炎症恶性转化的肠癌内源性分子调控网络的建立

项目名称： 炎症恶性转化的肠癌内源性分子调控网络的建立

项目编号： No.91229104

项目类型： 重大研究计划

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 张苏展

作者单位： 浙江大学

项目金额： 90万元

中文摘要： 结肠炎相关结直肠癌（CAC）是一种与非可控性炎症密切相关的恶性肿瘤，且炎症微环境紊乱存在于肿瘤进展的各个阶段。但炎症因子在肿瘤发生发展过程中并非独立发挥作用，本项目拟建立一个符合生物学运作机理的内源性分子调控网络，将炎症因子模块与细胞代谢、细胞周期、细胞凋亡、生长因子、迁移和转移等其他分子调控模块整体考虑，使用随机微分方程方法计算使得该网络的状态对应于结直肠癌发病过程的各个临床病理阶段；并寻找结直肠癌临床病理过程中各个状态之间转换的关键节点基因；在肠癌细胞试验，小鼠慢性肠炎致癌模型，和临床组织样本多个水平上阐明关键节点的生理功能，验证通过调控这些节点而转换网络状态的可能性，为逆转非可控性肠道炎症以及肿瘤个体化治疗提供依据。

中文关键词： 结直肠癌；炎症；癌变；内源性网络；基因表达谱

英文摘要： Colitis-associated colorectal cancer (CAC) is a non-controlled inflammation is closely related tomalignant tumors, and inflammatory microenvironment disorders exist in various stages of tumor progression. Of inflammatory cytokines in the tumor development process is not an independentrole, The project intends to establish an the biologically operation mechanism of the endogenousmolecular regulatory networks, the module of inflammatory factors and cell metabolism, cell cycle, apoptosis, growth factors, migration and transfer of other molecules such as the regulationmodule as a whole to consider the stochastic differential equation to calculate the status of thenetwork correspond to the clinical and pathological stage of the process of colorectal cancer;and look for the conversion between the various states in the process of colorectal cancerclinicopathological clarify the physiological functions of the key nodes on the key node genes;trial in colorectal cancer cells, mice with chronic enteritis carcinogenic model, and clinical tissue samples from more than one level, verify the possibility of conversion of network status throughthe regulation of these nodes, can reverse the non-control of intestinal inflammation and tumorindividualized therapy.

英文关键词： colorectal cancer；inflammation；Carcinogenesis；internnally regulated network；Gene expression profiles