| pubmed-article:15001986 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15001986 | lifeskim:mentions | umls-concept:C0007600 | lld:lifeskim |
| pubmed-article:15001986 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:15001986 | lifeskim:mentions | umls-concept:C0007102 | lld:lifeskim |
| pubmed-article:15001986 | lifeskim:mentions | umls-concept:C0334227 | lld:lifeskim |
| pubmed-article:15001986 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:15001986 | lifeskim:mentions | umls-concept:C0312418 | lld:lifeskim |
| pubmed-article:15001986 | lifeskim:mentions | umls-concept:C0123931 | lld:lifeskim |
| pubmed-article:15001986 | lifeskim:mentions | umls-concept:C1332721 | lld:lifeskim |
| pubmed-article:15001986 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:15001986 | lifeskim:mentions | umls-concept:C0036667 | lld:lifeskim |
| pubmed-article:15001986 | lifeskim:mentions | umls-concept:C2349975 | lld:lifeskim |
| pubmed-article:15001986 | pubmed:issue | 9 | lld:pubmed |
| pubmed-article:15001986 | pubmed:dateCreated | 2004-3-5 | lld:pubmed |
| pubmed-article:15001986 | pubmed:abstractText | Mutations in the tumor-suppressor gene p53 have been associated with advanced colorectal cancer (CRC). Irinotecan (CPT-11), a DNA topoisomerase 1 inhibitor, has been recently incorporated to the adjuvant therapy. Since the DNA-damage checkpoint depends on p53 activation, the status of p53 might critically influence the response to CPT-11. We analysed the sensitivity to CPT-11 in the human colon cancer cell line HT29 (mut p53) and its wild-type (wt)-p53 stably transfected subclone HT29-A4. Cell-cycle analysis in synchronised cells demonstrated the activation of transfected wt-p53 and a p21(WAF1/CIP1)-dependent cell-cycle blockage in the S phase. Activated wt-p53 increased apoptosis and enhanced sensitivity to CPT-11. In p53-deficient cells, cDNA-macroarray analysis and western blotting showed an accumulation of the cyclin-dependent kinase (cdk)1/cyclin B complex. Subsequent p53-independent activation of the cdk-inhibitor (cdk-I) p21(WAF1/CIP1) prevented cell-cycle progression. Cdk1 induction was exploited in vivo to improve the sensitivity to CPT-11 by additional treatment with the cdk-I CYC-202. We demonstrate a gain of sensitivity to CPT-11 in a p53-mutated colon cancer model either by restoring wild-type p53 function or by sequential treatment with cdk-Is. Considering that mutations in p53 are among the most common genetic alterations in CRC, a therapeutic approach specifically targeting p53-deficient tumors could greatly improve the treatment outcomes. | lld:pubmed |
| pubmed-article:15001986 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15001986 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15001986 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:15001986 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15001986 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15001986 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15001986 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15001986 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15001986 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:15001986 | pubmed:issn | 0950-9232 | lld:pubmed |
| pubmed-article:15001986 | pubmed:author | pubmed-author:PouponMarie-F... | lld:pubmed |
| pubmed-article:15001986 | pubmed:author | pubmed-author:LouvardDaniel... | lld:pubmed |
| pubmed-article:15001986 | pubmed:author | pubmed-author:MagdelenatHen... | lld:pubmed |
| pubmed-article:15001986 | pubmed:author | pubmed-author:RobineSylvieS | lld:pubmed |
| pubmed-article:15001986 | pubmed:author | pubmed-author:AbalMiguelM | lld:pubmed |
| pubmed-article:15001986 | pubmed:author | pubmed-author:De... | lld:pubmed |
| pubmed-article:15001986 | pubmed:author | pubmed-author:Bras-Goncalve... | lld:pubmed |
| pubmed-article:15001986 | pubmed:author | pubmed-author:JuddeJean-Gab... | lld:pubmed |
| pubmed-article:15001986 | pubmed:author | pubmed-author:FsihiHafidaH | lld:pubmed |
| pubmed-article:15001986 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15001986 | pubmed:day | 4 | lld:pubmed |
| pubmed-article:15001986 | pubmed:volume | 23 | lld:pubmed |
| pubmed-article:15001986 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15001986 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15001986 | pubmed:pagination | 1737-44 | lld:pubmed |
| pubmed-article:15001986 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:15001986 | pubmed:meshHeading | pubmed-meshheading:15001986... | lld:pubmed |
| pubmed-article:15001986 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:15001986 | pubmed:articleTitle | Enhanced sensitivity to irinotecan by Cdk1 inhibition in the p53-deficient HT29 human colon cancer cell line. | lld:pubmed |
| pubmed-article:15001986 | pubmed:affiliation | Transfer Laboratory, Institut Curie-CNRS, Paris 75248, France. | lld:pubmed |
| pubmed-article:15001986 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15001986 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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