CORE--CHEMOTHERAPY AND TOXICOLOGY

核心——化疗与毒理学

• 批准号: 6236693
• 负责人: WILLIAM R WAUD
• 金额: $ 28.2万
• 依托单位: SOUTHERN RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-01 至 1998-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6236693
• 关键词: antineoplastics; biomedical facility; drug screening /evaluation; laboratory mouse; neoplasm /cancer chemotherapy; tissue /cell culture; toxicology

This core component is comprised of laboratory facilities, equipment, and services that will be shared by the three projects of the proposed program. The core is service-oriented in concept. Its objective will be to provide in a timely, efficient, and cost-effective manner the evaluation of the antitumor activity of candidate drugs that may be at various stages of development in proposed program. Evaluations may range from initial screening (cytotoxicity compared to relevant standard agents) to detailed evaluations in support of an IND application (e.g., dose and treatment schedule optimization). Evaluations will be conducted in an array of in vitro and in vivo models configured to provide a standardized approach to the development of agents with unknown activity but flexible enough to provide customized approaches for agents about which more is known. Data from a panel of human tumor cell lines in culture will provide additional guidance in the selection of in vivo models (human tumor xenografts) for detailed evaluation of drug activity. These studies may be complemented by evaluations in conventional murine tumor models. This approach, although not exclusive, emphasizes discovery an development of agents active against solid tumors. Data will be presented in terms of comparative IC50 values from in vitro studies and clinically relevant endpoints (e.g., cures, regressions, or prolonged time to treatment failure) from in vivo studies. Dose-response relationships will be assessed in all studies. Limited preliminary toxicological evaluations will also be conducted. Use of these data in drug development decision making will be a cooperative effort among the core component leader, the core co-leaders, the individual project leaders, and the program PI.

该核心部分由实验室设施、设备和 拟议计划的三个项目将共享的服务。 其核心理念是面向服务。 其目标是提供 及时、高效和具有成本效益的方式进行评估 可能处于不同阶段的候选药物的抗肿瘤活性 拟议计划的发展。 评估范围可能从最初的 筛选（与相关标准药物相比的细胞毒性）以详细 支持 IND 申请的评估（例如剂量和治疗 日程优化）。 评估将在一系列方面进行 配置体外和体内模型以提供标准化方法 开发具有未知活性但足够灵活的代理 为了解更多的代理商提供定制方法。 数据 来自一组培养中的人类肿瘤细胞系将提供额外的 选择体内模型（人类肿瘤异种移植物）的指导 详细评价药物活性。 这些研究可能会得到补充 传统小鼠肿瘤模型的评估。 这种做法虽然 不是排他性的，强调发现和开发具有活性的药物 实体瘤。 数据将以比较 IC50 值的形式呈现 来自体外研究和临床相关终点（例如治愈、 体内研究中的回归或治疗失败时间延长）。 所有研究都将评估剂量-反应关系。 有限的 还将进行初步毒理学评估。 使用这些 药物开发决策中的数据将是各方的合作努力 核心组件领导者、核心共同领导者、单个项目 领导者和项目 PI。