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Article: A novel glioblastoma cancer gene therapy using AAV-mediated long-term expression of human TERT C-terminal polypeptide

TitleA novel glioblastoma cancer gene therapy using AAV-mediated long-term expression of human TERT C-terminal polypeptide
Authors
KeywordsAAV
Glioblastoma
hTERTC27
Issue Date2007
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/cgt
Citation
Cancer Gene Therapy, 2007, v. 14 n. 6, p. 561-572 How to Cite?
AbstractGlioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosis, infiltration of polymorphonuclear neutrophils and reduced microvessel density in the tumor samples. To study the molecular mechanism of rAAV-hTERTC27-mediated antitumor effects, we analyzed the global gene expression profiles of the rAAV-hTERTC27-treated tumor tissues and cell line as compared with that of the control rAAV-green fluorescent protein-treated samples by DNA microarray. Our results suggest that hTERTC27 exerts its effect through complex mechanisms, which involve genes regulating apoptosis, cell adhesion, cell cycle, immune responses, metabolism, signal transduction, transport, transcription and telomere maintenance. © 2007 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/68803
ISSN
2015 Impact Factor: 2.532
2015 SCImago Journal Rankings: 1.020
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorNg, SSMen_HK
dc.contributor.authorGao, Yen_HK
dc.contributor.authorChau, DHWen_HK
dc.contributor.authorLi, GHYen_HK
dc.contributor.authorLai, LHen_HK
dc.contributor.authorHuang, PTen_HK
dc.contributor.authorHuang, CFen_HK
dc.contributor.authorHuang, JJen_HK
dc.contributor.authorChen, YCen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorLin, MCMen_HK
dc.date.accessioned2010-09-06T06:07:52Z-
dc.date.available2010-09-06T06:07:52Z-
dc.date.issued2007en_HK
dc.identifier.citationCancer Gene Therapy, 2007, v. 14 n. 6, p. 561-572en_HK
dc.identifier.issn0929-1903en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68803-
dc.description.abstractGlioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosis, infiltration of polymorphonuclear neutrophils and reduced microvessel density in the tumor samples. To study the molecular mechanism of rAAV-hTERTC27-mediated antitumor effects, we analyzed the global gene expression profiles of the rAAV-hTERTC27-treated tumor tissues and cell line as compared with that of the control rAAV-green fluorescent protein-treated samples by DNA microarray. Our results suggest that hTERTC27 exerts its effect through complex mechanisms, which involve genes regulating apoptosis, cell adhesion, cell cycle, immune responses, metabolism, signal transduction, transport, transcription and telomere maintenance. © 2007 Nature Publishing Group All rights reserved.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/cgten_HK
dc.relation.ispartofCancer Gene Therapyen_HK
dc.subjectAAVen_HK
dc.subjectGlioblastomaen_HK
dc.subjecthTERTC27en_HK
dc.titleA novel glioblastoma cancer gene therapy using AAV-mediated long-term expression of human TERT C-terminal polypeptideen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0929-1903&volume=14&issue=6&spage=561&epage=72&date=2007&atitle=A+Novel+Glioblastoma+Cancer+Gene+Therapy+Using+AAV-mediated+Long-term+Expression+of+Human+TERT+C-terminal+Polypeptideen_HK
dc.identifier.emailNg, SSM: ssmng@hku.hken_HK
dc.identifier.emailLin, MCM: mcllin@hkucc.hku.hken_HK
dc.identifier.authorityNg, SSM=rp00767en_HK
dc.identifier.authorityLin, MCM=rp00746en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.cgt.7701038en_HK
dc.identifier.pmid17384579-
dc.identifier.scopuseid_2-s2.0-34249027012en_HK
dc.identifier.hkuros126385en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34249027012&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume14en_HK
dc.identifier.issue6en_HK
dc.identifier.spage561en_HK
dc.identifier.epage572en_HK
dc.identifier.isiWOS:000246550800005-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridNg, SSM=7403358718en_HK
dc.identifier.scopusauthoridGao, Y=54792979500en_HK
dc.identifier.scopusauthoridChau, DHW=16315084100en_HK
dc.identifier.scopusauthoridLi, GHY=37045133800en_HK
dc.identifier.scopusauthoridLai, LH=12445800200en_HK
dc.identifier.scopusauthoridHuang, PT=7403658582en_HK
dc.identifier.scopusauthoridHuang, CF=7406879416en_HK
dc.identifier.scopusauthoridHuang, JJ=7407194640en_HK
dc.identifier.scopusauthoridChen, YC=24075600300en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridLin, MCM=7404816359en_HK
dc.identifier.citeulike1183912-

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