Lin Shu-Fu, Yu Zhenkun, Riedl Christopher, Woo Yanghee, Zhang Qian, Yu Yong A, Timiryasova Tatyana, Chen Nanhai, Shah Jatin P, Szalay Aladar A, Fong Yuman, Wong Richard J
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Surgery. 2007 Dec;142(6):976-83; discussion 976-83. doi: 10.1016/j.surg.2007.09.017. Epub 2007 Nov 5.
Anaplastic thyroid carcinoma (ATC) is a fatal disease resistant to all conventional treatments. Novel therapies are needed to improve dismal outcomes.
A replication-competent vaccinia virus (GLV-1h68) was engineered by inserting expression cassettes encoding Renilla luciferase-green fluorescent protein (GFP), beta-galactosidase, and beta-glucuronidase into the genome of LIVP strain. Infection of 6 ATC cell lines by GLV-1h68 was detected in vitro at 12, 24, and 36 hours. Viral proliferation was measured through viral plaque assays. Cytotoxicity was measured daily at a multiplicity of infection (MOI) of 0.01, 0.1 and 1.
Viral infection was detected in all cell lines by 24 hours and increased in intensity at 36 hours. Logarithmic viral replication was detected in all cell lines. At MOI 1, <13% cell survival was measured in 5 cell lines by day 7. At MOI 0.01, 3 cell lines showed <21% cell survival by day 7. Luciferase and beta-galactosidase activity at 24 hours correlated with cytotoxicity at MOI 0.01 on day 5.
A replication-competent vaccinia virus has significant infectious and oncolytic activity against a panel of human ATC. These results encourage future in vivo and clinical studies for this novel agent to treat this fatal cancer.
间变性甲状腺癌（ATC）是一种对所有传统治疗均耐药的致命性疾病。需要新的治疗方法来改善其糟糕的预后。
通过将编码海肾荧光素酶-绿色荧光蛋白（GFP）、β-半乳糖苷酶和β-葡萄糖醛酸酶的表达盒插入LIVP株基因组中，构建了一种具有复制能力的痘苗病毒（GLV-1h68）。在体外分别于12、24和36小时检测GLV-1h68对6种ATC细胞系的感染情况。通过病毒蚀斑试验测量病毒增殖。每天以感染复数（MOI）为0.01、0.1和1测量细胞毒性。
所有细胞系在24小时时均检测到病毒感染，且在36小时时感染强度增加。所有细胞系均检测到病毒的对数增殖。在MOI为1时，到第7天，5种细胞系的细胞存活率<13%。在MOI为0.01时，3种细胞系到第7天的细胞存活率<21%。24小时时的荧光素酶和β-半乳糖苷酶活性与第5天MOI为0.01时的细胞毒性相关。
一种具有复制能力的痘苗病毒对一组人ATC具有显著的感染和溶瘤活性。这些结果鼓励对这种新型药物进行未来的体内和临床研究，以治疗这种致命癌症。
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