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Jeffrey Gordon

Franz L Ricklefs, Quazim Alayo, Harald Krenzlin, Ahmad B Mahmoud, Maria C Speranza, Hiroshi Nakashima, Josie L Hayes, Kyungheon Lee, Leonora Balaj, Carmela Passaro, Arun K Rooj, Susanne Krasemann, Bob S Carter, Clark C Chen, Tyler Steed, Jeffrey Treiber, Scott Rodig, Katherine Yang, Ichiro Nakano, Hakho Lee, Ralph Weissleder, Xandra O Breakefield, Jakub Godlewski, Manfred Westphal, Katrin Lamszus, Gordon J Freeman, Agnieszka Bronisz, Sean E Lawler, E Antonio Chiocca
Binding of programmed death ligand-1 (PD-L1) to programmed cell death protein-1 (PD1) leads to cancer immune evasion via inhibition of T cell function. One of the defining characteristics of glioblastoma, a universally fatal brain cancer, is its profound local and systemic immunosuppression. Glioblastoma has also been shown to generate extracellular vesicles (EVs), which may play an important role in tumor progression. We thus hypothesized that glioblastoma EVs may be important mediators of immunosuppression and that PD-L1 could play a role...
March 2018: Science Advances
Jie An, Liping Wang, Michael L Patnode, Vanessa K Ridaura, Jonathan M Haldeman, Robert D Stevens, Olga Ilkayeva, James R Bain, Michael J Muehlbauer, Erin L Glynn, Steven Thomas, Deborah Muoio, Scott A Summers, James E Vath, Thomas E Hughes, Jeffrey I Gordon, Christopher B Newgard
Current obesity interventions suffer from lack of durable effects and undesirable complications. Fumagillin, an inhibitor of methionine aminopeptidase-2, causes weight loss by reducing food intake, but with effects on weight that are superior to pair-feeding. Here, we show that feeding of rats on a high-fat diet supplemented with fumagillin (HF/FG) suppresses the aggressive feeding observed in pair-fed controls (HF/PF) and alters expression of circadian genes relative to the HF/PF group. Multiple indices of reduced energy expenditure are observed in HF/FG but not HF/PF rats...
March 8, 2018: JCI Insight
Jon S Patricios, Clare L Ardern, Michael David Hislop, Mark Aubry, Paul Bloomfield, Carolyn Broderick, Patrick Clifton, Ruben J Echemendia, Richard G Ellenbogen, Éanna Cian Falvey, Gordon Ward Fuller, Julie Grand, Dallas Hack, Peter Rex Harcourt, David Hughes, Nathan McGuirk, Willem Meeuwisse, Jeffrey Miller, John T Parsons, Simona Richiger, Allen Sills, Kevin B Moran, Jenny Shute, Martin Raftery
The 2017 Berlin Concussion in Sport Group Consensus Statement provides a global summary of best practice in concussion prevention, diagnosis and management, underpinned by systematic reviews and expert consensus. Due to their different settings and rules, individual sports need to adapt concussion guidelines according to their specific regulatory environment. At the same time, consistent application of the Berlin Consensus Statement's themes across sporting codes is likely to facilitate superior and uniform diagnosis and management, improve concussion education and highlight collaborative research opportunities...
March 2, 2018: British Journal of Sports Medicine
Marcel Tongo, Gordon W Harkins, Jeffrey R Dorfman, Erik Billings, Sodsai Tovanabutra, Tulio de Oliveira, Darren P Martin
Subtype A is one of the rare HIV-1 group M (HIV-1M) lineages that is both widely distributed throughout the world and persists at high frequencies in the Congo Basin (CB), the site where HIV-1M likely originated. This, together with its high degree of diversity suggests that subtype A is amongst the fittest HIV-1M lineages. Here we use a comprehensive set of published near full-length subtype A sequences and A-derived genome fragments from both circulating and unique recombinant forms (CRFs/URFs) to obtain some insights into how frequently these lineages have independently seeded HIV-1M sub-epidemics in different parts of the world...
