Linked Life Data

10656431

Source:http://linkedlifedata.com/resource/pubmed/id/10656431

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-2-28
pubmed:abstractText
The value of p53 to predict the cytotoxic effect of two commonly used chemotherapy regimens was assessed in patients with advanced breast cancer. Response to a DNA-damaging combination therapy [fluorouracil, epirubicin, cyclophosphamide (FEC] considered to induce p53-dependent apoptosis was compared with a microtubule stabilizing therapy (paclitaxel) expected to be independent of p53 function. The p53 status of the patients' breast tumors was assessed using both immunohistochemistry (IHC) and direct sequencing of the entire p53 gene. p53 findings were correlated with treatment response, and linkage between p53 function and cellular response was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. In a series of 67 breast tumors, 19% had TP53 gene mutations, 40% had a positive p53 IHC, and 12% had both. In the FEC group, treatment failure was related to both the presence of TP53 gene mutations (P = 0.0029) and a positive IHC (P < 0.0001). Apoptosis was almost exclusively found in tumors having normal p53 in both parameters (P < 0.0001). In the paclitaxel group, treatment response was neither related to apoptosis nor to normal p53. Combination of sequencing and IHC results revealed a significant association between abnormal p53 and response to paclitaxel (P = 0.011). We found TP53 mutations, as well as p53 protein overexpression, to be associated with response to chemotherapy. Whereas clinical response to FEC was found to be dependent on normal p53, the cytotoxicity of paclitaxel was related to defective p53. The efficiency of paclitaxel during mitosis might be supported by lack of G1 arrest due to p53 deficiency. Therefore, patients with p53-deficient tumors may benefit from paclitaxel.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
50-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10656431-Antineoplastic Agents, Phytogenic, pubmed-meshheading:10656431-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:10656431-Apoptosis, pubmed-meshheading:10656431-Breast Neoplasms, pubmed-meshheading:10656431-Codon, pubmed-meshheading:10656431-Cyclophosphamide, pubmed-meshheading:10656431-Epirubicin, pubmed-meshheading:10656431-Exons, pubmed-meshheading:10656431-Female, pubmed-meshheading:10656431-Fluorouracil, pubmed-meshheading:10656431-Genes, p53, pubmed-meshheading:10656431-Humans, pubmed-meshheading:10656431-Immunohistochemistry, pubmed-meshheading:10656431-Introns, pubmed-meshheading:10656431-Mutation, pubmed-meshheading:10656431-Neoadjuvant Therapy, pubmed-meshheading:10656431-Neoplasm Staging, pubmed-meshheading:10656431-Paclitaxel, pubmed-meshheading:10656431-Tumor Suppressor Protein p53
pubmed:year
2000
pubmed:articleTitle
TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients.
pubmed:affiliation
Department of Surgery, University of Vienna Medical School, Austra. Daniela.Kandioler@akh-wien.ac.at
pubmed:publicationType
Journal Article, Clinical Trial, Controlled Clinical Trial, Research Support, Non-U.S. Gov't, Clinical Trial, Phase II