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One Hour In Vivo-like Phenotypic Screening System for Anti-cancer Drugs Using a High Precision Surface Plasmon Resonance Device

机译:使用高精度表面等离振子共振装置的一小时体内类表型筛选系统用于抗癌药物

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In anti-cancer drug (candidate) screening, there is the need for evaluation at physiological concentrations similar to in vivo . This is often performed by three-dimensionally (3D) cultured cells; however, it requires a long culture period of 2 – 4 weeks with tedious experimental procedures. Here, we report on a high precision surface plasmon resonance (HP-SPR)-3D system. We developed the system with average fluctuation of 50 ndeg s~(?1) using two-dimensionally cultured cells attached onto a sensor chip by applying collagen on the top to change their activity into in vivo -like conditions without cell division. It allowed in vivo -like phenotypic screening for anti-cancer drugs within 1 h of drug addition. The data were collected as the stable linear signal change parts for at least 5 min after 25 min following drug addition. The results provided compatibility to clinically related chemosensitivity test for anti-cancer (P <0.001) using two cell lines of pancreatic cancer and three anti-cancer drugs to represent differences in individual gene expression and drug mode of action.
机译:在抗癌药物(候选)筛选中,需要在与体内相似的生理浓度下进行评估。这通常由三维(3D)培养的细胞执行;但是,这需要2到4周的长时间培养,而且实验过程繁琐。在这里,我们报告了高精度表面等离子体共振(HP-SPR)-3D系统。我们使用附着在传感器芯片上的二维培养细胞,通过在其顶部施加胶原蛋白将其活性改变为体内类似的状态而无需细胞分裂,开发出了平均波动为50 ndeg s〜(?1)的系统。在添加药物后1小时内,可以进行体内类表型筛选抗癌药物。药物添加后25分钟后至少5分钟,收集数据作为稳定的线性信号变化部分。该结果与使用两种胰腺癌细胞系和三种抗癌药物代表个体基因表达和药物作用方式的差异的抗癌临床相关化学敏感性测试(iP <0.001)兼容。

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