Cancer Biology

by
Edition: 4th
Format: Hardcover
Pub. Date: 2007-04-05
Publisher(s): Oxford University Press
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Summary

The fourth edition of this classic text provides a thorough, yet concise review of the cellular and molecular mechanisms involved in the transformation of normal into malignant cells, the invasiveness of cancer cells into host tissues, and the metastatic spread of cancer cells in the host organism. It defines the fundamental pathophysiologic changes that occur in tumor tissue and in the host animal or patient. Each chapter discusses the historical development of a field, citing the key experimental advances to the present day, and evaluates the current evidence that best supports or rules out concepts of the molecular and cellular mechanisms regulating cancer cell behavior. For all the areas of fundamental cancer research, an effort has been made to relate basic research findings to the clinical disease states. The book is well written and well illustrated, with schematic diagrams and actual research data to demonstrate points made in the text. There is also an extensive, up-to-date bibliography, making the book valuable to scientists, and to physicians, students, and nurses interested in the field of cancer biology. The topics covered include pathologic characterization of human tumors, epidemiology of human cancer, regulation of cell proliferation and differentiation, cellular and molecular phenotypic characteristics of the cancer cell, mechanisms of carcinogenesis, tumor initiation and promotion, viral carcinogenesis, oncogenes and oncogene products, growth factors, chromosomal alterations in cancer, mechanisms of tumor metastasis, host-tumor interactions, fundamental aspects of tumor immunology, and the advances in cancer cell biology that will lead to improved diagnosis and treatment of cancer in the future.

Author Biography

Raymond Ruddons joined the faculty of University of Nebraska, Medical Center in 1990, and was the Eppley Professor of Oncology and Director of the UNMC Eppley Cancer Center.

Table of Contents

Characteristics of Human Cancerp. 3
What Everyone Wants to Know about Cancerp. 3
Patientsp. 3
Physicians and Health Care Professionalsp. 3
Cancer Researchersp. 3
What is Cancer?p. 4
Definition of Cancerp. 4
Description of Cancerp. 4
What Significant Events Have Happened in Cancer Research in the Last 20 Years?p. 5
Basic Facts about Cancerp. 7
Hallmarks of Malignant Diseasesp. 9
Classification of Human Cancersp. 12
Macroscopic and Microscopic Features of Neoplasmsp. 13
Grade and Stage of Neoplasmsp. 14
Histologic Grade of Malignancyp. 14
Tumor Stagingp. 14
Causes of Cancerp. 17
The Theory of "Hits"p. 17
Chemical Carcinogenesisp. 19
Historical Perspectivesp. 19
Metabolic Activation of Chemical Carcinogensp. 21
Donors of simple alkyl groupsp. 21
Cytochrome P-450-mediated activationp. 21
2-acetylaminofluorenep. 22
Other aromatic aminesp. 23
Polycyclic aromatic hydrocarbonsp. 24
DNA Adduct Formationp. 26
Interaction of Chemical Carcinogens with Oncogenes and Tumor Suppressor Genesp. 27
Carcinogen-Induced Epigenetic Changesp. 27
Tumor Initiation, Promotion, and Progressionp. 27
Mechanisms of tumor initiationp. 31
Endogenous carcinogenesisp. 33
Mechanisms of tumor promotion and progressionp. 34
Central dogma of tumor progressionp. 35
Mechanisms of tumor-promoting agentsp. 36
Experimental Models for the Study of Carcinogenesisp. 38
Validity of Tests for Carcinogenicityp. 40
Irradiation Carcinogenesisp. 43
