GENE AND CYTOKINE EXPRESSION IN THE CNS RADIORESPONSE

描述：减轻或防止辐射诱导的能力 中枢神经系统损伤在肿瘤治疗中具有明显优势。然而， 在这种干预策略的合理发展之前 继续进行下去，首先需要增加我们对 这一关键的正常组织的基础放射生物学。中国政府的回应 中枢神经系统对其他类型的损伤涉及到特定细胞因子水平的升高， 它们被认为是内在恢复过程的中介。现在已经很好了 确定电离辐射的生物效应包括 不仅细胞死亡，还改变了多个基因的表达。 拟议的研究是基于这样一个前提，即 CNS至少在一定程度上受到特定药物产量增加的影响 细胞因子：辐射诱导基因表达的产物。终极的 这个项目的目标是开发出操纵 辐射介导的体内细胞因子产生的变化，这将使 以研究诱导基因表达在 中枢神经系统的放射反应。首先，有必要确定 受中枢神经系统照射影响的特异性基因和细胞因子 追究责任机制(S)。这些研究将被执行 主要采用大鼠星形胶质细胞的体外培养。在此基础上 信息，将制定策略来操纵辐射诱导 细胞因子在成年大鼠颈椎模型中的表达 电源线。在这些调查中，将使用两种操纵方法： 辐射诱导基因表达的药理抑制及体外研究 基因疗法。这些研究的目标是检验这一假设 诱导的基因表达，因此，特定的细胞因子发挥着 在中枢神经系统的辐射反应中起重要作用。建议进行的研究 不仅应该为人类的基本放射生物学 CNS，但也应该建议治疗策略，以减少 在这个关键的正常组织中由辐射引起的损伤。

DESCRIPTION: The ability to alleviate or protect against radiation-induced CNS injury would be of obvious advantage in cancer treatment. However, before the rational development of such interventional strategies can proceed, it will first be necessary to increase our understanding of the fundamental radiobiology of this critical normal tissue. The response of CNS to other types of injury involves enhanced levels of specific cytokines, which are thought to mediate intrinsic recovery processes. It is now well established that the biological effects of ionizing radiation includes not only cell death, but also changes in the expression of a number of genes. The proposed research is based on the premise that the radioresponse of the CNS is at least partially governed by the increased production of specific cytokines: the products of radiation-induced gene expression. The ultimate aim of this project is to develop approaches for manipulating the radiation-mediated changes in cytokine production in vivo, which will allow for investigations into the role of induced gene expression in the radioresponse of the CNS. First, it will be necessary to identify the specific genes and cytokines that are affected by CNS irradiation and investigate the mechanism(s) responsible. These studies will be performed primarily using in vitro cultures of rat astrocytes. Based on this information, strategies will be developed for manipulating radiation-induced cytokine expression in an in vivo model -- the adult rat cervical spinal cord. For these investigations two methods of manipulation will be used: pharmacological inhibition of radiation-induced gene expression and ex vivo gene therapy. The goal of these studies is to test the hypothesis that induced gene expression and, consequently, specific cytokines play a significant role in the radioresponse of the CNS. The proposed studies should not only provide insights into the fundamental radiobiology of the CNS, but should also suggest therapeutic strategies for reducing radiation-induced damage in this critical normal tissue.