Liver Regeneration And Carcinogenesis

Because of its marked capacity to regenerate and the ability of chemical carcinogens and viruses to ready transform hepatocytes, the liver has been used extensively as a model for investigating the molecular mechanisms of cellular proliferation and carcinogenesis. Recently, striking advances have occured in the understanding of hepatocyte growth regulation and the manner in which chemical agents and viruses alter these normal growth regulatory pathways in liver carcinogenesis. This explosion of information has occured in a multitude of researh disciplines. This book brings together current findings in a coherent manner, from a molecular point of view. Three sections cover in detail the areas of liver regeneration, liver carcinogenesis, and liver tumor therapy. The contributors are pioneers and leaders in this field. * Logical organization of material in three detailed and comprehensive sections: liver regeneration, liver carcinogenesis, and liver tumor treatment * Contributors are pioneers and leaders in the field * There are currently no books on this subject on the market * Research focus is at the molecular level

Presents an approach to the hepatic physiology and multiple developments about cellular biology such as cell cycle regulation, growth factors and oncogenes.

Stem Cells and Cancer in Hepatology: From the Essentials to Application offers basic scientists and clinicians in the fields of stem cells, hepatology and oncology an overview of the interaction between liver biology, stem cells and cancer. It discusses how the liver performs regeneration and repair, the role stem cells play in these processes, and the mechanisms by which liver cancers are initiated and developed. As the field of stem cells and cancer stem cells in hepatology is new and dynamic, thus making it difficult for researchers and clinicians to understand the most relevant historic and novel studies, this volume addresses that challenge. Addresses both the basic and clinical perspectives of the topic, including sections on normal and cancer stem cells of the liver Provides coverage of the molecular mechanisms of liver development, the proliferation of hepatic progenitor cells during development, epithelial cell plasticity, generation of hepatocytes by transdifferentiation, liver tissue engineering, and more Presents a study of hepatic stem cells that will help readers understand critical events during development, stem cell differentiation towards functional liver cell fate, and tumor initiation

During the last years much attention has been given to the investigation of the roles of specific growth modulators acting on liver cell populations. HGF functions as a pleotropic factor in the liver as well as in other extrahepatic tissues. The hepatic stem cell compartment is thought to play a major role in liver tissue restoration. Mechanisms of cell growth and cell death of the liver are described in detail, with particular emphasis on apoptosis. The functions of HBV-pX protein and the roles of hepatitis B virus gene expression relation to hepatocellular carcinoma are discussed. Techniques for obtaining human and nonhuman hepatocytes and other liver cell types and for efficient transfer and expression of genes in hepatocytes and liver-derived cell lines are presented.

Although cell turnover in normal adult liver is extremely low, hepatic tissue is notorious for its almost infinite capacity to regenerate in cases of viral, toxic or traumatic damage. Hepatocellular carcinoma is one of the most frequent malignancies worldwide and causes more than a million deaths per year. The mechanisms governing normal proliferation and malignant transformation of liver cells are of utmost interest for the understanding of regeneration and hepatocarcinogenesis and for the development of new therapeutic strategies. Therefore, the International Falk Workshop held in Halle, Germany, on January 29-30 1998, focused on the issues of normal and malignant liver cell growth. Knowledge in this area of research has expanded rapidly during recent years. This book of proceedings summarizes the latest advances both in basic science and clinical research. Stimulating discussion set the basis for the development of new strategies in diagnosis and treatment of hepatocellular carcinoma and for the manipulation of regeneration in cases of acute or chronic loss of functional liver tissue.

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.

Nelson Fausto The Greek myth of Prometheus with its picture of a vulture feasting on its chained victimhas traditionallyprovided a visualimageofliverregeneration. Itis apowerful and frightening representationbut ifone were to substitute the vulture by a surgeon and Prometheus by a patient laying on a properly prepared operating table, the outcomeoftheprocedurewould not differ significantlyfrom that describedbyGreek poets. Yet few of us who work in the field have stopped long enough to ask where this myth originated. Did the poet observe a case of liver regeneration in a human being? Was it brilliant intuition or perhaps, literally, just a 'gut feeling' of a poet looking for good rhymes that led to the prediction that livers grow when part of the tissueisremoved? Thisbookdoesnotattemptto solve these historical issues. Itdoes, instead, cover in detail some of the major modem themes of research on liver regen eration, injury and repair. As indicated in Dr. N. Bucher's chapter, the modem phase ofexperimental studies on liver regeneration started in 1931 with the publication by Higgins and Anderson of a method to perform a two-thirds resection of the liver of a rat. The technique described has 3 remarkable features: 1) it is highly reproducible, resulting in the removal of 68% of the liver, 2) it has minimal if any mortality, and 3) it consists only of blood vessel ligation and does not involve cutting through or wounding hepatic tissue.