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https://www.readbyqxmd.com/read/29676596/lung-dendritic-cells-drive-nk-cytotoxicity-in-chronic-obstructive-pulmonary-disease-via-il-15r%C3%AE
#1
Donna K Finch, Valerie R Stolberg, John Ferguson, Henrih Alikaj, Mohamed R Kady, Bradley W Richmond, Vasiliy V Polosukhin, Timothy S Blackwell, Lisa McCloskey, Jeffrey L Curtis, Christine M Freeman
RATIONALE: Lung natural killer (NK) cells kill a greater percentage of autologous lung parenchymal cells in COPD than in non-obstructed smokers. To become cytotoxic, NKs require priming, typically by dendritic cells (DC), but whether priming occurs in the lungs in COPD is unknown. METHODS: We used lung tissue and in some cases peripheral blood from patients undergoing clinically-indicated resections to determine in vitro killing of CD326+ lung epithelial cells by isolated lung CD56+ NKs...
April 20, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29615305/early-stage-her2-positive-breast-cancers-not-achieving-a-pcr-from-neoadjuvant-trastuzumab-or-pertuzumab-based-regimens-have-an-immunosuppressive-phenotype
#2
Jeremy Force, Lynn J Howie, Sara E Abbott, Rex Bentley, P Kelly Marcom, Gretchen Kimmick, Kelly Westbrook, Sarah L Sammons, Michelle Parks, Donna L Topping, Ryan Emerson, Gloria Broadwater, Terry Hyslop, Kimberly L Blackwell, Smita K Nair
BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) might predict pathologic complete response (pCR) in patients with HER2-positive (HER2+ ) breast cancer treated with trastuzumab (H). Docetaxel (T), carboplatin (C), H, and pertuzumab (P) have immune-modulating effects. Pre- and post-treatment immune biomarkers in cancers treated with neoadjuvant TCH with or without P are lacking. In this study we quantified baseline and changes in TILs, cluster of differentiation (CD) 4+ , CD8+ , FoxP3+ , and PD-L1+ cells using immunohistochemistry (IHC) and quantified productive T-cell receptor β (TCRβ) rearrangements and TCRβ clonality using next-generation sequencing (NGS) in 30 HER2+ breast cancer tissues treated with neoadjuvant H with or without P regimens...
February 24, 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29567045/advancing-the-science-of-children-s-positive-health-in-the-national-institutes-of-health-environmental-influences-on-child-health-outcomes-echo-research-program
#3
Christopher B Forrest, Courtney K Blackwell, Carlos A Camargo
No abstract text is available yet for this article.
March 19, 2018: Journal of Pediatrics
https://www.readbyqxmd.com/read/29507109/epitope-binding-characteristics-for-risk-versus-protective-drb1-alleles-for-visceral-leishmaniasis
#4
Toolika Singh, Michaela Fakiola, Joyce Oommen, Akhil Pratap Singh, Abhishek K Singh, Noel Smith, Jaya Chakravarty, Shyam Sundar, Jenefer M Blackwell
HLA-DRB1 is the major genetic risk factor for visceral leishmaniasis (VL). We used SNP2HLA to impute HLA-DRB1 alleles and SNPTEST to carry out association analyses in 889 human cases and 977 controls from India. NetMHCIIpan 2.1 was used to map epitopes and binding affinities across 49 Leishmania vaccine candidates, as well as across peptide epitopes captured from dendritic cells treated with crude Leishmania Ag and identified using mass spectrometry and alignment to amino acid sequences of a reference Leishmania genome...
March 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29498417/phosphorus-acquisition-by-citrate-and-phytase-exuding-nicotiana-tabacum-plant-mixtures-depends-on-soil-phosphorus-availability-and-root-intermingling
#5
Courtney D Giles, Alan E Richardson, Barbara J Cade-Menun, Malika M Mezeli, Lawrie K Brown, Daniel Menezes-Blackburn, Tegan Darch, Martin Sa Blackwell, Charles A Shand, Marc I Stutter, Renate Wendler, Patricia Cooper, David G Lumsdon, Catherine Wearing, Hao Zhang, Philip M Haygarth, Timothy S George
Citrate and phytase root exudates contribute to improved phosphorus (P) acquisition efficiency in Nicotiana tabacum (tobacco) when both exudates are produced in a P deficient soil. To test the importance of root intermingling in the interaction of citrate and phytase exudates, Nicotiana tabacum plant-lines with constitutive expression of heterologous citrate (Cit) or fungal phytase (Phy) exudation traits were grown under two root treatments (roots separated or intermingled) and in two soils with contrasting soil P availability...
