%3BBhat%2C+Dhananjaya+I%3BNarasinga+Rao%2C+K+V+L%3BChetan%2C+G+K&rft.aulast=Lavanya&rft.aufirst=Ch&rft.date=2016-12-01&rft.volume=68&rft.issue=6&rft.spage=2311&rft.isbn=&rft.btitle=&rft.title=Cytotechnology&rft.issn=09209069&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Identification and characterization of PPARα ligands in the hippocampus. AN - 1835442303; 27748752 AB - Peroxisome proliferator-activated receptor-α (PPARα) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently we found that PPARα is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here we report the discovery of three endogenous PPARα ligands-3-hydroxy-(2,2)-dimethyl butyrate, hexadecanamide, and 9-octadecenamide-in mouse brain hippocampus. Mass spectrometric detection of these compounds in mouse hippocampal nuclear extracts, in silico interaction studies, time-resolved FRET analyses, and thermal shift assay results clearly indicated that these three compounds served as ligands of PPARα. Site-directed mutagenesis studies further revealed that PPARα Y464 and Y314 are involved in binding these hippocampal ligands. Moreover, these ligands activated PPARα and upregulated the synaptic function of hippocampal neurons. These results highlight the discovery of hippocampal ligands of PPARα capable of modulating synaptic functions. JF - Nature chemical biology AU - Roy, Avik AU - Kundu, Madhuchhanda AU - Jana, Malabendu AU - Mishra, Rama K AU - Yung, Yeni AU - Luan, Chi-Hao AU - Gonzalez, Frank J AU - Pahan, Kalipada AD - Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. ; Medicinal and Synthetic Chemistry Core, Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois, USA. ; Research Resources Center, University of Illinois at Chicago, Chicago, Illinois, USA. ; High Throughput Analysis Laboratory and Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1075 EP - 1083 VL - 12 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835442303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+chemical+biology&rft.atitle=Identification+and+characterization+of+PPAR%CE%B1+ligands+in+the+hippocampus.&rft.au=Roy%2C+Avik%3BKundu%2C+Madhuchhanda%3BJana%2C+Malabendu%3BMishra%2C+Rama+K%3BYung%2C+Yeni%3BLuan%2C+Chi-Hao%3BGonzalez%2C+Frank+J%3BPahan%2C+Kalipada&rft.aulast=Roy&rft.aufirst=Avik&rft.date=2016-12-01&rft.volume=12&rft.issue=12&rft.spage=1075&rft.isbn=&rft.btitle=&rft.title=Nature+chemical+biology&rft.issn=1552-4469&rft_id=info:doi/10.1038%2Fnchembio.2204 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/nchembio.2204 ER - TY - JOUR T1 - Preventive effects of dietary walnuts on high-fat-induced hepatic fat accumulation, oxidative stress and apoptosis in mice. AN - 1835409331; 27732911 AB - We hypothesized that dietary walnut would prevent high-fat-diet (HFD)-induced hepatic apoptosis based on its antioxidant properties. Male C57BL/6J mice were fed a rodent chow or HFD (45% energy-derived)±walnuts (21.5% energy-derived) for 6 weeks. Liver histological and biochemical analyses revealed significantly elevated fat accumulation in mice fed HFD compared to mice fed the chow or HFD±walnuts. Walnut supplementation prevented HFD-mediated alteration of the levels of key proteins in lipid homeostasis such as Sirt1, AMPK and FAS, leading to decreased fat accumulation. In addition, walnut supplementation to HFD significantly decreased the hepatic levels of cytochrome P450-2E1, nitrated proteins and lipid peroxidation. Furthermore, walnut supplementation decreased the activated cell-death-associated p-JNK and p-p38K accompanied with increased hepatocyte apoptosis in HFD group. The beneficial effects of dietary walnut likely result, at least partially, from its antioxidant ingredients and attenuating HFD-induced hepatic steatosis, nitroxidative stress and apoptosis. Published by Elsevier Inc. JF - The Journal of nutritional biochemistry AU - Choi, Youngshim AU - Abdelmegeed, Mohamed A AU - Song, Byoung-Joon AD - Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. ; Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. Electronic address: bj.song@nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 70 EP - 80 VL - 38 KW - JNK KW - Walnut KW - Apoptosis KW - Oxidative stress KW - High-fat diet KW - Liver KW - CYP2E1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835409331?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutritional+biochemistry&rft.atitle=Preventive+effects+of+dietary+walnuts+on+high-fat-induced+hepatic+fat+accumulation%2C+oxidative+stress+and+apoptosis+in+mice.&rft.au=Choi%2C+Youngshim%3BAbdelmegeed%2C+Mohamed+A%3BSong%2C+Byoung-Joon&rft.aulast=Choi&rft.aufirst=Youngshim&rft.date=2016-12-01&rft.volume=38&rft.issue=&rft.spage=70&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutritional+biochemistry&rft.issn=1873-4847&rft_id=info:doi/10.1016%2Fj.jnutbio.2016.08.013 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jnutbio.2016.08.013 ER - TY - JOUR T1 - Editor's Highlight: Comparative Toxicity of Organophosphate Flame Retardants and Polybrominated Diphenyl Ethers to Caenorhabditis elegans. AN - 1835377030; 27566445 AB - With the phasing-out of the polybrominated diphenyl ether (PBDE) flame retardants due to concerns regarding their potential developmental toxicity, the use of replacement compounds such as organophosphate flame retardants (OPFRs) has increased. Limited toxicity data are currently available to estimate the potential adverse health effects of the OPFRs. The toxicological effects of 4 brominated flame retardants, including 3 PBDEs and 3,3',5,5'-tetrabromobisphenol A, were compared with 6 aromatic OPFRs and 2 aliphatic OPFRs. The effects of these chemicals were determined using 3 biological endpoints in the nematode Caenorhabditis elegans (feeding, larval development, and reproduction). Because C. elegans development was previously reported to be sensitive to mitochondrial function, results were compared with those from an in vitro mitochondrial membrane permeabilization (MMP) assay. Overall 11 of the 12 flame retardants were active in 1 or more C. elegans biological endpoints, with only tris(2-chloroethyl) phosphate inactive across all endpoints including the in vitro MMP assay. For 2 of the C. elegans endpoints, at least 1 OPFR had similar toxicity to the PBDEs: triphenyl phosphate (TPHP) inhibited larval development at levels comparable to the 3 PBDEs; whereas TPHP and isopropylated phenol phosphate (IPP) affected C. elegans reproduction at levels similar to the PBDE commercial mixture, DE-71. The PBDEs reduced C. elegans feeding at lower concentrations than any OPFR. In addition, 9 of the 11 chemicals that inhibited C. elegans larval development also caused significant mitochondrial toxicity. These results suggest that some of the replacement aromatic OPFRs may have levels of toxicity comparable to PBDEs. Published by Oxford University Press on behalf of the Society of Toxicology 2016. This work is written by US Government employees and is in the public domain in the US. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Behl, Mamta AU - Rice, Julie R AU - Smith, Marjo V AU - Co, Caroll A AU - Bridge, Matthew F AU - Hsieh, Jui-Hua AU - Freedman, Jonathan H AU - Boyd, Windy A AD - Division of the National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina. ; Social & Scientific Systems, Inc., Durham, North Carolina. ; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky. ; Division of the National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina boydw@niehs.nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 241 EP - 252 VL - 154 IS - 2 KW - flame retardants KW - Caenorhabditis elegans KW - mitochondrial toxicity. UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835377030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Editor%27s+Highlight%3A+Comparative+Toxicity+of+Organophosphate+Flame+Retardants+and+Polybrominated+Diphenyl+Ethers+to+Caenorhabditis+elegans.&rft.au=Behl%2C+Mamta%3BRice%2C+Julie+R%3BSmith%2C+Marjo+V%3BCo%2C+Caroll+A%3BBridge%2C+Matthew+F%3BHsieh%2C+Jui-Hua%3BFreedman%2C+Jonathan+H%3BBoyd%2C+Windy+A&rft.aulast=Behl&rft.aufirst=Mamta&rft.date=2016-12-01&rft.volume=154&rft.issue=2&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=1096-0929&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - A simple tube adapter to expedite and automate thawing of viably frozen cells. AN - 1835372137; 27594593 AB - Although cryopreserved cell specimens are used throughout biomedical research, the process for thawing samples is labor-intensive and prone to error. Here we describe a small laboratory device that couples an uncapped vial of frozen cells to a conical tube containing warm cell culture media. The entire complex is loaded directly into a centrifuge; within 5min, cells are thawed and diluted out of toxic cryopreservation medium. The recovery and viability of cells are slightly reduced compared to the common (traditional) method. However, antigen-specific T-cell function is not affected. Since no technician time is required (beyond uncapping of vials), our device allows the parallel processing of as many samples as a centrifuge can hold (up to 96, in some models). Moreover, since the samples are not thawed manually in a water bath, the problems associated with technician-to-technician differences in sample handling are minimized, as is the potential for contamination. Importantly, the elimination of substantial labor involving subjective decisions standardizes this process and can reduce variability in results from cryopreserved specimens. Copyright © 2016. Published by Elsevier B.V. JF - Journal of immunological methods AU - Beddall, Margaret AU - Chattopadhyay, Pratip K AU - Kao, Shing-Fen AU - Foulds, Kathy AU - Roederer, Mario AD - ImmunoTechnology Section, Vaccine Research Center, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892, United States. ; ImmunoTechnology Section, Vaccine Research Center, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892, United States. Electronic address: pchattop@mail.nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 74 EP - 78 VL - 439 KW - T-cells KW - flow cytometry KW - Cryopreservation KW - Immunoassay UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835372137?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunological+methods&rft.atitle=A+simple+tube+adapter+to+expedite+and+automate+thawing+of+viably+frozen+cells.&rft.au=Beddall%2C+Margaret%3BChattopadhyay%2C+Pratip+K%3BKao%2C+Shing-Fen%3BFoulds%2C+Kathy%3BRoederer%2C+Mario&rft.aulast=Beddall&rft.aufirst=Margaret&rft.date=2016-12-01&rft.volume=439&rft.issue=&rft.spage=74&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunological+methods&rft.issn=1872-7905&rft_id=info:doi/10.1016%2Fj.jim.2016.08.009 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jim.2016.08.009 ER - TY - JOUR T1 - Off-pathway assembly of fimbria subunits is prevented by chaperone CfaA of CFA/I fimbriae from enterotoxigenic E. coli. AN - 1835369711; 27627030 AB - The assembly of the class 5 colonization factor antigen I (CFA/I) fimbriae of enterotoxigenic E. coli was proposed to proceed via the alternate chaperone-usher pathway. Here, we show that in the absence of the chaperone CfaA, CfaB, the major pilin subunit of CFA/I fimbriae, is able to spontaneously refold and polymerize into cyclic trimers. CfaA kinetically traps CfaB to form a metastable complex that can be stabilized by mutations. Crystal structure of the stabilized complex reveals distinctive interactions provided by CfaA to trap CfaB in an assembly competent state through donor-strand complementation (DSC) and cleft-mediated anchorage. Mutagenesis indicated that DSC controls the stability of the chaperone-subunit complex and the cleft-mediated anchorage of the subunit C-terminus additionally assist in subunit refolding. Surprisingly, over-stabilization of the chaperone-subunit complex led to delayed fimbria assembly, whereas destabilizing the complex resulted in no fimbriation. Thus, CfaA acts predominantly as a kinetic trap by stabilizing subunit to avoid its off-pathway self-polymerization that results in energetically favorable trimers and could serve as a driving force for CFA/I pilus assembly, representing an energetic landscape unique to class 5 fimbria assembly. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Molecular Microbiology published by John Wiley & Sons Ltd. JF - Molecular microbiology AU - Bao, Rui AU - Liu, Yang AU - Savarino, Stephen J AU - Xia, Di AD - Division of Infectious Diseases, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospitals, Sichuan University, Chengdu, 610041, China. ; Enteric Diseases Department, Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, MD, 20910-7500, USA. ; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 975 EP - 991 VL - 102 IS - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835369711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+microbiology&rft.atitle=Off-pathway+assembly+of+fimbria+subunits+is+prevented+by+chaperone+CfaA+of+CFA%2FI+fimbriae+from+enterotoxigenic+E.+coli.&rft.au=Bao%2C+Rui%3BLiu%2C+Yang%3BSavarino%2C+Stephen+J%3BXia%2C+Di&rft.aulast=Bao&rft.aufirst=Rui&rft.date=2016-12-01&rft.volume=102&rft.issue=6&rft.spage=975&rft.isbn=&rft.btitle=&rft.title=Molecular+microbiology&rft.issn=1365-2958&rft_id=info:doi/10.1111%2Fmmi.13530 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/mmi.13530 ER - TY - JOUR T1 - Nanomedicine strategies to overcome the pathophysiological barriers of pancreatic cancer. AN - 1835366182; 27531700 AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer- related deaths. PDAC remains one of the most difficult-to-treat cancers, owing to its unique pathobiological features: a nearly impenetrable desmoplastic stroma, and hypovascular and hypoperfused tumour vessels render most treatment options largely ineffective. Progress in understanding the pathobiology and signalling pathways involved in disease progression is helping researchers to develop novel ways to fight PDAC, including improved nanotechnology-based drug-delivery platforms that have the potential to overcome the biological barriers of the disease that underlie persistent drug resistance. So-called 'nanomedicine' strategies have the potential to enable targeting of the Hedgehog-signalling pathway, the autophagy pathway, and specific RAS-mutant phenotypes, among other pathological processes of the disease. These novel therapies, alone or in combination with agents designed to disrupt the pathobiological barriers of the disease, could result in superior treatments, with increased efficacy and reduced off-target toxicities compared with the current standard-of-care regimens. By overcoming drug-delivery challenges, advances can be made in the treatment of PDAC, a disease for which limited improvement in overall survival has been achieved over the past several decades. We discuss the approaches to nanomedicine that have been pursued to date and those that are the focus of ongoing research, and outline their potential, as well as the key challenges that must be overcome. JF - Nature reviews. Clinical oncology AU - Adiseshaiah, Pavan P AU - Crist, Rachael M AU - Hook, Sara S AU - McNeil, Scott E AD - Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA. ; Office of the Director, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 750 EP - 765 VL - 13 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835366182?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+reviews.+Clinical+oncology&rft.atitle=Nanomedicine+strategies+to+overcome+the+pathophysiological+barriers+of+pancreatic+cancer.&rft.au=Adiseshaiah%2C+Pavan+P%3BCrist%2C+Rachael+M%3BHook%2C+Sara+S%3BMcNeil%2C+Scott+E&rft.aulast=Adiseshaiah&rft.aufirst=Pavan&rft.date=2016-12-01&rft.volume=13&rft.issue=12&rft.spage=750&rft.isbn=&rft.btitle=&rft.title=Nature+reviews.+Clinical+oncology&rft.issn=1759-4782&rft_id=info:doi/10.1038%2Fnrclinonc.2016.119 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/nrclinonc.2016.119 ER - TY - JOUR T1 - Autocrine IL-10 functions as a rheostat for M1 macrophage glycolytic commitment by tuning nitric oxide production. AN - 1835365897; 27676159 AB - Inflammatory maturation of M1 macrophages by proinflammatory stimuli such as toll like receptor ligands results in profound metabolic reprogramming resulting in commitment to aerobic glycolysis as evidenced by repression of mitochondrial oxidative phosphorylation (OXPHOS) and enhanced glucose utilization. In contrast, "alternatively activated" macrophages adopt a metabolic program dominated by fatty acid-fueled OXPHOS. Despite the known importance of these developmental stages on the qualitative aspects of an inflammatory response, relatively little is know regarding the regulation of these metabolic adjustments. Here we provide evidence that the immunosuppressive cytokine IL-10 defines a metabolic regulatory loop. Our data show for the first time that lipopolysaccharide (LPS)-induced glycolytic flux controls IL-10-production via regulation of mammalian target of rapamycin (mTOR) and that autocrine IL-10 in turn regulates macrophage nitric oxide (NO) production. Genetic and pharmacological manipulation of IL-10 and nitric oxide (NO) establish that metabolically regulated autocrine IL-10 controls glycolytic commitment by limiting NO-mediated suppression of OXPHOS. Together these data support a model where autocine IL-10 production is controlled by glycolytic flux in turn regulating glycolytic commitment by preserving OXPHOS via suppression of NO. We propose that this IL-10-driven metabolic rheostat maintains metabolic equilibrium during M1 macrophage differentiation and that perturbation of this regulatory loop, either directly by exogenous cellular sources of IL-10 or indirectly via limitations in glucose availability, skews the cellular metabolic program altering the balance between inflammatory and immunosuppressive phenotypes. Copyright © 2016. Published by Elsevier B.V. JF - Redox biology AU - Baseler, Walter A AU - Davies, Luke C AU - Quigley, Laura AU - Ridnour, Lisa A AU - Weiss, Jonathan M AU - Hussain, S Perwez AU - Wink, David A AU - McVicar, Daniel W AD - Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, United States. ; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, United States; Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK. ; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, United States. ; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, United States. Electronic address: mcvicard@mail.nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 12 EP - 23 VL - 10 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835365897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=The+new+psychoactive+substances+5-%282-aminopropyl%29indole+%285-IT%29+and+6-%282-aminopropyl%29indole+%286-IT%29+interact+with+monoamine+transporters+in+brain+tissue.&rft.au=Marusich%2C+Julie+A%3BAntonazzo%2C+Kateland+R%3BBlough%2C+Bruce+E%3BBrandt%2C+Simon+D%3BKavanagh%2C+Pierce+V%3BPartilla%2C+John+S%3BBaumann%2C+Michael+H&rft.aulast=Marusich&rft.aufirst=Julie&rft.date=2016-02-01&rft.volume=101&rft.issue=&rft.spage=68&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=1873-7064&rft_id=info:doi/10.1016%2Fj.neuropharm.2015.09.004 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.redox.2016.09.005 ER - TY - JOUR T1 - Equilibrative nucleoside transporter ENT1 as a biomarker of Huntington disease. AN - 1835365254; 27567601 AB - The initial goal of this study was to investigate alterations in adenosine A2A receptor (A2AR) density or function in a rat model of Huntington disease (HD) with reported insensitivity to an A2AR antagonist. Unsuspected negative results led to the hypothesis of a low striatal adenosine tone and to the search for the mechanisms involved. Extracellular striatal concentrations of adenosine were measured with in vivo microdialysis in two rodent models of early neuropathological stages of HD disease, the Tg51 rat and the zQ175 knock-in mouse. In view of the crucial role of the equilibrative nucleoside transporter (ENT1) in determining extracellular content of adenosine, the binding properties of the ENT1 inhibitor [3H]-S-(4-Nitrobenzyl)-6-thioinosine were evaluated in zQ175 mice and the differential expression and differential coexpression patterns of the ENT1 gene (SLC29A1) were analyzed in a large human cohort of HD disease and controls. Extracellular striatal levels of adenosine were significantly lower in both animal models as compared with control littermates and striatal ENT1 binding sites were significantly upregulated in zQ175 mice. ENT1 transcript was significantly upregulated in HD disease patients at an early neuropathological severity stage, but not those with a higher severity stage, relative to non-demented controls. ENT1 transcript was differentially coexpressed (gained correlations) with several other genes in HD disease subjects compared to the control group. The present study demonstrates that ENT1 and adenosine constitute biomarkers of the initial stages of neurodegeneration in HD disease and also predicts that ENT1 could constitute a new therapeutic target to delay the progression of the disease. Published by Elsevier Inc. JF - Neurobiology of disease AU - Guitart, Xavier AU - Bonaventura, Jordi AU - Rea, William AU - Orrú, Marco AU - Cellai, Lucrezia AU - Dettori, Ilaria AU - Pedata, Felicita AU - Brugarolas, Marc AU - Cortés, Antonio AU - Casadó, Vicent AU - Chang, Ching-Pang AU - Narayanan, Manikandan AU - Chern, Yijuang AU - Ferré, Sergi AD - Integrative Neurobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, United States. ; Department NEUROFARBA, Division of Pharmacology and Toxicology, University of Florence, 50139 Florence, Italy. ; Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona and Center for Biomedical Research in Neurodegenerative Diseases Network and Institute of Biomedicine, 08028 Barcelona, Spain. ; Division of Neuroscience Institute of Biomedical Sciences, Academia Sinica, 11529 Taipei, Taiwan. ; Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, United States. ; Integrative Neurobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, United States. Electronic address: sferre@intra.nida.nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 47 EP - 53 VL - 96 KW - A(2A) receptor KW - Huntington disease KW - ENT1 KW - Adenosine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835365254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+of+disease&rft.atitle=Equilibrative+nucleoside+transporter+ENT1+as+a+biomarker+of+Huntington+disease.&rft.au=Guitart%2C+Xavier%3BBonaventura%2C+Jordi%3BRea%2C+William%3BOrr%C3%BA%2C+Marco%3BCellai%2C+Lucrezia%3BDettori%2C+Ilaria%3BPedata%2C+Felicita%3BBrugarolas%2C+Marc%3BCort%C3%A9s%2C+Antonio%3BCasad%C3%B3%2C+Vicent%3BChang%2C+Ching-Pang%3BNarayanan%2C+Manikandan%3BChern%2C+Yijuang%3BFerr%C3%A9%2C+Sergi&rft.aulast=Guitart&rft.aufirst=Xavier&rft.date=2016-12-01&rft.volume=96&rft.issue=&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+disease&rft.issn=1095-953X&rft_id=info:doi/10.1016%2Fj.nbd.2016.08.013 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-30 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.nbd.2016.08.013 ER - TY - JOUR T1 - Prenatal mercury exposure and offspring behaviour in childhood and adolescence. AN - 1835358317; 27633321 AB - There is considerable discussion over the possible harm caused by fetal exposure to mercury, but evidence of such harm is contradictory at levels commonly found in populations with moderate intakes of fish. Further information is needed to inform debate and clarify policy recommendations. Data were collected prospectively for the Avon Longitudinal Study of Parents and Children (ALSPAC). Whole blood taken in the first half of pregnancy was assayed for mercury. The outcomes were offspring behavioural assessments collected using the Strengths and Difficulties Questionnaire at seven time points between ages 4 and 16-17 years; five were completed by the mother and two by the teacher. Socioeconomic and biological confounders were first taken into account; further analyses added maternal blood selenium. Separate analyses compared the relationships between prenatal mercury levels and behaviour traits treated as continuous measures in women who ate fish with those who ate no fish in order to determine whether the relationships differed; the hypothesis was that fish consumption had benefits on the brain and masked any mercury effects. In order to prevent Type II errors, the P value for significance was set at 0.10. Prenatal mercury measurements and offspring behaviour results were available for between 2776 (at 47 months) to 1599 mother-child pairs (at 16-17 years). Even given a P value of 0.10, the number of significant results was no greater than expected apart from the relationships with peer problems at 4, 6 and 10-11 years where the relationships with prenatal mercury were negative (i.e. the greater the level of mercury the fewer the problems the child had with his/her peers). There were no significant differences between the associations with mercury found among the offspring of women who ate fish in pregnancy and those who did not, nor did adjustment for selenium make a difference. There were no adverse effects of maternal prenatal mercury levels on the behaviour of the offspring. A similar lack of relationship was found when the analyses were confined to those offspring whose mothers had eaten fish in pregnancy, and no consistent differences were found between the fish and non-fish eaters. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved. JF - Neurotoxicology AU - Golding, Jean AU - Gregory, Steven AU - Emond, Alan AU - Iles-Caven, Yasmin AU - Hibbeln, Joseph AU - Taylor, Caroline M AD - Centre for Child and Adolescent Health, University of Bristol, UK. Electronic address: jean.golding@bristol.ac.uk. ; Centre for Child and Adolescent Health, University of Bristol, UK. ; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 87 EP - 94 VL - 57 KW - Child behaviour KW - Dietary fish KW - ALSPAC KW - Prenatal mercury exposure KW - Adolescent behaviour UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835358317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Prenatal+mercury+exposure+and+offspring+behaviour+in+childhood+and+adolescence.&rft.au=Golding%2C+Jean%3BGregory%2C+Steven%3BEmond%2C+Alan%3BIles-Caven%2C+Yasmin%3BHibbeln%2C+Joseph%3BTaylor%2C+Caroline+M&rft.aulast=Golding&rft.aufirst=Jean&rft.date=2016-12-01&rft.volume=57&rft.issue=&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=1872-9711&rft_id=info:doi/10.1016%2Fj.neuro.2016.09.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.neuro.2016.09.003 ER - TY - JOUR T1 - Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children. AN - 1835352444; 27697762 AB - Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited pharmacokinetic (PK) data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. Our objective was to describe the pharmacokinetics of LAmB in children aged 1 to 17 years with suspected or documented IFD. Thirty-five children were treated with LAmB at doses of 2.5 to 10 mg kg-1 daily. Samples were taken at baseline and at 0.5- to 2.0-h intervals for 24 h after receipt of the first dose (n = 35 patients) and on the final day of therapy (n = 25 patients). LAmB was measured using high-performance liquid chromatography (HPLC). The relationship between drug exposure and development of toxicity was explored. An evolution in PK was observed during the course of therapy, resulting in a proportion of patients (n = 13) having significantly higher maximum serum concentrations (Cmax) and areas under the concentration-time curve from 0 to 24 h (AUC0-24) later in the course of therapy, without evidence of drug accumulation (trough plasma concentration accumulation ratio of <1.2). The fit of a 2-compartment model incorporating weight and an exponential decay function describing volume of distribution best described the data. There was a statistically significant relationship between mean AUC0-24 and probability of nephrotoxicity (odds ratio, 2.37; 95% confidence interval, 1.84 to 3.22; P = 0.004). LAmB exhibits nonlinear pharmacokinetics. A third of children appear to experience a time-dependent change in PK, which is not explained by weight, maturation, or observed clinical factors. Copyright © 2016, American Society for Microbiology. All Rights Reserved. JF - Antimicrobial agents and chemotherapy AU - Lestner, Jodi M AU - Groll, Andreas H AU - Aljayyoussi, Ghaith AU - Seibel, Nita L AU - Shad, Aziza AU - Gonzalez, Corina AU - Wood, Lauren V AU - Jarosinski, Paul F AU - Walsh, Thomas J AU - Hope, William W AD - Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, United Kingdom jlestner@liverpool.ac.uk. ; Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children's Hospital Münster, Münster, Germany. ; Liverpool School of Tropical Medicine, Liverpool, United Kingdom. ; Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA. ; Clinical Investigations Branch, Cancer Treatment Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA. ; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Georgetown University Medical Center, Washington, DC, USA. ; Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA. ; Pharmacy Department, National Institutes of Health Clinical Center, Bethesda, Maryland, USA. ; Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, United Kingdom. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 7340 EP - 7346 VL - 60 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835352444?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Population+Pharmacokinetics+of+Liposomal+Amphotericin+B+in+Immunocompromised+Children.&rft.au=Lestner%2C+Jodi+M%3BGroll%2C+Andreas+H%3BAljayyoussi%2C+Ghaith%3BSeibel%2C+Nita+L%3BShad%2C+Aziza%3BGonzalez%2C+Corina%3BWood%2C+Lauren+V%3BJarosinski%2C+Paul+F%3BWalsh%2C+Thomas+J%3BHope%2C+William+W&rft.aulast=Lestner&rft.aufirst=Jodi&rft.date=2016-12-01&rft.volume=60&rft.issue=12&rft.spage=7340&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=1098-6596&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - The Afro-Cardiac Study: Cardiovascular Disease Risk and Acculturation in West African Immigrants in the United States: Rationale and Study Design AN - 1829718292 AB - Cardiovascular disease (CVD) remains the leading cause of death in the United States (US). African-descent populations bear a disproportionate burden of CVD risk factors. With the increase in the number of West African immigrants (WAIs) to the US over the past decades, it is imperative to specifically study this new and substantial subset of the African-descent population and how acculturation impacts their CVD risk. The Afro-Cardiac study, a community-based cross-sectional study of adult WAIs in the Baltimore-Washington metropolis. Guided by the PRECEDE-PROCEED model, we used a modification of the World Health Organization Steps survey to collect data on demographics, socioeconomic status, migration-related factors and behaviors. We obtained physical, biochemical, acculturation measurements as well as a socio-demographic and health history. Our study provides critical data on the CVD risk of WAIs. The framework used is valuable for future epidemiological studies addressing CVD risk and acculturation among immigrants. JF - Journal of Immigrant and Minority Health AU - Commodore-mensah, Yvonne AU - Sampah, Maame AU - Berko, Charles AU - Cudjoe, Joycelyn AU - Abu-bonsrah, Nancy AU - Obisesan, Olawunmi AU - Agyemang, Charles AU - Adeyemo, Adebowale AU - Himmelfarb, Cheryl Dennison AD - Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA ; Johns Hopkins School of Medicine, Baltimore, MD, USA ; Department of Internal Medicine, St. Agnes Hospital, Baltimore, MD, USA ; Johns Hopkins School of Nursing, Baltimore, MD, USA ; A.T Still University, Kirksville, MO, USA ; Amsterdam Medical Centre, University of Amsterdam, Amsterdam, Netherlands ; Center for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD, USA ; Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA Y1 - 2016/12// PY - 2016 DA - Dec 2016 SP - 1301 EP - 1308 CY - New York PB - Springer Science & Business Media VL - 18 IS - 6 SN - 1557-1912 KW - Medical Sciences KW - African immigrants KW - Cardiovascular disease KW - Immigrants KW - Acculturation KW - Sociodemographic aspects KW - Modification KW - Socioeconomic status KW - African people KW - Migration KW - Death KW - Cardiovascular diseases KW - Risk factors KW - United States--US UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1829718292?