『徳島大学 教育・研究者情報データベース (EDB)』---[学外] /
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EID=273787EID:273787, Map:0, LastModified:2014年2月13日(木) 13:06:57, Operator:[松井 栄里], Avail:TRUE, Censor:0, Owner:[宮本 洋二], Read:継承, Write:継承, Delete:継承.
種別 (必須): 学術論文 (審査論文) [継承]
言語 (必須): 英語 [継承]
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著者 (必須): 1.栗林 伸行
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2.内田 大亮
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3. (英) Kinouchi Makoto (日) 木内 誠 (読)
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4.髙丸 菜都美
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5.玉谷 哲也
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6.永井 宏和
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7.宮本 洋二 ([徳島大学.大学院医歯薬学研究部.歯学域.口腔科学部門.臨床歯学系.口腔外科学])
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題名 (必須): (英) The Role of Metabotropic Glutamate Receptor 5 on the Stromal Cell-Derived Factor-1/CXCR4 System in Oral Cancer  (日)    [継承]
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要約 (任意): (英) We have demonstrated that blocking CXCR4 may be a potent anti-metastatic therapy for CXCR4-related oral cancer. However, as CXCR4 antagonists are currently in clinical use to induce the mobilization of hematopoietic stem cells, continuous administration as an inhibitor for the metastasis may lead to persistent leukocytosis. In this study, we investigated the novel therapeutic downstream target(s) of the SDF-1/CXCR4 system, using B88-SDF-1 cells, which have an autocrine SDF-1/CXCR4 system and exhibit distant metastatic potential in vivo. Microarray analysis revealed that 418 genes were upregulated in B88-SDF-1 cells. We identified a gene that is highly upregulated in B88-SDF-1 cells, metabotropic glutamate receptor 5 (mGluR5), which was downregulated following treatment with 1,1' -[1,4-Phenylenebis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane octahydrochloride (AMD3100), a CXCR4 antagonist. The upregulation of mGluR5 mRNA in the SDF-1/CXCR4 system was predominately regulated by the Ras-extracellular signal-regulated kinase (ERK)1/2 pathway. Additionally, the growth of B88-SDF-1 cells was not affected by the mGluR5 agonist (S)-3,5-DHPG (DHPG) or the mGluR5 antagonists 2-Methyl-6-(phenylethynyl)pyridine (MPEP) and 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP). However, we observed that DHPG promoted B88-SDF-1 cell migration, whereas both MPEP and MTEP inhibited B88-SDF-1 cell migration. To assess drug toxicity, the antagonists were intraperitoneally injected into immunocompetent mice for 4 weeks. Mice injected with MPEP (5 mg/kg) and MTEP (5 mg/kg) did not exhibit any side effects, such as hematotoxicity, allergic reactions or weight loss. The administration of antagonists significantly inhibited the metastasis of B88-SDF-1 cells to the lungs of nude mice. These results suggest that blocking mGluR5 with antagonists such as MPEP and MTEP could prevent metastasis in CXCR4-related oral cancer without causing side effects.  (日)    [継承]
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誌名 (必須): PLoS ONE (Public Library of Science)
(eISSN: 1932-6203)

ISSN (任意): 1932-6203
ISSN: 1932-6203 (eISSN: 1932-6203)
Title: PloS one
Title(ISO): PLoS ONE
Publisher: Public Library of Science
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
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(必須): e80773 e80773 [継承]
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年月日 (必須): 西暦 2013年 11月 13日 (平成 25年 11月 13日) [継承]
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DOI (任意): 10.1371/journal.pone.0080773    (→Scopusで検索) [継承]
PMID (任意): 24236200    (→Scopusで検索) [継承]
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WOS (任意): 000327254700203 [継承]
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備考 (任意): 1.(英) Article.ELocationID: 10.1371/journal.pone.0080773  (日)    [継承]
2.(英) Article.Affiliation: Department of Oral Surgery, Subdivision of Molecular Oral Medicine, Division of Integrated Sciences of Translational Research, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan.  (日)    [継承]
3.(英) Article.PublicationTypeList.PublicationType: Journal Article  (日)    [継承]
4.(英) OtherID: PMC3827474  (日)    [継承]

標準的な表示

和文冊子 ● Nobuyuki Kuribayashi, Daisuke Uchida, Makoto Kinouchi, Natsumi Takamaru, Tetsuya Tamatani, Hirokazu Nagai and Youji Miyamoto : The Role of Metabotropic Glutamate Receptor 5 on the Stromal Cell-Derived Factor-1/CXCR4 System in Oral Cancer, PLoS ONE, Vol.8, No.11, e80773, 2013.
欧文冊子 ● Nobuyuki Kuribayashi, Daisuke Uchida, Makoto Kinouchi, Natsumi Takamaru, Tetsuya Tamatani, Hirokazu Nagai and Youji Miyamoto : The Role of Metabotropic Glutamate Receptor 5 on the Stromal Cell-Derived Factor-1/CXCR4 System in Oral Cancer, PLoS ONE, Vol.8, No.11, e80773, 2013.

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