The utility of a tissue slice model system to determine breast cancer infectivity by oncolytic adenoviruses.
The utility of a tissue slice model system to determine breast cancer infectivity by oncolytic adenoviruses.
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利用组织切片模型系统确定溶瘤腺病毒对乳腺癌的感染性。
DOI：
10.1016/j.jss.2010.03.072
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Mathis,JMichael
中科院分区：
文献类型：
--
作者：
Pennington,Krista;Chu,QuyenD;Curiel,DavidT;Li,BenjaminDL;Mathis,JMichael
背景：由于病毒设计的进步，溶瘤腺病毒已成为治疗乳腺癌的一种很有前途的方法。肿瘤组织切片为腺病毒治疗的临床前评估提供了严格的模型系统，因为切片保留了比细胞系培养更接近于体内环境的形态和表型，并且该系统已被证明在评估病毒感染性和复制方面具有实用性。在这项研究中，我们利用嗜性修饰的溶瘤腺病毒来评估病毒感染和复制的效果。方法用嗜性修饰的溶瘤腺病毒和野生型腺病毒感染乳腺组织切片进行比较。使用荧光显微镜评估感染效率，因为使用的病毒已被修饰以表达红色荧光蛋白。采用实时定量聚合酶链反应（PCR）检测病毒E4基因组拷贝数（病毒粒子数量的替代指标），评估病毒的复制能力。采用免疫组化方法检测乳腺肿瘤组织切片CD46的表达情况。结果在乳腺癌组织切片模型系统中观察到趋向性修饰溶瘤病毒的感染和复制，并与野生型病毒进行了比较。观察到红色荧光蛋白（RFP）表达的细胞数量的定性增加与感染次数的增加有关。与正常乳腺组织相比，在肿瘤组织中观察到较高的相对传染性。在人乳腺肿瘤切片中，感染后48和72小时，E4拷贝数增加，证明了病毒的复制能力。结论趋向性修饰的溶瘤腺病毒在乳腺癌组织切片中具有感染和复制的能力，这可能是其治疗效果的重要临床前指标。
BACKGROUNDDue to advances in viral design, oncolytic adenoviruses have emerged as a promising approach for treatment of breast cancer. Tumor tissue slices offer a stringent model system for preclinical evaluation of adenovirus therapies, since the slices retain a morphology and phenotype that more closely resembles the in vivo setting than cell line cultures, and this system has been shown to have utility in the evaluation of viral infectivity and replication. In this study, we evaluated the efficacy of viral infection and replication using a tropism-modified oncolytic adenovirus.METHODSBreast tumor tissue slices were infected with a tropism-modified oncolytic adenovirus, and a wild-type adenovirus for comparison. Efficiency of infection was evaluated using fluorescent microscopy, as the viruses used have been modified to express red fluorescent protein. Replication of the viruses was evaluated with quantitative real-time polymerase chain reaction (PCR) to assay viral E4 genome copy number, a surrogate indicator for the number of virions. The breast tumor tissue slices were evaluated for the expression of CD46 expression by immunohistochemistry.RESULTSInfection and replication of our tropism modified oncolytic virus has been observed in the breast cancer tissue slice model system and is comparative to wild-type virus. A qualitative increase in the number of cells showing red fluorescent protein (RFP) expression was observed correlating with increasing multiplicity of infection. Higher relative infectivity of the virus was observed in tumor tissue compared with normal breast tissue. Replication of the virus was demonstrated through increases in E4 copy number at 48 and 72 h after infection in human breast tumor slices.CONCLUSIONSWe have shown that a tropism modified oncolytic adenovirus can infect and replicate in breast cancer tissue slices, which may be an important preclinical indicator for its therapeutic utility.
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影响因子：
5.7
作者：
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DOI：
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