Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-12-5
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
115-25
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14654948-Animals, pubmed-meshheading:14654948-Antineoplastic Agents, pubmed-meshheading:14654948-Blotting, Western, pubmed-meshheading:14654948-Cisplatin, pubmed-meshheading:14654948-Doxorubicin, pubmed-meshheading:14654948-Female, pubmed-meshheading:14654948-Fluorouracil, pubmed-meshheading:14654948-Humans, pubmed-meshheading:14654948-Immunohistochemistry, pubmed-meshheading:14654948-Mice, pubmed-meshheading:14654948-Mice, Inbred Strains, pubmed-meshheading:14654948-Mice, Nude, pubmed-meshheading:14654948-Mutation, pubmed-meshheading:14654948-Neoplasms, pubmed-meshheading:14654948-Saccharomyces cerevisiae, pubmed-meshheading:14654948-Transformation, Genetic, pubmed-meshheading:14654948-Tumor Suppressor Protein p53, pubmed-meshheading:14654948-Xenograft Model Antitumor Assays
pubmed:year
2004
pubmed:articleTitle
The role of p53 in the chemotherapeutic responses to cisplatin, doxorubicin and 5-fluorouracil treatment.
pubmed:affiliation
Cancer Research Unit, University of Bradford, Bradford BD7 1DP, UK.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't