Source:http://linkedlifedata.com/resource/pubmed/id/10969793
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
16
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pubmed:dateCreated |
2000-9-14
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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.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2',5'-oligoadenylate,
http://linkedlifedata.com/resource/pubmed/chemical/Adenine Nucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Cation Exchange Resins,
http://linkedlifedata.com/resource/pubmed/chemical/Cations,
http://linkedlifedata.com/resource/pubmed/chemical/Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/Lipofectamine,
http://linkedlifedata.com/resource/pubmed/chemical/Liposomes,
http://linkedlifedata.com/resource/pubmed/chemical/Oligoribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Oligoribonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Telomerase
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
60
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4461-7
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pubmed:dateRevised |
2007-11-14
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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
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pubmed:year |
2000
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pubmed:articleTitle |
2-5A antisense telomerase RNA therapy for intracranial malignant gliomas.
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pubmed:affiliation |
Center for Surgery Research, The Cleveland Clinic Foundation, Ohio 44195, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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