Cellular Fluctuations Alpha Fetoprotein Expression And The Question Of Stem Cells In Experimental Liver Regeneration And Hepatocarcinogenesis

Hepatocytes and bile ductular cells possess stem-like potential in restoring liver tissue. This was derived from rat and mouse injury models such as (a) partial hepatectomy by surgery; (b) acute carbon tetrachloride intoxication; © injuries by D-galactosamine (GalN) or by N-nitrosomorpholine (NNM); (d) experimental hepatocarcinogenesis with NNM using different doses. Liver parenchyma was restored by adult hepatocytes after partial hepatectomy as well as after carbon tetrachloride intoxication. Concurrently, hepatocytes resumed synthesis of alpha-1-fetoprotein (AFP) which depended to a high degree on the animal species and strains used in that studies. In contrast to this way of regeneration, liver repair after heavy injuries by agents such as GalN and NNM was initiated by oval cell proliferation deriving from ductular epithelial cells of the canaliculi of HERING (canals of Hering, intrahepatic bile ductules) as sources of endogenous progenitors. Progenitor populations reach levels of differentiation with fetal gene reactivation and significant AFP expression. Proliferating oval cells operated as transit and amplification compartment during liver regeneration. Oval cell proliferation and concurrent AFP synthesis occurred also in the early stages of hepatocarcinogenesis when the carcinogen NNM was applied in toxic doses. The histologic features compared to those seen in GalN intoxication. NNM carcinogenicity was of concern for both oval cells and adult hepatocytes with risks of transformation and malignant development. At the cancer stage, carcinomas either synthesizing AFP or not can be found side by side in the same liver. AFP expression by cancer cells seems to be a special attribute to differentiation stages in carcinogenesis. Clonality, maturation arrest and retro-differentiation feature cells with high autonomy.

This volume looks at the liver’s epithelial cells—hepatocytes and cholangiocytes—and their progenitors. This book is divided into five parts: isolation of progenitor cells; characterization of liver progenitors in vivo; generation of hepatocytes, cholangiocytes, and their progenitors; reconstitution of liver tissue structures; and liver injury models. The chapters in this book cover topics such as expansion of bipotential liver stem/progenitor cells (LPCs) from fetal and neonatal liver; identifying progenitor cells involved in liver regeneration in vivo; methods for generating hepatocytes and cholangiocytes from multiple cellular sources; 3D tissue structures ex vivo; and resolving hepatic fibrosis by bone marrow transplantation. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Hepatic Stem Cells: Methods and Protocols is a valuable resource to help researchers understand the current theories used to study hepatic stem/progenitor cells, and aid them in performing experiments related to liver biology and pathophysiology.

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.

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.

Increasing evidence suggests that liver stem cells have the capacity to differentiate into parenchymal hepatocytes or into bile ductular cells. These stem cells may be activated to proliferate after severe liver injury or exposure to hepatocarcinogens. Stem cell replacement strategies are being investigated as an alternative approach to liver repair and regeneration. Additionally, stem cell transplantation has been shown to significantly improve liver function and increase survival in experimentally-induced liver-injury models in animals. In Liver Stem Cells: Methods and Protocols, expert researchers focus on several hepatic progenitor cells, hepatic differentiation form stem cells, bile ductal cell formation from stem cells, liver stem cells and hepatocarcinogenesi, and application of liver stem cells for cell therapy. These topics shed light on stem cell technology which may lead to the development of effective clinical modalities for human liver diseases. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Thorough and intuitive, Liver Stem Cells: Methods and Protocols seeks to aid scientists in the further study of preclinical and clinical investigations that explore the therapeutic potential of stem cells in repair of liver injuries.

This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.

Stem cell biology has drawn tremendous interest in recent years as it promises cures for a variety of incurable diseases. This book deals with the basic and clinical aspects of stem cell research and involves work on the full spectrum of stem cells isolated today. It also covers the conversion of stem cell types into a variety of useful tissues which may be used in the future for transplantation therapy. It is thus aimed at undergraduates, postgraduates, scientists, embryologists, doctors, tissue engineers and anyone who wishes to gain some insight into stem cell biology. This book is important as it is comprehensive and covers all aspects of stem cell biology, from basic research to clinical applications. It will have 33 chapters written by renowned stem cell scientists worldwide. It will be up-to-date and all the chapters include self-explanatory figures, color photographs, graphics and tables. It will be easy to read and give the reader a complete understanding and state of the art of the exciting science and its applications.