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	Molecular Determinants of the Anticancer Efficacy of Topoisomerase I Inhibitors
	Fung-Ming Siu
	2015
会议名称	MMHS-2015
会议地点	Shanghai, China
英文摘要	Camptothecin and its analogs (CPTs) are effective anticancer agents and are the only class of FDA-approved topoisomerase I (top1) inhibitors or cancer treatment. A panel of 60 diverse human cancer cell lines (NCI-60) has been profiled at DNA, RNA, protein and pharmacological levels by the US National Cancer Institute. In this article, we asked the question of what characteristics of the NCI-60 cell lines are associated with the responses (sensitive or resistant) to the CPTs-treatment. In the present study, a total of 3283 mRNAs, 52 microRNAs and 10 proteins were defined as determinant markers, whose expression levels correlate with the cytotoxicity of CPTs across the NCI-60 panel. Bioinformatics analysis was performed to gain insights (associated pathways or gene ontology terms) from the determinant markers. The results suggest that (i) E-cadherin plays an important role in the chemosensitivity to CPTs; (ii) pretreatment of cancer cells with histone deacetylase inhibitors has antagonistic effects on the anticancer efficacy of CPTs; and (iii) the expression levels of the majority of the determinant gene markers do not change upon CPT-treatment. The present study provides detailed analysis on the determinant markers that can be exploited in future studies to ultimately improve the outcome of CPTs-based cancer treatment. We envision our study can be considered as a paradigm of the combined use of the CellMiner database (National Cancer Institute) and the Connectivity Map databases (Broad Institute of MIT and Harvard) to predict drug combination effects.
收录类别	其他
语种	英语
内容类型	会议论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/6986]
专题	深圳先进技术研究院_数字所
作者单位	2015
推荐引用方式 GB/T 7714	Fung-Ming Siu. Molecular Determinants of the Anticancer Efficacy of Topoisomerase I Inhibitors[C]. 见:MMHS-2015. Shanghai, China.

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