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著作: [内田 大亮]/[尾上 富太郎]/[栗林 伸行]/Tomizuka Yoshifumi/[玉谷 哲也]/[永井 宏和]/[宮本 洋二]/Blockade of CXCR4 in oral squamous cell carcinoma inhibits lymph node metastases./[European Journal of Cancer]

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EID
228666
EOID
908628
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0
LastModified
2018年6月12日(火) 16:09:28
Operator
三木 ちひろ
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Owner
玉谷 哲也
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種別 必須 学術論文(審査論文)
言語 必須 英語
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著者 必須
  1. 内田 大亮
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  2. 尾上 富太郎
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  3. 栗林 伸行
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  4. (英) Tomizuka Yoshifumi
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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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(英) Blockade of CXCR4 in oral squamous cell carcinoma inhibits lymph node metastases.

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(英) We have previously demonstrated that a stromal cell-derived factor-1 (SDF-1; CXCL12)/CXCR4 system is involved in the establishment of lymph node metastasis in oral squamous cell carcinoma (OSCC). In this study, we investigated whether the blockade of CXCR4 inhibits lymph node metastasis in B88 OSCC cells. These cells harbour a functional CXCR4 and have the potential to metastasise to the lymph node in vivo. Following introduction of a vector that expresses short hairpin small interfering RNA (shRNA) against CXCR4, we isolated three clones (shCXCR4-16, -17 and -21) that showed decreased expression of CXCR4 mRNA. These clones also had reduced CXCR4 protein levels and showed impairments in calcium flux and cell migration in response to SDF-1. These cells were orthotopically inoculated into the masseter muscle of nude mice. Lymph node metastases, loss in body weight and tumour volumes were significantly inhibited in mice inoculated with shCXCR4-17 cells compared to mice inoculated with control cells. SDF-1-induced migration of B88 cells was significantly inhibited in vitro by the treatment with 1,1'-[1,4-phenylenebis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane octahydrochloride (AMD3100), a CXCR4 antagonist. Subcutaneous administration of AMD3100 significantly inhibited the lymph node metastases of B88 cells when they were orthotopically inoculated into the masseter muscle of nude mice. Moreover, the enhanced production of interleukin (IL)-6 and IL-8 in response to SDF-1 was inhibited by shRNA against CXCR4 or by treatment with AMD3100. These results suggest that blockade of CXCR4 may be a potent anti-metastatic therapy against lymph node metastases in cases of CXCR4-related OSCC.

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誌名 必須 European Journal of Cancer(The European CanCer Organisation/European Organization for Research and Treatment of Cancer/The European Association for Cancer Research/The European Society of Breast Cancer Specialists)
(pISSN: 0959-8049, eISSN: 1879-0852)
ISSN 任意 1879-0852
ISSN: 0959-8049 (pISSN: 0959-8049, eISSN: 1879-0852)
Title: European journal of cancer (Oxford, England : 1990)
Title(ISO): Eur. J. Cancer
Publisher: Elsevier Ltd.
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 47
必須 3
必須 452 459
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年月日 必須 2011年 2月 初日
URL 任意
DOI 任意 10.1016/j.ejca.2010.09.028    (→Scopusで検索)
PMID 任意 20965717    (→Scopusで検索)
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  1. (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, 3-18-15 Kuramoto, Tokushima, Japan. daisuke@dent.tokushima-u.ac.jp

  2. (英) Article.PublicationTypeList.PublicationType: Journal Article

  3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't