Title
Kinetic modelling of the role of the aldehyde dehydrogenase enzyme and the breast cancer resistance protein in drug resistance and transport
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.
Year
DOI
Venue
2011
10.1016/j.cmpb.2010.06.008
Computer Methods and Programs in Biomedicine
Keywords
Field
DocType
extended model,vitro uptake kinetics,vitro data,unknown model parameter,scanning-laser microscopy data,compartmental model,aldehyde dehydrogenase enzyme,dna target,breast cancer resistance protein,drug resistance,output structure,drug activity,kinetic modelling,parameter estimation,hplc,efflux pumps,aldehyde dehydrogenase,efflux pump,liquid chromatography,kinetics,aldh,glycoprotein,dna,enzyme
Computer vision,Enzyme,Abcg2,Aldehyde dehydrogenase,Computer science,Biophysics,In vitro,Camptothecin,Multidrug Resistance Protein 1,Artificial intelligence,P-glycoprotein,Efflux
Journal
Volume
Issue
ISSN
104
2
1872-7565
Citations 
PageRank 
References 
0
0.34
0
Authors
5
Name
Order
Citations
PageRank
M. I. Atari100.34
Michael J. Chappell2407.97
R. J. Errington300.34
P. J. Smith400.34
N. D. Evans561.37