应用同步辐射X射线相衬成像研究HER2与TGFbeta1交互作用介导胃癌肺转移机制

项目名称： 应用同步辐射X射线相衬成像研究HER2与TGFbeta1交互作用介导胃癌肺转移机制

项目编号： No.U1532107

项目类型： 联合基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 张欢

作者单位： 上海交通大学

项目金额： 66万元

中文摘要： HER2与TGFbeta1的交互作用对胃癌转移发生发展至关重要。研究发现针对HER2的靶向药物可促进TGFbeta1升高，加速肺转移癌的发展，但机制尚不明确。建立活体肺部微小转移灶动物模型对探索其发生机制十分必要。我们前期工作证明同步辐射相衬成像能检测肺微小转移灶及转移灶内直径约30微米的肿瘤新生血管，初步探索无创监测肺转移癌发生发展的影像学检查手段。本课题将进一步利用同步辐射吸收和相衬成像、双能量CT、免疫组化以及cDNA微阵列分析等技术，在裸鼠肺转移模型中，探索：1）活体动态观察裸鼠肺组织HER2与TGFbeta1交互作用对肺转移癌发生发展的影响；2）调控TGFbeta1和HER2表达对交互作用效应是否可以影响肺转移的发生与发展；3）阻断TGFbeta1可否抑制肺转移癌发生发展，以提高靶向药物的疗效。本研究将为胃癌的靶向治疗奠定理论基础，同时为影像学无创评估肿瘤肺转移提供有效手段。

中文关键词： 同步辐射；相衬成像；交互作用；靶向治疗；TGFbeta1

英文摘要： Crosstalk between HER2 and TGFbeta1 plays a vital role in the pulmonary metastasis of gastric cancer. Previous reports implied that activating of TGFbeta1 signaling in HER2-overexpression cancers after targeted chemical therapy can accelerate the pulmonary metastatic; however, the mechanism remains unclear. Developing in vivo animal model of pulmonary metastasis to explore the mechanism is necessary. Novel models and unique technologies that detecting small tumors and micro-metastases are integral not only to developing effective diagnosis, but also to the exploring the pathogenesis. Our previous study demonstrated that without contrast agents, X-ray phase-contrast imaging could detect angiogenesis within the metastatic tumor with high spatial resolution. This result made it possible for noninvasive monitoring the pulmonary metastases occurrence and development. In present study, we will use the synchrotron radiation X-ray absorption and phase contrast imaging, dual energy CT, immunohistochemistry and cDNA microarray analysis technologies on pulmonary metastasis models in nude mice, to explore: 1) dynamic changes of the pulmonary metastases occurrence and development via crosstalk between HER2 and TGFbeta1 signaling; 2) whether the regulation of the crosstalk between TGFbeta1 and HER2 influence pulmonary metastases occurrence and development; 3) whether knocking down TGFbeta1 inhibit pulmonary metastases occurrence and development, and eventually improve the efficacy in the targeted treatment of gastric cancer. Our study will provide a new avenue to understand the aggressiveness and metastasis and to develop targeted therapies against gastric cancer. Meanwhile it will provide a noninvasive imaging assessment method for pulmonary metastases from other tumors.

英文关键词： synchrotron radiation;X-ray phase-contrast imaging;crosstalk;targeted therapy;TGFbeta1