Bronner / Farach-Carson Bone and Cancer

1. Auflage 2009
ISBN: 978-1-84882-019-7
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 5, 246 Seiten

Reihe: Topics in Bone Biology

The fifth in a series of reviews, centered on a single major topic (vol. 1 Bone Formation, vol. 2 Bone Resorption, vol. 3 Engineering of Functional Skeletal Tissues, vol. 4 Osteoarthritis) written by acknowledged authorities in the field, and aimed at researchers, clinicians and others involved in the bone field.

Series Editors of Topics in Bone Biology are: Professors Felix Bronner, PhD - University of Connecticut Health Center, Farmington, CT, USA, and Dr Mary C. Farach-Carson, PhD - the Department of Biology, University of Delaware, Newark, DE, USA

Autoren/Hrsg.

Bronner, Felix

Farach-Carson, Mary C.

Inhaltsverzeichnis

1;Preface;6
2;Contents;12
3;Contributors;14
4;1 Blood0Bone Axis and Bone Marrow Microenvironment;20
4.1;1.1 Introduction;20
4.2;1.2 The HSC Niche in Marrow;21
4.3;1.3 Components of the Niche;22
4.4;1.4 Endosteal Niches;22
4.5;1.5 Vascular Niches;26
4.6;1.6 Other Marrow Niches;26
4.7;1.7 Reticular Cells;27
4.8;1.8 HSC Homing to the Marrow and Occupancy;27
4.9;1.9 Parasitism of the Niche by Cancers;28
4.10;1.10 Conclusions;29
4.11;1.11 Acknowledgments;30
5;2 Genetics of Osteosarcoma;37
5.1;2.1 Histopathology of Osteosarcoma;37
5.2;2.2 Unconventional Osteosarcoma Subtypes;38
5.3;2.3 Head and Neck Osteosarcoma;39
5.4;2.4 Osteosarcoma and Bilateral Retinoblastoma;40
5.5;2.5 Osteosarcoma and LiFraumeni Syndrome;41
5.6;2.6 Osteosarcoma and RothmundThomson Syndrome;41
5.7;2.7 Osteosarcoma and Pagets Disease of Bone;41
5.8;2.8 Genetics of Osteosarcoma;42
5.9;2.9 RB1 and Osteosarcoma;42
5.10;2.10 TP53 and Osteosarcoma;43
5.11;2.11 Wnt Signaling Pathway;43
5.12;2.12 Ezrin and Metastasis;43
5.13;2.13 FAS and FASL Signaling;44
5.14;2.14 erbB2/HER2 and Its Role in Osteosarcoma;44
5.15;2.15 RECQL4 and Genomic Stability;45
5.16;2.16 Role of Chromosomal Instability and Telomere Maintenance in Osteosarcoma;45
5.17;2.17 Comparative Genomic Hybridization;46
5.18;2.18 Microarray Analysis of Osteosarcoma;47
5.19;2.19 Summary;48
5.20;2.20 Acknowledgments;48
6;3 Multiple Myeloma and Other Hematological Malignanciesof Bone;61
6.1;3.1 Multiple Myeloma and Bone Disease;61
6.2;3.2 Pathophysiology of Bone Disease in Multiple Myeloma;61
6.3;3.3 Osteoclast Activation/Stimulation;61
6.4;3.4 RANKL;62
6.5;3.5 MIP-1;62
6.6;3.6 Parathyroid Hormone Related Peptide (PTHrP);63
6.7;3.7 IL-6;63
6.8;3.8 Osteoblast Inhibition in Myeloma;63
6.9;3.9 IL-7 and IL-3;64
6.10;3.10 DKK1;64
6.11;3.11 Clinical Manifestations of Myeloma;65
6.12;3.12 Bone Destruction;65
6.13;3.13 Hypercalcemia;65
6.14;3.14 Neurologic Symptoms;65
6.15;3.15 Other Systemic Complications;65
6.16;3.16 Diagnosis;66
6.17;3.17 Evaluation of Bone Involvement;66
6.18;3.18 Prognosis;66
6.19;3.19 Treatment of Myeloma Bone Disease;67
6.20;3.20 Bone Involvement in Hodgkins Disease;68
6.21;3.21 Bone Involvement in Non-Hodgkins Lymphoma (NHL);68
