Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, accounting for 50% of all cases. GBM patients have a five-year survival rate of merely 5.6% and a median overall survival of 14.6 months with the “Stupp” regimen, 20.9 months with tumor treatment fields (TTF, OptuneR) in patients who participated in clinical trials, and 11 months for all GBM patients prior to TTF use. Objective: Our group recently developed a brain cancer chip which generates tumor spheroids, and provides large-scale assessments on the response of tumor cells to various concentrations and combinations of drugs. This platform could optimize the use of tumor samples derived from GBM patients to provide valuable insight on the tumor growth and responses to drug therapies. To minimize any sample loss in vitro, we improved our brain cancer chip system by adding an additional laminar flow distribution layer, which reduces sample loss during cell seeding and prevents spheroids from escaping from the microwells. Methods: In this study, we cultured 3D spheroids from GBM cell lines and patient-derived GBM cells in vitro, and investigated the effect of the combination of Temozolomide and nuclear factor-κB inhibitor on tumor growth. Results: Our study revealed that these drugs have synergistic effects in inhibiting spheroid formation when used in combination. Conclusions: These results suggest that the brain cancer chip enables large-scale, inexpensive and sample-effective drug screening to 3D cancer tumors in vitro, and could be applied to related tissue engineering drug screening studies.

中文翻译：

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替莫唑胺与 NF-κB 抑制剂联合显着破坏多形性胶质母细胞瘤球状体的形成


多形性胶质母细胞瘤（GBM）是最常见的恶性原发性脑肿瘤，占所有病例的50%。 GBM患者的五年生存率仅为5.6%，采用“Stupp”方案的患者中位总生存期为14.6个月，参加临床试验的患者采用肿瘤治疗领域（TTF、OptuneR）的中位总生存期为20.9个月，而采用“Stupp”方案的患者的中位总生存期为11个月。对于使用 TTF 之前的所有 GBM 患者。目的：我们课题组最近开发了一种脑癌芯片，可以生成肿瘤球体，并对肿瘤细胞对不同浓度和药物组合的反应进行大规模评估。该平台可以优化来自 GBM 患者的肿瘤样本的使用，为肿瘤生长和药物治疗反应提供有价值的见解。为了最大限度地减少体外样品损失，我们通过添加额外的层流分布层改进了我们的脑癌芯片系统，这减少了细胞接种过程中的样品损失并防止球体从微孔中逸出。方法：在本研究中，我们在体外培养了 GBM 细胞系和患者来源的 GBM 细胞的 3D 球体，并研究了替莫唑胺和核因子-κB 抑制剂联合使用对肿瘤生长的影响。结果：我们的研究表明，这些药物联合使用时在抑制球状体形成方面具有协同作用。结论：这些结果表明，脑癌芯片能够在体外对3D癌症肿瘤进行大规模、廉价且样品有效的药物筛选，并可应用于相关的组织工程药物筛选研究。