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|a Liver regeneration :
|b basic mechanisms, relevant models and clinical applications /
|c edited by Udayan Apte, PhD Dabt.
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|a London :
|b Elsevier :
|b Academic Press,
|c [2015]
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|a 1 online resource
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|a Includes bibliographical references and index.
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|a Liver Regeneration: Basic Mechanisms, Relevant Models and Clinical Applications presents cutting-edge information on liver regeneration research through an integrated, systems-wide perspective. The book addresses discoveries on hepatic progenitor cells, liver regeneration after chemical damage, and liver regeneration as a prime therapy for liver failure and disease. By addressing the urgent need for translating basic research findings into clinically relevant modalities and potential therapeutic applications, the book provides the data needed to improve liver patient management. Hundreds of full-color, graphic photographs and illustrations underline key elements and show researchers and students important aspects of liver transplantation, immunofluorescence, and other techniques used in liver regeneration. Summarizes current liver regeneration studies and discussions on expected discoveries Provides an overview of standard scientific and cutting-edge technologies to study liver regeneration Presents details on the molecular mechanisms that affect liver regeneration Highly illustrated, with hundreds of full-color, graphic photographs and illustrations to enhance the learning process.
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|a Front Cover -- Liver Regeneration: Basic Mechanisms, Relevant Models and Clinical Applications -- Copyright -- Dedication -- Contents -- Contributors -- Preface -- Part I: Introduction -- Chapter 1: Liver Regeneration: An Introduction -- 1.1. History -- 1.2. Models of Liver Regeneration -- 1.3. Mechanisms of Liver Regeneration -- 1.4. Regeneration Using Progenitor Cells -- 1.5. Mitogen-Induced Hepatocyte Proliferation -- 1.6. Frontiers -- References -- Part II: Methods to Assess Liver Regeneration -- Chapter 2: Models to Study Liver Regeneration -- 2.1. Introduction -- 2.2. Main Models -- 2.2.1. Partial Hepatectomy -- 2.2.1.1. PH Procedure -- 2.2.1.2. Establishing Baseline, Time Course, and Proper Controls -- 2.2.2. Models of Liver Regeneration After Chemical-Induced Liver Injury -- 2.2.2.1. d-Galactosamine: Mechanism of Hepatotoxicity -- 2.2.2.1.1. d-Galactosamine: Hepatic Regenerative Response -- 2.2.2.2. Carbon Tetrachloride: Mechanism of Hepatotoxicity -- 2.2.2.2.1. CCl4: Hepatic Regenerative Response -- 2.2.2.3. Thioacetamide -- 2.2.2.4. Acetaminophen -- 2.2.2.5. Regeneration After Ischemia/Reflow -- 2.2.2.5.1. Mechanisms of I/R Injury and Repair -- 2.3. Alternate Models of Liver Growth -- 2.3.1. Postnatal Liver Growth -- 2.3.2. Pregnancy-Induced Liver Growth -- 2.4. Models to Study HPCs -- 2.4.1. 2-Acetylaminofluorene Combined with Partial Hepatectomy -- 2.4.2. The DDC Diet Model -- 2.4.3. The CDE Diet Model -- 2.5. Assays Used to Assess Liver Regeneration -- 2.5.1. PCNA Immunolocalization -- 2.5.2. 3H-TdR and BrdU Incorporation -- 2.5.3. Ki67 Immunolocalization -- 2.6. Additional Methods -- References -- Chapter 3: Liver Regeneration in Zebrafish -- 3.1. Introduction -- 3.2. The Therapeutic Impact of Zebrafish Research -- 3.3. Adult Liver Anatomy and Physiology -- 3.4. Liver Regeneration Following Partial Hepatectomy.