6.22;3.22 Adult T Cell Leukemia/Lymphoma (ATL) Bone Disease;69
6.23;3.23 Hypercalcemia Associated with ATL;69
6.24;3.24 Pathophysiology of ATL Bone Disease;70
6.25;3.25 Treatment of ATL Bone Disease;70
7;4 Mechanism of Metastasis to Bone: The Role of BoneMarrow Endothelium;75
7.1;4.1 Introduction;75
7.2;4.2 The Clinical Sequelae of Bone Metastasis;75
7.3;4.3 Natural History;76
7.4;4.4 Prognosis and Clinical Course;76
7.5;4.5 Hypercalcemia;77
7.6;4.6 Pathologic Fracture;77
7.7;4.7 Bone Pain;78
7.8;4.8 Spinal Cord Compression;78
7.9;4.9 Costs of Treatment;78
7.10;4.10 Endothelial Cells: A Brief Overview;78
7.11;4.11 Bone Marrow Endothelial Cells and Bone Physiology;80
7.12;4.12 Bone-Marrow Endothelial Cells in Tumor Angiogenesis;80
7.13;4.13 Bone-Marrow Endothelial Cells as an Adhesive Substrate for Circulating Cancer Cells;81
7.14;4.14 Rho GTPases: A Brief Background;82
7.15;4.15 Rho GTPases and Angiogenesis;83
7.16;4.16 Rho-Mediated Endothelial Cell Motility;84
7.17;4.17 Closing Comments and an Emerging Concept;85
8;5 Lysophosphatidic Acid: Role in Bone and Bone Cancer;90
8.1;5.1 List of Abbreviations;90
8.2;5.1 Lysophosphatidic Acid;90
8.3;5.2 In vivo Sources of LPA;91
8.4;5.3 Biological Activities of LPA;92
8.5;5.4 LPA Receptors;92
8.6;5.5 Expression of LPA Receptors in Skeletal Cells;93
8.7;5.6 Rapid Effects of LPA on Bone and Cartilage Cells;94
8.7.1;5.6.1 Ca 2+ Signaling;94
8.7.2;5.6.2 MAP Kinase Activation;94
8.7.3;5.6.3 Cytoskeletal Rearrangements;95
8.8;5.7 Long-Term Effects of LPA on Skeletal Cells;95
8.8.1;5.7.1 Cell Proliferation, Survival, and Differentiation;95
8.8.2;5.7.2 Cytoskeletal Changes, Adhesion, and Migration;96
8.8.3;5.7.3 Gene Expression;97
8.9;5.8 Potential Regulatory Roles of LPA in Bone;97
8.9.1;5.8.1 Fracture Healing;97
8.9.2;5.8.2 Regulation of Mechanotransduction;98
8.9.3;5.8.3 The Pathology of Arthritis;98
8.9.4;5.8.4 Regulation of Bone Mass by Leptin;99
8.10;5.9 LPA and Cancers That Metastasize to Bone;99
8.10.1;5.9.1 LPA and Thyroid Cancer;99
8.10.2;5.9.2 LPA and Prostate Cancer;99
8.10.3;5.9.3 LPA and Breast Cancer;99
8.11;5.10 LPA and Bone Metastasis;99
9;6 Role of Bone Microenvironment/Metastatic Nichein Cancer Progression;106
9.1;6.1 Introduction;106
9.2;6.2 Tumor-Derived Growth Factors, Cytokines, and Chemokines Mediate Early Changes in the Bone and Tumor Microenvironment;106
9.2.1;6.2.1 Angiogenic Growth Factors -- The VEGF Family Proteins;107
9.2.2;6.2.2 Other Growth Factors;108
9.2.3;6.2.3 Pharmacological Inhibition of the Soluble Factors that Promote Metastasis;108
9.3;6.3 Within the Bone NicheNiche Interactions Promote Tumor Progression;108
9.3.1;6.3.1 Stem Cell and Tumor Cell Migratory Pathways;109
9.4;6.4 Bone Marrow-Derived Cells Are Recruited to Primary Tumor, Promoting Invasion, Migration, and Dissemination;109
9.5;6.5 Accessory Bone Marrow-Derived Cells Support Tumor Cell Survival and Dissemination;110
9.6;6.6 Bone Marrow-Derived Cells Are Recruited to Sites of Future Metastasis, Forming the Pre-metastatic Niche;111
9.6.1;6.6.1 Early Stromal Changes at Sites of Future Metastasis;111