January 2018: Virus Evolution
Jeffrey R Whiteaker, Lei Zhao, Rick Saul, Jan A Kaczmarczyk, Regine M Schoenherr, Heather D Moore, Corey Jones-Weinert, Richard G Ivey, Chenwei Lin, Tara Hiltke, Kerryn W Reding, Gordon Whiteley, Pei Wang, Amanda G Paulovich
A lack of analytically robust and multiplexed assays has hampered studies of the large, branched phosphosignaling network responsive to DNA damage. To address this need, we developed and fully analytically characterized a 62-plex assay quantifying protein expression and post-translational modification (phosphorylation and ubiquitination) after induction of DNA damage. The linear range was over 3 orders of magnitude, the median inter-assay variability was 10% CV and the vast majority (∼85%) of assays were stable after extended storage...
February 23, 2018: Radiation Research
Gilles Dutilh, Jeffrey Annis, Scott D Brown, Peter Cassey, Nathan J Evans, Raoul P P P Grasman, Guy E Hawkins, Andrew Heathcote, William R Holmes, Angelos-Miltiadis Krypotos, Colin N Kupitz, Fábio P Leite, Veronika Lerche, Yi-Shin Lin, Gordon D Logan, Thomas J Palmeri, Jeffrey J Starns, Jennifer S Trueblood, Leendert van Maanen, Don van Ravenzwaaij, Joachim Vandekerckhove, Ingmar Visser, Andreas Voss, Corey N White, Thomas V Wiecki, Jörg Rieskamp, Chris Donkin
Most data analyses rely on models. To complement statistical models, psychologists have developed cognitive models, which translate observed variables into psychologically interesting constructs. Response time models, in particular, assume that response time and accuracy are the observed expression of latent variables including 1) ease of processing, 2) response caution, 3) response bias, and 4) non-decision time. Inferences about these psychological factors hinge upon the validity of the models' parameters...
February 15, 2018: Psychonomic Bulletin & Review
W Samuel Fagg, Naiyou Liu, Ming-Jim Yang, Ke Cheng, Eric Chung, Jae-Sung Kim, Gordon Wu, Jeffrey Fair
Attaining consistent robust engraftment in the structurally normal liver is an obstacle for cellular transplantation. Most experimental approaches to increase transplanted cells' engraftment involve recipient-centered deleterious methods such as partial hepatectomy or irradiation which may be unsuitable in the clinic. Here, we present a cell-based strategy that increases engraftment into the structurally normal liver using a combination of magnetic targeting and proliferative endoderm progenitor (EPs) cells...
December 2017: Cell Transplantation
Jeffrey Sordahl, India C King, Kyle Davis, Rick Tivis, Scott C Smith, Amber Fisher, Janet Willis, Timothy Gordon, William G Weppner
Transition to interprofessional team-based care is a quickly progressing healthcare model and requires changes in medical training approaches. The Department of Veteran Affairs (VA) has taken a lead role in creating such training experiences, one of which is the establishment of multiple Centers of Excellence in Primary Care Education (CoEPCE). These sites are tasked with developing teaching innovations to better facilitate interprofessional team-based care. The patient-aligned care team interprofessional care update (PACT-ICU) is an interprofessional workplace learning activity with the goals of simultaneously addressing educational and patient care needs...
January 27, 2018: Translational Behavioral Medicine
Reem Karmali, Vineela Chukkapalli, Leo I Gordon, Jeffrey A Borgia, Andrey Ugolkov, Andrew P Mazar, Francis J Giles
The complexities of GSK-3β function and interactions with PI3K/AKT/mTOR signaling, cell cycling, and apoptotic pathways are poorly understood in the context of lymphomagenesis and cancer therapeutics. In this study, we explored the anti-tumor effects of the GSK-3β inhibitor, 9-ING-41, in lymphoma cell lines as a single agent and in combination with novel agents comprising BCL-2 inhibitor (Venetoclax), CDK-9 inhibitor (BAY-1143572) and p110δ-PI3K inhibitor (Idelalisib). Treatment of Daudi, SUDHL-4, Karpas 422, KPUM-UH1, and TMD8 lymphoma cell lines with 1 μM 9-ING-41 reduced cell viability by 40-70% (p<0...
