Real-time intraoperative detection of melanoma lymph node metastases using recombinant vaccinia virus GLV-1h68 in an immunocompetent animal model.
Real-time intraoperative detection of melanoma lymph node metastases using recombinant vaccinia virus GLV-1h68 in an immunocompetent animal model.
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DOI：
10.1002/ijc.24037
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发表时间：
2009-02-15
影响因子：
6.4
通讯作者：
Fong, Yuman
中科院分区：
文献类型：
--
作者：
Kelly, Kaitlyn J.;Brader, Peter;Woo, Yanghee;Li, Sen;Chen, Nanhai;Yu, Yong A.;Szalay, Aladar A.;Fong, Yuman
临床需要改进恶性黑色素瘤（MM）淋巴结转移的术中检测。我们的目的是研究使用表达绿色荧光蛋白 (GFP) 的重组牛痘病毒 GLV-1h68 在免疫功能正常的动物模型中实时检测黑色素瘤淋巴结转移。携带足垫肿瘤的小鼠接受 GLV-1h68 瘤内注射，48 小时后使用非侵入性生物发光成像和荧光成像评估腘淋巴结转移。对淋巴结进行组织学分析以确定病毒介导的检测的敏感性和特异性。将 GLV-1h68 瘤内注射到原发性足垫黑色素瘤肿瘤中，导致病毒传播到腘淋巴结、淋巴转移感染以及可靠且易于检测的转基因表达。组织学确认证明了该测定的良好操作特性（敏感性 80%，特异性 100%，阳性预测值 [PPV] 100%，阴性预测值 [NPV] 91%）。通过 GLV-1h68 检测标记基因表达，可以检测免疫功能正常的 MM 动物模型中的淋巴转移。该测定快速、灵敏、特异且易于执行和解释。作为杀死癌症的候选基因治疗病毒，GLV-1h68 在癌症患者的分期中也可能具有显着的伴随诊断用途。
There is a clinical need for improved intraoperative detection of lymph node metastases from malignant melanoma (MM). We aimed to investigate the use of recombinant vaccinia virus GLV-1h68, expressing green fluorescent protein (GFP), for real-time intraoperative detection of melanoma lymph node metastases in an immunocompetent animal model. Mice bearing foot pad tumors received intratumoral injections of GLV-1h68 and 48 hours later were evaluated for popliteal lymph node metastasis using noninvasive bioluminescence imaging and fluorescence imaging. Histologic analysis of lymph nodes was performed to determine sensitivity and specificity of virus-mediated detection. Intratumoral injection of GLV-1h68 into primary foot pad melanoma tumors resulted in viral transmission to popliteal lymph nodes, infection of lymphatic metastases, and transgene expression that was reliably and easily detected. Histologic confirmation demonstrated favorable operating characteristics of this assay (sensitivity 80%, specificity 100%, positive predictive value [PPV] 100%, negative predictive value [NPV] 91%). Detection of marker gene expression by GLV-1h68 allowed the detection of lymphatic metastases in an immunocompetent animal model of MM. This assay is rapid, sensitive, specific, and easy to perform and interpret. As a candidate gene therapy virus for killing cancer, GLV-1h68 may also have significant concomitant diagnostic utility in the staging of cancer patients.
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DOI：
10.1038/nrmicro1099
发表时间：
2005-03
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.4
作者：
Chalikonda, S.;Kivlen, M. H.;Bartlett, D. L.
通讯作者：
Bartlett, D. L.
影响因子：
3.8
作者：
Lin, Shu-Fu;Yu, Zhenkun;Wong, Richard J.
通讯作者：
Wong, Richard J.
影响因子：
3.1
作者：
Zettersten, E;Shaikh, L;Kashani-Sabet, M
通讯作者：
Kashani-Sabet, M
影响因子：
46.9
作者：
Yu, YA;Shabahang, S;Szalay, AA
通讯作者：
Szalay, AA