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国家自然科学基金(30872469)

作品数:3 被引量:13H指数:3
相关作者:汤坚强汪欣万远廉朱静吴问汉更多>>
相关机构:北京大学第一医院北京世纪坛医院北京航天总医院更多>>
发文基金:国家自然科学基金更多>>
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组织因子/凝血因子Ⅶ在大肠癌中的异位表达及其临床意义被引量:5
2009年
目的:探讨凝血因子Ⅶ(coagulation factorⅦ,FⅦ)和组织因子(tissue factor,TF)在大肠癌中的表达情况及其与临床病理因素的关系。方法:应用免疫组织化学法及Western blot对FⅦ蛋白在大肠癌组织中的表达情况进行研究;应用实时荧光定量PCR技术检测FⅦ和TF基因在45例结直肠癌患者癌及相应癌旁正常黏膜的表达。结果:(1)免疫组织化学及Western blot结果均显示FⅦ蛋白在大肠癌组织中存在异位高表达现象,癌旁正常黏膜不表达FⅦ蛋白;(2)免疫组织化学方法证实FⅦ蛋白定位表达于肿瘤细胞的胞浆和胞膜,大肠癌Ⅰ期、Ⅱ期、Ⅲ期及Ⅳ期的FⅦ表达阳性率分别为33.3%,40.0%,64.7%及80.0%(P=0.001);(3)实时荧光定量PCR方法显示大肠癌肝转移组FⅦmRNA表达明显高于非转移组,肝转移组表达量为5.33±2.88,无转移组为1.47±0.51(P=0.03),FⅦmRNA表达与肿瘤大小、分化、浸润深度、有无淋巴结转移及TNM分期无关,Spearman相关分析显示FⅦ在mRNA和蛋白水平表达呈一定的相关性,相关系数为0.58(P=0.03);(4)TF mRNA表达与大肠癌淋巴结转移、肝转移及TNM分期均有关,Logistic多因素回归分析影响肝转移的因素,结果表明TF表达是肝转移发生的重要因素(P=0.001)。结论:大肠癌组织可异源性地表达和分泌FⅦ,TF高表达是大肠癌发生肝转移的重要因素,肿瘤细胞周围高FⅦ的微环境可能促进大肠癌的转移。
汤坚强樊庆万远廉刘玉村汪欣吴涛潘义生吴问汉朱静
关键词:结直肠肿瘤凝血致活酶肿瘤转移
热疗联合组织因子靶向治疗对人大肠癌细胞增殖及凋亡的影响被引量:4
2012年
目的探讨热疗联合组织因子(TF)靶向治疗在体内和体外对人大肠癌细胞增殖及凋亡的影响。方法用RNA干扰的方法敲低大肠癌LOVO细胞系中TF的表达,MTT法、流式细胞术、Western blot方法测定热疗联合TF敲低对LOVO细胞体外增殖抑制及细胞凋亡的影响。将人大肠癌细胞注射到裸鼠腹股沟皮下建立裸鼠皮下移植瘤模型,观察不同治疗方法对肿瘤生长的影响。结果用RNA干扰的方法可以有效降低大肠癌LOVO细胞系中TF的表达。与单独热疗和单独TF敲低相比,联合治疗能够明显抑制细胞增殖和促进细胞凋亡的发生(P<0.05)。热疗联合TF敲低能够有效抑制裸鼠体内的肿瘤生长。结论热疗和TF敲低联合应用能够抑制大肠癌细胞增殖并且诱导其凋亡,热疗联合TF靶向治疗是一个潜在的治疗大肠癌的新策略。
李辉张静汤坚强万远廉于歌汪欣朱静
关键词:结直肠肿瘤凝血致活酶细胞凋亡热疗
Extrahepatic synthesis of coagulation factor Ⅶ by colorectal cancer cells promotes tumor invasion and metastasis被引量:4
2010年
Background Blood coagulation factor Ⅶ (FⅦ) is physiologically synthesized in the liver and released into the blood. Binding of FⅦ to tissue factor (TF) is related to the metastatic potential of tumor cells, also a significant risk factor in the development of hepatic metastasis in patients with colorectal cancer (CRC). It has been found that some cancer cells can produce FⅦ extrahepatically. However, litte is known about FⅦ and CRC. We therefore hypothesized that CRC cells may synthese FⅦ, leading to tumor invasion and metastasis.Methods We detected the expression of FⅦ protein in 55 CRC specimens by immunohistochemical staining. The FⅦ mRNA in 45 of 55 CRC cases, 6 colon cancer cell lines and one hepatoma cell line was measured by real-time reverse transcription-PCR (RT-PCR). Transwell invasion assays were performed to evaluate the changes of cell migration and invasion of LoVo cancer cells in vitro. We further observed the likely effectors regulated by the TF/FⅦa complex Western blotting assay.Results Extrahepatic synthesis of FⅦ was detected in the cytoplasm of 32 (58.2%) CRC specimens byimmunohistochemistry, but not in normal mucosa. Liver metastasis (P=0.003) and TNM staging (P=0.005) were significantly correlated with FⅦ antigen expression. The positive ratios in stages Ⅰ, Ⅱ, Ⅲ and Ⅳ were 33.3%, 40.0%,52.4% and 87.5%, respectively. The expression of FⅦ mRNA in CRC with hepatic metastasis was significantly higher than CRC without hepatic metastasis (5.33±2.88 vs. 1.47±0.51, P=0.03). Ectopic FⅦa induced a slight increase (1.34-fold) in the number of migrating cells, which was inhibited by the specific TF antibody. The formation of TF/FⅦacomplex resulted in a marked increase in the expression of matrix metalloproteinases (MMP)-2 (3.5-fold) and MMP-9(4.7-fold) in a time-dependent and dose-dependent manner.Conclusions Extrahepatic synthesis of FⅦ by CRC cells may promote tumor invasion and metastasis. MMPs, as downstream effe
TANG Jian-qiangFAN QingWU Wen-hanJIA Zhi-chaoLI HuiYANG Yin-moLIU Yu-cunWAN Yuan-lian
关键词:THROMBOPLASTIN
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