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An advanced discrete state-discrete event multiscale simulation model of the response of a solid tumor to chemotherapy: Mimicking a clinical study

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dc.contributor.author Stamatakos, GS en
dc.contributor.author Kolokotroni, EA en
dc.contributor.author Dionysiou, DD en
dc.contributor.author Georgiadi, E en
dc.contributor.author Desmedt, C en
dc.date.accessioned 2014-03-01T01:32:37Z
dc.date.available 2014-03-01T01:32:37Z
dc.date.issued 2010 en
dc.identifier.issn 0022-5193 en
dc.identifier.uri https://dspace.lib.ntua.gr/xmlui/handle/123456789/20198
dc.subject Breast cancer en
dc.subject Cancer modeling en
dc.subject Chemotherapy en
dc.subject In silico oncology en
dc.subject Simulation en
dc.subject.classification Biology en
dc.subject.classification Mathematical & Computational Biology en
dc.subject.other epirubicin en
dc.subject.other cancer en
dc.subject.other chemotherapy en
dc.subject.other histology en
dc.subject.other optimization en
dc.subject.other sensitivity analysis en
dc.subject.other simulation en
dc.subject.other tumor en
dc.subject.other article en
dc.subject.other breast tumor en
dc.subject.other cancer chemotherapy en
dc.subject.other cancer model en
dc.subject.other cell kinetics en
dc.subject.other cell proliferation en
dc.subject.other clinical study en
dc.subject.other computer model en
dc.subject.other drug response en
dc.subject.other pharmacodynamics en
dc.subject.other priority journal en
dc.subject.other sensitivity analysis en
dc.subject.other stem cell en
dc.subject.other tumor growth en
dc.subject.other tumor volume en
dc.subject.other Algorithms en
dc.subject.other Antigens, Neoplasm en
dc.subject.other Apoptosis en
dc.subject.other Breast Neoplasms en
dc.subject.other Cell Cycle en
dc.subject.other Cell Proliferation en
dc.subject.other Clinical Trials as Topic en
dc.subject.other Computer Simulation en
dc.subject.other DNA Topoisomerases, Type II en
dc.subject.other DNA-Binding Proteins en
dc.subject.other Epirubicin en
dc.subject.other Female en
dc.subject.other Gene Expression en
dc.subject.other Humans en
dc.subject.other Individualized Medicine en
dc.subject.other Models, Biological en
dc.subject.other Necrosis en
dc.subject.other Neoplasms en
dc.subject.other Neoplastic Stem Cells en
dc.subject.other Software Design en
dc.subject.other Treatment Outcome en
dc.title An advanced discrete state-discrete event multiscale simulation model of the response of a solid tumor to chemotherapy: Mimicking a clinical study en
heal.type journalArticle en
heal.identifier.primary 10.1016/j.jtbi.2010.05.019 en
heal.identifier.secondary http://dx.doi.org/10.1016/j.jtbi.2010.05.019 en
heal.language English en
heal.publicationDate 2010 en
heal.abstract In this paper an advanced, clinically oriented multiscale cancer model of breast tumor response to chemotherapy is presented. The paradigm of early breast cancer treated by epirubicin according to a branch of an actual clinical trial (the Trial of Principle, TOP trial) has been addressed. The model, stemming from previous work of the In Silico Oncology Group, National Technical University of Athens, is characterized by several crucial new features, such as the explicit distinction of proliferating cells into stem cells of infinite mitotic potential and cells of limited proliferative capacity, an advanced generic cytokinetic model and an improved tumor constitution initialization technique. A sensitivity analysis regarding critical parameters of the model has revealed their effect on the behavior of the biological system. The favorable outcome of an initial step towards the clinical adaptation and validation of the simulation model, based on the use of anonymized data from the TOP clinical trial, is presented and discussed. Two real clinical cases from the TOP trial with variable molecular profile have been simulated. A realistic time course of the tumor diameter and a reduction in tumor size in agreement with the clinical data has been achieved for both cases by selection of reasonable model parameter values, thus demonstrating a possible adaptation process of the model to real clinical trial data. Available imaging, histological, molecular and treatment data are exploited by the model in order to strengthen patient individualization modeling. The expected use of the model following thorough clinical adaptation, optimization and validation is to simulate either several candidate treatment schemes for a particular patient and support the selection of the optimal one or to simulate the expected extent of tumor shrinkage for a given time instant and decide on the adequacy or not of the simulated scheme. (C) 2010 Elsevier Ltd. All rights reserved. en
heal.publisher ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD en
heal.journalName Journal of Theoretical Biology en
dc.identifier.doi 10.1016/j.jtbi.2010.05.019 en
dc.identifier.isi ISI:000280929800013 en
dc.identifier.volume 266 en
dc.identifier.issue 1 en
dc.identifier.spage 124 en
dc.identifier.epage 139 en


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