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https://www.readbyqxmd.com/read/28193779/combination-targeted-therapy-to-disrupt-aberrant-oncogenic-signaling-and-reverse-epigenetic-dysfunction-in-idh2-and-tet2-mutant-acute-myeloid-leukemia
#1
Alan H Shih, Cem Meydan, Kaitlyn Shank, Francine E Garrett-Bakelman, Patrick S Ward, Andrew Intlekofer, Abbas Nazir, Eytan Stein, Kristina Knapp, Jacob Glass, Jeremy Travins, Kim Straley, Camelia Gliser, Chris Mason, Katharine Yen, Craig B Thompson, Ari Melnick, Ross L Levine
Genomic studies in acute myeloid leukemias (AML) have identified mutations which drive altered DNA methylation, including TET2 and IDH2. Here we show that models of AMLs resulting from TET2 or IDH2 mutations combined with FLT3ITD mutations are sensitive to 5-Azacytidine or to the IDH2 inhibitor AG-221, respectively. 5-Azacytidine and AG-221 treatment induced an attenuation of aberrant DNA methylation and transcriptional output, and resulted in a reduction in leukemic blasts consistent with anti-leukemic activity...
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28135282/mesenchymal-cell-reprogramming-in-experimental-mplw515l-mouse-model-of-myelofibrosis
#2
Ying Han, Lanzhu Yue, Max Wei, Xiubao Ren, Zonghong Shao, Ling Zhang, Ross L Levine, Pearlie K Epling-Burnette
Myelofibrosis is an indicator of poor prognosis in myeloproliferative neoplasms (MPNs), but the precise mechanism(s) contributing to extracellular matrix remodeling and collagen deposition in the bone marrow (BM) niche remains unanswered. In this study, we isolated mesenchymal stromal cells (MSCs) from mice transplanted with wild-type thrombopoietin receptor (MPLWT) and MPLW515L retroviral-transduced bone marrow. Using MSCs derived from MPLW515-transplant recipients, excessive collagen deposition was maintained in the absence of the virus and neoplastic hematopoietic cells suggested that the MSCs were reprogrammed in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28123069/cd99-is-a-therapeutic-target-on-disease-stem-cells-in-myeloid-malignancies
#3
Stephen S Chung, William S Eng, Wenhuo Hu, Mona Khalaj, Francine E Garrett-Bakelman, Montreh Tavakkoli, Ross L Levine, Martin Carroll, Virginia M Klimek, Ari M Melnick, Christopher Y Park
Acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS) are initiated and sustained by self-renewing malignant stem cells; thus, eradication of AML and MDS stem cells is required for cure. We identified CD99 as a cell surface protein frequently overexpressed on AML and MDS stem cells. Expression of CD99 allows for prospective separation of leukemic stem cells (LSCs) from functionally normal hematopoietic stem cells in AML, and high CD99 expression on AML blasts enriches for functional LSCs as demonstrated by limiting dilution xenotransplant studies...
