PHYSIOLOGICAL FACTORS IN HYPERTHERMIA

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Hyperthermia used in combination with radiotherapy or chemotherapy is becoming an established modality for the treatment of cancer. Although malignant cells are not necessarily more heat-sensitive than normal cells, tumors are generally more vulnerable to heat than are normal tissues. It is believed that the intrinsic difference in the vascular structure as well as the thermal response of vasculature and related physiological and metabolic factors in tumors and normal tissues is the main cause of such preferential effect of hyperthermia on tumors. Specifically, the temperature in tumors tends to rise higher than that in adjacent normal tissues during heating, owing to the inefficient heat dissipation by the sluggish blood flow in the tumors relative to that in the normal tissues. It has been known that the thermosensitivity of mammalian cells is profoundly enhanced by acidic and poor nutritional conditions. Interestingly, the intratumor environment is acidic and nutritionally deprived. This condition is further enhanced in the heated tumor probably due to vascular function and related physiological and biochemical factors for the effective use of hyperthermia. The longterm objective of this sutdy is to further understand the role of blood flow and related microenvironment in the hyperthermic treatment of cancer. The specific aim of this application is to elucidate the heatinduced vascular changes in normal internal organs. The heatedinduced change in blood flow in cutaneous tissue has been extensively studied, but the effect of heat on the blood flow in other normal tissues, including the organs in the body cavity, is virtually unknown. This may be attributed to the fact that a suitable device to heat the deep internal organs has not been available. We recently acquired a capacitive heating device capable of heating deep internal organs of experimental animals. We propose to investigate the effect of heat on the blood flow and also determine the threshold thermal dose for vascular damage in various internal organs of rats. The blood flow will be measured with the radioactive microsphere method, which has long been established in our laboratory. We strongly believe the information obtained in this study will provide a rationale basis on which an effective use of hyperthermia to treat deepseated human tumors can be planned.