Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-7-14
pubmed:abstractText
Ependymomas are the third most common pediatric brain tumor with an overall survival of approximately 50%. Recently, we showed that telomerase [human telomerase reverse transcriptase (hTERT)] expression is a predictor of poor outcome in pediatric ependymoma. Thus, we hypothesized that ependymomas with functional telomerase may behave more aggressively and that these patients may benefit from anti-telomerase therapy. To address our hypothesis, we investigated the effect of telomerase inhibition on primary ependymoma cells harvested at the time of surgery, as no animal models or established cell lines are readily available for this tumor. The cells were characterized for glial fibrillary acidic protein (GFAP) and hTERT expression, initial telomere length and telomerase activity. They were then subjected to telomerase inhibition (MST-312, 1 microM) and tested for effects on cell viability (MTT assay), proliferation (MIB-1), apoptosis (cleaved caspase 3) and DNA damage (gammaH2AX). After 72 h of telomerase inhibition, primary ependymoma cells showed a significant decrease in cell number (P < 0.001), accompanied by increased DNA damage (gammaH2AX expression) (P < 0.01) and decreased proliferative index (MIB-1) (P < 0.01). Half showed an increase in apoptosis (cleaved caspase 3). These data suggest that telomerase inhibition may be an effective adjuvant therapy in pediatric ependymoma, potentially inducing tumor growth arrest in the short term, independent of telomere shortening.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1750-3639
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
780-6
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Telomerase inhibition as a novel therapy for pediatric ependymoma.
pubmed:affiliation
Division of Pathology, The Hospital for Sick Children, Toronto, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't