Advances in Cancer Research (eBook)

Cover 1
Contents 6
Contributors to Volume 71 10
Chapter 1. p53 and ATM: Cell Cycle, Cell Death, and Cancer 12
I. Introduction 12
II. The p53 Tumor Suppressor Gene 13
III. ATM 20
IV. Cell Cycle Control 27
References 30
Chapter 2. Deletions of the Short Arm of Chromosome 3 in Solid Tumors and the Search for Suppressor Genes 38
I. Tumor Suppressor Genes: The Concept 39
II. Methods of Localizing Tumor Suppressor Genes 41
III. Chromosome 3 Losses in Different Types of Tumors 46
IV. Functional Assays of Tumor Suppression on Chromosome 3 65
V. (Presumed) Tumor Suppressor Genes on the Short Arm of Chromosome 3 69
VI. Evolutionary Aspects of Human Chromosome 3 84
VII. Concluding Remarks 86
References 88
Chapter 3. Mutations Predisposing to Hereditary Nonpolyposis Colorectal Cancer 104
I. Introduction 105
II. The HNPCC Syndrome 106
III. HNPCC and DNA MMR 108
IV. Mutations Predisposing to HNPCC 112
V. Phenotypic Effects of MMR Gene Mutations 122
VI. Implications of Mutation Findings 125
References 126
Chapter 4. Functional Aspects of Apoptosis in Hematopoiesis and Consequences of Failure 132
I. Introduction 133
II. Morphological and Biochemical Features of Apoptosis 134
III. Molecular Mechanisms in Apoptosis 136
IV. Functional Aspects of Apoptosis in the Hematopoietic System 142
V. Disruption of Apoptosis in Hematopoiesis 152
VI. Future Perspectives 163
References 165
Chapter 5. Cyclin-Dependent Kinase Regulation during G 1 Phase and Cell Cycle Regulation by TGF-ß 176
I. Introduction 177
II. Cyclins and Cyclin-Dependent Kinases 179
III. Conclusions 209
References 210
Chapter 6. The Natural Somatic Mutation Frequency and Human Carcinogenesis 220
I. Introduction 221
II. Somatic Mutation of Microsatellite Sequences 222
III. Somatic Mutations of Minisatellite Sequences 228
IV. Somatic Mutation of the HPRT Gene 228
V. The Frequency of Somatic Mutation in Solid Tissues Can Account for Multistep Carcinogenesis 232
VI. Cellular Proliferation as a Risk Factor for Cancer 233
VII. Germline Mutations 235
VIII. The Mutation Rate as the Fundamental Biological Pacemaker 242
IX. The Importance of Measuring Somatic Mutation Rates 244
X. The Mutational Clock and Cancer Prevention 245
References 246
Chapter 7. CD44: Structure, Function, and Association with the Malignant Process 252
I. Introduction 254
II. CD44 Nomenclature 256
III. CD44 Biochemical Structure 257
IV. CD44 Expression on Normal Cells 264
V. Hyaluronic Acid Is the Principal Ligand of CD44 270
VI. Non-HA Ligands of CD44 283
VII. Soluble CD44 285
VIII. Genetic Control of CD44 Expression 286
IX. CD44 Functions 286
X. Involvement of CD44 in Physiological and Pathological Cell Activities 296
XI. CD44 Association with the Malignant Process in Experimental Models 298
XII. CD44 Expression in Human Neoplasms and Its Correlation with the Malignant Status 302
XIII. CD44 Association with Malignancy: Some Practical Comments 315
XIV. Conclusions 316
References 318
Chapter 8. Human Papillomaviruses and Cervical Cancer 332
I. Introduction 332
II. Biology of Papillomaviruses 333
III. Taxonomy and Genomic Variability of Papillomaviruses 336
IV. Epidemiological Aspects 338
V. HPV Interaction with Cofactors 341
VI. Viral Persistence and Disease Progression 342
VII. Viral Burden and Cervical Disease 344
VIII. HPV in Cervical Screening Programs 344
References 346
Chapter 9. HER-2/neu Protein: A Target for Antigen-Specific Immunotherapy of Human Cancer 354
I. Introduction 355
II. HER-2/neu Vaccines For Cancer Therapy 357
III. Potential Pitfalls Associated with HER-2/neu-Specific Immunotherapy 367
IV. HER-2/neu-Specific Antibodies for Cancer Therapy 371
V. Conclusion 377
References 378
Index 384