March 2, 2018: Physiologia Plantarum
https://www.readbyqxmd.com/read/29494294/discrete-physiological-effects-of-beetroot-juice-and-potassium-nitrate-supplementation-following-4-weeks-sprint-interval-training
#6
Christopher Thompson, Anni Vanhatalo, Stefan Kadach, Lee J Wylie, Jonathan Fulford, Scott K Ferguson, Jamie R Blackwell, Stephen J Bailey, Andrew M Jones
The physiological and exercise performance adaptations to sprint interval training (SIT) may be modified by dietary nitrate (NO3 - ) supplementation. However, it is possible that different types of NO3 - supplementation evoke divergent physiological and performance adaptations to SIT. The purpose of this study was to compare the effects of 4 weeks SIT with and without concurrent dietary NO3 - supplementation administered as either NO3 - -rich beetroot juice (BR) or potassium NO3 - (KNO3 ). Thirty recreationally-active subjects completed a battery of exercise tests before and after a 4 week intervention in which they were allocated to one of three groups: 1) SIT undertaken without dietary NO3 - supplementation (SIT); 2) SIT accompanied by concurrent BR supplementation (SIT+BR); or 3) SIT accompanied by concurrent KNO3 supplementation (SIT+KNO3 )...
March 1, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29490108/the-stable-oxygen-isotope-ratio-of-resin-extractable-phosphate-derived-from-fresh-cattle-faeces
#7
Steven J Granger, Yuguo Yang, Verena Pfahler, Chris Hodgson, Andrew C Smith, Kate Le Cocq, Adrian L Collins, Martin S A Blackwell, Nicholas J K Howden
RATIONALE: Phosphorus losses from agriculture pose an environmental threat to watercourses. A new approach using the stable oxygen isotope ratio of oxygen in phosphate (δ18 OPO4 value) may help elucidate some phosphorus sources and cycling. Accurately determined and isotopically distinct source values are essential for this process. The δ18 OPO4 values of animal wastes have, up to now, received little attention. METHODS: Phosphate (PO4 ) was extracted from cattle faeces using anion resins and the contribution of microbial PO4 was assessed...
February 28, 2018: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/29447402/intraoperative-endotracheal-cuff-pressure-study-how-education-and-availability-of-manometers-help-guide-safer-pressures
#8
Gregory J Stevens, Joel W Warfel, James K Aden, Scott D Blackwell
Introduction: Endotracheal intubation is a medical procedure that is often indicated in both the perioperative and critical care environments. Cuffed endotracheal tubes (ETT) allow for safer and more efficient delivery of positive pressure ventilation, as well as create a barrier to reduce the risk of micro-aspiration and anesthetic pollution in the operating room environment. Over-inflation of the endotracheal cuff can lead to serious and harmful sequelae. This study aimed to assess if departmental education paired with ready access to a manometer to assess cuff pressure would result in an improvement in the proportion of ETT cuff pressures in the goal range...
February 13, 2018: Military Medicine
https://www.readbyqxmd.com/read/29437911/developing-a-core-outcome-set-for-fistulising-perianal-crohn-s-disease
#9
Kapil Sahnan, Phil J Tozer, Samuel O Adegbola, Matthew J Lee, Nick Heywood, Angus G K McNair, Daniel Hind, Nuha Yassin, Alan J Lobo, Steven R Brown, Shaji Sebastian, Robin K S Phillips, Phillip F C Lung, Omar D Faiz, Kay Crook, Sue Blackwell, Azmina Verjee, Ailsa L Hart, Nicola S Fearnhead
OBJECTIVE: Lack of standardised outcomes hampers effective analysis and comparison of data when comparing treatments in fistulising perianal Crohn's disease (pCD). Development of a standardised set of outcomes would resolve these issues. This study provides the definitive core outcome set (COS) for fistulising pCD. DESIGN: Candidate outcomes were generated through a systematic review and patient interviews. Consensus was established via a three-round Delphi process using a 9-point Likert scale based on how important they felt it was in determining treatment success culminating in a final consensus meeting...
