The Mathematical Institute, University of Oxford, Eprints Archive

Quiescience as a mechanism for cyclical hypoxia and acidosis

Smallbone, K. and Gavaghan, D. J. and Maini, P. K. and Brady, J. M. (2007) Quiescience as a mechanism for cyclical hypoxia and acidosis. Journal of Mathematical Biology, 55 (5-6). pp. 767-779. ISSN n/a

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Abstract

Tumour tissue characteristically experiences fluctuations in substrate supply. This unstable microenvironment drives constitutive metabolic changes within cellular populations and, ultimately, leads to a more aggressive phenotype. Previously, variations in substrate levels were assumed to occur through oscillations in the hæmodynamics of nearby and distant blood vessels. In this paper we examine an alternative hypothesis, that cycles of metabolite concentrations are also driven by cycles of cellular quiescence and proliferation. Using a mathematical modelling approach, we show that the interdependence between cell cycle and the microenvironment will induce typical cycles with the period of order hours in tumour acidity and oxygenation. As a corollary, this means that the standard assumption of metabolites entering diffusive equilibrium around the tumour is not valid; instead temporal dynamics must be considered.

Item Type:Article
Additional Information:n/a
Uncontrolled Keywords:Acidity - Hypoxia - Delay differential equations
Subjects:A - C > Biology and other natural sciences
Research Groups:Centre for Mathematical Biology
ID Code:669
Deposited By:Philip Maini
Deposited On:14 Nov 2007
Last Modified:20 Jul 2009 14:23

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