Establishment of human tumor xenotransplantation models as a pre-clinical assisting tool for translational research

在最近的癌症治疗策略中，出现了订单式治疗和靶向治疗等概念。为了将基于这些概念的基础研究成果转化为临床前体内模型，评估此类治疗策略是非常重要的。我们一直在建立人类肿瘤异种移植，我们保留了600多株来自人类来源的各种器官肿瘤。在这项研究中，我们分析了这些人肿瘤异种移植瘤的基因表达谱和化疗敏感性。我们使用代表23,040个基因的cDNA微阵列分析了一组来自人类乳房、肺、胃、结肠、胰腺和其他四个器官的85个肿瘤移植瘤的表达谱。我们还检测了这些肿瘤对包括顺铂、丝裂霉素C、5-FU在内的9种抗癌药物的敏感性。比较肿瘤的基因表达谱和化疗敏感性，发现1,578个基因的表达水平与药物疗效显著相关；其中333个基因与两种或两种以上药物显著相关。这些数据应该有助于识别药物敏感性的预测标记物，最终可能为个别患者提供个性化的化疗。

In the recent strategy for treatment of cancer disease, concepts such as the order-made treatment and the target-oriented therapy are arising in consideration. To translate the basic research results based on these concepts, pre-clinical in vivo models to evaluate such treatment strategies are very important. We have been establishing human tumor xenografts, and we maintain over 600 lines of various organ tumors from human origin. In this study, we analyzed gene expression profiles and chemosensitivities of those human tumor xenografts. We used cDNA microarray representing 23,040 genes to analyze expression profiles in a panel of 85 tumor xenografts derived from human breast, lung, stomach, colon, pancreas, and other four organs. We also examine chemosensitivities for these tumors on 9 antitumor drugs including CDDP, mitomycin C,5-FU. Comparison of the gene expression profiles and chemosensitivities of the tumors identified that 1,578 genes whose expression levels correlated significantly with drug effectiveness; 333 of those genes showed significant correlation with two or more drugs. These data should contribute useful information for identifying predictive markers for drug sensitivity that may eventually provide personalized chemotherapy for individual patients.