| Targeting for insulin-like growth factor-I receptor with short hairpin RNA for human digestive/gastrointestinal cancers. | |
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MedLine Citation:
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PMID: 19902140 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND AIMS: Insulin-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. METHODS: 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. RESULTS: 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. CONCLUSIONS: shIGF-IR may have therapeutic utility in human digestive/gastrointestinal cancers, both alone and in combination with chemotherapy. |
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Authors:
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Yu Wang; Yasushi Adachi; Arisa Imsumran; Hiroyuki Yamamoto; Wenhua Piao; Hua Li; Masanori Ii; Yoshiaki Arimura; Mi Young Park; Dalrae Kim; Choon-Taek Lee; David P Carbone; Kohzoh Imai; Yasuhisa Shinomura |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-10 |
Journal Detail:
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Title: Journal of gastroenterology Volume: 45 ISSN: 1435-5922 ISO Abbreviation: J. Gastroenterol. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-02-15 Completed Date: 2010-05-11 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9430794 Medline TA: J Gastroenterol Country: Japan |
Other Details:
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Languages: eng Pagination: 159-70 Citation Subset: IM |
Affiliation:
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First Department of Internal Medicine, Sapporo Medical University, W-16 Chuo-ku, Sapporo 060-8543, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics Animals Antineoplastic Agents / pharmacology Apoptosis Cell Line, Tumor Cell Proliferation Combined Modality Therapy Dose-Response Relationship, Drug Female Gastrointestinal Neoplasms / physiopathology, therapy* Gene Targeting / methods Genetic Vectors Humans Insulin / metabolism Mice Mice, Inbred BALB C Mice, Nude RNA, Small Interfering / administration & dosage* Receptor, IGF Type 1 / antagonists & inhibitors*, metabolism Receptor, Insulin / metabolism* Signal Transduction Xenograft Model Antitumor Assays |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/RNA, Small Interfering; 11061-68-0/Insulin; EC 2.7.10.1/Receptor, IGF Type 1; EC 2.7.10.1/Receptor, Insulin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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