ID | 50689 |
フルテキストURL | |
著者 |
Onishi, Manabu
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg
Ichikawa, Tomotsugu
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg
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Kurozumi, Kazuhiko
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg
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Fujii, Kentaro
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg
Yoshida, Koichi
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg
Inoue, Satoshi
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg
Michiue, Hiroyuki
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg
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Chiocca, E. Antonio
Brigham & Womens Faulkner Hosp, Dept Neurosurg
Kaur, Balveen
Ohio State Univ, Dept Neurol Surg, Dardinger Lab Neurooncol & Neurosci
Date, Isao
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg
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抄録 | Integrins are expressed in tumor cells and tumor endothelial cells, and likely play important roles in glioma angiogenesis and invasion. We investigated the anti-glioma mechanisms of cilengitide (EMD121974), an v3 integrin inhibitor, utilizing the novel invasive glioma models, J3T-1 and J3T-2. Immunohistochemical staining of cells in culture and brain tumors in rats revealed positive v3 integrin expression in J3T-2 cells and tumor endothelial cells, but not in J3T-1 cells. Established J3T-1 and J3T-2 orthotopic gliomas in athymic rats were treated with cilengitide or solvent. J3T-1 gliomas showed perivascular tumor cluster formation and angiogenesis, while J3T-2 gliomas showed diffuse single-cell infiltration without obvious angiogenesis. Cilengitide treatment resulted in a significantly decreased diameter of the J3T-1 tumor vessel clusters and its core vessels when compared with controls, while an anti-invasive effect was shown in the J3T-2 glioma with a significant reduction of diffuse cell infiltration around the tumor center. The survival of cilengitide-treated mice harboring J3T-1 tumors was significantly longer than that of control animals (median survival: 57.5 days and 31.8 days, respectively, P<0.005), while cilengitide had no effect on the survival of mice with J3T-2 tumors (median survival: 48.9 days and 48.5, P=0.69). Our results indicate that cilengitide exerts a phenotypic anti-tumor effect by inhibiting angiogenesis and glioma cell invasion. These two mechanisms are clearly shown by the experimental treatment of two different animal invasive glioma models.
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キーワード | angiogenesis
animal model
glioma
integrin
invasion
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発行日 | 2013-04
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出版物タイトル |
Neuropathology
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巻 | 33巻
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号 | 2号
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開始ページ | 162
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終了ページ | 174
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ISSN | 0919-6544
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資料タイプ |
学術雑誌論文
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オフィシャル URL | http://dx.doi.org/10.1111/j.1440-1789.2012.01344.x
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関連URL | http://ousar.lib.okayama-u.ac.jp/metadata/50658
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言語 |
英語
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論文のバージョン | author
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査読 |
有り
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DOI | |
Web of Science KeyUT |