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Do Hematopoietic Cell Transplant Patients Treated on a Clinical Trial Do Better? Comparison of Characteristics and Outcomes of Patients Enrolled Versus Not Enrolled on Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) 0201 Trial

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Blood 2014年第21期124卷 209-209页

作者： Nandita Khera Navneet S. Majhail Ruta Brazauskas Zhiwei Wang Mahmoud Aljurf Görgün Akpek Yoshiko Atsuta Sara Beattie Christopher N. Bredeson Linda J. Burns Allen R. Chen Jason Dehn César O Freytes Vikas Gupta Gregory A. Hale Yoshihiro Inamoto Hillard M. Lazarus Charles F. LeMaistre Jeanne M. Palmer Kristjan Paulson Stephanie J. Lee Mayo Clinic Arizona Phoenix AZ Cleveland Clinic Cleveland OH Medical College of Wisconsin Milwaukee WI King Faisal Specialist Hospital and Research Centre Riyadh Saudi Arabia Section of Hematology Oncology Gilbert AZ Japanese Data Center for Hematopoietic Cell Transplantation Nagoya Japan University of Ottawa Ottawa Canada The Ottawa Hospital Ottawa Canada University of Minnesota Minneapolis MN Johns Hopkins University Baltimore MD National Marrow Donor Program Minneapolis MN University of Texas Health Science Center at San Antonio San Antonio TX Princess Margaret Cancer Centre University of Toronto Toronto Canada All Children’s Hospital St. Petersburg FL Fred Hutchinson Cancer Research Center Seattle WA University Hospitals Seidman Cancer Center and Case Western Reserve University Cleveland OH Sarah Cannon Nashville TN Mayo Clinic Arizona and Phoenix Children’s Hospital Phoenix AZ CancerCare Manitoba University of Manitoba Winnipeg Canada

Background: The association of clinical trial participation with outcomes in cancer patients is controversial, with some studies reporting better outcomes for trial participants while others do not. It is possible that the difference in outcomes is due to differences in baseline characteristics of participants and non-participants. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 trial was a large randomized, multi-center study comparing peripheral blood (PB) with bone marrow (BM) for hematopoietic cell transplantation (HCT) from HLA-matched or 1 allele mismatched unrelated donors (URD) in patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndromes. The trial reported no significant survival differences between PB and BM; there was decreased risk of graft failure but increased risk of chronic graft-versus-host disease (GVHD) with PB grafts (Anasetti et al NEJM 2012). Methods: We compared characteristics of BMT CTN 0201 study participants (n=494) with HCT recipients who did not participate on the trial (n=1384) but were potentially eligible by virtue of known characteristics. These patients received similar conditioning and GVHD prophylaxis as trial participants at 38 United States trial centers during the study time-period. Centers that had no eligible non-trial participants were excluded. Outcomes between patients on and off trial were compared using Cox proportional hazards regression models. data were obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR) that collects patient data on all trial and non-trial allogeneic HCT recipients through its registry function. Results: Approximately 29% [494/1878] of apparently eligible patients were randomized and analyzed as part of the trial. There were no significant differences between study participants and non-participants in age or sex distribution, disease types, HLA or sex matching, comorbidities, or interval from diagnosis to HCT. High

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Clinical "MUTATOME" Of Myelodysplastic Syndrome;Comparison To Primary Acute Myelogenous Leukemia

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BLOOD 2013年第21期122卷 518-518页