February 3, 2018: Gut
https://www.readbyqxmd.com/read/29406440/measurement-framework-for-the-environmental-influences-on-child-health-outcomes-research-program
#10
Courtney K Blackwell, Lauren S Wakschlag, Richard C Gershon, David Cella
PURPOSE OF REVIEW: Diverse methodological approaches pose significant challenges to assess environmental exposure effects on child health outcomes. Although transdisciplinary research efforts offer unique opportunities for understanding the complex and multidimensional facets of lifespan health and disease trajectories, a shared measurement strategy is necessary for ensuring cohesion and comprehensibility across disciplines and domains. RECENT FINDINGS: Exposure science often focuses on one life stage, one primary outcome domain and/or one environmental context without regard for understanding the complexity of exposome pathways and outcomes across a developmental continuum...
February 5, 2018: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29398641/diagnosis-and-management-of-duchenne-muscular-dystrophy-part-3-primary-care-emergency-management-psychosocial-care-and-transitions-of-care-across-the-lifespan
#11
REVIEW
David J Birnkrant, Katharine Bushby, Carla M Bann, Susan D Apkon, Angela Blackwell, Mary K Colvin, Linda Cripe, Adrienne R Herron, Annie Kennedy, Kathi Kinnett, James Naprawa, Garey Noritz, James Poysky, Natalie Street, Christina J Trout, David R Weber, Leanne M Ward
Improvements in the function, quality of life, and longevity of patients with Duchenne muscular dystrophy (DMD) have been achieved through a multidisciplinary approach to management across a range of health-care specialties. In part 3 of this update of the DMD care considerations, we focus on primary care, emergency management, psychosocial care, and transitions of care across the lifespan. Many primary care and emergency medicine clinicians are inexperienced at managing the complications of DMD. We provide a guide to the acute and chronic medical conditions that these first-line providers are likely to encounter...
February 1, 2018: Lancet Neurology
https://www.readbyqxmd.com/read/29395990/diagnosis-and-management-of-duchenne-muscular-dystrophy-part-2-respiratory-cardiac-bone-health-and-orthopaedic-management
#12
REVIEW
David J Birnkrant, Katharine Bushby, Carla M Bann, Benjamin A Alman, Susan D Apkon, Angela Blackwell, Laura E Case, Linda Cripe, Stasia Hadjiyannakis, Aaron K Olson, Daniel W Sheehan, Julie Bolen, David R Weber, Leanne M Ward
A coordinated, multidisciplinary approach to care is essential for optimum management of the primary manifestations and secondary complications of Duchenne muscular dystrophy (DMD). Contemporary care has been shaped by the availability of more sensitive diagnostic techniques and the earlier use of therapeutic interventions, which have the potential to improve patients' duration and quality of life. In part 2 of this update of the DMD care considerations, we present the latest recommendations for respiratory, cardiac, bone health and osteoporosis, and orthopaedic and surgical management for boys and men with DMD...
January 23, 2018: Lancet Neurology
https://www.readbyqxmd.com/read/29360107/erratum-sequence-data-and-association-statistics-from-12-940-type-2-diabetes-cases-and-controls
#13
