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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Efficacy of Asparaginase Erwinia chrysanthemi With and Without Temozolomide Against Glioma Cells and Intracranial Mouse Medulloblastoma
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Efficacy of Asparaginase Erwinia chrysanthemi With and Without Temozolomide Against Glioma Cells and Intracranial Mouse Medulloblastoma

机译：芦瓜蛋白酶生物植物对胶质瘤细胞和颅内小鼠髓质母细胞瘤的疗效芦苇蛋白酶生物植物的疗效

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Background: Anti-metabolites are less-myelosuppressive than DNA-damaging anticancer drugs and may be useful against brain tumors. Materials and Methods: We evaluated the asparagine/glutamine-deaminating agent Erwinaze with/without temozolomide against brain tumor cells and mouse medulloblastomas. Results. Erwinaze treatment of cell lines and neurospheres led to dose-dependent reductions of cells (reversible by L-glutamine), with half maximal inhibitory concentrations (IC(50)s) of 0.12-10 IU/ml. Erwinaze at 1 IU/ml reduced temozolomide IC(50)s by 3.6- to 13-fold (300-1,200 mu M to 40-330 mu M). Seven-week-old SMO/SMO mice treated with Erwinaze (regardless of temozolomide treatment) had better survival 11 weeks post-therapy, compared to those not treated with Erwinaze (81.25% vs. 46.15, p=0.08). Temozolomide-treated mice developed 10% weight loss, impairing survival. All 16 mice treated with temozolomide (regardless of Erwinaze treatment) succumbed by 40-weeks of age, whereas 5/8 animals treated with Erwinaze alone and 2/6 controls survived (p=0.035). Conclusion: Erwinaze enhances cytotoxicity of temozolomide in vitro, and improves survival in SMO/SMO mice, likely by reducing cerebrospinal fluid glutamine. Temozolomide-associated toxicity prevented demonstration of any potential combinatorial advantage with Erwinaze in vivo.
机译：背景：抗代谢物比DNA损伤抗癌药物少于髓鞘，并且可用于脑肿瘤。材料和方法：我们评估了紫酰胺/谷氨酰胺 - 脱氨酸酯的ERWinaze，而不针对脑肿瘤细胞和小鼠Medulloblastomas。结果。 Erwinaze治疗细胞系和神经球导致细胞的剂量依赖性（L-谷氨酰胺可逆），半最大抑制浓度（IC（50））为0.12-＆ 10IU / ml。在＆ 1 iu / ml降低替莫唑胺IC（50）S的eRwinaze。用Erwinaze治疗的七周历史的SMO / SMO小鼠（无论替代替代橄榄族治疗），治疗后11周都有更好的存活率，而不是用Erwinaze治疗的那些（81.25％与46.15，p = 0.08）。替莫唑胺处理的小鼠产生了10％的体重减轻，存活损害。所有16只小鼠用替代唑胺治疗（无论奥尔韦兹治疗如何）均以40周龄待命，而用单独用Erwinaze治疗的5/8只动物，并存活2/6对照（P = 0.035）。结论：Erwinaze在体外增强Temozolomide的细胞毒性，并改善了Smo / Smo小鼠的存活，可能通过减少脑脊液谷氨酰胺。泛唑啉基相关的毒性阻止了在体内中Erwinaze的任何潜在的组合优势。

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