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

建立人类肿瘤异种移植模型作为转化研究的临床前辅助工具

• 批准号: 13480283
• 负责人: OHNISHI Yasuyuki
• 金额: $ 8.26万
• 依托单位: Central Institute for Experimental Animals
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13480283/
• 关键词: xenograft; human tumor; nude mouse; microarray; ant-cancer drug; eresistance; htranslational research; personalized chemotherapy

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.

在最近的癌症治疗战略中，正在考虑有序治疗和靶向治疗等概念。为了转化基于这些概念的基础研究成果，临床前体内模型来评估这些治疗策略是非常重要的。我们已经建立了人类肿瘤异种移植，我们保存了超过600种来自人类的各种器官肿瘤。在这项研究中，我们分析了这些人类肿瘤异种移植物的基因表达谱和化学敏感性。我们使用代表23,040个基因的cDNA微阵列分析了来自人类乳腺、肺、胃、结肠、胰腺和其他四个器官的85个肿瘤异种移植物的表达谱。我们还检测了这些肿瘤对9种抗肿瘤药物的化学敏感性，包括CDDP，丝裂霉素C，5-FU。比较肿瘤基因表达谱和化疗敏感性，发现1578个基因表达水平与药物疗效显著相关；其中333个基因显示出与两种或两种以上药物的显著相关性。这些数据应该为确定药物敏感性的预测标记提供有用的信息，最终可能为个体患者提供个性化的化疗。

项目成果

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