December 29, 2017: Oncotarget
Gina C Gordon, Jeffrey C Cameron, Brian F Pfleger
RNase III is a ribonuclease that recognizes and cleaves double-stranded RNA. Across bacteria, RNase III is involved in rRNA maturation, CRISPR RNA maturation, controlling gene expression, and turnover of messenger RNAs. Many organisms have only one RNase III while others have both a full-length RNase III and another version that lacks a double-stranded RNA binding domain (mini-III). The genome of the cyanobacterium Synechococcus sp. strain PCC 7002 (PCC 7002) encodes three homologs of RNase III, two full-length and one mini-III, that are not essential even when deleted in combination...
January 24, 2018: Nucleic Acids Research
Svetlana Lorenzano, Natalia S Rost, Muhib Khan, Hua Li, Fabricio O Lima, Matthew B Maas, Rebecca E Green, Tijy K Thankachan, Allison J Dipietro, Ken Arai, Angel T Som, Loc-Duyen D Pham, Ona Wu, Gordon J Harris, Eng H Lo, Jeffrey B Blumberg, Paul E Milbury, Steven K Feske, Karen L Furie
BACKGROUND AND PURPOSE: Oxidative stress is an early response to cerebral ischemia and is likely to play an important role in the pathogenesis of cerebral ischemic injury. We sought to evaluate whether hyperacute plasma concentrations of biomarkers of oxidative stress, inflammation, and tissue damage predict infarct growth (IG). METHODS: We prospectively measured plasma F2-isoprostane (F2-isoP), urinary 8-oxo-7,8-dihydro-2'-deoxyguoanosine, plasma oxygen radical absorbance capacity assay, high sensitivity C reactive protein, and matrix metalloproteinase 2 and 9 in consecutive patients with acute ischemic stroke presenting within 9 hours of symptom onset...
January 25, 2018: Stroke; a Journal of Cerebral Circulation
R William Stein, Christopher G Mull, Tyler S Kuhn, Neil C Aschliman, Lindsay N K Davidson, Jeffrey B Joy, Gordon J Smith, Nicholas K Dulvy, Arne O Mooers
In an era of accelerated biodiversity loss and limited conservation resources, systematic prioritization of species and places is essential. In terrestrial vertebrates, evolutionary distinctness has been used to identify species and locations that embody the greatest share of evolutionary history. We estimate evolutionary distinctness for a large marine vertebrate radiation on a dated taxon-complete tree for all 1,192 chondrichthyan fishes (sharks, rays and chimaeras) by augmenting a new 610-species molecular phylogeny using taxonomic constraints...
January 18, 2018: Nature Ecology & Evolution
A Gordon Robertson, Juliann Shih, Christina Yau, Ewan A Gibb, Junna Oba, Karen L Mungall, Julian M Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M Lichtenberg, Melanie Kucherlapati, Patrick K Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A Bristow, Katherine A Hoadley, Lisa Iype, Matthew T Chang, Andrew D Cherniack, Christopher Benz, Gordon B Mills, Roel G W Verhaak, Klaus G Griewank, Ina Felau, Jean C Zenklusen, Jeffrey E Gershenwald, Lynn Schoenfield, Alexander J Lazar, Mohamed H Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M Cebulla, Michelle D Williams, Martine J Jager, Sarah E Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E Woodman
No abstract text is available yet for this article.
January 8, 2018: Cancer Cell
D Ross Camidge, Eudocia Q Lee, Nancy U Lin, Kim Margolin, Manmeet S Ahluwalia, Martin Bendszus, Susan M Chang, Janet Dancey, Elisabeth G E de Vries, Gordon J Harris, F Stephen Hodi, Andrew B Lassman, David R Macdonald, David M Peereboom, David Schiff, Ricardo Soffietti, Martin J van den Bent, Jeffrey S Wefel, Patrick Y Wen
Patients with active CNS disease are often excluded from clinical trials, and data regarding the CNS efficacy of systemic agents are usually obtained late in the drug development process or not at all. In this guideline from the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group, we provide detailed recommendations on when patients with brain metastases from solid tumours should be included or excluded in clinical trials of systemic agents. We also discuss the limitations of retrospective studies in determining the CNS efficacy of systemic drugs...
