Biological Basis of Oncologic Thermotherapy

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.

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This volume deals with the biological and pathophysiological basis of thermotherapy in a comprehensive manner and thus provides basic information to researchers investigating the various phenomena involved in the interaction between heat and living cells or tissue, as well as to clinicians who are undertaking therapeutic trials of hyperthermia, especially in cancer treatment. Along with an updated review of the mechanisms of cell killing by heat, particular emphasis is laid upon ongoing research on topics which are of utmost importance with regard to the definition of treatment protocols and understanding of the tumor response to thermotherapy. These include effects of hyperthermia on blood flow rates and microcirculation in normal and malignant tissue, enhancement of radiation and drug-induced cell killing by hyperthermia, genetic and biochemical processes governing the heat schock response, and the phenomena of thermosensitivity and thermotolerance vs. thermoresistance.

Contenu
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.- 1.5 Mechanisms of Action in Cell Killing.- 1.6 Responses of Normal Tissues and Tumors.- 1.7 Combination of Hyperthermia and Drugs.- 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.- 2.2 Microvascular Permeability in Tumors.- 2.3 Temperature Distribution in Tumors.- 2.4 Hyperthermia-Induced Changes in Nutrient and Oxygen Consumption Rates in Tumors.- 2.5 Impact of Hyperthermia on the Cellular Microenvironment in 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.- 3.2 Events Before Gene Activation.- 3.3 Events During and Immediately After Gene Activation.- 3.4 Late Events.- 3.5 Conclusion.- References.