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immigrant+and+Minority+Health&rft.atitle=The+Afro-Cardiac+Study%3A+Cardiovascular+Disease+Risk+and+Acculturation+in+West+African+Immigrants+in+the+United+States%3A+Rationale+and+Study+Design&rft.au=Commodore-mensah%2C+Yvonne%3BSampah%2C+Maame%3BBerko%2C+Charles%3BCudjoe%2C+Joycelyn%3BAbu-bonsrah%2C+Nancy%3BObisesan%2C+Olawunmi%3BAgyemang%2C+Charles%3BAdeyemo%2C+Adebowale%3BHimmelfarb%2C+Cheryl+Dennison&rft.aulast=Commodore-mensah&rft.aufirst=Yvonne&rft.date=2016-12-01&rft.volume=18&rft.issue=6&rft.spage=1301&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immigrant+and+Minority+Health&rft.issn=15571912&rft_id=info:doi/10.1007%2Fs10903-015-0291-0 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-10-18 N1 - SubjectsTermNotLitGenreText - United States--US DO - http://dx.doi.org/10.1007/s10903-015-0291-0 ER - TY - JOUR T1 - Cheminformatics analysis of the AR agonist and antagonist datasets in PubChem AN - 1827902304; PQ0003731672 AB - As one of the largest publicly accessible databases for hosting chemical structures and biological activities, PubChem has been processing bioassay submissions from the community since 2004. With the increase in volume for the deposited data in PubChem, the diversity and wealth of information content also grows. Recently, the Tox21 program, has deposited a series of pairwise data in PubChem regarding to different mechanism of actions (MOA), such as androgen receptor (AR) agonist and antagonist datasets, to study cell toxicity. To the best of our knowledge, little work has been reported from cheminformatics study for these especially pairwise datasets, which may provide insight into the mechanism of actions of the compounds and relationship between chemical structures and functions, as well as guidance for lead compound selection and optimization. Thus, to fill the gap, we performed a comprehensive cheminformatics analysis, including scaffold analysis, matched molecular pair (MMP) analysis as well as activity cliff analysis to investigate the structural characteristics and discontinued structure-activity relationship of the individual dataset (i.e., AR agonist dataset or AR antagonist dataset) and the combined dataset (i.e., the common compounds between the AR agonist and antagonist datasets). Scaffolds associated only with potential agonists or antagonists were identified. MMP-based activity cliffs, as well as a small group of compounds with dual MOA reported were recognized and analyzed. Moreover, MOA-cliff, a novel concept, was proposed to indicate one pair of structurally similar molecules which exhibit opposite MOA. Cheminformatics methods were successfully applied to the pairwise AR datasets and the identified molecular scaffold characteristics, MMPs as well as activity cliffs might provide useful information when designing new lead compounds for the androgen receptor. JF - Journal of Cheminformatics AU - Hao, Ming AU - Bryant, Stephen H AU - Wang, Yanli AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA, ywang@ncbi.nlm.nih.gov Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1 EP - 13 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 8 IS - 1 KW - Biotechnology and Bioengineering Abstracts KW - Androgen receptors KW - Databases KW - Computer programs KW - Data processing KW - Informatics KW - Toxicity KW - Structure-activity relationships KW - scaffolds KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827902304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Cheminformatics&rft.atitle=Cheminformatics+analysis+of+the+AR+agonist+and+antagonist+datasets+in+PubChem&rft.au=Hao%2C+Ming%3BBryant%2C+Stephen+H%3BWang%2C+Yanli&rft.aulast=Hao&rft.aufirst=Ming&rft.date=2016-12-01&rft.volume=8&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cheminformatics&rft.issn=1758-2946&rft_id=info:doi/10.1186%2Fs13321-016-0150-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 34 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Androgen receptors; Computer programs; Databases; Data processing; Informatics; Toxicity; Structure-activity relationships; scaffolds DO - http://dx.doi.org/10.1186/s13321-016-0150-6 ER - TY - JOUR T1 - Literature information in PubChem: associations between PubChem records and scientific articles AN - 1827902115; PQ0003731662 AB - PubChem is an open archive consisting of a set of three primary public databases (BioAssay, Compound, and Substance). It contains information on a broad range of chemical entities, including small molecules, lipids, carbohydrates, and (chemically modified) amino acid and nucleic acid sequences (including siRNA and miRNA). Currently (as of Nov. 2015), PubChem contains more than 150 million depositor-provided chemical substance descriptions, 60 million unique chemical structures, and 225 million biological activity test results provided from over 1 million biological assay records. Many PubChem records (substances, compounds, and assays) include depositor-provided cross-references to scientific articles in PubMed. Some PubChem contributors provide bioactivity data extracted from scientific articles. Literature-derived bioactivity data complement high-throughput screening (HTS) data from the concluded NIH Molecular Libraries Program and other HTS projects. Some journals provide PubChem with information on chemicals that appear in their newly published articles, enabling concurrent publication of scientific articles in journals and associated data in public databases. In addition, PubChem links records to PubMed articles indexed with the Medical Subject Heading (MeSH) controlled vocabulary thesaurus. Literature information, both provided by depositors and derived from MeSH annotations, can be accessed using PubChem's web interfaces, enabling users to explore information available in literature related to PubChem records beyond typical web search results. [Figure not available: see fulltext.] JF - Journal of Cheminformatics AU - Kim, Sunghwan AU - Thiessen, Paul A AU - Cheng, Tiejun AU - Yu, Bo AU - Shoemaker, Benjamin A AU - Wang, Jiyao AU - Bolton, Evan E AU - Wang, Yanli AU - Bryant, Stephen H AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Department of Health and Human Services, 8600 Rockville Pike, Bethesda, MD, 20894, USA, kimsungh@ncbi.nlm.nih.gov Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1 EP - 15 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 8 IS - 1 KW - Biotechnology and Bioengineering Abstracts KW - Databases KW - Computer programs KW - Data processing KW - nucleic acids KW - siRNA KW - Informatics KW - Lipids KW - miRNA KW - high-throughput screening KW - Carbohydrates KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827902115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Cheminformatics&rft.atitle=Literature+information+in+PubChem%3A+associations+between+PubChem+records+and+scientific+articles&rft.au=Kim%2C+Sunghwan%3BThiessen%2C+Paul+A%3BCheng%2C+Tiejun%3BYu%2C+Bo%3BShoemaker%2C+Benjamin+A%3BWang%2C+Jiyao%3BBolton%2C+Evan+E%3BWang%2C+Yanli%3BBryant%2C+Stephen+H&rft.aulast=Kim&rft.aufirst=Sunghwan&rft.date=2016-12-01&rft.volume=8&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cheminformatics&rft.issn=1758-2946&rft_id=info:doi/10.1186%2Fs13321-016-0142-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 31 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Computer programs; Databases; nucleic acids; Data processing; siRNA; Informatics; Lipids; miRNA; high-throughput screening; Carbohydrates DO - http://dx.doi.org/10.1186/s13321-016-0142-6 ER - TY - JOUR T1 - A phase I trial of cabozantinib and gemcitabine in advanced pancreatic cancer. AN - 1826727501; 27439894 AB - Background Cabozantinib and gemcitabine improve tumor control in pancreatic ductal adenocarcinoma (PDAC) in preclinical models through c-Met inhibition. We sought to determine the maximum tolerated dose (MTD) of this combination in patients with advanced PDAC. Methods Patients with ≤1 prior treatment and adequate performance status were eligible. Cabozantinib was given orally once daily, beginning day (-)7 and continued with gemcitabine given intravenously on days 1, 8, and 15 every 28 days. Dose level was assigned using Time to Event Continual Reassessment Method (TITE-CRM). Primary endpoint was MTD, defined as the highest dose level at which ≤25 % of patients incurred a dose-limiting toxicity (DLT). Secondary endpoints included response rate, progression-free survival (PFS), overall survival (OS) and urinary biomarker assessment. Results Twelve patients were enrolled and treated with 10 patients evaluable for DLT. The probability of DLT was >25 % for all dose levels tested, and thus an MTD was not determined. DLTs included grade 3 ALT/AST elevations and thrombocytopenia. Three patients had partial responses, but each discontinued therapy due to toxicity. Median PFS and OS were 4.7 (95 % CI: 1.4-9.7) and 10.1 months (95 % CI: 3.6-20.6). Exploratory biomarker analysis showed correlation of c-Met and VEGF levels with response. Conclusions An MTD for the combination was not established. Cabozantinib and gemcitabine appear impractical for further development due to DLT at low doses and continuing toxicities with ongoing therapy. Acknowledging the small sample size, responses were seen suggesting further investigation of c-Met inhibition in PDAC may be warranted. JF - Investigational new drugs AU - Zhen, David B AU - Griffith, Kent A AU - Ruch, Joshua M AU - Camphausen, Kevin AU - Savage, Jason E AU - Kim, Edward J AU - Sahai, Vaibhav AU - Simeone, Diane M AU - Zalupski, Mark M AD - Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, 3-219 CC, 1500 E Medical Center Dr., SPC 5934, Ann Arbor, MI, 48109-5934, USA. ; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA. ; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ; Department of Surgery, University of Michigan, Ann Arbor, MI, USA. ; Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, 3-219 CC, 1500 E Medical Center Dr., SPC 5934, Ann Arbor, MI, 48109-5934, USA. zalupski@med.umich.edu. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 733 EP - 739 VL - 34 IS - 6 KW - XL-184 KW - Pancreatic cancer KW - Cabozantinib KW - Gemcitabine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826727501?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigational+new+drugs&rft.atitle=A+phase+I+trial+of+cabozantinib+and+gemcitabine+in+advanced+pancreatic+cancer.&rft.au=Zhen%2C+David+B%3BGriffith%2C+Kent+A%3BRuch%2C+Joshua+M%3BCamphausen%2C+Kevin%3BSavage%2C+Jason+E%3BKim%2C+Edward+J%3BSahai%2C+Vaibhav%3BSimeone%2C+Diane+M%3BZalupski%2C+Mark+M&rft.aulast=Zhen&rft.aufirst=David&rft.date=2016-12-01&rft.volume=34&rft.issue=6&rft.spage=733&rft.isbn=&rft.btitle=&rft.title=Investigational+new+drugs&rft.issn=1573-0646&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Effects of Age, Sex, Body Weight, and Quantity of Alcohol Consumption on Occurrence and Severity of Alcoholic Hepatitis. AN - 1826704402; 27320325 AB - Only a minority of heavy drinking individuals develop alcoholic hepatitis (AH), for unclear reasons. We analyzed data from the Translational Research and Evolving Alcoholic Hepatitis Treatment cohort, consisting of subjects who drink heavily with normal results from liver tests (controls) and patients with AH. We examined risk factors for the development of AH including body mass index (BMI), drinking pattern and quantity, and sex. We compared data from 145 patients with AH and 124 controls based on BMI when they joined the cohort; groups were matched for sex and race. Drinking patterns were assessed using the timeline followback method, the Alcohol Use Disorders Identification Test, and the National Institute of Alcohol Abuse and Alcoholism 6-question survey. We performed univariable and multivariable analyses to assess the effects of these factors and their interaction in increasing the risk for AH. We also explored the association between PNPLA3 variants and AH. Cases with AH were older (47 vs 44 y; P = .03). For nearly all measures of quantity of alcohol consumed or frequency of binge drinking, controls drank more heavily than cases with AH. We did not find an association between BMI, sex, drinking patterns, and the presence of AH. Age and BMI were independent predictors for the severity of AH. When we analyzed cases and controls of European ancestry, the PNPLA3 single-nucleotide polymorphism rs738409 was associated with risk for AH (odds ratio, 1.89; P = .007). Compared with heavy drinkers without liver disease, subjects with AH consumed lower levels of alcohol and had less binge drinking, suggesting an increased sensitivity to the toxic effects of alcohol. The risk for AH may be associated with the PNPLA3 rs738409 polymorphism. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved. JF - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association AU - Liangpunsakul, Suthat AU - Puri, Puneet AU - Shah, Vijay H AU - Kamath, Patrick AU - Sanyal, Arun AU - Urban, Thomas AU - Ren, Xiaowei AU - Katz, Barry AU - Radaeva, Svetlana AU - Chalasani, Naga AU - Crabb, David W AU - Translational Research and Evolving Alcoholic Hepatitis Treatment Consortium AD - Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Medicine, Roudebush Veterans Administration Medical Center, Indianapolis, Indiana. Electronic address: sliangpu@iupui.edu. ; Division of Gastroenterology and Hepatology, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia. ; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. ; Division of Pharmacotherapy and Experimental Therapeutics, Center for Pharmacogenomics and Individualized Therapy, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina. ; Department of Biostatistics, Richard M. Fairbanks School of Public Health, Indiana University School of Medicine, Indianapolis, Indiana. ; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland. ; Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana. ; Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Eskenazi Health, Indianapolis, Indiana. ; Translational Research and Evolving Alcoholic Hepatitis Treatment Consortium Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1831 EP - 1838.e3 VL - 14 IS - 12 KW - Body Weight KW - Gender KW - TLFB KW - Alcoholic Hepatitis KW - TREAT KW - Alcohol Intake UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826704402?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+gastroenterology+and+hepatology+%3A+the+official+clinical+practice+journal+of+the+American+Gastroenterological+Association&rft.atitle=Effects+of+Age%2C+Sex%2C+Body+Weight%2C+and+Quantity+of+Alcohol+Consumption+on+Occurrence+and+Severity+of+Alcoholic+Hepatitis.&rft.au=Liangpunsakul%2C+Suthat%3BPuri%2C+Puneet%3BShah%2C+Vijay+H%3BKamath%2C+Patrick%3BSanyal%2C+Arun%3BUrban%2C+Thomas%3BRen%2C+Xiaowei%3BKatz%2C+Barry%3BRadaeva%2C+Svetlana%3BChalasani%2C+Naga%3BCrabb%2C+David+W%3BTranslational+Research+and+Evolving+Alcoholic+Hepatitis+Treatment+Consortium&rft.aulast=Liangpunsakul&rft.aufirst=Suthat&rft.date=2016-12-01&rft.volume=14&rft.issue=12&rft.spage=1831&rft.isbn=&rft.btitle=&rft.title=Clinical+gastroenterology+and+hepatology+%3A+the+official+clinical+practice+journal+of+the+American+Gastroenterological+Association&rft.issn=1542-7714&rft_id=info:doi/10.1016%2Fj.cgh.2016.05.041 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.cgh.2016.05.041 ER - TY - JOUR T1 - Age-dependent PPARα activation induces hepatic sulfatide accumulation in transgenic mice carrying the hepatitis C virus core gene. AN - 1826704368; 27318478 AB - Sulfatides, a type of glycosphingolipid, are associated with carcinogenesis. Peroxisome proliferator-activated receptor α (PPARα) is involved in the regulation of sulfatide metabolism as well as in cancer development. We previously reported that transgenic (Tg) mice expressing hepatitis C virus core protein (HCVcp) exhibited age-dependent PPARα activation and carcinogenesis in liver. However, the metabolism of sulfatides in hepatocellular carcinoma is unknown. To examine the relationship between sulfatide metabolism, carcinogenesis, HCVcp, and PPARα, age-dependent changes of these factors were examined in HCVcpTg, PPARα inhibitor-treated HCVcpTg, and non-Tg mice. The sulfatide content in liver, the hepatic expression of two key enzymes catalyzing the initial and last reactions in sulfatide synthesis, the hepatic expression of known sulfatide-transferring protein, oxidative stress, and hepatic PPARα expression and its activation were age-dependently increased in HCVcpTg mice. The increased synthesis and accumulation of sulfatides and PPARα activation were significantly enhanced in liver cancer lesions. These changes were attenuated by PPARα inhibitor treatment and not observed in non-Tg mice. These results suggest that HCVcp-induced age-dependent PPARα activation increases synthesis of sulfatides and the resulting sulfatide accumulation affects HCV-related liver cancer. The monitoring of hepatic sulfatide content and the modulation of sulfatide generation by intervention using a PPARα inhibitor might be useful for the prediction and prevention of HCV-related hepatocarcinogenesis, respectively. JF - Glycoconjugate journal AU - Tian, Yangyang AU - Yang, Yang AU - Zhang, Xiaowei AU - Nakajima, Takero AU - Tanaka, Naoki AU - Sugiyama, Eiko AU - Kamijo, Yuji AU - Lu, Yu AU - Moriya, Kyoji AU - Koike, Kazuhiko AU - Gonzalez, Frank J AU - Aoyama, Toshifumi AD - Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Matsumoto, 390-8621, Japan. ; Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China. ; Department of Nutritional Science, Prefectural College, Nagano, Nagano, 380-8525, Japan. ; Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. yujibeat@shinshu-u.ac.jp. ; Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan. ; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 927 EP - 936 VL - 33 IS - 6 KW - Sphingolipid KW - HCV KW - Sulfatide KW - Cancer KW - PPARα KW - Core protein UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826704368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Glycoconjugate+journal&rft.atitle=Age-dependent+PPAR%CE%B1+activation+induces+hepatic+sulfatide+accumulation+in+transgenic+mice+carrying+the+hepatitis+C+virus+core+gene.&rft.au=Tian%2C+Yangyang%3BYang%2C+Yang%3BZhang%2C+Xiaowei%3BNakajima%2C+Takero%3BTanaka%2C+Naoki%3BSugiyama%2C+Eiko%3BKamijo%2C+Yuji%3BLu%2C+Yu%3BMoriya%2C+Kyoji%3BKoike%2C+Kazuhiko%3BGonzalez%2C+Frank+J%3BAoyama%2C+Toshifumi&rft.aulast=Tian&rft.aufirst=Yangyang&rft.date=2016-12-01&rft.volume=33&rft.issue=6&rft.spage=927&rft.isbn=&rft.btitle=&rft.title=Glycoconjugate+journal&rft.issn=1573-4986&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Phase II trial of everolimus in patients with previously treated recurrent or metastatic head and neck squamous cell carcinoma. AN - 1826693603; 27232378 AB - Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) demonstrate aberrant activation of the phosphotidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. We examined the efficacy of everolimus, an mTOR inhibitor, in patients with recurrent or metastatic HNSCC. This single-arm phase II study enrolled biomarker-unselected patients with recurrent or metastatic HNSCC who failed at least 1 prior therapy. Everolimus was administered until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and evaluation of tissue and serum biomarkers related to the PIK3CA pathway. Seven of 9 patients treated in the first stage were evaluable. No objective responses were seen; CBR was 28%. Three patients discontinued everolimus because of toxicity. Median PFS and OS were 1.5 and 4.5 months, respectively. No activating PI3K mutations were identified in available tumor tissue. Everolimus was not active as monotherapy in unselected patients with recurrent/metastatic HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1759-1764, 2016. © 2016 Wiley Periodicals, Inc. JF - Head & neck AU - Geiger, Jessica L AU - Bauman, Julie E AU - Gibson, Michael K AU - Gooding, William E AU - Varadarajan, Prakash AU - Kotsakis, Athanasios AU - Martin, Daniel AU - Gutkind, Jorge Silvio AU - Hedberg, Matthew L AU - Grandis, Jennifer R AU - Argiris, Athanassios AD - Department of Internal Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania. ; Department of Internal Medicine, Division of Hematology/Oncology, Case Western University, Cleveland, Ohio. ; Biostatistics Facility, University of Pittsburgh, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. ; Department of Medicine, Division of Hematology/Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas. ; School of Medicine, University of Crete, Crete, Greece. ; National Institute of Dental and Craniofacial Research, Bethesda, Maryland. ; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania. ; Department of Otolaryngology, University of California San Francisco, San Francisco, California. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1759 EP - 1764 VL - 38 IS - 12 KW - PIK3CA mutations KW - mammalian target of rapamycin (mTOR) inhibitors KW - head and neck squamous cell carcinoma (HNSCC) KW - clinical trial KW - everolimus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826693603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Head+%26+neck&rft.atitle=Phase+II+trial+of+everolimus+in+patients+with+previously+treated+recurrent+or+metastatic+head+and+neck+squamous+cell+carcinoma.&rft.au=Geiger%2C+Jessica+L%3BBauman%2C+Julie+E%3BGibson%2C+Michael+K%3BGooding%2C+William+E%3BVaradarajan%2C+Prakash%3BKotsakis%2C+Athanasios%3BMartin%2C+Daniel%3BGutkind%2C+Jorge+Silvio%3BHedberg%2C+Matthew+L%3BGrandis%2C+Jennifer+R%3BArgiris%2C+Athanassios&rft.aulast=Geiger&rft.aufirst=Jessica&rft.date=2016-12-01&rft.volume=38&rft.issue=12&rft.spage=1759&rft.isbn=&rft.btitle=&rft.title=Head+%26+neck&rft.issn=1097-0347&rft_id=info:doi/10.1002%2Fhed.24501 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/hed.24501 ER - TY - JOUR T1 - Impact of lysosome status on extracellular vesicle content and release. AN - 1826689810; 27238186 AB - Extracellular vesicles (EVs) are nanoscale size bubble-like membranous structures released from cells. EVs contain RNA, lipids and proteins and are thought to serve various roles including intercellular communication and removal of misfolded proteins. The secretion of misfolded and aggregated proteins in EVs may be a cargo disposal alternative to the autophagy-lysosomal and ubiquitin-proteasome pathways. In this review we will discuss the importance of lysosome functionality for the regulation of EV secretion and content. Exosomes are a subtype of EVs that are released by the fusion of multivesicular bodies (MVB) with the plasma membrane. MVBs can also fuse with lysosomes, and the trafficking pathway of MVBs can therefore determine whether or not exosomes are released from cells. Here we summarize data from studies of the effects of lysosome inhibition on the secretion of EVs and on the possibility that cells compensate for lysosome malfunction by disposal of potentially toxic cargos in EVs. A better understanding of the molecular mechanisms that regulate trafficking of MVBs to lysosomes and the plasma membrane may advance an understanding of diseases in which pathogenic proteins, lipids or infectious agents accumulate within or outside of cells. Copyright © 2016. Published by Elsevier B.V. JF - Ageing research reviews AU - Eitan, Erez AU - Suire, Caitlin AU - Zhang, Shi AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD 21224, USA. Electronic address: erez.eitan@nih.gov. ; Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD 21224, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 65 EP - 74 VL - 32 KW - Parkinson’s disease KW - Alzheimer’s disease KW - Niemann pick disease KW - HIV AIDS UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826689810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ageing+research+reviews&rft.atitle=Impact+of+lysosome+status+on+extracellular+vesicle+content+and+release.&rft.au=Eitan%2C+Erez%3BSuire%2C+Caitlin%3BZhang%2C+Shi%3BMattson%2C+Mark+P&rft.aulast=Eitan&rft.aufirst=Erez&rft.date=2016-12-01&rft.volume=32&rft.issue=&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Ageing+research+reviews&rft.issn=1872-9649&rft_id=info:doi/10.1016%2Fj.arr.2016.05.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.arr.2016.05.001 ER - TY - JOUR T1 - The role of hepatitis E virus infection in adult Americans with acute liver failure. AN - 1826689111; 27215797 AB - Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western countries. Given that antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV-related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the U.S. Acute Liver Failure Study Group were tested for anti-HEV immunoglobulin (Ig) M and anti-HEV IgG levels. Subjects with a detectable anti-HEV IgM also underwent testing for HEV RNA. Mean patient age was 41.8 years, 32.9% were male, and ALF etiologies included acetaminophen (APAP) hepatotoxicity (29%), indeterminate ALF (23%), idiosyncratic drug-induced liver injury DILI (22%), acute hepatitis B virus infection (12%), autoimmune hepatitis (12%), and pregnancy-related ALF (2%). Three men ages 36, 39, and 70 demonstrated repeatedly detectable anti-HEV IgM, but all were HEV-RNA negative and had other putative diagnoses. The latter 2 subjects died within 3 and 11 days of enrollment whereas the 36-year-old underwent emergency liver transplantation on study day 2. At admission, 294 (43.4%) of the ALF patients were anti-HEV IgG positive with the seroprevalence being highest in those from the Midwest (50%) and lowest in those from the Southeast (28%). Anti-HEV IgG+ subjects were significantly older, less likely to have APAP overdose, and had a lower overall 3-week survival compared to anti-HEV IgG- subjects (63% vs. 70%; P = 0.018). Acute HEV infection is very rare in adult Americans with ALF (i.e., 0.4%) and could not be implicated in any indeterminate, autoimmune, or pregnancy-related ALF cases. Past exposure to HEV with detectable anti-HEV IgG was significantly more common in the ALF patients compared to the general U.S. (Hepatology 2016;64:1870-1880). © 2016 by the American Association for the Study of Liver Diseases. JF - Hepatology (Baltimore, Md.) AU - Fontana, Robert John AU - Engle, Ronald E AU - Scaglione, Steven AU - Araya, Victor AU - Shaikh, Obaid AU - Tillman, Holly AU - Attar, Nahid AU - Purcell, Robert H AU - Lee, William M AU - US Acute Liver Failure Study Group AD - Department of Internal Medicine, University of Michigan, Ann Arbor, MI. ; National Institute of Allergy and Infectious Diseases, Bethesda, MD. ; Department of Internal Medicine, Loyola Medical Center, Maywood, IL. ; Einstein Medical Center, Philadelphia, PA. ; Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA. ; Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC. ; University of Texas Southwestern, Dallas, TX. ; US Acute Liver Failure Study Group Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1870 EP - 1880 VL - 64 IS - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826689111?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=The+role+of+hepatitis+E+virus+infection+in+adult+Americans+with+acute+liver+failure.&rft.au=Fontana%2C+Robert+John%3BEngle%2C+Ronald+E%3BScaglione%2C+Steven%3BAraya%2C+Victor%3BShaikh%2C+Obaid%3BTillman%2C+Holly%3BAttar%2C+Nahid%3BPurcell%2C+Robert+H%3BLee%2C+William+M%3BUS+Acute+Liver+Failure+Study+Group&rft.aulast=Fontana&rft.aufirst=Robert&rft.date=2016-12-01&rft.volume=64&rft.issue=6&rft.spage=1870&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=1527-3350&rft_id=info:doi/10.1002%2Fhep.28649 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/hep.28649 ER - TY - JOUR T1 - Critical concepts, practice recommendations, and research perspectives of pixantrone therapy in non-Hodgkin lymphoma: a SIE, SIES, and GITMO consensus paper. AN - 1826680952; 27124765 AB - In this paper, we present a review of critical concepts and research perspectives and produce recommendations on the optimal use of pixantrone in non-Hodgkin lymphoma (NHL) by group discussion from an expert panel appointed by the Italian Society of Hematology and the affiliate societies, Società Italiana di Ematologia Sperimentale and Gruppo Italiano Trapianto di Midollo Osseo. Recommendations were produced using the Delphi process. Scientific evidence on pixantrone efficacy was analyzed using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology in the areas where at least one randomized trial was published. The following key issues were addressed for practical recommendations: pixantrone monotherapy in aggressive relapsed or refractory non-Hodgkin B-cell lymphomas and toxicity risk management in patients candidates to pixantrone. After a balanced and value-oriented discussion, the panel agreed that the benefit/risk profile was in favor of pixantrone in the treatment of adult patients with multiply relapsed or refractory aggressive NHL B-cell lymphomas. Pixantrone was deemed to be contraindicated in patients with uncontrolled cardiovascular disease. Despite a low rate of cardiotoxicity of pixantrone reported in clinical trials, the panel recommended that all patients receiving pixantrone should undergo periodical cardiac monitoring. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. JF - European journal of haematology AU - Zinzani, Pier Luigi AU - Corradini, Paolo AU - Martelli, Maurizio AU - Minotti, Giorgio AU - Oliva, Stefano AU - Spina, Michele AU - Barosi, Giovanni AU - Tura, Sante AD - Institute of Hematology "Seràgnoli", University of Bologna, Bologna, Italy. ; Division of Hematology and Bone Marrow Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Milano, Milan, Italy. ; Dipartimento Biotecnologie Cellulari ed Ematologia, Universitá La Sapienza, Rome, Italy. ; Department of Medicine and Units of Drug Sciences and Clinical Pharmacology, University Campus Bio-Medico, Rome, Italy. ; Cardiology Unit, National Cancer Institute IRCCS "Giovanni Paolo II", Bari, Italy. ; Division of Medical Oncology A, National Cancer Institute, Aviano, Italy. ; Center of the Study of Myelofibrosis, Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy. ; University of Bologna, Bologna, Italy. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 554 EP - 561 VL - 97 IS - 6 KW - guidelines KW - pixantrone KW - GRADE methodology KW - non-Hodgkin lymphoma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826680952?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+haematology&rft.atitle=Critical+concepts%2C+practice+recommendations%2C+and+research+perspectives+of+pixantrone+therapy+in+non-Hodgkin+lymphoma%3A+a+SIE%2C+SIES%2C+and+GITMO+consensus+paper.&rft.au=Zinzani%2C+Pier+Luigi%3BCorradini%2C+Paolo%3BMartelli%2C+Maurizio%3BMinotti%2C+Giorgio%3BOliva%2C+Stefano%3BSpina%2C+Michele%3BBarosi%2C+Giovanni%3BTura%2C+Sante&rft.aulast=Zinzani&rft.aufirst=Pier&rft.date=2016-12-01&rft.volume=97&rft.issue=6&rft.spage=554&rft.isbn=&rft.btitle=&rft.title=European+journal+of+haematology&rft.issn=1600-0609&rft_id=info:doi/10.1111%2Fejh.12768 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/ejh.12768 ER - TY - JOUR T1 - MiR-16 mediates trastuzumab and lapatinib response in ErbB-2-positive breast and gastric cancer via its novel targets CCNJ and FUBP1. AN - 1826677374; 27157613 AB - ErbB-2 amplification/overexpression accounts for an aggressive breast cancer (BC) subtype (ErbB-2-positive). Enhanced ErbB-2 expression was also found in gastric cancer (GC) and has been correlated with poor clinical outcome. The ErbB-2-targeted therapies trastuzumab (TZ), a monoclonal antibody, and lapatinib, a tyrosine kinase inhibitor, have proved highly beneficial. However, resistance to such therapies remains a major clinical challenge. We here revealed a novel mechanism underlying the antiproliferative effects of both agents in ErbB-2-positive BC and GC. TZ and lapatinib ability to block extracellular signal-regulated kinases 1/2 and phosphatidylinositol-3 kinase (PI3K)/AKT in sensitive cells inhibits c-Myc activation, which results in upregulation of miR-16. Forced expression of miR-16 inhibited in vitro proliferation in BC and GC cells, both sensitive and resistant to TZ and lapatinib, as well as in a preclinical BC model resistant to these agents. This reveals miR-16 role as tumor suppressor in ErbB-2-positive BC and GC. Using genome-wide expression studies and miRNA target prediction algorithms, we identified cyclin J and far upstream element-binding protein 1 (FUBP1) as novel miR-16 targets, which mediate miR-16 antiproliferative effects. Supporting the clinical relevance of our results, we found that high levels of miR-16 and low or null FUBP1 expression correlate with TZ response in ErbB-2-positive primary BCs. These findings highlight a potential role of miR-16 and FUBP1 as biomarkers of sensitivity to TZ therapy. Furthermore, we revealed miR-16 as an innovative therapeutic agent for TZ- and lapatinib-resistant ErbB-2-positive BC and GC. JF - Oncogene AU - Venturutti, L AU - Cordo Russo, R I AU - Rivas, M A AU - Mercogliano, M F AU - Izzo, F AU - Oakley, R H AU - Pereyra, M G AU - De Martino, M AU - Proietti, C J AU - Yankilevich, P AU - Roa, J C AU - Guzmán, P AU - Cortese, E AU - Allemand, D H AU - Huang, T H AU - Charreau, E H AU - Cidlowski, J A AU - Schillaci, R AU - Elizalde, P V AD - Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina. ; Department of Medicine, Weill Cornell Medicine, New York, NY, USA. ; Department of Health and Human Services, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA. ; Instituto de Investigación en Biomedicina de Buenos Aires, CONICET-Partner Institute of the Max Planck Society, Buenos Aires, Argentina. ; Departamento de Anatomía Patológica (BIOREN), Universidad de La Frontera, Temuco, Chile. ; Servicio de Ginecología, Hospital Aeronáutico Central, Buenos Aires, Argentina. ; Unidad de Patología Mamaria, Hospital General de Agudos 'Juan A Fernández', Buenos Aires, Argentina. ; Department of Molecular Medicine/Institute of Biotechnology, Cancer Therapy and Research Center, University of Texas, San Antonio, TX, USA. Y1 - 2016/12/01/ PY - 2016 DA - 2016 Dec 01 SP - 6189 EP - 6202 VL - 35 IS - 48 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826677374?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=MiR-16+mediates+trastuzumab+and+lapatinib+response+in+ErbB-2-positive+breast+and+gastric+cancer+via+its+novel+targets+CCNJ+and+FUBP1.&rft.au=Venturutti%2C+L%3BCordo+Russo%2C+R+I%3BRivas%2C+M+A%3BMercogliano%2C+M+F%3BIzzo%2C+F%3BOakley%2C+R+H%3BPereyra%2C+M+G%3BDe+Martino%2C+M%3BProietti%2C+C+J%3BYankilevich%2C+P%3BRoa%2C+J+C%3BGuzm%C3%A1n%2C+P%3BCortese%2C+E%3BAllemand%2C+D+H%3BHuang%2C+T+H%3BCharreau%2C+E+H%3BCidlowski%2C+J+A%3BSchillaci%2C+R%3BElizalde%2C+P+V&rft.aulast=Venturutti&rft.aufirst=L&rft.date=2016-12-01&rft.volume=35&rft.issue=48&rft.spage=6189&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=1476-5594&rft_id=info:doi/10.1038%2Fonc.2016.151 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/onc.2016.151 ER - TY - JOUR T1 - Influence of 6-Hydroxydopamine Toxicity on α-Synuclein Phosphorylation, Resting Vesicle Expression, and Vesicular Dopamine Release. AN - 1826666228; 27064513 AB - Post mortem studies on familial and sporadic Parkinson's disease patient striatal tissue have shown that nearly 90% of α-synuclein deposited in Lewy-bodies is phosphorylated at serine-129 (pSyn-129) as opposed to only 4% in normal human brain. We aimed to find the influence of endogenous neurotoxin 6-hydroxydopamine (6-OHDA) on α-synuclein phosphorylation, resting vesicles, and vesicular dopamine release. The relative distribution of pSyn-129+ cells in apoptotic and non-apoptotic populations at different 6-OHDA concentrations was assessed along with changes in oxidant-antioxidant system, mitochondrial membrane-potential, and intracellular-Ca2+ . Exposing SH-SY5Y cells to different concentrations of 6-OHDA for 48 h showed cell-death and apoptosis. Immunocytochemical analysis indicated an increase in pSyn-129 with increasing 6-OHDA concentration, and ELISA-estimation showed a significant increase in the pSyn-129 to α-synuclein ratio. FACS analysis also showed a significant increase in pSyn-129; and at sub-lethal 6-OHDA concentrations, pSyn-129+ cells were primarily distributed in the non-apoptotic population, suggesting that phosphorylation of α-synuclein precedes apoptosis. At higher 6-OHDA concentrations, the pSyn-129+ cell count significantly increased in the apoptotic population and decreased in the non-apoptotic population. Cytosolic co-localization of α-synuclein and ubiquitin was noticed at higher doses of 6-OHDA. FACS analysis showed decrease in vesicular monoamine transporter-2 (VMAT2) expression in 6-OHDA-treated cells, confirmed by reduction in functional dopamine-release on KCl and ATP stimulation. Significant decrease in VMAT2 expression and vesicular dopamine-release were observed with the lower 6-OHDA concentration, together with mild occurrence of apoptosis and significant increase in phosphorylated α-synuclein. This suggests that at sub-lethal 6-OHDA concentrations, the decrease in resting vesicles (VMAT2) and vesicular dopamine release are not attributable to apoptotic cell death and occur concomitantly with the phosphorylation of α-synuclein. J. Cell. Biochem. 