The Impact of RB Deficiency on Hepatocyte Biology and Tumorigenesis PDF Download
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Author: Ryan J. Bourgo
Publisher:
ISBN:
Category :
Languages : en
Pages : 266
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Book Description
The integrity of the RB tumor suppressor pathway is critical for inhibition of inappropriate proliferation and suppression of tumor development in a wide variety of human tissues. RB has been shown to play a number of distinct roles in contributing to tumor suppression; studies have implicated the RB pathway in DNA damage response, genome instability, establishment of senescence, and promotion of differentiation, among other processes. Despite intensive research, however, the specific functions of RB as they relate to individual disease contexts and distinct facets of cellular stress response remain unclear. Herein, research is directed at first unmasking the immediate underlying impact of RB deletion in vivo , and then subsequently probing the specific disease-relevant functions of RB deficiency during DNA damage response and subsequent liver tumorigenesis. Tissue specific deletion of RB revealed a profound induction of E2F-mediated DNA replication that was characterized by hyper-physiological formation of pre-replication complexes. These phenotypes were not accompanied by productive mitoses. Uniquely, RB-deficient hepatocytes accumulated aberrant ploidy and significant levels of DNA damage. Furthermore, in vitro and in vivo analyses demonstrate the LXCXE-binding function of RB, while dispensable for E2F-promoter association, is required for mediating appropriate transcriptional control during DNA damage response in the liver. Such aberrant responses were mediated preferentially through E2F3. Long-term studies demonstrated that disruption of LXCXE-binding accelerated DNA damage mediated tumorigenesis in vivo and gene expression profiling revealed that the transcriptional program mediated by this function of RB was associated with progression to HCC in humans. Surprisingly, gene expression profiling also revealed an unexpected role for RB in modulation of immune response gene transcription. Together, these studies demonstrate and establish highly tissue-specific and context-depentent roles for RB in transcriptional control and tumor suppression.
Author: Ryan J. Bourgo
Publisher:
ISBN:
Category :
Languages : en
Pages : 266
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Book Description
The integrity of the RB tumor suppressor pathway is critical for inhibition of inappropriate proliferation and suppression of tumor development in a wide variety of human tissues. RB has been shown to play a number of distinct roles in contributing to tumor suppression; studies have implicated the RB pathway in DNA damage response, genome instability, establishment of senescence, and promotion of differentiation, among other processes. Despite intensive research, however, the specific functions of RB as they relate to individual disease contexts and distinct facets of cellular stress response remain unclear. Herein, research is directed at first unmasking the immediate underlying impact of RB deletion in vivo , and then subsequently probing the specific disease-relevant functions of RB deficiency during DNA damage response and subsequent liver tumorigenesis. Tissue specific deletion of RB revealed a profound induction of E2F-mediated DNA replication that was characterized by hyper-physiological formation of pre-replication complexes. These phenotypes were not accompanied by productive mitoses. Uniquely, RB-deficient hepatocytes accumulated aberrant ploidy and significant levels of DNA damage. Furthermore, in vitro and in vivo analyses demonstrate the LXCXE-binding function of RB, while dispensable for E2F-promoter association, is required for mediating appropriate transcriptional control during DNA damage response in the liver. Such aberrant responses were mediated preferentially through E2F3. Long-term studies demonstrated that disruption of LXCXE-binding accelerated DNA damage mediated tumorigenesis in vivo and gene expression profiling revealed that the transcriptional program mediated by this function of RB was associated with progression to HCC in humans. Surprisingly, gene expression profiling also revealed an unexpected role for RB in modulation of immune response gene transcription. Together, these studies demonstrate and establish highly tissue-specific and context-depentent roles for RB in transcriptional control and tumor suppression.
Author: Yujin Hoshida
Publisher: Springer
ISBN: 3030215407
Category : Medical
Languages : en
Pages : 366
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Book Description
This book provides a comprehensive overview of the current limitations and unmet needs in Hepatocellular Carcinoma (HCC) diagnosis, treatment, and prevention. It also provides newly emerging concepts, approaches, and technologies to address challenges. Topics covered include changing landscape of HCC etiologies in association with health disparities, framework of clinical management algorithm, new and experimental modalities of HCC diagnosis and prognostication, multidisciplinary treatment options including rapidly evolving molecular targeted therapies and immune therapies, multi-omics molecular characterization, and clinically relevant experimental models. The book is intended to assist collaboration between the diverse disciplines and facilitate forward and reverse translation between basic and clinical research by providing a comprehensive overview of relevant areas, covering epidemiological trend and population-level patient management strategies, new diagnostic and prognostic tools, recent advances in the standard care and novel therapeutic approaches, and new concepts in pathogenesis and experimental approaches and tools, by experts and opinion leaders in their respective fields. By thoroughly and concisely covering whole aspects of HCC care, Hepatocellular Carcinoma serves as a valuable reference for multidisciplinary readers, and promotes the development of personalized precision care strategies that lead to substantial improvement of disease burden and patient prognosis in HCC.
Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 030905088X
Category : Medical
Languages : en
Pages : 560
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Book Description
The physiological or psychological stresses that employees bring to their workplace affect not only their own performance but that of their co-workers and others. These stresses are often compounded by those of the job itself. Medical personnel, firefighters, police, and military personnel in combat settingsâ€"among othersâ€"experience highly unpredictable timing and types of stressors. This book reviews and comments on the performance-enhancing potential of specific food components. It reflects the views of military and non-military scientists from such fields as neuroscience, nutrition, physiology, various medical specialties, and performance psychology on the most up-to-date research available on physical and mental performance enhancement in stressful conditions. Although placed within the context of military tasks, the volume will have wide-reaching implications for individuals in any job setting.
