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Compartmental modelling of the uptake kinetics of the anti‐cancer agent topotecan in human breast cancer cells
Author(s) -
Evans Neil D.,
Errington Rachel J.,
Chapman Michael J.,
Smith Paul J.,
Chappell Michael J.,
Godfrey Keith R.
Publication year - 2005
Publication title -
international journal of adaptive control and signal processing
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 66
eISSN - 1099-1115
pISSN - 0890-6327
DOI - 10.1002/acs.856
Subject(s) - topotecan , in silico , kinetics , human breast , cytoplasm , extracellular , cancer cell , biophysics , in vitro , chemistry , breast cancer , cell culture , cancer research , cancer , biological system , biology , biochemistry , physics , genetics , chemotherapy , quantum mechanics , gene
A compartmental model for the in vitro uptake kinetics of the anti‐cancer agent topotecan is proposed. This model provides a description of the activity of the drug, and subsequent delivery of active form to the nuclear DNA target. The unknown model parameters are estimated from two‐photon laser‐scanning microscopy data, which provide concentrations of topotecan (active plus inactive forms) in the extracellular region containing live human breast tumour cells (MCF‐7 cell line), the cytoplasm and the nucleus. This determines an output structure for which the model is uniquely identifiable, that is, the unknown parameters are uniquely determined from noise‐free, continuous and perfect data. The model allows in silico predictions of the dose dependence of target binding. Copyright © 2005 John Wiley & Sons, Ltd.