The Mathematical Institute, University of Oxford, Eprints Archive

A mathematical model of tumour & blood pHe regulation: The HCO-3/CO2 buffering system

Martin, N K and Gaffney, E. A. and Gatenby, R A and Gillies, R. J. and Robey, I F and Maini, P. K. (2011) A mathematical model of tumour & blood pHe regulation: The HCO-3/CO2 buffering system. Mathematical Biosciences, 230 (1). pp. 1-11.

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Abstract

Malignant tumours are characterised by a low, acidic extracellular pH (pHe) which facilitates invasion and metastasis. Previous research has proposed the potential benefits of manipulating systemic pHe, and recent experiments have highlighted the potential for buffer therapy to raise tumour pHe, prevent metastases, and prolong survival in laboratory mice. To examine the physiological regulation of tumour buffering and investigate how perturbations of the buffering system (via metabolic/respiratory disorders or changes in parameters) can alter tumour and blood pHe, we develop a simple compartmentalised ordinary differential equation model of pHe regulation by the View the MathML source buffering system. An approximate analytical solution is constructed and used to carry out a sensitivity analysis, where we identify key parameters that regulate tumour pHe in both humans and mice. From this analysis, we suggest promising alternative and combination therapies, and identify specific patient groups which may show an enhanced response to buffer therapy. In addition, numerical simulations are performed, validating the model against well-known metabolic/respiratory disorders and predicting how these disorders could change tumour pHe.

Item Type:Article
Uncontrolled Keywords: Buffering; Acidity; Cancer; Bicarbonate
Subjects:A - C > Biology and other natural sciences
Research Groups:Centre for Mathematical Biology
ID Code:1051
Deposited By:Philip Maini
Deposited On:02 Mar 2011 08:10
Last Modified:02 Mar 2011 08:10

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