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|a 3.5. Drug-Induced Hepatotoxicity -- 3.6. Genetic Hepatocyte Ablation -- 3.7. Summary -- References -- Part III: Molecular Mechanisms of Liver Regeneration -- Chapter 4: The Priming and Progression Theory of Liver Regeneration -- 4.1. Overview of Studies of Liver Regeneration -- 4.2. Salient Features of Liver Regeneration Prior to 1970 -- 4.3. Identifying Hepatomitogens in the 1970s-1980s -- 4.4. 1990s: Development of the Priming and Progression Model, with a Focus on Inflammatory Stimuli During Regeneration -- 4.5. Priming Alone Versus Priming and Progression: 1/3 Versus 2/3 Hepatectomy -- 4.6. Controversies Regarding the Importance of Priming in Regeneration -- 4.7. Recent Insight into Cell-Cycle C̀̀ompetency ́́ -- 4.8. The Role of NPCs in Priming and Progression -- 4.9. Future Directions -- References -- Chapter 5: Extracellular Signals Involved in Liver Regeneration: Direct and Auxiliary Mitogens -- 5.1. Hepatocyte Growth Assay -- 5.2. Complete Versus Auxiliary Mitogens -- 5.3. Complete or Direct Mitogens -- 5.3.1. Hepatocyte Growth Factor -- 5.3.2. Ligands of EGFR -- 5.4. Auxiliary Mitogens -- 5.5. TNFÜ -- 5.6. IL6 -- 5.7. Norepinephrine -- 5.8. Insulin -- 5.9. Summary -- References -- Chapter 6: Developmental Pathways in Liver Regeneration-I -- 6.1. Introduction -- 6.2. Wnt/Ý-Catenin Signaling -- 6.2.1. Wnt/Ý-Catenin Signaling in Liver Growth -- 6.2.2. Ý-Catenin Signaling During Liver Regeneration After Partial Hepatectomy -- 6.2.2.1. Ý-Catenin Activation and Downstream Signaling After Partial Hepatectomy -- 6.2.2.2. Ý-Catenin Signaling in Toxicant-Induced Liver Injury and Regeneration -- 6.2.3. Enhanced Ý-Catenin Activation Stimulates Regeneration of Liver -- 6.2.4. Exogenous Ý-Catenin Activation and Liver Regeneration -- 6.2.5. Cell-Molecule Circuitry of Wnt Signaling in Liver Regeneration After Hepatectomy -- 6.3. Notch Signaling.
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|a 6.3.1. Notch Signaling in Hepatic Pathophysiology -- 6.3.2. Notch Signaling in Liver Regeneration After PH -- 6.4. Hippo Signaling -- 6.4.1. Hippo Signaling in Hepatic Pathophysiology -- 6.4.2. Hippo Signaling in Liver Regeneration After PH -- 6.5. NF-mB Signaling -- 6.5.1. Signaling Upstream of NF-mB -- 6.5.2. Signaling Downstream of NF-mB -- 6.5.3. Role of NF-mB Signaling in Liver Pathophysiology -- 6.5.4. Role of NF-mB Signaling in Liver Regeneration -- 6.6. Conclusions -- References -- Chapter 7: Mechanisms of Termination of Liver Regeneration -- 7.1. Introduction -- 7.2. Transforming Growth Factor Ý -- 7.3. Extracellular Matrix and Integrin-Linked Kinase -- 7.4. Glypican-3 -- 7.5. Activin -- 7.6. C/EBPÜ -- 7.7. Cyclin E1 and E2 -- 7.8. Nuclear Receptors -- 7.9. Hippo/Yap Signaling Pathway -- 7.10. MicroRNAs 34a and 23b -- 7.11. Conclusions -- References -- Chapter 8: Role of CXC Chemokines in Liver Repair and Regeneration -- 8.1. Introduction -- 8.2. Clinical Scenarios and Their Analogous Injury Models -- 8.3. General Principles of Liver Regeneration -- 8.4. Chemokines and Their Receptors -- 8.5. Roles for CXC Chemokines in Liver Regeneration -- 8.5.1. ELR+ Chemokines -- 8.5.2. ELR- Chemokines -- 8.6. CXC Chemokines and Hepatocyte Exosomes -- 8.7. Conclusion -- References -- Chapter 9: Bile Acid Receptors and Liver Regeneration -- 9.1. Introduction -- 9.2. Metabolic Signals and Liver Regeneration -- 9.3. BA Signaling and Liver Regeneration -- 9.4. FXR and Liver Regeneration -- 9.5. Intestine-FXR and Liver Regeneration -- 9.6. TGR5 and Liver Regeneration -- 9.7. FXR and HCC Development -- 9.8. Conclusions and Perspective -- References -- Chapter 10: Role of Developmental Morphogens in Liver Regeneration -- 10.1. Introduction -- 10.2. Overview of the Hedgehog Pathway -- 10.2.1. Understanding Hedgehog Ligands Physiology.
