Lister strain of vaccinia virus armed with endostatin-angiostatin fusion gene as a novel therapeutic agent for human pancreatic cancer.

Lister strain of vaccinia virus armed with endostatin-angiostatin fusion gene as a novel therapeutic agent for human pancreatic cancer.
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携带内皮抑素-血管抑制素融合基因的痘苗病毒李斯特株作为人类胰腺癌的新型治疗剂

DOI:
10.1038/gt.2009.74
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发表时间:
2009-10
期刊:
影响因子:
5.1
通讯作者:
--
中科院分区:
医学3区
文献类型:
--
作者:

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尽管外科手术和辅助治疗取得了进步,但胰腺癌后的存活率仍然很低,需要新的治疗策略。溶瘤病毒疗法是一种有吸引力的癌症治疗方法。在这项研究中,我们评估了携带内皮抑素-血管抑素融合基因(VVhEA)的牛痘病毒Lister疫苗株作为一种新的胰腺癌治疗方法的有效性。牛痘病毒LISTER疫苗株对所有体外测试的人胰腺癌细胞都有效,特别是对溶瘤腺病毒不敏感的细胞。该病毒对肿瘤细胞表现出很高的选择性,在体外和体内都没有感染正常细胞,在静脉注射后有效地感染了肿瘤。和瘤内(I.T.)行政部门。在体外和体内的胰腺癌模型中都证实了内皮抑素-血管抑素融合蛋白的表达,并有证据表明血管生成受到抑制。这种新型痘苗病毒在体内对I.T.的Suit-2模型显示出显著的抗肿瘤活性。行政管理。本研究提示携带内皮抑素-血管抑素融合基因的新型痘苗病毒Lister株是一种潜在的胰腺癌治疗药物。
Survival after pancreatic cancer remains poor despite incremental advances in surgical and adjuvant therapy, and new strategies for treatment are needed. Oncolytic virotherapy is an attractive approach for cancer treatment. In this study, we have evaluated the effectiveness of the Lister vaccine strain of vaccinia virus armed with the endostatin-angiostatin fusion gene (VVhEA) as a novel therapeutic approach for pancreatic cancer. The Lister vaccine strain of vaccinia virus was effective against all human pancreatic carcinoma cells tested in vitro, especially those insensitive to oncolytic adenovirus. The virus displayed inherently high selectivity for cancer cells, sparing normal cells both in vitro and in vivo, with effective infection of tumors after both intravenous (i.v.) and intratumoral (i.t.) administrations. The expression of the endostatin-angiostatin fusion protein was confirmed in a pancreatic cancer model both in vitro and in vivo, with evidence of inhibition of angiogenesis. This novel vaccinia virus showed significant antitumor potency in vivo against the Suit-2 model by i.t. administration. This study suggests that the novel Lister strain of vaccinia virus armed with the endostatin-angiostatin fusion gene is a potential therapeutic agent for pancreatic cancer.
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