DCTD In Vivo Preclinical Testing

In Vivo临床前支持实验室-In Vivo临床前支持小组通过在体内测试潜在的抗癌药物，为生物测试科提供支持。提交给DTP的新试剂在中空纤维试验中进行评估，以使用最少的测试材料和最少的动物数量来评估它们在体内活性的潜力。然后在适当的啮齿动物肿瘤模型(例如，免疫缺陷小鼠的异种移植或同基因小鼠的啮齿动物肿瘤)中测试在该检测中有效的药物，在该模型中，除了抗肿瘤作用外，还检查给药途径、剂量和给药时间表。除了疗效研究，该小组还通过评估化合物对啮齿动物生长的肿瘤的药效学(PD)效应，为0期和CBC计划提供支持。该小组是DTP抗癌药物开发工作、0期PD标记物验证工作和CBC体内疗效评估途径的组成部分。 化合物配方和化合物筛选-化合物配方和化合物筛选小组通过准备测试试剂为生物测试科提供支持，用于体内疗效模型的评估，包括中空纤维和异种移植研究。该小组维护测试试剂的库存，并准确称重和溶解测试材料以进行测试。此外，他们还根据需要确定测试试剂在拟议车辆中的溶解度。该小组还为2008年开展的新的联合药物筛选工作提供技术支持。这些分析提供了临床批准的药物与第二个临床批准的药物或临床试验中的药物联合使用的研究的体外疗效数据。这些检测是在3个不同的细胞系中进行的，使用每个测试剂的3个剂量水平。

In Vivo Preclinical Support Laboratory - The In Vivo Preclinical Support group provides support to the Biological Testing Branch through its testing of potential anticancer agents in vivo. New agents submitted to the DTP are evaluated in the hollow fiber assay to assess their potential for in vivo activity using minimal amounts of test material as well as a minimal number of animals. Agents that are active in this assay are then tested in appropriate rodent tumor models (e.g., xenografts in immunodeficient mice or rodent tumors in syngeneic mice) where the route of administration, dose, and dose schedules are examined, in addition to the antitumor effect. Along with efficacy studies, this group provides support to the Phase 0 and CBC initiatives through evaluation of the pharmacodynamic (PD) effect of compounds on tumors growing in rodent species. This group is an integral part of the DTP anticancer drug development effort, the Phase 0 PD marker validation effort, and the CBC in vivo efficacy evaluation pathway. Compound Formulation & Compound Screening - The Compound Formulation & Compound Screening group provides support to the Biological Testing Branch through its preparation of test agents for assessment in the in vivo efficacy models including the hollow fiber and xenograft studies. This group maintains an inventory of test agents and accurately weighs and solubilizes the test material for testing. In addition, they determine the solubility of test agents in proposed vehicles as needed. This group also provides the technical support for the new combination drug screening effort undertaken in 2008. These assays provide in vitro efficacy data from studies in which a clinically approved agent is combined with a second clinically approved agent or an agent in clinical trials. These assays are conducted in 3 distinct cell lines using 3 dose levels of each test agent.