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Origin of Cancers - Clinical Perspectives and Implications of a Stem-Cell Theory of Cancer
von: Shi-Ming Tu
Springer-Verlag, 2010
ISBN: 9781441959683 , 237 Seiten
Format: PDF, OL
Kopierschutz: Wasserzeichen
Preis: 106,99 EUR
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Origin of Cancers - Clinical Perspectives and Implications of a Stem-Cell Theory of Cancer
Preface
6
Contents
12
Chapter 1: Introduction
20
Chapter 2: Cancer Myths
25
Introduction
26
Stem-Cell Origin of Cancers
26
Dedifferentiation of Cancer
27
Magic Bullets
27
Multistep Carcinogenesis
29
Cancer Signatures
31
Epithelial-to-Mesenchymal Transition
31
Gene Therapy
32
Cancer Vaccine
32
“Hypothesis-Generating” Research
33
“Translational” Research
33
Technologic vs. Scientific Breakthroughs
34
Curing Cancer
35
Conclusion
36
References
36
Chapter 3: History of Cancer
37
Introduction
37
Paleo-oncology
38
Civilization vs. Age
39
Written Evidence
40
Brief History of Cancer
42
History of the Stem-Cell Theory
43
Saint Peregrine
45
War on Cancer
46
Conclusion
46
References
47
Chapter 4: Origin of Cancer
50
Introduction
50
Cancer Statistics
51
Origin of Cancer
51
Theoretical Oncologists
52
Oncogenes
53
The “Two-Hit” Hypothesis
53
Initiation and Promotion
53
Multistep Carcinogenesis
54
Origins of Cancer, Revisited
55
Stem-Cell Origin of Cancers
56
Defining Idea
57
Conclusion
58
References
58
Chapter 5: Stem Cells
59
Précis
59
Introduction
59
Meristem Cells
60
Regeneration
60
The Cell Concept
61
Finding Stem Cells
61
The Nature of Stem Cells
62
Stemness
62
The Question of Stemness
64
The Stemness Within
64
Parthenogenesis
65
Beyond Stemness
65
Cloning
66
Reprogramming
66
Unknown Unknowns
68
Portrait of a Stem Cell
68
Conclusion
69
References
70
Chapter 6: Stem Cells and Cancer
71
Introduction
72
A Tale of Two Cells
72
Plight of the Tasmanian Devil
72
Secondary Malignancy
74
Stem-Cell Therapy
75
Chronic Injury and Repair
75
Cancer and Aging
76
Met: The Missing Link?
78
Telomerase in Cancer and Stem Cells
79
Aneuploidy
80
Conclusion
81
References
81
Chapter 7: Cancer Stem Cells
83
Précis
83
Introduction
83
Matter and Energy
84
Invention of the Telephone
84
Pioneers of Cancer Stem Cell Research
85
Cancer Stem Cells
86
Origin of Cancer Stem Cells
86
The Making of a Rogue Cell
87
Snags in the Stem-Cell Theory
88
Spontaneous Remissions
89
Succisa Virescit
90
Putative Progenitor Stem Cells
91
The CML Model
91
Stem Cell vs. Progenitor Cell
92
Stem-Cell Theory of Cancer
95
Conclusion
95
References
96
Chapter 8: Cancer Niche
98
Introduction
98
The Dynamic Niche
99
The Embryonic Niche
99
Yin and Yang
100
Niche Matters
100
Donor-Cell Leukemia
101
Stromal Factors
102
Epithelial–Stromal Interactions
102
Hypoxia
103
Niche as an Investigative Medium
104
Niche as a Therapeutic Medium
104
Conclusion
105
References
106
Chapter 9: Ontogeny and Oncology
107
Précis
107
Introduction
107
The Nature of the Beast
108
The Power of Reiteration
108
Reactivation of Embryonic Genes
109
Resurgence vs. Reprogramming
110
Asymmetric Division
111
Polycomb Silencers
112
Epithelial-to-Mesenchymal Transition
113
Compartmentalization of Cancer
113
Clinical Implications
114
Conclusion
115
References
115
Chapter 10: Diagnosis and Prognosis
117
Introduction
117
Cancer 101
118
Personalized Cancer
119
Lethal vs. Indolent Ca.ncers
119
Stem-Cell Hierarchy
120
Selection vs. Evolution
121
Disease Selection by Therapy
122
Diagnosis and Prognosis
122
Methods and Norms
124
Rosetta Stone or Tower of Babel?
125
A Modest Proposal
126
Conclusion
126
References
127
Chapter 11: Cancer Targets
128
Précis
128
Introduction
129
Target du Jour
129
Paradigm Shift
129
Stem-Cell Theory
130
Death by a Thousand “Hits”
130
The Problem with the Gene Theory
131
Necessity or Redundancy?