Ionizing Radiationp. 44
Ultraviolet Radiationp. 45
Oxygen Free Radicals, Aging, and Cancerp. 45
Genetic Susceptibility and Cancerp. 47
Multiple Mutations in Cancerp. 47
DNA Repair Mechanismsp. 48
Viral Carcinogenesisp. 51
Historical Perspectivesp. 51
Role of Viruses in the Causation of Human Cancerp. 53
Association of Epstein-Barr virus and human cancersp. 54
Hepatitis virus and hepatocellular carcinomap. 54
Papillomaviruses and cervical cancerp. 55
HTLV-1 and adult T-cell leukemiap. 55
The Epidemiology of Human Cancerp. 62
Trends in Cancer Incidence and Mortalityp. 62
U.S. Datap. 62
Cancer Is a Clobal Problemp. 64
Data for Some Prevalent Human Cancersp. 65
Lung Cancerp. 65
Breast Cancerp. 67
Colorectal Cancerp. 69
Liver Cancerp. 70
Pancreatic Cancerp. 70
Cancers of the Female Reproductive Tractp. 70
Cervical cancerp. 70
Ovarian cancerp. 71
Endometrial cancerp. 71
Prostate Cancerp. 71
Urinary Bladder Cancerp. 72
Lymphomap. 73
Leukemiap. 75
Skin Cancerp. 75
Cancers of the Central Nervous Systemp. 77
Role of Various Factors in the Development of Cancersp. 78
Cigarette Smokingp. 80
Alcoholp. 83
Dietp. 83
Sexual Development, Reproductive Patterns, and Sexual Behaviorp. 85
Industrial Chemicals and Occupational Cancersp. 85
Herbicidesp. 86
Air and Water Pollutantsp. 87
Radiationp. 89
Ultravioletp. 89
Ionizing radiationp. 90
Radonp. 91
Drugsp. 92
Hormonesp. 93
Infectionp. 94
Aging and Cancerp. 94
Genetic Factors in Cancerp. 96
Inherited Cancersp. 97
Gene Environment Interactionsp. 98
Avoidability of Cancerp. 99
Risk Assessmentp. 100
The Great Cancer Mythsp. 102
Passive Smokingp. 103
Radon in the Homep. 104
Cell Phonesp. 105
Electromagnetic Fieldsp. 105
Alcoholp. 106
Organochlorine Compounds, Polycyclic Aromatic Hydrocarbons, and Breast Cancerp. 106
Antiperspirantsp. 107
Water Chlorinationp. 107
Abortion or Miscarriage and Breast Cancerp. 108
Asbestosp. 108
Saccharinp. 108
Acrylamide in Foodsp. 109
Alarp. 109
SV40 Virus in Early Polio Vaccinesp. 110
The Biochemistry and Cell Biology of Cancerp. 117
Historical Perspectivesp. 117
Growth Characteristics of Malignant Cellsp. 120
Phenotypic Alterations in Cancer Cellsp. 120
Immortality of Transformed Cells in Culturep. 121
Decreased Requirement for Growth Factorsp. 122
Loss of Anchorage Dependencep. 122
Loss of Cell Cycle Control and Resistance to Apoptosisp. 122
Changes in Cell Membrane Structure and Functionp. 123
Alterations in cell surface glycolipids, glycoproteins, proteoglycans, and mucinsp. 123
Role of glycosyl transferases and oligosaccharide processing enzymesp. 124
Mucinsp. 125
Proteoglycansp. 125
Modification of Extracellular Matrix Componentsp. 126
Cell-Extracellular Matrix and Cell-Cell Adhesionp. 126
Cell Proliferation versus Differentiationp. 128
Mechanisms of Cellular Differentiationp. 129
Slime moldsp. 131
Yeastp. 134
Sea urchinp. 134
Drosophilia melanogasterp. 136
Mousep. 136
Pathways: getting to know all the playersp. 136
Stimulation of cancer cell differentiationp. 139
Stem Cellsp. 139
Cell Cycle Regulationp. 143
Historical Perspectivesp. 143
The Molecular Playersp. 146
Cyclin-dependent protein kinasesp. 146
CDK inhibitorsp. 146
Cyclinsp. 147
Cell cycle checkpointsp. 148
Cell cycle regulatory factors as targets for anticancer agentsp. 150
Apoptosisp. 151
Historical Perspectivesp. 152
Biochemical Mechanisms of Apoptosisp. 153
Caspasesp. 154
Bcl-2 familyp. 156
Role of mitochondria in apoptosisp. 156
Anoikisp. 157
Resistance to Apoptosis in Cancer and Potential Targets for Therapyp. 157
Growth Factorsp. 158
Historical Perspectivesp. 158
