Advances in Cancer Research (eBook)

Cover 1
Title Page 4
Copyright Page 5
Contents 6
Contributors to Volume 83 10
Chapter 1. Suppressor and Oncogenic Roles of Transforming Growth ß and Its Signaling Pathways in Tumorigenesis 12
I. Introduction 13
II. The Tgf-ß Signaling Pathway 14
III. Bimodal Action of Tgf-ß in Tumorigenesis 25
IV. Activities of Tgf-ß Important for Oncogenesis 29
V. Dysregulated Expression or Activity of Components of Tgf-ß Signaling Pathways in Oncogenesis 44
VI. Summary 52
References 53
Chapter 2. Hereditary Diffuse Gastric Cancer 66
I. Introduction 66
II. Hereditary Diffuse Gastric Cancer 67
III. Mutations in CDH-1 69
IV. The Tumor Spectrum of Hdgc 71
V. Inactivation of the Second CDH-1 Allele 71
VI. Molecular Mechanism of Hdgc Susceptibility 72
VII. Clinical Criteria and Management of Hdgc 73
VIII. Conclusion 74
References 74
Chapter 3. Role of Heparan Sulfate Proteoglycans in Cell Signaling and Cancer 78
I. Introduction 78
II. Hspgs and Cancer 80
III. Fgf Signaling and Hspgs in Drosophila 82
IV. Dpp Signaling and Hspgs in Drosophila 84
V. Wg and Hh Signaling and Hspgs in Drosophila 84
VI. The Role of Glypicans in Wg Signaling 86
VII. Hspgs Are Involved in Hh Movement 88
VIII. Conclusion 89
References 90
Chapter 4. The Occurrence and Significance of V Gene Mutations in B Cell–Derived Human Malignancy 92
I. Introduction 93
II. Immunoglobulin Genes in Normal B Cell Development 94
III. Immunoglobulin Genes in B Cell Tumors 101
IV. Somatic Mutation in B Cell Tumors 103
V. Chronic Lymphocytic Leukemia 106
VI. Follicular Lymphoma 111
VII. Diffuse Large B Cell Lymphoma 113
VIII. Plasma Cell Tumors 115
IX. Conclusion 120
References 121
Chapter 5. Mhc Antigens and Tumor Escape from Immune Surveillance 128
I. Introduction 128
II. Hla Class I Antigen Expression in Primary Tumors 130
III. Changes in MHC Class I Antigen Expression during Metastatic Colonization 150
IV. T Cell Immunoselection of MHC Class I–Negative Tumor Clones 152
V. Expression of Nonclassical Hla Class I Molecules in Tumors 154
VI. Tumor Nk Escape Mechanisms 156
VII. Hla Class I Loss and T Cell–Based Immunotherapy 157
VIII. Hla Class II Antigens in Tumors 158
IX. Conclusions 160
References 162
Chapter 6. The Role of Selection in Progressive Neoplastic Transformation 170
I. Introduction 171
II. Spontaneous Neoplastic Transformation in Cell Culture 173
III. Selection in Transformation of Established Cell Lines 179
IV. The Contribution of Apoptosis to Selection in Neoplastic Transformation 195
V. Inhibition of Growth of Transformed Cells by Surrounding Nontransformed Cells 198
VI. Confounding Effects of Variable Cell Behavior on the Dynamics of Transformation 199
VII. Summary of the Major Features of Spontaneous Transformation 199
VIII. Evidence for Selection in Experimental and Human Cancer 201
IX. Sources of Genetic Variation for Possible Selection in Tumor Development 206
X. The Nature of Selection in Vivo 207
XI. Selection in Carcinogenesis by Polycyclic Aromatic Hydrocarbons 210
XII. Conclusions 212
References 213
Chapter 7. Atm Genome Stability, Neuronal Development, and Cancer Cross Paths 220
I. Introduction 221
II. Ataxia-Telangiectasia A Disease Caused by Atm Deficiency 222
III. The Atm Gene and Its Mutations 227
IV. The Atm Protein From Sequence to Function 229
V. Atm Functions Lessons from Knockout Mice 242
VI. Atm Deficiency Leads to Increased Oxidative Stress 249
VII. Atm Interplay with Signaling Pathways Associated with Growth and Differentiation 251
VIII. Defects in Dna Damage Response and Cancer Predisposition 252
IX. Conclusions 254
References 255
Index 266