January 2018: Lancet Oncology
Cecelia R Miller, Amy S Ruppert, Nyla A Heerema, Kami J Maddocks, Jadwiga Labanowska, Heather Breidenbach, Gerard Lozanski, Weiqiang Zhao, Amber L Gordon, Jeffrey A Jones, Joseph M Flynn, Samantha M Jaglowski, Leslie A Andritsos, Kristie A Blum, Farrukh T Awan, Kerry A Rogers, Michael R Grever, Amy J Johnson, Lynne V Abruzzo, Erin K Hertlein, James S Blachly, Jennifer A Woyach, John C Byrd
Ibrutinib is a highly effective targeted therapy for chronic lymphocytic leukemia (CLL). However, ibrutinib must be discontinued in a subset of patients due to progressive CLL or transformation to aggressive lymphoma (Richter transformation). Transformation occurs early in the course of therapy and has an extremely poor prognosis. Thus, identification of prognostic markers associated with transformation is of utmost importance. Near-tetraploidy (4 copies of most chromosomes within a cell) has been reported in various lymphomas, but its incidence and significance in CLL has not been described...
August 22, 2017: Blood Advances
Mei Lu, Yueren Zhou, Irina V Haller, Robert J Romanelli, Jeffrey J VanWormer, Carla V Rodriguez, Heather Anderson, Joseph A Boscarino, Mark A Schmidt, Yihe G Daida, Amandeep Sahota, Jennifer Vincent, Christopher L Bowlus, Keith Lindor, Talan Zhang, Sheri Trudeau, Jia Li, Loralee B Rupp, Stuart C Gordon
BACKGROUND & AIMS: There are few data from longitudinal studies of trends in primary biliary cholangitis (PBC) among patients under routine clinical care in the United States (US). We collected data from the Fibrotic Liver Disease consortium to investigate changes in incidence and prevalence of PBC and the effects of patient demographics, clinical features, and treatment on mortality. METHODS: We collected demographic and clinical data for the general patient population as well as PBC patients receiving care from 11 health systems in different regions of the US (Northeast, Midwest, Northwest, and South) from January 1, 2003 through December 31, 2014...
December 22, 2017: Clinical Gastroenterology and Hepatology
Valérie Turcot, Yingchang Lu, Heather M Highland, Claudia Schurmann, Anne E Justice, Rebecca S Fine, Jonathan P Bradfield, Tõnu Esko, Ayush Giri, Mariaelisa Graff, Xiuqing Guo, Audrey E Hendricks, Tugce Karaderi, Adelheid Lempradl, Adam E Locke, Anubha Mahajan, Eirini Marouli, Suthesh Sivapalaratnam, Kristin L Young, Tamuno Alfred, Mary F Feitosa, Nicholas G D Masca, Alisa K Manning, Carolina Medina-Gomez, Poorva Mudgal, Maggie C Y Ng, Alex P Reiner, Sailaja Vedantam, Sara M Willems, Thomas W Winkler, Gonçalo Abecasis, Katja K Aben, Dewan S Alam, Sameer E Alharthi, Matthew Allison, Philippe Amouyel, Folkert W Asselbergs, Paul L Auer, Beverley Balkau, Lia E Bang, Inês Barroso, Lisa Bastarache, Marianne Benn, Sven Bergmann, Lawrence F Bielak, Matthias Blüher, Michael Boehnke, Heiner Boeing, Eric Boerwinkle, Carsten A Böger, Jette Bork-Jensen, Michiel L