作者： Makishima, Hideki LaFramboise, Thomas Przychodzen, Bartlomiej P. Yoshida, Kenichi Ruffalo, Matthew Gomez-Segui, Ines Husseinzadeh, Holleh D. Shiraishi, Yuichi Sanada, Masashi Nagata, Yasunobu Sato, Yusuke Sato-Otsubo, Aiko Chiba, Kenichi Tanaka, Hiroko Nakamaki, Tsuyoshi Hofmann, Wolf-Karsten Miyawaki, Shuichi Shih, Lee-Yung Chiba, Shigeru Miyano, Satoru Hosono, Naoko Polprasert, Chantana Thota, Swapna Dienes, Brittney Guinta, Kathryn M. Sauntharatajah, Yogen Sekeres, Mikkael A. Ogawa, Seishi Maciejewski, Jaroslaw P. Translational Hematology and Oncology Research Cleveland Clinic Taussig Cancer Institute Cleveland OH USA Department of Electrical Engineering and Computer Science Case Western Reserve University Cleveland OH USA Department of Pathology and Tumor biology Kyoto University Kyoto Japan Electrical Engineering and Computer Science Case Western Reserve University Cleveland OH USA Hematology Department University Hospital La Fe Valencia Spain Laboratory of DNA Information Analysis Human Genome Center Institute of Medical Science The University of Tokyo Tokyo Japan Department of Pathology and Tumor Biology Graduate School of Medicine Kyoto University Kyoto Japan Cancer Genomics Project Graduate School of Medicine The University of Tokyo Tokyo Japan Laboratory of Sequence Data Analysis Human Genome Center Institute of Medical Science The University of Tokyo Tokyo Japan Division of Hematology Department of Medicine Showa University School of Medicine Tokyo Japan Department of Hematology and Oncology University Hospital Mannheim Mannheim Germany Division of Hematology Department of Internal Medicine Tokyo Metropolitan Ohtsuka Hospital Tokyo Japan Chang Gung Memorial Hospital Taoyuan Taiwan Department of Hematology Faculty of Medicine University of Tsukuba Tsukuba Japan Translational Hematology Oncology Research Cleveland Clinic Taussig Cancer Institute Cleveland OH USA Department of Translational Hematology and Oncology Research Taussig Cancer Institute Cleveland Clinic Cleveland OH USA Translational Hematology and Oncology Research Taussig Cancer Institute Cleveland Clinic Cleveland OH USA Leukemia Program Department of Hematologic Oncology and Blood Disorders Taussig Cancer Institute Cleveland Clinic Cleveland OH USA

Chromosomal aberrations and somatic mutations constitute key elements of the pathogenesis of myelodysplastic syndromes (MDS), a clonal hematologic malignancy characterized by cytopenias, a dysplastic bone marrow and propensity to clonal evolution. Next generation sequencing (NGS) enables definition of somatic mutational patterns and clonal architecture as a discovery platform, and for clinical *** systematically applied NGS to 707 cases of MDS and MDS-related disorders. 205 cases (low-risk MDS: N=78, high-risk MDS: N=42, MDS/MPN: N=48 and sAML: N=37) were tested by whole exome sequencing (WES). For validation in an additional 502 patients (low-risk MDS: N=192, high-risk MDS: N=104, MDS/MPN: N=111 and sAML: N=95), targeted deep NGS was applied for 60 index genes which were most commonly affected in the cohort analyzed by WES. For NGS data analysis a statistical pipeline was developed to focus on: i) identification of the most relevant somatic mutations, and ii) minimization of false positive results. We studied serial samples from 21 exemplary informative patients. We also compared somatic mutational patterns to those seen in primary AML TCGA cohort (N=201). Given the size of the cohort, there was, for example, a 87% chance of seeing mutations at a frequency of 1% and a 98% of seeing those with a frequency of 2%. While focusing on the most common events, we observed 1117 somatic mutations in 199 genes. The 88 genes mutated mutated in >1% of cases with MDS carried 388 mutations in MDS+sAML (2.5/case), 128 in MDS/MPN (2.7/case) and 398 in pAML (2.0/case). The average number of mutations per case increased during progression (2.2 in lower-risk, 2.8 in higher-risk MDS, 3.4 in sAML). In MDS, the 30 most frequently affected genes were present at least once in 70% of patients. The 30 most frequently mutated genes in MDS/MPN were mutated in 82% of patients. Individual mutations were also sub-grouped according to their function. When we compared three MDS subcateg

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Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science : Seattle, WA, USA. 24-26 September 2015

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Implementation science : IS 2016年第1期11 Suppl 1卷 85页

