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.
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