Insulinp. 161
Insulin-Like Growth Factorsp. 161
Nerve Growth Factorp. 164
Epidermal Growth Factorp. 165
Fibroblast Growth Factorp. 171
Platelet-Derived Growth Factorp. 173
Transforming Growth Factorsp. 176
TGF-[alpha]p. 177
TGF-[Beta]p. 178
Hematopoietic Growth Factorsp. 181
Hepatocyte Growth Factor and Scatter Factorp. 185
Miscellaneous Growth Factorsp. 186
Signal Transduction Mechanismsp. 186
Some Key Signal Transduction Conceptsp. 191
Transcriptional regulation by signal transductionp. 191
Protein-protein interaction domainsp. 191
Spatial and temporal regulationp. 192
Signaling networks and crosstalkp. 193
Overview of Some Signal Transduction Pathways Important in Cancerp. 194
G protein-linked receptorsp. 194
The phosphoinositide 3-kinase pathwayp. 198
mTORp. 198
Tyrosine kinase pathwaysp. 200
Protein phosphatasesp. 200
JAK-STAT pathwayp. 201
Estrogen receptor pathwayp. 202
Hypoxia-inducible factorp. 204
Tumor necrosis factor receptor signalingp. 205
Tumor growth factor-[Beta] signal transductionp. 205
Heat shock protein-mediated eventsp. 206
Angiogenesisp. 207
Vascular Endothelial Growth Factorp. 210
Platelet-Derived Growth Factorp. 211
Angiopoietinsp. 211
Ephrinsp. 212
Angiogenesis Inhibitorsp. 212
Inhibitors of proangiogenic factorsp. 212
Metalloproteinasesp. 213
Integrinsp. 213
Endogenous inhibitorsp. 213
HIF-1[alpha]p. 213
Miscellaneous anti-angiogenic agentsp. 214
Clinical datap. 214
Lymphangiogenesisp. 215
Tumor Dormancyp. 215
Biology of Tumor Metastasisp. 216
The "Classic" Theory of Tumor Metastasisp. 216
Alternate Theory of Tumor Metastasisp. 219
Invasion and Metastasis: The Hallmarks of Malignant Neoplasiap. 219
Metastasis Is at Least Partly a Selective Processp. 223
Biochemical Characteristics of Metastatic Tumor Cellsp. 225
Relationship of cancer metastasis to normal tissue invasion eventsp. 225
Role of lytic enzymes in the metastasis cascadep. 226
Role of plasma membrane components in metastasisp. 229
Role of extracellular matrix components and the basement membranes in tumor metastasisp. 230
Tissue adhesion properties of metastatic cellsp. 232
Ability of metastatic tumor cells to escape the host's immune responsep. 234
Chemotactic factors in cancer cell migrationp. 234
Role of oncogenes in tumor metastasisp. 235
Identification of the "Metastatic Genes" and "Metastasis Suppressor Genes"p. 236
Molecular Genetics of Cancerp. 257
Chromatin Structure and Functionp. 258
Components of Chromatinp. 358
Chemical Modifications of Chromatin-Associated Proteinsp. 259
Packaging of Chromatinp. 262
Structure and Function of Interphase Chromosomesp. 264
Nuclear Organizationp. 266
Nuclease Sensitivityp. 267
Transcriptional Activation and the Cancer Connectionp. 268
Control of Gene Expression during Embryonic Stem Cell Differentiationp. 269
Split Genes and RNA Processingp. 270
Genetic Recombinationp. 273
Gene Amplificationp. 277
Cis-Acting Regulatory Elements: Promoters and Enchancersp. 279
Transcription Factorsp. 282
Structural Motifs of Regulatory DNA-Binding Proteinsp. 282
Repressorsp. 284
General (Basal) Transciption Factorsp. 285
Promoter- and Enhancer-Specific Transcription Factorsp. 287
AP-1/Fos/Junp. 287
ATF/CREBp. 287
SP1p. 290
Oct-3p. 290
The superfamily of hormone receptorsp. 290
YY1p. 291
LEF-1p. 291
E2Fp. 291
Tissue specific transcription factorsp. 291
MyoDp. 292
Liver specific transcription factorsp. 293
Pit-1p. 293
E2Ap. 293
NF-[Kappa]Bp. 293
POU-domain binding proteinsp. 294
Ets1 and Ets2p. 294
Homeobox proteinsp. 294
DNA Methylationp. 297
DNA Methyltransferasesp. 298