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|a 10.2.2. Hedgehog Pathway in Target Cells -- 10.2.3. The Role of Primary Cilium -- 10.2.4. Regulation of the Pathway and Noncanonical Pathway -- 10.3. Hedgehog Pathway After Partial Hepatectomy-Feeding Prometheus' Liver -- 10.4. Regenerating the Sick Liver -- 10.5. Conclusion -- References -- Chapter 11: Regulation of Cell Cycle During Liver Regeneration -- 11.1. Introduction -- 11.2. Rb and E2F1 -- 11.3. Cyclin D-Cdk4/Cdk6 -- 11.4. Cyclin E-Cdk2 -- 11.5. Cyclin A -- 11.6. Cyclin B -- 11.7. Cdk1 -- 11.8. Cell-Cycle Inhibitors -- 11.9. Concluding Remarks -- References -- Chapter 12: Changes in Hepatocyte Ploidy During Liver Regeneration -- 12.1. Introduction -- 12.2. Polyploidy in the Liver -- 12.2.1. Mechanisms for Hepatic Polyploidization -- 12.2.2. Function of Polyploid Hepatocytes -- 12.3. Genetic Diversity in the Liver -- 12.3.1. Ploidy Reversal and Aneuploidy in the Liver -- 12.3.2. Hepatic Cell Divisions with Multipolar Spindles -- 12.3.3. Control of Liver Diversity and the Link to Cancer -- 12.4. An Integrated Model for Polyploidy, Ploidy Reversal, and Aneuploidy in the Liver -- 12.4.1. The Ploidy Conveyor -- 12.4.2. The Ploidy Conveyor as a Mechanism for Liver Adaptation -- 12.5. Conclusion -- References -- Chapter 13: Computational Modeling as an Approach to Study the Cellular and Molecular Regulatory Networks Driving Liver Re ... -- 13.1. Introduction -- 13.2. Extended Computational Model of Liver Regeneration Including Cell Growth -- 13.3. Modes of Regeneration Identified by Sampling Computational Model Parameter Space -- 13.4. Dynamic Regulation of the Regenerating Liver Revealed Using Sensitivity Analyses -- 13.5. Model Limitations, Future Directions, and Experimental Insights -- 13.6. Conclusions -- References -- Chapter 14: Mitogen-Induced Cell Proliferation and Cancer Promotion in the Liver -- 14.1. Introduction.
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|a 14.2. Cancer Promotion -- 14.3. Cytokine-Activating Mitogens -- 14.4. Drug-Induced Hyperplasia -- 14.5. PPAR-Induced Proliferation -- 14.6. CAR-Induced Proliferation -- 14.7. THR-Induced Proliferation -- 14.8. Minor Proliferative Responses Induced by Nuclear Receptors -- 14.9. Human Proliferative Responses -- 14.10. Conclusions -- References -- Chapter 15: Metabolic Regulation of Liver Regeneration -- 15.1. Introduction -- 15.2. The Metabolic Response to Hepatic Insufficiency -- 15.3. Evidence for the Metabolic Regulation of Liver Regeneration -- 15.3.1. PH-Induced Liver Regeneration Occurs in Proportion to Associated Alterations in Metabolism -- 15.3.2. Glucose Supplementation Impairs Experimental Liver Regeneration -- 15.3.3. Disrupting Regenerative Hepatic Steatosis Compromises Liver Regeneration -- 15.3.4. Amino Acid Metabolism is Specifically Altered During Experimental Liver Regeneration -- 15.3.5. Regenerative Regulation of Metabolism -- 15.4. Candidate Mechanisms Linking Metabolism to Regeneration -- 15.4.1. Nuclear Hormone Receptor-Dependent Hepatocellular Proliferation -- 15.4.2. Metabolic Influences on Epigenetic Regulation of Liver Regeneration -- 15.4.3. Other Considerations and Areas for Future Basic Research -- 15.5. Clinical Implications -- 15.5.1. Nonalcoholic Fatty Liver Disease -- 15.5.2. Aging -- 15.5.3. Subtotal Hepatectomy -- 15.5.4. Hepatic Regenerative Metabolomic Biomarkers -- 15.6. Summary and Conclusions -- References -- Chapter 16: Liver Regeneration: The Biliary Perspective -- 16.1. Introduction -- 16.1.1. Biliary Function -- 16.1.2. Anatomy and Heterogeneity of the Biliary Tree -- 16.2. Characteristics of Biliary Regeneration -- 16.2.1. Type I or T̀̀ypical ́́Cholangiocyte Proliferation -- 16.2.2. Type II or À̀typical ́́Cholangiocyte Proliferation -- 16.2.3. Type III or Oval Cell Proliferation.
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