Cancer Biology / Edition 4

Cancer Biology / Edition 4

by Raymond W. Ruddon

ISBN-10: 0195175441

ISBN-13: 9780195175448

Pub. Date: 03/15/2007

Publisher: Oxford University Press, USA

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, as well as the hallmarks of cancer cells' behavior in host tissues. It defines the fundamental pathophysiologic changes that occur in tumor tissue and in the host animal or patient. Each


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, as well as the hallmarks of cancer cells' behavior in host tissues. 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. Clearly written and well illustrated, there is also an extensive, up-to-date bibliography, making the book valuable to basic scientists, physicians, nurses, and students interested in the field. The topics covered include pathologic characterization of human tumors, epidemiology of human cancer, regulation of cell proliferation and differentiation, cellular and molecular genetic 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, treatment, and prevention of cancer in the future.

About the Author:
Raymond Ruddon's served as the Associate Director for Basic Science Research of theUniversity's Comprehensive Cancer Center

Product Details

Oxford University Press, USA
Publication date:
Edition description:
Product dimensions:
10.00(w) x 7.00(h) x 1.30(d)

Table of Contents

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

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