HYPERTHERMIA STUDIES WITH HUMAN-DERIVED CARCINOMA CELLS

人源癌细胞的热疗研究

• 批准号: 3185083
• 负责人: LAURIE A ROIZIN-TOWLE
• 金额: $ 11.25万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1989-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3185083
• 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

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，热疗是最有效的，当用于 与其他形式的已建立的癌症治疗相结合。 迫在眉睫 III期临床试验的增加需要更全面的 了解人体肿瘤中的热效应及其与 辐射和药物。 已建立的生化测定和单细胞 生存率将作为研究临床 热疗的各个方面。 原代和已建立的人乳腺培养物， 肺癌和结肠癌细胞将用于评估基本方面 热耐受和热化疗的关键。 主要目标是建立 一种方法，用于发信号的耐热性的发展， 新鲜活检的人类肿瘤中的热处理细胞。 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 作为研究热细胞毒性和热损伤的血管模型 阻力 来自已建立的细胞系的人癌细胞将用于研究 热化疗的定量方面。 指数阶段和平台阶段 培养物将暴露于急性和分次热处理， 与X射线或化学治疗剂（即L-PAM、顺式-DDP和 他莫昔芬）。 这模拟了骑自行车的反应， 增殖细胞 热、X射线或药物的杀伤效果 将通过耐热比率建立耐热细胞。 硫醇 耗尽将被用作一种策略，以扭转保护作用， 耐热性 化疗药物转运的改变 将使用放射性标记药物研究体温过高。 肿瘤源性癌细胞中热耐受性的诱导和 热与药物和辐射的相互作用研究应该扩大我们的 预测人类肿瘤对临床治疗的生物学反应的基础 体温过高