Treatment of anaplastic thyroid carcinoma in vitro with a mutant vaccinia virus
Treatment of anaplastic thyroid carcinoma in vitro with a mutant vaccinia virus
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DOI：
10.1016/j.surg.2007.09.017
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发表时间：
2007-12-01
期刊：
影响因子：
3.8
通讯作者：
Wong, Richard J.
中科院分区：
文献类型：
--
作者：
Lin, Shu-Fu;Yu, Zhenkun;Wong, Richard J.
背景。甲状腺未分化癌（ATC）是一种对所有传统治疗方法均无效的致命疾病。需要新的疗法来改善令人沮丧的结果。方法。通过将编码海肾荧光素酶绿色荧光蛋白（GTP）、β-半乳糖苷酶和β-葡萄糖醛酸酶的表达盒插入LIVP菌株的基因组中，设计出具有复制能力的痘苗病毒（GLV-1h68）。体外检测GLV-1h68对6种ATC细胞系的感染12、24、36小时。通过病毒噬斑测定来测量病毒增殖。每天以 0.01、0.1 和 1 的感染复数 (MOI) 测量细胞毒性。结果。 24 小时时在所有细胞系中均检测到病毒感染，并在 36 小时时强度增加。在所有细胞系中均检测到对数病毒复制。在 MOI 1 时，第 7 天时在 5 个细胞系中测量到 < 13% 的细胞存活率。在 MOI 0.01 时，3 个细胞系在第 7 天时显示出 < 21% 细胞存活率。24 小时时的荧光素酶和 β-半乳糖苷酶活性与第 5 天 MOI 0.01 时的细胞毒性相关。结论。具有复制能力的痘苗病毒对一组人类 ATC 具有显着的感染和溶瘤活性。这些结果鼓励未来对这种新药治疗这种致命癌症的体内和临床研究。
Background. Anaplastic thyroid carcinoma (ATC) is a fatal disease resistant to all conventional treatments. Novel therapies are needed to improve dismal outcomes.Methods. A replication-competent vaccinia virus (GLV-1h68) was engineered by inserting expression cassettes encoding Renilla luciferase-green fluorescent protein (GTP), 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.Results. 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.Conclusion. 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.