Cancer biology / Raymond W. Ruddon.

Format:

Book

Author/Creator:

Ruddon, Raymond W., 1936-

Language:

English

Subjects (All):

Cancer.

Carcinogenesis.

Molecular biology.

Cell Transformation, Neoplastic.

Neoplasms--etiology.

Medical Subjects:

Cell Transformation, Neoplastic.

Neoplasms--etiology.

Physical Description:

xiv, 530 pages, 24 unnumbered pages of plates : illustrations (partly color) ; 26 cm

Edition:

Fourth edition.

Place of Publication:

Oxford ; New York : Oxford University Press, 2007.

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, 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.

Contents:

1 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

2 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

3 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

4 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

5 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

6 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

7 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

8 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

9 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.

Notes:

Includes bibliographical references and index.

ISBN:

0195175433

9780195175431

0195175441

9780195175448

OCLC:

65341108