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通过 CD46 和 nectin 4 非依赖性途径,利用工程化麻疹病毒 Edmonston 株作为新型溶瘤病毒系统来对抗人神经母细胞瘤。

Engineered measles virus Edmonston strain used as a novel oncolytic viral system against human neuroblastoma through a CD46 and nectin 4-independent pathway.

机构信息

Department of Pediatric Surgery, Major Laboratory of the Chinese Health Ministry for Congenital Malformations, Shengjing Hospital of China Medical University, Heping District, Shenyang, PR China.

出版信息

Cancer Lett. 2012 Dec 28;325(2):227-37. doi: 10.1016/j.canlet.2012.07.008. Epub 2012 Jul 13.

Abstract

Neuroblastoma (NB) is the most common extracranial solid tumor in children. In this study, we investigated the potential antitumor capability of the engineered Edmonston strain of the carcinoembryonic antigen-expressing measles virus (MV-CEA) against human NB. The infection of a variety of NB cell lines, including SK-N-SH, SMS-KCNR, and primary NB cells, resulted in significant cytopathic effects. None of the NB cell lines showed an overexpression of the measles virus receptor CD46 and nectin 4, but the cell lines did support robust viral replication. The efficacy of this approach was examined in murine SK-N-SH xenograft models. Flow cytometry and TUNEL assays indicated an apoptotic mechanism of cell death. In summary, MV-CEA has potent therapeutic efficacy against NB mediated by a CD46- and nectin 4-independent pathway.

摘要

神经母细胞瘤(NB)是儿童最常见的颅外实体瘤。在这项研究中,我们研究了表达癌胚抗原的麻疹病毒(MV-CEA)工程化 Edmonston 株对人 NB 的潜在抗肿瘤能力。多种 NB 细胞系(包括 SK-N-SH、SMS-KCNR 和原代 NB 细胞)的感染导致了明显的细胞病变效应。NB 细胞系均未过度表达麻疹病毒受体 CD46 和 nectin 4,但细胞系确实支持病毒的有效复制。在鼠源性 SK-N-SH 异种移植模型中检验了这种方法的疗效。流式细胞术和 TUNEL 检测表明细胞死亡的凋亡机制。总之,MV-CEA 通过 CD46 和 nectin 4 非依赖性途径对 NB 具有强大的治疗效果。

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