117: 2719-2736, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. JF - Journal of cellular biochemistry AU - Ganapathy, Kavina AU - Datta, Indrani AU - Sowmithra, Sowmithra AU - Joshi, Preeti AU - Bhonde, Ramesh AD - School of Regenerative Medicine, Manipal University, Bengaluru, Karnataka, India. ; Department of Biophysics, National Institute of Mental Health and Neurosciences, an Institute of National Importance, Bengaluru, Karnataka, India. indranidatta.nimhans@gmail.com. ; Department of Biophysics, National Institute of Mental Health and Neurosciences, an Institute of National Importance, Bengaluru, Karnataka, India. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 2719 EP - 2736 VL - 117 IS - 12 KW - APOPTOSIS KW - SUB-LETHAL CONCENTRATION OF 6-OHDA KW - PHOSPHO SERINE129 α-SYNUCLEIN KW - MITOCHONDRIAL MEMBRANE POTENTIAL KW - VESICULAR MONOAMINE TRANSPORTER KW - IN VITRO PD MODEL UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826666228?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry&rft.atitle=Influence+of+6-Hydroxydopamine+Toxicity+on+%CE%B1-Synuclein+Phosphorylation%2C+Resting+Vesicle+Expression%2C+and+Vesicular+Dopamine+Release.&rft.au=Ganapathy%2C+Kavina%3BDatta%2C+Indrani%3BSowmithra%2C+Sowmithra%3BJoshi%2C+Preeti%3BBhonde%2C+Ramesh&rft.aulast=Ganapathy&rft.aufirst=Kavina&rft.date=2016-12-01&rft.volume=117&rft.issue=12&rft.spage=2719&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry&rft.issn=1097-4644&rft_id=info:doi/10.1002%2Fjcb.25570 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/jcb.25570 ER - TY - JOUR T1 - PPARα-dependent cholesterol/testosterone disruption in Leydig cells mediates 2,4-dichlorophenoxyacetic acid-induced testicular toxicity in mice. AN - 1826658977; 26838045 AB - It was reported that 2,4-dichlorophenoxyacetic acid (2,4-D), a commonly used herbicide and a possible endocrine disruptor, can disturb spermatogenesis, but the precise mechanism is not understood. Since 2,4-D is a weak peroxisome proliferator in hepatocytes and peroxisome proliferator-activated receptor α (PPARα) is also expressed in Leydig cells, this study aimed to investigate the link between PPARα and 2,4-D-mediated testicular dysfunction. 2,4-D (130 mg/kg/day) was administered to wild-type and Ppara-null mice for 2 weeks, and the alterations in testis and testosterone/cholesterol metabolism in Leydig cells were examined. Treatment with 2,4-D markedly decreased testicular testosterone in wild-type mice, leading to degeneration of spermatocytes and Sertoli cells. The 2,4-D decreased cholesterol levels in Leydig cells of wild-type mice through down-regulating the expression of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 and reductase, involved in de novo cholesterogenesis. However, the mRNAs encoding the important proteins involved in testosterone synthesis were unchanged by 2,4-D except for CYP17A1, indicating that exhausted cholesterol levels in the cells is a main reason for reduced testicular testosterone. Additionally, pregnancy rate and the number of pups between 2,4-D-treated wild-type male mice and untreated female mice were significantly lower compared with those between untreated couples. These phenomena were not observed in 2,4-D-treated Ppara-null males. Collectively, these results suggest a critical role for PPARα in 2,4-D-induced testicular toxicity due to disruption of cholesterol/testosterone homeostasis in Leydig cells. This study yields novel insights into the possible mechanism of testicular dysfunction and male infertility caused by 2,4-D. JF - Archives of toxicology AU - Harada, Yukiko AU - Tanaka, Naoki AU - Ichikawa, Motoki AU - Kamijo, Yuji AU - Sugiyama, Eiko AU - Gonzalez, Frank J AU - Aoyama, Toshifumi AD - Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. ; Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. naopi@shinshu-u.ac.jp. ; Department of Family and Child Nursing, Shinshu University School of Health Sciences, Matsumoto, Japan. ; Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan. ; Department of Nutritional Science, Nagano Prefectural College, Nagano, Japan. ; Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 3061 EP - 3071 VL - 90 IS - 12 KW - Testosterone KW - 2,4-dichlorophenoxyacetic acid KW - Testicular toxicity KW - Leydig cell KW - Cholesterol KW - PPARα UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826658977?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+toxicology&rft.atitle=PPAR%CE%B1-dependent+cholesterol%2Ftestosterone+disruption+in+Leydig+cells+mediates+2%2C4-dichlorophenoxyacetic+acid-induced+testicular+toxicity+in+mice.&rft.au=Harada%2C+Yukiko%3BTanaka%2C+Naoki%3BIchikawa%2C+Motoki%3BKamijo%2C+Yuji%3BSugiyama%2C+Eiko%3BGonzalez%2C+Frank+J%3BAoyama%2C+Toshifumi&rft.aulast=Harada&rft.aufirst=Yukiko&rft.date=2016-12-01&rft.volume=90&rft.issue=12&rft.spage=3061&rft.isbn=&rft.btitle=&rft.title=Archives+of+toxicology&rft.issn=1432-0738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-02-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - BODY SIZE-SPECIFIC EFFECTIVE DOSE CONVERSION COEFFICIENTS FOR CT SCANS. AN - 1826644645; 26755767 AB - Effective dose from computed tomography (CT) examinations is usually estimated using the scanner-provided dose-length product and using conversion factors, also known as k-factors, which correspond to scan regions and differ by age according to five categories: 0, 1, 5, 10 y and adult. However, patients often deviate from the standard body size on which the conversion factor is based. In this study, a method for deriving body size-specific k-factors is presented, which can be determined from a simple regression curve based on patient diameter at the centre of the scan range. Using the International Commission on Radiological Protection reference paediatric and adult computational phantoms paired with Monte Carlo simulation of CT X-ray beams, the authors derived a regression-based k-factor model for the following CT scan types: head-neck, head, neck, chest, abdomen, pelvis, abdomen-pelvis (AP) and chest-abdomen-pelvis (CAP). The resulting regression functions were applied to a total of 105 paediatric and 279 adult CT scans randomly sampled from patients who underwent chest, AP and CAP scans at the National Institutes of Health Clinical Center. The authors have calculated and compared the effective doses derived from the conventional age-specific k-factors with the values computed using their body size-specific k-factor. They found that by using the age-specific k-factor, paediatric patients tend to have underestimates (up to 3-fold) of effective dose, while underweight and overweight adult patients tend to have underestimates (up to 2.6-fold) and overestimates (up to 4.6-fold) of effective dose, respectively, compared with the effective dose determined from their body size-dependent factors. The authors present these size-specific k-factors as an alternative to the existing age-specific factors. The body size-specific k-factor will assess effective dose more precisely and on a more individual level than the conventional age-specific k-factors and, hence, improve awareness of the true exposure, which is important for the clinical community to understand. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US. JF - Radiation protection dosimetry AU - Romanyukha, Anna AU - Folio, Les AU - Lamart, Stephanie AU - Simon, Steven L AU - Lee, Choonsik AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA. ; Radiology and Imaging Sciences Clinical Center, National Institutes of Health, Bethesda, MD, USA. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA leechoonsik@mail.nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 428 EP - 437 VL - 172 IS - 4 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826644645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+protection+dosimetry&rft.atitle=BODY+SIZE-SPECIFIC+EFFECTIVE+DOSE+CONVERSION+COEFFICIENTS+FOR+CT+SCANS.&rft.au=Romanyukha%2C+Anna%3BFolio%2C+Les%3BLamart%2C+Stephanie%3BSimon%2C+Steven+L%3BLee%2C+Choonsik&rft.aulast=Romanyukha&rft.aufirst=Anna&rft.date=2016-12-01&rft.volume=172&rft.issue=4&rft.spage=428&rft.isbn=&rft.btitle=&rft.title=Radiation+protection+dosimetry&rft.issn=1742-3406&rft_id=info:doi/10.1093%2Frpd%2Fncv511 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-01-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/rpd/ncv511 ER - TY - JOUR T1 - Cranberry Extract Standardized for Proanthocyanidins Alleviates β-Amyloid Peptide Toxicity by Improving Proteostasis Through HSF-1 in Caenorhabditis elegans Model of Alzheimer's Disease. AN - 1826627541; 26405062 AB - A growing body of evidence suggests that nutraceuticals with prolongevity properties may delay the onset of Alzheimer's disease (AD). We recently demonstrated that a proanthocyanidins-standardized cranberry extract has properties that prolong life span and promote innate immunity in Caenorhabditis elegans In this article, we report that supplementation of this cranberry extract delayed Aβ toxicity-triggered body paralysis in the C elegans AD model. Genetic analyses indicated that the cranberry-mediated Aβ toxicity alleviation required heat shock transcription factor (HSF)-1 rather than DAF-16 and SKN-1. Moreover, cranberry supplementation increased the transactivity of HSF-1 in an IIS-dependent manner. Further studies found that the cranberry extract relies on HSF-1 to significantly enhance the solubility of proteins in aged worms, implying an improved proteostasis in AD worms. Considering that HSF-1 plays a pivotal role in maintaining proteostasis, our results suggest that cranberry maintains the function of proteostasis through HSF-1, thereby protecting C elegans against Aβ toxicity. Together, our findings elucidated the mechanism whereby cranberry attenuated Aβ toxicity in C elegans and stressed the significance of proteostasis in the prevention of age-related diseases from a practical point of view. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. JF - The journals of gerontology. Series A, Biological sciences and medical sciences AU - Guo, Hong AU - Cao, Min AU - Zou, Sige AU - Ye, Boping AU - Dong, Yuqing AD - Department of Biological Sciences, Clemson University, South Carolina. ; Functional Genomics Unit, Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland. ; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. ; Department of Biological Sciences, Clemson University, South Carolina. ydong@clemson.edu. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1564 EP - 1573 VL - 71 IS - 12 KW - hsf-1 KW - Proteostasis KW - Alzheimer’s disease KW - β-Amyloid KW - Cranberry KW - Caenorhabditis elegans UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826627541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+journals+of+gerontology.+Series+A%2C+Biological+sciences+and+medical+sciences&rft.atitle=Cranberry+Extract+Standardized+for+Proanthocyanidins+Alleviates+%CE%B2-Amyloid+Peptide+Toxicity+by+Improving+Proteostasis+Through+HSF-1+in+Caenorhabditis+elegans+Model+of+Alzheimer%27s+Disease.&rft.au=Guo%2C+Hong%3BCao%2C+Min%3BZou%2C+Sige%3BYe%2C+Boping%3BDong%2C+Yuqing&rft.aulast=Guo&rft.aufirst=Hong&rft.date=2016-12-01&rft.volume=71&rft.issue=12&rft.spage=1564&rft.isbn=&rft.btitle=&rft.title=The+journals+of+gerontology.+Series+A%2C+Biological+sciences+and+medical+sciences&rft.issn=1758-535X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2015-09-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Attention training normalises combat-related post-traumatic stress disorder effects on emotional Stroop performance using lexically matched word lists AN - 1822503465 AB - We examined two groups of combat veterans, one with post-traumatic stress disorder (PTSD) (n = 27) and another without PTSD (n = 16), using an emotional Stroop task (EST) with word lists matched across a series of lexical variables (e.g. length, frequency, neighbourhood size, etc.). Participants with PTSD exhibited a strong EST effect (longer colour-naming latencies for combat-relevant words as compared to neutral words). Veterans without PTSD produced no such effect, t < .918, p > .37. Participants with PTSD then completed eight sessions of attention training (Attention Control Training or Attention Bias Modification Training) with a dot-probe task utilising threatening and neutral faces. After training, participants-especially those undergoing Attention Control Training-no longer produced longer colour-naming latencies for combat-related words as compared to other words, indicating normalised attention allocation processes after treatment. JF - Cognition & Emotion AU - Khanna, Maya M AU - Badura-Brack, Amy S AU - McDermott, Timothy J AU - Shepherd, Alex AU - Heinrichs-Graham, Elizabeth AU - Pine, Daniel S AU - Bar-Haim, Yair AU - Wilson, Tony W AD - Department of Psychology, Creighton University, Omaha, NE, USA ; Department of Psychology, University of Nebraska-Omaha, Omaha, NE, USA ; National Institute of Mental Health, Rockville, MD, USA ; Department of Psychology and Neuroscience, School of Psychological Sciences, Tel-Aviv University, Tel Aviv-Yafo, Isreal ; Department of Pharmacology and Experimental Neuroscience, Department of Neurological Sciences, and the Center for Magnetoencephalography, University of Nebraska Medical Center, Omaha, NE, USA ; Department of Psychology, Creighton University, Omaha, NE, USA Y1 - 2016/12// PY - 2016 DA - Dec 2016 SP - 1521 EP - 1528 CY - Hove PB - Taylor & Francis Ltd. VL - 30 IS - 8 SN - 0269-9931 KW - Psychology KW - PTSD KW - attention training KW - emotional Stroop KW - lexically matched lists KW - attention bias modification KW - Combat related posttraumatic stress disorder KW - Modification KW - Attentional bias KW - Emotional Stroop task KW - Veterans KW - Words KW - Naming KW - Threatening KW - Traumatic stress UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1822503465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cognition+%26+Emotion&rft.atitle=Attention+training+normalises+combat-related+post-traumatic+stress+disorder+effects+on+emotional+Stroop+performance+using+lexically+matched+word+lists&rft.au=Khanna%2C+Maya+M%3BBadura-Brack%2C+Amy+S%3BMcDermott%2C+Timothy+J%3BShepherd%2C+Alex%3BHeinrichs-Graham%2C+Elizabeth%3BPine%2C+Daniel+S%3BBar-Haim%2C+Yair%3BWilson%2C+Tony+W&rft.aulast=Khanna&rft.aufirst=Maya&rft.date=2016-12-01&rft.volume=30&rft.issue=8&rft.spage=1521&rft.isbn=&rft.btitle=&rft.title=Cognition+%26+Emotion&rft.issn=02699931&rft_id=info:doi/10.1080%2F02699931.2015.1076769 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © 2015 Taylor & Francis N1 - Last updated - 2016-09-26 DO - http://dx.doi.org/10.1080/02699931.2015.1076769 ER - TY - JOUR T1 - Is cancer a severe delayed hypersensitivity reaction and histamine a blueprint? AN - 1814660433; 27558401 AB - Longevity and accumulation of multiple context-dependent signaling pathways of long-standing inflammation (antigen-load or oxidative stress) are the results of decreased/altered regulation of immunity and loss of control switch mechanisms that we defined as Yin and Yang of acute inflammation or immune surveillance. Chronic inflammation is initiated by immune disruptors-induced progressive changes in physiology and function of susceptible host tissues that lead to increased immune suppression and multistep disease processes including carcinogenesis. The interrelated multiple hypotheses that are presented for the first time in this article are extension of author's earlier series of 'accidental' discoveries on the role of inflammation in developmental stages of immune dysfunction toward tumorigenesis and angiogenesis. Detailed analyses of data on chronic diseases suggest that nearly all age-associated illnesses, generally categorized as 'mild' (e.g., increased allergies), 'moderate' (e.g., hypertension, colitis, gastritis, pancreatitis, emphysema) or 'severe' (e.g., accelerated neurodegenerative and autoimmune diseases or site-specific cancers and metastasis) are variations of hypersensitivity responses of tissues that are manifested as different diseases in immune-responsive or immune-privileged tissues. Continuous release/presence of low level histamine (subclinical) in circulation could contribute to sustained oxidative stress and induction of 'mild' or 'moderate' or 'severe' (immune tsunami) immune disorders in susceptible tissues. Site-specific cancers are proposed to be 'severe' (irreversible) forms of cumulative delayed hypersensitivity responses that would induce immunological chaos in favor of tissue growth in target tissues. Shared or special features of growth from fetus development into adulthood and aging processes and carcinogenesis are briefly compared with regard to energy requirements of highly complex function of Yin and Yang. Features of Yang (growth-promoting) arm of acute inflammation during fetus and cancer growth will be compared for consuming low energy from glycolysis (Warburg effect). Growth of fetus and cancer cells under hypoxic conditions and impaired mitochondrial energy requirements of tissues including metabolism of essential branched amino acids (e.g., val, leu, isoleu) will be compared for proposing a working model for future systematic research on cancer biology, prevention and therapy. Presentation of a working model provides insightful clues into bioenergetics that are required for fetus growth (absence of external threat and lack of high energy-demands of Yin events and parasite-like survival in host), normal growth in adulthood (balance in Yin and Yang processes) or disease processes and carcinogenesis (loss of balance in Yin-Yang). Future studies require focusing on dynamics and promotion of natural/inherent balance between Yin (tumoricidal) and Yang (tumorigenic) of effective immunity that develop after birth. Lawless growth of cancerous cells and loss of cell contact inhibition could partially be due to impaired mitochondria (mitophagy) that influence metabolism of branched chain amino acids for biosynthesis of structural proteins. The author invites interested scientists with diverse expertise to provide comments, confirm, dispute and question and/or expand and collaborate on many components of the proposed working model with the goal to better understand cancer biology for future designs of cost-effective research and clinical trials and prevention of cancer. Initial events during oxidative stress-induced damages to DNA/RNA repair mechanisms and inappropriate expression of inflammatory mediators are potentially correctable, preventable or druggable, if future studies were to focus on systematic understanding of early altered immune response dynamics toward multistep chronic diseases and carcinogenesis. JF - Clinical and translational medicine AU - Khatami, Mahin AD - National Cancer Institute (NCI), the National Institutes of Health (NIH), Bethesda, MD, USA. mkgoodness@aol.com. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 35 VL - 5 IS - 1 KW - Bioenergetics KW - Allergy KW - Fetal growth KW - Aging KW - Angiogenesis KW - Mitochondria KW - Branched amino acids KW - Cancer KW - Histamine KW - Taurine KW - Hypersensitivity KW - Yin and Yang of inflammation KW - Placenta KW - Immune-privileged and immune-responsive tissues UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1814660433?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+and+translational+medicine&rft.atitle=Is+cancer+a+severe+delayed+hypersensitivity+reaction+and+histamine+a+blueprint%3F&rft.au=Khatami%2C+Mahin&rft.aulast=Khatami&rft.aufirst=Mahin&rft.date=2016-12-01&rft.volume=5&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Clinical+and+translational+medicine&rft.issn=&rft_id=info:doi/10.1186%2Fs40169-016-0108-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-25 N1 - Date created - 2016-08-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s40169-016-0108-3 ER - TY - JOUR T1 - Impact of work-related cancers in Taiwan-Estimation with QALY (quality-adjusted life year) and healthcare costs. AN - 1804861949; 27413666 AB - This study estimates the annual numbers of eight work-related cancers, total losses of quality-adjusted life years (QALYs), and lifetime healthcare expenditures that possibly could be saved by improving occupational health in Taiwan. Three databases were interlinked: the Taiwan Cancer Registry, the National Mortality Registry, and the National Health Insurance Research Database. Annual numbers of work-related cancers were estimated based on attributable fractions (AFs) abstracted from a literature review. The survival functions for eight cancers were estimated and extrapolated to lifetime using a semi-parametric method. A convenience sample of 8846 measurements of patients' quality of life with EQ-5D was collected for utility values and multiplied by survival functions to estimate quality-adjusted life expectancies (QALEs). The loss-of-QALE was obtained by subtracting the QALE of cancer from age- and sex-matched referents simulated from national vital statistics. The lifetime healthcare expenditures were estimated by multiplying the survival probability with mean monthly costs paid by the National Health Insurance for cancer diagnosis and treatment and summing this for the expected lifetime. A total of 3010 males and 726 females with eight work-related cancers were estimated in 2010. Among them, lung cancer ranked first in terms of QALY loss, with an annual total loss-of-QALE of 28,463 QALYs and total lifetime healthcare expenditures of US$36.6 million. Successful prevention of eight work-related cancers would not only avoid the occurrence of 3736 cases of cancer, but would also save more than US$70 million in healthcare costs and 46,750 QALYs for the Taiwan society in 2010. JF - Preventive medicine reports AU - Lee, Lukas Jyuhn-Hsiarn AU - Lin, Cheng-Kuan AU - Hung, Mei-Chuan AU - Wang, Jung-Der AD - National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan; Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Environmental and Occupational Medicine, National Taiwan University Hospital, Taipei, Taiwan. ; Department of Environmental Health, Harvard T.H. Chan School of Public Health, United States; Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. ; Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. ; Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 87 EP - 93 VL - 4 KW - LTHE, Lifetime healthcare expenditure KW - QALY, Quality-adjusted life year KW - NMR, National Mortality Registry KW - QOL, Quality of life KW - DALY, Disability-adjusted life year KW - Quality-adjusted life expectancy (QALE) KW - AF, Attributable fraction KW - WHO, World Health Organization KW - TCR, Taiwan Cancer Registry KW - Attributable fraction (AF) KW - Work-related cancer KW - CAREX, CARcinogen EXposure KW - IARC, International Agency for Research on Cancer KW - NHIRD, National Health Insurance Research Database KW - NHI, National Health Insurance KW - Lifetime healthcare expenditure (LTHE) KW - QALE, Quality-adjusted life expectancy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1804861949?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Preventive+medicine+reports&rft.atitle=Impact+of+work-related+cancers+in+Taiwan-Estimation+with+QALY+%28quality-adjusted+life+year%29+and+healthcare+costs.&rft.au=Lee%2C+Lukas+Jyuhn-Hsiarn%3BLin%2C+Cheng-Kuan%3BHung%2C+Mei-Chuan%3BWang%2C+Jung-Der&rft.aulast=Lee&rft.aufirst=Lukas&rft.date=2016-12-01&rft.volume=4&rft.issue=&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Preventive+medicine+reports&rft.issn=&rft_id=info:doi/10.1016%2Fj.pmedr.2016.05.015 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-14 N1 - Date created - 2016-07-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.pmedr.2016.05.015 ER - TY - JOUR T1 - Engineering anti-Lewis-Y hu3S193 antibodies with improved therapeutic ratio for radioimmunotherapy of epithelial cancers. AN - 1774528217; 26983636 AB - The aim of the study was to explore Fc mutations of a humanised anti-Lewis-Y antibody (IgG1) hu3S193 as a strategy to improve therapeutic ratios for therapeutic payload delivery. Four hu3S193 variants (I253A, H310A, H435A and I253A/H310A) were generated via site-directed mutagenesis and radiolabelled with diagnostic isotopes iodine-125 or indium-111. Biodistribution studies in Lewis-Y-positive tumour-bearing mice were used to calculate the dose in tumours and organs for therapeutic isotopes (iodine-131, yttrium-90 and lutetium-177). (111)In-labelled I253A and H435A showed similar slow kinetics (t 1/2β, 63.2 and 62.2 h, respectively) and a maximum tumour uptake of 33.11 ± 4.05 and 33.69 ± 3.77 percentage injected dose per gramme (%ID/g), respectively. (111)In-labelled I253A/H310A cleared fastest (t 1/2β, 9.1 h) with the lowest maximum tumour uptake (23.72 ± 0.85 %ID/g). The highest increase in tumour-to-blood area under the curve (AUC) ratio was observed with the metal-labelled mutants ((90)Y and (177)Lu). (177)Lu-CHX-A" DTPA-hu3S193 I253A/H310A (6:1) showed the highest tumour-to-blood AUC ratio compared to wild type (3:1) and other variants and doubling of calculated dose to tumour based on red marrow dose constraints. These results suggest that hu3S193 Fc can be engineered with improved therapeutic ratios for (90)Y- and (177)Lu-based therapy, with the best candidate being hu3S193 I253A/H310A for (177)Lu-based therapy. JF - EJNMMI research AU - Burvenich, Ingrid J G AU - Lee, Fook-Thean AU - O'Keefe, Graeme J AU - Makris, Dahna AU - Cao, Diana AU - Gong, Sylvia AU - Rigopoulos, Angela AU - Allan, Laura C AU - Brechbiel, Martin W AU - Liu, Zhanqi AU - Ramsland, Paul A AU - Scott, Andrew M AD - Tumour Targeting Laboratory, Ludwig Institute for Cancer Research and Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia. ; School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia. ; Department of Molecular Imaging and Therapy, Austin Health, Melbourne, Australia. ; Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. ; School of Science, RMIT University, Bundoora, VIC, Australia. ; Tumour Targeting Laboratory, Ludwig Institute for Cancer Research and Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia. andrew.scott@onjcri.org.au. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 26 VL - 6 IS - 1 KW - Lewis-Y KW - Small animal imaging KW - Payload delivery KW - Antibody engineering KW - Therapeutic ratio UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1774528217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EJNMMI+research&rft.atitle=Engineering+anti-Lewis-Y+hu3S193+antibodies+with+improved+therapeutic+ratio+for+radioimmunotherapy+of+epithelial+cancers.&rft.au=Burvenich%2C+Ingrid+J+G%3BLee%2C+Fook-Thean%3BO%27Keefe%2C+Graeme+J%3BMakris%2C+Dahna%3BCao%2C+Diana%3BGong%2C+Sylvia%3BRigopoulos%2C+Angela%3BAllan%2C+Laura+C%3BBrechbiel%2C+Martin+W%3BLiu%2C+Zhanqi%3BRamsland%2C+Paul+A%3BScott%2C+Andrew+M&rft.aulast=Burvenich&rft.aufirst=Ingrid+J&rft.date=2016-12-01&rft.volume=6&rft.issue=1&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=EJNMMI+research&rft.issn=&rft_id=info:doi/10.1186%2Fs13550-016-0180-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-03-17 N1 - Date created - 2016-03-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s13550-016-0180-0 ER - TY - JOUR T1 - Prediction of pharmacokinetic and toxicological parameters of a 4-phenylcoumarin isolated from geopropolis: In silico and in vitro approaches. AN - 1835540190; 27773722 AB - In silico and in vitro methodologies have been used as important tools in the drug discovery process, including from natural sources. The aim of this study was to predict pharmacokinetic and toxicity (ADME/Tox) properties of a coumarin isolated from geopropolis using in silico and in vitro approaches. Cinnamoyloxy-mammeisin (CNM) isolated from Brazilian M. scutellaris geopropolis was evaluated for its pharmacokinetic parameters by in silico models (ACD/Percepta™ and MetaDrug™ software). Genotoxicity was assessed by in vitro DNA damage signaling PCR array. CNM did not pass all parameters of Lipinski's rule of five, with a predicted low oral bioavailability and high plasma protein binding, but with good predicted blood brain barrier penetration. CNM was predicted to show low affinity to cytochrome P450 family members. Furthermore, the predicted Ames test indicated potential mutagenicity of CNM. Also, the probability of toxicity for organs and tissues was classified as moderate and high for liver and kidney, and moderate and low for skin and eye irritation, respectively. The PCR array analysis showed that CNM significantly upregulated about 7% of all DNA damage-related genes. By exploring the biological function of these genes, it was found that the predicted CNM genotoxicity is likely to be mediated by apoptosis. The predicted ADME/Tox profile suggests that external use of CNM may be preferable to systemic exposure, while its genotoxicity was characterized by the upregulation of apoptosis-related genes after treatment. The combined use of in silico and in vitro approaches to evaluate these parameters generated useful hypotheses to guide further preclinical studies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. JF - Toxicology letters AU - da Cunha, Marcos Guilherme AU - Franco, Gilson César Nobre AU - Franchin, Marcelo AU - Beutler, John A AU - de Alencar, Severino Matias AU - Ikegaki, Masaharu AU - Rosalen, Pedro Luiz AD - Department of Physiological Sciences, Piracicaba Dental School, University of Campinas (UNICAMP), SP, Brazil; Molecular Targets Laboratory, National Cancer Institute (NCI), National Institute of Health (NIH), Frederick, MD, USA. ; Department of General Biology, Laboratory of Physiology and Pathophysiology, State University of Ponta Grossa, Ponta Grossa, PR, Brazil. ; Department of Physiological Sciences, Piracicaba Dental School, University of Campinas (UNICAMP), SP, Brazil. ; Molecular Targets Laboratory, National Cancer Institute (NCI), National Institute of Health (NIH), Frederick, MD, USA. ; Department of Agri-Food industry, Food and Nutrition, "Luiz de Queiroz" College of Agriculture, University of São Paulo (USP), Piracicaba, SP, Brazil. ; College of Pharmaceutical Sciences, Federal University of Alfenas, Minas Gerais, Brazil. ; Department of Physiological Sciences, Piracicaba Dental School, University of Campinas (UNICAMP), SP, Brazil. Electronic address: rosalen@fop.unicamp.br. Y1 - 2016/11/30/ PY - 2016 DA - 2016 Nov 30 SP - 6 EP - 10 VL - 263 KW - In silico KW - Genotoxicity KW - Coumarin KW - in vitro KW - Geopropolis KW - Pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835540190?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Prediction+of+pharmacokinetic+and+toxicological+parameters+of+a+4-phenylcoumarin+isolated+from+geopropolis%3A+In+silico+and+in+vitro+approaches.&rft.au=da+Cunha%2C+Marcos+Guilherme%3BFranco%2C+Gilson+C%C3%A9sar+Nobre%3BFranchin%2C+Marcelo%3BBeutler%2C+John+A%3Bde+Alencar%2C+Severino+Matias%3BIkegaki%2C+Masaharu%3BRosalen%2C+Pedro+Luiz&rft.aulast=da+Cunha&rft.aufirst=Marcos&rft.date=2016-11-30&rft.volume=263&rft.issue=&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=1879-3169&rft_id=info:doi/10.1016%2Fj.toxlet.2016.10.010 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.toxlet.2016.10.010 ER - TY - JOUR T1 - Ameliorative effect of an oxovanadium (IV) complex against oxidative stress and nephrotoxicity induced by cisplatin. AN - 1844603624; 27897082 AB - The present study was designed to investigate the chemoprotective efficacy of an L-cysteine-based oxovanadium (IV) complex, namely, oxovanadium (IV)-L-cysteine methyl ester complex (VC-IV) against cisplatin (CDDP)-induced renal injury in Swiss albino mice. CDDP was administered intraperitoneally (5 mg/kg body weight) and VC-IV was administered orally (1 mg/kg body weight) in concomitant and 7 days pre-treatment schedule. CDDP-treated mice showed marked kidney damage and renal failure. Administration of VC-IV caused significant attenuation of renal oxidative stress and elevation of antioxidant status. VC-IV also significantly decreased serum levels of creatinine and blood urea nitrogen, and improved histopathological lesions. Western blot analysis of the kidneys showed that VC-IV treatment resulted in nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) through modulation of cytosolic Kelch-like ECH-associated protein 1. Thus, VC-IV stimulated Nrf2-mediated activation of antioxidant response element (ARE) pathway and promoted expression of ARE-driven cytoprotective proteins, heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1, and enhanced activity of antioxidant enzymes. Interestingly, VC-IV did not alter the bioavailability and renal accumulation of CDDP in mice. In this study, VC-IV exhibited strong nephroprotective efficacy by restoring antioxidant defense mechanisms and hence may serve as a promising chemoprotectant in cancer chemotherapy. JF - Redox report : communications in free radical research AU - Basu, Abhishek AU - Bhattacharjee, Arin AU - Hajra, Subhadip AU - Samanta, Amalesh AU - Bhattacharya, Sudin AD - a Department of Cancer Chemoprevention , Chittaranjan National Cancer Institute , Kolkata , India. ; b Division of Microbiology, Department of Pharmaceutical Technology , Jadavpur University , Kolkata , India. Y1 - 2016/11/29/ PY - 2016 DA - 2016 Nov 29 SP - 1 EP - 11 KW - Vanadium KW - kidney damage KW - apoptosis KW - reactive oxygen species KW - Nrf2/ARE pathway KW - antioxidant enzymes KW - atomic absorption spectroscopy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844603624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Redox+report+%3A+communications+in+free+radical+research&rft.atitle=Ameliorative+effect+of+an+oxovanadium+%28IV%29+complex+against+oxidative+stress+and+nephrotoxicity+induced+by+cisplatin.