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溶瘤性疱疹病毒疗法在治疗肝癌细胞系方面有效。

Oncolytic herpes viral therapy is effective in the treatment of hepatocellular carcinoma cell lines.

作者信息

Song Tae-Jin, Eisenberg David P, Adusumilli Prasad S, Hezel Michael, Fong Yuman

机构信息

Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

出版信息

J Gastrointest Surg. 2006 Apr;10(4):532-42. doi: 10.1016/j.gassur.2005.08.036.

Abstract

The rising incidence of hepatocellular carcinoma (HCC) in western countries, along with the poor prognosis offered by present-day treatment modalities, makes novel therapies for this disease necessary. Oncolytic herpes simplex viruses (HSV) are replication-competent viruses that are highly effective in the treatment of a wide variety of experimental models of human malignancies. This study seeks to investigate the effectiveness of oncolytic herpes viruses in the treatment of primary HCC cell lines. Sixteen commercially available human HCC cell lines were studied. G207 is an attenuated, replication-competent, oncolytic HSV engineered to selectively replicate within cancer cells. Cell lines were tested for viral sensitivity to G207 and their ability to support viral replication using standard cytotoxicity and viral replication assays. Eleven of 16 cell lines were moderately to highly sensitive to G207 viral oncolysis. HCC cell lines additionally demonstrated the ability to support viral replication in vitro with as high as 800-fold amplification of the administered viral dose observed. G207 is cytotoxic to, and efficiently replicates within, HCC cell lines in vitro. From these data, we suggest that oncolytic HSV therapy may have a role in the treatment of HCC, and in vivo studies are warranted.

摘要

西方国家肝细胞癌(HCC)的发病率不断上升,加之当今治疗方式预后不佳,使得针对该疾病的新疗法成为必要。溶瘤单纯疱疹病毒(HSV)是具有复制能力的病毒,在多种人类恶性肿瘤实验模型的治疗中具有高效性。本研究旨在探究溶瘤疱疹病毒在原发性肝癌细胞系治疗中的有效性。对16种市售人类肝癌细胞系进行了研究。G207是一种减毒的、具有复制能力的溶瘤HSV,经改造后可在癌细胞内选择性复制。使用标准细胞毒性和病毒复制试验,检测细胞系对G207的病毒敏感性及其支持病毒复制的能力。16种细胞系中有11种对G207病毒溶瘤表现出中度至高度敏感性。肝癌细胞系在体外还表现出支持病毒复制的能力,观察到所施用病毒剂量有高达800倍的扩增。G207在体外对肝癌细胞系具有细胞毒性,并能在其中有效复制。基于这些数据,我们认为溶瘤HSV疗法可能在肝癌治疗中发挥作用,有必要开展体内研究。

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本文引用的文献

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Oncolytic viral therapies.溶瘤病毒疗法
Cancer Gene Ther. 2004 Oct;11(10):643-64. doi: 10.1038/sj.cgt.7700733.
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TP53 and liver carcinogenesis.TP53与肝癌发生
Hum Mutat. 2003 Mar;21(3):201-16. doi: 10.1002/humu.10176.
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Molecular pathogenesis of human hepatocellular carcinoma.人类肝细胞癌的分子发病机制
Toxicology. 2002 Dec 27;181-182:43-7. doi: 10.1016/s0300-483x(02)00253-6.

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