Methyl DNA Binding Proteinsp. 299
DNA Methylation and Cancerp. 300
Genomic Imprintingp. 302
Loss of Heterozygosityp. 304
Telomeres and Telomerasep. 304
Post-transcriptional Regulationp. 305
Molecular Genetic Alterations in Cancer Cellsp. 307
Translocations and Inversionsp. 308
Chromosomal Deletionsp. 312
Gene Amplificationp. 314
Point Mutationsp. 314
Aneuploidyp. 314
Disomyp. 316
Trinucleotide Expansionp. 316
Microsatellite Instabilityp. 317
Mismatch DNA Repair Defectsp. 317
Gene Derepression in Cancer Cellsp. 318
Ectopic hormone production by human cancersp. 318
Possible mechanisms of ectopic protein productionp. 319
Chromosomal Abnormalities in Leukemic Patients Exposed to Genotoxic Agentsp. 320
Cancer Genetic Changes Summed Upp. 321
Oncogenesp. 321
Historical Perspectivesp. 321
The provirus, protovirus, and oncogene hypothesisp. 321
The src genep. 323
Oncogene Familiesp. 324
Cell Transforming Ability of onc Genesp. 326
Functional Classes of Oncogenesp. 328
Characteristics of Individual Oncogenesp. 330
rasp. 330
mycp. 333
srcp. 335
jun and fosp. 338
etsp. 338
bcr-ablp. 340
mybp. 341
bcl-2p. 341
NF-KB/relp. 342
erbAp. 342
sisp. 343
erbBp. 344
erbB-2 (Her-2/neu)p. 344
Other growth factor or growth factor receptor oncogenesp. 345
fmsp. 345
kitp. 345
trkp. 346
metp. 346
Pokemonp. 346
Cellular onc Gene Expression during Normal Embryonic Developmentp. 346
DNA Tumor Virusesp. 347
SV40 and Polyomap. 347
Papilloma Viruses E6 and E7p. 349
Adenoviruses E1A and E1Bp. 350
Hepatitis B Virusp. 351
Herpes Virusesp. 351
Tumor Suppressor Genesp. 352
Historical Perspectivesp. 352
Properties of Individual Tumor Suppressor Genesp. 354
rbp. 354
Characterization of the rb proteinp. 354
Interactions of Rb proteinsp. 355
Role of rb in reversing the malignant phenotypep. 356
Requirement of a functional rb-1 gene in developmentp. 356
Cell cycle regulation by Rbp. 356
Interactions of Rb protein with transcription factors and DNA regulatory elementsp. 357
p53p. 357
Characteristics of p53 and its mutationsp. 357
Mutagenesis of p53p. 359
Ability of p53 to reverse cellular transformation and tumorigenesisp. 359
Role of p53 in cell cycle progression and in inducing apoptosisp. 360
Mechanism of p53's actionsp. 360
Wilms' tumor suppressor gene wt-1p. 362
Adenomatous polyposis coli (apc) genep. 364
Deleted in colorectal cancer (dcc) genep. 364
Hereditary nonpolyposis colorectal cancer (hnpcc) genep. 364
Neurofibromatosis genes nf-1 and nf-2p. 365
Von Hippel-Lindau syndrome and renal cell carcinoma genep. 365
BRCA1 and BRCA2p. 366
Identification of Tumor Suppressor Genesp. 366
Mechanisms of Gene Silencingp. 367
Antisensep. 367
Ribozymesp. 368
DNAzymesp. 370
RNAip. 370
Transitive RNAip. 372
Micro-RNAp. 373
Small temporal RNAp. 374
Short hairpin RNAp. 374
Gene Therapyp. 374
Gene Therapy for Cancerp. 375
Personalized Medicine and Systems Biologyp. 376
Tumor Immunologyp. 400
Historical Perspectivesp. 400
Mechanisms of the Immune Response to Cancerp. 404
Antigen Presenting Cellsp. 404
How Antigens Are Processedp. 406
T Lymphocytes and T Cell Activationp. 406
The Immunological Synapsep. 408
B Lymphocytes and B Cell Activationp. 409
Natural Killer Cellsp. 410
Cell-Mediated Cytotoxicityp. 411
Danger Theoryp. 412
Role of Gene Rearrangement in the Tumor Responsep. 413
Heat Shock Proteins as Regulators of the Immune Responsep. 414
Inflammation and Cancerp. 414
Immunotherapyp. 415
Rationale for Immunotherapyp. 415
Identification and Characterization of Tumor-Derived Antigenic Peptidesp. 417
Cytokinesp. 417
Interferonsp. 418
Interleukinsp. 420
