Atari, M. I., Chappell, M. J. (Michael J.), Errington, Rachel J., Smith, Paul J. and Evans, Neil D. (2011) Kinetic modelling of the role of the aldehyde dehydrogenase enzyme and the breast cancer resistance protein in drug resistance and transport. Computer Methods and Programs in Biomedicine, Vol.104 (No.2). pp. 93-103. doi:10.1016/j.cmpb.2010.06.008 ISSN 01692607.

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Abstract

A compartmental model for the in vitro uptake kinetics of the anti-cancer agent topotecan (TPT) has been extended from a previously published model. The extended model describes the drug activity and delivery of the pharmacologically active form to the DNA target as well as the catalysis of the aldehyde dehydrogenase (ALDH) enzyme and the elimination of drug from the cytoplasm via the efflux pump. Verification of the proposed model is achieved using scanning-laser microscopy data from live human breast cancer cells. Before estimating the unknown model parameters from the experimental in vitro data it is essential to determine parameter uniqueness (or otherwise) from this imposed output structure. This is formally performed as a structural identifiability analysis, which demonstrates that all of the unknown model parameters are uniquely determined by the output structure corresponding to the experiment.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology T Technology > TA Engineering (General). Civil engineering (General)
Divisions:	Faculty of Science, Engineering and Medicine > Engineering > Engineering
Library of Congress Subject Headings (LCSH):	Pharmacokinetics -- Mathematical models, Aldehyde dehydrogenase, Parameter estimation, Breast -- Cancer -- Treatment -- Research
Journal or Publication Title:	Computer Methods and Programs in Biomedicine
Publisher:	Elsevier Ireland Ltd.
ISSN:	01692607
Official Date:	November 2011
Dates:	Date Event November 2011 Published
Volume:	Vol.104
Number:	No.2
Page Range:	pp. 93-103
DOI:	10.1016/j.cmpb.2010.06.008
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Date of first compliant deposit:	17 December 2015
Date of first compliant Open Access:	17 December 2015
Version or Related Resource:	This item was also submitted to the 7th IFAC Symposium on Modelling and Control in Biomedical Systems, Aalborg, Denmark, Aug 12 - 14, 2009.

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