作者： Cara Lewis Doyanne Darnell Suzanne Kerns Maria Monroe-DeVita Sara J. Landes Aaron R. Lyon Cameo Stanick Shannon Dorsey Jill Locke Brigid Marriott Ajeng Puspitasari Caitlin Dorsey Karin Hendricks Andria Pierson Phil Fizur Katherine A. Comtois Lawrence A. Palinkas Patricia Chamberlain Gregory A. Aarons Amy E. Green Mark. G. Ehrhart Elise M. Trott Cathleen E. Willging Maria E. Fernandez Nicholas H. Woolf Shuting Lily Liang Natalia I. Heredia Michelle Kegler Betsy Risendal Andrea Dwyer Vicki Young Dayna Campbell Michelle Carvalho Yvonne Kellar-Guenther Laura J. Damschroder Julie C. Lowery Sarah S. Ono Kathleen F. Carlson Erika K. Cottrell Maya E. O’Neil Travis L. Lovejoy Joanna J. Arch Jill L. Mitchell Cara C. Lewis Brigid R. Marriott Kelli Scott Jennifer Schurer Coldiron Eric J. Bruns Alyssa N. Hook Benjamin C. Graham Katelin Jordan Rochelle F. Hanson Angela Moreland Benjamin E. Saunders Heidi S. Resnick Shannon Wiltsey Stirman Cassidy A. Gutner Jennifer Gamarra Dawne Vogt Michael Suvak Jennifer Schuster Wachen Katherine Dondanville Jeffrey S. Yarvis Jim Mintz Alan L. Peterson Elisa V. Borah Brett T. Litz Alma Molino Stacey Young McCaughan Patricia A. Resick Nancy Pandhi Nora Jacobson Neftali Serrano Armando Hernandez Elizabeth Zeidler- Schreiter Natalie Wietfeldt Zaher Karp Michael D. Pullmann Barbara Lucenko Bridget Pavelle Jacqueline A. Uomoto Andrea Negrete Molly Cevasco Suzanne E. U. Kerns Robert P. Franks Christopher Bory Edward J. Miech Teresa M. Damush Jason Satterfield Derek Satre Maria Wamsley Patrick Yuan Patricia O’Sullivan Helen Best Susan Velasquez Miya Barnett Lauren Brookman-Frazee Jennifer Regan Nicole Stadnick Alison Hamilton Anna Lau Scott Roesch Byron J. Powell Thomas J. Waltz Matthew J. Chinman Laura Damschroder Jeffrey L. Smith Monica M. Matthieu Enola K. Proctor JoAnn E. Kirchner Monica J. Matthieu Craig S. Rosen Sarah C. Walker Asia S. Bishop Mariko Lockhart Allison L. Rodriguez Luisa Manfredi Andrea Nevedal Joel Rosenthal Daniel M. Blonigen Anne M. Mauricio Thomas D. Dishion Jenna Rudo-Stern Department of Psychological and Brain Sciences Indiana University Bloomington USA Department of Psychiatry & Behavioral Sciences University of Washington Seattle USA Psychology Department University of Montana Missoula USA Department of Psychology La Salle University Philadelphia USA Division of Public Behavioral Health and Justice Policy University of Washington Seattle USA National Center for PTSD VA Palo Alto Health Care System Menlo Park USA Department of Psychiatry University of Arkansas for Medical Sciences Little Rock USA Department of Psychology University of Washington Seattle USA Department of Speech and Hearing Sciences University of Washington Seattle USA Department of Psychological Sciences University of Missouri Columbia USA Department of Children Youth and Families School of Social Work University of Southern California Los Angeles USA Oregon Social Learning Center Eugene USA Department of Psychiatry University of California San Diego La Jolla USA Child and Adolescent Services Research Center (CASRC) San Diego USA Department of Psychology San Diego State University San Diego USA Pacific Institute for Research and Evaluation Behavioral Health Research Center of the Southwest Albuquerque USA School of Public Health University of Texas Health Science Center at Houston Houston USA Woolf Consulting Santa Barbara USA Rollins School of Public Health Emory University Atlanta USA University of Colorado Cancer Center at Denver Aurora USA South Carolina Primary Health Care Association Columbia USA Veterans Affairs (VA) Ann Arbor Center for Clinical Management Research Ann Arbor USA Personalizing Options through Veteran Engagement (PROVE) Quality Enhancement Research Initiative (QUERI) Program Ann Arbor USA Center to Improve Veteran Involvement in Care (CIVIC) Veterns Affairs (VA) Portland Health Care System (VAPORHCS) Portland USA Department of Family Medicine Oregon Health & Science University Portland USA Division of General Internal Medi

