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找到改善的手段 高温A A佐剂对放射治疗的有效性 肿瘤和生理因素的差异和 正常组织。 当前临床热疗的策略是 选择性损害肿瘤血管。 我们发现当肿瘤血液 血管在中等温度下加热，血管热功率 开发，从而减少了破坏肿瘤血管的机会 随后的加热。 我们的第一个具体目的是详细研究 血管温度耐热的动力学。 我们最近的研究表明 在中等温度下加热时肿瘤PO2显着增加 特别是当肿瘤血管具有热耐剂时。 它出现了 这种血管耐热可能是对破坏的 血管，但希望改善肿瘤氧合和 增加肿瘤的辐射响应。 我们的第二特定是 确定在高温之前和之后，高温肿瘤中PO2的增加 诱导血管耐热。 细胞内酸度的增加 增加细胞热敏。 肿瘤细胞具有有效的PHI 调节机制，细胞内细胞内酸度 尽管有酸性肿瘤，但仍将肿瘤保持在中性附近 环境。 我们的第三个具体目的是探索 通过干扰PHI调节机制来降低PHI 增加肿瘤的热敏。 它变得越来越 明显凋亡是高温诱导细胞死亡的一种主要方式。 我们的第四个具体目的是描述PHI在高质量诱导的 凋亡。 在研究中获得的有关我血液变化的信息 肿瘤中的流量和PO2可能使我们能够设计新的策略 高温以增加肿瘤的辐射响应。 关于 PHI在热敏化和热诱导的凋亡中的作用可能会提供 利用酸性肿瘤内环境来改善的手段 高温治疗肿瘤的功效。