HYPERTHERMIA STUDIES WITH HUMAN-DERIVED CARCINOMA CELLS

临床结果表明，热疗是最有效的治疗方法 与其他形式的既定癌症治疗相结合。迫在眉睫 第三阶段临床试验的出现需要更全面的 对人体肿瘤热效应的认识及其与肿瘤的联合作用 辐射和毒品。建立生化分析和单细胞 存活率将作为研究临床的量化终点 体温过高的一些方面。人类乳房的原代和已建立的培养， 肺癌和结肠癌细胞将被用于评估基本方面 耐热性和热化疗。一个主要目标是建立 一种反映植物耐热性发育的方法学 新鲜活检的人类肿瘤中的热处理细胞。高水平的 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。人脐静脉内皮细胞将 成为研究热、细胞毒性和热的血管系统模型 抵抗。 已建立的株系中的人类癌细胞将用于研究 热化疗的量化方面。指数和平台期 培养物将暴露在急性和分级的热处理中 与X射线或化疗药物(即L-PAM、顺铂和 他莫昔芬)。这模拟了骑车和慢行的反应 正在增殖的细胞。热、x光或药物的杀伤力 通过耐热率建立耐热细胞。硫醇 耗尽将被用作一种策略来逆转 耐热性。药物对化疗药物转运的影响 体温过高将使用放射性标记药物进行研究。 诱导肿瘤来源癌细胞的耐热性 热与药物和辐射的互动研究应该扩大我们的 预测人类肿瘤对临床生物学反应的依据 体温过高。

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.