Linked Life Data

15201989

Source:http://linkedlifedata.com/resource/pubmed/id/15201989

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-6-17
pubmed:abstractText
Recently, we have reported the therapeutic efficacy of delivering initiator caspase (caspase-8) or executioner active caspase (rev-caspase-6) to telomerase-positive malignant glioma cells using the human telomerase reverse transcriptase (hTERT) gene promoter system (hTERT/caspase-8 or hTERT/rev-caspase-6). In the present study, we investigated if conventional treatments for malignant gliomas augment the efficacy of the hTERT/caspase therapy. First, we demonstrated that hTERT/rev-caspase-6 exhibited a greater ability to induce apoptosis in malignant glioma U87-MG and U373-MG cells than hTERT/caspase-8. Next, as conventional treatments to combine with hTERT/rev-caspase-6, apoptosis-inducing agents [cisplatin (CDDP), paclitaxel (PTX), and BCNU] and non-apoptosis-inducing therapies [temozolomide (TMZ) and gamma-irradiation (IR)] were used. Combination of hTERT/rev-caspase-6 gene therapy with PTX yielded a dose-dependent additive effect, while CDDP and BCNU had additive effect only when tumor cells were treated at IC75 of each agent. A decline in the combination effect of CDDP and BCNU at IC50 was due to decreased activity of telomerase in treated tumor cells prior to the hTERT/rev-caspase-6 transfer. On the other hand, TMZ or IR had no significant additive effect on induction of apoptosis. These results suggest that agents, which induce apoptosis without inhibiting telomerase activity are a promising counterpart to combine with hTERT/rev-caspase-6 therapy for the management of malignant gliomas.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
57-63
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Combination of caspase transfer using the human telomerase reverse transcriptase promoter and conventional therapies for malignant glioma cells.
pubmed:affiliation
Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't