Hyperthermia and Cancer

1. Introduction: Historical and General Comments.- 2. Mammalian Cell Survival Responses after Exposure to Elevated Temperatures.- 2.1. Introduction.- 2.2. Heat Sensitivity of Mammalian Cells: Definition.- 2.3. Assays.- 2.4. Survival of Cells Exposed to Single Heat Treatments.- 2.4.1. Stable Heat-Resistant Variants.- 2.4.2. Stable Heat-Sensitive Variants.- 2.4.3. Sensitivities of Normal and Malignant Cells.- 2.4.4. Influence of Ploidy, Cell Density, and Cell Cycle on Heat Sensitivity.- 2.5. Modifications of Heat Responses.- 2.5.1. Modification by Changes in pH.- 2.5.2. Nutrients.- 2.5.3. Protective Agents.- 2.6. Survival of Cells Exposed to Multiple Heat Treatments.- 2.6.1. Recovery Phenomena.- 2.6.2. Thermotolerance.- 2.7. Summation.- 3. Thermal Enhancement of the Actions of Anticancer Agents.- 3.1. Introduction.- 3.2. Thermal Enhancement of Radiation Sensitivity.- 3.2.1. Upper Limit of Heat Sensitization.- 3.2.2. The Survival Surface.- 3.2.3. X-Ray Sensitivity and Thermosensitization of Thermotolerant Cells.- 3.2.4. Thermal Enhancement of the X-Ray Response of Normal and Malignant Cells.- 3.2.5. Oxygen Enhancement Ratios.- 3.2.6. Hyperthermia and High LET Radiations.- 3.2.7. Sequencing and Timing.- 3.2.8. Hyperthermia, Radiation, and the Cell Cycle.- 3.2.9. Proliferation Kinetics.- 3.2.10. Recovery Phenomena: X Irradiation and Heat.- 3.3. Enhancement by Hyperthermia of Drug Cytotoxicity.- 3.3.1. Classification of Interactions.- 3.3.2. Technical Aspects of Drug Studies In Vitro.- 3.3.3. Drugs Showing No Threshold Effects.- 3.3.4. Drugs Showing Marked Threshold Effects.- 3.3.5. Thermosensitizers.- 3.3.6. Modification of Drug-Heat Interactions.- 3.3.7. Negative Studies.- 3.4. Summary.- 4. Mechanisms of Heat Action.- 4.1. Introduction.- 4.2. Heat Death of Cells.- 4.2.1. Definition of Heat Dose.- 4.2.2. A Nonspecific Model of Heat Inactivation.- 4.2.3. Macromolecules as Heat “Targets”.- 4.2.4. Cellular Organelles as Heat “Targets”.- 4.2.5. Thermotolerance.- 4.3. Heat-Enhanced X-Ray Cytotoxicity.- 4.4. Drug Cytotoxicities at Elevated Temperatures.- 4.4.1. Alkylating Agents.- 4.4.2. Bleomycin and Adriamycin.- 4.4.3. Cis-Diamminedichloroplatinum(II).- 4.5. Summary.- 5. Responses of Murine Tumors and Normal Tissues.- 5.1. Introduction.- 5.1.1. Model Systems.- 5.2. Responses of Murine Tumors to Hyperthermia Alone.- 5.2.1. Methodology of Heating Murine Tumors.- 5.2.2. Tumor Cures and Survival of Tumor Cells.- 5.2.3. Effects of Different Heating Modalities.- 5.2.4. Modulation of Glucose Blood Levels.- 5.2.5. Factors Governing Variability of Tumor Responses.- 5.3. Normal Tissue Responses to Heat.- 5.3.1. Skin.- 5.3.2. Cartilage.- 5.3.3. Other Tissues.- 5.3.4. Discussion.- 5.4. Responses of Tumor and Normal Tissue to Combinations of Heat and X-Ray.- 5.4.1. Effects on Tumors.- 5.4.2. Effects on Normal Tissue: Therapeutic Gain Factors.- 5.5. Responses of Tumors to Combinations of Heat and Drugs.- 5.5.1. Alkylating Agents.- 5.5.2. Antitumor Antibiotics.- 5.5.3. Nitrosoureas.- 5.5.4. Platinum Compounds.- 5.5.5. Electron Affinic Compounds.- 5.5.6. Lidocaine.- 5.6. Do Tumor Cells Die in the Same Manner In Vivo as They Do In Vitro?.- 5.6.1. The Role of Immune Responses.- 5.6.2. Effect of Hyperthermia on Spread and Growth of Metastases.- 5.7. Summary.- 6. Technical Aspects of Hyperthermia.- 6.1. Introduction.- 6.2. Localized Heating.- 6.2.1. System Requirements.- 6.2.2. Blood Flow in Normal Tissue and in Tumors.- 6.2.3. Methods of Local Heating.- 6.3. Regional Heating.- 6.3.1. Perfusion with Extracorporeally Heated Blood.- 6.3.2. Other Techniques.- 6.4. Whole-Body Heating.- 6.4.1. “Pettigrew” Technique.- 6.4.2. “Blanket” Technique.- 6.4.3. Heating Cabinet.- 6.4.4. Perfusion with Extracorporeally Heated Blood.- 6.4.5. Discussion of Whole-Body Heating Techniques.- 6.5. Possible Adverse Aspects of Heating.- 6.5.1. Dangers Associated with High Temperatures.- 6.5.2. Dangers Associated with Methods of Induction of Hyperthermia.- 6.6. Measurement of Temperatures.- 6.6.1. Invasive Techniques.- 6.6.2. Noninvasive Techniques.- 6.7. Summary.- 7. Effects of Hyperthermia Against Spontaneous Cancers.- 7.1. Introduction.- 7.2. Historical Background.- 7.3. Cancers in Out-Bred Animal Populations.- 7.4. Human Cancers: Heat Alone.- 7.4.1. Whole-Body Heating.- 7.4.2. Regional Heating.- 7.4.3. Heating of Isolated Lesions.- 7.4.4. Discussion.- 7.5. Human Cancer: Heat Plus Irradiation.- 7.5.1. Tumor Responses.- 7.5.2. Discussion.- 7.6. Human Cancers: Heat Plus Drugs.- 7.7. Conclusion.- 7.8. Summary.- References.