Advances in Cancer Research (eBook)

Front Cover 1
Advances in Cancer Research 4
Copyright Page 5
Contents 6
Contributors 8
Chapter 1: Update on Human Polyomaviruses and Cancer 10
I. Introduction 10
II. Biology of Polyomaviruses 12
A. Classification and Phylogeny 12
B. Genome Organization 12
C. Viral Life Cycle 16
D. Natural Infection, Reactivation, and Clinical Disease 16
III. Merkel Cell Polyomavirus and Human Cancer 19
A. Human Polyomaviruses and Cancer 19
B. Merkel Cell Polyomavirus 19
IV. SV40 as a Classic Model System 25
A. Large T Antigen 26
B. Small t Antigen 38
C. Transgenic Model Systems 41
V. Conclusion 43
Acknowledgments 43
References 43
Chapter 2: The Tyrosine Phosphatase Shp2 in Development and Cancer 62
I. Introduction 63
II. Shp2 Activation and Signaling 63
III. Lessons from Human and Murine Gain-of-Function Mutations of Shp2 68
A. Shp2 Gain-of-Function Mutations and Noonan Syndrome 68
B. Shp2 Gain-of-Function Mutations in Cancer 69
IV. Lessons from Loss-of-Function Mutations of Shp2 72
A. Shp2 LOF Mutations in Invertebrates and in Xenopus 72
B. Null Mutations of Shp2 in Mice 73
C. LOF Mutations of Shp2 in Humans: LEOPARD Syndrome 75
V. Organ Specific Roles of Shp2: Lessons from Mutations in Mice 76
A. Shp2 and Heart Development 76
B. Shp2 in T-Cell Development 79
C. Shp2 in the CNS 80
D. Shp2 and Neural Crest-Derived Tissues 82
E. Shp2 in Pancreas, the Liver, and Mammary Gland 84
VI. Conclusions and Perspectives 86
References 87
Chapter 3: CXC Chemokines in Cancer Angiogenesis and Metastases 100
I. Introduction 101
II. Angiogenic CXC Chemokines and Receptors 102
III. Angiostatic CXC Chemokines and Receptors 102
IV. Immunoangiostasis 104
V. Chemokine-Induced Angiogenesis in Tumor Models 105
A. Melanoma 106
B. Pancreatic Cancer 106
C. Ovarian Cancer 107
D. Gastrointestinal Cancer 107
E. Bronchogenic Cancer 108
F. Prostate Cancer 109
G. Glioblastoma 110
H. Head and Neck Cancer 110
I. Renal Cell Cancer 110
VI. Chemokines Affect on Cancer Metastases 111
A. The CXCL12–CXCR4 Axis in Mediating Homing of Metastases 111
B. CXCR7, A Novel Receptor for CXCL11 and CXCL12 112
VII. Conclusion 113
References 113
Chapter 4: Genetically Engineered Mouse Models in Cancer Research 122
I. Introduction 123
II. Generation of Genetically Engineered Mouse Models 125
A. Studying Loss of Gene Function in Mouse Models 126
B. Studying Gain of Gene Function in Mouse Models 132
C. Modeling Chromosomal Translocations in Mice 134
D. Studying the Mechanisms and Timing of Tumorigenesis 136
E. Discovery of Novel Tumor Genes 141
III. Cancer Paradigms and Lessons from the Mouse 150
A. The Cancer Stem Cell and Initiating Cell 150
B. The Tumor Microenvironment 154
IV. Summary 162
Acknowledgments 163
References 163
Index 174
Color Plates 180