Advances in Cancer Research

Opis

ADVANCES IN CANCER RESEARCH is a biannual publication that includes timely reviews on the most cutting-edge issues in cancer research. Volume 66 contains encompassing overviews of p53 and its role in both breast cancer and in the cell cycle. Approximately 50% of all human tumors involve mutations of the p53 gene, suggesting that proper understanding of its properties and mechanisms could offer real hope for finding successful clinical therapy. Other themes presented in Volume 66 include cyclins and cyclin-dependent kinases in the cell cycle. Approximately 50% of all human tumors involve mutations of the p53 gene, suggesting that proper understanding of its properties and mechanisms could offer real hope for finding sucessful clinical therapy. Other themes presented in Volume 66 include cyclins and cyclin-dependant kinases in the cell cycle: the molecular genetics of 11q23 chromosome translocations: the possible link between the aberrant expression of Scatter Factor and c-Met with AIDS Associated kaposi's Sarcoma, the use of Radiation Leukemia Virus to induce leukemogenesis, and the Adenovirus system as a model for the insertion of foreign DNA into mammalian genomes. Also of note in the "Foundations of cancer Research" section are articles by two prominent cancer researchers recollecting the ideas and paths taken in their lifelong work. Paradigms proposed in these reviews mark thoughtful progress toward preventative therapy in oncogenesis and gene therapy of cancer. They also cast light on the fact that the ideas presented in these chapters are only the tip of the iceburg in this complex and ever evolving field, and suggest many more to come in future volumes.

Contains two Foundations in Cancer Research articles with personal accounts by prominent biologists on their careers in cancer research
Presents overviews of the role of p53 in breast cancer and cell cycle regulation
Describes the regulatory role of cyclins and cyclin dependent kinases in DNA replication and cell division
Explains the puzzling link between HIV infection and Kaposis Sarcoma
Includes models for retrovirus-induced tumorigenesis and foreign DNA insertion into mammalian genomes

Spis treści

Front Cover 2
Advances in Cancer Research, Volume 66 5
Copyright Page 6
Contents 7
Contributors to Volume 66 12
Chapter 1. Foundations in Cancer Research: The Adventures of a Biologist: Prenatal Diagnosis, Hematopoiesis,Leukemia, Carcinogen 15
- I. Studies in England and Move to Israel: Amniocentesis and Prenatal Diagnosis on Amniotic Fluid Cells 15
- II. Hematopoiesis and Lcukemia 17
- III. Carcinogenesis: Tumor Viruses, Chemical Carcinogens, and Irradiation 35
- IV. Chromosome Changes and Tumor suppression 38
- V. Concluding Remarks 42
- VI. Short Curriculum Vitae 44
- References 45
Chapter 2. Foundations in Cancer Research: From Aristotle, through Spemann, to Tumor Immunology: A Personal Experience 55
- I. Dreams 56