January 25, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28103614/enrichment-of-putative-pax8-target-genes-at-serous-epithelial-ovarian-cancer-susceptibility-loci
#4
Siddhartha P Kar, Emily Adler, Jonathan Tyrer, Dennis Hazelett, Hoda Anton-Culver, Elisa V Bandera, Matthias W Beckmann, Andrew Berchuck, Natalia Bogdanova, Louise Brinton, Ralf Butzow, Ian Campbell, Karen Carty, Jenny Chang-Claude, Linda S Cook, Daniel W Cramer, Julie M Cunningham, Agnieszka Dansonka-Mieszkowska, Jennifer Anne Doherty, Thilo Dörk, Matthias Dürst, Diana Eccles, Peter A Fasching, James Flanagan, Aleksandra Gentry-Maharaj, Rosalind Glasspool, Ellen L Goode, Marc T Goodman, Jacek Gronwald, Florian Heitz, Michelle A T Hildebrandt, Estrid Høgdall, Claus K Høgdall, David G Huntsman, Allan Jensen, Beth Y Karlan, Linda E Kelemen, Lambertus A Kiemeney, Susanne K Kjaer, Jolanta Kupryjanczyk, Diether Lambrechts, Douglas A Levine, Qiyuan Li, Jolanta Lissowska, Karen H Lu, Jan Lubiński, Leon F A G Massuger, Valerie McGuire, Iain McNeish, Usha Menon, Francesmary Modugno, Alvaro N Monteiro, Kirsten B Moysich, Roberta B Ness, Heli Nevanlinna, James Paul, Celeste L Pearce, Tanja Pejovic, Jennifer B Permuth, Catherine Phelan, Malcolm C Pike, Elizabeth M Poole, Susan J Ramus, Harvey A Risch, Mary Anne Rossing, Helga B Salvesen, Joellen M Schildkraut, Thomas A Sellers, Mark Sherman, Nadeem Siddiqui, Weiva Sieh, Honglin Song, Melissa Southey, Kathryn L Terry, Shelley S Tworoger, Christine Walsh, Nicolas Wentzensen, Alice S Whittemore, Anna H Wu, Hannah Yang, Wei Zheng, Argyrios Ziogas, Matthew L Freedman, Simon A Gayther, Paul D P Pharoah, Kate Lawrenson
BACKGROUND: Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors (TFs) critical to somatic tumorigenesis. METHODS: All 615 TF-target sets from the Molecular Signatures Database were evaluated using gene set enrichment analysis (GSEA) and three GWAS for SOC risk: discovery (2196 cases/4396 controls), replication (7035 cases/21 693 controls; independent from discovery), and combined (9627 cases/30 845 controls; including additional individuals)...
February 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28078910/gain-of-chromosome-1q-portends-worse-prognosis-in-multiple-myeloma-despite-novel-agent-based-induction-regimens-and-autologous-transplantation
#5
Gunjan L Shah, Heather Landau, Dory Londono, Sean M Devlin, Satyajit Kosuri, Alexander M Lesokhin, Nikoletta Lendvai, Hani Hassoun, David J Chung, Guenther Koehne, Suresh C Jhanwar, Ola Landgren, Ross Levine, Sergio A Giralt
We aimed to identify whether the use of autologous hematopoietic cell transplantation (HCT) impacts outcomes for multiple myeloma patients with gains of chromosome 1q (+1q). We retrospectively identified 95 patients, 21% having +1q. For patients with +1q, the overall response rate to induction was 85%, with 40% having ≥ VGPR and 20% achieving a CR, similar to non +1q patients (p = .64). The median PFS from diagnosis with +1q was 2.1 years (95% CI: 1.2-not reached (NR)) vs 4.3 years (95% CI: 3...
January 12, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28077417/aid-is-a-key-regulator-of-myeloid-erythroid-differentiation-and-dna-methylation-in-hematopoietic-stem-progenitor-cells
#6
Hiroyoshi Kunimoto, Anna Sophia McKenney, Cem Meydan, Kaitlyn Shank, Abbas Nazir, Franck Rapaport, Benjamin Durham, Francine E Garrett-Bakelman, Elodie Pronier, Alan H Shih, Ari Melnick, Jayanta Chaudhuri, Ross L Levine
Recent studies have reported activation-induced cytidine deaminase (AID) and ten-eleven-translocation (TET) family members regulate active DNA demethylation. Genetic alterations of TET2 occur in myeloid malignancies and hematopoietic specific loss of Tet2 induces aberrant hematopoietic stem cell (HSC) self-renewal/differentiation, implicating TET2 as a master regulator of normal and malignant hematopoiesis. Despite the functional link between AID and TET in epigenetic gene regulation, the role of AID loss in hematopoiesis and myeloid transformation remains to be investigated...
January 11, 2017: Blood
https://www.readbyqxmd.com/read/28026719/politics-health-systems-and-population-health-an-interview-with-david-levine
#7
J Ross Graham
No abstract available.
