Title of article :
A mathematical model of tumour and blood pHe regulation: The buffering system
Author/Authors :
Martin، نويسنده , , Natasha K. and Gaffney، نويسنده , , Eamonn A. and Gatenby، نويسنده , , Robert A. and Gillies، نويسنده , , Robert J. and Robey، نويسنده , , Ian F. and Maini، نويسنده , , Philip K.، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2011
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 HCO 3 - / CO 2 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.
Keywords :
bicarbonate , Acidity , Buffering , CANCER
Journal title :
Mathematical Biosciences
Journal title :
Mathematical Biosciences