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HYPERTHERMIA STUDIES WITH HUMAN-DERIVED CARCINOMA CELLS

人源癌细胞的热疗研究

基本信息

批准号：
3185084
负责人：
LAURIE A ROIZIN-TOWLE
金额：
$ 10.79万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-08-01 至 1990-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3185084
关键词：
antineoplastics carcinoma cellular oncology human tissue hyperthermia therapy neoplasm /cancer chemotherapy neoplasm /cancer radiation therapy physical chemical interaction radiotracer thiols tissue /cell culture

项目摘要

Clinical results indicate that hyperthermia is most effective when used in conjunction with other forms of established cancer therapy. The imminence of Phase III clinical trials creates a need for a more comprehensive understanding of heat effects in human tumors and its combined action with radiation and drugs. Established biochemical assays and single cell survival will serve as quantitative endpoints to investigate clinical aspects of hyperthermia. Primary and established cultures of human breast, lung and colon carcinoma cells will be used to evaluate fundamental aspects of thermotolerance and thermochemotherapy. A primary goal is to establish a methodology for signalling the development of thermotolerance in heat-treated cells in freshly biopsied human tumors. Elevated levels of heat shock proteins (HSP) and glutathione (GSH) will serve as the chemical expression of heat resistance. Human umbilical vein endothelial cells will be a model for vasculature in studying heat cytotoxicity and heat resistance. Human carcinoma cells from established lines will be used to study quantitative aspects of thermochemotherapy. Exponential and plateau-phase cultures will be exposed to acute and fractionated treatments of heat in combination with x-rays or chemotherapeutic agents (i.E. L-PAM, Cis-DDP and Tamoxifen). This simulates the response of cycling and slowly proliferating cells. The efficacy of heat, x-rays or drugs in killing thermotolerant cells will be established by thermotolerant ratios. Thiol depletion will be used as a strategy to reverse the protective effects of thermotolerance. Alteration of chemotherapeutic drug transport by hyperthermia will be investigated using radiolabelled drugs. Induction of thermotolerance in tumor-derived carcinoma cells and interactive studies of heat with drugs and radiation should broaden our basis for predicting the biological response of human tumors to clinical hyperthermia.

临床结果表明，热疗在以下情况下使用时最有效：与其他形式的已建立的癌症疗法相结合。迫在眉睫 III 期临床试验需要更全面的了解人类肿瘤的热效应及其与热效应的联合作用辐射和药物。建立生化测定和单细胞生存率将作为研究临床的定量终点高热方面。人类乳房的主要和已建立的文化，肺癌和结肠癌细胞将用于评估基本方面耐热性和热化疗。主要目标是建立一种指示耐热性发展的方法新鲜活检的人类肿瘤中经过热处理的细胞。水平升高热休克蛋白（HSP）和谷胱甘肽（GSH）将作为化学物质耐热性的表达。人脐静脉内皮细胞会成为研究热细胞毒性和热的脉管系统模型反抗。来自已建立细胞系的人类癌细胞将用于研究热化疗的定量方面。指数期和平台期培养物将受到急性和分次热处理与 X 射线或化疗药物（即 L-PAM、Cis-DDP 和他莫昔芬）。这模拟了骑自行车时缓慢的反应增殖细胞。热、X射线或药物的杀伤功效耐热细胞将通过耐热比来建立。硫醇消耗将被用作逆转保护作用的策略耐热性。化疗药物转运的改变将使用放射性标记药物对高热进行研究。诱导肿瘤来源的癌细胞耐热性和热与药物和辐射的相互作用研究应该拓宽我们的视野预测人类肿瘤对临床的生物学反应的基础高热。