PHYSIOLOGICAL FACTORS IN HYPERTHERMIA

这项研究的长远目标是寻找方法，以改善 利用热疗辅助放射治疗的效果 肿瘤与肿瘤生理生化因素的差异 正常组织。当前临床热疗的策略是 选择性损伤肿瘤血管。我们发现当肿瘤血液 血管在中等温度下加热，血管耐热 它可以通过以下方式减少破坏肿瘤血管的机会 随后的加热。我们的第一个具体目标是详细调查 血管耐热性的动力学。我们最近的研究表明 在中等温度加热时，肿瘤的PO2显著增加 尤其是当肿瘤血管耐热时。它看起来 血管的耐热性可能不适合于破坏 血管，但这是可取的改善肿瘤的氧合和 增强肿瘤的放射反应。我们的第二个特定上午是 测定肿瘤热疗前后血氧分压的变化 血管耐热性的诱导。细胞内酸度增加 提高细胞的热敏性。肿瘤细胞具有有效的PHI 细胞内酸度的调节机制 尽管肿瘤内呈酸性，肿瘤仍保持近中性。 环境。我们的第三个具体目标是探索 通过干扰phi调节机制来降低phi 增加肿瘤的热敏性。它已经变得越来越多 明确细胞凋亡是高温诱导细胞死亡的主要方式。 我们的第四个特定目标是描述phi在体温过低诱导的作用。 细胞凋亡。在研究中获得的关于血液变化的信息 肿瘤中的血流和pO2可能使我们能够设计新的策略来使用 热疗可提高肿瘤的放射反应。关于网络安全问题的研究 Phi在热敏化和热诱导细胞凋亡中的作用可能提供 开发酸性肿瘤内环境以改善肿瘤的手段 热疗治疗肿瘤的疗效观察。

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.