The contribution of age structure to cell population responses to targeted therapeutics

Cells grown in culture act as a model system for analyzing the effects of anticancer compounds, which may affect cell behavior in a cell cycle position-dependent manner. Cell synchronization techniques have been generally employed to minimize the variation in cell cycle position. However, synchroniz...

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Bibliographic Details
Published in:Journal of theoretical biology 2012-10, Vol.311, p.19-27
Main Authors: Gabriel, Pierre, Garbett, Shawn P., Quaranta, Vito, Tyson, Darren R., Webb, Glenn F.
Format: Article
Language:English
Subjects:
age structure
Analysis of PDEs
anticarcinogenic activity
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Cancer
Cell cycle
Cell Cycle - drug effects
cell structures
Cellular Senescence - drug effects
Exponentially modified Gaussian
Humans
Intermitotic time
Life Sciences
Mathematics
microscopy
Models, Biological
Neoplasms - drug therapy
Neoplasms - metabolism
Neoplasms - pathology
Renewal equation
therapeutics
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Summary:Cells grown in culture act as a model system for analyzing the effects of anticancer compounds, which may affect cell behavior in a cell cycle position-dependent manner. Cell synchronization techniques have been generally employed to minimize the variation in cell cycle position. However, synchronization techniques are cumbersome and imprecise and the agents used to synchronize the cells potentially have other unknown effects on the cells. An alternative approach is to determine the age structure in the population and account for the cell cycle positional effects post hoc. Here we provide a formalism to use quantifiable lifespans from live cell microscopy experiments to parameterize an age-structured model of cell population response. ► We present a method to recover the division rate of an age-structured model from experimental data. ► This method is based on the fitting of experimental intermitotic time distributions. ► We present an application of the results concerning the treatment of cancer cells by erlotinib.
ISSN:0022-5193
1095-8541
DOI:10.1016/j.jtbi.2012.07.001