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腺病毒介导的内皮抑素预防大肠癌术后肝转移 被引量:12

Adenoviral transduction of endostatin gene prevents the liver metastasis of colorectal carcinoma in postoperation
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摘要 目的 研究腺病毒介导的内皮抑素对大肠癌术后肝转移的预防作用。 方法 构建内皮抑素的重组体腺病毒 ,观察转导表达后的生物学活性。建立人结肠癌术后肝转移裸小鼠动物模型 ,分析基因转导后动物外周血和肝静脉血内皮抑素水平、肝脏转移瘤形成以及转移瘤微血管生成情况。结果 感染上清处理人脐静脉内皮细胞后 ,细胞增殖受到明显抑制。重组腺病毒单次注射后第 2、5、10、14天 ,小鼠外周血中内皮抑素水平显著增高 ,分别为 376ng/ml、2 0 19ng/ml、1387ng/ml和 92 4ng/ml,肝静脉血中内皮抑素升高更明显 ,在第 2、5、10、14天分别为 2 0 1ng/ml、316 0ng/ml、2 4 80ng/ml和174 5ng/ml。治疗组动物肝转移发生率下降、平均肝转移瘤数和转移瘤内微血管生成减少。 结论重组体腺病毒的单次静脉注射 ,实现了内皮抑素基因在体内 ,特别是肝组织内的高效、稳定表达。于肝转移形成的萌芽时期 ,阻止肝脏微小转移瘤的血管形成 。 Objective To study the prevention of colorectal cancer liver metastasis by adenoviral transduction of the endostatin gene. Methods The recombinant adenovirus expressing endostatin was constructed. Its biological activities were surveyed in vitro, as determined in human umbilicus vein endothelium cell (HUVEC )proliferation inhibition, and in vivo, by reduction of liver metastasis. Results HUVEC proliferation was obviously inhibited by the infecting supernatant of recombinant adenovirus. Persistent high serum levels of endostatin in peripheral blood, especially in the liver vein were observed. The production of liver metastasis was intervened. Conclusions The single injection in the vein of the recombinant adenovirus realizes the high effective and stable expression of endostatin in general body and liver, which brings about the ideal prevention of liver metastasis.
出处 《中华外科杂志》 CAS CSCD 北大核心 2002年第5期375-378,共4页 Chinese Journal of Surgery
关键词 腺病毒介导 内皮抑素 预防 大肠癌 术后 肝转移 Colorectal neoplasms Neoplasm metastasis Primary prevention Adenoviruses, human Endostatin
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