Cancer Biology
by Ruddon, Raymond W.-
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Summary
Author Biography
Table of Contents
| Characteristics of Human Cancer | p. 3 |
| What Everyone Wants to Know about Cancer | p. 3 |
| Patients | p. 3 |
| Physicians and Health Care Professionals | p. 3 |
| Cancer Researchers | p. 3 |
| What is Cancer? | p. 4 |
| Definition of Cancer | p. 4 |
| Description of Cancer | p. 4 |
| What Significant Events Have Happened in Cancer Research in the Last 20 Years? | p. 5 |
| Basic Facts about Cancer | p. 7 |
| Hallmarks of Malignant Diseases | p. 9 |
| Classification of Human Cancers | p. 12 |
| Macroscopic and Microscopic Features of Neoplasms | p. 13 |
| Grade and Stage of Neoplasms | p. 14 |
| Histologic Grade of Malignancy | p. 14 |
| Tumor Staging | p. 14 |
| Causes of Cancer | p. 17 |
| The Theory of "Hits" | p. 17 |
| Chemical Carcinogenesis | p. 19 |
| Historical Perspectives | p. 19 |
| Metabolic Activation of Chemical Carcinogens | p. 21 |
| Donors of simple alkyl groups | p. 21 |
| Cytochrome P-450-mediated activation | p. 21 |
| 2-acetylaminofluorene | p. 22 |
| Other aromatic amines | p. 23 |
| Polycyclic aromatic hydrocarbons | p. 24 |
| DNA Adduct Formation | p. 26 |
| Interaction of Chemical Carcinogens with Oncogenes and Tumor Suppressor Genes | p. 27 |
| Carcinogen-Induced Epigenetic Changes | p. 27 |
| Tumor Initiation, Promotion, and Progression | p. 27 |
| Mechanisms of tumor initiation | p. 31 |
| Endogenous carcinogenesis | p. 33 |
| Mechanisms of tumor promotion and progression | p. 34 |
| Central dogma of tumor progression | p. 35 |
| Mechanisms of tumor-promoting agents | p. 36 |
| Experimental Models for the Study of Carcinogenesis | p. 38 |
| Validity of Tests for Carcinogenicity | p. 40 |
| Irradiation Carcinogenesis | p. 43 |
| Ionizing Radiation | p. 44 |
| Ultraviolet Radiation | p. 45 |
| Oxygen Free Radicals, Aging, and Cancer | p. 45 |
| Genetic Susceptibility and Cancer | p. 47 |
| Multiple Mutations in Cancer | p. 47 |
| DNA Repair Mechanisms | p. 48 |
| Viral Carcinogenesis | p. 51 |
| Historical Perspectives | p. 51 |
| Role of Viruses in the Causation of Human Cancer | p. 53 |
| Association of Epstein-Barr virus and human cancers | p. 54 |
| Hepatitis virus and hepatocellular carcinoma | p. 54 |
| Papillomaviruses and cervical cancer | p. 55 |
| HTLV-1 and adult T-cell leukemia | p. 55 |
| The Epidemiology of Human Cancer | p. 62 |
| Trends in Cancer Incidence and Mortality | p. 62 |
| U.S. Data | p. 62 |
| Cancer Is a Clobal Problem | p. 64 |
| Data for Some Prevalent Human Cancers | p. 65 |
| Lung Cancer | p. 65 |
| Breast Cancer | p. 67 |
| Colorectal Cancer | p. 69 |
| Liver Cancer | p. 70 |
| Pancreatic Cancer | p. 70 |
| Cancers of the Female Reproductive Tract | p. 70 |
| Cervical cancer | p. 70 |
| Ovarian cancer | p. 71 |
| Endometrial cancer | p. 71 |
| Prostate Cancer | p. 71 |
| Urinary Bladder Cancer | p. 72 |
| Lymphoma | p. 73 |
| Leukemia | p. 75 |
| Skin Cancer | p. 75 |
| Cancers of the Central Nervous System | p. 77 |
| Role of Various Factors in the Development of Cancers | p. 78 |
| Cigarette Smoking | p. 80 |
| Alcohol | p. 83 |
