HYPERTHERMIA AND CHEMOTHERAPY ON TUMOR AND NORMAL TISSUE

对肿瘤和正常组织的热疗和化疗

• 批准号: 3185011
• 负责人: JOAN M. BULL
• 金额: $ 15.53万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-15 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3185011
• 关键词: bleomycin; cis platinum compound; combination cancer therapy; cytotoxicity; disease /disorder model; doxorubicin; drug adverse effect; drug metabolism; fibrosarcoma; human tissue; laboratory rat; lung neoplasms; neoplasm /cancer chemotherapy; neoplasm /cancer thermotherapy

Hyperthermia significantly increases chemotherapy induced cytotoxicity for both tumor and normal tissue. Thus, normal tissue injury limits the application of this powerful anti-cancer therapy. in the light of this serious restriction to a potentially effective therapy, there are surprisingly few studies of acute normal tissues reaction to chemotherapy with either local/regional or systemic heat, and no studies of late normal tissue response. The general objective of this continuing research is to establish an optimal thermo-chemotherapy treatment regiment that provides both minimal injury to normal tissue with maximum tumor ablation. The response of a rat fibrosarcoma will be used as a tumor model. We hypothesize that known vascular, metabolic, pH and repair differences between tumors and normal tissues may be exploited to reduce normal tissue damage while maintaining anti-tumor effect. We propose to utilize these dissimilarities between tumor and normal tissues by first establishing dose response curves of local/regional and systemic heat administered simultaneously with the single agents cisplatin, doxorubicin, bleomycin and their respective less toxic analogs. We will first quantitate normal tissue response to the thermochemotherapy; we will then use pharmacokinetic and biochemical pharmacologic studies to optimize drug/heat schedules in order to reduce normal tissue toxicities, retain anti-tumor efficacy of the combined therapy in sensitive tumors and demonstrate activity against resistant tumors. Protective compounds known to reduce specific drug toxicities at normal temperature will then be tested with hyperthermia and drugs to further increase the therapeutic index of the combined modality therapy. Information learned from these studies will be applied to the rational design of a multi-agent chemotherapy-hyperthermia therapy to be used in cancer patients.

热疗显著增加化疗诱导的细胞毒性