Introduction to the 3rd Biennial Conference of the Society for Implementation Research Collaboration: advancing efficient methodologies through team science and community partnerships Cara Lewis, Doyanne Darnell, Suzanne Kerns, Maria Monroe-DeVita, Sara J. Landes, Aaron R. Lyon, Cameo Stanick, Shannon Dorsey, Jill Locke, Brigid Marriott, Ajeng Puspitasari, Caitlin Dorsey, Karin Hendricks, Andria Pierson, Phil Fizur, Katherine A. Comtois A1: A behavioral economic perspective on adoption, implementation, and sustainment of evidence-based interventions Lawrence A. Palinkas A2: Towards making scale up of evidence-based practices in child welfare systems more efficient and affordable Patricia Chamberlain A3: Mixed method examination of strategic leadership for evidence-based practice implementation Gregory A. Aarons, Amy E. Green, Mark. G. Ehrhart, Elise M. Trott, Cathleen E. Willging A4: Implementing practice change in Federally Qualified Health Centers: Learning from leaders’ experiences Maria E. Fernandez, Nicholas H. Woolf, Shuting (Lily) Liang, Natalia I. Heredia, Michelle Kegler, Betsy Risendal, Andrea Dwyer, Vicki Young, Dayna Campbell, Michelle Carvalho, Yvonne Kellar-Guenther A3: Mixed method examination of strategic leadership for evidence-based practice implementation Gregory A. Aarons, Amy E. Green, Mark. G. Ehrhart, Elise M. Trott, Cathleen E. Willging A4: Implementing practice change in Federally Qualified Health Centers: Learning from leaders’ experiences Maria E. Fernandez, Nicholas H. Woolf, Shuting (Lily) Liang, Natalia I. Heredia, Michelle Kegler, Betsy Risendal, Andrea Dwyer, Vicki Young, Dayna Campbell, Michelle Carvalho, Yvonne Kellar-Guenther A5: Efficient synthesis: Using qualitative comparative analysis and the Consolidated Framework for Implementation Research across diverse studies Laura J. Damschroder, Julie C. Lowery A6: Establishing a veterans engagement group to empower patients and inform Veterans Affairs (VA) health services research Sara

关键词： Veteran Affair Motivational Interview Veteran Health Administration Dialectical Behavior Therapy Qualitative Comparative Analysis

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Lsh, chromatin remodeling family member, modulates genome-wide cytosine methylation patterns at nonrepeat sequences (vol 108, pg 5626, 2011)

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PROCEEDINGS OF THE NATIONAL ACADEMY OF scienceS OF THE UNITED STATES OF AMERICA 2011年第37期108卷 15535-15535页

作者： Tao, Yongguang Xi, Sichuan Shan, Jigui Maunakea, Alika Che, Anney Briones, Victorino Lee, Eunice Y. Geiman, Theresa Huang, Jiaqiang Stephens, Robert Leighty, Robert M. Zhao, Keji Muegge, Kathrin [a]Basic Science Program Laboratory of Cancer Prevention [b]Advanced Biomedical Computing Center and [d]Data Management Services Science Applications International Corporation Frederick Inc. National Cancer Institute Frederick Frederick MD 21702 and [c]Laboratory of Molecular Immunology National Heart Lung and Blood Institute National Institutes of Health Bethesda MD 20817

DNA methylation is critical for normal development and plays important roles in genome organization and transcriptional regulation. Although DNA methyltransferases have been identified, the factors that establish and contribute to genome-wide methylation patterns remain elusive. Here, we report a high-resolution cytosine methylation map of the murine genome modulated by Lsh, a chromatin remodeling family member that has previously been shown to regulate CpG methylation at repetitive sequences. We provide evidence that Lsh also controls genome-wide cytosine methylation at nonrepeat sequences and relate those changes to alterations in H4K4me3 modification and gene expression. Deletion of Lsh alters the allocation of cytosine methylation in chromosomal regions of 50 kb to 2 Mb and, in addition, leads to changes in the methylation profile at the 5' end of genes. Furthermore, we demonstrate that loss of Lsh promotes--as well as prevents--cytosine methylation. Our data indicate that Lsh is an epigenetic modulator that is critical for normal distribution of cytosine methylation throughout the murine genome.