&rft.au=Basu%2C+Abhishek%3BBhattacharjee%2C+Arin%3BHajra%2C+Subhadip%3BSamanta%2C+Amalesh%3BBhattacharya%2C+Sudin&rft.aulast=Basu&rft.aufirst=Abhishek&rft.date=2016-11-29&rft.volume=&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Redox+report+%3A+communications+in+free+radical+research&rft.issn=1743-2928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Ruxolitinib in clinical practice for primary and secondary myelofibrosis: an analysis of safety and efficacy of Gruppo Laziale of Ph-negative MPN. AN - 1844351083; 27889820 AB - Ruxolitinib, a JAK1 and JAK2 inhibitor, has been tested and approved for the treatment of primary and secondary myelofibrosis (MF). Aim of our study is to report safety and efficacy of ruxolitinib in 98 patients affected by MF treated outside clinical trials and collected and treated consecutively by the Lazio Cooperative Group for Ph negative myeloproliferative diseases.There were 45 males and 53 females; median age was 61.8 years (range 35.3-88). Forty-five patients were diagnosed as primary MF and 53 as secondary MF. Seventy-seven patients (78.5%) experienced constitutional symptoms at baseline, and out of 94 patients tested, 66 (70%) were JAK2V617F mutated. Overall, 40 patients received hydroxyurea as firstline treatment, 30 patients received other chemotherapeutic approaches, whereas 28 were treated with ruxolitinib frontline. Median time from diagnosis to start of ruxolitinib in the whole cohort was 34.6 months. Fifty-eight patients (59%) required a dose reduction during the first 3 months due to hematological toxicity in the majority of cases. At 48 weeks, 52% of patients obtained a clinical benefit: of them 7 patients (7%) had a CR, 10 (10%) a PR, 6 patients (6%) a CI, and 28 patients (28.5%) a spleen response. Overall, 66% of patients had disappearance of baseline symptoms burden. After 1 year, of 72 evaluable patients, 52% achieved and maintained a clinical benefit. Adverse events of special interest at any grade included anemia (39.7%), thrombocytopenia (25.5%), infections (16.3%, of which 10 were bronchopneumonia), fluid retention (3%), diarrhea (2%) and abdominal pain (2%). After a median follow-up of 16 months from start of ruxolitinib, median daily dose decreased to 10 mg BID and 21 patients (21%) discontinued the drug. The results of this retrospective multicentric analysis confirmed the efficacy of ruxolitinib outside clinical trials with more than half of treated patients achieving and maintaining a clinical benefit and most of them reporting relief from symptoms. JF - Annals of hematology AU - Breccia, Massimo AU - Andriani, Alessandro AU - Montanaro, Marco AU - Abruzzese, Elisabetta AU - Buccisano, Francesco AU - Cedrone, Michele AU - Centra, Antonietta AU - Villivà, Nicoletta AU - Celesti, Francesca AU - Trawinska, Malgorzata Monica AU - Massaro, Fulvio AU - Di Veroli, Ambra AU - Anaclerico, Barbara AU - Colafigli, Gioia AU - Molica, Matteo AU - Spadea, Antonio AU - Petriccione, Luca AU - Cimino, Giuseppe AU - Latagliata, Roberto AD - Department of Cellular Biotechnologies and Hematology, Sapienza University, Via Benevento 6, 00161, Rome, Italy. breccia@bce.uniroma1.it. ; Hematology, Nuovo Regina Margherita Hospital, Rome, Italy. ; Hematology, Belcolle Hospital, Viterbo, Italy. ; Hematology, S. Eugenio Hospital, Rome, Italy. ; Tor Vergata University, Rome, Italy. ; Hematology, S. Giovanni Hospital, Rome, Italy. ; Hematology, S. Maria Goretti Hospital, Latina, Italy. ; Azienda Policlinico Umberto 1-Sapienza University, Rome, Italy. ; Hematology and Stem Cell Transplantation Unit, Regina Elena National Cancer Institute, Rome, Italy. ; Hematology, Fabrizio Spaziani Hospital, Frosinone, Italy. Y1 - 2016/11/26/ PY - 2016 DA - 2016 Nov 26 KW - Ruxolitinib KW - Myelofibrosis KW - Response rate KW - Outcome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844351083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hormones+%26+cancer&rft.atitle=Estrogen+Metabolism+and+Risk+of+Postmenopausal+Endometrial+and+Ovarian+Cancer%3A+the+B+%E2%88%BC+FIT+Cohort.&rft.au=Dallal%2C+Cher+M%3BLacey%2C+James+V%3BPfeiffer%2C+Ruth+M%3BBauer%2C+Douglas+C%3BFalk%2C+Roni+T%3BBuist%2C+Diana+S+M%3BCauley%2C+Jane+A%3BHue%2C+Trisha+F%3BLaCroix%2C+Andrea+Z%3BTice%2C+Jeffrey+A%3BVeenstra%2C+Timothy+D%3BXu%2C+Xia%3BBrinton%2C+Louise+A%3BB%E2%88%BCFIT+Research+Group&rft.aulast=Dallal&rft.aufirst=Cher&rft.date=2016-02-01&rft.volume=7&rft.issue=1&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Hormones+%26+cancer&rft.issn=1868-8500&rft_id=info:doi/10.1007%2Fs12672-015-0237-y LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Regulation of Cytochrome P450 2B10 (CYP2B10) Expression in Liver by Peroxisome Proliferator-activated Receptor-β/δ Modulation of SP1 Promoter Occupancy. AN - 1835517050; 27765815 AB - Alcoholic liver disease is a pathological condition caused by overconsumption of alcohol. Because of the high morbidity and mortality associated with this disease, there remains a need to elucidate the molecular mechanisms underlying its etiology and to develop new treatments. Because peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) modulates ethanol-induced hepatic effects, the present study examined alterations in gene expression that may contribute to this disease. Chronic ethanol treatment causes increased hepatic CYP2B10 expression inPparβ/δ+/+ mice but not in Pparβ/δ-/- mice. Nuclear and cytosolic localization of the constitutive androstane receptor (CAR), a transcription factor known to regulate Cyp2b10 expression, was not different between genotypes. PPARγ co-activator 1α, a co-activator of both CAR and PPARβ/δ, was up-regulated in Pparβ/δ+/+ liver following ethanol exposure, but not in Pparβ/δ-/- liver. Functional mapping of the Cyp2b10 promoter and ChIP assays revealed that PPARβ/δ-dependent modulation of SP1 promoter occupancy up-regulated Cyp2b10 expression in response to ethanol. These results suggest that PPARβ/δ regulates Cyp2b10 expression indirectly by modulating SP1 and PPARγ co-activator 1α expression and/or activity independent of CAR activity. Ligand activation of PPARβ/δ attenuates ethanol-induced Cyp2b10 expression in Pparβ/δ+/+ liver but not in Pparβ/δ-/- liver. Strikingly, Cyp2b10 suppression by ligand activation of PPARβ/δ following ethanol treatment occurred in hepatocytes and was mediated by paracrine signaling from Kupffer cells. Combined, results from the present study demonstrate a novel regulatory role of PPARβ/δ in modulating CYP2B10 that may contribute to the etiology of alcoholic liver disease. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Koga, Takayuki AU - Yao, Pei-Li AU - Goudarzi, Maryam AU - Murray, Iain A AU - Balandaram, Gayathri AU - Gonzalez, Frank J AU - Perdew, Gary H AU - Fornace, Albert J AU - Peters, Jeffrey M AD - From the Department of Veterinary and Biomedical Sciences and the Center of Molecular Toxicology and Carcinogenesis, Pennsylvania State University, University Park, Pennsylvania 16802. ; the Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, D. C., 20057, and. ; the Laboratory of Metabolism, National Cancer Institute, Bethesda, Maryland 20892. ; From the Department of Veterinary and Biomedical Sciences and the Center of Molecular Toxicology and Carcinogenesis, Pennsylvania State University, University Park, Pennsylvania 16802, jmp21@psu.edu. Y1 - 2016/11/25/ PY - 2016 DA - 2016 Nov 25 SP - 25255 EP - 25263 VL - 291 IS - 48 KW - Kupffer cells KW - cytochrome P450 2B10 KW - peroxisome proliferator-activated receptor (PPAR) KW - liver injury KW - peroxisome proliferator-activated receptor-β/δ KW - gene regulation KW - liver KW - cytochrome P450 KW - alcoholic liver disease UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835517050?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Regulation+of+Cytochrome+P450+2B10+%28CYP2B10%29+Expression+in+Liver+by+Peroxisome+Proliferator-activated+Receptor-%CE%B2%2F%CE%B4+Modulation+of+SP1+Promoter+Occupancy.&rft.au=Koga%2C+Takayuki%3BYao%2C+Pei-Li%3BGoudarzi%2C+Maryam%3BMurray%2C+Iain+A%3BBalandaram%2C+Gayathri%3BGonzalez%2C+Frank+J%3BPerdew%2C+Gary+H%3BFornace%2C+Albert+J%3BPeters%2C+Jeffrey+M&rft.aulast=Koga&rft.aufirst=Takayuki&rft.date=2016-11-25&rft.volume=291&rft.issue=48&rft.spage=25255&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Ozone-derived Oxysterols Affect Liver X Receptor (LXR) Signaling: A POTENTIAL ROLE FOR LIPID-PROTEIN ADDUCTS. AN - 1835359842; 27703007 AB - When inhaled, ozone (O3) interacts with cholesterols of airway epithelial cell membranes or the lung-lining fluid, generating chemically reactive oxysterols. The mechanism by which O3-derived oxysterols affect molecular function is unknown. Our data show that in vitro exposure of human bronchial epithelial cells to O3 results in the formation of oxysterols, epoxycholesterol-α and -β and secosterol A and B (Seco A and Seco B), in cell lysates and apical washes. Similarly, bronchoalveolar lavage fluid obtained from human volunteers exposed to O3 contained elevated levels of these oxysterol species. As expected, O3-derived oxysterols have a pro-inflammatory effect and increase NF-κB activity. Interestingly, expression of the cholesterol efflux pump ATP-binding cassette transporter 1 (ABCA1), which is regulated by activation of the liver X receptor (LXR), was suppressed in epithelial cells exposed to O3 Additionally, exposure of LXR knock-out mice to O3 enhanced pro-inflammatory cytokine production in the lung, suggesting LXR inhibits O3-induced inflammation. Using alkynyl surrogates of O3-derived oxysterols, our data demonstrate adduction of LXR with Seco A. Similarly, supplementation of epithelial cells with alkynyl-tagged cholesterol followed by O3 exposure causes observable lipid-LXR adduct formation. Experiments using Seco A and the LXR agonist T0901317 (T09) showed reduced expression of ABCA1 as compared with stimulation with T0901317 alone, indicating that Seco A-LXR protein adduct formation inhibits LXR activation by traditional agonists. Overall, these data demonstrate that O3-derived oxysterols have pro-inflammatory functions and form lipid-protein adducts with LXR, thus leading to suppressed cholesterol regulatory gene expression and providing a biochemical mechanism mediating O3-derived formation of oxidized lipids in the airways and subsequent adverse health effects. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Speen, Adam M AU - Kim, Hye-Young H AU - Bauer, Rebecca N AU - Meyer, Megan AU - Gowdy, Kymberly M AU - Fessler, Michael B AU - Duncan, Kelly E AU - Liu, Wei AU - Porter, Ned A AU - Jaspers, Ilona AD - From the Curriculum in Toxicology, Departments of Pediatrics and Microbiology and Immunology, Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill, North Carolina 27599. ; the Department of Chemistry and Center for Molecular Toxicology, Vanderbilt University, Nashville, Tennessee 37235. ; the Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, and. ; the Immunity, Inflammation, and Disease Laboratory, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709. ; From the Curriculum in Toxicology, Departments of Pediatrics and Microbiology and Immunology, Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill, North Carolina 27599, ilona_jaspers@med.unc.edu. Y1 - 2016/11/25/ PY - 2016 DA - 2016 Nov 25 SP - 25192 EP - 25206 VL - 291 IS - 48 KW - secosterol A KW - oxysterol KW - ozone KW - lung KW - liver X receptor KW - inflammation KW - ABC transporter KW - lipid-protein interaction KW - cholesterol KW - epithelial cells UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835359842?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Ozone-derived+Oxysterols+Affect+Liver+X+Receptor+%28LXR%29+Signaling%3A+A+POTENTIAL+ROLE+FOR+LIPID-PROTEIN+ADDUCTS.&rft.au=Speen%2C+Adam+M%3BKim%2C+Hye-Young+H%3BBauer%2C+Rebecca+N%3BMeyer%2C+Megan%3BGowdy%2C+Kymberly+M%3BFessler%2C+Michael+B%3BDuncan%2C+Kelly+E%3BLiu%2C+Wei%3BPorter%2C+Ned+A%3BJaspers%2C+Ilona&rft.aulast=Speen&rft.aufirst=Adam&rft.date=2016-11-25&rft.volume=291&rft.issue=48&rft.spage=25192&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Reproductive history and risk of colorectal adenocarcinoma in parous women: a Nordic population-based case-control study. AN - 1835379465; 27701386 AB - Data are conflicting regarding the role of endogenous sex hormones in colorectal carcinogenesis. In this large population-based study, we pooled data from birth and cancer registries in four Nordic countries, to evaluate the risk of colorectal adenocarcinoma in relation to women's reproductive history. We conducted a population-based case-control study among women registered in Nordic birth registries. The study included colorectal adenocarcinoma cases diagnosed in Denmark, Finland, Norway, and Sweden during 1967-2013 and up to 10 matched controls per case, in total 22 185 cases and 220 246 controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived from conditional logistic regression models. We had limited information available on possible confounders. We found no evidence for associations between colorectal adenocarcinoma and parity, age at first and last birth, and time since first and last birth. The risk estimates were also close to unity for specific cancer subsites (proximal and distal colon and rectum). As well, when the analyses were stratified on menopausal status, parity, and mother's year of birth, no indication of associations was found. In this large, Nordic population-based study, no evidence for associations was found between women's reproductive history and colorectal adenocarcinoma in parous women. JF - British journal of cancer AU - Bjørge, Tone AU - Gissler, Mika AU - Ording, Anne Gulbech AU - Engeland, Anders AU - Glimelius, Ingrid AU - Leinonen, Maarit AU - Sørensen, Henrik Toft AU - Tretli, Steinar AU - Ekbom, Anders AU - Troisi, Rebecca AU - Grotmol, Tom AD - Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway. ; National Institute for Health and Welfare (THL), Helsinki, Finland. ; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. ; Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. ; Cancer Society of Finland, Finnish Cancer Registry, Helsinki, Finland. ; Cancer Registry of Norway, Oslo, Norway. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. Y1 - 2016/11/22/ PY - 2016 DA - 2016 Nov 22 SP - 1416 EP - 1420 VL - 115 IS - 11 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835379465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=Reproductive+history+and+risk+of+colorectal+adenocarcinoma+in+parous+women%3A+a+Nordic+population-based+case-control+study.&rft.au=Bj%C3%B8rge%2C+Tone%3BGissler%2C+Mika%3BOrding%2C+Anne+Gulbech%3BEngeland%2C+Anders%3BGlimelius%2C+Ingrid%3BLeinonen%2C+Maarit%3BS%C3%B8rensen%2C+Henrik+Toft%3BTretli%2C+Steinar%3BEkbom%2C+Anders%3BTroisi%2C+Rebecca%3BGrotmol%2C+Tom&rft.aulast=Bj%C3%B8rge&rft.aufirst=Tone&rft.date=2016-11-22&rft.volume=115&rft.issue=11&rft.spage=1416&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=1532-1827&rft_id=info:doi/10.1038%2Fbjc.2016.315 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/bjc.2016.315 ER - TY - JOUR T1 - Transcriptional Induction of Periostin by a Sulfatase 2-TGFβ1-SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma. AN - 1842599925; 27872089 AB - Existing antiangiogenic approaches to treat metastatic hepatocellular carcinoma (HCC) are weakly effectual, prompting further study of tumor angiogenesis in this disease setting. Here, we report a novel role for sulfatase 2 (SULF2) in driving HCC angiogenesis. Sulf2-deficient mice (Sulf2 KO) exhibited resistance to diethylnitrosamine-induced HCC and did not develop metastases like wild-type mice (Sulf2 WT). The smaller and less numerous tumors formed in Sulf2 KO mice exhibited a markedly lower microvascular density. In human HCC cells, SULF2 overexpression increased endothelial proliferation, adhesion, chemotaxis, and tube formation in a paracrine fashion. Mechanistic analyses identified the extracellular matrix protein periostin (POSTN), a ligand of αvβ3/5 integrins, as an effector protein in SULF2-induced angiogenesis. POSTN silencing in HCC cells attenuated SULF2-induced angiogenesis and tumor growth in vivo The TGFβ1/SMAD pathway was identified as a critical signaling axis between SULF2 and upregulation of POSTN transcription. In clinical HCC specimens, elevated levels of SULF2 correlated with increased microvascular density, POSTN levels, and relatively poorer patient survival. Together, our findings define an important axis controlling angiogenesis in HCC and a mechanistic foundation for rational drug development. Cancer Res; 77(3); 1-14. ©2016 AACR. ©2016 American Association for Cancer Research. JF - Cancer research AU - Chen, Gang AU - Nakamura, Ikuo AU - Dhanasekaran, Renumathy AU - Iguchi, Eriko AU - Tolosa, Ezequiel J AU - Romecin, Paola A AU - Vera, Renzo E AU - Almada, Luciana L AU - Miamen, Alexander G AU - Chaiteerakij, Roongruedee AU - Zhou, Mengtao AU - Asiedu, Michael K AU - Moser, Catherine D AU - Han, Shaoshan AU - Hu, Chunling AU - Banini, Bubu A AU - Oseini, Abdul M AU - Chen, Yichun AU - Fang, Yong AU - Yang, Dongye AU - Shaleh, Hassan M AU - Wang, Shaoqing AU - Wu, Dehai AU - Song, Tao AU - Lee, Ju-Seog AU - Thorgeirsson, Snorri S AU - Chevet, Eric AU - Shah, Vijay H AU - Fernandez-Zapico, Martin E AU - Roberts, Lewis R AD - Division of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. ; Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota. ; Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota. ; Department of Systems Biology, MD Anderson Cancer Center, Houston, Texas. ; Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland. ; INSERM U1242, Chemistry, Oncogenesis Stress Signaling, Université Rennes 1, and Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, France. ; Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota. roberts.lewis@mayo.edu. Y1 - 2016/11/21/ PY - 2016 DA - 2016 Nov 21 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1842599925?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Transcriptional+Induction+of+Periostin+by+a+Sulfatase+2-TGF%CE%B21-SMAD+Signaling+Axis+Mediates+Tumor+Angiogenesis+in+Hepatocellular+Carcinoma.&rft.au=Chen%2C+Gang%3BNakamura%2C+Ikuo%3BDhanasekaran%2C+Renumathy%3BIguchi%2C+Eriko%3BTolosa%2C+Ezequiel+J%3BRomecin%2C+Paola+A%3BVera%2C+Renzo+E%3BAlmada%2C+Luciana+L%3BMiamen%2C+Alexander+G%3BChaiteerakij%2C+Roongruedee%3BZhou%2C+Mengtao%3BAsiedu%2C+Michael+K%3BMoser%2C+Catherine+D%3BHan%2C+Shaoshan%3BHu%2C+Chunling%3BBanini%2C+Bubu+A%3BOseini%2C+Abdul+M%3BChen%2C+Yichun%3BFang%2C+Yong%3BYang%2C+Dongye%3BShaleh%2C+Hassan+M%3BWang%2C+Shaoqing%3BWu%2C+Dehai%3BSong%2C+Tao%3BLee%2C+Ju-Seog%3BThorgeirsson%2C+Snorri+S%3BChevet%2C+Eric%3BShah%2C+Vijay+H%3BFernandez-Zapico%2C+Martin+E%3BRoberts%2C+Lewis+R&rft.aulast=Chen&rft.aufirst=Gang&rft.date=2016-11-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=1538-7445&rft_id=info:doi/10.1158%2F0008-5472.CAN-15-2556 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-22 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1158/0008-5472.CAN-15-2556 ER - TY - JOUR T1 - Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy. AN - 1835399335; 27722328 AB - The reactive oxygen species (ROS)-mediated mechanism is the major cause underlying the efficacy of photodynamic therapy (PDT). The PDT procedure is based on the cascade of synergistic effects between light, a photosensitizer (PS) and oxygen, which greatly favors the spatiotemporal control of the treatment. This procedure has also evoked several unresolved challenges at different levels including (i) the limited penetration depth of light, which restricts traditional PDT to superficial tumours; (ii) oxygen reliance does not allow PDT treatment of hypoxic tumours; (iii) light can complicate the phototherapeutic outcomes because of the concurrent heat generation; (iv) specific delivery of PSs to sub-cellular organelles for exerting effective toxicity remains an issue; and (v) side effects from undesirable white-light activation and self-catalysation of traditional PSs. Recent advances in nanotechnology and nanomedicine have provided new opportunities to develop ROS-generating systems through photodynamic or non-photodynamic procedures while tackling the challenges of the current PDT approaches. In this review, we summarize the current status and discuss the possible opportunities for ROS generation for cancer therapy. We hope this review will spur pre-clinical research and clinical practice for ROS-mediated tumour treatments. JF - Chemical Society reviews AU - Zhou, Zijian AU - Song, Jibin AU - Nie, Liming AU - Chen, Xiaoyuan AD - Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China. nielm@xmu.edu.cn and Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA. shawn.chen@nih.gov. ; Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA. shawn.chen@nih.gov. ; Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China. nielm@xmu.edu.cn. Y1 - 2016/11/21/ PY - 2016 DA - 2016 Nov 21 SP - 6597 EP - 6626 VL - 45 IS - 23 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835399335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Society+reviews&rft.atitle=Reactive+oxygen+species+generating+systems+meeting+challenges+of+photodynamic+cancer+therapy.&rft.au=Zhou%2C+Zijian%3BSong%2C+Jibin%3BNie%2C+Liming%3BChen%2C+Xiaoyuan&rft.aulast=Zhou&rft.aufirst=Zijian&rft.date=2016-11-21&rft.volume=45&rft.issue=23&rft.spage=6597&rft.isbn=&rft.btitle=&rft.title=Chemical+Society+reviews&rft.issn=1460-4744&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Phenanthriplatin Acts As a Covalent Poison of Topoisomerase II Cleavage Complexes. AN - 1835390280; 27648475 AB - Drugs capable of trapping topoisomerase II (Top2), an essential enzyme that cleaves DNA to remove naturally occurring knots and tangles, can serve as potent anticancer agents. The monofunctional platinum agent phenanthriplatin, cis-[Pt(NH3)2(phenanthridine)Cl](NO3), is shown here to trap Top2 in addition to its known modes of inhibition of DNA and RNA polymerases. Its potency therefore combines diverse modes of action by which phenanthriplatin kills cancer cells. The observation that phenanthriplatin can act as a Top2 poison highlights opportunities to design nonclassical platinum anticancer agents with this novel mechanism of action. Such complexes have the potential to overcome current limitations with chemotherapy, such as resistance, and to provide treatment options for cancers that do not respond well to classical agents. Covalent DNA-platinum lesions implicated in Top2 poisoning are distinctive from those generated by known therapeutic topoisomerase poisons, which typically exert their action by reversible binding at the interface of Top2-DNA cleavage complexes. JF - ACS chemical biology AU - Riddell, Imogen A AU - Agama, Keli AU - Park, Ga Young AU - Pommier, Yves AU - Lippard, Stephen J AD - Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States. ; Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892, United States. Y1 - 2016/11/18/ PY - 2016 DA - 2016 Nov 18 SP - 2996 EP - 3001 VL - 11 IS - 11 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835390280?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ACS+chemical+biology&rft.atitle=Phenanthriplatin+Acts+As+a+Covalent+Poison+of+Topoisomerase+II+Cleavage+Complexes.&rft.au=Riddell%2C+Imogen+A%3BAgama%2C+Keli%3BPark%2C+Ga+Young%3BPommier%2C+Yves%3BLippard%2C+Stephen+J&rft.aulast=Riddell&rft.aufirst=Imogen&rft.date=2016-11-18&rft.volume=11&rft.issue=11&rft.spage=2996&rft.isbn=&rft.btitle=&rft.title=ACS+chemical+biology&rft.issn=1554-8937&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-20 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 ER - TY - JOUR T1 - Role of the lipid-regulated NF-κB/IL-6/STAT3 axis in alpha-naphthyl isothiocyanate-induced liver injury. AN - 1841138389; 27853831 AB - Alpha-naphthyl isothiocyanate (ANIT)-induced liver damage is regarded as a useful model to study drug-induced cholestatic hepatitis. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based metabolomics revealed clues to the mechanism of ANIT-induced liver injury, which facilitates the elucidation of drug-induced liver toxicity. 1-Stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:0) and 1-oleoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:1) were significantly increased in serum from ANIT-treated mice, and this increase resulted from altered expression of genes encoding the lipid metabolism enzymes Chka and Scd1. ANIT also increased NF-κB/IL-6/STAT3 signaling, and in vitro luciferase reporter gene assays revealed that LPC 18:0 and LPC 18:1 can activate NF-κB in a concentration-dependent manner. Activation of PPARα through feeding mice a Wy-14,643-containing diet (0.1%) reduced ANIT-induced liver injury, as indicated by lowered ALT and AST levels, and liver histology. In conclusion, the present study demonstrated a role for the lipid-regulated NF-κB/IL-6/STAT3 axis in ANIT-induced hepatotoxicity, and that PPARα may be a potential therapeutic target for the prevention of drug-induced cholestatic liver injury. JF - Archives of toxicology AU - Fang, Zhong-Ze AU - Tanaka, Naoki AU - Lu, Dan AU - Jiang, Chang-Tao AU - Zhang, Wei-Hua AU - Zhang, Chunze AU - Du, Zuo AU - Fu, Zhi-Wei AU - Gao, Peng AU - Cao, Yun-Feng AU - Sun, Hong-Zhi AU - Zhu, Zhi-Tu AU - Cai, Yan AU - Krausz, Kristopher W AU - Yao, Zhi AU - Gonzalez, Frank J AD - Department of Toxicology, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China. ; Laboratory of Metabolism, Center for Cancer Research, National Institutes of Health, Building 37, Room 3106, Bethesda, MD, 20892, USA. ; Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 30070, China. ; Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, 300121, China. ; Key Laborotary of Liaoning Tumor Clinical Metabolomics (KLLTCM), Jinzhou, Liaoning, China. ; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and The First Affiliated Hospital of Liaoning Medical University, No. 457, Zhongshan Road, Dalian, 116023, China. ; Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 30070, China. yaozhi@tijmu.edu.cn. ; Laboratory of Metabolism, Center for Cancer Research, National Institutes of Health, Building 37, Room 3106, Bethesda, MD, 20892, USA. gonzalef@mail.nih.gov. Y1 - 2016/11/16/ PY - 2016 DA - 2016 Nov 16 KW - Drug toxicity KW - NF-κB/IL-6/STAT3 axis KW - Metabolomics KW - Alpha-naphthyl isothiocyanate UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841138389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+toxicology&rft.atitle=Role+of+the+lipid-regulated+NF-%CE%BAB%2FIL-6%2FSTAT3+axis+in+alpha-naphthyl+isothiocyanate-induced+liver+injury.&rft.au=Fang%2C+Zhong-Ze%3BTanaka%2C+Naoki%3BLu%2C+Dan%3BJiang%2C+Chang-Tao%3BZhang%2C+Wei-Hua%3BZhang%2C+Chunze%3BDu%2C+Zuo%3BFu%2C+Zhi-Wei%3BGao%2C+Peng%3BCao%2C+Yun-Feng%3BSun%2C+Hong-Zhi%3BZhu%2C+Zhi-Tu%3BCai%2C+Yan%3BKrausz%2C+Kristopher+W%3BYao%2C+Zhi%3BGonzalez%2C+Frank+J&rft.aulast=Fang&rft.aufirst=Zhong-Ze&rft.date=2016-11-16&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Archives+of+toxicology&rft.issn=1432-0738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual AN - 1846422792; PQ0003881661 AB - Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408-16. copyright 2016 AACR.See related commentary by Mileham and Kim, p. 5397 JF - Clinical Cancer Research AU - Massett, Holly A AU - Mishkin, Grace AU - Rubinstein, Larry AU - Ivy, SPercy AU - Denicoff, Andrea AU - Godwin, Elizabeth AU - DiPiazza, Kate AU - Bolognese, Jennifer AU - Zwiebel, James A AU - Abrams, Jeffrey S AD - National Cancer Institute, Bethesda, Maryland, massetth@mail.nih.gov Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 5408 EP - 5416 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 22 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts KW - Toxicity KW - Clinical trials KW - Cancer KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846422792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Challenges+Facing+Early+Phase+Trials+Sponsored+by+the+National+Cancer+Institute%3A+An+Analysis+of+Corrective+Action+Plans+to+Improve+Accrual&rft.au=Massett%2C+Holly+A%3BMishkin%2C+Grace%3BRubinstein%2C+Larry%3BIvy%2C+SPercy%3BDenicoff%2C+Andrea%3BGodwin%2C+Elizabeth%3BDiPiazza%2C+Kate%3BBolognese%2C+Jennifer%3BZwiebel%2C+James+A%3BAbrams%2C+Jeffrey+S&rft.aulast=Massett&rft.aufirst=Holly&rft.date=2016-11-15&rft.volume=22&rft.issue=22&rft.spage=5408&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0338 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Toxicity; Clinical trials; Cancer DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0338 ER - TY - JOUR T1 - Circulating Tumor DNA as an Early Indicator of Response to T-cell Transfer Immunotherapy in Metastatic Melanoma AN - 1846407346; PQ0003881670 AB - Purpose: Adoptive transfer of activated autologous tumor-infiltrating lymphocytes (TIL) can mediate complete, durable regressions in patients with metastatic melanoma. Responding patients generally do not have significant changes in noncutaneous RECIST targets before 30 to 60 days following TIL infusion, and complete responses are often not confirmed for 1 to 2 years. There is a critical need for a biomarker that can provide early information regarding the likelihood and duration of a response to enable rational decisions about altering therapy. We wished to evaluate the role of circulating tumor DNA (ctDNA) in separating responding from nonresponding patients.Experimental Design: We studied BRAF V600E ctDNA levels by a sensitive allele-specific PCR assay in 388 serum samples from 48 patients who received TIL immunotherapy at the NCI and correlated differences in the dynamic patterns of their ctDNA measurements with response outcomes.Results: A strong correlation was found between the presence or absence of an early serum peak of V600E ctDNA, and the likelihood of an objective response. Furthermore, patients that developed an early ctDNA peak and cleared their serum of V600E ctDNA were highly likely to achieve a complete response over the next 1 to 2 years. Patients that showed no peak of V600E ctDNA failed to achieve an objective response, with one exception.Conclusions: We show that the dynamic changes occurring in BRAF V600E ctDNA levels within the first month following T-cell transfer immunotherapy in metastatic melanoma can be used to rapidly identify responding from nonresponding patients, potentially allowing clinicians to make critical treatment-related decisions in a more timely manner. These data also suggest that the majority of tumor killing by TIL occurs very early after the initiation of therapy. Clin Cancer Res; 22(22); 5480-6. copyright 2016 AACR. JF - Clinical Cancer Research AU - Xi, Liqiang AU - Pham, Trinh Hoc-Tran AU - Payabyab, Eden C AU - Sherry, Richard M AU - Rosenberg, Steven A AU - Raffeld, Mark AD - Molecular Diagnostics Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, mraff@mail.nih.gov Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 5480 EP - 5486 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 22 SN - 1078-0432, 1078-0432 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Data processing KW - Immunotherapy KW - Tumor-infiltrating lymphocytes KW - Tumors KW - biomarkers KW - Cancer KW - Melanoma KW - Metastases KW - Decision making KW - Lymphocytes T KW - Adoptive transfer KW - Polymerase chain reaction KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846407346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Circulating+Tumor+DNA+as+an+Early+Indicator+of+Response+to+T-cell+Transfer+Immunotherapy+in+Metastatic+Melanoma&rft.au=Xi%2C+Liqiang%3BPham%2C+Trinh+Hoc-Tran%3BPayabyab%2C+Eden+C%3BSherry%2C+Richard+M%3BRosenberg%2C+Steven+A%3BRaffeld%2C+Mark&rft.aulast=Xi&rft.aufirst=Liqiang&rft.date=2016-11-15&rft.volume=22&rft.issue=22&rft.spage=5480&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0613 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2017-02-01 N1 - SubjectsTermNotLitGenreText - Metastases; Decision making; Data processing; Immunotherapy; Adoptive transfer; Lymphocytes T; Polymerase chain reaction; Tumor-infiltrating lymphocytes; Tumors; biomarkers; Cancer; Melanoma DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0613 ER - TY - JOUR T1 - The National Disease Research Interchange and Collaborators on: What Are the Major Hurdles to the Recovery of Human Tissue to Advance Research? AN - 1839737563; 27845557 JF - Biopreservation and biobanking AU - VonDran, Melissa AU - Thomas, Jeffrey A AU - Freund, Michelle P AU - Ritsick, Maggie AU - Orr, Maureen AU - Kaye, Wendy E AU - Bakker, Annette AU - Knight, Pamela AD - 1 National Disease Research Interchange , Philadelphia, Pennsylvania. ; 2 Office of Technology Development and Coordination, NIH NeuroBioBank, National Institute of Mental Health , NIH, Bethesda, Maryland. ; 3 McKing Consulting Corporation , Atlanta, Georgia . ; 4 Agency for Toxic Substances and Disease Registry , Atlanta, Georgia . ; 5 Children's Tumor Foundation , New York, New York. Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839737563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biopreservation+and+biobanking&rft.atitle=The+National+Disease+Research+Interchange+and+Collaborators+on%3A+What+Are+the+Major+Hurdles+to+the+Recovery+of+Human+Tissue+to+Advance+Research%3F&rft.au=VonDran%2C+Melissa%3BThomas%2C+Jeffrey+A%3BFreund%2C+Michelle+P%3BRitsick%2C+Maggie%3BOrr%2C+Maureen%3BKaye%2C+Wendy+E%3BBakker%2C+Annette%3BKnight%2C+Pamela&rft.aulast=VonDran&rft.aufirst=Melissa&rft.date=2016-11-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Biopreservation+and+biobanking&rft.issn=1947-5543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Mammalian Target of Rapamycin Inhibition With Rapamycin Mitigates Radiation-Induced Pulmonary Fibrosis in a Murine Model. AN - 1835527932; 27663762 AB - Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation. Signaling of the mammalian target of rapamycin drives several processes implicated in RIPF, including inflammatory cytokine production, fibroblast proliferation, and epithelial senescence. We sought to determine if mammalian target of rapamycin inhibition with rapamycin would mitigate RIPF. C57BL/6NCr mice received a diet formulated with rapamycin (14 mg/kg food) or a control diet 2 days before and continuing for 16 weeks after exposure to 5 daily fractions of 6 Gy of thoracic irradiation. Fibrosis was assessed with Masson trichrome staining and hydroxyproline assay. Cytokine expression was evaluated by quantitative real-time polymerase chain reaction. Senescence was assessed by staining for β-galactosidase activity. Administration of rapamycin extended the median survival of irradiated mice compared with the control diet from 116 days to 156 days (P=.006, log-rank test). Treatment with rapamycin reduced hydroxyproline content compared with the control diet (irradiation plus vehicle, 45.9 ± 11.8 μg per lung; irradiation plus rapamycin, 21.4 ± 6.0 μg per lung; P=.001) and reduced visible fibrotic foci. Rapamycin treatment attenuated interleukin 1β and transforming growth factor β induction in irradiated lungs compared with the control diet. Type II pneumocyte senescence after irradiation was reduced with rapamycin treatment at 16 weeks (3-fold reduction at 16 weeks, P<.001). Rapamycin protected against RIPF in a murine model. Rapamycin treatment reduced inflammatory cytokine expression, extracellular matrix production, and senescence in type II pneumocytes. Published by Elsevier Inc. JF - International journal of radiation oncology, biology, physics AU - Chung, Eun Joo AU - Sowers, Anastasia AU - Thetford, Angela AU - McKay-Corkum, Grace AU - Chung, Su I AU - Mitchell, James B AU - Citrin, Deborah E AD - Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland. ; Radiation Biology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland. ; Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland. Electronic address: citrind@mail.nih.gov. Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 857 EP - 866 VL - 96 IS - 4 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835527932?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.atitle=Mammalian+Target+of+Rapamycin+Inhibition+With+Rapamycin+Mitigates+Radiation-Induced+Pulmonary+Fibrosis+in+a+Murine+Model.&rft.au=Chung%2C+Eun+Joo%3BSowers%2C+Anastasia%3BThetford%2C+Angela%3BMcKay-Corkum%2C+Grace%3BChung%2C+Su+I%3BMitchell%2C+James+B%3BCitrin%2C+Deborah+E&rft.aulast=Chung&rft.aufirst=Eun&rft.date=2016-11-15&rft.volume=96&rft.issue=4&rft.spage=857&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=1879-355X&rft_id=info:doi/10.1016%2Fj.ijrobp.2016.07.026 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ijrobp.2016.07.026 ER - TY - JOUR T1 - Electrophysiological characterization of Nsc-34 cell line using Microelectrode Array. AN - 1835525005; 27772743 AB - Neurons communicate with each other through intricate network to evolve higher brain functions. The electrical activity of the neurons plays a crucial role in shaping the connectivity. With motor neurons being vulnerable to neurodegenerative diseases, understanding the electrophysiological properties of motor neurons is the need of the hour, in order to comprehend the impairment of connectivity in these diseases. NSC-34 cell line serves as an excellent model to study the properties of motor neurons as they express Choline acetyltransferase (ChAT). Although NSC-34 cell lines have been used to study the effect of various toxicological, neurotrophic and neuroprotective agents, the electrical activity of these cells has not been elucidated. In the current study, we have characterized the electrophysiological properties of NSC-34 cell lines using Micro-Electrode Array (MEA) as a tool. Based on the spike waveform, firing frequency, auto- and cross-correlogram analysis, we demonstrate that NSC-34 cell culture has >2 distinct types of neuronal population: principal excitatory neurons, putative interneurons and unclassified neurons. The presence of interneurons in the NSC-34 culture was characterized by increased expression of GAD-67 markers. Thus, finding an understanding of the electrophysiological properties of different population of neurons in NSC-34 cell line, will have multiple applications in the treatment of neurological disorders. Copyright © 2016 Elsevier B.V. All rights reserved. JF - Journal of the neurological sciences AU - Sabitha, K R AU - Sanjay, D AU - Savita, B AU - Raju, T R AU - Laxmi, T R AD - Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bengaluru 560 029, India. ; Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bengaluru 560 029, India. Electronic address: laxmir@gmail.com. Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 134 EP - 139 VL - 370 KW - NSC-34 cell line KW - Motor neurons KW - Microelectrode Array KW - Electrophysiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835525005?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+neurological+sciences&rft.atitle=Electrophysiological+characterization+of+Nsc-34+cell+line+using+Microelectrode+Array.&rft.au=Sabitha%2C+K+R%3BSanjay%2C+D%3BSavita%2C+B%3BRaju%2C+T+R%3BLaxmi%2C+T+R&rft.aulast=Sabitha&rft.aufirst=K&rft.date=2016-11-15&rft.volume=370&rft.issue=&rft.spage=134&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+neurological+sciences&rft.issn=1878-5883&rft_id=info:doi/10.1016%2Fj.jns.2016.09.038 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jns.2016.09.038 ER - TY - JOUR T1 - Estimation of human percutaneous bioavailability for two novel brominated flame retardants, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP). AN - 1835418628; 27732871 AB - 2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) are novel brominated flame retardants used in consumer products. A parallelogram approach was used to predict human dermal absorption and flux for EH-TBB and BEH-TEBP. [14C]-EH-TBB or [14C]-BEH-TEBP was applied to human or rat skin at 100nmol/cm2 using a flow-through system. Intact rats received analogous dermal doses. Treated skin was washed and tape-stripped to remove "unabsorbed" [14C]-radioactivity after continuous exposure (24h). "Absorbed" was quantified using dermally retained [14C]-radioactivity; "penetrated" was calculated based on [14C]-radioactivity in media (in vitro) or excreta+tissues (in vivo). Human skin absorbed EH-TBB (24±1%) while 0.2±0.1% penetrated skin. Rat skin absorbed more (51±10%) and was more permeable (2±0.5%) to EH-TBB in vitro; maximal EH-TBB flux was 11±7 and 102±24pmol-eq/cm2/h for human and rat skin, respectively. In vivo, 27±5% was absorbed and 13% reached systemic circulation after 24h (maximum flux was 464±65pmol-eq/cm2/h). BEH-TEBP in vitro penetrance was minimal (<0.01%) for rat or human skin. BEH-TEBP absorption was 12±11% for human skin and 41±3% for rat skin. In vivo, total absorption was 27±9%; 1.2% reached systemic circulation. In vitro maximal BEH-TEBP flux was 0.3±0.2 and 1±0.3pmol-eq/cm2/h for human and rat skin; in vivo maximum flux for rat skin was 16±7pmol-eq/cm2/h. EH-TBB was metabolized in rat and human skin to tetrabromobenzoic acid. BEH-TEBP-derived [14C]-radioactivity in the perfusion media could not be characterized. <1% of the dose of EH-TBB and BEH-TEHP is estimated to reach the systemic circulation following human dermal exposure under the conditions tested. 2-Ethylhexyl 2,3,4,5-tetrabromobenzoate (PubChem CID: 71316600; CAS No. 183658-27-7 FW: 549.92g/mol logPest: 7.73-8.75 (12)) Abdallah et al., 2015a. Other published abbreviations for 2-ethylhexyl-2,3,4,5-tetrabromobenzoate are TBB EHTeBB or EHTBB Abdallah and Harrad, 2011. bis(2-ethylhexyl) tetrabromophthalate (PubChem CID: 117291; CAS No. 26040-51-7 FW: 706.14g/mol logPest: 9.48-11.95 (12)). Other published abbreviations for bis(2-ethylhexyl)tetrabromophthalate are TeBrDEPH TBPH or BEHTBP. Published by Elsevier Inc. JF - Toxicology and applied pharmacology AU - Knudsen, Gabriel A AU - Hughes, Michael F AU - Sanders, J Michael AU - Hall, Samantha M AU - Birnbaum, Linda S AD - NCI Laboratory of Toxicology and Toxicokinetics, 111 T W Alexander Dr., Research Triangle Park, NC, USA. Electronic address: gabriel.knudsen@nih.gov. ; Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. ; NCI Laboratory of Toxicology and Toxicokinetics, 111 T W Alexander Dr., Research Triangle Park, NC, USA. Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 117 EP - 127 VL - 311 KW - Bis(2-ethylhexyl) tetrabromophthalate KW - 2-Ethylhexyl 2–3,4,5-tetrabromobenzoate KW - Dermal bioavailability KW - Parallelogram method KW - Brominated flame retardant KW - Persistent organic pollutant UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835418628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Estimation+of+human+percutaneous+bioavailability+for+two+novel+brominated+flame+retardants%2C+2-ethylhexyl+2%2C3%2C4%2C5-tetrabromobenzoate+%28EH-TBB%29+and+bis%282-ethylhexyl%29+tetrabromophthalate+%28BEH-TEBP%29.&rft.au=Knudsen%2C+Gabriel+A%3BHughes%2C+Michael+F%3BSanders%2C+J+Michael%3BHall%2C+Samantha+M%3BBirnbaum%2C+Linda+S&rft.aulast=Knudsen&rft.aufirst=Gabriel&rft.date=2016-11-15&rft.volume=311&rft.issue=&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=1096-0333&rft_id=info:doi/10.1016%2Fj.taap.2016.10.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.taap.2016.10.005 ER - TY - JOUR T1 - Genetic variants in PTPRD and risk of gestational diabetes mellitus. AN - 1835418111; 27738328 AB - Genome-wide association studies (GWASs) showed that two single nucleotide polymorphisms (SNPs) (rs17584499 and rs649891) in the protein tyrosine phosphatase receptor type D (PTPRD) were associated with type 2 diabetes (T2D). We sought to determine the influence of the PTPRD variants on the gestational diabetes mellitus (GDM) risk. In this research, two SNPs in PTPRD reported in T2D GWASs and six PTPRD expression-related SNPs were genotyped in 964 GDM cases and 1,021 controls using the Sequenom platform. Logistic regression analyses in additive models showed consistently significant associations of PTPRD rs10511544 A>C, rs10756026 T>A and rs10809070 C>G with a decreased risk of GDM [adjusted OR (95% CI) = 0.83 (0.72-0.97) for rs10511544; adjusted OR (95% CI) = 0.81 (0.70-0.94) for rs10756026; adjusted OR (95% CI) = 0.78 (0.65-0.92) for rs10809070]. Furthermore, the risk of GDM was significantly decreased with an increasing number of variant alleles of the three SNPs in a dose-dependent manner (Ptrend = 0.008). Moreover, the haplotype containing variant alleles of the three SNPs were significantly associated with a decreased risk of GDM [adjusted OR (95% CI) = 0.77 (0.64-0.92), P = 0.005], when compared with the most frequent haplotype. However, there were no significant associations for the SNPs reported in the T2D GWASs. Altogether, these findings indicate that the variants of rs10511544, rs10756026 and rs10809070 in PTPRD may contribute to a decreased susceptibility to GDM. Further validation in different ethnic backgrounds and biological function analyses are needed. JF - Oncotarget AU - Chen, Ting AU - Xu, Juan AU - Liu, Guangquan AU - Liu, Heng AU - Chen, Minjian AU - Qin, Yufeng AU - Wu, Wei AU - Xia, Yankai AU - Ji, Chenbo AU - Guo, Xirong AU - Wen, Juan AU - Wang, Xinru AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China. ; Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China. ; Epigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 76101 EP - 76107 VL - 7 IS - 46 KW - PTPRD KW - polymorphism KW - susceptibility KW - gestational diabetes mellitus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835418111?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncotarget&rft.atitle=Genetic+variants+in+PTPRD+and+risk+of+gestational+diabetes+mellitus.&rft.au=Chen%2C+Ting%3BXu%2C+Juan%3BLiu%2C+Guangquan%3BLiu%2C+Heng%3BChen%2C+Minjian%3BQin%2C+Yufeng%3BWu%2C+Wei%3BXia%2C+Yankai%3BJi%2C+Chenbo%3BGuo%2C+Xirong%3BWen%2C+Juan%3BWang%2C+Xinru&rft.aulast=Chen&rft.aufirst=Ting&rft.date=2016-11-15&rft.volume=7&rft.issue=46&rft.spage=76101&rft.isbn=&rft.btitle=&rft.title=Oncotarget&rft.issn=1949-2553&rft_id=info:doi/10.18632%2Foncotarget.12599 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.18632/oncotarget.12599 ER - TY - JOUR T1 - The prognostic value of DNA damage level in peripheral blood lymphocytes of chemotherapy-naïve patients with germ cell cancer. AN - 1835409757; 27732956 AB - Germ cell tumors (GCTs) are extraordinarily sensitive to cisplatin (CDDP)-based chemotherapy. DNA damage represents one of the most important factors contributing to toxic effects of CDDP-based chemotherapy. This study was aimed to evaluate the prognostic value of DNA damage level in peripheral blood lymphocytes (PBLs) from chemo-naïve GCT patients. PBLs isolated from 59 chemotherapy-naïve GCT patients were included into this prospective study. DNA damage levels in PBLs were evaluated by the Comet assay and scored as percentage tail DNA by the Metafer-MetaCyte analyzing software. The mean ± SEM (standard error of the mean) of endogenous DNA damage level was 5.25 ± 0.64. Patients with DNA damage levels lower than mean had significantly better progression free survival (hazard ratio [HR] = 0.19, 95% CI (0.04 - 0.96), P = 0.01) and overall survival (HR = 0.00, 95% CI (0.00 - 0.0), P < 0.001) compared to patients with DNA damage levels higher than mean. Moreover, there was significant correlation between the DNA damage level and presence of mediastinal lymph nodes metastases, IGCCCG (International Germ Cell Cancer Collaborative Group) risk group, and serum tumor markers level. These data suggest that DNA damage levels in PBLs of GCT patients may serve as an important prognostic marker early identifying patients with poor outcome. JF - Oncotarget AU - Sestakova, Zuzana AU - Kalavska, Katarina AU - Hurbanova, Lenka AU - Jurkovicova, Dana AU - Gursky, Jan AU - Chovanec, Michal AU - Svetlovska, Daniela AU - Miskovska, Vera AU - Obertova, Jana AU - Palacka, Patrik AU - Rejlekova, Katarina AU - Sycova-Mila, Zuzana AU - Cingelova, Silvia AU - Spanik, Stanislav AU - Mardiak, Jozef AU - Chovanec, Miroslav AU - Mego, Michal AD - Department of Genetics Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia. ; nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia. ; Translational Research Unit, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia. ; st Department of Oncology, Faculty of Medicine, Comenius University and St. Elisabeth Cancer Institute, Bratislava, Slovakia. ; Department of Oncology, National Cancer Institute, Bratislava, Slovakia. Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 75996 EP - 76005 VL - 7 IS - 46 KW - prognostic marker KW - DNA damage KW - germ cell tumors KW - cisplatin KW - DNA repair UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835409757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncotarget&rft.atitle=The+prognostic+value+of+DNA+damage+level+in+peripheral+blood+lymphocytes+of+chemotherapy-na%C3%AFve+patients+with+germ+cell+cancer.&rft.au=Sestakova%2C+Zuzana%3BKalavska%2C+Katarina%3BHurbanova%2C+Lenka%3BJurkovicova%2C+Dana%3BGursky%2C+Jan%3BChovanec%2C+Michal%3BSvetlovska%2C+Daniela%3BMiskovska%2C+Vera%3BObertova%2C+Jana%3BPalacka%2C+Patrik%3BRejlekova%2C+Katarina%3BSycova-Mila%2C+Zuzana%3BCingelova%2C+Silvia%3BSpanik%2C+Stanislav%3BMardiak%2C+Jozef%3BChovanec%2C+Miroslav%3BMego%2C+Michal&rft.aulast=Sestakova&rft.aufirst=Zuzana&rft.date=2016-11-15&rft.volume=7&rft.issue=46&rft.spage=75996&rft.isbn=&rft.btitle=&rft.title=Oncotarget&rft.issn=1949-2553&rft_id=info:doi/10.18632%2Foncotarget.12515 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.18632/oncotarget.12515 ER - TY - JOUR T1 - Altered glutamate release in the dorsal striatum of the MitoPark mouse model of Parkinson's disease. AN - 1834995342; 27659966 AB - Mitochondrial dysfunction has been implicated in the degeneration of dopamine (DA) neurons in Parkinson's disease (PD). In addition, animal models of PD utilizing neurotoxins, such as 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, have shown that these toxins disrupt mitochondrial respiration by targeting complex I of the electron transport chain, thereby impairing DA neurons in these models. A MitoPark mouse model was created to mimic the mitochondrial dysfunction observed in the DA system of PD patients. These mice display the same phenotypic characteristics as PD, including accelerated decline in motor function and DAergic systems with age. Previously, these mice have responded to L-Dopa treatment and develop L-Dopa induced dyskinesia (LID) as they age. A potential mechanism involved in the formation of LID is greater glutamate release into the dorsal striatum as a result of altered basal ganglia neurocircuitry due to reduced nigrostriatal DA neurotransmission. Therefore, the focus of this study was to assess various indicators of glutamate neurotransmission in the dorsal striatum of MitoPark mice at an age in which nigrostriatal DA has degenerated. At 28 weeks of age, MitoPark mice had, upon KCl stimulation, greater glutamate release in the dorsal striatum compared to control mice. In addition, uptake kinetics were slower in MitoPark mice. These findings were coupled with reduced expression of the glutamate re-uptake transporter, GLT-1, thus providing an environment suitable for glutamate excitotoxic events, leading to altered physiological function in these mice. Copyright © 2016 Elsevier B.V. All rights reserved. JF - Brain research AU - Farrand, Ariana Q AU - Gregory, Rebecca A AU - Bäckman, Cristina M AU - Helke, Kristi L AU - Boger, Heather A AD - Department of Neuroscience and Center on Aging, Medical University of South Carolina, 173 Ashley Ave, BSB 403, MSC 510, Charleston, SC 29425, USA. ; Department of Neuroscience and Center on Aging, Medical University of South Carolina, 173 Ashley Ave, BSB 403, MSC 510, Charleston, SC 29425, USA; Department of Comparative Medicine, Medical University of South Carolina, 114 Doughty St, STB 648, MSC 777, Charleston, SC 29425, USA. ; Integrative Neuroscience Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, 251 Bayview Blvd, Baltimore, MD 21224, USA. ; Department of Comparative Medicine, Medical University of South Carolina, 114 Doughty St, STB 648, MSC 777, Charleston, SC 29425, USA. ; Department of Neuroscience and Center on Aging, Medical University of South Carolina, 173 Ashley Ave, BSB 403, MSC 510, Charleston, SC 29425, USA. Electronic address: boger@musc.edu. Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 88 EP - 94 VL - 1651 KW - In vivo electrochemistry KW - MitoPark KW - Dopamine KW - Glutamate KW - Striatum KW - Neurodegeneration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1834995342?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Altered+glutamate+release+in+the+dorsal+striatum+of+the+MitoPark+mouse+model+of+Parkinson%27s+disease.&rft.au=Farrand%2C+Ariana+Q%3BGregory%2C+Rebecca+A%3BB%C3%A4ckman%2C+Cristina+M%3BHelke%2C+Kristi+L%3BBoger%2C+Heather+A&rft.aulast=Farrand&rft.aufirst=Ariana&rft.date=2016-11-15&rft.volume=1651&rft.issue=&rft.spage=88&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=1872-6240&rft_id=info:doi/10.1016%2Fj.brainres.2016.09.025 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.brainres.2016.09.025 ER - TY - JOUR T1 - Potentiating NK cell activity by combination of Rosuvastatin and Difluoromethylornithine for effective chemopreventive efficacy against Colon Cancer. AN - 1839106785; 27841323 AB - Colorectal cancer (CRC) is the second highest cause of cancer-related deaths. A successful strategy to improve chemopreventive efficacies is by down-regulating tumor polyamines and enhancing NK cell activities. Colonic carcinogenesis was induced by azoxymethane (AOM) in male F344 rats. Eight weeks after AOM treatment, animals were fed diets containing Rosuvastatin and difluromethylornithine (DFMO) individually and in combination for 40 weeks. Both agents showed significant suppression of adenocarcinoma multiplicity and incidence with no toxicity compared to untreated rats. Low-dose Rosuvastatin plus DFMO suppressed colon adenocarcinoma multiplicity by 76% compared to low-dose Rosuvastatin (29%) and DFMO (46%), suggesting additive efficacy. Furthermore, low-dose combination caused a delay in colonic adenocarcinoma progression. DFMO, Rosuvastatin and/or combinations significantly decreased polyamine content and increased intra-tumoral NK cells expressing perforin plus IFN-γ compared to untreated colon tumors. Further ex-vivo analysis of splenic NK cells exposed to DFMO, Rosuvastatin or combination resulted in an increase of NKs with perforin expression. This is the first report on Rosuvastatin alone or combination strategy using clinically relevant statin plus DFMO doses which shows a significant suppression of colon adenocarcinomas, and their potential in increasing functional NK cells. This strategy has potential for further testing in high risk individuals for colon cancer. JF - Scientific reports AU - Janakiram, Naveena B AU - Mohammed, Altaf AU - Bryant, Taylor AU - Zhang, Yuting AU - Brewer, Misty AU - Duff, Ashley AU - Biddick, Laura AU - Singh, Anil AU - Lightfoot, Stan AU - Steele, Vernon E AU - Rao, Chinthalapally V AD - Center for Cancer Prevention and Drug Development, Department of Medicine, Hematology Oncology Section, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. ; Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2016/11/14/ PY - 2016 DA - 2016 Nov 14 SP - 37046 VL - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839106785?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Potentiating+NK+cell+activity+by+combination+of+Rosuvastatin+and+Difluoromethylornithine+for+effective+chemopreventive+efficacy+against+Colon+Cancer.&rft.au=Janakiram%2C+Naveena+B%3BMohammed%2C+Altaf%3BBryant%2C+Taylor%3BZhang%2C+Yuting%3BBrewer%2C+Misty%3BDuff%2C+Ashley%3BBiddick%2C+Laura%3BSingh%2C+Anil%3BLightfoot%2C+Stan%3BSteele%2C+Vernon+E%3BRao%2C+Chinthalapally+V&rft.aulast=Janakiram&rft.aufirst=Naveena&rft.date=2016-11-14&rft.volume=6&rft.issue=&rft.spage=37046&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep37046 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep37046 ER - TY - JOUR T1 - Impact of Ribonucleotide Backbone on Translesion Synthesis and Repair of 7,8-Dihydro-8-oxoguanine. AN - 1839131535; 27660390 AB - Numerous ribonucleotides are incorporated into the genome during DNA replication. Oxidized ribonucleotides can also be erroneously incorporated into DNA. Embedded ribonucleotides destabilize the structure of DNA and retard DNA synthesis by DNA polymerases (pols), leading to genomic instability. Mammalian cells possess translesion DNA synthesis (TLS) pols that bypass DNA damage. The mechanism of TLS and repair of oxidized ribonucleotides remains to be elucidated. To address this, we analyzed the miscoding properties of the ribonucleotides riboguanosine (rG) and 7,8-dihydro-8-oxo-riboguanosine (8-oxo-rG) during TLS catalyzed by the human TLS pols κ and η in vitro The primer extension reaction catalyzed by human replicative pol α was strongly blocked by 8-oxo-rG. pol κ inefficiently bypassed rG and 8-oxo-rG compared with dG and 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG), whereas pol η easily bypassed the ribonucleotides. pol α exclusively inserted dAMP opposite 8-oxo-rG. Interestingly, pol κ preferentially inserted dCMP opposite 8-oxo-rG, whereas the insertion of dAMP was favored opposite 8-oxo-dG. In addition, pol η accurately bypassed 8-oxo-rG. Furthermore, we examined the activity of the base excision repair (BER) enzymes 8-oxoguanine DNA glycosylase (OGG1) and apurinic/apyrimidinic endonuclease 1 on the substrates, including rG and 8-oxo-rG. Both BER enzymes were completely inactive against 8-oxo-rG in DNA. However, OGG1 suppressed 8-oxo-rG excision by RNase H2, which is involved in the removal of ribonucleotides from DNA. These results suggest that the different sugar backbones between 8-oxo-rG and 8-oxo-dG alter the capacity of TLS and repair of 8-oxoguanine. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Sassa, Akira AU - Çağlayan, Melike AU - Rodriguez, Yesenia AU - Beard, William A AU - Wilson, Samuel H AU - Nohmi, Takehiko AU - Honma, Masamitsu AU - Yasui, Manabu AD - From the Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan and a-sassa@nihs.go.jp. ; the Genome Integrity and Structural Biology Laboratory, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. ; From the Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan and. ; From the Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan and m-yasui@nihs.go.jp. Y1 - 2016/11/11/ PY - 2016 DA - 2016 Nov 11 SP - 24314 EP - 24323 VL - 291 IS - 46 KW - DNA damage KW - base excision repair (BER) KW - 8-oxoguanine (8-oxoG) KW - translesion DNA synthesis KW - DNA polymerase KW - ribonucleotide KW - oxidative stress UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839131535?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Impact+of+Ribonucleotide+Backbone+on+Translesion+Synthesis+and+Repair+of+7%2C8-Dihydro-8-oxoguanine.&rft.au=Sassa%2C+Akira%3B%C3%87a%C4%9Flayan%2C+Melike%3BRodriguez%2C+Yesenia%3BBeard%2C+William+A%3BWilson%2C+Samuel+H%3BNohmi%2C+Takehiko%3BHonma%2C+Masamitsu%3BYasui%2C+Manabu&rft.aulast=Sassa&rft.aufirst=Akira&rft.date=2016-11-11&rft.volume=291&rft.issue=46&rft.spage=24314&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Selenoprotein Gene Nomenclature. AN - 1835507096; 27645994 AB - The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4, and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine sulfoxide reductase B1), and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15-kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV), and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing, and ambiguous designations for selenoprotein genes and is applicable to selenoproteins across vertebrates. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Gladyshev, Vadim N AU - Arnér, Elias S AU - Berry, Marla J AU - Brigelius-Flohé, Regina AU - Bruford, Elspeth A AU - Burk, Raymond F AU - Carlson, Bradley A AU - Castellano, Sergi AU - Chavatte, Laurent AU - Conrad, Marcus AU - Copeland, Paul R AU - Diamond, Alan M AU - Driscoll, Donna M AU - Ferreiro, Ana AU - Flohé, Leopold AU - Green, Fiona R AU - Guigó, Roderic AU - Handy, Diane E AU - Hatfield, Dolph L AU - Hesketh, John AU - Hoffmann, Peter R AU - Holmgren, Arne AU - Hondal, Robert J AU - Howard, Michael T AU - Huang, Kaixun AU - Kim, Hwa-Young AU - Kim, Ick Young AU - Köhrle, Josef AU - Krol, Alain AU - Kryukov, Gregory V AU - Lee, Byeong Jae AU - Lee, Byung Cheon AU - Lei, Xin Gen AU - Liu, Qiong AU - Lescure, Alain AU - Lobanov, Alexei V AU - Loscalzo, Joseph AU - Maiorino, Matilde AU - Mariotti, Marco AU - Sandeep Prabhu, K AU - Rayman, Margaret P AU - Rozovsky, Sharon AU - Salinas, Gustavo AU - Schmidt, Edward E AU - Schomburg, Lutz AU - Schweizer, Ulrich AU - Simonović, Miljan AU - Sunde, Roger A AU - Tsuji, Petra A AU - Tweedie, Susan AU - Ursini, Fulvio AU - Whanger, Philip D AU - Zhang, Yan AD - From the Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, vgladyshev@rics.bwh.harvard.edu. ; the Department of Medical Biochemistry and Biophysics (MBB), Division of Biochemistry, Karolinska Institutet, SE-171 77, Stockholm, Sweden. ; the Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813. ; the German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany. ; the HUGO Gene Nomenclature Committee (HGNC), European Bioinformatics Institute-European Molecular Biology Laboratory (EMBL-EBI), Hinxton CB10 1SD, United Kingdom. ; the Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee 37232. ; the Molecular Biology of Selenium Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland 20892. ; the Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany. ; the Centre International de Recherche en Infectiologie, CIRI, INSERM U1111, and CNRS/ENS UMR5308, 69007 Lyon, France. ; the Helmholtz Zentrum München, Institute of Developmental Genetics, 85764 Neuherberg, Germany. ; the Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854. ; the Department of Pathology, University of Illinois at Chicago, Chicago, Illinois 60607. ; the Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195. ; the Pathophysiology of Striated Muscles Laboratory, Unit of Functional and Adaptive Biology (BFA), University Paris Diderot, Sorbonne Paris Cité, BFA, UMR CNRS 8251, 75250 Paris, France. ; the Universidad de la República, Facultad de Medicina, Departamento de Bioquímica, 11800 Montevideo, Uruguay. ; the Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom. ; the Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain. ; the Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115. ; the Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom. ; the Department of Biochemistry, University of Vermont, Burlington, Vermont 05405. ; the Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112. ; the Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, Peoples Republic of China. ; the Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu 42415, South Korea. ; the College of Life Sciences and Biotechnology, Korea University, Seoul 02841, South Korea. ; the Institute for Experimental Endocrinology, Charité-Universitaetsmedizin Berlin, D-13353 Berlin, Germany. ; the Architecture et Réactivité de l'ARN, Université de Strasbourg, Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 67084 Strasbourg, France. ; the KSQ Therapeutics, Cambridge, Massachusetts 02139. ; the School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea. ; the Department of Animal Science, Cornell University, Ithaca, New York 14853. ; the Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Science, Shenzhen University, Shenzhen, 518060, Guangdong Province, Peoples Republic of China. ; From the Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115. ; the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115. ; the Department of Molecular Medicine, University of Padova, I-35121 Padova, Italy. ; the Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802. ; the Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom. ; the Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716. ; the Cátedra de Inmunología, Facultad de Química, Instituto de Higiene, CP11600 Montevideo, Uruguay. ; the Department of Microbiology and Immunology, Montana State University, Bozeman, Montana 59717. ; the Rheinische Friedrich-Wilhelms Universität Bonn, Institut für Biochemie und Molekularbiologie, 53115 Bonn, Germany. ; the Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607. ; the Department of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin 53706. ; the Department of Biological Sciences, Towson University, Towson, Maryland 21252, and. ; the Department of Environmental and Molecular Toxicology, College of Agricultural Sciences, Oregon State University, Corvallis, Oregon 97331. Y1 - 2016/11/11/ PY - 2016 DA - 2016 Nov 11 SP - 24036 EP - 24040 VL - 291 IS - 46 KW - nomenclature KW - selenoprotein KW - gene name KW - selenium KW - selenocysteine KW - structure-function KW - genomics KW - function UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835507096?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Selenoprotein+Gene+Nomenclature.&rft.au=Gladyshev%2C+Vadim+N%3BArn%C3%A9r%2C+Elias+S%3BBerry%2C+Marla+J%3BBrigelius-Floh%C3%A9%2C+Regina%3BBruford%2C+Elspeth+A%3BBurk%2C+Raymond+F%3BCarlson%2C+Bradley+A%3BCastellano%2C+Sergi%3BChavatte%2C+Laurent%3BConrad%2C+Marcus%3BCopeland%2C+Paul+R%3BDiamond%2C+Alan+M%3BDriscoll%2C+Donna+M%3BFerreiro%2C+Ana%3BFloh%C3%A9%2C+Leopold%3BGreen%2C+Fiona+R%3BGuig%C3%B3%2C+Roderic%3BHandy%2C+Diane+E%3BHatfield%2C+Dolph+L%3BHesketh%2C+John%3BHoffmann%2C+Peter+R%3BHolmgren%2C+Arne%3BHondal%2C+Robert+J%3BHoward%2C+Michael+T%3BHuang%2C+Kaixun%3BKim%2C+Hwa-Young%3BKim%2C+Ick+Young%3BK%C3%B6hrle%2C+Josef%3BKrol%2C+Alain%3BKryukov%2C+Gregory+V%3BLee%2C+Byeong+Jae%3BLee%2C+Byung+Cheon%3BLei%2C+Xin+Gen%3BLiu%2C+Qiong%3BLescure%2C+Alain%3BLobanov%2C+Alexei+V%3BLoscalzo%2C+Joseph%3BMaiorino%2C+Matilde%3BMariotti%2C+Marco%3BSandeep+Prabhu%2C+K%3BRayman%2C+Margaret+P%3BRozovsky%2C+Sharon%3BSalinas%2C+Gustavo%3BSchmidt%2C+Edward+E%3BSchomburg%2C+Lutz%3BSchweizer%2C+Ulrich%3BSimonovi%C4%87%2C+Miljan%3BSunde%2C+Roger+A%3BTsuji%2C+Petra+A%3BTweedie%2C+Susan%3BUrsini%2C+Fulvio%3BWhanger%2C+Philip+D%3BZhang%2C+Yan&rft.aulast=Gladyshev&rft.aufirst=Vadim&rft.date=2016-11-11&rft.volume=291&rft.issue=46&rft.spage=24036&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Identification of vascular disruptor compounds by analysis in zebrafish embryos and mouse embryonic endothelial cells. AN - 1839115643; 27838387 AB - To identify vascular disruptor compounds (VDCs), this study utilized an in vivo zebrafish embryo vascular model in conjunction with a mouse endothelial cell model to screen a subset of the U.S. Environmental Protection Agency (EPA) ToxCast Phase I chemical inventory. In zebrafish, 161 compounds were screened and 34 were identified by visual inspection as VDCs, of which 28 were confirmed as VDCs by quantitative image analysis. Testing of the zebrafish VDCs for their capacity to inhibit endothelial tube formation in the murine yolk-sac-derived endothelial cell line C166 identified 22 compounds that both disrupted zebrafish vascular development and murine endothelial in vitro tubulogenesis. Putative molecular targets for the VDCs were predicted using EPA's Toxicological Prioritization Index tool and a VDC signature based on a proposed adverse outcome pathway for developmental vascular toxicity. In conclusion, our screening approach identified 22 novel VDCs, some of which were active at nanomolar concentrations. