HYPERTHERMIA, CHEMOTHERAPY AND ONCOGENIC TRANSFORMATION

热疗、化疗和致癌转化

• 批准号: 3185204
• 负责人: ERIC J HALL
• 金额: $ 21.14万
• 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 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3185204
• 关键词: antineoplastics; bleomycin; carmustine; cis platinum compound; combination cancer therapy; combination chemotherapy; drug adverse effect; drug carcinogenesis; drug interactions; gel electrophoresis; laboratory mouse; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; neoplasm /cancer thermotherapy; stress proteins; thermostability; tissue /cell culture; vincristine

There is increasing concern for the oncogenic potential of agents used to treat cancer. To some extent, concern about the production of a second malignancy is the price of success. After all, the patient must be a long-term survivor, with the first malignancy cured--or at least controlled--before the possibility of a treatment-induced second malignancy becomes a problem. Hyperthermia is one of the few modalities used to treat cancer which does not of itself induce oncogenic transformations; by comparison, radiation is a weak oncogenic agent, while some chemotherapy agents are relatively potent. The purpose of the present application is to explore pragmatic and mechanistic aspects of the interaction of heat, chemotherapy agents, and radiation as they relate to oncogenic transformation. The first aims is to determine whether hyperthermia, used to potentiate chemotherapy agents, enhances the transformation incidence to the same extent as it enhances cell lethality. To be specific, for a given level of cell killing, does not thermochemotherapy produce an equally elevated level of oncogenic transformation, or can a sequence be found where cytotoxicity is enhanced without a concomitant increase in oncogenicity? This has proved to be the case for X rays and for the chemotherapy agents investigated to date, namely actinomycin-D, BCNU and mitomycin-C. The range of chemotherapy agents tested in combination with heat will be extended to include bleomycin, melphalan, and cis-platinum, and oncogenic transformation will be monitored in vitro using C3H 10T1/2 cells. Attention will focus also on the transient phenomenon of thermotolerance, whereby cells exposed to an initial heat treatment develop resistance to killing by subsequent heat exposures. We will determine whether or not thermotolerant cells are also resistant to the induction of transformation by X rays and chemotherapeutic agents. The development of thermotolerance will be monitored by the appearance of "heat-shock" proteins and checked by enhanced cell survival.

越来越关注曾经的药物的致癌潜力 治疗癌症。 在某种程度上，对生产的关注 恶性肿瘤是成功的代价。 毕竟，患者必须是 长期幸存者，第一种恶性肿瘤治愈 - 至少 在受到治疗引起的第二次恶性肿瘤的可能性之前。 成为问题。 热疗是用于治疗的少数几种方式之一 癌症本身不会诱导致癌转化；经过 比较，辐射是一种弱致癌剂，而某些化学疗法 代理人相对有效。 本申请的目的是探索务实和 热量，化学疗法剂和 辐射与致癌转化有关。 第一个目的是确定高温是否用于增强 化学疗法剂，将转化的发生率提高到同一 随着它增强细胞致死率的范围。 具体，给定的水平 细胞杀死，不能热化学疗法产生同样升高的水平 致癌性转化，或者可以在细胞毒性的情况下找到序列 没有增强的致癌性而增强吗？ 这就是 事实证明是X射线和化学疗法剂的情况 迄今为止的研究，即放线霉素D，BCNU和丝裂霉素C。 这 结合热测试的化学疗法范围将是 扩展到包括博来霉素，Melphalan和CIS-Platinum和致癌 将使用C3H 10T1/2细胞在体外监测转化。 注意也将集中在热液的瞬时现象上， 在这种细胞中暴露于初始热处理的细胞会产生对 通过随后的热量暴露杀死。 我们将确定是否 温耐剂细胞也有抵抗力的诱导转化 由X射线和化学治疗剂。 耐热性的开发将通过出现 “热震”蛋白质，并通过增强的细胞存活进行检查。