大肠癌与Fas配体及其调控的实验和临床研究

Colon carcinoma was one of the most common malignant neoplasms and was the fifth death reason in our country. The compromise treatments mainly by surgery are the fundamental therapies at present, however, yet have the high recurrence rate. The survival rate of colon carcinoma was improved by traditional chemical and immune therapies, however yet satisfactory. For further investigating and improving the effect of clinically common cytokines and chemical drugs to colon carcinomas and decreasing side effect. The following three items were studied. 1. Fas ligand (FasL) expression in colon carcinoma and its clinical significance 2. The cytokines modulation of FasL expression and its function in colon carcinoma.3.the mechanisms of the chemical drug modulation of Fas receptor and FasL expression and their function..It was suggested that FasL mRNA positive rate was higher in Dukes D stage than Dukes B and Dukes C stages, by using RT-PCR, ISH and Western blot. The postoperative 5 year overall survival rate was lower in FasL mRNA positive group than in negative group. FasL protein expression in colon carcinoma and its function of counterattack to T lymphocytes were upregulated by endogenous cytokines such as IL-18, TNF-α and IFN-γ. 100μg IL-18 upregulated FasL protein expression in SW620, which induced 38.4%, Jurkat cells to apoptosis. 5-Fu, mitomycin and cisplatin can also upregulated FasL protein expression ion colon carcinoma cells, which induced T lymphocytes to death. 260μM 5-Fu, 3μM mitomycin and 30μM cisplatin upregulated FasL protein expression in SW620, which induced over 40%, Jurkat cells to apoptosis. .It was first suggested that FasL might be associated with the staging and prognosis of colon carcinoma. And it was first found that FasL protein expression in colon carcinoma and its function of counterattack to T lymphocytes were upregulated by endogenous cytokines such as IL-18, TNF-α and IFN-γ and chemotherapeutic drugs such as 5-Fu, mitomycin and cisplatin. On the basis of studying on Fas expression of colon carcinoma, it was first suggested that 5-Fu upregulated Fas expression in colon carcinoma, not depending on the status of its p53 function. It was further improved that FasL mRNA and protein was expressed in colon carcinoma cells and tissues and counterattacked T lymphocytes.Over 10 papers concerning on the study was published on the main medical journals in China such as Chinese Journal of Medicine, Chinese Journal of General Surgery, Chinese Journal of experimental Surgery, Cancer, etc. The study made the profit for our hospital and was widespread in many hospitals in Shanghai, in Henan Province and in Guangdong Province. And one Graduate of Doctor degree and one Graduate of Master degree were trained in our experiment.

大肠癌FasL免疫逃避研究国内外刚起步有待深入探讨。本课题用TGF-B和IL-18等细胞因子处理大肠癌细胞观察其FasL mRNA和蛋白表达和Fas依赖活性及肿瘤微环境细胞因子表达状态，分析其与肿瘤细胞增殖程度和临床预后的相关性，推测肿瘤微环境FasL及细胞因子表达水平对肿瘤发生，发展及预后的影响。探索逆转FasL逃免疫监视的途径和治疗大肠癌的全新思路。