| Diet | p. 83 |
| Sexual Development, Reproductive Patterns, and Sexual Behavior | p. 85 |
| Industrial Chemicals and Occupational Cancers | p. 85 |
| Herbicides | p. 86 |
| Air and Water Pollutants | p. 87 |
| Radiation | p. 89 |
| Ultraviolet | p. 89 |
| Ionizing radiation | p. 90 |
| Radon | p. 91 |
| Drugs | p. 92 |
| Hormones | p. 93 |
| Infection | p. 94 |
| Aging and Cancer | p. 94 |
| Genetic Factors in Cancer | p. 96 |
| Inherited Cancers | p. 97 |
| Gene Environment Interactions | p. 98 |
| Avoidability of Cancer | p. 99 |
| Risk Assessment | p. 100 |
| The Great Cancer Myths | p. 102 |
| Passive Smoking | p. 103 |
| Radon in the Home | p. 104 |
| Cell Phones | p. 105 |
| Electromagnetic Fields | p. 105 |
| Alcohol | p. 106 |
| Organochlorine Compounds, Polycyclic Aromatic Hydrocarbons, and Breast Cancer | p. 106 |
| Antiperspirants | p. 107 |
| Water Chlorination | p. 107 |
| Abortion or Miscarriage and Breast Cancer | p. 108 |
| Asbestos | p. 108 |
| Saccharin | p. 108 |
| Acrylamide in Foods | p. 109 |
| Alar | p. 109 |
| SV40 Virus in Early Polio Vaccines | p. 110 |
| The Biochemistry and Cell Biology of Cancer | p. 117 |
| Historical Perspectives | p. 117 |
| Growth Characteristics of Malignant Cells | p. 120 |
| Phenotypic Alterations in Cancer Cells | p. 120 |
| Immortality of Transformed Cells in Culture | p. 121 |
| Decreased Requirement for Growth Factors | p. 122 |
| Loss of Anchorage Dependence | p. 122 |
| Loss of Cell Cycle Control and Resistance to Apoptosis | p. 122 |
| Changes in Cell Membrane Structure and Function | p. 123 |
| Alterations in cell surface glycolipids, glycoproteins, proteoglycans, and mucins | p. 123 |
| Role of glycosyl transferases and oligosaccharide processing enzymes | p. 124 |
| Mucins | p. 125 |
| Proteoglycans | p. 125 |
| Modification of Extracellular Matrix Components | p. 126 |
| Cell-Extracellular Matrix and Cell-Cell Adhesion | p. 126 |
| Cell Proliferation versus Differentiation | p. 128 |
| Mechanisms of Cellular Differentiation | p. 129 |
| Slime molds | p. 131 |
| Yeast | p. 134 |
| Sea urchin | p. 134 |
| Drosophilia melanogaster | p. 136 |
| Mouse | p. 136 |
| Pathways: getting to know all the players | p. 136 |
| Stimulation of cancer cell differentiation | p. 139 |
| Stem Cells | p. 139 |
| Cell Cycle Regulation | p. 143 |
| Historical Perspectives | p. 143 |
| The Molecular Players | p. 146 |
| Cyclin-dependent protein kinases | p. 146 |
| CDK inhibitors | p. 146 |
| Cyclins | p. 147 |
| Cell cycle checkpoints | p. 148 |
| Cell cycle regulatory factors as targets for anticancer agents | p. 150 |
| Apoptosis | p. 151 |
| Historical Perspectives | p. 152 |
| Biochemical Mechanisms of Apoptosis | p. 153 |
| Caspases | p. 154 |
| Bcl-2 family | p. 156 |
| Role of mitochondria in apoptosis | p. 156 |
| Anoikis | p. 157 |
| Resistance to Apoptosis in Cancer and Potential Targets for Therapy | p. 157 |
| Growth Factors | p. 158 |
| Historical Perspectives | p. 158 |
| Insulin | p. 161 |
| Insulin-Like Growth Factors | p. 161 |
| Nerve Growth Factor | p. 164 |
| Epidermal Growth Factor | p. 165 |
| Fibroblast Growth Factor | p. 171 |
| Platelet-Derived Growth Factor | p. 173 |