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Reproductive toxicology (Elmsford, N.Y.) AU - McCollum, Catherine W AU - Conde-Vancells, Javier AU - Hans, Charu AU - Vazquez-Chantada, Mercedes AU - Kleinstreuer, Nicole AU - Tal, Tamara AU - Knudsen, Thomas AU - Shah, Shishir S AU - Merchant, Fatima A AU - Finnell, Richard H AU - Gustafsson, Jan-Åke AU - Cabrera, Robert AU - Bondesson, Maria AD - Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204, USA. ; Department of Nutritional Sciences, Dell Pediatric Research Institute, The University of Texas at Austin, Austin, TX 78723, USA. ; Department of Computer Science, University of Houston, Houston, TX 77204, USA. ; NIEHS/DNTP/NICEATM, RTP, NC 27560, USA. ; U.S. EPA/ORD/ISTD, RTP, NC 27711, USA. ; U.S. EPA/ORD/NCCT RTP, NC 27711, USA. ; Department of Computer Science, University of Houston, Houston, TX 77204, USA; Department of Engineering Technology, University of Houston, Houston, TX 77204, USA. ; Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204, USA; Department of Biosciences and Nutrition, Novum, Karolinska Institutet, 141 83 Stockholm, Sweden. ; Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204, USA; Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX 77204, USA. Electronic address: mbondessonbolin@uh.edu. Y1 - 2016/11/10/ PY - 2016 DA - 2016 Nov 10 KW - Mouse endothelial cells KW - Vascular disruptor compounds KW - Angiogenesis KW - Zebrafish KW - Vascular development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839115643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.atitle=Identification+of+vascular+disruptor+compounds+by+analysis+in+zebrafish+embryos+and+mouse+embryonic+endothelial+cells.&rft.au=McCollum%2C+Catherine+W%3BConde-Vancells%2C+Javier%3BHans%2C+Charu%3BVazquez-Chantada%2C+Mercedes%3BKleinstreuer%2C+Nicole%3BTal%2C+Tamara%3BKnudsen%2C+Thomas%3BShah%2C+Shishir+S%3BMerchant%2C+Fatima+A%3BFinnell%2C+Richard+H%3BGustafsson%2C+Jan-%C3%85ke%3BCabrera%2C+Robert%3BBondesson%2C+Maria&rft.aulast=McCollum&rft.aufirst=Catherine&rft.date=2016-11-10&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=1873-1708&rft_id=info:doi/10.1016%2Fj.reprotox.2016.11.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-13 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.reprotox.2016.11.005 ER - TY - JOUR T1 - Rapid antimicrobial susceptibility test for identification of new therapeutics and drug combinations against multidrug-resistant bacteria. AN - 1839107904; 27826141 AB - Current antimicrobial susceptibility testing has limited screening capability for identifying empirical antibiotic combinations to treat severe bacterial infections with multidrug-resistant (MDR) organisms. We developed a new antimicrobial susceptibility assay using automated ultra-high-throughput screen technology in combination with a simple bacterial growth assay. A rapid screening of 5170 approved drugs and other compounds identified 25 compounds with activities against MDR Klebsiella pneumoniae. To further improve the efficacy and reduce the effective drug concentrations, we applied a targeted drug combination approach that integrates drugs' clinical antimicrobial susceptibility breakpoints, achievable plasma concentrations, clinical toxicities and mechanisms of action to identify optimal drug combinations. Three sets of three-drug combinations were identified with broad-spectrum activities against 10 MDR clinical isolates including K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae and Escherichia coli. Colistin-auranofin-ceftazidime and colistin-auranofin-rifabutin suppressed >80% growth of all 10 MDR strains; while rifabutin-colistin-imipenem inhibited >75% of these strains except two Acinetobacter baumannii isolates. The results demonstrate this new assay has potential as a real-time method to identify new drugs and effective drug combinations to combat severe clinical infections with MDR organisms. JF - Emerging microbes & infections AU - Sun, Wei AU - Weingarten, Rebecca A AU - Xu, Miao AU - Southall, Noel AU - Dai, Sheng AU - Shinn, Paul AU - Sanderson, Philip E AU - Williamson, Peter R AU - Frank, Karen M AU - Zheng, Wei AD - National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA. ; Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, MD 20892, USA. ; Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2016/11/09/ PY - 2016 DA - 2016 Nov 09 SP - 1 VL - 5 IS - 11 KW - Anti-Bacterial Agents KW - 0 KW - Antirheumatic Agents KW - Drug Combinations KW - Auranofin KW - 3H04W2810V KW - Colistin KW - Z67X93HJG1 KW - Index Medicus KW - Pseudomonas aeruginosa -- growth & development KW - Acinetobacter Infections -- microbiology KW - Bacterial Infections -- microbiology KW - Humans KW - Klebsiella pneumoniae -- isolation & purification KW - Acinetobacter baumannii -- growth & development KW - Acinetobacter baumannii -- drug effects KW - Klebsiella pneumoniae -- growth & development KW - Pseudomonas aeruginosa -- isolation & purification KW - Klebsiella pneumoniae -- drug effects KW - Pseudomonas aeruginosa -- drug effects KW - Drug Synergism KW - Acinetobacter baumannii -- isolation & purification KW - Auranofin -- pharmacology KW - Colistin -- pharmacology KW - Anti-Bacterial Agents -- pharmacology KW - Antirheumatic Agents -- pharmacology KW - Drug Resistance, Multiple, Bacterial KW - Microbial Sensitivity Tests KW - Drug Discovery -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839107904?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Emerging+microbes+%26+infections&rft.atitle=Rapid+antimicrobial+susceptibility+test+for+identification+of+new+therapeutics+and+drug+combinations+against+multidrug-resistant+bacteria.&rft.au=Sun%2C+Wei%3BWeingarten%2C+Rebecca+A%3BXu%2C+Miao%3BSouthall%2C+Noel%3BDai%2C+Sheng%3BShinn%2C+Paul%3BSanderson%2C+Philip+E%3BWilliamson%2C+Peter+R%3BFrank%2C+Karen+M%3BZheng%2C+Wei&rft.aulast=Sun&rft.aufirst=Wei&rft.date=2016-11-09&rft.volume=5&rft.issue=11&rft.spage=e116&rft.isbn=&rft.btitle=&rft.title=Emerging+microbes+%26+infections&rft.issn=2222-1751&rft_id=info:doi/10.1038%2Femi.2016.123 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-31 N1 - Date created - 2016-11-09 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1038/emi.2016.123 ER - TY - JOUR T1 - l-tetrahydropalmatine reduces nicotine self-administration and reinstatement in rats. AN - 1837031128; 27817750 AB - The negative consequences of nicotine use are well known and documented, however, abstaining from nicotine use and achieving abstinence poses a major challenge for the majority of nicotine users trying to quit. l-Tetrahydropalmatine (l-THP), a compound extracted from the Chinese herb Corydalis, displayed utility in the treatment of cocaine and heroin addiction via reduction of drug-intake and relapse. The present study examined the effects of l-THP on abuse-related effects of nicotine. Self-administration and reinstatement testing was conducted. Rats trained to self-administer nicotine (0.03 mg/kg/injection) under a fixed-ratio 5 schedule (FR5) of reinforcement were pretreated with l-THP (3 or 5 mg/kg), varenicline (1 mg/kg), bupropion (40 mg/kg), or saline before daily 2-h sessions. Locomotor, food, and microdialysis assays were also conducted in separate rats. l-THP significantly reduced nicotine self-administration (SA). l-THP's effect was more pronounced than the effect of varenicline and similar to the effect of bupropion. In reinstatement testing, animals were pretreated with the same compounds, challenged with nicotine (0.3 mg/kg, s.c.), and reintroduced to pre-extinction conditions. l-THP blocked reinstatement of nicotine seeking more effectively than either varenicline or bupropion. Locomotor data revealed that therapeutic doses of l-THP had no inhibitory effects on ambulatory ability and that l-THP (3 and 5 mg/kg) significantly blocked nicotine induced hyperactivity when administered before nicotine. In in-vivo microdialysis experiments, l-THP, varenicline, and bupropion alone elevated extracellular dopamine (DA) levels in the nucleus accumbens shell (nAcb). Since l-THP reduces nicotine taking and blocks relapse it could be a useful alternative to varenicline and bupropion as a treatment for nicotine addiction. JF - BMC pharmacology & toxicology AU - Faison, Shamia L AU - Schindler, Charles W AU - Goldberg, Steven R AU - Wang, Jia Bei AD - Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, USA. ; Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of Health, DHHS, Baltimore, MD, USA. ; Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, USA. jwang@rx.umaryland.edu. Y1 - 2016/11/07/ PY - 2016 DA - 2016 Nov 07 SP - 49 VL - 17 IS - 1 KW - levo-Tetrahydropalmatine KW - Nicotine KW - Addiction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837031128?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+pharmacology+%26+toxicology&rft.atitle=l-tetrahydropalmatine+reduces+nicotine+self-administration+and+reinstatement+in+rats.&rft.au=Faison%2C+Shamia+L%3BSchindler%2C+Charles+W%3BGoldberg%2C+Steven+R%3BWang%2C+Jia+Bei&rft.aulast=Faison&rft.aufirst=Shamia&rft.date=2016-11-07&rft.volume=17&rft.issue=1&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=BMC+pharmacology+%26+toxicology&rft.issn=2050-6511&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Structure and Function of FS50, a salivary protein from the flea Xenopsylla cheopis that blocks the sodium channel NaV1.5. AN - 1837026227; 27819327 AB - Naturally occurring toxins have been invaluable tools for the study of structural and functional relationships of voltage-gated sodium channels (VGSC). Few studies have been made of potential channel-modulating substances from blood-feeding arthropods. He we describe the characterization FS50, a salivary protein from the flea, Xenopsylla cheopis, that exhibits an inhibitory activity against the NaV1.5 channel with an IC50 of 1.58 μM. The pore-blocking mechanism of this toxin is evident from the kinetics of activation and inactivation suggesting that FS50 does not interfere with the voltage sensor of NaV1.5. FS50 exhibits high specificity for NaV1.5, since 10 μM FS50 had no discernable effect on voltage-gated Na+, K+ and Ca2+ channels in rat dorsal root ganglia or VGSC forms individually expressed in HEK 293T cells. Furthermore, intravenous injection of FS50 into rats and monkeys elicited recovery from arrhythmia induced by BaCl2, as would be expected from a blockade of NaV1.5. The crystal structure of FS50 revealed a βαββ domain similar to that of scorpion β toxin and a small N-terminal βαβ domain. Site-directed mutagenesis experiments have implicated a basic surface including the side chains of Arg 6, His 11 and Lys 32 as potentially important in the FS50 NaV1.5 interaction. JF - Scientific reports AU - Xu, Xueqing AU - Zhang, Bei AU - Yang, Shilong AU - An, Su AU - Ribeiro, José M C AU - Andersen, John F AD - Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, China. ; The Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China. ; The Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, Maryland 20852 USA. Y1 - 2016/11/07/ PY - 2016 DA - 2016 Nov 07 SP - 36574 VL - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837026227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Structure+and+Function+of+FS50%2C+a+salivary+protein+from+the+flea+Xenopsylla+cheopis+that+blocks+the+sodium+channel+NaV1.5.&rft.au=Xu%2C+Xueqing%3BZhang%2C+Bei%3BYang%2C+Shilong%3BAn%2C+Su%3BRibeiro%2C+Jos%C3%A9+M+C%3BAndersen%2C+John+F&rft.aulast=Xu&rft.aufirst=Xueqing&rft.date=2016-11-07&rft.volume=6&rft.issue=&rft.spage=36574&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep36574 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep36574 ER - TY - JOUR T1 - Inhibition of Insulin Amyloid Fibrillation by a Novel Amphipathic Heptapeptide: MECHANISTIC DETAILS STUDIED BY SPECTROSCOPY IN COMBINATION WITH MICROSCOPY. AN - 1836729698; 27679488 AB - The aggregation of insulin into amyloid fibers has been a limiting factor in the development of fast acting insulin analogues, creating a demand for excipients that limit aggregation. Despite the potential demand, inhibitors specifically targeting insulin have been few in number. Here we report a non-toxic and serum stable-designed heptapeptide, KR7 (KPWWPRR-NH2), that differs significantly from the primarily hydrophobic sequences that have been previously used to interfere with insulin amyloid fibrillation. Thioflavin T fluorescence assays, circular dichroism spectroscopy, and one-dimensional proton NMR experiments suggest KR7 primarily targets the fiber elongation step with little effect on the early oligomerization steps in the lag time period. From confocal fluorescence and atomic force microscopy experiments, the net result appears to be the arrest of aggregation in an early, non-fibrillar aggregation stage. This mechanism is noticeably different from previous peptide-based inhibitors, which have primarily shifted the lag time with little effect on later stages of aggregation. As insulin is an important model system for understanding protein aggregation, the new peptide may be an important tool for understanding peptide-based inhibition of amyloid formation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Ratha, Bhisma N AU - Ghosh, Anirban AU - Brender, Jeffrey R AU - Gayen, Nilanjan AU - Ilyas, Humaira AU - Neeraja, Chilukoti AU - Das, Kali P AU - Mandal, Atin K AU - Bhunia, Anirban AD - From the Department of Biophysics and. ; Radiation Biology Branch, National Institutes of Health, Bethesda, Maryland 20814. ; Department of Molecular Medicine, Bose Institute, P-1/12 CIT Scheme VII (M), Kolkata 700054, India. ; TIFR Centre for Interdisciplinary Sciences (TCIS), Narsingi, Hyderabad 500075, India, and. ; Department of Chemistry, 93/1 APC Road, Bose Institute, Kolkata 700009, India. ; From the Department of Biophysics and anirbanbhunia@gmail.com bhunia@jcbose.ac.in. Y1 - 2016/11/04/ PY - 2016 DA - 2016 Nov 04 SP - 23545 EP - 23556 VL - 291 IS - 45 KW - atomic force microscopy (AFM) KW - fluorescence anisotropy KW - insulin KW - inhibitor KW - amyloid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836729698?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Inhibition+of+Insulin+Amyloid+Fibrillation+by+a+Novel+Amphipathic+Heptapeptide%3A+MECHANISTIC+DETAILS+STUDIED+BY+SPECTROSCOPY+IN+COMBINATION+WITH+MICROSCOPY.&rft.au=Ratha%2C+Bhisma+N%3BGhosh%2C+Anirban%3BBrender%2C+Jeffrey+R%3BGayen%2C+Nilanjan%3BIlyas%2C+Humaira%3BNeeraja%2C+Chilukoti%3BDas%2C+Kali+P%3BMandal%2C+Atin+K%3BBhunia%2C+Anirban&rft.aulast=Ratha&rft.aufirst=Bhisma&rft.date=2016-11-04&rft.volume=30&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Fundamental+%26+clinical+pharmacology&rft.issn=1472-8206&rft_id=info:doi/10.1111%2Ffcp.12157 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-28 N1 - Date revised - 2017-01-14 N1 - Genetic sequence - 2ZP6; PDB N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Serum Metabolomic Profiles in Neonatal Mice following Oral Brominated Flame Retardant Exposures to Hexabromocyclododecane (HBCD) Alpha, Gamma, and Commercial Mixture. AN - 1836726594; 27814246 AB - Hexabromocyclododecane (HBCD) is a high production volume brominated flame retardant added to building insulation foams, electronics, and textiles. HBCD is a commercial-mixture (CM-HBCD) composed of 3 main stereoisomers: α-HBCD (10%); β-HBCD (10%); γ-HBCD (80%). A shift from the dominant stereoisomer γ-HBCD to α-HBCD is detected in humans and wildlife. Considering CM-HBCD has been implicated in neurodevelopment and endocrine disruption, with expected metabolism perturbations, metabolomics was performed on mice serum obtained during a window-of-developmental neurotoxicity to draw correlations between early-life exposures, developmental outcomes, and predict health risks. Ten postnatal day (PND) female C57BL/6 mice were administered a single gavage dose of α-, γ-, or CM-HBCD at 3, 10, and 30 mg/kg. NMR metabolomics was used to analyze 60 µL serum aliquots of blood collected 4 days post-oral exposure. Infantile mice exposed to α-, γ-, or CM-HBCD demonstrated differences in endogenous metabolites by treatment- and dose-groups, including metabolites involved in glycolysis, gluconeogenesis, lipid metabolism, citric acid cycle, and neurodevelopment. Ketone bodies, 3-hydroxybutyrate and acetoacetate, were non-statistically elevated, compared to mean control levels, in all treatment- and dose-groups while glucose, pyruvate, and alanine varied. Acetoacetate was significantly increased in the 10 mg/kg α-HBCD, and was non-significantly decreased with CM-HBCD. A third ketone body, acetone, was significantly lower in the 30 mg/kg α-HBCD group with significant increases in pyruvate at the same treatment- and dose group. Metabolites significant in differentiating treatment- and dose-groups were also identified, including decreases in amino acids glutamate (excitatory neurotransmitter in learning and memory) and phenylalanine (neurotransmitter precursor) after α-HBCD and γ-HBCD exposure, respectively. We demonstrate that four days following a single neonatal oral exposure to α-, γ-, and CM-HBCD results in different serum metabolomic profiles, indicating stereoisomer- and mixture-specific effects and possible mechanisms of action. JF - Environmental health perspectives AU - Szabo, David T AU - Pathmasiri, Wimal AU - Sumner, Susan AU - Birnbaum, Linda S AD - US Environmental Protection Agency, National Human Environmental Exposure Research Laboratory, Research Triangle Park, North Carolina, USA. ; Discovery Sciences, Research Triangle Institute International, Research Triangle Park, North Carolina, USA. ; National Institute of Environmental Health Sciences and National Toxicology Program, Research Triangle Park, North Carolina, USA. Y1 - 2016/11/04/ PY - 2016 DA - 2016 Nov 04 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836726594?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Serum+Metabolomic+Profiles+in+Neonatal+Mice+following+Oral+Brominated+Flame+Retardant+Exposures+to+Hexabromocyclododecane+%28HBCD%29+Alpha%2C+Gamma%2C+and+Commercial+Mixture.&rft.au=Szabo%2C+David+T%3BPathmasiri%2C+Wimal%3BSumner%2C+Susan%3BBirnbaum%2C+Linda+S&rft.aulast=Szabo&rft.aufirst=David&rft.date=2016-11-04&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - TNF-α modulates genome-wide redistribution of ΔNp63α/TAp73 and NF-κB cREL interactive binding on TP53 and AP-1 motifs to promote an oncogenic gene program in squamous cancer. AN - 1826672972; 27132513 AB - The Cancer Genome Atlas (TCGA) network study of 12 cancer types (PanCancer 12) revealed frequent mutation of TP53, and amplification and expression of related TP63 isoform ΔNp63 in squamous cancers. Further, aberrant expression of inflammatory genes and TP53/p63/p73 targets were detected in the PanCancer 12 project, reminiscent of gene programs comodulated by cREL/ΔNp63/TAp73 transcription factors we uncovered in head and neck squamous cell carcinomas (HNSCCs). However, how inflammatory gene signatures and cREL/p63/p73 targets are comodulated genome wide is unclear. Here, we examined how the inflammatory factor tumor necrosis factor-α (TNF-α) broadly modulates redistribution of cREL with ΔNp63α/TAp73 complexes and signatures genome wide in the HNSCC model UM-SCC46 using chromatin immunoprecipitation sequencing (ChIP-seq). TNF-α enhanced genome-wide co-occupancy of cREL with ΔNp63α on TP53/p63 sites, while unexpectedly promoting redistribution of TAp73 from TP53 to activator protein-1 (AP-1) sites. cREL, ΔNp63α and TAp73 binding and oligomerization on NF-κB-, TP53- or AP-1-specific sequences were independently validated by ChIP-qPCR (quantitative PCR), oligonucleotide-binding assays and analytical ultracentrifugation. Function of the binding activity was confirmed using TP53-, AP-1- and NF-κB-specific REs or p21, SERPINE1 and IL-6 promoter luciferase reporter activities. Concurrently, TNF-α regulated a broad gene network with cobinding activities for cREL, ΔNp63α and TAp73 observed upon array profiling and reverse transcription-PCR. Overlapping target gene signatures were observed in squamous cancer subsets and in inflamed skin of transgenic mice overexpressing ΔNp63α. Furthermore, multiple target genes identified in this study were linked to TP63 and TP73 activity and increased gene expression in large squamous cancer samples from PanCancer 12 TCGA by CircleMap. PARADIGM inferred pathway analysis revealed the network connection of TP63 and NF-κB complexes through an AP-1 hub, further supporting our findings. Thus, inflammatory cytokine TNF-α mediates genome-wide redistribution of the cREL/p63/p73, and AP-1 interactome, to diminish TAp73 tumor suppressor function and reciprocally activate NF-κB and AP-1 gene programs implicated in malignancy. JF - Oncogene AU - Si, H AU - Lu, H AU - Yang, X AU - Mattox, A AU - Jang, M AU - Bian, Y AU - Sano, E AU - Viadiu, H AU - Yan, B AU - Yau, C AU - Ng, S AU - Lee, S K AU - Romano, R-A AU - Davis, S AU - Walker, R L AU - Xiao, W AU - Sun, H AU - Wei, L AU - Sinha, S AU - Benz, C C AU - Stuart, J M AU - Meltzer, P S AU - Van Waes, C AU - Chen, Z AD - Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. ; Department of Chemistry and Biochemistry, University of California, San Diego, CA, USA. ; Instituto de Química, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior, Ciudad Universitaria, Mexico City, MÉXICO. ; LKS Faculty of Medicine and School of Biomedical Sciences, LKS Faculty of Medicine and Center of Genome Sciences, The University of Hong Kong, Hong Kong, China. ; Buck Institute for Research on Aging, Novato, CA, USA. ; Department of Biomolecular Engineering, Center for Biomolecular Sciences and Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA. ; Department of Biochemistry, State University of New York at Buffalo, Center for Excellence in Bioinformatics and Life Sciences, Buffalo, New York, USA. ; Cancer Genetics Branch, National Cancer Institute, Bethesda, Maryland, USA. ; Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AK, USA. ; Biodata Mining and Discovery Section, National Institute of Arthritis, Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA. ; Clinical Immunology Section, National Eye Institute, NIH, Bethesda, Maryland, USA. Y1 - 2016/11/03/ PY - 2016 DA - 2016 Nov 03 SP - 5781 EP - 5794 VL - 35 IS - 44 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826672972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=TNF-%CE%B1+modulates+genome-wide+redistribution+of+%CE%94Np63%CE%B1%2FTAp73+and+NF-%CE%BAB+cREL+interactive+binding+on+TP53+and+AP-1+motifs+to+promote+an+oncogenic+gene+program+in+squamous+cancer.&rft.au=Si%2C+H%3BLu%2C+H%3BYang%2C+X%3BMattox%2C+A%3BJang%2C+M%3BBian%2C+Y%3BSano%2C+E%3BViadiu%2C+H%3BYan%2C+B%3BYau%2C+C%3BNg%2C+S%3BLee%2C+S+K%3BRomano%2C+R-A%3BDavis%2C+S%3BWalker%2C+R+L%3BXiao%2C+W%3BSun%2C+H%3BWei%2C+L%3BSinha%2C+S%3BBenz%2C+C+C%3BStuart%2C+J+M%3BMeltzer%2C+P+S%3BVan+Waes%2C+C%3BChen%2C+Z&rft.aulast=Si&rft.aufirst=H&rft.date=2016-11-03&rft.volume=35&rft.issue=44&rft.spage=5781&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=1476-5594&rft_id=info:doi/10.1038%2Fonc.2016.112 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/onc.2016.112 ER - TY - JOUR T1 - Genomic profiling of multiple sequentially acquired tumor metastatic sites from an "exceptional responder" lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response AN - 1850780150; PQ0003898815 AB - We used next-generation sequencing to identify somatic alterations in multiple metastatic sites from an "exceptional responder" lung adenocarcinoma patient during his 7-yr course of ERBB2-directed therapies. The degree of heterogeneity was unprecedented, with ~1% similarity between somatic alterations of the lung and lymph nodes. One novel translocation, PLAG1-ACTA2, present in both sites, up-regulated ACTA2 expression. ERBB2, the predominant driver oncogene, was amplified in both sites, more pronounced in the lung, and harbored an L869R mutation in the lymph node. Functional studies showed increased proliferation, migration, metastasis, and resistance to ERBB2-directed therapy because of L869R mutation and increased migration because of ACTA2 overexpression. Within the lung, a nonfunctional CDK12, due to a novel G879V mutation, correlated with down-regulation of DNA damage response genes, causing genomic instability, and sensitivity to chemotherapy. We propose a model whereby a subclone metastasized early from the primary site and evolved independently in lymph nodes. JF - Cold Spring Harbor Molecular Case Studies AU - Biswas, Romi AU - Gao, Shaojian AU - Cultraro, Constance M AU - Maity, Tapan K AU - Venugopalan, Abhilash AU - Abdullaev, Zied AU - Shaytan, Alexey K AU - Carter, Corey A AU - Thomas, Anish AU - Rajan, Arun AD - Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA Y1 - 2016/11// PY - 2016 DA - November 2016 PB - Cold Spring Harbor Laboratory Press, Fulfillment & Distribution Dept. Woodbury NY 11797-2924 United States VL - 2 IS - 6 KW - Biotechnology and Bioengineering Abstracts KW - ErbB-2 protein KW - Chemotherapy KW - Tumors KW - Migration KW - Lymph nodes KW - Models KW - Metastases KW - DNA damage KW - Genomic instability KW - Oncogenes KW - Lung KW - Adenocarcinoma KW - Translocation KW - Mutation KW - W 30940:Products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1850780150?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cold+Spring+Harbor+Molecular+Case+Studies&rft.atitle=Genomic+profiling+of+multiple+sequentially+acquired+tumor+metastatic+sites+from+an+%22exceptional+responder%22+lung+adenocarcinoma+patient+reveals+extensive+genomic+heterogeneity+and+novel+somatic+variants+driving+treatment+response&rft.au=Biswas%2C+Romi%3BGao%2C+Shaojian%3BCultraro%2C+Constance+M%3BMaity%2C+Tapan+K%3BVenugopalan%2C+Abhilash%3BAbdullaev%2C+Zied%3BShaytan%2C+Alexey+K%3BCarter%2C+Corey+A%3BThomas%2C+Anish%3BRajan%2C+Arun&rft.aulast=Biswas&rft.aufirst=Romi&rft.date=2016-11-01&rft.volume=2&rft.issue=6&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Cold+Spring+Harbor+Molecular+Case+Studies&rft.issn=2373-2873&rft_id=info:doi/10.1101%2Fmcs.a001263 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-21 N1 - SubjectsTermNotLitGenreText - ErbB-2 protein; Chemotherapy; Tumors; Migration; Lymph nodes; Models; Metastases; DNA damage; Oncogenes; Genomic instability; Lung; Adenocarcinoma; Mutation; Translocation DO - http://dx.doi.org/10.1101/mcs.a001263 ER - TY - JOUR T1 - Relation of Pericardial Fat, Intrathoracic Fat, and Abdominal Visceral Fat With Incident Atrial Fibrillation (from the Framingham Heart Study) AN - 1846419309; PQ0003845105 AB - Obesity is associated with increased risk of developing atrial fibrillation (AF). Different fat depots may have differential associations with cardiac pathology. We examined the longitudinal associations between pericardial, intrathoracic, and visceral fat with incident AF. We studied Framingham Heart Study Offspring and Third-Generation Cohorts who participated in the multidetector computed tomography substudy examination 1. We constructed multivariable-adjusted Cox proportional hazard models for risk of incident AF. Body mass index was included in the multivariable-adjusted model as a secondary adjustment. We included 2,135 participants (53.3% women; mean age 58.8 years). During a median follow-up of 9.7 years, we identified 162 cases of incident AF. Across the increasing tertiles of pericardial fat volume, age- and gender-adjusted incident AF rate per 1,000 person-years of follow-up were 8.4, 7.5, and 10.2. Based on an age- and gender-adjusted model, greater pericardial fat (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.03 to 1.34) and intrathoracic fat (HR 1.24, 95% CI 1.06 to 1.45) were associated with an increased risk of incident AF. The HRs (95% CI) for incident AF were 1.13 (0.99 to 1.30) for pericardial fat, 1.19 (1.01 to 1.40) for intrathoracic fat, and 1.09 (0.93 to 1.28) for abdominal visceral fat after multivariable adjustment. After additional adjustment of body mass index, none of the associations remained significant (all p >0.05). Our findings suggest that cardiac ectopic fat depots may share common risk factors with AF, which may have led to a lack of independence in the association between pericardial fat with incident AF. JF - American Journal of Cardiology AU - Lee, Jane J AU - Yin, Xiaoyan AU - Hoffmann, Udo AU - Fox, Caroline S AU - Benjamin, Emelia J AD - Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and, Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1486 EP - 1492 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 118 IS - 10 SN - 0002-9149, 0002-9149 KW - Biotechnology and Bioengineering Abstracts KW - Heart KW - Obesity KW - Age KW - Fibrillation KW - Risk factors KW - Computed tomography KW - Progeny KW - Body mass index KW - Models KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846419309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Cardiology&rft.atitle=Relation+of+Pericardial+Fat%2C+Intrathoracic+Fat%2C+and+Abdominal+Visceral+Fat+With+Incident+Atrial+Fibrillation+%28from+the+Framingham+Heart+Study%29&rft.au=Lee%2C+Jane+J%3BYin%2C+Xiaoyan%3BHoffmann%2C+Udo%3BFox%2C+Caroline+S%3BBenjamin%2C+Emelia+J&rft.aulast=Lee&rft.aufirst=Jane&rft.date=2016-11-01&rft.volume=118&rft.issue=10&rft.spage=1486&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Cardiology&rft.issn=00029149&rft_id=info:doi/10.1016%2Fj.amjcard.2016.08.011 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Number of references - 30 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Heart; Obesity; Age; Risk factors; Fibrillation; Computed tomography; Progeny; Body mass index; Models DO - http://dx.doi.org/10.1016/j.amjcard.2016.08.011 ER - TY - JOUR T1 - Understanding the Intersection of Young Age, Mucosal Injury, and HIV Susceptibility AN - 1846418070; PQ0003879920 AB - Adolescent boys and girls are disproportionately affected in the current HIV epidemic. Numerous sociobehavioral studies have addressed the indirect drivers surrounding this vulnerability-for example, socioeconomic, geographical locale, and all forms of violence. However, the direct factors that may influence infection, such as the anatomical and physiological maturation of the anogenital tracts of adolescents or the trauma and wound-healing processes of injured mucosal tissue, are understudied and represent a gap within the HIV prevention field. This article reviews the epidemiology of HIV infection and violence in adolescents and the available basic science knowledge attending this research area. More importantly, this review highlights the most critical gaps that need to be addressed to design preventive interventions that are safe and effective for this population, which is key to ending the HIV pandemic. JF - AIDS Research and Human Retroviruses AU - Porter, Kristen A AU - Turpin, Jim AU - Begg, Lisa AU - Brown, Gina AU - Chakhtoura, Nahida AU - Church, Elizabeth AU - Grossman, Cynthia AU - Wira, Charles AU - Veronese, Fulvia AD - Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1149 EP - 1158 PB - Mary Ann Liebert, Inc., 140 Huguenot Street New Rochelle NY 10801 United States VL - 32 IS - 10-11 SN - 0889-2229, 0889-2229 KW - Health & Safety Science Abstracts; Virology & AIDS Abstracts KW - HIV KW - HIV/AIDS pathogenesis KW - HIV transmission KW - HIV prevention KW - mucosal KW - Acquired immune deficiency syndrome KW - Prevention KW - Lentivirus KW - Injuries KW - Retroviridae KW - Physiology KW - Intervention KW - Socioeconomics KW - Infection KW - Violence KW - Adolescents KW - H 6000:Natural Disasters/Civil Defense/Emergency Management UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846418070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+Research+and+Human+Retroviruses&rft.atitle=Understanding+the+Intersection+of+Young+Age%2C+Mucosal+Injury%2C+and+HIV+Susceptibility&rft.au=Porter%2C+Kristen+A%3BTurpin%2C+Jim%3BBegg%2C+Lisa%3BBrown%2C+Gina%3BChakhtoura%2C+Nahida%3BChurch%2C+Elizabeth%3BGrossman%2C+Cynthia%3BWira%2C+Charles%3BVeronese%2C+Fulvia&rft.aulast=Porter&rft.aufirst=Kristen&rft.date=2016-11-01&rft.volume=32&rft.issue=10-11&rft.spage=1149&rft.isbn=&rft.btitle=&rft.title=AIDS+Research+and+Human+Retroviruses&rft.issn=08892229&rft_id=info:doi/10.1089%2Faid.2016.0206 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Number of references - 48 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Prevention; Acquired immune deficiency syndrome; Injuries; Physiology; Socioeconomics; Intervention; Infection; Violence; Adolescents; Lentivirus; Retroviridae DO - http://dx.doi.org/10.1089/aid.2016.0206 ER - TY - JOUR T1 - Type I Interferon-Mediated Induction of Antiviral Genes and Proteins Fails to Protect Cells from the Cytopathic Effects of Sendai Virus Infection AN - 1846405368; PQ0003818914 AB - Sendai virus (SeV), a murine paramyxovirus, has been used to study the induction of type I interferon (IFN) subtypes in robust quantities. Few studies have measured whether the IFN that SeV induces actually fulfills its intended purpose of interfering with virus-mediated effects in the cells in which it is produced. We determined the effects of IFN on SeV-mediated cytopathic effects (CPE) and the ability of IFN to protect against virus infection. SeV-induced biologically active IFN resulted in Jak/STAT activation and the production of a number of interferon-stimulated genes (ISGs). However, these responses did not inhibit SeV replication or CPE. This observation was not due to SeV effects on canonical IFN signaling. Furthermore, pretreating cells with type I IFN and establishing an antiviral state before infection did not mediate SeV effects. Therefore, the induction of canonical IFN signaling pathways and ISGs does not always confer protection against the IFN-inducing virus. Because type I IFNs are approved to treat various infections, our findings suggest that typical markers of IFN activity may not be indicative of a protective antiviral response and should not be used alone to determine whether an antiviral state against a particular virus is achieved. JF - Journal of Interferon & Cytokine Research AU - Bedsaul, Jacquelyn R AU - Zaritsky, Luna A AU - Zoon, Kathryn C AD - Cytokine Biology Section, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 652 EP - 665 PB - Mary Ann Liebert, Inc., 2 Madison Ave Larchmont NY 10538 United States VL - 36 IS - 11 SN - 1079-9907, 1079-9907 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Immunology Abstracts KW - interferon KW - Sendai virus KW - antiviral state KW - signaling KW - Interferon KW - Replication KW - Antiviral state KW - Paramyxovirus KW - Infection KW - Signal transduction KW - A 01340:Antibiotics & Antimicrobials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846405368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Interferon+%26+Cytokine+Research&rft.atitle=Type+I+Interferon-Mediated+Induction+of+Antiviral+Genes+and+Proteins+Fails+to+Protect+Cells+from+the+Cytopathic+Effects+of+Sendai+Virus+Infection&rft.au=Bedsaul%2C+Jacquelyn+R%3BZaritsky%2C+Luna+A%3BZoon%2C+Kathryn+C&rft.aulast=Bedsaul&rft.aufirst=Jacquelyn&rft.date=2016-11-01&rft.volume=36&rft.issue=11&rft.spage=652&rft.isbn=&rft.btitle=&rft.title=Journal+of+Interferon+%26+Cytokine+Research&rft.issn=10799907&rft_id=info:doi/10.1089%2Fjir.2016.0051 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Number of references - 50 N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Interferon; Replication; Antiviral state; Infection; Signal transduction; Sendai virus; Paramyxovirus DO - http://dx.doi.org/10.1089/jir.2016.0051 ER - TY - JOUR T1 - Transcription Factor GLIS3: A New and Critical Regulator of Postnatal Stages of Mouse Spermatogenesis AN - 1846400355; PQ0003835262 AB - Abstract In this study, we identify a novel and essential role for the Krueppel-like zinc finger transcription factor GLI-similar 3 (GLIS3) in the regulation of postnatal spermatogenesis. We show that GLIS3 is expressed in gonocytes, spermatogonial stem cells (SSCs) and spermatogonial progenitors (SPCs), but not in differentiated spermatogonia and later stages of spermatogenesis or in somatic cells. Spermatogenesis is greatly impaired in GLIS3 knockout mice. Loss of GLIS3 function causes a moderate reduction in the number of gonocytes, but greatly affects the generation of SSCs/SPCs, and as a consequence the development of spermatocytes. Gene expression profiling demonstrated that the expression of genes associated with undifferentiated spermatogonia was dramatically decreased in GLIS3-deficient mice and that the cytoplasmic-to-nuclear translocation of FOXO1, which marks the gonocyte-to-SSC transition and is necessary for SSC self-renewal, is inhibited. These observations suggest that GLIS3 promotes the gonocyte-to-SSC transition and is a critical regulator of the dynamics of early postnatal spermatogenesis. Stem Cells 2016; 34:2772-2783 JF - Stem Cells AU - Kang, Hong Soon AU - Chen, Liang-Yu AU - Lichti-Kaiser, Kristin AU - Liao, Grace AU - Gerrish, Kevin AU - Bortner, Carl D AU - Yao, Humphrey H-C AU - Eddy, Edward M AU - Jetten, Anton M AD - Immunity, Inflammation and Disease Laboratory, National Institutes of Health, Research Triangle Park, North Carolina, USA. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 2772 EP - 2783 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 34 IS - 11 SN - 1066-5099, 1066-5099 KW - Biotechnology and Bioengineering Abstracts KW - Gene expression KW - Stem cells KW - Transcription factors KW - Zinc finger proteins KW - FOXO1 protein KW - Somatic cells KW - Spermatogenesis KW - Translocation KW - Spermatocytes KW - Spermatogonia KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846400355?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+Cells&rft.atitle=Transcription+Factor+GLIS3%3A+A+New+and+Critical+Regulator+of+Postnatal+Stages+of+Mouse+Spermatogenesis&rft.au=Kang%2C+Hong+Soon%3BChen%2C+Liang-Yu%3BLichti-Kaiser%2C+Kristin%3BLiao%2C+Grace%3BGerrish%2C+Kevin%3BBortner%2C+Carl+D%3BYao%2C+Humphrey+H-C%3BEddy%2C+Edward+M%3BJetten%2C+Anton+M&rft.aulast=Kang&rft.aufirst=Hong&rft.date=2016-11-01&rft.volume=34&rft.issue=11&rft.spage=2772&rft.isbn=&rft.btitle=&rft.title=Stem+Cells&rft.issn=10665099&rft_id=info:doi/10.1002%2Fstem.2449 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Gene expression; Stem cells; Transcription factors; Zinc finger proteins; FOXO1 protein; Somatic cells; Translocation; Spermatogenesis; Spermatocytes; Spermatogonia DO - http://dx.doi.org/10.1002/stem.2449 ER - TY - JOUR T1 - The long terminal repeat negative control region is a critical element for insertional oncogenesis after gene transfer into hematopoietic progenitors with Moloney murine leukemia viral vectors AN - 1846399307; PQ0003838671 AB - Integrating vectors based on gamma -retroviruses and containing full-length long terminal repeats (LTRs) have been associated with activation of oncogene expression and leukemogenesis in human gene therapy trials. Identification of the specific molecular elements of the LTRs that have a role in insertional oncogenesis events is important as it can lead to the development of safer gene transfer vectors. The negative control region (NCR) of the LTR is a particularly well-conserved sequence among mammalian gamma -retroviruses with demonstrated regulatory activity of gene transcription in hematopoietic cells, which led us to hypothesize that this region may have a role in insertional oncogenesis after gamma -retroviral vector (GV)-mediated gene transfer into hematopoietic progenitors. We used an in vitro assay of murine bone marrow cell immortalization to compare the immortalization capabilities of a series of GVs carrying murine leukemia virus (MLV) LTR deletion mutants. Compared with GV carrying the full-length MLV LTR, deletion of the complete LTR enhancer sequence showed significant reduction of immortalization rates. However, the use of a mutant LTR deleted of the enhancer sequence, with exception of the NCR, did not affect immortalization. Importantly, the inclusion of an LTR mutant devoid only of the NCR did show significant reduction of immortalization rates compared with the full LTR sequence. Therefore, our data point to the NCR as a key element for immortalization and justify additional studies to evaluate its specific role in MLV-mediated insertional oncogenesis. JF - Gene Therapy AU - Ikawa, Y AU - Uchiyama, T AU - Jagadeesh, G J AU - Candotti, F AD - Genetics and Molecular Biology Branch, National Human Genome Research Institute (NHGRI), Bethesda, MD, USA; Department of Pediatrics, Kanazawa University Hospital, Kanazawa, Japan Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 815 EP - 818 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 23 IS - 11 SN - 0969-7128, 0969-7128 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Cell immortalization KW - Data processing KW - Deletion mutant KW - Gene therapy KW - Long terminal repeat KW - Regulatory sequences KW - Retroviridae KW - Tumorigenesis KW - Bone marrow KW - Leukemogenesis KW - Transcription KW - Expression vectors KW - Enhancers KW - Stem cells KW - Oncogenes KW - Hemopoiesis KW - Immortalization KW - W 30905:Medical Applications KW - G 07880:Human Genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846399307?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=The+long+terminal+repeat+negative+control+region+is+a+critical+element+for+insertional+oncogenesis+after+gene+transfer+into+hematopoietic+progenitors+with+Moloney+murine+leukemia+viral+vectors&rft.au=Ikawa%2C+Y%3BUchiyama%2C+T%3BJagadeesh%2C+G+J%3BCandotti%2C+F&rft.aulast=Ikawa&rft.aufirst=Y&rft.date=2016-11-01&rft.volume=23&rft.issue=11&rft.spage=815&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/10.1038%2Fgt.2016.51 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Cell immortalization; Deletion mutant; Data processing; Gene therapy; Long terminal repeat; Regulatory sequences; Tumorigenesis; Leukemogenesis; Bone marrow; Transcription; Expression vectors; Enhancers; Stem cells; Oncogenes; Hemopoiesis; Immortalization; Retroviridae DO - http://dx.doi.org/10.1038/gt.2016.51 ER - TY - JOUR T1 - Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior. AN - 1842601058; 27870848 AB - The master circadian clock in fish has been considered to reside in the pineal gland. This dogma is challenged, however, by the finding that most zebrafish tissues contain molecular clocks that are directly reset by light. To further examine the role of the pineal gland oscillator in the zebrafish circadian system, we generated a transgenic line in which the molecular clock is selectively blocked in the melatonin-producing cells of the pineal gland by a dominant-negative strategy. As a result, clock-controlled rhythms of melatonin production in the adult pineal gland were disrupted. Moreover, transcriptome analysis revealed that the circadian expression pattern of the majority of clock-controlled genes in the adult pineal gland is abolished. Importantly, circadian rhythms of behavior in zebrafish larvae were affected: rhythms of place preference under constant darkness were eliminated, and rhythms of locomotor activity under constant dark and constant dim light conditions were markedly attenuated. On the other hand, global peripheral molecular oscillators, as measured in whole larvae, were unaffected in this model. In conclusion, characterization of this novel transgenic model provides evidence that the molecular clock in the melatonin-producing cells of the pineal gland plays a key role, possibly as part of a multiple pacemaker system, in modulating circadian rhythms of behavior. JF - PLoS genetics AU - Ben-Moshe Livne, Zohar AU - Alon, Shahar AU - Vallone, Daniela AU - Bayleyen, Yared AU - Tovin, Adi AU - Shainer, Inbal AU - Nisembaum, Laura G AU - Aviram, Idit AU - Smadja-Storz, Sima AU - Fuentes, Michael AU - Falcón, Jack AU - Eisenberg, Eli AU - Klein, David C AU - Burgess, Harold A AU - Foulkes, Nicholas S AU - Gothilf, Yoav AD - Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel. ; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany. ; Unit on Behavioral Neurogenetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America. ; Sorbonne Universités, UPMC Univ Paris 06, CNRS, Biologie Intégrative des Organismes Marins, Observatoire Océanologique, Banyuls/Mer, France. ; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel. ; Section on Neuroendocrinology and Office of the Scientific Directory, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1 VL - 12 IS - 11 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1842601058?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PLoS+genetics&rft.atitle=Genetically+Blocking+the+Zebrafish+Pineal+Clock+Affects+Circadian+Behavior.&rft.au=Ben-Moshe+Livne%2C+Zohar%3BAlon%2C+Shahar%3BVallone%2C+Daniela%3BBayleyen%2C+Yared%3BTovin%2C+Adi%3BShainer%2C+Inbal%3BNisembaum%2C+Laura+G%3BAviram%2C+Idit%3BSmadja-Storz%2C+Sima%3BFuentes%2C+Michael%3BFalc%C3%B3n%2C+Jack%3BEisenberg%2C+Eli%3BKlein%2C+David+C%3BBurgess%2C+Harold+A%3BFoulkes%2C+Nicholas+S%3BGothilf%2C+Yoav&rft.aulast=Ben-Moshe+Livne&rft.aufirst=Zohar&rft.date=2016-11-01&rft.volume=12&rft.issue=11&rft.spage=e1006445&rft.isbn=&rft.btitle=&rft.title=PLoS+genetics&rft.issn=1553-7404&rft_id=info:doi/10.1371%2Fjournal.pgen.1006445 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1371/journal.pgen.1006445 ER - TY - JOUR T1 - Ferumoxytol as an intraprostatic MR contrast agent for lymph node mapping of the prostate: a feasibility study in non-human primates AN - 1837336120; PQ0003757229 AB - Background A variety of magnetic resonance (MR) lymphographic agents have been proposed for mapping the lymph nodes draining the prostate. Purpose To investigate the feasibility of using ferumoxytol (an FDA-approved iron oxide agent) for lymph node mapping of the prostate on imaging (MRI) in a non-human primate (NHP) Macaque model. Material and Methods Four NHPs weighing 5-13kg underwent injection of ferumoxytol after a needle was introduced transrectally under MRI guidance into the prostate using a commercially available intrarectal MRI biopsy guide. Ferumoxytol was administered at dosage in the range of 0.15-0.75mg Fe/kg in a fixed injection volume of 0.2mL. T1-weighted MRI was performed at 3T starting immediately and extending at least 45min post-injection. Two readers evaluated the images in consensus. The NHPs tolerated the ferumoxytol injections at all doses with no evident side effects. Results It was determined that the lowest dose of 0.15mg Fe/kg produced the best outcome in terms of lymph node visualization and draining nodes were reliably visualized at this dose and volume. Conclusion Thus, MRI with intraprostatic injection of ferumoxytol may be considered an effective T1 contrast agent for prospective mapping of lymph nodes draining the prostate and, thus, for attempted sentinel lymph node identification in prostate cancer. Large clinical trials to determine safety and efficacy are needed. JF - Acta Radiologica AU - Sankineni, Sandeep AU - Smedley, Jeremy AU - Bernardo, Marcelino AU - Brown, Anna M AU - Johnson, Linda AU - Muller, Berrend AU - Griffiths, Gary L AU - Kobayashi, Hisataka AU - Rais-Bahrami, Soroush AU - Pinto, Peter A AU - Wood, Bradford J AU - Keele, Brandon AU - Choyke, Peter L AU - Turkbey, Baris AD - 1 .Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, turkbeyi@mail.nih.gov Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1396 EP - 1401 PB - Sage Publications, Inc., 2455 Teller Road Thousand Oaks CA 91320 United States VL - 57 IS - 11 SN - 0284-1851, 0284-1851 KW - Biotechnology and Bioengineering Abstracts KW - Ferumoxytol KW - lymph node KW - prostate cancer KW - iron oxide nanoparticles KW - magnetic resonance imaging (MRI) KW - iron oxides KW - Macaca KW - Magnetic resonance imaging KW - Animal models KW - Biopsy KW - Clinical trials KW - Lymph nodes KW - Prostate cancer KW - Computed tomography KW - Contrast media KW - N.M.R. KW - Mapping KW - Side effects KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837336120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+Radiologica&rft.atitle=Ferumoxytol+as+an+intraprostatic+MR+contrast+agent+for+lymph+node+mapping+of+the+prostate%3A+a+feasibility+study+in+non-human+primates&rft.au=Sankineni%2C+Sandeep%3BSmedley%2C+Jeremy%3BBernardo%2C+Marcelino%3BBrown%2C+Anna+M%3BJohnson%2C+Linda%3BMuller%2C+Berrend%3BGriffiths%2C+Gary+L%3BKobayashi%2C+Hisataka%3BRais-Bahrami%2C+Soroush%3BPinto%2C+Peter+A%3BWood%2C+Bradford+J%3BKeele%2C+Brandon%3BChoyke%2C+Peter+L%3BTurkbey%2C+Baris&rft.aulast=Sankineni&rft.aufirst=Sandeep&rft.date=2016-11-01&rft.volume=57&rft.issue=11&rft.spage=1396&rft.isbn=&rft.btitle=&rft.title=Acta+Radiologica&rft.issn=02841851&rft_id=info:doi/10.1177%2F0284185115586023 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Number of references - 9 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Prostate cancer; iron oxides; Computed tomography; Magnetic resonance imaging; Animal models; Contrast media; N.M.R.; Biopsy; Mapping; Clinical trials; Side effects; Lymph nodes; Macaca DO - http://dx.doi.org/10.1177/0284185115586023 ER - TY - JOUR T1 - Gene-environment interactions linking air pollution and inflammation in Parkinson's disease AN - 1837321812; PQ0003763505 AB - Both air pollution exposure and systemic inflammation have been linked to Parkinson's disease (PD). In the PASIDA study, 408 incident cases of PD diagnosed in 2006-2009 and their 495 population controls were interviewed and provided DNA samples. Markers of long term traffic related air pollution measures were derived from geographic information systems (GIS)-based modeling. Furthermore, we genotyped functional polymorphisms in genes encoding proinflammatory cytokines, namely rs1800629 in TNF alpha (tumor necrosis factor alpha) and rs16944 in IL1B (interleukin-1 beta ). In logistic regression models, long-term exposure to NO2 increased PD risk overall (odds ratio (OR)=1.06 per 2.94 mu g/m3 increase, 95% CI=1.00-1.13). The OR for PD in individuals with high NO2 exposure (75th percentile) and the AA genotype of IL1B rs16944 was 3.10 (95% CI=1.14-8.38) compared with individuals with lower NO2 exposure (<75th percentile) and the GG genotype. The interaction term was nominally significant on the multiplicative scale (p=0.01). We did not find significant gene-environment interactions with TNF rs1800629. Our finds may provide suggestive evidence that a combination of traffic-related air pollution and genetic variation in the proinflammatory cytokine gene IL1B contribute to risk of developing PD. However, as statistical evidence was only modest in this large sample we cannot rule out that these results represent a chance finding, and additional replication efforts are warranted. JF - Environmental Research AU - Lee, Pei-Chen AU - Raaschou-Nielsen, Ole AU - Lill, Christina M AU - Bertram, Lars AU - Sinsheimer, Janet S AU - Hansen, Johnni AU - Ritz, Beate AD - Department of Health Care Management, College of Health Technology, National Taipei University of Nursing and Health Sciences, 89, Nei-Chiang St. Wan-Hua Dist, Taipei 10845, Taiwan Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 713 EP - 720 PB - Elsevier B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands VL - 151 SN - 0013-9351, 0013-9351 KW - Genetics Abstracts; Pollution Abstracts; Environment Abstracts KW - PM10 particles of less than 10 mu m diameter KW - PM2.5 particles of less than 2.5 mu m diameter KW - O3 ozone KW - CO carbon monoxide KW - NO2 nitrogen dioxide KW - SO2 sulfur dioxide KW - IQR interquartile range KW - SD standard deviation KW - PD Parkinson's disease KW - GIS geographic information systems KW - TNF alpha tumor necrosis factor alpha KW - IL1B interleukin-1 beta KW - CNS central nervous system KW - Traffic-related air pollution KW - Inflammation KW - Parkinson's disease KW - Gene-environment interaction KW - Statistics KW - Gene polymorphism KW - Tumor necrosis factor KW - Interleukin 1 KW - Remote sensing KW - Genetic diversity KW - Genotypes KW - Models KW - Risk factors KW - Regression analysis KW - Replication KW - Tumors KW - Traffic KW - Air pollution KW - Neurodegenerative diseases KW - Population control KW - Movement disorders KW - DNA KW - Geographic information systems KW - Tumor necrosis factor- alpha KW - G 07720:Immunogenetics KW - P 0000:AIR POLLUTION KW - ENA 01:Air Pollution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837321812?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Research&rft.atitle=Gene-environment+interactions+linking+air+pollution+and+inflammation+in+Parkinson%27s+disease&rft.au=Lee%2C+Pei-Chen%3BRaaschou-Nielsen%2C+Ole%3BLill%2C+Christina+M%3BBertram%2C+Lars%3BSinsheimer%2C+Janet+S%3BHansen%2C+Johnni%3BRitz%2C+Beate&rft.aulast=Lee&rft.aufirst=Pei-Chen&rft.date=2016-11-01&rft.volume=151&rft.issue=&rft.spage=713&rft.isbn=&rft.btitle=&rft.title=Environmental+Research&rft.issn=00139351&rft_id=info:doi/10.1016%2Fj.envres.2016.09.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Statistics; Replication; Tumor necrosis factor; Parkinson's disease; Gene polymorphism; Interleukin 1; Genetic diversity; Traffic; Inflammation; Models; Air pollution; Neurodegenerative diseases; Movement disorders; Regression analysis; Tumor necrosis factor- alpha; Geographic information systems; Population control; Risk factors; DNA; Remote sensing; Tumors; Genotypes DO - http://dx.doi.org/10.1016/j.envres.2016.09.006 ER - TY - JOUR T1 - Health Disparities and the Microbiome AN - 1837316662; PQ0003764019 AB - An individual's microbiome is likely to be an important contributor to certain health disparity diseases and conditions. We present a framework to study the role of the microbiome and the multiple factors that are likely to influence differences in disease predisposition, onset, and progression at the individual and population level. JF - Trends in Microbiology AU - Findley, Keisha AU - Williams, David R AU - Grice, Elizabeth A AU - Bonham, Vence L AD - Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, 31 Center Drive Room B1B37-G, Bethesda, MD 20892, USA Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 847 EP - 850 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 24 IS - 11 SN - 0966-842X, 0966-842X KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - microbiome KW - health disparities KW - interdisciplinary studies KW - environment KW - Reviews KW - Population levels KW - A 01490:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837316662?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Microbiology&rft.atitle=Health+Disparities+and+the+Microbiome&rft.au=Findley%2C+Keisha%3BWilliams%2C+David+R%3BGrice%2C+Elizabeth+A%3BBonham%2C+Vence+L&rft.aulast=Findley&rft.aufirst=Keisha&rft.date=2016-11-01&rft.volume=24&rft.issue=11&rft.spage=847&rft.isbn=&rft.btitle=&rft.title=Trends+in+Microbiology&rft.issn=0966842X&rft_id=info:doi/10.1016%2Fj.tim.2016.08.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Reviews; Population levels DO - http://dx.doi.org/10.1016/j.tim.2016.08.001 ER - TY - JOUR T1 - FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence AN - 1837310053; PQ0003759942 AB - Background A common single nucleotide polymorphism (C385A) in the human fatty acid amide hydrolase (FAAH) gene has been associated with decreased distress responses in healthy volunteers, but its role in psychiatric disorders remains unknown. Here, we obtained genotypes and carried out a secondary analysis of subjects from a trial of comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD). We evaluated the effects of C385A variation on behavioral and biochemical biomarkers of distress responses. Methods Forty-nine patients with PTSD and AD were admitted for 4 weeks to an experimental medicine unit at the National Institutes of Health Clinical Center. Following detoxification, stress reactivity and peripheral endocannabinoid (eCB) levels were assessed in response to a challenge session using personalized auditory guided imagery. Over the course of the study, subjects were also evaluated for changes in PTSD symptom severity. Results FAAH C385A allele carriers showed a marked increase in serum anandamide levels at baseline and throughout the stress challenge procedure compared with C allele homozygotes, while levels of eCBs primarily metabolized through other enzymatic activity, such as 2-arachidonoylglycerol, did not differ between genotype groups. FAAH C385A carriers also had decreased subjective anxiety responses to the stress challenge. Similar effects of FAAH C385A genotype were found at the level of clinical PTSD symptom severity, in particular in the arousal domain. Conclusions This is to our knowledge the first study showing that FAAH C385A variation modulates stress responses in subjects with disorders characterized by increased stress reactivity. These findings point to the eCB pathway as a promising target for future antistress therapeutics. In patients with PTSD and comorbid alcohol dependence, a common single nucleotide polymorphism (C385A) in the fatty acid amide hydrolase (FAAH) gene is associated with a marked increase in serum anandamide levels and with faster decline of the anxiety responses to a stressor. These findings indicate that FAAH 385A variation facilitates habituation to and extinction of chronic stress response, without influencing response to acute stress. This points to the endocannabinoid pathway as a promising target for future antistress therapeutics. JF - Alcoholism: Clinical and Experimental Research AU - Spagnolo, Primavera A AU - Ramchandani, Vijay A AU - Schwandt, Melanie L AU - Kwako, Laura E AU - George, David T AU - Mayo, Leah M AU - Hillard, Cecilia J AU - Heilig, Markus AD - Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 2426 EP - 2434 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 40 IS - 11 SN - 0145-6008, 0145-6008 KW - Toxicology Abstracts KW - Detoxification KW - Anandamide KW - Anxiety KW - Extinction KW - Arousal KW - Stress KW - Drug abuse KW - biomarkers KW - Clinical trials KW - Post-traumatic stress disorder KW - Homozygotes KW - Habituation KW - Fatty-acid amide hydrolase KW - Drug dependence KW - Mental disorders KW - Cannabinoids KW - Single-nucleotide polymorphism KW - Alcoholism KW - 2-Arachidonylglycerol KW - X 24380:Social Poisons & Drug Abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837310053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%3A+Clinical+and+Experimental+Research&rft.atitle=FAAH+Gene+Variation+Moderates+Stress+Response+and+Symptom+Severity+in+Patients+with+Posttraumatic+Stress+Disorder+and+Comorbid+Alcohol+Dependence&rft.au=Spagnolo%2C+Primavera+A%3BRamchandani%2C+Vijay+A%3BSchwandt%2C+Melanie+L%3BKwako%2C+Laura+E%3BGeorge%2C+David+T%3BMayo%2C+Leah+M%3BHillard%2C+Cecilia+J%3BHeilig%2C+Markus&rft.aulast=Spagnolo&rft.aufirst=Primavera&rft.date=2016-11-01&rft.volume=40&rft.issue=11&rft.spage=2426&rft.isbn=&rft.btitle=&rft.title=Alcoholism%3A+Clinical+and+Experimental+Research&rft.issn=01456008&rft_id=info:doi/10.1111%2Facer.13210 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Detoxification; Extinction; Anxiety; Anandamide; Arousal; Stress; Drug abuse; Post-traumatic stress disorder; Clinical trials; biomarkers; Homozygotes; Fatty-acid amide hydrolase; Habituation; Drug dependence; Mental disorders; Cannabinoids; Single-nucleotide polymorphism; Alcoholism; 2-Arachidonylglycerol DO - http://dx.doi.org/10.1111/acer.13210 ER - TY - JOUR T1 - Do coping strategies mediate the effects of emotional support on emotional well-being among Spanish-speaking Latina breast cancer survivors? AN - 1836009687 AB - Objective This study aimed to assess the relationship between emotional social support and emotional well-being among Latina immigrants with breast cancer and test whether two culturally relevant coping strategies, fatalism and acceptance, mediate this relationship. Methods One hundred fifty Spanish-speaking Latinas within 1 year of breast cancer diagnosis participating in a randomized trial of a stress management intervention were assessed in person at baseline and via telephone 6 months later. Survey measures included baseline emotional support, fatalism, and acceptance and emotional well-being 6 months later. Generalized linear models estimated direct effects of emotional support on emotional well-being and indirect effects through fatalism and acceptance. Results Mean age was 50.1 (SD=10.9) years; most women had low education and acculturation levels. Emotional support was negatively associated with fatalism (r=-0.24, p<0.01) and positively associated with acceptance (r=0.30, p<0.001). Emotional support (r=0.23, p=0.005) and acceptance (r=0.28, p=0.001) were positively associated with emotional well-being, whereas fatalism (r=-0.36, p<0.0001) was negatively associated with emotional well-being. In multivariable models, emotional support was associated with emotional well-being (b=0.88, 95% CI: 0.24, 1.52). This direct effect remained significant when additionally controlling for fatalism (b=0.66, 95% CI: 0.03, 1.30) and acceptance (b=0.73, 95% CI: 0.09, 1.37) in separate models. There was a significant indirect effect of emotional support on emotional well-being through fatalism (b=0.21, 95% CI: 0.04, 0.51) as well as a marginally significant effect through acceptance (b=0.15, 95% CI: 0.001, 0.43). Conclusions Emotional support may increase well-being among Spanish-speaking Latina cancer survivors by reducing cancer fatalism.Copyright © 2015 John Wiley & Sons, Ltd. JF - Psycho-Oncology AU - Gonzales, Felisa A AU - Hurtado-de-Mendoza, Alejandra AU - Santoyo-Olsson, Jasmine AU - Napoles, Anna María AD - Cancer Prevention Fellowship Program, Healthcare Delivery Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA ; Department of Oncology, Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA ; Division of General Internal Medicine and the Center for Aging in Diverse Communities, Department of Medicine, University of California San Francisco, San Francisco, CA, USA ; Cancer Prevention Fellowship Program, Healthcare Delivery Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA Y1 - 2016/11// PY - 2016 DA - Nov 2016 SP - 1286 EP - 1292 CY - Chichester PB - Wiley Subscription Services, Inc. VL - 25 IS - 11 SN - 1057-9249 KW - Medical Sciences--Psychiatry And Neurology KW - Women KW - Acceptance KW - Indirect effects KW - Survivors KW - Coping strategies KW - Emotional wellbeing KW - Breast cancer KW - Immigrants KW - Linear models KW - Latin American people KW - Emotional support KW - Acculturation KW - Fatalism KW - Stress management KW - Diagnosis KW - Social support UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836009687?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psycho-Oncology&rft.atitle=Do+coping+strategies+mediate+the+effects+of+emotional+support+on+emotional+well-being+among+Spanish-speaking+Latina+breast+cancer+survivors%3F&rft.au=Gonzales%2C+Felisa+A%3BHurtado-de-Mendoza%2C+Alejandra%3BSantoyo-Olsson%2C+Jasmine%3BNapoles%2C+Anna+Mar%C3%ADa&rft.aulast=Gonzales&rft.aufirst=Felisa&rft.date=2016-11-01&rft.volume=25&rft.issue=11&rft.spage=1286&rft.isbn=&rft.btitle=&rft.title=Psycho-Oncology&rft.issn=10579249&rft_id=info:doi/10.1002%2Fpon.3953 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 John Wiley & Sons, Ltd. N1 - Last updated - 2016-11-04 DO - http://dx.doi.org/10.1002/pon.3953 ER - TY - JOUR T1 - Absolute Measurement of Cardiac Injury-Induced microRNAs in Biofluids across Multiple Test Sites. AN - 1835684828; 27605421 AB - Extracellular microRNAs (miRNAs) represent a promising new source of toxicity biomarkers that are sensitive indicators of site of tissue injury. In order to establish reliable approaches for use in biomarker validation studies, the HESI technical committee on genomics initiated a multi-site study to assess sources of variance associated with quantitating levels of cardiac injury induced miRNAs in biofluids using RT-qPCR. Samples were generated at a central site using a model of acute cardiac injury induced in male Wistar rats by 0.5 mg/kg isoproterenol. Biofluid samples were sent to 11 sites for measurement of 3 cardiac enriched miRNAs (miR-1-3p, miR-208a-3p, and miR-499-5p) and 1 miRNA abundant in blood (miR-16-5p) or urine (miR-192-5p) by absolute quantification using calibration curves of synthetic miRNAs. The samples included serum and plasma prepared from blood collected at 4 h, urine collected from 6 to 24 h, and plasma prepared from blood collected at 24 h post subcutaneous injection. A 3 parameter logistic model was utilized to fit the calibration curve data and estimate levels of miRNAs in biofluid samples by inverse prediction. Most sites observed increased circulating levels of miR-1-3p and miR-208a-3p at 4 and 24 h after isoproterenol treatment, with no difference seen between serum and plasma. The biological differences in miRNA levels and sample type dominated as sources of variance, along with outlying performance by a few sites. The standard protocol established in this study was successfully implemented across multiple sites and provides a benchmark method for further improvements in quantitative assays for circulating miRNAs. Published by Oxford University Press on behalf of the Society of Toxicology 2016. This work is written by US Government employees and is in the public domain in the US. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Thompson, Karol L AU - Boitier, Eric AU - Chen, Tao AU - Couttet, Philippe AU - Ellinger-Ziegelbauer, Heidrun AU - Goetschy, Manuela AU - Guillemain, Gregory AU - Kanki, Masayuki AU - Kelsall, Janet AU - Mariet, Claire AU - de La Moureyre-Spire, Catherine AU - Mouritzen, Peter AU - Nassirpour, Rounak AU - O'Lone, Raegan AU - Pine, P Scott AU - Rosenzweig, Barry A AU - Sharapova, Tatiana AU - Smith, Aaron AU - Uchiyama, Hidefumi AU - Yan, Jian AU - Yuen, Peter S AU - Wolfinger, Russ AD - Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland 20993. ; Sanofi R&D, Disposition Safety and Animal Research, Vitry-Sur-Seine, France. ; Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arizona 72079. ; Novartis Pharma AG, Basel, CH 4057, Switzerland. ; Toxicology, Bayer Pharma, Wuppertal, AG 42096, Germany. ; Astellas Pharma Inc, Osaka 532-8514, Japan. ; AstraZeneca Ltd, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. ; Institut De Recherches Servier, 78290 Croissy Sur Seine, France. ; Exiqon, Vedbaek DK-2950, Denmark. ; Pfizer, Andover, Massachusetts 01810. ; ILSI Health and Environmental Sciences Institute, Washington, DC 20005 Rolone@hesiglobal.org. ; National Institute of Standards and Technology, Stanford, California 94305. ; AbbVie, Abbott Park, Illinois 60064. ; Eli Lilly, Indianapolis, Indiana 46285. ; Takeda Pharmaceutical Co Ltd, Fujisawa, Kanagawa 251-8555, Japan. ; NIH/NIDDK, Bethesda, Maryland 20892. ; SAS Institute Inc, Cary, North Carolina 27513. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 115 EP - 125 VL - 154 IS - 1 KW - biomarker KW - variance KW - microRNA KW - interlaboratory UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835684828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Absolute+Measurement+of+Cardiac+Injury-Induced+microRNAs+in+Biofluids+across+Multiple+Test+Sites.&rft.au=Thompson%2C+Karol+L%3BBoitier%2C+Eric%3BChen%2C+Tao%3BCouttet%2C+Philippe%3BEllinger-Ziegelbauer%2C+Heidrun%3BGoetschy%2C+Manuela%3BGuillemain%2C+Gregory%3BKanki%2C+Masayuki%3BKelsall%2C+Janet%3BMariet%2C+Claire%3Bde+La+Moureyre-Spire%2C+Catherine%3BMouritzen%2C+Peter%3BNassirpour%2C+Rounak%3BO%27Lone%2C+Raegan%3BPine%2C+P+Scott%3BRosenzweig%2C+Barry+A%3BSharapova%2C+Tatiana%3BSmith%2C+Aaron%3BUchiyama%2C+Hidefumi%3BYan%2C+Jian%3BYuen%2C+Peter+S%3BWolfinger%2C+Russ&rft.aulast=Thompson&rft.aufirst=Karol&rft.date=2016-11-01&rft.volume=154&rft.issue=1&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=1096-0929&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Pharmacogenomics and histone deacetylase inhibitors. AN - 1835522797; 27767376 AB - The histone deacetylase inhibitor valproic acid (VPA) has been used for many decades in neurology and psychiatry. The more recent introduction of the histone deacetylase inhibitors (HDIs) belinostat, romidepsin and vorinostat for treatment of hematological malignancies indicates the increasing popularity of these agents. Belinostat, romidepsin and vorinostat are metabolized or transported by polymorphic enzymes or drug transporters. Thus, genotype-directed dosing could improve pharmacotherapy by reducing the risk of toxicities or preventing suboptimal treatment. This review provides an overview of clinical studies on the effects of polymorphisms on the pharmacokinetics, efficacy or toxicities of HDIs including belinostat, romidepsin, vorinostat, panobinostat, VPA and a number of novel compounds currently being tested in Phase I and II trials. Although pharmacogenomic studies for HDIs are scarce, available data indicate that therapy with belinostat (UGT1A1), romidepsin (ABCB1), vorinostat (UGT2B17) or VPA (UGT1A6) could be optimized by upfront genotyping. JF - Pharmacogenomics AU - Goey, Andrew Kl AU - Sissung, Tristan M AU - Peer, Cody J AU - Figg, William D AD - Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1807 EP - 1815 VL - 17 IS - 16 KW - HDAC inhibitors KW - panobinostat KW - valproic acid KW - pharmacogenomics KW - romidepsin KW - vorinostat KW - UGT1A1 KW - belinostat UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835522797?