Bots, Erwin P Bottinger, Donald W Bowden, Ivan Brandslund, Gerome Breen, Murray H Brilliant, Linda Broer, Marco Brumat, Amber A Burt, Adam S Butterworth, Peter T Campbell, Stefania Cappellani, David J Carey, Eulalia Catamo, Mark J Caulfield, John C Chambers, Daniel I Chasman, Yii-Der I Chen, Rajiv Chowdhury, Cramer Christensen, Audrey Y Chu, Massimiliano Cocca, Francis S Collins, James P Cook, Janie Corley, Jordi Corominas Galbany, Amanda J Cox, David S Crosslin, Gabriel Cuellar-Partida, Angela D'Eustacchio, John Danesh, Gail Davies, Paul I W Bakker, Mark C H Groot, Renée Mutsert, Ian J Deary, George Dedoussis, Ellen W Demerath, Martin Heijer, Anneke I Hollander, Hester M Ruijter, Joe G Dennis, Josh C Denny, Emanuele Angelantonio, Fotios Drenos, Mengmeng Du, Marie-Pierre Dubé, Alison M Dunning, Douglas F Easton, Todd L Edwards, David Ellinghaus, Patrick T Ellinor, Paul Elliott, Evangelos Evangelou, Aliki-Eleni Farmaki, I Sadaf Farooqi, Jessica D Faul, Sascha Fauser, Shuang Feng, Ele Ferrannini, Jean Ferrieres, Jose C Florez, Ian Ford, Myriam Fornage, Oscar H Franco, Andre Franke, Paul W Franks, Nele Friedrich, Ruth Frikke-Schmidt, Tessel E Galesloot, Wei Gan, Ilaria Gandin, Paolo Gasparini, Jane Gibson, Vilmantas Giedraitis, Anette P Gjesing, Penny Gordon-Larsen, Mathias Gorski, Hans-Jörgen Grabe, Struan F A Grant, Niels Grarup, Helen L Griffiths, Megan L Grove, Vilmundur Gudnason, Stefan Gustafsson, Jeff Haessler, Hakon Hakonarson, Anke R Hammerschlag, Torben Hansen, Kathleen Mullan Harris, Tamara B Harris, Andrew T Hattersley, Christian T Have, Caroline Hayward, Liang He, Nancy L Heard-Costa, Andrew C Heath, Iris M Heid, Øyvind Helgeland, Jussi Hernesniemi, Alex W Hewitt, Oddgeir L Holmen, G Kees Hovingh, Joanna M M Howson, Yao Hu, Paul L Huang, Jennifer E Huffman, M Arfan Ikram, Erik Ingelsson, Anne U Jackson, Jan-Håkan Jansson, Gail P Jarvik, Gorm B Jensen, Yucheng Jia, Stefan Johansson, Marit E Jørgensen, Torben Jørgensen, J Wouter Jukema, Bratati Kahali, René S Kahn, Mika Kähönen, Pia R Kamstrup, Stavroula Kanoni, Jaakko Kaprio, Maria Karaleftheri, Sharon L R Kardia, Fredrik Karpe, Sekar Kathiresan, Frank Kee, Lambertus A Kiemeney, Eric Kim, Hidetoshi Kitajima, Pirjo Komulainen, Jaspal S Kooner, Charles Kooperberg, Tellervo Korhonen, Peter Kovacs, Helena Kuivaniemi, Zoltán Kutalik, Kari Kuulasmaa, Johanna Kuusisto, Markku Laakso, Timo A Lakka, David Lamparter, Ethan M Lange, Leslie A Lange, Claudia Langenberg, Eric B Larson, Nanette R Lee, Terho Lehtimäki, Cora E Lewis, Huaixing Li, Jin Li, Ruifang Li-Gao, Honghuang Lin, Keng-Hung Lin, Li-An Lin, Xu Lin, Lars Lind, Jaana Lindström, Allan Linneberg, Ching-Ti Liu, Dajiang J Liu, Yongmei Liu, Ken S Lo, Artitaya Lophatananon, Andrew J Lotery, Anu Loukola, Jian'an Luan, Steven A Lubitz, Leo-Pekka Lyytikäinen, Satu Männistö, Gaëlle Marenne, Angela L Mazul, Mark I McCarthy, Roberta McKean-Cowdin, Sarah E Medland, Karina Meidtner, Lili Milani, Vanisha