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The role of p53 in the chemotherapeutic responses to cisplatin, doxorubicin and 5-fluorouracil treatment

Dart, Dafydd Alwyn, Picksley, Steven M., Cooper, Patricia A., Double, John A. and Bibby, Michael C. 2004. The role of p53 in the chemotherapeutic responses to cisplatin, doxorubicin and 5-fluorouracil treatment. International Journal of Oncology 24 (1) , pp. 115-125.

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Abstract

A panel of tumour models used extensively for in vivo evaluation of new drugs was characterised for their p53 status. Basal p53 protein levels were measured by immunodetection on both formalin-fixed tumour tissue and from protein extracts of fresh tumours. High levels of nuclear-specific staining, indicative of p53 mutation, was seen in 15/25 tumours, with the remainder showing intermittent or no staining. The functional status of p53 cDNA from these tumours was assayed within the functional analysis of separated alleles in yeast (F.A.S.A.Y.) reporter system. The cDNA from those tumours with high levels of p53 protein showed 14/15 failing to activate the reporter gene. The cDNA from tumours with low or non-detectable p53 levels showed 8/10 with wild-type p53. Tumours were grown subcutaneously in mice (n=10). Each mouse was given maximum tolerated doses for either doxorubicin, 5-fluorouracil or cisplatin. Tumour volumes were measured daily, alongside untreated controls. The specific growth delay values for each tumour were separated into two groups, those with functional p53 (wild-type) and those without (mutant and null status). The Mann-Whitney U test was performed on the groups of data, to evaluate differences in their response on the basis of p53 status. Cisplatin was moderately active against tumours with wild-type and mutant p53 genes with no significant difference seen between both groups. However, a significant difference in specific growth delay was seen between the two groups when treated with doxorubicin or 5-fluorouracil (P=0.05), indicating a role for p53 protein in modulating the in vivo efficacy of these agents.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/1019-6439/ (accessed 21/02/2014).
Publisher: Spandidos Publications
ISSN: 1019-6439
Date of First Compliant Deposit: 30 March 2016
Last Modified: 17 May 2023 15:41
URI: https://orca.cardiff.ac.uk/id/eprint/50282

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