December 27, 2016: Canadian Journal of Public Health. Revue Canadienne de Santé Publique
https://www.readbyqxmd.com/read/28000664/endothelial-specific-inhibition-of-nf-%C3%AE%C2%BAb-enhances-functional-haematopoiesis
#8
Michael G Poulos, Pradeep Ramalingam, Michael C Gutkin, Maria Kleppe, Michael Ginsberg, Michael J P Crowley, Olivier Elemento, Ross L Levine, Shahin Rafii, Jan Kitajewski, Matthew B Greenblatt, Jae-Hyuck Shim, Jason M Butler
Haematopoietic stem cells (HSCs) reside in distinct niches within the bone marrow (BM) microenvironment, comprised of endothelial cells (ECs) and tightly associated perivascular constituents that regulate haematopoiesis through the expression of paracrine factors. Here we report that the canonical NF-κB pathway in the BM vascular niche is a critical signalling axis that regulates HSC function at steady state and following myelosuppressive insult, in which inhibition of EC NF-κB promotes improved HSC function and pan-haematopoietic recovery...
December 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27911851/inherited-variants-affecting-rna-editing-may-contribute-to-ovarian-cancer-susceptibility-results-from-a-large-scale-collaboration
#9
Jennifer B Permuth, Brett Reid, Madalene Earp, Y Ann Chen, Alvaro N A Monteiro, Zhihua Chen, Georgia Chenevix-Trench, Peter A Fasching, Matthias W Beckmann, Diether Lambrechts, Adriaan Vanderstichele, Els Van Niewenhuyse, Ignace Vergote, Mary Anne Rossing, Jennifer Anne Doherty, Jenny Chang-Claude, Kirsten Moysich, Kunle Odunsi, Marc T Goodman, Yurii B Shvetsov, Lynne R Wilkens, Pamela J Thompson, Thilo Dörk, Natalia Bogdanova, Ralf Butzow, Heli Nevanlinna, Liisa Pelttari, Arto Leminen, Francesmary Modugno, Robert P Edwards, Roberta B Ness, Joseph Kelley, Florian Heitz, Beth Karlan, Jenny Lester, Susanne K Kjaer, Allan Jensen, Graham Giles, Michelle Hildebrandt, Dong Liang, Karen H Lu, Xifeng Wu, Douglas A Levine, Maria Bisogna, Andrew Berchuck, Daniel W Cramer, Kathryn L Terry, Shelley S Tworoger, Elizabeth M Poole, Elisa V Bandera, Brooke Fridley, Julie Cunningham, Stacey J Winham, Sara H Olson, Irene Orlow, Line Bjorge, Lambertus A Kiemeney, Leon Massuger, Tanja Pejovic, Melissa Moffitt, Nhu Le, Linda S Cook, Angela Brooks-Wilson, Linda E Kelemen, Jacek Gronwald, Jan Lubinski, Nicolas Wentzensen, Louise A Brinton, Jolanta Lissowska, Hanna Yang, Estrid Hogdall, Claus Hogdall, Lene Lundvall, Paul D P Pharoah, Honglin Song, Ian Campbell, Diana Eccles, Iain McNeish, Alice Whittemore, Valerie McGuire, Weiva Sieh, Joseph Rothstein, Catherine M Phelan, Harvey Risch, Steven Narod, John McLaughlin, Hoda Anton-Culver, Argyrios Ziogas, Usha Menon, Simon Gayther, Susan J Ramus, Aleksandra Gentry-Maharaj, Celeste Leigh Pearce, Anna H Wu, Jolanta Kupryjanczyk, Agnieszka Dansonka-Mieszkowska, Joellen M Schildkraut, Jin Q Cheng, Ellen L Goode, Thomas A Sellers
RNA editing in mammals is a form of post-transcriptional modification in which adenosine is converted to inosine by the adenosine deaminases acting on RNA (ADAR) family of enzymes. Based on evidence of altered ADAR expression in epithelial ovarian cancers (EOC), we hypothesized that single nucleotide polymorphisms (SNPs) in ADAR genes modify EOC susceptibility, potentially by altering ovarian tissue gene expression. Using directly genotyped and imputed data from 10,891 invasive EOC cases and 21,693 controls, we evaluated the associations of 5,303 SNPs in ADAD1, ADAR, ADAR2, ADAR3, and SND1...
8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27895058/diagnosis-and-management-of-aml-in-adults-2017-eln-recommendations-from-an-international-expert-panel
#10
REVIEW
Hartmut Döhner, Elihu Estey, David Grimwade, Sergio Amadori, Frederick R Appelbaum, Thomas Büchner, Hervé Dombret, Benjamin L Ebert, Pierre Fenaux, Richard A Larson, Ross L Levine, Francesco Lo-Coco, Tomoki Naoe, Dietger Niederwieser, Gert J Ossenkoppele, Miguel Sanz, Jorge Sierra, Martin S Tallman, Hwei-Fang Tien, Andrew H Wei, Bob Löwenberg, Clara D Bloomfield
The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations...
