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

本课题主要取得了以下研究成果：1.初步研究了人膀胱癌细胞株裸鼠移植瘤的放射敏感性。利用该模型，我们建立了辐射照射条件（单次照射5戈伊），并证实肿瘤生长延迟反应可作为评价辐射敏感性的终点。2. Xenogarft模型的建立：18只小鼠（60%，18/30）出现肿瘤生长。从组织学上看，18例中有15例是与原始肿瘤相似的上皮癌，发病率为50%（15/30）。未发现肿瘤发生率与患者肿瘤的临床病理特征、TP 53突变状态或Ki 67 LI之间存在相关性。在15个异种移植物中，11个异种移植物从3代到10代。TP 53突变状态在传代过程中保持稳定，尽管Ki 67 LI在大多数异种移植物中略有增加。放射性生长延迟试验：为了评价这些异种移植物用于治疗模拟的有效性，我们对4个异种移植物进行放射性生长延迟试验，并检查异种移植物肿瘤的生物学参数与反应之间的关系。4种模型的辐射响应差异很大。绝对生长延迟范围为20.3 ± 2.4（平均值±标准误）至76.4±7.4天。特异性生长延迟（SGD）与体内肿瘤生长速度或Ki 67 Il无关。在TP 53基因突变的3号模型中观察到最小的SGD值。

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.