RADIATION SENSITIZERS AND BIOREDUCTIVE DRUGS

此计划项目申请结合了四家公司的不同专业知识 合作实验室开展辐射增敏研究 和在癌症中的生物还原活性的新化合物包括 双官能团和其他硝基杂环试剂，稠合吡嗪单-N- 丝裂霉素C的氧化物和喹酮类似物 包含本应用程序，其总体目标是： 项目1.生物还原药物的鉴定和评价。《博大》 该项目的目的是优化小说的选择和发展 生物还原药物可用作临床放射增敏剂和 用于化疗的低氧选择性药物。 项目2.生物还原药物的微环境和有效性 椭球体。人和啮齿动物细胞系的多细胞肿瘤球体 将用于评估细胞毒性的结构-活性关系 和化学增敏，以及细胞微环境的作用。 项目3.生物还原药物AS的疗效和机制 化学增敏剂。该项目的中心目标是确定 这些生物还原药物的有效性和作用机制 体外和体内缺氧细胞毒素或化学增强剂。 项目4：生物还原药物的致癌转化机制。 基本目的是阐明决定因素和机制。 致瘤性，并提供输入以确定理想的物理化学 生物还原药物的性质。 这四个项目中的实验提供的信息将是 整合以指导新一代生物还原材料的发展 用于癌症治疗和诊断的药物。

This Program Project application combines the different expertise of four collaborating laboratories to perform research on the radiation sensitizing and bioreductive activity in cancer of novel compounds including bifunctional and other nitroheterocyclic agents, fused pyrazine mono-N- oxides and quinonoid analogs of mitomycin C. The four projects which comprise this application and their general objectives are: Project 1. Identification and Evaluation of Bioreductive Drugs. The broad aim of this project is to optimize the selection and development of novel bioreductive drugs that may be used as clinical radiation sensitizers and hypoxia-selective drugs for use in chemotherapy. Project 2. Microenvironments and Effectiveness of Bioreductive Drugs in Spheroids. Multicellular tumor spheroids of human and rodent cell lines will be used to assess structure-activity relationships for cytotoxicity and chemosensitization, and the role of cell microenvironments. Project 3. Efficacy and Mechanisms of Bioreductive Drugs as Chemosensitizing Agents. The central goal of this project is to determine the effectiveness and mechanisms of action of these bioreductive drugs as in vitro and in vivo hypoxic cell cytotoxins or chemopotentiating agents. Project 4. Mechanisms of Oncogenic Transformation by Bioreductive Drugs. The basic aim is to elucidate the mechanisms and factors that determine oncogenicity and provide input to identify the ideal physico-chemical properties of a bioreductive drug. Information provided by the experiments in these four projects will be integrated to guide the development of a new generation of bioreductive drugs for application in the treatment and diagnosis of cancer.