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dc.contributor.authorLorz, Alexander
dc.contributor.authorBotesteanu, Dana-Adriana
dc.contributor.authorLevy, Doron
dc.date.accessioned2018-09-03T13:24:23Z
dc.date.available2018-09-03T13:24:23Z
dc.date.issued2018-06-12
dc.identifier.citationLorz A, Botesteanu D-A, Levy D (2018) Universal response in the RKO colon cancer cell line to distinct antimitotic therapies. Scientific Reports 8. Available: http://dx.doi.org/10.1038/s41598-018-27267-7.
dc.identifier.issn2045-2322
dc.identifier.doi10.1038/s41598-018-27267-7
dc.identifier.urihttp://hdl.handle.net/10754/628447
dc.description.abstractBoth classic and newer antimitotics commonly induce a prolonged mitotic arrest in cell culture. During arrest, cells predominantly undergo one of two fates: cell death by apoptosis, or mitotic slippage and survival. To refine this binary description, a quantitative understanding of these cell responses is needed. Herein, we propose a quantitative description of the kinetics of colon carcinoma RKO cell fates in response to different antimitotics, using data from the single cell experiments of Gascoigne and Taylor (2008). The mathematical model is calibrated using the in vitro experiments of Gascoigne and Taylor (2008). We show that the time-dependent probability of cell death or slippage is universally identical for monastrol, nocodazole and two different doses of AZ138, but significantly different for taxol. Death and slippage responses across drugs can be characterized by Gamma distributions. We demonstrate numerically that these rates increase with prolonged mitotic arrest. Our model demonstrates that RKO cells exhibit a triphasic response - first, remain in mitosis, then undergo fast and slow transition, respectively- dependent on the length of mitotic arrest and irrespective of cell fate, drug type or dose.
dc.description.sponsorshipThe work of AL was supported by the King Abdullah University of Science and Technology (KAUST) baseline and start-up funds (BAS/1/1648-01-01 and BAS/1/1648-01-02). The work of DAB was partially supported by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute as part of a seed grant from the UMD-NCI Partnership for Cancer Technology. The work of DL was supported in part by the National Science Foundation under Grant Number DMS-1713109 and the Jayne Koskinas Ted Giovanis Foundation. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript
dc.publisherSpringer Nature
dc.relation.urlhttp://link.springer.com/article/10.1038/s41598-018-27267-7
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleUniversal response in the RKO colon cancer cell line to distinct antimitotic therapies
dc.typeArticle
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
dc.identifier.journalScientific Reports
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionSorbonne Universités, Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche 7598, Laboratoire Jacques-Louis Lions, Paris, , , , , France
dc.contributor.institutionDepartment of Discovery ADME, Boehringer Ingelheim RCV GmbH and Co KG, Vienna, , Austria
dc.contributor.institutionDepartment of Mathematics, Center for Scientific Computation and Mathematical Modeling, University of Maryland, College Park, MD, , United States
dc.contributor.institutionWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, , , United States
kaust.personLorz, Alexander
kaust.grant.numberBAS/1/1648-01-01
kaust.grant.numberBAS/1/1648-01-02
refterms.dateFOA2018-09-06T11:10:10Z
dc.date.published-online2018-06-12
dc.date.published-print2018-12


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This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.