Studying the growth kinetics of untreated clinical tumors by using an advanced discrete simulation model

Kolokotroni, EA; Dionysiou, DD; Uzunoglu, NK; Stamatakos, GS

dc.contributor.author	Kolokotroni, EA	en
dc.contributor.author	Dionysiou, DD	en
dc.contributor.author	Uzunoglu, NK	en
dc.contributor.author	Stamatakos, GS	en
dc.date.accessioned	2014-03-01T01:37:10Z
dc.date.available	2014-03-01T01:37:10Z
dc.date.issued	2011	en
dc.identifier.issn	0895-7177	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/21469
dc.subject	Cancer modeling	en
dc.subject	Exponential tumor growth	en
dc.subject	In silico oncology	en
dc.subject	Tumor free growth	en
dc.subject	Tumor kinetics	en
dc.subject.classification	Computer Science, Interdisciplinary Applications	en
dc.subject.classification	Computer Science, Software Engineering	en
dc.subject.classification	Mathematics, Applied	en
dc.subject.other	Analytical treatment	en
dc.subject.other	Biological mechanisms	en
dc.subject.other	Cancer modeling	en
dc.subject.other	Cell cycle	en
dc.subject.other	Cell populations	en
dc.subject.other	Clinical data	en
dc.subject.other	Discrete models	en
dc.subject.other	Discrete simulation model	en
dc.subject.other	Dynamic behaviors	en
dc.subject.other	Exponential tumor growth	en
dc.subject.other	Growth behavior	en
dc.subject.other	Histological data	en
dc.subject.other	In silico oncology	en
dc.subject.other	In-depth investigation	en
dc.subject.other	Malignant tumors	en
dc.subject.other	Model parameters	en
dc.subject.other	Parametric analysis	en
dc.subject.other	Parametric study	en
dc.subject.other	Possible solutions	en
dc.subject.other	Transition rates	en
dc.subject.other	Tumor cells	en
dc.subject.other	Tumor growth	en
dc.subject.other	Cell culture	en
dc.subject.other	Cell proliferation	en
dc.subject.other	Computer simulation	en
dc.subject.other	Kinetics	en
dc.subject.other	Mathematical models	en
dc.subject.other	Population statistics	en
dc.subject.other	Tumors	en
dc.subject.other	Growth kinetics	en
dc.title	Studying the growth kinetics of untreated clinical tumors by using an advanced discrete simulation model	en
heal.type	journalArticle	en
heal.identifier.primary	10.1016/j.mcm.2011.05.007	en
heal.identifier.secondary	http://dx.doi.org/10.1016/j.mcm.2011.05.007	en
heal.language	English	en
heal.publicationDate	2011	en
heal.abstract	Prior to an eventual clinical adaptation and validation of any clinically oriented model, a thorough study of its dynamic behavior is a sine qua non. Such a study can also elucidate aspects of the interplay of the involved biological mechanisms. Toward this goal, the paper focuses on an in-depth investigation of the free growth behavior of a macroscopically homogeneous malignant tumor system, using a discrete model of tumor growth. We demonstrate that when a clinical tumor grows exponentially, the following preconditions must be fulfilled: (a) time- and space-independent tumor dynamics, in terms of the transition rates among the considered cell categories and the duration of the cell cycle phases, and (b) a tumor system in a state of population equilibrium. Moreover, constant tumor dynamics during the simulation are assumed. In order to create a growing tumor, a condition that the model parameters must fulfill has been derived based on an analytical treatment of the model's assumptions. A detailed parametric analysis of the model has been performed, in order to determine the impact and the interdependences of its parameters with focus on the free growth rate and the composition of cell population. Constraining tumor cell kinetics, toward limiting the number of possible solutions (i.e., sets of parameters) to the problem of adaptation to the real macroscopic features of a tumor, is also discussed. After completing all parametric studies and after adapting and validating the model on clinical data, it is envisaged to end up with a reliable tool for supporting clinicians in selecting the most appropriate pattern, extracted from several candidate therapeutic schemes, by exploiting tumor- and patient-specific imaging, molecular and histological data. (C) 2011 Elsevier Ltd. All rights reserved.	en
heal.publisher	PERGAMON-ELSEVIER SCIENCE LTD	en
heal.journalName	Mathematical and Computer Modelling	en
dc.identifier.doi	10.1016/j.mcm.2011.05.007	en
dc.identifier.isi	ISI:000293829300011	en
dc.identifier.volume	54	en
dc.identifier.issue	9-10	en
dc.identifier.spage	1989	en
dc.identifier.epage	2006	en