| Transforming Growth Factors | p. 176 |
| TGF-[alpha] | p. 177 |
| TGF-[Beta] | p. 178 |
| Hematopoietic Growth Factors | p. 181 |
| Hepatocyte Growth Factor and Scatter Factor | p. 185 |
| Miscellaneous Growth Factors | p. 186 |
| Signal Transduction Mechanisms | p. 186 |
| Some Key Signal Transduction Concepts | p. 191 |
| Transcriptional regulation by signal transduction | p. 191 |
| Protein-protein interaction domains | p. 191 |
| Spatial and temporal regulation | p. 192 |
| Signaling networks and crosstalk | p. 193 |
| Overview of Some Signal Transduction Pathways Important in Cancer | p. 194 |
| G protein-linked receptors | p. 194 |
| The phosphoinositide 3-kinase pathway | p. 198 |
| mTOR | p. 198 |
| Tyrosine kinase pathways | p. 200 |
| Protein phosphatases | p. 200 |
| JAK-STAT pathway | p. 201 |
| Estrogen receptor pathway | p. 202 |
| Hypoxia-inducible factor | p. 204 |
| Tumor necrosis factor receptor signaling | p. 205 |
| Tumor growth factor-[Beta] signal transduction | p. 205 |
| Heat shock protein-mediated events | p. 206 |
| Angiogenesis | p. 207 |
| Vascular Endothelial Growth Factor | p. 210 |
| Platelet-Derived Growth Factor | p. 211 |
| Angiopoietins | p. 211 |
| Ephrins | p. 212 |
| Angiogenesis Inhibitors | p. 212 |
| Inhibitors of proangiogenic factors | p. 212 |
| Metalloproteinases | p. 213 |
| Integrins | p. 213 |
| Endogenous inhibitors | p. 213 |
| HIF-1[alpha] | p. 213 |
| Miscellaneous anti-angiogenic agents | p. 214 |
| Clinical data | p. 214 |
| Lymphangiogenesis | p. 215 |
| Tumor Dormancy | p. 215 |
| Biology of Tumor Metastasis | p. 216 |
| The "Classic" Theory of Tumor Metastasis | p. 216 |
| Alternate Theory of Tumor Metastasis | p. 219 |
| Invasion and Metastasis: The Hallmarks of Malignant Neoplasia | p. 219 |
| Metastasis Is at Least Partly a Selective Process | p. 223 |
| Biochemical Characteristics of Metastatic Tumor Cells | p. 225 |
| Relationship of cancer metastasis to normal tissue invasion events | p. 225 |
| Role of lytic enzymes in the metastasis cascade | p. 226 |
| Role of plasma membrane components in metastasis | p. 229 |
| Role of extracellular matrix components and the basement membranes in tumor metastasis | p. 230 |
| Tissue adhesion properties of metastatic cells | p. 232 |
| Ability of metastatic tumor cells to escape the host's immune response | p. 234 |
| Chemotactic factors in cancer cell migration | p. 234 |
| Role of oncogenes in tumor metastasis | p. 235 |
| Identification of the "Metastatic Genes" and "Metastasis Suppressor Genes" | p. 236 |
| Molecular Genetics of Cancer | p. 257 |
| Chromatin Structure and Function | p. 258 |
| Components of Chromatin | p. 358 |
| Chemical Modifications of Chromatin-Associated Proteins | p. 259 |
| Packaging of Chromatin | p. 262 |
| Structure and Function of Interphase Chromosomes | p. 264 |
| Nuclear Organization | p. 266 |
| Nuclease Sensitivity | p. 267 |
| Transcriptional Activation and the Cancer Connection | p. 268 |
| Control of Gene Expression during Embryonic Stem Cell Differentiation | p. 269 |
| Split Genes and RNA Processing | p. 270 |
| Genetic Recombination | p. 273 |
| Gene Amplification | p. 277 |