9.6.2;6.6.2 Tumor-Secreted Factors Preparing Distant Sites for Future Metastasis;111
9.6.3;6.6.3 Stem Cell Niche Dynamics at Pre-metastatic Sites;112
9.6.4;6.6.4 Pre-metastatic Lymph Nodes;112
9.6.5;6.6.5 Therapeutic Inhibition of the Pre-metastatic Niche;112
9.7;6.7 Metastatic Cancer Stem Cells Home Back to Bone;113
9.8;6.8 Genetic Regulation of Metastasis;113
9.8.1;6.8.1 Tumor Suppressor Genes;114
9.8.2;6.8.2 Metastasis Suppressor Genes;114
9.8.3;6.8.3 Genetic Targeting;114
9.9;6.9 Therapeutic Implications;115
10;7 Detection and Characterization of Disseminated Tumor Cells present in Bone Marrow of Cancer Patients;119
10.1;7.1 Summary;119
10.2;7.2 Background: Clinical Relevance of DTC Detection in BM;119
10.3;7.3 Potential and Limitations of DTC Enrichment and Detection Methods;120
10.3.1;7.3.1 Enrichment Methods;120
10.3.2;7.3.2 Detection Methods;121
10.3.3;7.3.3 Immunocytochemical Techniques;121
10.3.3.1;7.3.3.0 Advantages;122
10.3.3.2;7.3.3.1 Disadvantages;122
10.3.4;7.3.4 Polymerase Chain Reaction Based Assays;122
10.3.4.1;7.3.4.0 Advantages;123
10.3.4.2;7.3.4.1 Disadvantages;123
10.3.5;7.3.5 Enzyme-Linked Immunospot (ELISPOT) Technology;123
10.3.5.1;7.3.5.0 Advantages;123
10.3.5.2;7.3.5.1 Disadvantages;123
10.4;7.4 Characterization of DTCs;124
10.4.1;7.4.1 Phenotypic and Molecular Characterization of DTCs;124
10.4.2;7.4.2 Features Enabling Homing, Dormancy, and Re-growth of DTCs;125
10.4.3;7.4.3 Stem Cell-Like Phenotypes of DTCs;126
10.4.4;7.4.4 Identification of Therapeutic Targets for DTCs;127
11;8 Molecular Imaging of Cancer Cells Growing in Bone;134
11.1;8.1 Introduction and Background;134
11.2;8.2 Molecular Imaging Strategies;134
11.2.1;8.2.1 Biomarker Imaging;134
11.2.2;8.2.2 Direct Molecular Imaging;135
11.2.3;8.2.3 Indirect (Reporter Gene) Molecular Imaging;136
11.2.3.1;8.2.3.0 Radiotracer Reporter Gene Imaging;137
11.2.3.2;8.2.3.1 Optical Imaging Genes;140
11.3;8.3 Imaging of Cancer Cells Growing in Bone;141
11.3.1;8.3.1 Clinical Application;141
11.3.1.1;8.3.1.0 Scintigraphy;142
11.3.1.2;8.3.1.1 Computed Tomography;143
11.3.1.3;8.3.1.2 Magnetic Resonance Imaging (MRI);143
11.3.1.4;8.3.1.3 Positron Emission Tomography (PET);143
11.3.2;8.3.2 The Applications of Imaging Technologies in Mouse Models;144
11.3.2.1;8.3.2.0 Bioluminescence and Fluorescence Imaging in the Detection of Bone Metastasis Coupled with Other Imaging Techniques;145
11.4;8.4 Issues for the Future;150
12;9 Inflammatory Cytokines and Their Role in BoneMetastasis and Osteolysis;156
12.1;9.1 Introduction;156
12.2;9.2 The Link Between Inflammation and Cancer Progression;156
12.3;9.3 The Inflammatory Bone Microenvironment in Cancer Progression;157
12.4;9.4 Mediators of the Inflammatory Response;157
12.5;9.5 TNF-;158
12.6;9.6 TGF-;159
12.7;9.7 Interleukin-6;160
12.8;9.8 CXCL12/CXCR4;161
12.9;9.9 Interleukin-8;162
12.10;9.10 Interleukin-10;163
12.11;9.11 Interleukin-12 and -23;163
12.11.1;9.11.1 Interleukin-12;164
12.11.2;9.11.2 Interleukin-23;164
12.12;9.12 Summary;165
12.13;9.13 Acknowledgments;165
