Linked Life Data

15956259

Source:http://linkedlifedata.com/resource/pubmed/id/15956259

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-6-15
pubmed:abstractText
Conditionally replicative adenoviruses (CRAd) are under investigation as anticancer agents. Previously, we found that the CRAd AdDelta24-p53, expressing the p53 tumor suppressor protein from its genome, more effectively killed most human cancer cells than did its parent AdDelta24. However, a minority of cancer cell lines poorly responded to the oncolysis-enhancing effect of p53. Here we show that refractory cell lines expressed high levels of the major negative p53 regulator murine double minute 2 (MDM2). To obviate MDM2-mediated inactivation of CRAd-encoded p53, we constructed the new CRAd AdDelta24-p53(14/19) encoding a p53 variant incapable of binding to MDM2. AdDelta24-p53(14/19) was approximately 10 times more effective than AdDelta24-p53 in killing cancer cell lines with high levels of human MDM2, but not cells with low MDM2. This finding supports the notion that exogenous expression of functional p53 augments the anticancer efficacy of CRAds. In addition, it confirms that high MDM2 expression is a molecular determinant of resistance against oncolysis enhancement by exogenous wild-type p53. Moreover, it shows that efficacy enhancement by restoration of functional p53 can also be accomplished in cancer cells expressing a p53 inhibitor. This further expands the utility of CRAds expressing functional p53 variants for effective virotherapy of cancer and thus their possible contribution to the advancement of individualized molecular medicine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1013-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Conditionally replicative adenovirus expressing degradation-resistant p53 for enhanced oncolysis of human cancer cells overexpressing murine double minute 2.
pubmed:affiliation
Division of Gene Therapy, Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands. vw.vanbeusechem@vumc.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't