RADIOTHERPY OF HS/TK TRANSDUCED TUMORS BY A VIRAL AGENTS

病毒因子对 HS/TK 转导肿瘤的放射治疗

• 批准号: 2748765
• 负责人: JAE HO KIM
• 金额: $ 24.74万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2748765
• 关键词: DNA binding protein; Herpes simplex disease; antiviral agents; combination cancer therapy; gene therapy; glioma; ionizing radiation; laboratory rat; neoplasm /cancer radiation therapy; neoplastic cell; nonhuman therapy evaluation; radiation resistance; radiation sensitivity; radiobiology; tissue /cell culture; transfection /expression vector; tumor suppressor genes; virus genetics

DESCRIPTION: (adapted from the investigator's abstract) The overall objective of this proposal is to determine whether the combination of suicide gene therapy and radiation therapy is superior to single modality therapy in the treatment of human tumors. Based on the investigators' in vitro cell culture studies with the HSV-tk transduced human glioma cells, three specific approaches will be used to accomplish the objective. The first approach will test the hypothesis that tumors which contain wild type (wt) p53 function will be more sensitive to the combination of suicide gene therapy and radiation than tumors which lack wt-p53 or contain mutated (mut) p53 genes. Two other important questions relevant to the combined therapy to be answered are: 1) Is there sufficient radiosensitization to produce an increased tumor cure rate? and 2) Can an appropriate delivery system be developed? This group will use a genetically well characterized human glioma cell line, U-251 cells, growing in nude rat brains. The major significance of this approach would be to determine whether the use of suicide genes in combination with radiation would improve the cure rates of radioresistant human tumors.

描述：（改编自研究者摘要）总体 本提案的目的是确定 自杀基因治疗和放射治疗优于单一的上级 在人类肿瘤治疗中的模态疗法。 基于 研究者用转导的HSV-tk进行的体外细胞培养研究 人神经胶质瘤细胞，三种特定的方法将用于实现 目标 第一种方法将测试肿瘤 含有野生型（wt）p53功能的细胞对肿瘤细胞的生长更敏感。 自杀基因治疗和放射治疗相结合， wt-p53或含有突变的（mut）p53基因。 另外两个重要 需要回答的与联合治疗相关的问题是：1） 有足够的放射增敏作用， 率？ （2）能否发展适当的输送系统？ 这 研究小组将使用一种基因特征良好的人神经胶质瘤细胞系， U-251细胞，生长在裸大鼠脑中。 这件事的主要意义 方法将是确定是否使用自杀基因， 与放射治疗相结合将提高治愈率 抗辐射的人类肿瘤。