January 26, 2017: Blood
https://www.readbyqxmd.com/read/27883997/cbt4bn-a-randomized-controlled-trial-of-online-chat-and-face-to-face-group-therapy-for-bulimia-nervosa
#11
Stephanie C Zerwas, Hunna J Watson, Sara M Hofmeier, Michele D Levine, Robert M Hamer, Ross D Crosby, Cristin D Runfola, Christine M Peat, Jennifer R Shapiro, Benjamin Zimmer, Markus Moessner, Hans Kordy, Marsha D Marcus, Cynthia M Bulik
OBJECTIVE: Although cognitive-behavioral therapy (CBT) represents the first-line evidence-based psychotherapy for bulimia nervosa (BN), most individuals seeking treatment do not have access to this specialized intervention. We compared an Internet-based manualized version of CBT group therapy for BN conducted via a therapeutic chat group (CBT4BN) to the same treatment conducted via a traditional face-to-face group therapy (CBTF2F). METHOD: In a two-site, randomized, controlled noninferiority trial, we tested the hypothesis that CBT4BN would not be inferior to CBTF2F...
2017: Psychotherapy and Psychosomatics
https://www.readbyqxmd.com/read/27881567/importance-of-assessing-cardiorespiratory-fitness-in-clinical-practice-a-case-for-fitness-as-a-clinical-vital-sign-a-scientific-statement-from-the-american-heart-association
#12
Robert Ross, Steven N Blair, Ross Arena, Timothy S Church, Jean-Pierre Després, Barry A Franklin, William L Haskell, Leonard A Kaminsky, Benjamin D Levine, Carl J Lavie, Jonathan Myers, Josef Niebauer, Robert Sallis, Susumu S Sawada, Xuemei Sui, Ulrik Wisløff
Mounting evidence has firmly established that low levels of cardiorespiratory fitness (CRF) are associated with a high risk of cardiovascular disease, all-cause mortality, and mortality rates attributable to various cancers. A growing body of epidemiological and clinical evidence demonstrates not only that CRF is a potentially stronger predictor of mortality than established risk factors such as smoking, hypertension, high cholesterol, and type 2 diabetes mellitus, but that the addition of CRF to traditional risk factors significantly improves the reclassification of risk for adverse outcomes...
13, 2016: Circulation
https://www.readbyqxmd.com/read/27862108/predictors-of-dropout-in-face-to-face-and-internet-based-cognitive-behavioral-therapy-for-bulimia-nervosa-in-a-randomized-controlled-trial
#13
Hunna J Watson, Michele D Levine, Stephanie C Zerwas, Robert M Hamer, Ross D Crosby, Caroline S Sprecher, Amy O'Brien, Benjamin Zimmer, Sara M Hofmeier, Hans Kordy, Markus Moessner, Christine M Peat, Cristin D Runfola, Marsha D Marcus, Cynthia M Bulik
OBJECTIVE: We sought to identify predictors and moderators of failure to engage (i.e., pretreatment attrition) and dropout in both Internet-based and traditional face-to-face cognitive-behavioral therapy (CBT) for bulimia nervosa. We also sought to determine if Internet-based treatment reduced failure to engage and dropout. METHOD: Participants (N = 191, 98% female) were randomized to Internet-based CBT (CBT4BN) or traditional face-to-face group CBT (CBTF2F). Sociodemographics, clinical history, eating disorder severity, comorbid psychopathology, health status and quality of life, personality and temperament, and treatment-related factors were investigated as predictors...
November 12, 2016: International Journal of Eating Disorders
https://www.readbyqxmd.com/read/27846385/an-unexpected-chink-in-the-transcriptional-armor-of-plasmacytoid-dendritic-neoplasms
#14
Maria Kleppe, Ross L Levine
In this issue of Cancer Cell, Ceribelli et al. use functional genomic and chemical screening to reveal the existence of a TCF4/BRD4-dependent oncogenic regulatory network in blastic plasmacytoid dendritic cell neoplasm (BPDCN) and demonstrate that BPDCN cells are highly sensitive to therapeutic targeting of this novel dependency.