Mistry, Paul Mitchell, Karen L Mohlke, Leena Moilanen, Marie Moitry, Grant W Montgomery, Dennis O Mook-Kanamori, Carmel Moore, Trevor A Mori, Andrew D Morris, Andrew P Morris, Martina Müller-Nurasyid, Patricia B Munroe, Mike A Nalls, Narisu Narisu, Christopher P Nelson, Matt Neville, Sune F Nielsen, Kjell Nikus, Pål R Njølstad, Børge G Nordestgaard, Dale R Nyholt, Jeffrey R O'Connel, Michelle L O'Donoghue, Loes M Olde Loohuis, Roel A Ophoff, Katharine R Owen, Chris J Packard, Sandosh Padmanabhan, Colin N A Palmer, Nicholette D Palmer, Gerard Pasterkamp, Aniruddh P Patel, Alison Pattie, Oluf Pedersen, Peggy L Peissig, Gina M Peloso, Craig E Pennell, Markus Perola, James A Perry, John R B Perry, Tune H Pers, Thomas N Person, Annette Peters, Eva R B Petersen, Patricia A Peyser, Ailith Pirie, Ozren Polasek, Tinca J Polderman, Hannu Puolijoki, Olli T Raitakari, Asif Rasheed, Rainer Rauramaa, Dermot F Reilly, Frida Renström, Myriam Rheinberger, Paul M Ridker, John D Rioux, Manuel A Rivas, David J Roberts, Neil R Robertson, Antonietta Robino, Olov Rolandsson, Igor Rudan, Katherine S Ruth, Danish Saleheen, Veikko Salomaa, Nilesh J Samani, Yadav Sapkota, Naveed Sattar, Robert E Schoen, Pamela J Schreiner, Matthias B Schulze, Robert A Scott, Marcelo P Segura-Lepe, Svati H Shah, Wayne H-H Sheu, Xueling Sim, Andrew J Slater, Kerrin S Small, Albert V Smith, Lorraine Southam, Timothy D Spector, Elizabeth K Speliotes, John M Starr, Kari Stefansson, Valgerdur Steinthorsdottir, Kathleen E Stirrups, Konstantin Strauch, Heather M Stringham, Michael Stumvoll, Liang Sun, Praveen Surendran, Amy J Swift, Hayato Tada, Katherine E Tansey, Jean-Claude Tardif, Kent D Taylor, Alexander Teumer, Deborah J Thompson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Betina H Thuesen, Anke Tönjes, Gerard Tromp, Stella Trompet, Emmanouil Tsafantakis, Jaakko Tuomilehto, Anne Tybjaerg-Hansen, Jonathan P Tyrer, Rudolf Uher, André G Uitterlinden, Matti Uusitupa, Sander W Laan, Cornelia M Duijn, Nienke Leeuwen, Jessica van Setten, Mauno Vanhala, Anette Varbo, Tibor V Varga, Rohit Varma, Digna R Velez Edwards, Sita H Vermeulen, Giovanni Veronesi, Henrik Vestergaard, Veronique Vitart, Thomas F Vogt, Uwe Völker, Dragana Vuckovic, Lynne E Wagenknecht, Mark Walker, Lars Wallentin, Feijie Wang, Carol A Wang, Shuai Wang, Yiqin Wang, Erin B Ware, Nicholas J Wareham, Helen R Warren, Dawn M Waterworth, Jennifer Wessel, Harvey D White, Cristen J Willer, James G Wilson, Daniel R Witte, Andrew R Wood, Ying Wu, Hanieh Yaghootkar, Jie Yao, Pang Yao, Laura M Yerges-Armstrong, Robin Young, Eleftheria Zeggini, Xiaowei Zhan, Weihua Zhang, Jing Hua Zhao, Wei Zhao, Wei Zhou, Krina T Zondervan, Jerome I Rotter, John A Pospisilik, Fernando Rivadeneira, Ingrid B Borecki, Panos Deloukas, Timothy M Frayling, Guillaume Lettre, Kari E North, Cecilia M Lindgren, Joel N Hirschhorn, Ruth J F Loos
Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR...