关键词： methylated DNA immunoprecipitation chIP-sequencing epigenetics

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THE OVERSELLING OF GENETIC ANXIETY

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HASTINGS CENTER REPORT 1982年第5期12卷 20-27页

作者： GOODMAN, MJ GOODMAN, LE MadeleineJ. Goodman Ph.D.is Director Women's Studies Program and associate professor General Science and Women's Studies University of Hawaii. She is also principal data analyst of the Hawaii Breast Cancer Detection Project. LennE. Goodman D. Phil.is professor of philosophy University of Hawaii. His most recent book isMonotheism: A Philosophic Inquiry into the Foundations of Natural Theology and Ethics.

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Roles of Cellular Neighborhoods in Hepatocellular Carcinoma Pathogenesis

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Pathology: Mechanisms of Disease 1000年第1期20卷 169-192页

作者： Lichun Ma Cherry Caiyi Li Xin Wei Wang 2Liver Cancer Program Center for Cancer Research National Cancer Institute Bethesda Maryland USA 1Cancer Data Science Laboratory Center for Cancer Research National Cancer Institute Bethesda Maryland USA email: lichun.ma@nih.gov 3Laboratory of Human Carcinogenesis Center for Cancer Research National Cancer Institute Bethesda Maryland USA

The development of hepatocellular carcinoma (HCC) involves an intricate interplay among various cell types within the liver. Unraveling the orchestration of these cells, particularly in the context of various etiologies, may hold the key to deciphering the underlying mechanisms of this complex disease. The advancement of single-cell and spatial technologies has revolutionized our ability to determine cellular neighborhoods and understand their crucial roles in disease pathogenesis. In this review, we highlight the current research landscape on cellular neighborhoods in chronic liver disease and HCC, as well as the emerging computational approaches applicable to delineate disease-associated cellular neighborhoods, which may offer insights into the molecular mechanisms underlying HCC pathogenesis and pave the way for effective disease interventions.

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cancer Genomic Rearrangements and Copy Number Alterations from Errors in Cell Division

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cancer Biology 1000年第1期6卷 245-268页

作者： Cheng-Zhong Zhang David Pellman 3Cancer Program Broad Institute of MIT and Harvard Cambridge Massachusetts USA 2Department of Biomedical Informatics Blavatnik Institute of Harvard Medical School Boston Massachusetts USA 1Department of Data Science Dana-Farber Cancer Institute Boston Massachusetts USA email: cheng-zhong_zhang@dfci.harvard.edu 4Howard Hughes Medical Institute Chevy Chase Maryland USA 5Department of Pediatric Oncology Dana-Farber Cancer Institute Boston Massachusetts USA email: david_pellman@dfci.harvard.edu 6Department of Cell Biology Blavatnik Institute of Harvard Medical School Boston Massachusetts USA

Analysis of cancer genomes has shown that a large fraction of chromosomal changes originate from catastrophic events including whole-genome duplication, chromothripsis, breakage-fusion-bridge cycles, and chromoplexy. Through sophisticated computational analysis of cancer genomes and experimental recapitulation of these catastrophic alterations, we have gained significant insights into the origin, mechanism, and evolutionary dynamics of cancer genome complexity. In this review, we summarize this progress and survey the major unresolved questions, with particular emphasis on the relative contributions of chromosome fragmentation and DNA replication errors to complex chromosomal alterations.

关键词： somatic copy number alterations chromosome rearrangement cancer evolution whole-genome duplication micronuclei chromosome bridge

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