132
Credentialing Cancer Targets
132
The Making of Human Cancer Cells
133
Field Defect
134
Cancer Targets in Nonmalignant Cells
134
Benign Prostatic Hypertrophy and Prostate Cancer
135
Endometriosis and Ovarian Cancer
136
Et Tu, Stromatogenesis?
137
Targeted Therapy
137
Clinical Implications
138
Conclusion
139
References
139
Chapter 12: Heterogeneity of Cancer
142
Précis
142
Introduction
142
Apples and Oranges
143
The Good, the Bad, and the Ugly
143
Stem-Cell Theory
143
Origin of Heterogeneity
144
HOX Genes
144
Stem Cells and Heterogeneity
145
Pluripotency
146
Genetic Instability
146
Clinical and Biologic Implications
147
Conclusion
148
References
149
Chapter 13: Metastasis
150
Précis
150
Introduction
150
Cell Migration and Tissue Repair
151
A Perfect Storm
151
The Metastatic Journey
152
A Modern “Seed-and-Soil” Theory
152
Stem Cells and Metastasis
153
Final Fury
154
Heterogeneity of Metastasis
154
Host–Cell Interactions
155
Stem-Cell Niche vs. Onco-Niche
155
Clinical and Biologic Implications
157
Conclusion
157
References
158
Chapter 14: Cancer Immunity
160
Précis
160
Introduction
160
Immune Surveillance
161
Immunotolerance
162
Human Leukocyte Antigen Expression
162
HLA-G and Immunotolerance
163
The Meaning of b2M
164
Immune Activation
165
Minimal Residual Disease
165
Cancer Vaccines
166
Melanoma
166
Renal-Cell Carcinoma
167
Cervical Carcinoma
167
Prostate Carcinoma
167
Autoimmunity
168
Conclusion
170
References
170
Chapter 15: Drug Resistance
173
Introduction
173
The Return of Cancer
174
Worst Enemies
174
ABC Transporters
175
DNA Repair
176
Apoptosis
176
“Teratomatous” Tumors
177
The Enigma of Somatic Cells
178
The Goldie–Coldman Principle
178
The Gompertzian Model
179
Clinical Pitfalls
180
Clinical Gems
182
An Exercise in Futility
183
An Uphill Battle
184
Conclusion
184
References
185
Chapter 16: Paradigm Shifts
188
Introduction
188
Dedifferentiation
189
Genetic Mutations
190
Multistep Carcinogenesis
191
The Story of Adenoma
192
It’s the Stem Cell!
193
Metastasis
194
Cancer Niche
195
Conclusion
196
References
196
Chapter 17: Experimental Proof
198
Précis
198
Introduction
198
The Culture of Cancer Research
199
Fundamental Flaws
200
Experimental Proof Already Extant?
200
Mesenchymal Origin
201
Transplantation Studies
201
Heterogeneity Studies
202
Metastasis Studies
203
Experimental Proof Still to Be Found!
203
Circulating Tumor Cells
204
Hox Genes
205
The Study of Stem Cells Helps the Study of Cancer
205
The Study of Cancer Helps the Study of Stem Cells
206
The Ultimate Experiment
206
A Modest Proposal
207
Conclusion
208
References
209
Chapter 18: Clinical Implications
211
Introduction
211
Response vs. Survival
212
Clinical Trials
213
The Problem with Randomization
214
Clinical Perspectives
215
Cancer Screening
215
Cancer Targets
216
Diagnosis and Prognosis
216
Therapeutic Implications
217
Chemoprevention
217
Surgery
218
Vaccine Therapy
219
Stem-Cell Therapy
220
Future Research Directions
220
Cancer Stem Cells
221
Stem-Cell Research
221
Cancer Epigenetics
222
Angiogenesis
223
Conclusion
223
References
224
Chapter 19: Curing Cancer
225
Précis
225
Introduction
225
Conquest vs. Cure
226
Personalized Therapy
227
Chemoprevention
228
Differentiation Therapy
229
Surgery: To Operate or Not to Operate?
230
Maintenance Therapy
231
Targeted Therapy
232
Basic Rules of Science
233
Conclusion
234
References
234
Chapter 20: Epilogue
236
Introduction
236
Cancer’s Boogeyman
237
Legend of the Fall
238
The Curse of Job
238
The Big Fix
239
A Tale of Two Cells
239
Old Dogma and New Doctrine
240
Trade-offs
241
Quo Vadimus?
241
Final Thoughts
242
Glossary
244
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