Virotherapy targeting cyclin E overexpression in tumors with adenovirus-enhanced cancer-selective promoter.

Virotherapy targeting cyclin E overexpression in tumors with adenovirus-enhanced cancer-selective promoter.
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使用腺病毒增强的癌症选择性启动子针对肿瘤中细胞周期蛋白 E 过度表达进行病毒疗法。

DOI:
10.1007/s00109-014-1214-6
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发表时间:
2015-02
影响因子:
4.7
通讯作者:
Zhou, H. Sam
Zhou, H. Sam
中科院分区:
医学2区
文献类型:
--
作者:
Cheng, Pei-Hsin;Rao, Xiao-Mei;Duan, Xiaoxian;Li, Xiao-Feng;Egger, Michael E.;McMasters, Kelly M.;Zhou, H. Sam

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溶瘤病毒疗法可以选择性地破坏癌细胞,是一种潜在的癌症治疗方法。增加肿瘤特异性选择性的策略是用肿瘤特异性启动子控制关键调控病毒基因的表达。我们以前发现,在腺病毒(Ad)感染后,癌细胞中细胞周期蛋白E的表达增强。因此,在癌细胞中被Ad进一步激活的周期蛋白E启动子可能具有增强溶瘤病毒复制的独特特性。我们已经证明,在感染Ad- cyce的癌细胞中,内源性Ad- E1a启动子被细胞周期蛋白E启动子取代,病毒E1a基因的高水平表达得以实现。Ad-cycE在体外显示出明显的选择性溶瘤作用,并破坏各种类型的癌细胞,包括对ONYX-015/dl1520耐药的癌细胞。此外,Ad-cycE在裸鼠中表现出强烈的抑制A549异种移植肿瘤生长的能力,并显著延长生存期。这项研究提示了Ad-cycE在癌症治疗中的潜力,并表明在溶瘤病毒的发展过程中,在癌细胞中使用可被病毒感染上调的启动子的优势。
Oncolytic virotherapy can selectively destroy cancer cells and is a potential approach in cancer treatment. A strategy to increase tumor-specific selectivity is to control the expression of a key regulatory viral gene with a tumor-specific promoter. We have previously found that cyclin E expression is augmented in cancer cells after adenovirus (Ad) infection. Thus, the cyclin E promoter that is further activated by Ad in cancer cells may have unique properties for enhancing oncolytic viral replication. We have shown that high levels of viral E1a gene expression are achieved in cancer cells infected with Ad-cycE, in which the endogenous Ad E1a promoter was replaced with the cyclin E promoter. Ad-cycE shows markedly selective oncolytic efficacy in vitro and destroys various types of cancer cells, including those resistant to ONYX-015/dl1520. Furthermore, Ad-cycE shows a strong capacity to repress A549 xenograft tumor growth in nude mice and significantly prolongs survival. This study suggests the potential of Ad-cycE in cancer therapy and indicates the advantages of using promoters that can be upregulated by virus infection in cancer cells in development of oncolytic viruses.
DOI: 10.1083/jcb.152.6.1267
发表时间: 2001-03-19
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影响因子: --
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期刊: CANCER LETTERS
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