Liver Regeneration and Carcinogenesis: Molecular and Cellular Mechanisms
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Table of contents
- Contentsvii
- Contributorsxvii
- Prefacexxi
- Chapter 1. Liver Regeneration Then and Now1
- I. Landmarks1
- II. Normal Adult Rat Liver2
- III. Liver Regeneration3
- IV. Hepatocyte Priming5
- V. Regeneration Signals7
- VI. Conclusions19
- References19
- Chapter 2. Hepatocyte Growth Factor (HGF) and Its Receptor (Met) in Liver Regeneration, Neoplasia, a27
- I. Introduction27
- II. Structural and Functional Aspects of HGF and the HGF Receptor28
- III. HGF Localization30
- IV. Liver and the Processing of HGF32
- V. HGF and the Early Proteolytic Events Following Partial Hepatectomy37
- VI. HGF Localization40
- VII. Summary43
- References44
- Chapter 3. Structure and Functions of the HGF Receptor (c-Met)51
- I. Hepatocyte Growth Factor and Scatter Factor51
- II. HGF Receptor53
- III. Regulation of c-met Expression60
- IV. Role of HGF in Tissue Regeneration and Embryogenesis61
- V. Role of c-met in Carcinogenesis62
- References63
- Chapter 4. Expression and Function of Growth-Induced Genes during Liver Regeneration71
- I. Liver Regeneration: The Important Questions71
- II. Immediate-Early Gene Expression in Hepatic Cells72
- III. Modification of Preexisting Transcription Factors Immediately Following Partial Hepatectomy Tur76
- IV. Induction Patterns of 70 Genes Following Partial Hepatectomy Define the Temporal Course of Liver78
- V. Transcription Factors Induced in the Regenerating Liver80
- VI. Immediate-Early Genes Involved in Signal Transduction84
- VII. Immediate-Early Genes That Are Secreted Proteins86
- VIII. Liver-Specific Immediate-Early Genes: Relationship to the Maintenance of Hepatocyte Differenti87
- IX. Immediate-Early Genes in H35 Cells That Are Expressed as Delayed-Early Genes in Regenerating Liv89
- X. Conclusions91
- References93
- Chapter 5. Stem Cells and Hepatocarcinogenesis99
- I. Introduction99
- II. Cellular Biology of the Hepatic Stem Cell Compartment101
- III. Neoplastic Development in the Liver104
- IV. Conclusions108
- References109
- Chapter 6. Contributions of Hepadnavirus Research to Our Understanding of Hepatocarcinogenesis113
- I. General Overview of Hepadnavirus Animal Models and Hepatocarcinogenesis113
- II. Hepatitis B Virus Envelope Protein (HBsAg) Transgenic Mice117
- III. Woodchuck Hepatitis Virus (WHV) Model of Hepatocarcinogenesis122
- IV. Hepadnavirus X Gene Encodes an Oncogenic Transcriptional Transactivator129
- V. Conclusions134
- References134
- Chapter 7. Apoptosis and Hepatocarcinogenesis141
- I. Apoptosis and Other Types of Active Cell Death141
- II. Active Cell Death in the Liver145
- III. Biochemical and Molecular Aspects of Apoptosis152
- IV. Active Cell Death in the Stages of Hepatocarcinogenesis158
- V. Conclusions166
- References167
- Chapter 8. Liver Tumor Promotion and the Suppression of p53-Dependent Cell Cycle Checkpoint Function179
- I. Introduction
- II. Mechanisms of Cell Cycle Control180
- III. Cell Cycle Checkpoints, Lifespan Extension, and Genetic Instability181
- IV. Isolation of EL/EGV Hepatocytes and Promotion of Hepatocarcinogenesis in Vitro183
- V. Immortal Rat Hepatocytes Require PB for Clonal Expansion186
- VI. Mechanisms of Promotion of Hepatocarcinogenesis by Phenobarbital191
- VII. Conclusions193
- References194
- Chapter 9. Mechanisms of Liver Tumor Promotion199
- I. Introduction199
- II. Stages of Liver Carcinogenesis201
- III. Cell Cycle Regulation and Liver Carcinogenesis204
- IV. TGFβ and Liver Carcinogenesis208
- V. Apoptosis and Liver Carcinogenesis216
- VI. Summary217
- References218
- Chapter 10. Hypomethylation of DNA: An Epigenetic Mechanism That Can Facilitate the Aberrant Oncogen227
- I. Introduction227
- II. Epigenetics230
- III. DNA Methylation230
- IV. Working Hypothesis and Experimental Model235
- V. Liver Tumor Promotion: A Role for Hypomethylation of DNA236
- VI. Methyl Deficient Diets238
- VII. DNA Damage and Altered DNA Methylation240
- VIII. DNA Methylation and Chemoprevention241
- IX. Differences in DNA Methylation between Rodents and Humans243
- X. Conclusions245
- XI. Summary246
- References247
- Chapter 11. Transgenic Models of Hepatic Growth Regulation and Hepatocarcinogenesis257
- I. Transgene-Based Strategies for Studying Liver Growth, Development, and Cancer257
- II. Oncogenic Transgenes and Hepatic Neoplasia259
- III. Growth Factor Transgenes and Hepatic Neoplasia268
- IV. Hepatotoxic Transgenes and Liver Neoplasia271
- V. Transgenes and Multistage Carcinogenesis276
- VI. Transgenes and Hepatic Growth Regulation282
- VII. Assessment and Future Directions289
- References290
- Chapter 12. Genetic Susceptibility to Liver Cancer301
- I. Introduction301
- II. Genetics of Human Liver Cancer302
- III. Genetics of Experimental Liver Cancer305
- IV. Conclusion314
- References315
- Chapter 13. Surgical Treatment of Hepatic Tumors and Its Molecular Basis323
- I. Introduction323
- II. Diagnosis of Surgical Liver Tumors324
- III. Indications for Surgical Treatment326
- IV. Surgical Anatomy336
- V. Hepatic Regeneration after Resection and Transplantation: Current Clinical Concepts342
- References345
- Chapter 14. Gene Therapy for the Treatment of Inherited and Acquired Diseases of the Liver351
- I. Human Gene Therapy„A Definition351
- II. Strategies for Liver-Directed Gene Therapy352
- III. Gene Transfer Techniques for Liver-Directed Gene Therapy361
- IV. Clinical Applications of Gene Therapy Directed to the Hepatic Compartment369
- V. Conclusions377
- References378
- Index385
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
* 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