Author: Irwin M. Arias
Publisher: John Wiley & Sons
ISBN: 1119436826
Category : Medical
Languages : en
Pages : 1156
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Book Description
Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume: Relates molecular physiology to understanding disease pathology and treatment Links the science and pathology of the liver to practical clinical applications Features 16 new “Horizons” chapters that explore new and emerging science and technology Includes plentiful full-color illustrations and figures The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism.
Author:
Publisher: Elsevier
ISBN: 0081006128
Category : Science
Languages : en
Pages : 8639
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Book Description
Comprehensive Toxicology, Third Edition, Fifteen Volume Set discusses chemical effects on biological systems, with a focus on understanding the mechanisms by which chemicals induce adverse health effects. Organized by organ system, this comprehensive reference work addresses the toxicological effects of chemicals on the immune system, the hematopoietic system, cardiovascular system, respiratory system, hepatic toxicology, renal toxicology, gastrointestinal toxicology, reproductive and endocrine toxicology, neuro and behavioral toxicology, developmental toxicology and carcinogenesis, also including critical sections that cover the general principles of toxicology, cellular and molecular toxicology, biotransformation and toxicology testing and evaluation. Each section is examined in state-of-the-art chapters written by domain experts, providing key information to support the investigations of researchers across the medical, veterinary, food, environment and chemical research industries, and national and international regulatory agencies. Thoroughly revised and expanded to 15 volumes that include the latest advances in research, and uniquely organized by organ system for ease of reference and diagnosis, this new edition is an essential reference for researchers of toxicology. Organized to cover both the fundamental principles of toxicology and unique aspects of major organ systems Thoroughly revised to include the latest advances in the toxicological effects of chemicals on the immune system Features additional coverage throughout and a new volume on toxicology of the hematopoietic system Presents in-depth, comprehensive coverage from an international author base of domain experts
Author: Sam Thiagalingam
Publisher: Cambridge University Press
ISBN: 0521493390
Category : Mathematics
Languages : en
Pages : 597
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Book Description
An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.
Author: Robert J. Washabau
Publisher: Elsevier Health Sciences
ISBN: 143770302X
Category : Medical
Languages : en
Pages : 1017
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Book Description
A comprehensive reference standard for the discipline, Canine and Feline Gastroenterology covers the biology, pathobiology, and diagnosis and treatment of diseases of the gastrointestinal, pancreatic, and hepatobiliary systems. An international team of experts, including 85 authors from 17 different countries, led by Robert Washabau and Michael Day, covers everything from minor problems such as adverse food reactions to debilitating inflammatory, infectious, metabolic, and neoplastic diseases of the digestive system. This authoritative text utilizes an evidence-based approach to reflect the latest science and research, complemented by principles of problem solving, algorithms to improve clinical diagnoses, and extensive full-color illustrations. For generalists and specialists alike, this gastroenterology reference should be part of every serious practitioner's professional library. - A comprehensive, 928-page reference standard covers the discipline of canine and feline gastroenterology. - An international focus is provided by 85 authors from 17 different countries, including renowned experts in veterinary gastroenterology, internal medicine, pathology, clinical pathology, radiology, and infectious disease. - Coverage of the entire breadth and depth of gastroenterology ranges from biology to pathobiology, as well as diagnosis and treatment of diseases of the gastrointestinal, pancreatic, and hepatobiliary systems. - Current information on GI microflora, immunology, cellular growth, and systems integration provides a foundation for treating clinical problems. - Coverage of diseases in dogs and cats includes the oral cavity, esophagus, stomach, small intestine, large intestine, colon, anorectum, liver and biliary tract, exocrine pancreas, peritoneum, and associated vasculature. - A focus on patient management examines the full range of procedures and techniques essential to diagnosis and treatment from clinical signs and diagnosis to nutritional support and pharmacologic management of disease. - Clear explanations of current diagnostic modalities include laboratory tests, molecular methods, diagnostic imaging, endoscopy, and histopathology, also showing how to interpret and utilize results. - A strong clinical approach emphasizes need-to-know information for managing the common and not-so-common G.I. clinical problems of everyday practice. - Full-color photographs and illustrations depict concepts, conditions, and procedures. - An evidence-based medicine perspective reflects the latest research as well as the modern practice of veterinary medicine. - Logical, coherent, and consistent internal organization makes this a reader-friendly edition. - Problem-based algorithms help in diagnosing every G.I. clinical problem from A to Z. - A stand-alone section on the pharmacologic approach to G.I. disease offers quick and easy drug reference.
Author: Ajit Varki
Publisher: CSHL Press
ISBN: 9780879696818
Category : Medical
Languages : en
Pages : 694
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Book Description
Sugar chains (glycans) are often attached to proteins and lipids and have multiple roles in the organization and function of all organisms. "Essentials of Glycobiology" describes their biogenesis and function and offers a useful gateway to the understanding of glycans.
Author:
Publisher:
ISBN:
Category : Biology, Experimental
Languages : en
Pages : 728
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Author:
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages : 1230
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