Biological Basis of Oncologic Thermotherapy

ISBN-13: 9783642749414 / Angielski / Miękka / 2011 / 169 str.

Michel Gautherie; C. Streffer; P. Vaupel

Opis

Studies on the effects of hyperthermia have aroused great interest in recent years. On the one hand, it has been demonstrated. that hyperthermia may be a useful treatment modality for tumors, in combination with ionizing radia tion or cytotoxic drugs. On the other hand, it is of great scientific interest to study the effects of increased temperature on biological systems. Although hyperthermia has been used in the treatment of cancer for cen turies, its therapeutic success was doubtful. However, since it has been shown that radiation-induced cell killirtg can be remarkably enhanced by hyperthermia, many investigations have been performed with cells in vitro, tumors in situ, and normal tissues. From these studies it has been concluded that many biological phenomena and their characteristics which are found in tumors may be conducive to the use of hyperthermia in cancer therapy. Many researchers are studying the cell-killing mechanisms of heat and fac tors that modify cell thermosensitivity. A very fascinating biological phenomenon is the general observation that living cells can enhance their thermoresistance within hours of heat treatment. The development of such thermotolerance is apparently a universal process, and its mechanism is of general scientific interest. Metabolic and physiological processes are changed during and after hyperthermic treatment. These changes exert a strong feedback on the thermo sensitivity of cells and tissues, and also in fluence the heating characteristics of tissues, especially in tumors."

