PHYSIOLOGICAL FACTORS IN HYPERTHERMIA

这项研究的长期目标是找到改善 热疗作为放射治疗辅助治疗的有效性 肿瘤生理生化因素的差异， 正常组织 目前临床热疗的策略是 选择性地破坏肿瘤血管。 我们发现当肿瘤血液 血管在中等温度下加热， 发展，这减少了破坏肿瘤血管的机会， 后续加热。 我们的第一个具体目标是详细调查 血管热耐受动力学 我们最近的研究表明， 在中等温度下加热时，肿瘤pO2显著增加 特别是当肿瘤血管耐热时。 似乎 血管的耐热性可能是不希望的破坏， 血管，但其对于改善肿瘤氧合是理想的， 增加肿瘤的放射反应。 我们的第二个具体目标是 通过热疗前后测定肿瘤中pO2的增加 诱导血管热耐受。 细胞内酸度增加 增加细胞的热敏性。 肿瘤细胞具有有效的pHi 调节机制，通过该调节机制， 尽管肿瘤内呈酸性， 环境 我们的第三个具体目标是探索 通过干扰pHi调节机制降低pHi， 增加肿瘤的温度敏感性。 已变得越来越 这清楚地表明凋亡是高血压诱导的细胞死亡的主要模式。 我们的第四个具体目标是描述pHi在过敏性休克诱导的 凋亡 研究中获得的血液变化信息 肿瘤中的血流和pO2可能使我们能够设计新的策略， 用于增加肿瘤的放射反应的热疗。 的研究 pHi在热敏化和热诱导的凋亡中的作用可能提供 利用酸性肿瘤内环境来改善肿瘤细胞生长的方法。 热疗治疗肿瘤的疗效。

The long-term objective of the study is to find means to improve the effectiveness of hyperthermia a an adjuvant to radiotherapy by exploiting the differences in physiological and biochemical factors in tumors and normal tissues. The strategy of current clinical hyperthermia is to selectively damage tumor blood vessels. We found that when tumor blood vessels are heated at moderate temperatures, vascular thermotolarance develops, which reduces the chance of destroying tumor vessels by subsequent heating. Our 1st specific aim is to investigate in detail the kinetics of vascular thermotolerance. Our recent studies indicate that tumor pO2 significantly increases upon heating at moderate temperatures particularly when the tumor blood vessels are thermotolerant. It appears that vascular thermotolerance may be undesirable for the destruction of blood vessels but it is desirable for improving tumor oxygenation and increasing the radioresponse of tumors. Our 2nd specific am is to determine the increase in pO2 in tumors by hyperthermia before and after induction of vascular thermotolerance. Increase in intracellular acidity increases cellular thermosensitivity. Tumor cells possess effective pHi regulatory mechanisms through which the intracellular acidity of cells in tumors is maintained near neutral despite the acidic intratumor environment. Our 3rd specific aim is to explore the possibility of lowering pHi by interfering with the pHi regulatory mechanisms thereby increasing the thermosensitivity of tumors. It has become increasingly clear that apoptosis is a major mode of hyperthermia-induced cell death. Our 4th specific aim is to delineate the role of pHi in hypethermia-induced apoptosis. The information obtained in the study on the changes i blood flow and pO2 in tumors may enable us to design new strategies to use hyperthermia for increasing the radioresponse of tumors. The study on the role of pHi in thermosensitization and heat-induced apoptosis may provide means to exploit the acidic intratumor environment for improving the efficacy of hyperthermia treatment of tumors.