January 2018: Nature Genetics
Noelia Nebot, H T Arkenau, Jeffrey R Infante, Jason C Chandler, Andrew Weickhardt, Jason D Lickliter, John Sarantopoulos, Michael S Gordon, Gabriel Mak, Annie St-Pierre, Lihua Tang, Bijoyesh Mookerjee, Stanley W Carson, Siobhan Hayes, Kenneth F Grossmann
AIMS: The effect of repeat oral supratherapeutic dosing of the BRAF inhibitor dabrafenib on QTc interval was assessed in patients with BRAF V600-mutant tumours. METHODS: Part 1 of this phase 1, multicentre, 2-part study (BRF113773/NCT01738451) assessed safety/tolerability of dabrafenib 225 or 300 mg twice daily (BID) to inform part 2 dosing. Patients in part 2 received dabrafenib-matched placebo on day -1, single-dose dabrafenib 300 mg on day 1, 300 mg BID on days 2 to 7, and 300 mg on day 8 (morning), followed by 24-hour Holter electrocardiographic monitoring and pharmacokinetics sample collection each dose day...
December 15, 2017: British Journal of Clinical Pharmacology
Veda N Giri, Karen E Knudsen, William K Kelly, Wassim Abida, Gerald L Andriole, Chris H Bangma, Justin E Bekelman, Mitchell C Benson, Amie Blanco, Arthur Burnett, William J Catalona, Kathleen A Cooney, Matthew Cooperberg, David E Crawford, Robert B Den, Adam P Dicker, Scott Eggener, Neil Fleshner, Matthew L Freedman, Freddie C Hamdy, Jean Hoffman-Censits, Mark D Hurwitz, Colette Hyatt, William B Isaacs, Christopher J Kane, Philip Kantoff, R Jeffrey Karnes, Lawrence I Karsh, Eric A Klein, Daniel W Lin, Kevin R Loughlin, Grace Lu-Yao, S Bruce Malkowicz, Mark J Mann, James R Mark, Peter A McCue, Martin M Miner, Todd Morgan, Judd W Moul, Ronald E Myers, Sarah M Nielsen, Elias Obeid, Christian P Pavlovich, Stephen C Peiper, David F Penson, Daniel Petrylak, Curtis A Pettaway, Robert Pilarski, Peter A Pinto, Wendy Poage, Ganesh V Raj, Timothy R Rebbeck, Mark E Robson, Matt T Rosenberg, Howard Sandler, Oliver Sartor, Edward Schaeffer, Gordon F Schwartz, Mark S Shahin, Neal D Shore, Brian Shuch, Howard R Soule, Scott A Tomlins, Edouard J Trabulsi, Robert Uzzo, Donald J Vander Griend, Patrick C Walsh, Carol J Weil, Richard Wender, Leonard G Gomella
Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing...
December 13, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Manish R Patel, John Ellerton, Jeffrey R Infante, Manish Agrawal, Michael Gordon, Raid Aljumaily, Carolyn D Britten, Luc Dirix, Keun-Wook Lee, Mathew Taylor, Patrick Schöffski, Ding Wang, Alain Ravaud, Arnold B Gelb, Junyuan Xiong, Galit Rosen, James L Gulley, Andrea B Apolo
BACKGROUND: The approval of anti-programmed death ligand 1 (PD-L1) and anti-programmed death 1 agents has expanded treatment options for patients with locally advanced or metastatic urothelial carcinoma. Avelumab, a human monoclonal anti-PD-L1 antibody, has shown promising antitumour activity and safety in this disease. We aimed to assess the safety profile in patients (both post-platinum therapy and cisplatin-naive) treated with avelumab and to assess antitumour activity of this drug in post-platinum patients...
January 2018: Lancet Oncology
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