Drug Screening of Human GBM Spheroids in Brain Cancer Chip.
Drug Screening of Human GBM Spheroids in Brain Cancer Chip.
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DOI：
10.1038/s41598-018-33641-2
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发表时间：
2018-10-18
影响因子：
4.6
通讯作者：
Zhu JJ
中科院分区：
文献类型：
--
作者：
Akay M;Hite J;Avci NG;Fan Y;Akay Y;Lu G;Zhu JJ
多形性胶质母细胞瘤（GBM）是一种极具侵袭性的高级别（IV级）胶质瘤，是最常见和最具侵袭性的脑癌。其预后不良，一般GBM人群的中位总生存期仅为11个月，而标准GBM治疗（包括最大安全开颅术、辅助放疗和化疗）的临床试验参与者的中位总生存期为14.6至21个月。因此，迫切需要开发有效治疗的新方法，例如在给予药物治疗之前评估肿瘤细胞药物反应的工具，以提高患者存活率。为了解决这个问题，我们开发了一种改进的脑癌芯片，它具有扩散预防机制，可以阻止药物从一个通道进入另一个通道。在目前的研究中，我们证明了该芯片具有从三名GBM患者获得的患者肿瘤细胞衍生的GBM细胞培养3D球体的能力。应用用于治疗GBM的两种临床药物替莫唑胺（TMZ）和贝伐单抗（Avastin，BEV），并且通过脑癌芯片中的微流体通道产生一系列相对浓度。结果表明，与TMZ单独使用相比，TMZ与BEV联合使用时更有效。我们相信，这种低成本的脑癌芯片可以进一步开发，以产生针对单个GBM患者的最佳化疗药物组合。
Glioblastoma multiforme (GBM), an extremely invasive and high-grade (grade IV) glioma, is the most common and aggressive form of brain cancer. It has a poor prognosis, with a median overall survival of only 11 months in the general GBM population and 14.6 to 21 months in clinical trial participants with standard GBM therapies, including maximum safe craniotomy, adjuvant radiation, and chemotherapies. Therefore, new approaches for developing effective treatments, such as a tool for assessing tumor cell drug response before drug treatments are administered, are urgently needed to improve patient survival. To address this issue, we developed an improved brain cancer chip with a diffusion prevention mechanism that blocks drugs crossing from one channel to another. In the current study, we demonstrate that the chip has the ability to culture 3D spheroids from patient tumor specimen-derived GBM cells obtained from three GBM patients. Two clinical drugs used to treat GBM, temozolomide (TMZ) and bevacizumab (Avastin, BEV), were applied and a range of relative concentrations was generated by the microfluidic channels in the brain cancer chip. The results showed that TMZ works more effectively when used in combination with BEV compared to TMZ alone. We believe that this low-cost brain cancer chip could be further developed to generate optimal combination of chemotherapy drugs tailored to individual GBM patients.
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影响因子：
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作者：
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通讯作者：
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影响因子：
4.7
作者：
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3
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通讯作者：
Blakeley, Jaishri O.
建立高通量三维体外胶质母细胞瘤模型
DOI：
10.1109/jtehm.2015.2410277
发表时间：
2015
影响因子：
3.4
作者：
Fan Y;Avci NG;Nguyen DT;Dragomir A;Akay YM;Xu F;Akay M
通讯作者：
Akay M