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首页> 外文期刊>Cancer: A Journal of the American Cancer Society >Systemic administration of reovirus (Reolysin) inhibits growth of human sarcoma xenografts.
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Systemic administration of reovirus (Reolysin) inhibits growth of human sarcoma xenografts.

机译：呼肠孤病毒（Reolysin）的全身给药抑制人肉瘤异种移植物的生长。

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摘要

BACKGROUND: Despite advancement in therapies, overall survival rates for relapsed pediatric sarcomas are dismal. Newer therapies are needed to effectively salvage these patients. Oncolytic viruses (such as reovirus) and other genetically altered viruses (such as herpes simplex viruses and adenoviruses) have shown efficacy in a variety of solid tumors including sarcomas. Reolysin is an unmodified oncolytic reovirus that selectively replicates in Ras-activated cancer cells while not causing any significant human illness in its wild form. METHODS: By using a panel of pediatric sarcoma cell lines in vitro and flank xenografts in vivo, Reolysin was evaluated as a single agent and in combination with cisplatin and radiation therapy. Electron microscopy and immunohistochemistry was used to demonstrated a cytopathic effect in treated tumors. RESULTS: Reolysin inhibited the proliferation and viability of sarcoma cell lines at a dose of 1 to 10 virus particles per cell. In vivo, 5 x 10(9) plaque-forming units (PFU) administered via the tail vein every other day for 3 doses every 21 days inhibited the growth of tumor xenografts with improvement in event-free survival. In the SKES1 Ewing sarcoma line, there was therapeutic enhancement when reovirus was administered in combination with radiation or cisplatin. In the RH30 line and the OS33 line, therapeutic enhancement was demonstrated with radiation and cisplatin, respectively. CONCLUSIONS: These results suggest that Reolysin alone or in combination with other cytotoxic agents may be effective therapy in pediatric sarcomas.
机译：背景：尽管疗法有所进步，但复发性小儿肉瘤的总生存率却令人沮丧。需要新的疗法来有效挽救这些患者。溶瘤病毒（如呼肠孤病毒）和其他遗传改变的病毒（如单纯疱疹病毒和腺病毒）已在包括肉瘤在内的各种实体瘤中显示出功效。溶血素是未经修饰的溶瘤性呼肠孤病毒，可以在Ras活化的癌细胞中选择性复制，而不会以野生形式引起任何重大的人类疾病。方法：通过使用一组儿科肉瘤细胞系体外和体内侧翼异种移植，Reolysin被评估为单一药物，并与顺铂和放射疗法相结合。电子显微镜和免疫组织化学被用来证明在治疗的肿瘤中具有细胞病变作用。结果：溶血素以每细胞1至10个病毒颗粒的剂量抑制肉瘤细胞系的增殖和生存能力。在体内，每21天通过尾静脉给予5 x 10（9）斑块形成单位（PFU），每21天3剂，可抑制肿瘤异种移植物的生长，并改善无事件存活率。在SKES1尤因氏肉瘤细胞系中，呼肠孤病毒与放疗或顺铂联合使用可增强治疗效果。在RH30品系和OS33品系中，分别用放射线和顺铂证明了治疗效果。结论：这些结果表明，单独的溶血素或与其他细胞毒剂联合使用，可能是治疗小儿肉瘤的有效方法。

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