Tumor necrosis factorp. 421
Adoptive Immunotherapyp. 422
Vaccinesp. 424
Monoclonal Antibodiesp. 424
How Tumor Cells Avoid the Immune Responsep. 424
Cancer Diagnosisp. 429
Medical and Scientific Drivers for Expanded Cancer Diagnostic Techniquesp. 429
Categories of Tumor Markersp. 433
Nucleic Acid-Based Markersp. 433
Cancer-associated mutationsp. 434
Loss of heterozygosity and microsatellite instabilityp. 434
DNA methylation patternsp. 435
Mitochondrial DNA mutationsp. 435
Viral DNAp. 435
Gene Expression Microarraysp. 436
Laser-Capture Microdissectionp. 437
Comparative Genome Hybridizationp. 437
Tissue Arraysp. 439
Gene Expression Microarrays in Individual Cancer Typesp. 439
Lymphomap. 439
Leukemiap. 440
Breast cancerp. 440
Ovarian cancerp. 442
Prostate cancerp. 442
Colorectal cancerp. 443
Lung cancerp. 444
Renal cancerp. 444
Hepatic cancerp. 445
Other cancers and cancer-related phenotypesp. 445
Proteomicsp. 446
Proteomics Methodsp. 447
Two-dimensional electrophoresisp. 447
Isotope-coded affinity tags (ICAT)p. 447
Mass spectrometry-based proteomicsp. 447
Protein chipsp. 449
Surface-enhanced laser desorption/ionization (SELDI)p. 449
Yeast two-hybrid systemp. 450
Phage displayp. 450
Organelle proteomicsp. 451
Plasma proteomep. 451
Tissue proteomics: imaging mass spectrometryp. 451
Pattern recognitionp. 452
The unfolded protein responsep. 452
Proteomics in Cancer Diagnosisp. 453
Lung cancerp. 454
Ovarian cancerp. 454
Breast cancerp. 454
Prostate cancerp. 454
Pancreatic cancerp. 455
Circulating Epithelial Cellsp. 455
Circulating Endothelial Cells and Endothelial Progenitor Cellsp. 456
Molecular Imagingp. 458
Protein-Protein Interactionsp. 459
Protein Degradationp. 459
Imaging Gene Expression In Vivop. 459
Bioluminescent detectionp. 460
Magnetic Resonance Spectroscopyp. 461
Ultrasound Imagingp. 461
Nanotechnologyp. 461
Gray Goop. 464
Pharmacogenomics and Pharmacogeneticsp. 464
Importance of Pharmacogenomics in Cancerp. 465
Haplotype Mappingp. 466
Sequelae of Cancer and Its Treatmentp. 472
Patient-Tumor Interactionsp. 472
Painp. 472
Nutritional Effectsp. 474
Hematologic Effectsp. 477
Erythropoiesisp. 477
Leukopoiesisp. 478
Plateletsp. 478
Thrombosisp. 478
Fever and Infectionp. 479
Hormonal Effectsp. 481
Hypercalcemiap. 481
Neurologic Effectsp. 482
Dermatologic Effectsp. 483
Fatiguep. 483
Sequelae of Cancer Treatmentp. 484
Cancer Preventionp. 487
Molecular Mechanisms of Aging and Its Preventionp. 487
Somatic Mutationp. 487
Telomere Lossp. 487
Mitochondrial Damagep. 488
Formation of Oxygen-Free Radicalsp. 488
Cell Senescencep. 488
DNA Repair and Genome Stabilityp. 488
Caloric Restrictionp. 490
Diet and Cancer Preventionp. 491
Chemopreventionp. 493
Molecular Targets for Chemopreventionp. 494
Antimutagens and Carcinogen-Blocking Agentsp. 494
Isothiocyanatesp. 494
Oltiprazp. 495
Other organosulfur compoundsp. 495
Ellagic acidp. 496
Dehydroepiandrosterone (DHEA)p. 496
Antiproliferative Agentsp. 496
Retinoids and [Beta]-carotenep. 496
Hormonal chemopreventionp. 498
Oral contraceptivesp. 498
Gonadotropin-releasing hormone analogs (GNRHAs)p. 498
Hormone replacement therapyp. 498
Tamoxifen, Raloxifene, and aromatase inhibitorsp. 499
Antiandrogensp. 499
Anti-inflammatory agentsp. 499
Cyclooxygenase-2 inhibitorsp. 500
Ornithine decarboxylase inhibitorsp. 500
Antioxidantsp. 500
Protease Inhibitorsp. 501
Histone Deacetylase Inhibitorsp. 501
Statinsp. 501
Multiagent chemopreventionp. 502
Indexp. 507
Table of Contents provided by Ingram. All Rights Reserved.

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