Diffusivity and distribution of vinblastine in three-dimensional tumour tissue: Experimental and mathematical modelling

被引:19
作者
Modok, Szabolcs
Hyde, Philip
Mellor, Howard R.
Roose, Tiina
Callaghan, Richard [1 ]
机构
[1] Univ Oxford, John Radcliffe Hosp, Oxford Drug Resistance Grp, Nuffield Dept Clin Lab Sci, Oxford OX3 9DU, England
[2] Univ Oxford, Inst Math, Oxford Ctr Ind & Appl Math, Oxford OX1 3LB, England
[3] Univ Oxford, Inst Math, Ctr Math Biol, Oxford OX1 3LB, England
关键词
multicellular resistance; colon cancer; 3-D tumour model; multicell layer; vinblastine; diffusion; mathematical modelling;
D O I
10.1016/j.ejca.2006.05.020
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The distribution of chemotherapeutics in solid tumours is poorly understood and the contribution it makes to treatment failure is unknown. Novel approaches are required to understand how the three-dimensional organisation of cancer cells in solid tumours affects drug availability. Since convective drug transport is limited by increased interstitial pressure in poorly vascularised cancers, the aim of this study was to measure the diffusive hindrance exerted by solid tumour tissue. Multicell layer tumour models comprising DLD1 colon cancer cells were characterised and fluxes were determined for [H-3]-vinblastine and [C-14]-sucrose. The mathematical models provided the diffusion coefficients for both compounds and predicted higher exposure of cells in the vicinity of vessels. The diffusion of vinblastine was three times slower than that of sucrose. Although slow diffusion delays vinblastine penetration into the avascular regions of tumours, the proliferating cells are generally in the marginal area of tumours. The mathematical model that we have developed enabled accurate quantification of drug pharmacokinetic behaviour, in particular, the diffusivity of vinblastine within solid tissue. This mathematical model may be adapted readily to incorporate the influence of factors mediating pharmacokinetic drug resistance. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2404 / 2413
页数:10
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