PHASE I MOLECULAR AND CLINICAL PHARMACODYNAMIC TRIALS

南加州大学（USC）和City of Hope National 医学中心（COH）对I期试验做出了重大承诺 新的抗癌药物。 临床前和临床研究者 就广泛的活动交换意见和分享资源 与这些试验相关;卤代嘧啶的生物化学调节， 叶酸生物化学和药物开发，局部治疗，剂量- 加强化疗，逆转多药耐药性， 铂作用的调节，抗肿瘤的生物还原活化 醌类，拓扑异构酶相互作用药物，以及与 分化、肿瘤血管生成和转移的生物学。 我们现在有机会建立一个正式的合作 由联合药代动力学核心设施支持的关系，以及 与国家癌症研究所的药物开发部门 程序. 这些合作将提高我们的执行能力 I期分子药效学试验侧重于药理学 这两个机构都有专门知识。 已知优势领域 可用于支持I期研究的材料包括我们的长期经验 在氟嘧啶的药代动力学和药效学中， 其他核苷类抗代谢药，作用机制方面的专业知识 抗癌醌类和铂类似物， 药代动力学/药效学关系， 定量来自少量的相对基因表达， 组织，以及可靠数据管理的可用性， 生物统计设施。

The University of Southern California (USC) and the City of Hope National Medical Center (COH) have made a significant commitment to Phase I trials of new anticancer drugs. Preclinical and clinical investigators have exchanged views and shared resources on a wide range of activities relevant to such trials; biochemical modulation of halopyrimidines, folate biochemistry and drug development, locoregional therapy, dose- intensification of chemotherapy, reversal of multidrug resistance, modulation of platinum action, bioreductive activation of antitumor quinones, topoisomerase-interacting drugs, and emerging targets related to the biology of differentiation, tumor angiogenesis and metastases. We now have the opportunity to establish a formal collaborative relationship supported by a joint pharmacokinetic core facility, and to work more closely with the National Cancer Institute's drug development programs. These collaborations will enhance our capability to perform Phase I molecular pharmacodynamic trials focused by the pharmacologic expertise available at both institutions. Areas of known strength available to support Phase I studies include our long-standing experience in the pharmacokinetics and pharmacodynamics of fluoropyrimidines and other nucleoside antimetabolites, expertise in the mechanism of action of the anticancer quinones and platinum analogs, and in modeling pharmacokinetic/pharmacodynamic relationships, pioneering experience in the quantitation of relative gene expression from small amounts of tissue, and the availability of reliable data management and biostatistical facilities.