Jason Flannick, Christian Fuchsberger, Anubha Mahajan, Tanya M Teslovich, Vineeta Agarwala, Kyle J Gaulton, Lizz Caulkins, Ryan Koesterer, Clement Ma, Loukas Moutsianas, Davis J McCarthy, Manuel A Rivas, John R B Perry, Xueling Sim, Thomas W Blackwell, Neil R Robertson, N William Rayner, Pablo Cingolani, Adam E Locke, Juan Fernandez Tajes, Heather M Highland, Josee Dupuis, Peter S Chines, Cecilia M Lindgren, Christopher Hartl, Anne U Jackson, Han Chen, Jeroen R Huyghe, Martijn van de Bunt, Richard D Pearson, Ashish Kumar, Martina Müller-Nurasyid, Niels Grarup, Heather M Stringham, Eric R Gamazon, Jaehoon Lee, Yuhui Chen, Robert A Scott, Jennifer E Below, Peng Chen, Jinyan Huang, Min Jin Go, Michael L Stitzel, Dorota Pasko, Stephen C J Parker, Tibor V Varga, Todd Green, Nicola L Beer, Aaron G Day-Williams, Teresa Ferreira, Tasha Fingerlin, Momoko Horikoshi, Cheng Hu, Iksoo Huh, Mohammad Kamran Ikram, Bong-Jo Kim, Yongkang Kim, Young Jin Kim, Min-Seok Kwon, Juyoung Lee, Selyeong Lee, Keng-Han Lin, Taylor J Maxwell, Yoshihiko Nagai, Xu Wang, Ryan P Welch, Joon Yoon, Weihua Zhang, Nir Barzilai, Benjamin F Voight, Bok-Ghee Han, Christopher P Jenkinson, Teemu Kuulasmaa, Johanna Kuusisto, Alisa Manning, Maggie C Y Ng, Nicholette D Palmer, Beverley Balkau, Alena Stančáková, Hanna E Abboud, Heiner Boeing, Vilmantas Giedraitis, Dorairaj Prabhakaran, Omri Gottesman, James Scott, Jason Carey, Phoenix Kwan, George Grant, Joshua D Smith, Benjamin M Neale, Shaun Purcell, Adam S Butterworth, Joanna M M Howson, Heung Man Lee, Yingchang Lu, Soo-Heon Kwak, Wei Zhao, John Danesh, Vincent K L Lam, Kyong Soo Park, Danish Saleheen, Wing Yee So, Claudia H T Tam, Uzma Afzal, David Aguilar, Rector Arya, Tin Aung, Edmund Chan, Carmen Navarro, Ching-Yu Cheng, Domenico Palli, Adolfo Correa, Joanne E Curran, Dennis Rybin, Vidya S Farook, Sharon P Fowler, Barry I Freedman, Michael Griswold, Daniel Esten Hale, Pamela J Hicks, Chiea-Chuen Khor, Satish Kumar, Benjamin Lehne, Dorothée Thuillier, Wei Yen Lim, Jianjun Liu, Marie Loh, Solomon K Musani, Sobha Puppala, William R Scott, Loïc Yengo, Sian-Tsung Tan, Herman A Taylor, Farook Thameem, Gregory Wilson, Tien Yin Wong, Pål Rasmus Njølstad, Jonathan C Levy, Massimo Mangino, Lori L Bonnycastle, Thomas Schwarzmayr, João Fadista, Gabriela L Surdulescu, Christian Herder, Christopher J Groves, Thomas Wieland, Jette Bork-Jensen, Ivan Brandslund, Cramer Christensen, Heikki A Koistinen, Alex S F Doney, Leena Kinnunen, Tõnu Esko, Andrew J Farmer, Liisa Hakaste, Dylan Hodgkiss, Jasmina Kravic, Valeri Lyssenko, Mette Hollensted, Marit E Jørgensen, Torben Jørgensen, Claes Ladenvall, Johanne Marie Justesen, Annemari Käräjämäki, Jennifer Kriebel, Wolfgang Rathmann, Lars Lannfelt, Torsten Lauritzen, Narisu Narisu, Allan Linneberg, Olle Melander, Lili Milani, Matt Neville, Marju Orho-Melander, Lu Qi, Qibin Qi, Michael Roden, Olov Rolandsson, Amy Swift, Anders H Rosengren, Kathleen Stirrups, Andrew R Wood, Evelin Mihailov, Christine Blancher, Mauricio O Carneiro, Jared Maguire, Ryan Poplin, Khalid Shakir, Timothy Fennell, Mark DePristo, Martin Hrabé de Angelis, Panos Deloukas, Anette P Gjesing, Goo Jun, Peter Nilsson, Jacquelyn Murphy, Robert Onofrio, Barbara Thorand, Torben Hansen, Christa Meisinger, Frank B Hu, Bo Isomaa, Fredrik Karpe, Liming Liang, Annette Peters, Cornelia Huth, Stephen P O'Rahilly, Colin N A Palmer, Oluf Pedersen, Rainer Rauramaa, Jaakko Tuomilehto, Veikko Salomaa, Richard M Watanabe, Ann-Christine Syvänen, Richard N Bergman, Dwaipayan Bharadwaj, Erwin P Bottinger, Yoon Shin Cho, Giriraj R Chandak, Juliana C N Chan, Kee Seng Chia, Mark J Daly, Shah B Ebrahim, Claudia Langenberg, Paul Elliott, Kathleen A Jablonski, Donna M Lehman, Weiping Jia, Ronald C W Ma, Toni I Pollin, Manjinder Sandhu, Nikhil Tandon, Philippe Froguel, Inês Barroso, Yik Ying Teo, Eleftheria Zeggini, Ruth J F Loos, Kerrin S Small, Janina S Ried, Ralph A DeFronzo, Harald Grallert, Benjamin Glaser, Andres Metspalu, Nicholas J Wareham, Mark Walker, Eric