Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2000-9-14
pubmed:abstractText
Malignant gliomas are the most common intracranial tumors and are considered incurable. Therefore, exploration of novel therapeutic modalities is essential. Telomerase is a ribonucleoprotein enzyme that is detected in the vast majority of malignant gliomas but not in normal brain tissues. We, therefore, hypothesized that telomerase inhibition could be a very promising approach for the targeted therapy of malignant gliomas. Thus, 2-5A (5'-phosphorylated 2'-5'-linked oligoadenylate)-linked antisense against human telomerase RNA component (2-5A-anti-hTER) was investigated for its antitumor effect on an intracranial malignant glioma model. 2-5A is a mediator of one pathway of IFN actions by activating RNase L, resulting in RNA degradation. By linking 2-5A to antisense, RNase L degrades the targeted RNA specifically and effectively. Prior to the experiments using intracranial tumor models in nude mice, we modified the in vitro and in vivo treatment modality of 2-5A-anti-hTER using a cationic liposome to enhance the effect of 2-5A-anti-hTER. Here we demonstrate that 2-5A-anti-hTER complexed with a cationic liposome reduced the viability of five malignant glioma cell lines to 20-43% within 4 days but did not influence the viability of cultured astrocytes lacking telomerase. Furthermore, treatment of intracranial malignant gliomas in nude mice with 2-5A-anti-hTER was therapeutically effective compared with the control (P < 0.01). These findings clearly suggest the therapeutic potentiality of 2-5A-anti-hTER as a novel approach for the treatment of intracranial malignant gliomas.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4461-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10969793-Adenine Nucleotides, pubmed-meshheading:10969793-Animals, pubmed-meshheading:10969793-Brain Neoplasms, pubmed-meshheading:10969793-Cation Exchange Resins, pubmed-meshheading:10969793-Cations, pubmed-meshheading:10969793-Female, pubmed-meshheading:10969793-Glioma, pubmed-meshheading:10969793-Humans, pubmed-meshheading:10969793-Lipids, pubmed-meshheading:10969793-Liposomes, pubmed-meshheading:10969793-Mice, pubmed-meshheading:10969793-Mice, Inbred BALB C, pubmed-meshheading:10969793-Mice, Nude, pubmed-meshheading:10969793-Neoplasm Transplantation, pubmed-meshheading:10969793-Oligoribonucleotides, pubmed-meshheading:10969793-Oligoribonucleotides, Antisense, pubmed-meshheading:10969793-RNA, Neoplasm, pubmed-meshheading:10969793-Telomerase, pubmed-meshheading:10969793-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
2-5A antisense telomerase RNA therapy for intracranial malignant gliomas.
pubmed:affiliation
Center for Surgery Research, The Cleveland Clinic Foundation, Ohio 44195, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't