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Novel cancer antiangiotherapy using the VEGF promoter-targeted artificial zinc-finger protein and oncolytic adenovirus

DC Field Value Language
dc.contributor.author유지영-
dc.contributor.author윤채옥-
dc.contributor.author강윤아-
dc.contributor.author김주항-
dc.date.accessioned2015-05-19T16:45:54Z-
dc.date.available2015-05-19T16:45:54Z-
dc.date.issued2008-
dc.identifier.issn1525-0016-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/106902-
dc.description.abstractInhibition of tumor angiogenesis through modulation of vascular endothelial growth factor (VEGF) and its signaling pathway has been clinically validated as a viable therapeutic modality in the treatment of cancer. The use of artificial transcription factors based on Cys2-His2 zinc-finger proteins (ZFPs) targeting the VEGF promoter offers a novel strategy for modulating VEGF levels in tumors. In order to demonstrate the utility of VEGF-targeted ZFPs as therapeutic agents, we generated adenoviruses (Ads) expressing VEGF promoter-targeted transcriptional repressor ZFP, F435-KOX. A replication-incompetent Ad expressing F435-KO X, namely, Ad-DeltaE1-KOX, significantly reduced VEGF expression and functionally led to inhibition of angiogenesis. In vivo, an oncolytic Ad expressing F435-KOX, namely, Ad-DeltaB7-KOX, elicited a pronounced antitumor effect against a human glioblastoma xenograft model, U87MG. Further, consistent with its expected mechanism of action, Ad-DeltaB7-KOX was shown to greatly reduce the level of VEGF and vessel density in tumor tissue and increase terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive apoptotic cells in tumors. Survival rates were also significantly increased in Ad-DeltaB7-KOX-treated mice. Taken together, the findings from this study identify F435-KOX as a novel and potent ZFP transcription factor that can inhibit VEGF-A-mediated angiogenesis and offer a novel therapeutic modality in the treatment of cancer.-
dc.description.statementOfResponsibilityopen-
dc.format.extent1033~1040-
dc.relation.isPartOfMOLECULAR THERAPY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdenoviridae/genetics*-
dc.subject.MESHAngiogenesis Inhibitors/pharmacology*-
dc.subject.MESHAnimals-
dc.subject.MESHApoptosis-
dc.subject.MESHEndothelium, Vascular/cytology-
dc.subject.MESHGlioblastoma/therapy-
dc.subject.MESHHumans-
dc.subject.MESHMice-
dc.subject.MESHNeoplasm Transplantation-
dc.subject.MESHOncolytic Viruses/genetics*-
dc.subject.MESHPromoter Regions, Genetic-
dc.subject.MESHRats-
dc.subject.MESHRats, Sprague-Dawley-
dc.subject.MESHVascular Endothelial Growth Factor A/genetics*-
dc.subject.MESHVascular Endothelial Growth Factor A/metabolism-
dc.subject.MESHZinc Fingers*-
dc.titleNovel cancer antiangiotherapy using the VEGF promoter-targeted artificial zinc-finger protein and oncolytic adenovirus-
dc.typeArticle-
dc.contributor.collegeResearcher Institutes (부설 연구소)-
dc.contributor.departmentInstitute for Cancer Research (암연구소)-
dc.contributor.googleauthorYoon-A Kang-
dc.contributor.googleauthorHyun-Chul Shin-
dc.contributor.googleauthorJi Young Yoo-
dc.contributor.googleauthorJoo-Hang Kim-
dc.contributor.googleauthorJin-Soo Kim-
dc.contributor.googleauthorChae-Ok Yun-
dc.identifier.doi10.1038/mt.2008.63-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA02516-
dc.contributor.localIdA02614-
dc.contributor.localIdA00066-
dc.contributor.localIdA00945-
dc.relation.journalcodeJ02271-
dc.identifier.eissn1525-0024-
dc.identifier.pmid18398429-
dc.identifier.urlhttp://www.nature.com/mt/journal/v16/n6/full/mt200863a.html-
dc.subject.keywordAdenoviridae/genetics*-
dc.subject.keywordAngiogenesis Inhibitors/pharmacology*-
dc.subject.keywordAnimals-
dc.subject.keywordApoptosis-
dc.subject.keywordEndothelium, Vascular/cytology-
dc.subject.keywordGlioblastoma/therapy-
dc.subject.keywordHumans-
dc.subject.keywordMice-
dc.subject.keywordNeoplasm Transplantation-
dc.subject.keywordOncolytic Viruses/genetics*-
dc.subject.keywordPromoter Regions, Genetic-
dc.subject.keywordRats-
dc.subject.keywordRats, Sprague-Dawley-
dc.subject.keywordVascular Endothelial Growth Factor A/genetics*-
dc.subject.keywordVascular Endothelial Growth Factor A/metabolism-
dc.subject.keywordZinc Fingers*-
dc.contributor.alternativeNameYoo, Ji Yeong-
dc.contributor.alternativeNameYun, Chae Ok-
dc.contributor.alternativeNameKang, Yoon-A-
dc.contributor.alternativeNameKim, Joo Hang-
dc.contributor.affiliatedAuthorYoo, Ji Yeong-
dc.contributor.affiliatedAuthorYun, Chae Ok-
dc.contributor.affiliatedAuthorKang, Yoon-A-
dc.contributor.affiliatedAuthorKim, Joo Hang-
dc.rights.accessRightsnot free-
dc.citation.volume16-
dc.citation.number6-
dc.citation.startPage1033-
dc.citation.endPage1040-
dc.identifier.bibliographicCitationMOLECULAR THERAPY, Vol.16(6) : 1033-1040, 2008-
dc.identifier.rimsid50923-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers

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