Banks, Christian Gieger, Erik Ingelsson, Hae Kyung Im, Thomas Illig, Paul W Franks, Gemma Buck, Joseph Trakalo, David Buck, Inga Prokopenko, Reedik Mägi, Lars Lind, Yossi Farjoun, Katharine R Owen, Anna L Gloyn, Konstantin Strauch, Tiinamaija Tuomi, Jaspal Singh Kooner, Jong-Young Lee, Taesung Park, Peter Donnelly, Andrew D Morris, Andrew T Hattersley, Donald W Bowden, Francis S Collins, Gil Atzmon, John C Chambers, Timothy D Spector, Markku Laakso, Tim M Strom, Graeme I Bell, John Blangero, Ravindranath Duggirala, E Shyong Tai, Gilean McVean, Craig L Hanis, James G Wilson, Mark Seielstad, Timothy M Frayling, James B Meigs, Nancy J Cox, Rob Sladek, Eric S Lander, Stacey Gabriel, Karen L Mohlke, Thomas Meitinger, Leif Groop, Goncalo Abecasis, Laura J Scott, Andrew P Morris, Hyun Min Kang, David Altshuler, Noël P Burtt, Jose C Florez, Michael Boehnke, Mark I McCarthy
This corrects the article DOI: 10.1038/sdata.2017.179.
January 23, 2018: Scientific Data
https://www.readbyqxmd.com/read/29357997/year-round-presence-of-neonicotinoid-insecticides-in-tributaries-to-the-great-lakes-usa
#14
Michelle L Hladik, Steven R Corsi, Dana W Kolpin, Austin K Baldwin, Brett R Blackwell, Jenna E Cavallin
To better characterize the transport of neonicotinoid insecticides to the world's largest freshwater ecosystem, monthly samples (October 2015-September 2016) were collected from 10 major tributaries to the Great Lakes, USA. For the monthly tributary samples, neonicotinoids were detected in every month sampled and five of the six target neonicotinoids were detected. At least one neonicotinoid was detected in 74% of the monthly samples with up to three neonicotinoids detected in an individual sample (10% of all samples)...
April 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29324603/pregnancy-associated-hypertension-and-offspring-cardiometabolic-health
#15
Madeline Murguia Rice, Mark B Landon, Michael W Varner, Brian M Casey, Uma M Reddy, Ronald J Wapner, Dwight J Rouse, Alan T N Tita, John M Thorp, Edward K Chien, George Saade, Alan M Peaceman, Sean C Blackwell
OBJECTIVE: To evaluate whether pregnancy-associated hypertension (gestational hypertension and preeclampsia) was associated with the cardiometabolic health of young offspring. METHODS: This was a prospective observational follow-up study from 2012 to 2013 of children born to women previously enrolled in a mild gestational diabetes mellitus treatment trial or nongestational diabetes mellitus observational study. At 5-10 years after birth, children were examined and fasting blood samples obtained to determine the following cardiometabolic risk factors: blood pressure (BP), high-density lipoprotein cholesterol, triglycerides, glucose, homeostatic model assessment of insulin resistance, waist circumference, and body mass index (BMI)...
February 2018: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29226570/campath-calcineurin-inhibitor-reduction-and-chronic-allograft-nephropathy-the-3c-study-results-of-a-randomized-controlled-clinical-trial
#16
(no author information available yet)
Calcineurin inhibitors (CNIs, eg, tacrolimus) reduce short-term kidney transplant failure, but chronic nephrotoxicity may contribute to late transplant loss. Elective conversion to inhibitors of the mammalian target of rapamycin (mTOR, eg, sirolimus) pathway might avoid long-term CNI renal damage and improve outcomes. The 3C Study was a pragmatic randomized controlled trial of sequential randomizations between alemtuzumab and basiliximab induction therapy (at the time of surgery) and between tacrolimus and sirolimus maintenance therapy at 6 months posttransplantation...
