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Targeting for insulin-like growth factor-I receptor with short hairpin RNA for human digestive/gastrointestinal cancers

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dc.contributor.authorWang, Yu-
dc.contributor.authorAdachi, Yasushi-
dc.contributor.authorImsumran, Arisa-
dc.contributor.authorYamamoto, Hiroyuki-
dc.contributor.authorLi, Hua-
dc.contributor.authorArimura, Yoshiaki-
dc.contributor.authorKim, Dalrae-
dc.contributor.authorCarbone, David P.-
dc.contributor.authorShinomura, Yasuhisa-
dc.contributor.authorImai, Kohzoh-
dc.contributor.authorLee, Choon-Taek-
dc.contributor.authorPark, Mi Young-
dc.contributor.authorIi, Masanori-
dc.contributor.authorPiao, Wenhua-
dc.date.accessioned2012-05-29T08:47:57Z-
dc.date.available2012-05-29T08:47:57Z-
dc.date.issued2010-02-
dc.identifier.citationJOURNAL OF GASTROENTEROLOGY; Vol.45 2; 159-170ko_KR
dc.identifier.issn0944-1174-
dc.identifier.urihttps://hdl.handle.net/10371/76574-
dc.description.abstractInsulin-like growth factor (IGF)-I receptor (IGF-IR) signaling plays important parts in both the tumorigenicity and progression of digestive/gastrointestinal malignancies. In this study, we sought to test the effectiveness of a practical approach to blocking IGF-IR signaling using RNA interference delivered by recombinant adenoviruses. We constructed a recombinant adenovirus expressing short hairpin RNA targeting IGF-IR (shIGF-IR) and assessed its effect on signal transduction, proliferation, and survival in digestive/gastrointestinal cancer cell lines representing colorectal, gastric, and pancreatic adenocarcinoma, esophageal squamous cell carcinoma, and hepatoma. We analyzed the effects of shIGF-IR alone and with chemotherapy in vitro and in nude mouse xenografts, as well as on insulin signaling and hybrid receptor formation between IGF-IR and insulin receptor. shIGF-IR blocked expression and autophosphorylation of IGF-IR and downstream signaling by the IGFs, but not by insulin. shIGF-IR suppressed proliferation and carcinogenicity in vitro and up-regulated apoptosis in a dose-dependent fashion. shIGF-IR augmented the effects of chemotherapy on in vitro growth and apoptosis induction. Moreover, the combination of shIGF-IR and chemotherapy was highly effective against tumors in mice. shIGF-IR reduced hybrid receptor formation without effect on expression of insulin receptor. shIGF-IR may have therapeutic utility in human digestive/gastrointestinal cancers, both alone and in combination with chemotherapy.ko_KR
dc.language.isoenko_KR
dc.publisherSPRINGER TOKYOko_KR
dc.subjectCombination therapyko_KR
dc.subjectRNAiko_KR
dc.subjectShort hairpin RNAko_KR
dc.subjectInsulin like growth factor-I receptor (IGF-IR)ko_KR
dc.subjectDigestive/gastrointestinal cancersko_KR
dc.titleTargeting for insulin-like growth factor-I receptor with short hairpin RNA for human digestive/gastrointestinal cancersko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor박미영-
dc.contributor.AlternativeAuthor김달래-
dc.contributor.AlternativeAuthor이춘택-
dc.identifier.doi10.1007/s00535-009-0151-6-
dc.citation.journaltitleJOURNAL OF GASTROENTEROLOGY-
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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