胃癌患者外周血细胞游离核酸标志物的检测和应用

目的:分析并评价10种外周血细胞游离核酸标志物在胃癌诊断中的应用价值。方法:提取胃癌患者及健康对照者的血清总RNA,反转录后采用实时荧光聚合酶链反应对候选基因进行检测,同时采用电化学发光免疫分析法检测癌胚抗原(CEA)、糖类抗原19-9(CA19-9)、CA724,并运用Logistic回归及受试者工作特征(ROC)曲线对标志物进行分析。结果:胃癌患者血清中TP73(DNp73α)及肝细胞生长因子受体c-MET表达量较健康对照者显著增高(P<0.05)。c-MET检测对胃癌诊断的灵敏度为65.5%,特异度为76.4%,曲线下面积(AUC)为0.73,与TP73(DNp73α)比较,两者间的AUC差异有统计学意义(P<0.05)。c-MET与CEA、CA199、CA724联合检测时,其诊断灵敏度为75.0%,特异度为87.3%,AUC为0.83;与仅CEA、CA199、CA724三者联合检测相比,AUC差异有统计学意义(P<0.05)。不同肿瘤转移情况、不同TNM分期的患者,其c-MET表达量明显不同(P<0.05)。结论:检测外周血c-MET表达在胃癌诊断中具有一定价值,可作为临床常用胃癌肿瘤标志物的补充。     

HGF、c-MET及VEGF在非小细胞肺癌中的表达和意义

目的 探讨肝细胞生长因子(HGF)、肝细胞生长因子受体(c-MET)及血管内皮生长因子(VEGF)的表达与非小细胞肺癌临床病理的关系.方法 将组织标本分为原发灶组(357例)和正常对照组(68例),分别采用免疫组织化学方法检测各组标本中HGF、c-MET及VEGF的表达情况.结果 非小细胞肺癌原发灶组织和正常组织中HGF表达阳性率分别为51.26％ (183/357)和10.29％ (7/68),两组之间差异有统计学意义(P＜0.05);非小细胞肺癌原发灶组织和正常组织中c-MET表达阳性率分别为60.22％ (215/357)和14.71％(10/68),两组间差异有统计学意义(P＜0.05);非小细胞肺癌原发灶组织和正常组织中VEGF表达阳性率分别为45.38％(162/357)和11.76％(8/68),两组间差异有统计学意义(P＜0.05);HGF阳性表达率与肿瘤组织分化程度及临床分期无关(P＞0.05),c-MET及VEGF阳性表达率与肿瘤组织分化程度及临床分期相关(P＜0.05).结论 HGF和c-MET、VEGF可能共同参与了非小细胞肺癌的发生和发展,c-MET和VEGF或可作为预测非小细胞肺癌患者预后的标记物.     

Antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET

Objective

Tyrosine-protein kinase MET (c-MET) has been reported to be a prognostic marker and suitable therapeutic target for ovarian cancer. BMS-777607, a small molecule, can inhibit MET and other protein kinase activities. The present study was conducted to investigate the mechanism of action and antitumor effect of BMS-777607 on ovarian cancer cells with constitutively activated c-MET.

Hepatocyte growth factor/scatter factor-induced intracellular signalling

Hepatocyte growth factor (HGF) identical to scatter factor (SF) is a glycoprotein involved in the development of a number of cellular phenotypes, including proliferation, mitogenesis, formation of branching tubules and, in the case of tumour cells, invasion and metastasis. This fascinating cytokine transduces its activities via its receptor encoded by the c-met oncogene, coupled to a number of transducers integrating the HGF/SF signal to the cytosol and the nucleus. The downstream transducers coupled to HGF/MET, most of which participate in overlapping pathways, determine the development of the cell's phenotype, which in most cell types is dual.     

c-MET Overexpression in Colorectal Cancer: A Poor Prognostic Factor for Survival

Introduction

Increased mesenchymal-epithelial transition factor gene (c-MET) expression in several human malignancies is related to increased tumor progression and is a new potential drug target for several types of cancers. In the present study, we investigated the incidence of c-MET overexpression and its prognostic significance in patients with colorectal cancer (CRC).

Targeted therapy in esophageal cancer

An increasing number of patients are diagnosed with esophageal cancer at an advanced stages, and only a small group of them can benefit from the traditional chemotherapy and radiotherapy. So far, multiple monoclonal antibodies and tyrosine kinase inhibitors have been developed, alone or in combination with traditional therapy, to improve the prognosis of patients with advanced esophageal cancer. This review summarizes the recent advances of targeted therapies against EGFR, HER2, VEGFR and c-MET in esophageal cancer. More clinical trials should be performed to evaluate the efficacy and safety of various targeted therapy regimens. Future basic research should focus on investigating the molecular mechanisms of therapeutic targets in esophageal cancer.     

白头翁皂苷D对胶质瘤细胞转移和凋亡的影响及机制研究

目的 探究白头翁皂苷D （PSD）对胶质瘤细胞U251MG转移和凋亡的影响及可能机制。方法 采用CCK-8试剂盒检测正常星形胶质细胞和U251MG细胞活力；选用0.0、1.0、2.0及5.0 μmol/L PSD处理U251MG，将细胞分为4组：PSD 0.0 μmol/L组、PSD 1.0 μmol/L组、PSD 2.0 μmol/L组和PSD 5.0 μmol/L组。划痕实验检测细胞迁移能力；Transwell检测细胞侵袭能力；Hoechst 33258染色检测细胞凋亡状况；RT-PCR检测mRNA表达水平；蛋白免疫印迹检测基质金属蛋白酶-2（MMP-2）、尿激酶型纤溶酶原激活物（uPA）、纤溶酶原激活物抑制剂-1（PAI-1）、血管内皮生长因子（VEGF）、cleaved caspase-3、cleaved caspase-9、肝细胞生长因子受体（c-MET）蛋白表达水平。结果 PSD抑制正常星形胶质细胞和胶质瘤细胞U251MG细胞活力。与PSD 0.0 μmol/L组相比较，PSD 1.0、2.0及5.0 μmol/L组细胞迁移率降低（P<0.01），MMP-2、uPA、PAI-1、VEGF、c-MET蛋白水平降低（P<0.05），PSD 1.0 μmol/L组细胞侵袭数降低（P<0.05），PSD 2.0及5.0 μmol/L组细胞侵袭数降低（P<0.01），细胞凋亡率升高（P<0.05），cleaved caspase-3、cleaved caspase-9蛋白水平升高（P<0.05）。结论 PSD通过靶向c-MET抑制胶质瘤细胞U251MG迁移和侵袭，并诱导细胞凋亡。