Developmental Biology of Neoplastic Growth

Front Cover
Alvaro Macieira-Coelho
Springer Science & Business Media, May 20, 2005 - Medical - 253 pages
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In this book, tumour growth is perceived as a deviation from the normal development of the human organism. The molecular, cellular, and tissue determinants of different tumours are discussed showing that each is a different disease, often corresponding to a particular developmental stage. The natural history of several cancers illustrates how clinical incidence can be just the visible part of the iceberg, while the first changes at the tissue level sometimes occur several years before tumour growth becomes manifest. Several mechanisms are proposed to explain the distribution of cancers during the human life span and the decline of the incidence of cancers during human senescence.

 

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Contents

The Hedgehog Signaling Pathway in Cancer
1
21 Synthesis and Processing of Hh Protein
2
23 Reception of Hh Signaling
4
24 Intracellular Signal Transduction
5
3 Hh Signaling in Tumor Formation and Growth
6
32 Experiments with Animal Models Link Hh Signaling to Tumorigenesis
7
331 A Subset of Sporadic Cancers Have Mutations in Genes Involved in Hh Signaling
8
Molecular Mechanisms for HhStimulated Tumor Growth
11
53 Evidence for Renal Stem Cells in the Adult Kidney
124
54 Lack of Clonogenicity of Wilms Tumor
125
References
126
Back to Pluripotent Stem Cells
133
2 Cellular Basis of Teratoma Formation
135
22 Human Testicular Cancers
136
23 Environmental Influences on Teratomas
137
32 PGC Growth Factors
138

343 Molecular Targets of Hh Signaling
12
4 SmallMolecule Hh Signaling Antagonists a Therapeutic Opportunity?
15
41 Discovery of SmallMolecule Hh Antagonists
16
5 Future Prospects
17
References
18
Rho GTPases and Cancer
29
2 Rho Proteins and Tumorigenesis
32
4 Upstream Regulation of Rho GTPases
34
5 Downstream Signaling Pathways
36
52 Rho GTPases and Cell Survival
39
53 Rho GTPases and InvasionMetastasis
41
6 Cross Talk Between Racl and Wnt Signaling Pathways
43
7 Rho GTPases as Therapeutic Targets
44
8 Future Directions
46
References
47
of Fibroblasts and Neoplastic Disease
55
21 Matrix Diversity in Situ
56
22 Diversity of Fibroblast Phenotypes in Situ
57
222 Functionalities of Cytoskeletal Proteins
59
3 Evidence of Fibroblast Diversity in a TwoDimensional 2D Culture Model
60
31 Differences Associated with Cytoskeletal and ECM Components
61
32 Expression of Other NonMesenchymal Cytoskeletal Proteins
63
33 Behavioral Dissimilarities Among Mrs
65
34 Diversity Associated with Cell Surface and Secreted Molecules
66
4 Fibroblasts from NonTumoral and Tumoral Breast Tissue
67
42 Discrimination of Fibroblast Subtypes by Multivariate Analysis of Gene Expression
68
5 What Really Are Fibroblasts?
69
52 Revisiting Fibroblast Diversity
71
6 Attempts to Study FibroblastEpithelial Cell Interaction in a Novel Dimension
72
References
74
The Extracellular Matrix During Normal Development and Neoplastic Growth
79
2 Extracellular Matrix During Development
80
21 Fibronectins in Development
83
3 Laminin Isoforms in Tumor Progression
84
31 Fibronectin in Malignant Growth
86
Matricryptins
88
5 Tumor Growth and Matrix Biosynthesis
90
6 Role of Receptor Signaling in Cell Matrix Interaction During Normal Development and Tumor Growth
91
61 The ElastinLaminin Receptor
93
7 Glycosaminoglycans and Proteoglycans in Normal Development and Tumor Progression
95
8 Discussion and Conclusions
97
References
99
Starting Off the Kidney All Over Again?
107
2 A Role for Other Genes and Chromosomal Regions in Wilms Tumor
110
3 Setting the Stage Normal Kidney Development
111
4 A Case for Disrupted Development
114
43 Presentation and Location
115
45 Continued Expression of Early Markers of Kidney Development
116
5 Lessons to be Learned
120
52 Persistence of a Stem Cell or Multipotential Progenitor?
121
34 Human EG Cells
139
35 Genomic Imprinting in PGCs and EG Cells
140
Genetic and Molecular Bases of Teratoma Formation
141
422 PI3 Kinase Signaling Pathway
142
423 Tumor Suppressor Trp53
143
Identification of the Tgct1 and Pgct1 Loci
144
Implications for Stem Cell Biology
145
References
146
Gatekeepers of the Intestine and Kidney
151
Current Understanding of the Molecular Mechanism
152
21 WNTβCatenin Signaling
153
22 StepWise CRC Progression
154
23 The APC Protein
157
24 APC in Cytoskeletal Dynamics
160
Current Understanding of the Molecular Mechanism
162
32 HIF Signaling
164
33 Stepwise RCC Progression
166
34 VHL Regulates Microtubule Stability
167
Precursors to RCC?
169
4 Discussion
170
Signaling vs Cytoskeleton Regulation
172
Hormonal and Stromal Regulation of Normal and Neoplastic Prostatic Growth
183
2 Prostatic Growth and Development
184
23 Prostate Lobes and Regions
185
24 Androgens and Prostatic Development
187
25 StromalEpithelial Interactions in Mature Prostate
190
26 Smooth Muscle of the Prostate
192
27 Estrogen Action in the Prostate
193
28 Prostatic Epithelial Cytodifferentiation
194
3 Prostate Cancer
195
32 StromalEpithelial Interactions During Prostate Cancer Progression
198
33 The Role of CarcinomaAssociated Fibroblasts in the Progression of Human Prostate Cancer
200
34 The Role of Steroid Hormones and Stroma in Prostate Cancer Progression
202
35 Androgens and Prostate Cancer
203
37 Mechanisms of Microenvironmental Influences During Carcinogenesis
204
4 Conclusion
207
References
208
Neoplastic Growth Through the Developmental Stages of the Organism
217
11 Childhood Cancers
218
12 Cancers in Adolescents
219
14 Cancers of the Postreproductive Stage
223
15 Cancers During Senescence
225
21 CellRelated Mechanisms
226
212 Stem Cells
227
213 The Cellular Environment
230
22 Molecularly Related Mechanisms
236
References
240
Subject Index
251
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