中文摘要
肝癌微环境在肝癌发生发展中发挥重要作用,炎症和缺血是肝癌微环境的两大重要特征。经导管肝动脉化疗栓塞(TACE)是肝癌常用的治疗手段,但总体疗效不理想。我们前期研究发现,肝癌微环境相关指标如炎症评级、纤维化程度及缺氧水平等较高的患者行TACE治疗后多预后不良,提示肝癌微环境相关因素可能参与了TACE治疗抵抗,但具体机制尚不明确。本课题拟利用肝癌临床标本及病例资料,针对肝癌微环境炎症及缺血特征,筛选可能参与TACE治疗抵抗的关键细胞、因子及缺血相关因素;再通过体内外实验验证上述细胞、因子及缺血相关因素对肝癌细胞适应缺氧缺营养微环境及化疗抵抗能力的影响;在此基础上通过对微环境相关因素的靶向干预明确微环境诱导肝癌细胞产生TACE治疗抵抗的机制;最后在临床分析微环境相关指标与TACE治疗预后的相关性, 探索形成新的TACE栓塞剂。预期结果有助于为提高肝癌TACE治疗效果提供新的理论依据和治疗策略。
英文摘要
The hepatoma microenviroment plays an important role in occurrence and development of hepatomas. There are two important characteristics of hepatoma microenviroment: inflammation and ischemia. Transhepatic Arterial Chemotherapy And Embolization (TACE) is a common clinical therapy for hepatomas. However, the overall curative effect of TACE is poor. Our previous research indicated that some indexes of hepatoma microenviroment, such as inflammatory classifications, fibrosis degrees and hypoxic levels, foreshow the bad prognosis of patients after TACE. This fact indicates hepatoma microenviroment related factors may be involved in resisting TACE. But the specific mechanisms are only partially understood. According to the characteristics of hepatoma microenvironments, our study project aims to screen out the posssibe key cells, cytokines and ischemia related factors by using patients’ records and their clinical samples of HCC. Furthermore, we would verify the impact of above-mentioned factors (key cells, cytokines and ischemia related factors) on hepatoma cells’ features: adapted to hypoxic and undernourished microenviroment and resisting chemotherapy. Based on the above study, we wanna verify the mechanisms of the chemotherapy-resistant of hepatoma cells by intervening site-specifically in microenviroment related factors. Eventually, to develop new embolization agents of TACE for promoting curative effect by analyzing the correlation between microenviroment related factors and prognosis of TACE.
