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

Diffusivity and distribution of vinblastine in three-dimensional tumour tissue: Experimental and mathematical modelling
Diffusivity and distribution of vinblastine in three-dimensional tumour tissue: Experimental and mathematical modelling
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 [3H]-vinblastine and [14C]-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
multicellular resistance, colon cancer, 3-D tumour model, multicell layer, vinblastine, diffusion, mathematical modelling
0959-8049
2404-2413
Modok, Szabolcs
548ec586-aa64-4fe1-a9ed-6db5fc82679d
Hyde, Phillip
576f8516-711f-4a68-b690-6e2685a1907b
Mellor, Howard R.
519439f0-1222-48eb-b1ac-3bbb8752f8ea
Roose, Tiina
3581ab5b-71e1-4897-8d88-59f13f3bccfe
Callaghan, Richard
92e7f9b1-3022-4411-ba0b-5bf9f0a3b67e
Modok, Szabolcs
548ec586-aa64-4fe1-a9ed-6db5fc82679d
Hyde, Phillip
576f8516-711f-4a68-b690-6e2685a1907b
Mellor, Howard R.
519439f0-1222-48eb-b1ac-3bbb8752f8ea
Roose, Tiina
3581ab5b-71e1-4897-8d88-59f13f3bccfe
Callaghan, Richard
92e7f9b1-3022-4411-ba0b-5bf9f0a3b67e

Modok, Szabolcs, Hyde, Phillip, Mellor, Howard R., Roose, Tiina and Callaghan, Richard (2006) Diffusivity and distribution of vinblastine in three-dimensional tumour tissue: Experimental and mathematical modelling. European Journal of Cancer, 42 (14), 2404-2413. (doi:10.1016/j.ejca.2006.05.020).

Record type: Article

Abstract

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 [3H]-vinblastine and [14C]-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

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More information

Published date: September 2006
Keywords: multicellular resistance, colon cancer, 3-D tumour model, multicell layer, vinblastine, diffusion, mathematical modelling

Identifiers

Local EPrints ID: 145143
URI: http://eprints.soton.ac.uk/id/eprint/145143
ISSN: 0959-8049
PURE UUID: d3f48751-194f-45a7-accc-6d7b6a94bf14
ORCID for Tiina Roose: ORCID iD orcid.org/0000-0001-8710-1063

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Date deposited: 21 Jun 2010 10:40
Last modified: 08 Jan 2022 03:08

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Contributors

Author: Szabolcs Modok
Author: Phillip Hyde
Author: Howard R. Mellor
Author: Tiina Roose ORCID iD
Author: Richard Callaghan

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