| Cis-Acting Regulatory Elements: Promoters and Enchancers | p. 279 |
| Transcription Factors | p. 282 |
| Structural Motifs of Regulatory DNA-Binding Proteins | p. 282 |
| Repressors | p. 284 |
| General (Basal) Transciption Factors | p. 285 |
| Promoter- and Enhancer-Specific Transcription Factors | p. 287 |
| AP-1/Fos/Jun | p. 287 |
| ATF/CREB | p. 287 |
| SP1 | p. 290 |
| Oct-3 | p. 290 |
| The superfamily of hormone receptors | p. 290 |
| YY1 | p. 291 |
| LEF-1 | p. 291 |
| E2F | p. 291 |
| Tissue specific transcription factors | p. 291 |
| MyoD | p. 292 |
| Liver specific transcription factors | p. 293 |
| Pit-1 | p. 293 |
| E2A | p. 293 |
| NF-[Kappa]B | p. 293 |
| POU-domain binding proteins | p. 294 |
| Ets1 and Ets2 | p. 294 |
| Homeobox proteins | p. 294 |
| DNA Methylation | p. 297 |
| DNA Methyltransferases | p. 298 |
| Methyl DNA Binding Proteins | p. 299 |
| DNA Methylation and Cancer | p. 300 |
| Genomic Imprinting | p. 302 |
| Loss of Heterozygosity | p. 304 |
| Telomeres and Telomerase | p. 304 |
| Post-transcriptional Regulation | p. 305 |
| Molecular Genetic Alterations in Cancer Cells | p. 307 |
| Translocations and Inversions | p. 308 |
| Chromosomal Deletions | p. 312 |
| Gene Amplification | p. 314 |
| Point Mutations | p. 314 |
| Aneuploidy | p. 314 |
| Disomy | p. 316 |
| Trinucleotide Expansion | p. 316 |
| Microsatellite Instability | p. 317 |
| Mismatch DNA Repair Defects | p. 317 |
| Gene Derepression in Cancer Cells | p. 318 |
| Ectopic hormone production by human cancers | p. 318 |
| Possible mechanisms of ectopic protein production | p. 319 |
| Chromosomal Abnormalities in Leukemic Patients Exposed to Genotoxic Agents | p. 320 |
| Cancer Genetic Changes Summed Up | p. 321 |
| Oncogenes | p. 321 |
| Historical Perspectives | p. 321 |
| The provirus, protovirus, and oncogene hypothesis | p. 321 |
| The src gene | p. 323 |
| Oncogene Families | p. 324 |
| Cell Transforming Ability of onc Genes | p. 326 |
| Functional Classes of Oncogenes | p. 328 |
| Characteristics of Individual Oncogenes | p. 330 |
| ras | p. 330 |
| myc | p. 333 |
| src | p. 335 |
| jun and fos | p. 338 |
| ets | p. 338 |
| bcr-abl | p. 340 |
| myb | p. 341 |
| bcl-2 | p. 341 |
| NF-KB/rel | p. 342 |
| erbA | p. 342 |
| sis | p. 343 |
| erbB | p. 344 |
| erbB-2 (Her-2/neu) | p. 344 |
| Other growth factor or growth factor receptor oncogenes | p. 345 |
| fms | p. 345 |
| kit | p. 345 |
| trk | p. 346 |
| met | p. 346 |
| Pokemon | p. 346 |
| Cellular onc Gene Expression during Normal Embryonic Development | p. 346 |
| DNA Tumor Viruses | p. 347 |
| SV40 and Polyoma | p. 347 |
| Papilloma Viruses E6 and E7 | p. 349 |
| Adenoviruses E1A and E1B | p. 350 |
| Hepatitis B Virus | p. 351 |
| Herpes Viruses | p. 351 |
| Tumor Suppressor Genes | p. 352 |
| Historical Perspectives | p. 352 |
| Properties of Individual Tumor Suppressor Genes | p. 354 |
| rb | p. 354 |
| Characterization of the rb protein | p. 354 |
| Interactions of Rb proteins | p. 355 |
| Role of rb in reversing the malignant phenotype | p. 356 |
| Requirement of a functional rb-1 gene in development | p. 356 |
| Cell cycle regulation by Rb | p. 356 |
