Hyperthermia and Cancer

ISBN-13: 9781468441956 / Angielski / Miękka / 2012 / 298 str.

George M. Hahn

Opis

Hyperthermia as a tool for the treatment of malignant disease is rapidly becoming a clinical reality. In this book I am attempting to summarize the known biological and physical underpinnings that have led to this development. I also present a compilation of existing clinical results, limited as these are. My aim is to provide oncologists and other physicians with up-to-date information on this modality, which is both new and old, as well as to make available to biologists, physicists and engineers sum maries of currently available information on specific areas of hyperthermic research. Many people have helped me with this book. Specifically, thanks are due to Drs. William Dewey, Jean Dutreix, Peter Fessenden, Gloria Li, and Jane Marmor. Their suggestions have been invaluable. I hope that not too many errors and omissions have crept into the volume, but in any case, for these I have only myself to blame. I also wish to express my appreciation to David Betten and Marie Graham for their help. Most of this material was written while I was on sabbatical leave on the shores of Lake Atitlan in Guatemala. There I enjoyed the hospitality of a gracious, friendly, and proud people who deserve better than fate seems to have in store for them."

Spis treści

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.