Exploration of the intercellular heterogeneity of topotecan uptake into human breast cancer cells through compartmental modelling
Cheung, S. Y. Amy, Evans, N. D., Chappell, M. J. (Michael J.), Godfrey, Keith, Smith, Paul J. (Paul James), 1953- and Errington, Rachel J.. (2008) Exploration of the intercellular heterogeneity of topotecan uptake into human breast cancer cells through compartmental modelling. Mathematical Biosciences, Vol.213 (No.2). pp. 119-134. ISSN 0025-5564
WRAP_Evans_9871863-es-081211-finalauthorversion.pdf - Accepted Version - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Official URL: http://dx.doi.org/10.1016/j.mbs.2008.03.008
A mathematical multi-cell model for the in vitro kinetics of the anti-cancer agent topotecan (TPT) following administration into a culture medium containing a population of human breast cancer cells (MCF-7 cell line) is described. This non-linear compartmental model is an extension of an earlier single-cell type model and has been validated using experimental data obtained using two-photon laser scanning microscopy (TPLSM).
A structural identifiability analysis is performed prior to parameter estimation to test whether the unknown parameters within the model are uniquely determined by the model outputs. The full model has 43 compartments, with 107 unknown parameters, and it was found that the structural identifiability result could not be established even when using the latest version of the symbolic computation software MATHEMATICA. However, by assuming that a priori knowledge is available for certain parameters, it was possible to reduce the number of parameters to 81, and it was found that this (Stage Two) model was globally (uniquely) structurally identifiable. The identifiability analysis demonstrated how valuable symbolic computation is in this context, as the analysis is far too lengthy and difficult to be performed by hand. (C) 2008 Elsevier Inc. All rights reserved.
|Item Type:||Journal Article|
|Subjects:||R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
|Divisions:||Faculty of Science > Engineering|
|Library of Congress Subject Headings (LCSH):||Breast -- Cancer -- Research, Pharmacokinetics -- Mathematical models, Cancer cells|
|Journal or Publication Title:||Mathematical Biosciences|
|Publisher:||Elsevier Science Inc.|
|Official Date:||June 2008|
|Number of Pages:||16|
|Page Range:||pp. 119-134|
|Access rights to Published version:||Restricted or Subscription Access|
 C. Bailly, Topoisomerase I poisons and suppressors as anticancer drugs, Current Medicinal Chemistry 7 (2000) p. 39-58.
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