| Interactions of Rb protein with transcription factors and DNA regulatory elements | p. 357 |
| p53 | p. 357 |
| Characteristics of p53 and its mutations | p. 357 |
| Mutagenesis of p53 | p. 359 |
| Ability of p53 to reverse cellular transformation and tumorigenesis | p. 359 |
| Role of p53 in cell cycle progression and in inducing apoptosis | p. 360 |
| Mechanism of p53's actions | p. 360 |
| Wilms' tumor suppressor gene wt-1 | p. 362 |
| Adenomatous polyposis coli (apc) gene | p. 364 |
| Deleted in colorectal cancer (dcc) gene | p. 364 |
| Hereditary nonpolyposis colorectal cancer (hnpcc) gene | p. 364 |
| Neurofibromatosis genes nf-1 and nf-2 | p. 365 |
| Von Hippel-Lindau syndrome and renal cell carcinoma gene | p. 365 |
| BRCA1 and BRCA2 | p. 366 |
| Identification of Tumor Suppressor Genes | p. 366 |
| Mechanisms of Gene Silencing | p. 367 |
| Antisense | p. 367 |
| Ribozymes | p. 368 |
| DNAzymes | p. 370 |
| RNAi | p. 370 |
| Transitive RNAi | p. 372 |
| Micro-RNA | p. 373 |
| Small temporal RNA | p. 374 |
| Short hairpin RNA | p. 374 |
| Gene Therapy | p. 374 |
| Gene Therapy for Cancer | p. 375 |
| Personalized Medicine and Systems Biology | p. 376 |
| Tumor Immunology | p. 400 |
| Historical Perspectives | p. 400 |
| Mechanisms of the Immune Response to Cancer | p. 404 |
| Antigen Presenting Cells | p. 404 |
| How Antigens Are Processed | p. 406 |
| T Lymphocytes and T Cell Activation | p. 406 |
| The Immunological Synapse | p. 408 |
| B Lymphocytes and B Cell Activation | p. 409 |
| Natural Killer Cells | p. 410 |
| Cell-Mediated Cytotoxicity | p. 411 |
| Danger Theory | p. 412 |
| Role of Gene Rearrangement in the Tumor Response | p. 413 |
| Heat Shock Proteins as Regulators of the Immune Response | p. 414 |
| Inflammation and Cancer | p. 414 |
| Immunotherapy | p. 415 |
| Rationale for Immunotherapy | p. 415 |
| Identification and Characterization of Tumor-Derived Antigenic Peptides | p. 417 |
| Cytokines | p. 417 |
| Interferons | p. 418 |
| Interleukins | p. 420 |
| Tumor necrosis factor | p. 421 |
| Adoptive Immunotherapy | p. 422 |
| Vaccines | p. 424 |
| Monoclonal Antibodies | p. 424 |
| How Tumor Cells Avoid the Immune Response | p. 424 |
| Cancer Diagnosis | p. 429 |
| Medical and Scientific Drivers for Expanded Cancer Diagnostic Techniques | p. 429 |
| Categories of Tumor Markers | p. 433 |
| Nucleic Acid-Based Markers | p. 433 |
| Cancer-associated mutations | p. 434 |
| Loss of heterozygosity and microsatellite instability | p. 434 |
| DNA methylation patterns | p. 435 |
| Mitochondrial DNA mutations | p. 435 |
| Viral DNA | p. 435 |
| Gene Expression Microarrays | p. 436 |
| Laser-Capture Microdissection | p. 437 |
| Comparative Genome Hybridization | p. 437 |
| Tissue Arrays | p. 439 |
| Gene Expression Microarrays in Individual Cancer Types | p. 439 |
| Lymphoma | p. 439 |
| Leukemia | p. 440 |
| Breast cancer | p. 440 |
| Ovarian cancer | p. 442 |
| Prostate cancer | p. 442 |
| Colorectal cancer | p. 443 |
| Lung cancer | p. 444 |
| Renal cancer | p. 444 |
| Hepatic cancer | p. 445 |
| Other cancers and cancer-related phenotypes | p. 445 |
| Proteomics | p. 446 |
| Proteomics Methods | p. 447 |
