CELL CYCLE TARGETS FOR DRUG AND RADIATION SENSITIVITY

这个修订后的计划项目的目标是研究细胞周期检查点 在潜在的治疗干预背景下进行控制。 本论文分三个部分：1）DNA损伤的机制和信号转导 检查点; 2）药物和辐射敏感性;和3）凋亡。这 应用程序汇集了五个基础科学家和临床医生- 来自宾夕法尼亚大学四个系的科学家和 福克斯蔡斯癌症中心。这个群体代表了不同的学科 涉及肿瘤学、病理学、遗传学、分子和细胞 生物学小组的每个成员都有一个强大的和既定的轨道 在细胞周期研究中的记录。拟议的方案项目建立在 建立实验室之间的互动和合作， 每一位科学家该项目的基本主题是 了解检查点控制的分子途径及其 与药物和辐射敏感性的关系。解剖 这些途径的组成部分可能导致其在临床中的开发， 肿瘤和正常组织的药物和放射敏感性可以 被操纵基础和临床科学家的混合代表 这个项目是必不可少的整合和重点放在他们的 研究细胞对DNA损伤的反应机制。 拥有一个高度集中的小组的优势将导致一个增强的 细胞反应的“大画面”。参与该项目的工作组 该项目将有助于将每个实验室的发现纳入 整体主题的背景。这将激发想法， 材料和信息的流动将扩大 有五个拟议的项目加上三个核心， 所有的调查员都会画出来该项目的最终结果 将更好地了解现在的放射治疗和化学治疗可能 将细胞周期检查点的知识整合到新的 治疗策略。

The goal of this revised program project is to study cell cycle checkpoint control in the context of the potential for therapeutic intervention. There are three sub-themes: 1) a mechanism and signaling of the DNA damage checkpoints; 2) drug and radiation sensitivity; and 3) apoptosis. This application bring together a group of five basic scientists and clinician- scientists from four departments at the University of Pennsylvania and the Fox Chase Cancer Center. This group represents diverse disciplines involved in oncology, pathology, genetics and molecular and cellular biology. Each member of the group has a strong and established track record in cell cycle research. The proposed program project builds on established interactions and collaborations between the laboratories of each of the scientists. The underlying theme of the project is to understand the molecular pathways for checkpoint control and their relationship to drug and radiation sensitivity. Dissection of the components of these pathways may lead to their exploitation in a clinical setting where drug and radiosensitivities of tumors and normal tissues can be manipulated. The mixture of basic and clinical scientists represented by this project is essential for the integration and focusing on their research efforts on the mechanism by which cells respond to DNA damage. The advantage of having a highly focused group will result in an enhanced "large picture" of the cell's response. The working group involved in the project will facilitate the placement of finding from each laboratory into the context of the overall theme. This will stimulate ideas, and the free flow of materials and information will expand the boundaries of the individual groups There are five proposed projects plus three cores from which all the investigators will draw. The ultimate result of the project will be a better understanding of now radio-therapy and chemotherapy may integrate knowledge of cell cycle checkpoints into the development of new treatment strategies.