13;10 Prostate Cancer Bone Colonization: Osteomimicryin the Bone Niche;171
13.1;10.1 Abbreviations;171
13.2;10.1 Introduction and Chapter Overview;171
13.3;10.2 Phenotypic Alterations in Prostate Cancer Cells Growing in Bone: A New Signaling Triad;172
13.4;10.3 The Plasticity of PCa Cells. Potential Evolutionary Significance;174
13.5;10.4 The Functional Role of Cancer Derived RANKL in Osteoclastogenesis;176
13.6;10.5 Perlecan Supports Signal Amplification Leading to Osteomimicry and PCa Disease Progression;177
13.7;10.6 Acknowledgments;177
14;11 Bone Pain Associated with Cancer Metastasis;181
14.1;11.1 Bone Cancer Pain;181
14.2;11.2 Treatment of Bone Cancer Pain;182
14.3;11.3 Animal Models Used to Study Bone Cancer;183
14.4;11.4 Therapeutics and Skeletal Remodeling;187
15;12 Small Animal Models for the Study of Cancer in Bone;194
15.1;12.1 Introduction;194
15.2;12.2 Breast Cancer;195
15.2.1;12.2.1 Models for the Study of Breast Cancer Metastasis to Bone;195
15.2.1.1;12.2.1.0 Spontaneous;195
15.2.1.2;12.2.1.1 Syngeneic;195
15.2.1.3;12.2.1.2 Xenografts;196
15.2.1.4;12.2.1.3 Transgenic;197
15.3;12.3 Lung Cancer;197
15.3.1;12.3.1 Models for the Study of Lung Cancer Metastasis to Bone;198
15.3.1.1;12.3.1.0 Spontaneous;198
15.3.1.2;12.3.1.1 Syngeneic;198
15.3.1.3;12.3.1.2 Xenograft;198
15.3.1.4;12.3.1.3 Transgenic;200
15.4;12.4 Prostate Cancer;200
15.4.1;12.4.1 Models for the Study of Prostate Cancer Metastasis to Bone;200
15.4.1.1;12.4.1.0 Spontaneous;200
15.4.1.2;12.4.1.1 Syngeneic;201
15.4.1.3;12.4.1.2 Xenograft;201
15.4.1.4;12.4.1.3 Transgenic;204
15.5;12.5 Renal Cancer;204
15.5.1;12.5.1 Models for the Study of Renal Cell Cancer Metastasis to Bone;205
15.5.1.1;12.5.1.0 Spontaneous;205
15.5.1.2;12.5.1.1 Xenograft;205
15.6;12.6 Multiple Myeloma;206
15.6.1;12.6.1 Models for the Study of MM Metastasis to Bone;206
15.6.1.1;12.6.1.0 Spontaneous;206
15.6.1.2;12.6.1.1 Syngeneic;206
15.6.1.3;12.6.1.2 Xenograft;206
15.6.1.4;12.6.1.3 Transgenic;207
15.7;12.7 Melanoma;207
15.7.1;12.7.1 Models for the Study of Melanoma Metastasis to Bone;207
15.7.1.1;12.7.1.0 Spontaneous;207
15.7.1.2;12.7.1.1 Syngeneic;208
15.7.1.3;12.7.1.2 Xenograft;208
15.8;12.8 Concluding Remarks;210
16;13 Hormonal therapies in Breast and Prostate Cancer: Effects on Bone and the Role of Bisphosphonates;217
16.1;13.1 Introduction;217
16.2;13.2 Hormonal Therapies in Breast and Prostate Cancer;217
16.2.1;13.2.1 Prostate Cancer;217
16.2.1.1;13.2.1.0 Use of Gonadotropin-Releasing Hormone Agonists (GnRH-Agonists) in Prostate Cancer;218
16.2.1.2;13.2.1.1 Neoadjuvant and Adjuvant Therapy with GnRH-Agonists for Prostate Cancer;218
16.2.1.3;13.2.1.2 Locally Advanced Disease;218
16.2.1.4;13.2.1.3 Metastatic Disease in PCa;218
16.2.1.5;13.2.1.4 Consequences of GnRH-Agonist Treatment;218
16.2.1.6;13.2.1.5 Loss of Bone Density;219
16.2.1.7;13.2.1.6 Estrogen Loss Due to GnRH-Agonist Treatment;219
16.2.1.8;13.2.1.7 Fractures and GnRH-Agonists;219
16.2.2;13.2.2 Breast Cancer (BCa);219
16.2.2.1;13.2.2.0 Tamoxifen and Bone;220
16.2.2.2;13.2.2.1 AIs and Bone;220
