High-content imaging characterization of cell cycle therapeutics through in vitro and in vivo subpopulation analysis

Molecular Cancer Therapeutics
Jonathan LowLouis Stancato

Abstract

Although the cycling of eukaryotic cells has long been a primary focus for cancer therapeutics, recent advances in imaging and data analysis allow even further definition of cellular events as they occur in individual cells and cellular subpopulations in response to treatment. High-content imaging (HCI) has been an effective tool to elucidate cellular responses to a variety of agents; however, these data were most frequently observed as averages of the entire captured population, unnecessarily decreasing the resolution of each assay. Here, we dissect the eukaryotic cell cycle into individual cellular subpopulations using HCI in conjunction with unsupervised K-means clustering. We generate distinct phenotypic fingerprints for each major cell cycle and mitotic compartment and use those fingerprints to screen a library of 310 commercially available chemotherapeutic agents. We determine that the cell cycle arrest phenotypes caused by these agents are similar to, although distinct from, those found in untreated cells and that these distinctions frequently suggest the mechanism of action. We then show via subpopulation analysis that these arrest phenotypes are similar in both mouse models and in culture. HCI analysis of cell cycle us...Continue Reading

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Citations

Apr 28, 2012·Cell Death and Differentiation·C M TateL Stancato
Jul 17, 2010·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Shuguang Huang
Jan 9, 2010·BMC Bioinformatics·Merlin VeronikaJagath Rajapakse
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Jun 1, 2009·Expert Opinion on Drug Discovery·Fabio Gasparri
Aug 16, 2013·Journal of Biomolecular Screening·Mariana Figuera-LosadaBarbara S Slusher
Jul 31, 2013·Journal of Biomolecular Screening·Paolo Cappella, Fabio Gasparri
Oct 11, 2013·Journal of Biomolecular Screening·Beverley J IsherwoodNeil O Carragher
Jul 20, 2010·Journal of Biomolecular Screening·Donald JacksonJames Gill
Oct 1, 2011·Journal of Biomolecular Screening·Jonathan LowLouis Stancato
Oct 11, 2016·Integrative Biology : Quantitative Biosciences From Nano to Macro·Susan E LeggettIan Y Wong
Jul 1, 2010·Optics Express·Ching-Wei Chang, Mary-Ann Mycek
Jan 12, 2013·Journal of Biomolecular Screening·Raquel Torres-GuzmánMaría José Lallena
Feb 24, 2017·SLAS Discovery·Albert GoughD Lansing Taylor
Sep 10, 2011·Molecular Cancer Therapeutics·Timothy MeierLouis Stancato
Mar 9, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Caitlin D LoweryLouis F Stancato
Aug 23, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michele DowlessLouis Stancato
Dec 20, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Caitlin D LoweryLouis F Stancato
Jun 10, 2010·Molecular Cancer Therapeutics·Peter D CaieNeil O Carragher

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