RESTORATION OF APOPTOSIS IN CANCER

该计划项目的总体目标是将了解癌症分子发病机制和程序性细胞死亡(细胞凋亡)机制的最新进展转化为新的癌症治疗方法。该计划项目是一组研究人员科学合作的合乎逻辑的发展，这些研究人员主要对研究细胞凋亡机制和恢复癌细胞凋亡途径感兴趣。这些研究人员在临床试验设计、基因转移临床试验、载体技术、实验辐射研究、生物化学、分子生物学、肿瘤抑制基因、细胞生物学和动物模型等领域具有互补的专业知识。这些项目是：(1)通过恢复野生型P53的表达来诱导人类癌细胞的辐射敏感性和凋亡，(2)P53/辐射诱导的细胞凋亡中Fas/FasL的相互作用，以及(3)肿瘤细胞死亡的调控策略。核心是(A)行政、(B)实验室服务和(C)信息学。该计划将临床试验与实验室研究项目相结合。这些项目是高度集成的，因此一个项目的研究将推进其他项目的目标，因此将有双向的信息流来产生新的假设。该计划项目的总体目标是检验这样一种假设，即癌细胞中关键基因功能的恢复可以调节治疗效果。该项目的主要重点是与细胞凋亡相关的基因。目前载体的治疗潜力将被优化，凋亡机制及其与电离辐射的相互作用将被研究，并将发现具有治疗潜力的新的基因靶点。包括在该计划项目中的研究可能导致针对癌细胞中特定遗传损伤的癌症治疗，从而代表了可以补充现有治疗的新的作用机制。

The overall goal of this Program Project is to translate recent advances in the understanding of the molecular pathogenesis of cancer and the mechanisms of programmed cell death (apoptosis) into new cancer treatments. This Program Project is a logical development of the scientific collaboration of a group of investigators with major interests in studying apoptotic mechanisms and restoring the cancer cell apoptotic pathway. These investigators have complementary expertise in the areas of clinical trial design, clinical trials in gene transfer, vector technology, experimental radiation research, biochemistry, molecular biology, tumor suppressor genes, cell biology, and animal models. The projects are (1) Induction of Radiation Sensitivity and Apoptosis in Human Cancer Cells By Restoration of Wildtype p53 Expression, (2) Fas/FasL Interations in p53/radiation-induced Apoptosis, and (3) Strategies for Cell Death Manipulation in Cancer. The Cores are (A) Administration, (B) Laboratory Services, and (C) Informatics. The Program combines a clinical trial with laboratory research projects. The Projects are highly integrated so that the research in one project will advance the goals of the other projects and so there will be a bidirectional flow of information to generate new hypotheses. The overall goal of the Program Project is to test the hypothesis that restoration of critical gene function in the cancer cell can mediate therapeutic effects. The major emphasis in the Program Project is on apoptosis-related genes. The therapeutic potential of current vectors will be optimized, apoptotic mechanisms and their interaction with ionizing radiation will be studied, and new gene targets with therapeutic potential will be identified. The studies included in the Program Project could lead to cancer treatments targeted to specific genetic lesions in the cancer cell, thus representing novel mechanisms of action that could complement existing therapies.