16.3;13.3 Efficacy of AIs;220
16.3.1;13.3.1 Studies of Healthy Women on AIs -- Effects on Bone Markers;220
16.3.2;13.3.2 Data on Premenopausal Women;221
16.4;13.4 AIs as First-Line Treatment for BCa Effect on Bone Loss and Fractures;221
16.4.1;13.4.1 AIs Compared to Tamoxifen;221
16.4.1.1;13.4.1.0 Anastrozole;221
16.4.1.2;13.4.1.1 Letrozole;222
16.4.1.3;13.4.1.2 Exemestane;222
16.4.2;13.4.2 AIs After 2--3 Yrs of Tamoxifen Versus Tamoxifen Alone;222
16.4.2.1;13.4.2.0 Anastrozole;222
16.4.2.2;13.4.2.1 Letrozole;222
16.4.2.3;13.4.2.2 Exemestane;222
16.4.3;13.4.3 AIs Versus Placebo After Tamoxifen for 5 Yrs;223
16.4.3.1;13.4.3.0 Letrozole;223
16.5;13.5 Role of Bisphosphonates in Prostate and Breast Cancer;223
16.5.1;13.5.1 Prevention and Treatment of Bone Metastases;223
16.5.2;13.5.2 Prostate Cancer;223
16.5.3;13.5.3 Breast Cancer;224
16.6;13.6 Prevention of Bone Loss in Prostate and BCa;224
16.6.1;13.6.1 Prostate Cancer;224
16.6.2;13.6.2 Prevention of Bone Loss with Bisphosphonates;224
16.6.3;13.6.3 Use of Estrogen to Prevent Bone Loss in PCa;225
16.6.4;13.6.4 Prevention and Treatment of Bone Loss in Breast Cancer;225
16.7;13.7 Osteoporosis Prevention and Treatment in Breast and Prostate Cancer Patients;226
16.7.1;13.7.1 Clinical Monitoring;226
17;14 Therapeutic Approaches to Metastatic Bone Cancer II:Targeted and Non-targeted Systemic Agents;231
17.1;14.1 Introduction;231
17.2;14.2 Renal Cell Carcinoma;232
17.3;14.3 Thyroid Cancer;233
17.3.1;14.3.1 Well-Differentiated Carcinoma of the Thyroid;233
17.3.2;14.3.2 Medullary Thyroid Carcinoma;233
17.3.3;14.3.3 Anaplastic Thyroid Carcinoma;234
17.4;14.4 Prostate Cancer;234
17.5;14.5 Breast Cancer;236
17.6;14.6 Lung Cancer;236
17.7;14.7 Radiopharmaceuticals;237
17.8;14.8 Conclusion;237
18;15 The Role of Allogeneic Bone Marrow Transplantin Cancer Treatment;240
18.1;15.1 Introduction and Historical Perspectives;240
18.2;15.2 Principles and Technical Aspects of Stem Cell Transplantation;241
18.3;15.3 Current Indications for Allogeneic Stem Cell Transplantation in Cancer Patients;242
18.3.1;15.3.1 Acute Myeloid Leukemia (AML);242
18.3.2;15.3.2 Acute Lymphoblastic Leukemia (ALL);243
18.3.3;15.3.3 Chronic Myeloid Leukemia (CML);243
18.3.4;15.3.4 Myelodysplastic Syndromes (MDSs);243
18.3.5;15.3.5 Lymphoid Malignancies (Non-Hodgkin's Lymphoma; Hodgkin's Lymphoma, Multiple Myeloma and Chronic Lymphocytic Leukemia);244
18.4;15.4 Transplant-Related Complications;245
18.5;15.5 The Future of SCT;246
19;16 The Role of Radiosurgery in the Treatment of BoneLocalized Cancers;251
19.1;16.1 Introduction;251
19.2;16.2 Historical Background;251
19.2.1;16.2.1 Discovery and Implementation of External Beam Radiation Therapy;251
19.2.2;16.2.2 Evolution of Radiosurgery;252
19.3;16.3 Radiobiological Considerations;253
19.4;16.4 Current Applications;254
19.4.1;16.4.1 Clinical Evaluation and Dosing for External Beam Radiation Therapy;254
19.4.2;16.4.2 Clinical Evaluation and Dosing for Stereotactic Radiosurgery;256
19.5;16.5 Conclusion/Future Directions;259
20;Index;262