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenomics&rft.atitle=Pharmacogenomics+and+histone+deacetylase+inhibitors.&rft.au=Goey%2C+Andrew+Kl%3BSissung%2C+Tristan+M%3BPeer%2C+Cody+J%3BFigg%2C+William+D&rft.aulast=Goey&rft.aufirst=Andrew&rft.date=2016-11-01&rft.volume=17&rft.issue=16&rft.spage=1807&rft.isbn=&rft.btitle=&rft.title=Pharmacogenomics&rft.issn=1744-8042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Safety Assessment of Liver Injury with Quetiapine Fumarate XR Management in Very Heavy Drinking Alcohol-Dependent Patients. AN - 1835518407; 27503091 AB - Studies have reported liver injury as a consequence of antipsychotic treatment. Very heavy alcohol drinking (ten or more drinks/day for men and eight for women) also causes liver injury. This study aims to evaluate liver injury with quetiapine extended release (XR) in very heavy drinking alcohol-dependent (AD) patients. Two hundred and eighteen AD patients, 18-65 years of age, received 12 weeks of quetiapine XR or placebo treatment in a dose-escalated manner reaching the full dose of 400 mg/day during week 4. Blood chemistry and hematology were assessed at baseline (W0), post-titration at the end of week 3 (W4), week 8 (W8), and end of week 12 (W13). Patients were further grouped as GR.1 (no liver injury, ALT ≤40) and GR.2 (pre-existing liver injury, ALT >40) within each treatment. Drinking history, fasting blood glucose concentration (FBG), and lipid panel were used as covariates in the analyses. Liver injury and total drinks and average drinking measures from the Timeline follow-back questionnaire (TLFB) were highly associated. No significant exacerbation in liver injury was observed in patients treated with quetiapine XR in GR.2. Liver injury as determined by elevated alanine aminotransaminase (ALT) was reported in a few patients in GR.1 who received quetiapine XR; however, the occurrence was low, and the level of liver injury was not significant. FBG and lipid measures showed some elevation, but did not show any significant association with liver injury. Quetiapine XR did not show any significant exacerbation of liver injury in very heavy drinking alcohol-dependent patients with pre-existing liver injury. Frequency and severity of new liver injury cases in quetiapine XR-treated patients without any pre-existing liver injury was also low. Study findings support medical management of AD patients with heavy drinking profile using quetiapine XR formulation. JF - Clinical drug investigation AU - Vatsalya, Vatsalya AU - Pandey, Akash AU - Schwandt, Melanie L AU - Cave, Matthew C AU - Barve, Shirish S AU - Ramchandani, Vijay A AU - McClain, Craig J AD - Department of Medicine, University of Louisville School of Medicine, 505 S. Hancock St., CTR Room 521A, Louisville, KY, 40202, USA. v0vats01@exchange.louisville.edu. ; Department of Pediatric Gastroenterology, Maria Fareri Children's Hospital - Westchester Medical Center, Valhalla, NY, USA. ; Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. ; Department of Medicine, University of Louisville School of Medicine, 505 S. Hancock St., CTR Room 521A, Louisville, KY, 40202, USA. ; Laboratory of Clinical and Translational Studies, Section on Human Psychopharmacology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 935 EP - 944 VL - 36 IS - 11 KW - Antipsychotic Agents KW - 0 KW - Delayed-Action Preparations KW - Quetiapine Fumarate KW - 2S3PL1B6UJ KW - Index Medicus KW - Young Adult KW - Double-Blind Method KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Alcohol Drinking -- adverse effects KW - Aged KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Quetiapine Fumarate -- adverse effects KW - Chemical and Drug Induced Liver Injury -- etiology KW - Antipsychotic Agents -- adverse effects KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835518407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+drug+investigation&rft.atitle=Safety+Assessment+of+Liver+Injury+with+Quetiapine+Fumarate+XR+Management+in+Very+Heavy+Drinking+Alcohol-Dependent+Patients.&rft.au=Vatsalya%2C+Vatsalya%3BPandey%2C+Akash%3BSchwandt%2C+Melanie+L%3BCave%2C+Matthew+C%3BBarve%2C+Shirish+S%3BRamchandani%2C+Vijay+A%3BMcClain%2C+Craig+J&rft.aulast=Vatsalya&rft.aufirst=Vatsalya&rft.date=2016-11-01&rft.volume=36&rft.issue=11&rft.spage=935&rft.isbn=&rft.btitle=&rft.title=Clinical+drug+investigation&rft.issn=1179-1918&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-02 N1 - Date created - 2016-08-09 N1 - Date revised - 2017-01-30 N1 - Last updated - 2017-01-30 ER - TY - JOUR T1 - Adjuvant chemotherapy does not improve disease-free survival in FIGO stage IC ovarian granulosa cell tumors: The MITO-9 study. AN - 1835516319; 27597380 AB - Evidence-based management of granulosa cell tumors of the ovary (GCT) has been not yet standardized: surgery, including fertility-sparing procedures for young women, has been traditionally the standard treatment; on the other hand, chemotherapy has been used for treatment of advanced and/or recurrent disease. However, very limited experience, has been selectively focused on the role of adjuvant chemotherapy in stage IC patients. The objective of this retrospective study was to assess the efficacy of first line postoperative chemotherapy in patients with stage IC treated at the Italian Centers involved in the MITO (Multicenter Italian Trials in Ovarian cancer) Group. A retrospective multi-institutional review of patients with GCT of the ovary at FIGO stage IC treated or referred to MITO centers was conducted. Surgical outcome, pathological findings and follow-up data were analysed. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors factors for disease free survival. A total of 40 patients with primary GCT of the ovary at FIGO stage IC were identified. The median follow-up period was 96months (range 7-300). At multivariate analysis, surgical treatment outside MITO centers and incomplete surgical staging were independent poor prognostic indicators for recurrence; adjuvant chemotherapy did not retain significant predictive value for recurrence. This study raises the question about the value of adjuvant chemotherapy in stage IC GCT: a comprehensive evaluation of a larger series is urgently needed in order to characterize stage IC substages who can be spared treatment toxicity. Copyright © 2016. Published by Elsevier Inc. JF - Gynecologic oncology AU - Mangili, G AU - Ottolina, J AU - Cormio, G AU - Loizzi, Vera AU - De Iaco, P AU - Pellegrini, D A AU - Candiani, M AU - Giorda, G AU - Scarfone, G AU - Cecere, S C AU - Frigerio, L AU - Gadducci, A AU - Marchetti, C AU - Ferrandina, G AD - Gynecology Department, San Raffaele Scientific Institute, Milan, Italy. Electronic address: mangili.giorgia@hsr.it. ; Gynecology Department, San Raffaele Scientific Institute, Milan, Italy. ; Department of Obstetrics and Gynecology, University of Bari, Bari, Italy. ; Department of Gynecologic Oncology, S. Orsola-Malpighi University Hospital, Bologna, Italy. ; Medical Oncology Division, National Cancer Institute Regina Elena, Rome, Italy. ; Gynecologic Oncology Department, Centro di riferimento Oncologico (CRO) National Cancer Institute, Aviano, Italy. ; Obstetrics and Gynecology Department, IRCCS Foundation Policlinico Mangiagalli Regina Elena Hospital, Milan, Italy. ; Uro-Gynecological Oncology, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy. ; Gynecology Department, Riuniti di Bergamo Hospital, Bergamo, Italy. ; Division of Gynecology and Obstetrics, Department of Clinical and Experimental Medicine, Pisa University, Pisa, Italy. ; Department of Gynecology, Obstetrics and Urology, Umberto I, "Sapienza" University of Rome, Rome, Italy. ; Department of Health Sciences and Medicine, University of Molise, Campobasso/Gynecologic Oncology Unit, Policlinico Universitario "Agostino Gemelli", Rome, Italy. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 276 EP - 280 VL - 143 IS - 2 KW - Granulosa cell tumors of the ovary KW - Stage IC KW - Relapse KW - Adjuvant chemotherapy KW - Prognostic factors KW - MITO UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835516319?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=Adjuvant+chemotherapy+does+not+improve+disease-free+survival+in+FIGO+stage+IC+ovarian+granulosa+cell+tumors%3A+The+MITO-9+study.&rft.au=Mangili%2C+G%3BOttolina%2C+J%3BCormio%2C+G%3BLoizzi%2C+Vera%3BDe+Iaco%2C+P%3BPellegrini%2C+D+A%3BCandiani%2C+M%3BGiorda%2C+G%3BScarfone%2C+G%3BCecere%2C+S+C%3BFrigerio%2C+L%3BGadducci%2C+A%3BMarchetti%2C+C%3BFerrandina%2C+G&rft.aulast=Mangili&rft.aufirst=G&rft.date=2016-11-01&rft.volume=143&rft.issue=2&rft.spage=276&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=1095-6859&rft_id=info:doi/10.1016%2Fj.ygyno.2016.08.316 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-06 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ygyno.2016.08.316 ER - TY - JOUR T1 - A phase I study of recombinant (r) vaccinia-CEA(6D)-TRICOM and rFowlpox-CEA(6D)-TRICOM vaccines with GM-CSF and IFN-α-2b in patients with CEA-expressing carcinomas. AN - 1835488633; 27581603 AB - Prime-boost vaccination with recombinant (r) vaccinia(V)-CEA(6D)-TRICOM (triad of co-stimulatory molecules B7.1, ICAM-1 and LFA-3) and rFowlpox(F)-CEA(6D)-TRICOM infect antigen-presenting cells and direct expression of co-stimulatory molecules. We hypothesized that co-administration of vaccine with GM-CSF and interferon alpha (IFN-α) would have efficacy in CEA-expressing cancers. Patients with CEA-expressing cancers received the rV-CEA(6D)-TRICOM vaccine subcutaneously (s.c.) on day 1 followed by GM-CSF s.c. to the injection site on days 1-4. In Cycle 1, patients received thrice weekly s.c. injections of IFN-α-2b the week after rV-CEA(6D)-TRICOM. In Cycles 2-4, patients received thrice weekly s.c. injections of IFN-α-2b the same week that rF-CEA(6D)-TRICOM was given. The first cohort received no IFN followed by dose escalation of IFN-α in subsequent cohorts. Thirty-three patients were accrued (mean 59.8 years). Grade 3 toxicities included fatigue and hyperglycemia. Grade 4-5 adverse events (unrelated to treatment) were confusion (1), elevated aspartate transaminase (AST)/alanine transaminase (ALT) (1), and sudden death (1). No patients had a partial response, and eight patients exhibited stable disease of ≥3 months. Median progression-free survival and overall survival (OS) were 1.8 and 6.3 months, respectively. Significantly higher serum CD27 levels were observed after vaccine therapy (p = 0.006 post 1-2 cycles, p = 0.003 post 3 cycles, p = 0.03 post 4-7 cycles) and 42 % of patients assayed developed CEA-specific T cell responses. Pre-treatment levels of myeloid-derived suppressor cells correlated with overall survival (p = 0.04). Administration of IFN-α led to significantly increased OS (p = 0.02) compared to vaccine alone. While the vaccine regimen produced no clinical responses, IFN-α administration was associated with improved survival. JF - Cancer immunology, immunotherapy : CII AU - Duggan, Megan C AU - Jochems, Caroline AU - Donahue, Renee N AU - Richards, Jacob AU - Karpa, Volodymyr AU - Foust, Elizabeth AU - Paul, Bonnie AU - Brooks, Taylor AU - Tridandapani, Susheela AU - Olencki, Thomas AU - Pan, Xueliang AU - Lesinski, Gregory B AU - Schlom, Jeffrey AU - Carson Iii, William E AD - Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA. ; National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, MD, USA. ; Division of Medical Oncology, The Ohio State University, Columbus, OH, USA. ; Center for Biostatistics, The Ohio State University, Columbus, OH, USA. ; Division of Surgical Oncology, The Ohio State University, N924 Doan Hall, 410 W. 10th Avenue, Columbus, OH, 43210, USA. william.carson@osumc.edu. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1353 EP - 1364 VL - 65 IS - 11 KW - Immunotherapy KW - Colorectal cancer KW - Vaccines KW - Interferon alpha-2b KW - Carcinoembryonic antigen (CEA) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835488633?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+immunology%2C+immunotherapy+%3A+CII&rft.atitle=A+phase+I+study+of+recombinant+%28r%29+vaccinia-CEA%286D%29-TRICOM+and+rFowlpox-CEA%286D%29-TRICOM+vaccines+with+GM-CSF+and+IFN-%CE%B1-2b+in+patients+with+CEA-expressing+carcinomas.&rft.au=Duggan%2C+Megan+C%3BJochems%2C+Caroline%3BDonahue%2C+Renee+N%3BRichards%2C+Jacob%3BKarpa%2C+Volodymyr%3BFoust%2C+Elizabeth%3BPaul%2C+Bonnie%3BBrooks%2C+Taylor%3BTridandapani%2C+Susheela%3BOlencki%2C+Thomas%3BPan%2C+Xueliang%3BLesinski%2C+Gregory+B%3BSchlom%2C+Jeffrey%3BCarson+Iii%2C+William+E&rft.aulast=Duggan&rft.aufirst=Megan&rft.date=2016-11-01&rft.volume=65&rft.issue=11&rft.spage=1353&rft.isbn=&rft.btitle=&rft.title=Cancer+immunology%2C+immunotherapy+%3A+CII&rft.issn=1432-0851&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Partnerships to Design Novel Regimens to Treat Childhood Tuberculosis, Sui Generis: The Road Ahead. AN - 1835414538; 27742642 AB - There has been a recent expansion of preclinical models to predict the efficacy of regimens to treat adults with tuberculosis. Despite increasing global interest in childhood tuberculosis, these same tools have not been employed to develop pediatric regimens. Children differ from adults in bacillary burden, spectrum of disease, the metabolism and distribution of antituberculosis drugs, and the toxicity experienced. The studies documented in this series describe a proof-of-concept approach to pediatric regimen development. We propose a program of investigation that would take this forward into a systematic and comprehensive method to find optimal drug combinations to use in children, ideal exposures, and required dosing. Although the number of possible drug combinations is extensive, a series of principles could be employed to select likely effective regimens. Regimens should avoid drugs with overlapping toxicity or linked mechanisms of resistance and should aim to include drugs with different mechanisms of action and ones that are able to target different subpopulations of mycobacteria. Finally drugs should penetrate into body sites necessary for treating pediatric disease. At an early stage, this body of work would need to engage with regulatory agencies and bodies that formulate guidelines, so that once regimens and dosages are identified, translation into clinical studies and clinical practice can be rapid. The development of child-friendly drug formulations would need to be carried out in parallel so that pharmacokinetic studies can be undertaken as formulations are created. Significant research and development would be required and a wide range of stakeholders would need to be engaged. The time is right to consider a more thoughtful and systematic approach toward identifying, testing, and comparing combinations of drugs for children with tuberculosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Gumbo, Tawanda AU - Makhene, Mamodikoe K AU - Seddon, James A AD - Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas Department of Medicine, University of Cape Town, Observatory, South Africa. ; Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. ; Centre for International Child Health, Department of Paediatrics, Imperial College London, United Kingdom. Y1 - 2016/11/01/ PY - 2016 DA - 2016 Nov 01 SP - S110 EP - S115 VL - 63 KW - tuberculosis KW - PK/PD KW - future KW - children KW - investment KW - hollow fiber UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835414538?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Partnerships+to+Design+Novel+Regimens+to+Treat+Childhood+Tuberculosis%2C+Sui+Generis%3A+The+Road+Ahead.&rft.au=Gumbo%2C+Tawanda%3BMakhene%2C+Mamodikoe+K%3BSeddon%2C+James+A&rft.aulast=Gumbo&rft.aufirst=Tawanda&rft.date=2016-11-01&rft.volume=63&rft.issue=&rft.spage=S110&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=1537-6591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - The antiandrogen flutamide is a novel aryl hydrocarbon receptor ligand that disrupts bile acid homeostasis in mice through induction of Abcc4. AN - 1835391648; 27569425 AB - Flutamide (FLU), an oral, nonsteroidal antiandrogen drug used in the treatment of prostate cancer, is associated with idiosyncratic hepatotoxicity that sometimes causes severe liver damage, including cholestasis, jaundice, and liver necrosis. To understand the mechanism of toxicity, a combination of aryl hydrocarbon receptor (Ahr)-deficient (Ahr-/-) mice, primary hepatocytes, luciferase reporter gene assays, in silico ligand docking and ultra-performance chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics was used. A significant increase of liver weights, and liver and serum bile acid levels was observed after FLU treatment, indicating hepatomegaly and disrupted bile acid homeostasis. Expression of the AhR gene battery was markedly increased in livers of wild-type mice Ahr+/+ treated with FLU, while no change was noted in Ahr-/- mice. Messenger RNAs encoded by AhR target genes were induced in primary mouse hepatocytes cultured with FLU, which confirmed the in vivo results. Ligand-docking analysis further predicted that FLU is an AhR agonist ligand which was confirmed by luciferase reporter gene assays. Multivariate data analysis showed that bile acids were responsible for the separation of vehicle- and FLU-treated Ahr+/+ mice, while there was no separation in Ahr-/- mice. Expression of mRNA encoding the bile acid transporter ABCC4 was increased and farnesoid X receptor signaling was inhibited in the livers of Ahr+/+ mice, but not in Ahr-/- mice treated with FLU, in agreement with the observed downstream metabolic alterations. These findings provide new insights into the mechanism of liver injury caused by FLU treatment involving activation of AhR and the alterations of bile acid homeostasis, which could guide clinical application. Published by Elsevier Inc. JF - Biochemical pharmacology AU - Gao, Xiaoxia AU - Xie, Cen AU - Wang, Yuanyuan AU - Luo, Yuhong AU - Yagai, Tomoki AU - Sun, Dongxue AU - Qin, Xuemei AU - Krausz, Kristopher W AU - Gonzalez, Frank J AD - Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, Shanxi 030006, China; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: gaoxiaoxia@sxu.edu.cn. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: cen.xie@nih.gov. ; Bioscience Research Department, 875 Union Ave, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: ywang197@uthsc.edu. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: yuhong.luo@nih.gov. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: tomoki.yagai@nih.gov. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; College of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China. Electronic address: dongxue.sun@nih.gov. ; Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, Shanxi 030006, China. Electronic address: qinxm@sxu.edu.cn. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: krauszk@intra.nci.nih.gov. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: gonzalef@mail.nih.gov. Y1 - 2016/11/01/ PY - 2016 DA - 2016 Nov 01 SP - 93 EP - 104 VL - 119 KW - Bile acid homeostasis KW - Aryl hydrocarbon receptor KW - ABCC4 KW - Flutamide KW - Metabolomics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835391648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=The+antiandrogen+flutamide+is+a+novel+aryl+hydrocarbon+receptor+ligand+that+disrupts+bile+acid+homeostasis+in+mice+through+induction+of+Abcc4.&rft.au=Gao%2C+Xiaoxia%3BXie%2C+Cen%3BWang%2C+Yuanyuan%3BLuo%2C+Yuhong%3BYagai%2C+Tomoki%3BSun%2C+Dongxue%3BQin%2C+Xuemei%3BKrausz%2C+Kristopher+W%3BGonzalez%2C+Frank+J&rft.aulast=Gao&rft.aufirst=Xiaoxia&rft.date=2016-11-01&rft.volume=119&rft.issue=&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=1873-2968&rft_id=info:doi/10.1016%2Fj.bcp.2016.08.021 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.bcp.2016.08.021 ER - TY - JOUR T1 - Sex-related differential susceptibility to doxorubicin-induced cardiotoxicity in B6C3F1 mice. AN - 1835384955; 27644598 AB - Sex is a risk factor for development of cardiotoxicity, induced by the anti-cancer drug, doxorubicin (DOX), in humans. To explore potential mechanisms underlying differential susceptibility to DOX between sexes, 8-week old male and female B6C3F1 mice were dosed with 3mg/kg body weight DOX or an equivalent volume of saline via tail vein once a week for 6, 7, 8, and 9 consecutive weeks, resulting in 18, 21, 24, and 27mg/kg cumulative DOX doses, respectively. At necropsy, one week after each consecutive final dose, the extent of myocardial injury was greater in male mice compared to females as indicated by higher plasma concentrations of cardiac troponin T at all cumulative DOX doses with statistically significant differences between sexes at the 21 and 24mg/kg cumulative doses. A greater susceptibility to DOX in male mice was further confirmed by the presence of cytoplasmic vacuolization in cardiomyocytes, with left atrium being more vulnerable to DOX cardiotoxicity. The number of TUNEL-positive cardiomyocytes was mostly higher in DOX-treated male mice compared to female counterparts, showing a statistically significant sex-related difference only in left atrium at 21mg/kg cumulative dose. DOX-treated male mice also had an increased number of γ-H2A.X-positive (measure of DNA double-strand breaks) cardiomyocytes compared to female counterparts with a significant sex effect in the ventricle at 27mg/kg cumulative dose and right atrium at 21 and 27mg/kg cumulative doses. This newly established mouse model provides a means to identify biomarkers and access potential mechanisms underlying sex-related differences in DOX-induced cardiotoxicity. Published by Elsevier Inc. JF - Toxicology and applied pharmacology AU - Jenkins, G Ronald AU - Lee, Taewon AU - Moland, Carrie L AU - Vijay, Vikrant AU - Herman, Eugene H AU - Lewis, Sherry M AU - Davis, Kelly J AU - Muskhelishvili, Levan AU - Kerr, Susan AU - Fuscoe, James C AU - Desai, Varsha G AD - Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States. ; Department of Mathematics, Korea University, Sejong, Republic of Korea. ; Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, The National Cancer Institute, Rockville, MD 20850-9734, United States. ; Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States. ; Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079, United States. ; Arkansas Heart Hospital, Little Rock, AR 72211, United States. ; Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States. Electronic address: varsha.desai@fda.hhs.gov. Y1 - 2016/11/01/ PY - 2016 DA - 2016 Nov 01 SP - 159 EP - 174 VL - 310 KW - DNA damage KW - Apoptosis KW - Mouse model KW - Sex-based differences KW - Cardiotoxicity KW - Doxorubicin UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835384955?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+research&rft.atitle=Sources+of+polycyclic+aromatic+hydrocarbons+are+associated+with+gene-specific+promoter+methylation+in+women+with+breast+cancer.&rft.au=White%2C+Alexandra+J%3BChen%2C+Jia%3BTeitelbaum%2C+Susan+L%3BMcCullough%2C+Lauren+E%3BXu%2C+Xinran%3BHee+Cho%2C+Yoon%3BConway%2C+Kathleen%3BBeyea%2C+Jan%3BStellman%2C+Steven+D%3BSteck%2C+Susan+E%3BMordukhovich%2C+Irina%3BEng%2C+Sybil+M%3BBeth+Terry%2C+Mary%3BEngel%2C+Lawrence+S%3BHatch%2C+Maureen%3BNeugut%2C+Alfred+I%3BHibshoosh%2C+Hanina%3BSantella%2C+Regina+M%3BGammon%2C+Marilie+D&rft.aulast=White&rft.aufirst=Alexandra&rft.date=2016-02-01&rft.volume=145&rft.issue=&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Environmental+research&rft.issn=1096-0953&rft_id=info:doi/10.1016%2Fj.envres.2015.11.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.taap.2016.09.012 ER - TY - JOUR T1 - Response to "Comment on 'Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures'". AN - 1834999165; 27801650 JF - Environmental health perspectives AU - Parks, Christine G AU - Hoppin, Jane A AU - De Roos, Anneclaire J AU - Costenbader, Karen H AU - Sandler, Dale P AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2016/11/01/ PY - 2016 DA - 2016 Nov 01 SP - 1 VL - 124 IS - 11 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1834999165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Response+to+%22Comment+on+%27Rheumatoid+Arthritis+in+Agricultural+Health+Study+Spouses%3A+Associations+with+Pesticides+and+Other+Farm+Exposures%27%22.&rft.au=Parks%2C+Christine+G%3BHoppin%2C+Jane+A%3BDe+Roos%2C+Anneclaire+J%3BCostenbader%2C+Karen+H%3BSandler%2C+Dale+P&rft.aulast=Parks&rft.aufirst=Christine&rft.date=2016-11-01&rft.volume=124&rft.issue=11&rft.spage=A197&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Attention bias modification for youth with social anxiety disorder AN - 1834802574 AB - Background Attention bias modification treatment (ABMT) targets threat-related attention biases in anxiety disorders. Most clinical trials of ABMT have focused on adults or small samples of youth. The current randomized controlled trial (RCT) examines ABMT efficacy in youth with social anxiety disorder (SAD) and tests possible moderators of treatment outcomes. Method Sixty-seven youth with SAD were randomly assigned to ABMT or attention control training (ACT) conditions. Anxiety severity was measured at baseline, posttreatment, and 3-month follow-up. ClinicalTrials.gov name and identifier: Attention bias modification treatment for children with social anxiety, NCT01397032; http://www.clinicaltrials.gov. Results Both ABMT and ACT induced significant reductions in clinician and self-rated social anxiety (ps < .001). An additional reduction was observed at the 3-month follow-up in clinician-rated anxiety symptoms (p = .03). Moderation effects were nonsignificant for the clinician-rated anxiety outcome, but age moderated self-reported anxiety. Older but not younger children, showed significant reduction in anxiety following ABMT relative to ACT (p < .001). Individual differences in attention control also moderated ABMT's effect on self-reported anxiety (p = .05). Children rated by their parents as lower on attention control benefited more from ABMT than those rated higher on attention control. Baseline attention bias did not moderate anxiety (p = .17). Conclusions Despite significant reductions in social anxiety, no specific evidence for ABMT was found relative to a control condition. Age and attention control moderated ABMT effects on self-reported SAD symptoms, with clinical effects for older relative to younger children and for those with lower attention control. These results highlight the need to consider developmental influences in the implementation of ABMT protocols. JF - Journal of Child Psychology and Psychiatry AU - Pergamin-Hight, Lee AU - Pine, Daniel S AU - Fox, Nathan A AU - Bar-Haim, Yair AD - School of Psychological Sciences, Tel-Aviv University, Tel-Aviv, Israel ; The Emotion and Development Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA ; The Department of Human Development and Quantitative Methodology, University of Maryland, College Park, MD, USA ; School of Psychological Sciences, Tel-Aviv University, Tel-Aviv, Israel; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel ; School of Psychological Sciences, Tel-Aviv University, Tel-Aviv, Israel Y1 - 2016/11// PY - 2016 DA - Nov 2016 SP - 1317 EP - 1325 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 11 KW - Psychology KW - Modification KW - Moderation KW - Clinical trials KW - Older children KW - Clinical research KW - Efficacy KW - Severity KW - Moderators KW - Clinical outcomes KW - Randomized controlled trials KW - Selfassessment KW - Young people KW - Attentional bias KW - Individual differences KW - Social anxiety KW - Children UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1834802574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Attention+bias+modification+for+youth+with+social+anxiety+disorder&rft.au=Pergamin-Hight%2C+Lee%3BPine%2C+Daniel+S%3BFox%2C+Nathan+A%3BBar-Haim%2C+Yair&rft.aulast=Pergamin-Hight&rft.aufirst=Lee&rft.date=2016-11-01&rft.volume=57&rft.issue=11&rft.spage=1317&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12599 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2016-11-02 DO - http://dx.doi.org/10.1111/jcpp.12599 ER - TY - JOUR T1 - Attentional bias training in girls at risk for depression AN - 1834802416 AB - Background This study examined, for the first time, whether attentional biases can be modified in adolescents at risk for depression. Methods The final sample consisted of 41 girls at familial risk for depression, who were randomly assigned to receive six sessions (864 trials) of real or sham attention bias training [Real attentional bias training (ABT) vs. Sham ABT]. Participants who received Real ABT completed a modified dot-probe task designed to train attention toward positive and away from negative facial expressions; in contrast, girls who received Sham ABT completed the standard dot-probe task. Attentional biases, self-reported mood, and psychophysiological responses to stress were measured at pre- and post-training assessments. Results As expected, girls who received Real ABT, but not those who received Sham ABT, exhibited significant increases from pre- to post-training in their attention toward happy faces and away from sad faces. Moreover, adolescents who received Real ABT were buffered against the negative outcomes experienced by adolescents who received Sham ABT. Specifically, only adolescents who received Sham ABT experienced an increase in negative mood and a pre- to post-training increase in heart rate in anticipation of the stressor. Conclusions The current findings provide the first experimental evidence that attentional biases can be modified in youth at risk for depression and further suggest that ABT modulates the heightened response to stress that is otherwise experienced by high-risk adolescents. JF - Journal of Child Psychology and Psychiatry AU - LeMoult, Joelle AU - Joormann, Jutta AU - Kircanski, Katharina AU - Gotlib, Ian H AD - Department of Psychology, Stanford University, California, CA, USA ; Department of Psychology, Yale University, New Haven, CT, USA ; Department of Health and Human Services, Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA ; Department of Psychology, Stanford University, California, CA, USA Y1 - 2016/11// PY - 2016 DA - Nov 2016 SP - 1326 EP - 1333 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 11 KW - Psychology KW - Bias KW - Teenagers KW - Heart rate KW - High risk KW - Psychophysiological aspects KW - Attentional bias KW - At risk KW - Facial expressions KW - Familial factors KW - Depression KW - First time KW - Adolescents KW - Girls UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1834802416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Attentional+bias+training+in+girls+at+risk+for+depression&rft.au=LeMoult%2C+Joelle%3BJoormann%2C+Jutta%3BKircanski%2C+Katharina%3BGotlib%2C+Ian+H&rft.aulast=LeMoult&rft.aufirst=Joelle&rft.date=2016-11-01&rft.volume=57&rft.issue=11&rft.spage=1326&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12587 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1111/jcpp.12587 ER - TY - JOUR T1 - Genome-scale RNA interference screen identifies antizyme 1 (OAZ1) as a target for improvement of recombinant protein production in mammalian cells AN - 1827933714; PQ0003703761 AB - For the purpose of improving recombinant protein production from mammalian cells, an unbiased, high-throughput whole-genome RNA interference screen was conducted using human embryonic kidney 293 (HEK 293) cells expressing firefly luciferase. A 21,585 human genes were individually silenced with three different siRNAs for each gene. The screen identified 56 genes that led to the greatest improvement in luciferase expression. These genes were found to be included in several pathways involved in spliceosome formation and mRNA processing, transcription, metabolic processes, transport, and protein folding. The 10 genes that most enhanced protein expression when downregulated, were further confirmed by measuring the effect of their silencing on the expression of three additional recombinant proteins. Among the confirmed genes, OAZ1-the gene encoding the ornithine decarboxylase antizyme1-was selected for detailed investigation, since its silencing improved the reporter protein production without affecting cell viability. Silencing OAZ1 caused an increase of the ornithine decarboxylase enzyme and the cellular levels of putrescine and spermidine; an indication that increased cellular polyamines enhances luciferase expression without affecting its transcription. The study shows that OAZ1 is a novel target for improving expression of recombinant proteins. The genome-scale screening performed in this work can establish the foundation for targeted design of an efficient mammalian cell platform for various biotechnological applications. Biotechnol. Bioeng. 2016; 113: 2403-2415. Improving recombinant protein production from mammalian cells for research and therapeutic purposes is of major interest. For identifying unknown genes and pathways useful for improving protein expression, the effect of non-coding RNA, both miRNA and siRNA, on recombinant protein expression in 293HEK cells was investigated by applying large scale screening of miRNA and siRNA. Screening of 21,585 genes led to the selection of OAZ1, a gene that encodes ornithine decarboxylase antizyme, as a potential target since its silencing enhanced recombinant protein expression without affecting cell viability. Further studies revealed that silencing OAZ1was associated with increased concentration of polyamines. JF - Biotechnology and Bioengineering AU - Xiao, Su AU - Chen, Yu Chi AU - Buehler, Eugen AU - Mandal, Swati AU - Mandal, Ajeet AU - Betenbaugh, Michael AU - Park, Myung Hee AU - Martin, Scott AU - Shiloach, Joseph AD - Biotechnology Core Laboratory NIDDK, NIH, Bethesda, Maryland, 20892. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 2403 EP - 2415 PB - Wiley Subscription Services VL -