December 11, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29091995/safety-and-efficacy-of-alternating-treatment-with-ep2006-a-filgrastim-biosimilar-and-reference-filgrastim-a-phase-iii-randomised-double-blind-clinical-study-in-the-prevention-of-severe-neutropenia-in-patients-with-breast-cancer-receiving-myelosuppressive-chemotherapy
#17
K Blackwell, P Gascon, A Krendyukov, S Gattu, Y Li, N Harbeck
Background: In 2015, the biosimilar filgrastim EP2006 became the first biosimilar approved by the US Food and Drug Administration for commercial use in the United States, marketed as Zarxio® (Sandoz). This phase III randomised, double-blind registration study in patients with breast cancer receiving (neo)adjuvant myelosuppressive chemotherapy (TAC; docetaxel + doxorubicin + cyclophosphamide) compares reference filgrastim, Neupogen® (Amgen), with two groups receiving alternating treatment with reference and biosimilar every other cycle...
January 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28866976/a-cross-sectional-survey-of-australian-and-new-zealand-public-opinion-on-methods-totriage-intensive-care-patients-in-an-influenza-pandemic
#18
Winston Cheung, John Myburgh, Shay McGuinness, Debra Chalmers, Rachael Parke, Fiona Blyth, Ian Seppelt, Michael Parr, Claire Hooker, Nikki Blackwell, Shannon DeMonte, Kalpesh Gandhi, Mark Kol, Ian Kerridge, Priya Nair, Nicholas M Saunders, Manoj K Saxena, Govindasamy Thanakrishnan, Vasi Naganathan
BACKGROUND AND OBJECTIVE: An influenza pandemic has the potential to overwhelm intensive care resources, but the views of the general public on how resources should be allocated in such a scenario were unknown. We aimed to determine Australian and New Zealand public opinion on how intensive care unit beds should be allocated during an influenza pandemic. DESIGN, SETTING, AND PARTICIPANTS: A postal questionnaire was sent to 4000 randomly selected registered voters; 2000 people each from the Australian Electoral Commission and New Zealand Electoral Commission rolls...
September 2017: Critical Care and Resuscitation: Journal of the Australasian Academy of Critical Care Medicine
https://www.readbyqxmd.com/read/28838463/beware-cold-agglutinins-in-organ-donors-ex%C3%A2-vivo-lung-perfusion-from-an-uncontrolled-donation-after-circulatory-determination-of-death-donor-with-a-cold-agglutinin-a-case-report
#19
A Venkataraman, J W Blackwell, W K Funkhouser, K R Birchard, S E Beamer, W T Simmons, S H Randell, T M Egan
BACKGROUND: We began to recover lungs from uncontrolled donation after circulatory determination of death to assess for transplant suitability by means of ex vivo lung perfusion (EVLP) and computerized tomographic (CT) scan. Our first case had a cold agglutinin with an interesting outcome. CASE REPORT: A 60-year-old man collapsed at home and was pronounced dead by Emergency Medical Services personnel. Next-of-kin consented to lung retrieval, and the decedent was ventilated and transported...
September 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28835384/ezh2-inhibition-by-tazemetostat-results-in-altered-dependency-on-b-cell-activation-signaling-in-dlbcl
#20
Dorothy Brach, Danielle Johnston-Blackwell, Allison Drew, Trupti Lingaraj, Vinny Motwani, Natalie M Warholic, Igor Feldman, Christopher Plescia, Jesse J Smith, Robert A Copeland, Heike Keilhack, Elayne Chan-Penebre, Sarah K Knutson, Scott A Ribich, Alejandra Raimondi, Michael J Thomenius
The EZH2 small-molecule inhibitor tazemetostat (EPZ-6438) is currently being evaluated in phase II clinical trials for the treatment of non-Hodgkin lymphoma (NHL). We have previously shown that EZH2 inhibitors display an antiproliferative effect in multiple preclinical models of NHL, and that models bearing gain-of-function mutations in EZH2 were consistently more sensitive to EZH2 inhibition than lymphomas with wild-type (WT) EZH2 Here, we demonstrate that cell lines bearing EZH2 mutations show a cytotoxic response, while cell lines with WT-EZH2 show a cytostatic response and only tumor growth inhibition without regression in a xenograft model...
November 2017: Molecular Cancer Therapeutics
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