Linked Life Data

15569999

Source:http://linkedlifedata.com/resource/pubmed/id/15569999

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2004-11-30
pubmed:abstractText
Overexpression of Bcl-2 protein in cancer cells can inhibit programmed cell death and engender chemoresistance. Reducing Bcl-2 protein levels by using antisense oligonucleotides targeting the gene message can increase the sensitivity of cancer cells to cytotoxic agents. The objective of this work was to investigate the antitumor efficacy of the Bcl-2 antisense oligonucleotide oblimersen (Genasense; G3139), alone and in combination with vinorelbine (VNB), in an ectopic and orthotopic xenograft model of NCI-H460 human non-small-cell lung cancer. In addition to assessing therapeutic effect, Bcl-2 protein expression in tumor tissue isolated from lung and heart was measured. In the ectopic xenograft model, oblimersen at 5 and 10 mg/kg significantly inhibited tumor growth compared with saline-treated control groups, and furthermore, the antitumor effect of oblimersen was associated with down-regulation of Bcl-2 protein in isolated tumor tissue. Moreover, the combination of oblimersen with VNB was more active in inhibiting tumor growth than either drug used alone. In the orthotopic model, oblimersen treatment (5 mg/kg) increased the median survival time of mice to 33 days in comparison with a median survival time of 21 days in the control animals. With this model, the anticancer effect was demonstrated by assessing tumor growth in lung and heart tissues by hematoxylin and eosin staining and Bcl-2 expression by immunohistochemistry. When VNB at 5 mg/kg was combined with oblimersen administered at 5 mg/kg, 33% of mice survived more than 90 days. These data suggest that the combination of oblimersen and VNB may provide enhanced antitumor activities against non-small-cell lung cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7662-70
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Antitumor efficacy of oblimersen Bcl-2 antisense oligonucleotide alone and in combination with vinorelbine in xenograft models of human non-small cell lung cancer.
pubmed:affiliation
Genzyme Corporation, Framingham, Massachusetts, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't