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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Clinical Trial

蛋白酶体抑制剂卡非佐米对小儿实体瘤的细胞毒性和靶点调节

卷 21, 期 9, 2021

发表于: 03 May, 2021

页: [804 - 811] 页: 8

弟呕挨: 10.2174/1568009621666210504085527

价格: $65

摘要

背景：大多数患有复发性转移性实体瘤的儿童死亡率很高。最近的研究表明，蛋白酶体抑制可有效杀死已获得治疗抗性和转移特性的细胞中的肿瘤。 目的：本研究的目的是测试蛋白酶体抑制剂卡非佐米 (CFZ) 在目前未知的难治性儿科实体瘤中的潜力。 方法：使用一组儿科实体瘤细胞系，包括神经母细胞瘤、尤文氏肉瘤、骨肉瘤、横纹肌肉瘤和非典型畸胎样横纹肌瘤 (ATRT)，评估 CFZ 的细胞毒性和蛋白酶体抑制作用。进行药物调度实验以确定获得有效细胞杀伤的最佳剂量和时间。对 CFZ 与不同类别的化疗药物进行联合研究以确定协同作用的程度。 结果：CFZ 对所有测试的细胞系均显示出有效的细胞毒性（平均 IC50 = 7nM，范围 = 1-20nM），并在荧光团标记的基于细胞的蛋白酶体测定中具有活性。药物调度实验表明，有效累积杀灭需要最少 4-8 小时/天的暴露时间。 CFZ与不同类别的化疗药物联合使用时，协同增强了细胞死亡的程度。 结论：CFZ 对所有测试的实体小儿癌细胞系均表现出细胞毒活性。本研究提供了关于 CFZ 治疗儿科实体瘤潜力的初步体外数据，并支持对未来儿童早期临床试验的药物调度、生物学相关性和药物组合的组成部分进行进一步研究。

关键词: 小儿肿瘤、实体瘤、卡非佐米、蛋白酶体抑制、神经母细胞瘤、ATRT、肉瘤。

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