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【编译】adenovector技术在治疗胰腺癌中的应用
作者：Jacob, Dietmar 1; Davis, John J 1,2; Zhang, Lidong 1; Zhu, Hongbo 1; Teraishi, Fuminori 1; Fang, Bingliang 1,2
杂志全名：Cancer Gene Therapy
年份，卷（期）: 起止页码： 12(2):109-115, February 2005.
Accession Number 00043884-200502000-00001.
英文摘要：
Local and locoregional administration of adenovectors expressing the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene has been demonstrated to be useful in treating established tumors in animals. Moreover, expression of the TRAIL gene from the human telomerase reverse transcriptase (hTERT) promoter can be used to prevent possible liver toxicity of the TRAIL gene. However, it remains unknown whether systemic administration of the TRAIL-expressing adenovector can be used for cancer therapy. Here, we showed that a combination of TRAIL gene therapy and gemcitabine, the first-line chemotheraphy agent for pancreatic cancer, had a synergistic effect on the induction of apoptosis in human pancreatic cancer cell lines in vitro. Systemic administration of an adenovector that contains an insertion of integrin-binding motif argine-glycine-aspartate (RGD) in the HI loop of the adenoviral fiber protein and expresses the human TRAIL gene from the hTERT promoter (designated Ad/TRAIL-F/RGD) suppressed the growth of human pancreatic tumor cells inoculated in the liver of nu/nu nude mice. Furthermore, Ad/TRAIL-F/RGD in combination with gemcitabine suppressed the tumor growth of pancreatic cancer in the liver more than did treatments consisting of each agent alone. No obvious liver toxicity was detected in any of the treatment groups. Our results suggest that TRAIL gene therapy in combination with gemcitabine might be a useful therapeutic approach for treating metastatic pancreatic cancers.
中文译文：
局部应用腺载体技术表达肿瘤坏死因子相关的凋亡诱导配体（TRAIL）基因已证明在肿瘤动物模型中是有用的。此外，从人端粒逆转录酶（hTERT）启动子表达TRAIL基因可以用来消除TRAIL基因可能的肝毒性。但是，是否能系统地应用TRAIL表达的腺载体来治疗癌症还不确定。在体外实验中，研究者已经证明联合应用TRAIL基因治疗与双氟脱氧胞嘧啶核苷（一线化疗药）来治疗胰腺癌，可以协同诱导人胰腺癌细胞凋亡。系统应用adenovector技术包括在腺病毒纤维蛋白的HI loop中插入一个整合素结合的精-甘-天冬肽（RGD）基序，并且表达来自hTERT启动子的人TRAIL基因（设计名称Ad/TRAIL-F/RGD）抑制了裸鼠肝脏中培养的人胰肿瘤细胞生长。而且，Ad/TRAIL-F/RGD在与双氟脱氧胞嘧啶核苷联合应用时，抑制了，裸鼠肝中的胰肿瘤细胞，其抑制作用超过单独应用任何一种的作用。在任何治疗组中都没有明显的肝毒性。因此，TRAIL基因治疗与双氟脱氧胞嘧啶核苷联合应用可能是治疗转移性胰腺癌的有效方法。 全文！
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作者:admin@医学,生命科学 2011-04-25 05:14
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