Analysis of expression pattern of the gene which is related to the radiation sensitivity in urothelial cancer and its clinical application

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From the present project, the following results were obtained.1.Initially, we evaluated radiation sensitivity in the nude mice transplanted with human bladder cancer cell lines. Utilizing this model, we set up the radiation exposure condition (single time irradiation of 5 Gy) and confirmed that tumor growth delayd reaction could be evaluated as an endpoint of radiation sensitivity.2.The establishment of Xenogarft model : Tumor growth was observed in 18 mice (60%, 18/30). Histologically, 15 of the18 were epithelial carcinomas similar to the original tumors, resulting in a 50% (15/30) take rate. No correlation was found between the tumor take rate and the clinicopathologic features, TP53 mutational status, or Ki67 LI of the patients' tumors. Of the 15 xenografts, 11 xenografts were passed from 3 to 10 generations. TP53 mutational status remained stable during the passages, though the Ki67 LI slightly increased in the majority of xenografts. Specific growth delay after irradiation in the 4 xenografts was observed independent of the original tumor growth speed and Ki67 LI.3.Radiological growth delay assay : To assess the usefulness of these xenografts for therapeutic simulation, we performed radiological growth-delay assay in 4 xenografts and examined the relation between the responses and the biological parameters of xenograft tumors. The radiation response considerably varied among the 4 models. Absolute growth delay ranged from 20.3+2.4 (mean+standard error) to 76.4±7.4 days. Specific growth delay (SGD) was not associated with in vivo tumor growth speed or the Ki67 Il. The smallest SGD value was observed in the No.3 model which harbored TP53 gene mutation.