| Two-dimensional electrophoresis | p. 447 |
| Isotope-coded affinity tags (ICAT) | p. 447 |
| Mass spectrometry-based proteomics | p. 447 |
| Protein chips | p. 449 |
| Surface-enhanced laser desorption/ionization (SELDI) | p. 449 |
| Yeast two-hybrid system | p. 450 |
| Phage display | p. 450 |
| Organelle proteomics | p. 451 |
| Plasma proteome | p. 451 |
| Tissue proteomics: imaging mass spectrometry | p. 451 |
| Pattern recognition | p. 452 |
| The unfolded protein response | p. 452 |
| Proteomics in Cancer Diagnosis | p. 453 |
| Lung cancer | p. 454 |
| Ovarian cancer | p. 454 |
| Breast cancer | p. 454 |
| Prostate cancer | p. 454 |
| Pancreatic cancer | p. 455 |
| Circulating Epithelial Cells | p. 455 |
| Circulating Endothelial Cells and Endothelial Progenitor Cells | p. 456 |
| Molecular Imaging | p. 458 |
| Protein-Protein Interactions | p. 459 |
| Protein Degradation | p. 459 |
| Imaging Gene Expression In Vivo | p. 459 |
| Bioluminescent detection | p. 460 |
| Magnetic Resonance Spectroscopy | p. 461 |
| Ultrasound Imaging | p. 461 |
| Nanotechnology | p. 461 |
| Gray Goo | p. 464 |
| Pharmacogenomics and Pharmacogenetics | p. 464 |
| Importance of Pharmacogenomics in Cancer | p. 465 |
| Haplotype Mapping | p. 466 |
| Sequelae of Cancer and Its Treatment | p. 472 |
| Patient-Tumor Interactions | p. 472 |
| Pain | p. 472 |
| Nutritional Effects | p. 474 |
| Hematologic Effects | p. 477 |
| Erythropoiesis | p. 477 |
| Leukopoiesis | p. 478 |
| Platelets | p. 478 |
| Thrombosis | p. 478 |
| Fever and Infection | p. 479 |
| Hormonal Effects | p. 481 |
| Hypercalcemia | p. 481 |
| Neurologic Effects | p. 482 |
| Dermatologic Effects | p. 483 |
| Fatigue | p. 483 |
| Sequelae of Cancer Treatment | p. 484 |
| Cancer Prevention | p. 487 |
| Molecular Mechanisms of Aging and Its Prevention | p. 487 |
| Somatic Mutation | p. 487 |
| Telomere Loss | p. 487 |
| Mitochondrial Damage | p. 488 |
| Formation of Oxygen-Free Radicals | p. 488 |
| Cell Senescence | p. 488 |
| DNA Repair and Genome Stability | p. 488 |
| Caloric Restriction | p. 490 |
| Diet and Cancer Prevention | p. 491 |
| Chemoprevention | p. 493 |
| Molecular Targets for Chemoprevention | p. 494 |
| Antimutagens and Carcinogen-Blocking Agents | p. 494 |
| Isothiocyanates | p. 494 |
| Oltipraz | p. 495 |
| Other organosulfur compounds | p. 495 |
| Ellagic acid | p. 496 |
| Dehydroepiandrosterone (DHEA) | p. 496 |
| Antiproliferative Agents | p. 496 |
| Retinoids and [Beta]-carotene | p. 496 |
| Hormonal chemoprevention | p. 498 |
| Oral contraceptives | p. 498 |
| Gonadotropin-releasing hormone analogs (GNRHAs) | p. 498 |
| Hormone replacement therapy | p. 498 |
| Tamoxifen, Raloxifene, and aromatase inhibitors | p. 499 |
| Antiandrogens | p. 499 |
| Anti-inflammatory agents | p. 499 |
| Cyclooxygenase-2 inhibitors | p. 500 |
| Ornithine decarboxylase inhibitors | p. 500 |
| Antioxidants | p. 500 |
| Protease Inhibitors | p. 501 |
| Histone Deacetylase Inhibitors | p. 501 |
| Statins | p. 501 |
| Multiagent chemoprevention | p. 502 |
| Index | p. 507 |
| Table of Contents provided by Ingram. All Rights Reserved. |
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