Lister strain vaccinia virus, a potential therapeutic vector targeting hypoxic tumours.
Lister strain vaccinia virus, a potential therapeutic vector targeting hypoxic tumours.
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作者：
缺氧导致胰腺导管腺癌（PDAC）的侵袭性和治疗耐药表型。溶瘤牛痘病毒具有作为抗肿瘤剂的潜力，但溶解缺氧肿瘤细胞的能力对于临床疗效至关重要。我们假设痘病毒生命周期的独特方面将保护其在缺氧条件下免受衰减。我们的特点和比较的病毒蛋白质的生产，病毒复制，细胞毒性和转基因表达的李斯特株牛痘病毒在一组胰腺癌细胞系后，暴露于常氧或缺氧条件。病毒蛋白质的生产不受缺氧的影响，高病毒滴度在常氧和缺氧条件下产生。有趣的是，在缺氧条件下，CFPac1和MiaPaca 2细胞系的病毒细胞毒性分别增加了5倍（P <0.001）和10倍（P<0.0001）。其余细胞系的细胞毒性相当。无论环境氧浓度如何，来自牛痘病毒载体的转基因表达（荧光素酶报告基因）水平是相当的。目前的研究表明，牛痘病毒是一个有前途的载体，针对胰腺癌和潜在的其他缺氧肿瘤类型。
Hypoxia contributes to the aggressive and treatment-resistant phenotype of pancreatic ductal adenocarcinoma (PDAC). Oncolytic vaccinia virus has potential as an anti-tumour agent but the ability to lyse hypoxic tumour cells is vital for clinical efficacy. We hypothesised that unique aspects of the poxvirus lifecycle would protect it from attenuation in hypoxic conditions. We characterised and compared the viral protein production, viral replication, cytotoxicity and transgene expression of Lister strain vaccinia virus in a panel of pancreatic cancer cell lines after exposure to normoxic or hypoxic conditions. Viral protein production was not affected by hypoxia, and high viral titres were produced in both normoxic and hypoxic conditions. Interestingly there was a five-fold (P<0.001) and 10-fold (P<0.0001) increase in viral cytotoxicity for CFPac1 and MiaPaca2 cell lines respectively in hypoxic conditions. Cytotoxicity was equivalent in the remaining cell lines. Levels of transgene expression (luciferase reporter gene) from the vaccinia viral vector were comparable regardless of the ambient oxygen concentration. The present study suggests that vaccinia virus is a promising vector for targeting pancreatic cancer and potentially other hypoxic tumour types.
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影响因子：
5.1
作者：
Binley, K;Askham, Z;Naylor, S
通讯作者：
Naylor, S
影响因子：
5.1
作者：
Shen, B. H.;Bauzon, M.;Hermiston, T. W.
通讯作者：
Hermiston, T. W.
影响因子：
5.1
作者：
Shen, BH;Hermiston, TW
通讯作者：
Hermiston, TW
DOI：
10.1016/j.ijrobp.2006.08.077
发表时间：
2007-01-01
影响因子：
7
作者：
Green, Melanie M. L.;Hiley, Crispin T.;Stratford, Ian J.
通讯作者：
Stratford, Ian J.
影响因子：
5.1
作者：
Binley, K;Iqball, S;Naylor, S
通讯作者：
Naylor, S