Cited 85 times in
Short hairpin RNA-expressing oncolytic adenovirus-mediated inhibition of IL-8: effects on antiangiogenesis and tumor growth inhibition
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 강윤아 | - |
dc.contributor.author | 김재성 | - |
dc.contributor.author | 김주항 | - |
dc.contributor.author | 윤채옥 | - |
dc.date.accessioned | 2015-05-19T16:46:34Z | - |
dc.date.available | 2015-05-19T16:46:34Z | - |
dc.date.issued | 2008 | - |
dc.identifier.issn | 0969-7128 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/106923 | - |
dc.description.abstract | RNA interference, due to its target specificity, may be highly effective as a novel therapeutic modality, but direct delivery of synthetic small interfering RNA still remains a major obstacle for this approach. To induce long-term expression and specific gene silencing, novel delivery vector system is also required. In this study, we have generated an efficient oncolytic adenovirus (Ad)-based short hairpin (shRNA) expression system (Ad-DeltaB7-U6shIL8) against IL-8, a potent proangiogenic factor. To demonstrate IL-8-specificity of this newly engineered Ad-based shRNA, we also manufactured replication-incompetent Ads (Ad-DeltaE1-CMVshIL8 and Ad-DeltaE1-U6shIL8) under the control of the cytomegalovirus (CMV) and U6 promoters, respectively. Ad-DeltaE1-U6shIL8 was highly effective in reducing IL-8 expression, and was much more effective in driving IL-8-specific shRNA than the CMV promoter-driven vector. The reduced IL-8 expression then translated into decreased angiogenesis in vitro as measured by migration, tube formation and rat aortic ring sprouting assays. In addition to its effect on endothelial cells, Ad-DeltaE1-U6shIL8 also effectively suppressed the migration and invasion of cancer cells. In vivo, intratumoral injection of Ad-DeltaB7-U6shIL8 significantly inhibited the growth of Hep3B and A549 human tumor xenografts. Histopathological analysis of Ad-DeltaB7-U6shIL8-treated tumors revealed an increase in apoptotic cells and a reduction in vessel density. Finally, Ad-DeltaB7-U6shIL8 was also shown to inhibit the growth of disseminated MDA-MB-231 breast cancer metastases. Taken together, these findings demonstrate the utility and antitumor effectiveness of oncolytic Ad expressing shRNA against IL-8. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 635~651 | - |
dc.relation.isPartOf | GENE THERAPY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Adenoviridae/genetics* | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Breast Neoplasms/therapy* | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Endothelial Cells/metabolism | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Gene Silencing | - |
dc.subject.MESH | Genetic Engineering | - |
dc.subject.MESH | Genetic Therapy/methods* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Interleukin-8/analysis | - |
dc.subject.MESH | Interleukin-8/genetics* | - |
dc.subject.MESH | Interleukin-8/metabolism | - |
dc.subject.MESH | Lung Neoplasms/secondary | - |
dc.subject.MESH | Lung Neoplasms/therapy | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Matrix Metalloproteinase 2/analysis | - |
dc.subject.MESH | Matrix Metalloproteinase 2/metabolism | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Nude | - |
dc.subject.MESH | Neoplasm Invasiveness | - |
dc.subject.MESH | Neovascularization, Pathologic/genetics | - |
dc.subject.MESH | Oncolytic Virotherapy/methods* | - |
dc.subject.MESH | Promoter Regions, Genetic | - |
dc.subject.MESH | RNA Interference | - |
dc.subject.MESH | RNA, Small Interfering/administration & dosage* | - |
dc.subject.MESH | Transduction, Genetic/methods | - |
dc.subject.MESH | Vascular Endothelial Growth Factor A/analysis | - |
dc.subject.MESH | Vascular Endothelial Growth Factor A/metabolism | - |
dc.subject.MESH | Xenograft Model Antitumor Assays | - |
dc.title | Short hairpin RNA-expressing oncolytic adenovirus-mediated inhibition of IL-8: effects on antiangiogenesis and tumor growth inhibition | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Medical Research Center (임상의학연구센터) | - |
dc.contributor.googleauthor | JY Yoo | - |
dc.contributor.googleauthor | J-H Kim | - |
dc.contributor.googleauthor | J Kim | - |
dc.contributor.googleauthor | J-H Huang | - |
dc.contributor.googleauthor | SN Zhang | - |
dc.contributor.googleauthor | Y-A Kang | - |
dc.contributor.googleauthor | H Kim | - |
dc.contributor.googleauthor | C-O Yun | - |
dc.identifier.doi | 10.1038/gt.2008.3 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00066 | - |
dc.contributor.localId | A00945 | - |
dc.contributor.localId | A02614 | - |
dc.contributor.localId | A00860 | - |
dc.relation.journalcode | J00924 | - |
dc.identifier.eissn | 1476-5462 | - |
dc.identifier.pmid | 18273054 | - |
dc.identifier.url | http://www.nature.com/gt/journal/v15/n9/full/gt20083a.html | - |
dc.subject.keyword | cancer gene therapy | - |
dc.subject.keyword | IL-8 | - |
dc.subject.keyword | short hairpin RNA (shRNA) | - |
dc.subject.keyword | oncolytic adenovirus | - |
dc.contributor.alternativeName | Kang, Yoon-A | - |
dc.contributor.alternativeName | Kim, Jae Sung | - |
dc.contributor.alternativeName | Kim, Joo Hang | - |
dc.contributor.alternativeName | Yun, Chae Ok | - |
dc.contributor.affiliatedAuthor | Kang, Yoon-A | - |
dc.contributor.affiliatedAuthor | Kim, Joo Hang | - |
dc.contributor.affiliatedAuthor | Yun, Chae Ok | - |
dc.contributor.affiliatedAuthor | Kim, Jaesung | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 15 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 635 | - |
dc.citation.endPage | 651 | - |
dc.identifier.bibliographicCitation | GENE THERAPY, Vol.15(9) : 635-651, 2008 | - |
dc.identifier.rimsid | 56368 | - |
dc.type.rims | ART | - |
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