Front Cover 2
Advances in Cancer Research, Volume 66 5
Copyright Page 6
Contents 7
Contributors to Volume 66 12
Chapter 1. Foundations in Cancer Research: The Adventures of a Biologist: Prenatal Diagnosis, Hematopoiesis,Leukemia, Carcinogen 15
- I. Studies in England and Move to Israel: Amniocentesis and Prenatal Diagnosis on Amniotic Fluid Cells 15
- II. Hematopoiesis and Lcukemia 17
- III. Carcinogenesis: Tumor Viruses, Chemical Carcinogens, and Irradiation 35
- IV. Chromosome Changes and Tumor suppression 38
- V. Concluding Remarks 42
- VI. Short Curriculum Vitae 44
- References 45
Chapter 2. Foundations in Cancer Research: From Aristotle, through Spemann, to Tumor Immunology: A Personal Experience 55
- I. Dreams 56
- II. Initial Experiments: Tumor Allografts 58
- III. Initial Realities: Tumor-Specific Transplantation Antigen 60
- IV. Actual Realities: T Cell Recognition of cell Surface Epitopes 61
- V. MHC Class I Genes Control the metastatic Phenotype of Tumor Cells 63
- VI. Upregulating the Expression of Endogenous H-2K Genes 67
- VII. The Tumor-Specific Immunogenic Epitope of a Murine Lung Carcinoma Is an Octapeptide Mutein of Connexin 37 69
- VIII. The New Era of Molecularly Characterized Tumor- Associated Antigens 70
- IX. Tumor Cells Transduced by Cytokine Genes 73
- X. Target Organ Specificity of Metastasis 77
- XI. Conclusion 78
- References 80
Chapter 3. Tumor Suppressor p53 Mutations and Breast Cancer: A Critical Analysis 85
- II. Somatic Changes in Human Breast Cancer 86
- I. Introduction 86
- III. History of p53 87
- IV. The p53 Gene 89
- V. The p53 Protein 91
- VI. Quaternary Structure of the p53 Protein 96
- VII. Functional Properties of WT p53 99
- VIII. Properties and Phenotypes of p53 Mutants 112
- IX. p53 Mutations and Breast Cancer 122
- X. Systems for Studying Genetic Changes Involved in Breast Cancer 134
- References 140
- XI. Summary 140
Chapter 4. p53: A Cell Cycle Regulator Activated by DNA Damage 157
- I. Introduction 157
- II. Biological Activiteis of p53 158
- III. Biochemical Functions of p53 163
- IV. Interactions with Viral and Cellular Proteins 175
- V. Regulation of p53 Function 180
- References 187
Chapter 5. Cyclins and Cyclin-Dependent Kinases: Theme and Variations 195
- I. Introduction 195
- II. Checkpoints and the Cell Cycle 196
- III. Cyclins 197
- IV. Cyclins Are Regulated by Proteolysis 197
- V. How CDKs Are Activated by Binding Cyclins 201
- VI. Modulation of the Cyclic–CDK Complexes: Phosphorylation and Inhibitor Proteins 202
- VII. START 206
- VIII. Fission Yeast START 208
- IX. Mammalian START 210
- X. D-Type Cyclins as Regulators of Rb 211
- XI. D-Type Cyclins are Involved in Differentiation 212
- XII. The G1 to S Cyclins 213
- XIII. S-Phase Cyclins 215
- XIV. Mitotic Cyclins 217
- XV. Nonmitotic Cell Cyclins 219
- XVI. With Apologies to Elgar 220
- References 220
Chapter 6. Molecular Genetics of 11q23 Chromosome Translocations 227
- I. Introduction 227
- II. Cytogenetics of 11q23 Abnormalities 228
- III. Clinical Considerations 230
- IV. Cloning the Breakpoint Cluster Region 231
- V. ALL-1: The Human Homologue of Drosophila trithorax 237
- VI. Fusion of ALL-1 to Partner Genes 240
- VII. Models for ALL-1 Leukemogenicity 245
- VIII. Conclusions 246
- References 247
Chapter 7. Role of Scatter Factor and the c-met Protooncogene in the Pathogenesis of AIDS-Associated Kaposi’s Sarcoma 251
- I. Introduction 251
- II. Epidemiology of AIDS-Associated Kaposi’s Sarcoma 252
- III. Agents Implicated in the Etiology of Kaposi,s Sarcoma 253
- IV. The Kaposi’s Sarcoma Phenotype 254
- V. Endothelial Cells Undergo Phenotypic Conversion to Kaposi’s Sarcoma-like Tumor Cells When Exposed to HIV-Infected T Lymphocyt 256
- VI. Scatter Factor and the c-met Receptor: A Paracrine and Autocrine Growth Signaling System 263
- VII. Proposed Role for Scatter Factor and c-met in Kaposi's Sarcoma Carcinogenesis 264
- VIII. Conclusions and Summary 267
- References 268
Chapter 8. REL/NF-kB/1kB Story 273
- I. Introduction 273
- II. κB-Binding Factors 275
- III. IκB Family of Proteins 284
- IV. Regulation of Rel/NF-κB Activity 291
- V. Rel/NF-κB Regulation of'the Target Gene Transcription 298
- VI. Drosophila System: Dorsal, Dif, and Cactus 300
- References 303
- VII. Concluding Remarks 303
Chapter 9. Radiation Leukemia Virus-Induced Leukemogenesis: A Paradigm of Preleukemia and Its Control by Preventive Therapy 311
- I. Introduction 311
- II. Tumorigenesis Induced by Chronic Retroviruses 312
- III. Radiation Leukemia Virus (RadLV)-Induced Leukemogenesis 313
- IV. Mechanism of Transformation by RadLV 315
- V. RadLV-Induced Preleukemic (PL) Cells 317
- VI. PL Cell Cultures 319
- VII. Clonal Nature of PL Cells 320
- VIII. IL-4 Dependency of PL Cells 320
- IX. Active Intervention in RadLV Leukemogenesis 323
- X. Conclusion 326
- References 327
Chapter 10. The Insertion of Foreign DNA into Mammalian Genomes and Its Consequences: A Concept in Oncogenesis 331
- I. Scope of Review 331
- II. The Adenovirus System as a Model 334
- III. On the Mechanism of Integrative Recombination 344
- IV. De novo DNA Methylation of Integrated Foreign DNA 349
- V. Alterations in Patterns of Cellular DNA Methylation and Gene Expression as Consequences of Foreign DNA Insertions into Mammal 356
- VI. Uptake of Foreign DNA through the Gastrointestinal Tract 358
- VII. A Concept for Oncogenesis—Implications for Gene Therapy and Research on Transgenic Organisms 359
- References 361
Index 365

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