PHYSIOLOGICAL FACTORS IN HYPERTHERMIA

热疗的生理因素

• 批准号: 6163904
• 负责人: Chang Won Song
• 金额: $ 23.72万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-01-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6163904
• 关键词: acid base balance; apoptosis; blood flow measurement; blood vessels; calcium; combination cancer therapy; gel electrophoresis; laboratory mouse; laboratory rat; muscle cells; neoplasm /cancer blood supply; neoplasm /cancer radiation therapy; neoplasm /cancer thermotherapy; neoplastic cell; respiratory oxygenation; skin; small intestines; tissue /cell culture

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.

该研究的长期目标是寻找改进方法 热疗辅助放射治疗的有效性 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，血管耐热性 发展，这减少了破坏肿瘤血管的机会 随后加热。 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 中等温度下加热时肿瘤 pO2 显着增加 特别是当肿瘤血管耐热时。 看来 血管耐热性可能不利于破坏 血管，但对于改善肿瘤氧合和 增加肿瘤的放射反应。 我们的第二个具体上午是 测定热疗前后肿瘤内 pO2 的增加 诱导血管耐热性。 细胞内酸度增加 增加细胞的热敏感性。 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，但肿瘤仍保持接近中性 环境。 我们的第三个具体目标是探索以下可能性： 通过干扰 pHi 调节机制来降低 pHi 增加肿瘤的热敏感性。 已经变得越来越 明确细胞凋亡是高热诱导细胞死亡的主要模式。 我们的第四个具体目标是描述 pHi 在体温过低引起的 细胞凋亡。 研究中获得的有关血液变化的信息 肿瘤中的血流和 pO2 可能使我们能够设计新的策略来使用 热疗可增加肿瘤的放射反应。 该研究关于 pHi 在热敏化和热诱导细胞凋亡中的作用可能提供 手段利用酸性瘤内环境来改善 热疗治疗肿瘤的疗效。