Spis treści

1 Biological Basis of Thermotherapy (With Special Reference to Oncology).- 1.1 Introduction.- 1.2 Methods of Hyperthermia Treatment.- 1.3 Heat Transfer to Tissues and Temperature.- 1.4 Biological Basis for the Action of Hyperthermia and of Combination with Ionizing Radiation.- 1.4.1 Mammalian Cell Survival After Exposure to Hyperthermia.- 1.4.2 Thermosensitivity of Normal and Malignant Cells.- 1.4.3 Cell Survival Dependent on the Cell Cycle.- 1.4.4 Modification of Cell Survival by the Microenvironment.- 1.4.5 Molecular and Metabolic Changes by Hyperthermia.- 1.4.5.1 Conformational Changes of Multimolecular Structures.- 1.4.5.2 Membranes.- 1.4.5.3 Mitotic Spindles and the Cytoskeleton.- 1.4.5.4 Inhibition of DNA, RNA, and Protein Synthesis.- 1.4.5.5 Glucose Metabolism and Hyperthermia.- 1.4.5.6 Redox Ratios and Hyperthermia.- 1.4.5.7 Oxygen Consumption, ATP Levels, and Hyperthermia.- 1.4.6 Thermotolerance.- 1.4.7 Combination of Hyperthermia and Ionizing Radiation.- 1.5 Mechanisms of Action in Cell Killing.- 1.5.1 Mechanisms of Action of Heat Alone.- 1.5.2 Mechanism of Action in Radiosensitization.- 1.6 Responses of Normal Tissues and Tumors.- 1.6.1 Responses of Normal Tissues to Heat.- 1.6.2 Thermoradiosensitization in Normal Tissues.- 1.6.3 Responses of Tumors to Heat.- 1.6.4 Radiosensitization by Heat in Tumors.- 1.7 Combination of Hyperthermia and Drugs.- 1.7.1 Alkylating Agents.- 1.7.2 Antibiotics.- 1.7.3 Antimetabolites.- 1.7.4 Vinca Alkaloids.- 1.7.5 Thermosensitizers.- 1.8 Conclusions.- References.- 2 Pathophysiological Mechanisms of Hyperthermia in Cancer Therapy.- 2.1 Effects of Hyperthermia on Blood Flow Rates and Microcirculation in Normal and Neoplastic Tissues.- 2.1.1 Normal Tissue Blood Flow upon Exposure to a Single Heating.- 2.1.2 Effect of Multiple Heatings on Normal Tissue Blood Flow.- 2.1.3 Laser Doppler Flowmetry in Normal Tissues During Localized Hyperthermia.- 2.1.4 Tumor Blood Flow During and After Hyperthermia.- 2.1.5 Effect of Multiple Heatings on Tumor Blood Flow Rate.- 2.1.6 Laser Doppler Flowmetry in Tumors During Localized Hyperthermia.- 2.1.7 Modification of Heat-Induced Changes in Timor Blood Flow.- 2.2 Microvascular Permeability in Tumors.- 2.2.1 Tumor Vascular Permeability During Normothermia.- 2.2.2 Tumor Vascular Permeability During Hyperthermia.- 2.3 Temperature Distribution in Tumors.- 2.3.1 Temperature Distribution in Tumors During Normothermia.- 2.3.2 Temperature Distribution in Neoplastic Tissues During Hyperthermia.- 2.4 Hyperthermia-Induced Changes in Nutrient and Oxygen Consumption Rates in Tumors.- 2.4.1 Nutrient and Oxygen Supply to Tumors During Hyperthermia.- 2.4.2 Oxygen and Glucose Uptake Rates by Tumors During Hyperthermia.- 2.4.3 Metabolic Imaging in Microregions of Tumors Using Bioluminescence and Photon Counting.- 2.4.4 Energy Status of Tumors upon Hyperthermia.- 2.5 Impact of Hyperthermia on the Cellular Microenvironment in Tumors.- 2.5.1 Tumor Tissue Oxygenation upon Hyperthermia.- 2.5.2 Impact of Localized Hyperthermia on the pH Distribution in Malignant Tumors.- 2.6 Effect of Hyperthermia on Intracellular Ion Concentrations.- 2.7 Conclusions.- References.- 3 The Heat Shock Response: Events Before, During, and After Gene Activation.- 3.1 Introduction.- 3.1.1 Scope of the Review.- 3.1.2 The Current State of Thermobiology.- 3.1.2.1 Heat Shock vs Temperature Shift.- 3.1.2.2 Thermotolerance vs Heat Resistance.- 3.1.2.3 Stress: At What Dose?.- 3.1.2.3.1 The Problem of Thermal and Other Dose.- 3.2 Events Before Gene Activation.- 3.2.1 The Thermotolerant Cell.- 3.2.1.1 Kinetics of Induction of Protection.- 3.2.2 Heat Resistance and Thermotolerance.- 3.2.3 The Cytoskeleton.- 3.2.4 Intracellular Species Unique to the Stressed Cell.- 3.2.4.1 Dinucleotides.- 3.2.4.2 Abnormal Proteins.- 3.2.5 Discussion.- 3.3 Events During and Immediately After Gene Activation.- 3.3.1 The Heat Shock Response at the DNA Level.- 3.3.1.1 Structure of the Heat Shock Genes and Regulation of the Heat Shock Response.- 3.3.1.2 Heat Shock Transcription Factor and Other Proteins Necessary for Transcription.- 3.3.2 The Heat Shock Proteins and Their Functions.- 3.3.2.1 The HSP 70 Family.- 3.3.2.2 The HSP 90 Family.- 3.3.2.3 Do HSPs Protect Cells Against Stress?.- 3.3.2.4 Stress-Induced Translocation of HSPs.- 3.4 Late Events.- 3.4.1 Heat Shock Response and Mitogenesis.- 3.4.2 Normal Development and Differentiation.- 3.4.2.1 Drosophila.- 3.4.2.2 Yeast.- 3.4.2.3 Protozoan Parasites.- 3.4.2.4 Induction of the Heat Shock Response in Early Embryos and in Undifferentiated Cells.- 3.4.2.5 Other Infectious Organisms.- 3.4.2.6 Humans.- 3.4.3 Abnormal Morphogenesis and Teratogenesis.- 3.4.3.1 Drosophila.- 3.4.3.2 Mammals (Nonhuman) and Birds.- 3.4.3.3 Humans.- 3.5 Conclusion.- References.