PERFLUOROCHEMICAL EMULSIONS AS ADJUNCTS

这个项目的长期目标是使用动物模型系统， 评估全氟化学品乳剂（PFC-E）的潜在价值， 并提供背景资料 需要设计和实施测试这些代理的临床rials。的 在这五年的更新申请中提出的研究将集中在 第二代PFC-E的研究，具有更多的特点 比先导化合物更适合用作癌症治疗的辅助药物 （Fluosol）在我们最初的实验室研究中使用， 正在进行的临床试验。 在大鼠和小鼠中移植肿瘤的研究将扩展到 评估更接近模型的分次治疗方案， 用于临床放射治疗，并确定最佳参数 用于在这些方案期间施用PFC-E。的潜在价值 将PFC-E与缺氧细胞致敏剂组合的多药剂方案，或 将检查对缺氧细胞有毒的药物，以评估是否使用 针对缺氧细胞的多种药物， 不同的缺氧细胞群，提供了更大的潜力， 治疗益处。观察到的肿瘤变化的生物学基础 将检查响应，以评估是否有变化以外的因素 PFC-E对肿瘤细胞的O2输送是PFC-E发挥作用的重要因素。 第二代全氟化学品乳剂对 正常组织（骨髓、皮肤、肺和骨）的辐射反应 将进行检查，以便获得治疗增益的潜力 这些代理商可以评估。这些PFC-E对肿瘤的影响 还将检查生长和进展，以确保这些 药物对恶性肿瘤没有意想不到的作用。数据从这些 研究将被用来帮助设计临床试验测试第二 第二代PFC-E作为放射治疗的替代品。

The long rang goal of this project is to use animal model systems to evaluate the potential value of perfluorochemical emulsions (PFC-E) as adjuncts to radiotherapy and to provide the background information needed to design and implement clinical rials testing these agents. The studies proposed in this five year renewal application will focus on studies of second generation PFC-E, having characteristics more appropriate for use as adjuncts to cancer therapy than the lead compound (Fluosol) used in our initial laboratory studies and in all past and ongoing clinical trials. Studies with transplanted tumors in rats and mice will be extended to assess fractionated treatment regimens which more closely model those used in clinical radiotherapy and to determine the optimal parameters for administering PFC-E during such regimens. The potential value of multi-agent regimens combining PFC-E with hypoxic cell sensitizers or drugs toxic to hypoxic cells will be examined, to assess whether the use of multiple agents directed against hypoxic cells, which may target different hypoxic cell populations, offer the potential for greater therapeutic benefit. The biological bases of observed changes in tumor response will be examined, to assess whether factors other than changes O2 delivery to tumor cells are important to the effects of the PFC-E. Effects of second generation perfluorochemical emulsions on the radiation responses of normal tissues (bone marrow, skin, lung and bone) will be examined so that the potential for obtaining therapeutic gain with these agents can be assessed. The effects of these PFC-E on tumor growth and progression will also be examined, to ensure that these agents have no unexpected effects on the malignancies. Data from these studies will be used to help design clinical trials testing second generation PFC-E as adjuncts to radiotherapy.