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27825124/acid-ceramidase-is-upregulated-in-aml-and-represents-a-novel-therapeutic-target
#15
Su-Fern Tan, Xin Liu, Todd E Fox, Brian M Barth, Arati Sharma, Stephen D Turner, Andy Awwad, Alden Dewey, Kenichiro Doi, Barbara Spitzer, Mithun Vinod Shah, Samy A F Morad, Dhimant Desai, Shantu Amin, Junjia Zhu, Jason Liao, Jong Yun, Mark Kester, David F Claxton, Hong-Gang Wang, Myles C Cabot, Edward H Schuchman, Ross L Levine, David J Feith, Thomas P Loughran
There is an urgent unmet need for new therapeutics in acute myeloid leukemia (AML) as standard therapy has not changed in the past three decades and outcome remains poor for most patients. Sphingolipid dysregulation through decreased ceramide levels and elevated sphingosine 1-phosphate (S1P) promotes cancer cell growth and survival. Acid ceramidase (AC) catalyzes ceramide breakdown to sphingosine, the precursor for S1P. We report for the first time that AC is required for AML blast survival. Transcriptome analysis and enzymatic assay show that primary AML cells have high levels of AC expression and activity...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27790103/a-voxel-based-morphometry-study-reveals-local-brain-structural-alterations-associated-with-ambient-fine-particles-in-older-women
#16
Ramon Casanova, Xinhui Wang, Jeanette Reyes, Yasuyuki Akita, Marc L Serre, William Vizuete, Helena C Chui, Ira Driscoll, Susan M Resnick, Mark A Espeland, Jiu-Chiuan Chen
Objective: Exposure to ambient fine particulate matter (PM2.5: PM with aerodynamic diameters < 2.5 μm) has been linked with cognitive deficits in older adults. Using fine-grained voxel-wise analyses, we examined whether PM2.5 exposure also affects brain structure. Methods: Brain MRI data were obtained from 1365 women (aged 71-89) in the Women's Health Initiative Memory Study and local brain volumes were estimated using RAVENS (regional analysis of volumes in normalized space). Based on geocoded residential locations and air monitoring data from the U...
2016: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/27766616/genomics-of-primary-chemoresistance-and-remission-induction-failure-in-paediatric-and-adult-acute-myeloid-leukaemia
#17
Fiona C Brown, Paolo Cifani, Esther Drill, Jie He, Eric Still, Shan Zhong, Sohail Balasubramanian, Dean Pavlick, Bahar Yilmazel, Kristina M Knapp, Todd A Alonzo, Soheil Meshinchi, Richard M Stone, Steven M Kornblau, Guido Marcucci, Alan S Gamis, John C Byrd, Mithat Gonen, Ross L Levine, Alex Kentsis
Cure rates of children and adults with acute myeloid leukaemia (AML) remain unsatisfactory partly due to chemotherapy resistance. We investigated the genetic basis of AML in 107 primary cases by sequencing 670 genes mutated in haematological malignancies. SETBP1, ASXL1 and RELN mutations were significantly associated with primary chemoresistance. We identified genomic alterations not previously described in AML, together with distinct genes that were significantly overexpressed in therapy-resistant AML. Defined gene mutations were sufficient to explain primary induction failure in only a minority of cases...
January 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/27738273/sex-scavengers-and-chaperones-transcriptome-secrets-of-divergent-symbiodinium-thermal-tolerances
#18
Rachel A Levin, Victor H Beltran, Ross Hill, Staffan Kjelleberg, Diane McDougald, Peter D Steinberg, Madeleine J H van Oppen
No abstract text is available yet for this article.
