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Batch Effect Adjustment to Lower the Drug Attrition Rate of MCF-7 Breast Cancer Cells Exposed to Silica Nanomaterial-Derived Scaffolds
ASSAY and Drug Development Technologies ( IF 1.8 ) Pub Date : 2021-01-13 , DOI: 10.1089/adt.2020.1016
Victor Akpe 1, 2 , Shweta Murhekar 1, 2 , Tak H Kim 1, 2 , Christopher L Brown 1, 2 , Ian E Cock 1, 2
Affiliation  

Drug attrition rate is the calculation or measure of the clinical efficacy of a candidate drug on a screen platform for a specific period. Determining the attrition rate of a prospective cancer drug is a reliable way of testing the clinical efficacy. A low attrition rate in the last phase of a preclinical trial increases the success of a drug discovery process. It has been reported that the attrition rates of antineoplastic drugs are much higher than for other therapeutic drugs. Among the factors identified for the high attrition rates in antineoplastic drugs are the nature of the screen-based platforms involving human-derived xenografts, extracellular matrix-derived scaffold systems, and the synthetic scaffolds, which all have propensity to proliferate tumor cells at faster rates than in vivo primary tumors. Other factors that affect the high attrition rates are induced scaffold toxicity and the use of assays that are irrelevant, yet affect data processing. These factors contribute to the wide variation in data and systematic errors. As a result, it becomes imperative to filter batch variations and to standardize the data. Importantly, understanding the interplay between the biological milieu and scaffold connections is also crucial. Here the cell viability of MCF-7 (breast cancer cell line) cells exposed to different scaffolds were screened before cisplatin dosing using the calculated p-values. The statistical significance (p-value) of data was calculated using the one-way analysis of variance, with the p-value set as: 0 < p < 0.06. In addition, the half-maximal inhibitory concentration (IC50) of the different scaffolds exposed to MCF-7 cells were calculated with the probit extension model and cumulative distribution (%) of the extension data. The chemotherapeutic dose (cisplatin, 56 mg/m2) reduced the cell viability of MCF-7 cells to 5% within 24 h on the scaffold developed from silica nanoparticles (SNPs) and polyethylene glycol (PEG) formulation (SNP:PEG) mixtures with a ratio of 1:10, respectively.

中文翻译:

批量效应调整以降低暴露于二氧化硅纳米材料衍生支架的 MCF-7 乳腺癌细胞的药物损耗率

药物损耗率是候选药物在特定时期在筛选平台上的临床​​疗效的计算或度量。确定预期抗癌药物的损耗率是测试临床疗效的可靠方法。临床前试验最后阶段的低损耗率提高了药物发现过程的成功率。据报道,抗肿瘤药物的损耗率远高于其他治疗药物。确定抗肿瘤药物高损耗率的因素包括基于屏幕的平台的性质,包括人源性异种移植物、细胞外基质源性支架系统和合成支架,它们都有以更快的速度增殖肿瘤细胞的倾向比体内原发肿瘤。影响高磨损率的其他因素是诱导支架毒性和使用无关但影响数据处理的化验。这些因素导致数据和系统误差的广泛变化。因此,过滤批次变化和标准化数据变得势在必行。重要的是,了解生物环境和支架连接之间的相互作用也至关重要。在此,使用计算的p值在顺铂给药之前筛选暴露于不同支架的 MCF-7(乳腺癌细胞系)细胞的细胞活力使用单向方差分析计算数据的统计显着性( p值), p值设置为:0 < p< 0.06。此外,使用概率扩展模型和扩展数据的累积分布(%)计算暴露于MCF-7细胞的不同支架的半数最大抑制浓度(IC 50)。在由二氧化硅纳米粒子 (SNP) 和聚乙二醇 (PEG) 制剂 (SNP:PEG) 混合物制成的支架上,化疗剂量(顺铂,56 mg/m 2)在 24 小时内将 MCF-7 细胞的细胞活力降低至 5%比例分别为 1:10。
更新日期:2021-01-14
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