November 2016: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/27706135/the-epichaperome-is-an-integrated-chaperome-network-that-facilitates-tumour-survival
#19
Anna Rodina, Tai Wang, Pengrong Yan, Erica DaGama Gomes, Mark P S Dunphy, Nagavarakishore Pillarsetty, John Koren, John F Gerecitano, Tony Taldone, Hongliang Zong, Eloisi Caldas-Lopes, Mary Alpaugh, Adriana Corben, Matthew Riolo, Brad Beattie, Christina Pressl, Radu I Peter, Chao Xu, Robert Trondl, Hardik J Patel, Fumiko Shimizu, Alexander Bolaender, Chenghua Yang, Palak Panchal, Mohammad F Farooq, Sarah Kishinevsky, Shanu Modi, Oscar Lin, Feixia Chu, Sujata Patil, Hediye Erdjument-Bromage, Pat Zanzonico, Clifford Hudis, Lorenz Studer, Gail J Roboz, Ethel Cesarman, Leandro Cerchietti, Ross Levine, Ari Melnick, Steven M Larson, Jason S Lewis, Monica L Guzman, Gabriela Chiosis
Transient, multi-protein complexes are important facilitators of cellular functions. This includes the chaperome, an abundant protein family comprising chaperones, co-chaperones, adaptors, and folding enzymes-dynamic complexes of which regulate cellular homeostasis together with the protein degradation machinery. Numerous studies have addressed the role of chaperome members in isolation, yet little is known about their relationships regarding how they interact and function together in malignancy. As function is probably highly dependent on endogenous conditions found in native tumours, chaperomes have resisted investigation, mainly due to the limitations of methods needed to disrupt or engineer the cellular environment to facilitate analysis...
October 20, 2016: Nature
https://www.readbyqxmd.com/read/27677730/no-evidence-that-genetic-variation-in-the-myeloid-derived-suppressor-cell-pathway-influences-ovarian-cancer-survival
#20
Lara E Sucheston-Campbell, Rikki Cannioto, Alyssa I Clay, John Lewis Etter, Kevin H Eng, Song Liu, Sebastiano Battaglia, Qiang Hu, J Brian Szender, Albina Minlikeeva, Janine Joseph, Paul Mayor, Scott I Abrams, Brahm Segal, Paul K Wallace, Kah Teong Soh, Emese Z Zsiros, Hoda Anton-Culver, Elisa V Bandera, Matthias W Beckmann, Andrew Berchuck, Line Bjørge, Amanda Bruegl, Ian G Campbell, Shawn Patrice Campbell, Georgia Chenevix-Trench, Daniel Cramer, Agnieszka Dansonka-Mieszkowska, Fanny Dao, Brenda Diergaarde, Thilo Doerk, Jennifer A Doherty, Andreas du Bois, Diana Eccles, Svend Aage Engelholm, Peter A Fasching, Simon A Gayther, Aleksandra Gentry-Maharaj, Rosalind M Glasspool, Marc T Goodman, Jacek Gronwald, Philipp Harter, Alexander Hein, Florian Heitz, Peter Hillemmanns, Claus Hogdall, Estrid V S Høgdall, Tomasz Huzarski, Allan Jensen, Sharon E Johnatty, Audrey Jung, Beth Karlan, Rüdiger Klapdor, Tomasz Kluz, Bozena Konopka, Susanne Krüger Kjær, Jolanta Kupryjanczyk, Diether Lambrechts, Jenny Lester, Jan Lubiński, Douglas A Levine, Lene Lundvall, Valerie McGuire, Iain A McNeish, Usha Menon, Francesmary Modugno, Roberta B Ness, Sandra Orsulic, James Paul, Celeste Leigh Pearce, Tanja Pejovic, Paul Pharoah, Susan J Ramus, Joseph Rothstein, Mary Anne Rossing, Matthias Rübner, Joellen M Schildkraut, Barbara Schmalfeldt, Ira Schwaab, Nadeem Siddiqui, Weiva Sieh, Piotr Sobiczewski, Honglin Song, Kathryn L Terry, Els Van Nieuwenhuysen, Adriaan Vanderstichele, Ignace Vergote, Christine S Walsh, Penelope M Webb, Nicolas Wentzensen, Alice S Whittemore, Anna H Wu, Argyrios Ziogas, Kunle Odunsi, Jenny Chang-Claude, Ellen L Goode, Kirsten B Moysich
BACKGROUND: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immune suppressive/pro-tumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be one prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. METHODS: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC...
September 27, 2016: Cancer Epidemiology, Biomarkers & Prevention
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