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Suppressive control of glioma invasions via inhibition of sodium ion/proton exchanger 1

Research Project

Project/Area Number 23592130
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cerebral neurosurgery
Research InstitutionEhime University

Principal Investigator

YANO Hajime  愛媛大学, 医学(系)研究科(研究院), 准教授 (00284414)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords神経膠腫 / 潜行性浸潤 / ナトリウムイオン/プロトン交換輸送体1 / EIPA / TGFbeta シグナル / ナトリウム/プロトン交換輸送体1 / 血管新生 / TGFbeta / 扁平上皮がん / リンパ節転移 / NHE1 / グリオーマ / マイクログリア / 脳マクロファージ / 活性酸素 / 臨床検体
Research Abstract

Preclinical evaluations for the development of a novel anti-tumor invasion medicine by utilization of 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) which had exhibited promising potential in vitro were performed, aiming at developing a novel powerful therapy against gliomas of which treatment has long been unimproved. On the way of the explorations of modes of action of EIPA, a characteristic blood vessel was found to contribute to the glioma cell invasions, and an implication that activation process of TGFbeta1 may participate in this step was obtained. Furthermore, the validity to consider EIPA as an anti-tumor invasion medicine was confirmed from the observation of contributions of the target of EIPA sodium ion/proton exchanger1 (NHE1) on lymph node metastasis of head and neck squamous cell carcinoma cells (SCC). Highly metastatic subline-cell of a SCC acquired enhanced expression of NHE1 compared with the non-metastatic parental cell line, and knockdown of NHE1 reduced the metastasis.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (45 results)

All 2014 2013 2012 2011 Other

All Journal Article (11 results) (of which Peer Reviewed: 7 results) Presentation (33 results) Remarks (1 results)

  • [Journal Article] Activated microglia in a rat stroke model express NG2 proteoglycan in peri-infarct tissue through the involvement of TGF-β12014

    • Author(s)
      SUGIMOTO Kana, NISHIOKA Ryutaro, IKEDA Airi, MISE Ayano, TAKAHASHI Hisaaki, YANO Hajime, KUMON Yoshiaki, OHNISHI Takanori, TANAKA Junya
    • Journal Title

      Glia

      Volume: 62 Issue: 2 Pages: 185-198

    • DOI

      10.1002/glia.22598

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activated microglia in a rat stroke model express NG2 proteoglycan in peri-infarct tissue through the involvement of TGF-β12013

    • Author(s)
      Sugimoto, K., Nishioka, R., Ikeda, A., Mise, A., Takahashi, H., Yano, H., Kumon, Y., Ohnishi, T., and Tanaka, J
    • Journal Title

      Glia

      Volume: 62 Pages: 185-198

    • Related Report
      2013 Final Research Report
  • [Journal Article] Expression of MCP-1 and fractalkine on endothelial cells and astrocytes may contribute to the invasion and migration of brain macrophages in ischemic rat brain lesions2013

    • Author(s)
      N., Tanaka, J., Sugimoto, K., Nishihara, T., Nishioka, R., Takahashi, H., Yano, H., Matsumoto, S., Ohue, S., Watanabe, H., Kumon, T., and Ohnishi, T. J. Neurosci
    • Journal Title

      Tei Res

      Volume: 91 Pages: 681-693

    • Related Report
      2013 Final Research Report
  • [Journal Article] Expression of MCP-1 and fractalkine on endothelial cells and astrocytes may contribute to the invasion and migration of brain macrophages in ischemic rat brain lesions2013

    • Author(s)
      Nari Tei
    • Journal Title

      J Neurosci Res

      Volume: 91 Issue: 5 Pages: 681693-681693

    • DOI

      10.1002/jnr.23202

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oct3/4 promotes migration and invasion of glioblastoma cells2012

    • Author(s)
      Kobayashi, K., Takahashi, H., Inoue, A., Harada, H., Toshimori, S., Kobayashi, Y., Goto, K., Sugimoto, K., Yano, H., Ohnishi, T., and Tanaka, J
    • Journal Title

      J. Cell. Biochem

      Volume: 113 Pages: 508-517

    • Related Report
      2013 Final Research Report
  • [Journal Article] Premetastatic vasculogenesis in oral squamous cell carcinoma xenograft-draining lymph nodes2012

    • Author(s)
      Mayorca-Guiliani, A, E., Yano, H., Nakashiro, K., Hamakawa, H., and Tanaka, J
    • Journal Title

      Oral Oncology

      Volume: 48 Pages: 663-758

    • Related Report
      2013 Final Research Report
  • [Journal Article] Premetastatic vasculogenesis in oral squamous cell carcinoma xenograft-draining lymph nodes2012

    • Author(s)
      Mayorca-Guiliani AE
    • Journal Title

      Oral Oncology

      Volume: 48 Issue: 8 Pages: 663670-663670

    • DOI

      10.1016/j.oraloncology.2012.02.007

    • Related Report
      2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oct-3/4 promotes migration and invasion of glioblastoma cells2012

    • Author(s)
      Kobayashi K
    • Journal Title

      J Cell Biochem

      Volume: 113 Issue: 2 Pages: 508517-508517

    • DOI

      10.1002/jcb.23374

    • Related Report
      2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transient ischemia-induced paresis and complete paraplegia displayed distinct reactions of microglia and macrophages2011

    • Author(s)
      Nakata, T., et al
    • Journal Title

      Brain research

      Volume: 1420 Pages: 114-124

    • DOI

      10.1016/j.brainres.2011.08.074

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] A cytokine mixture of GM-CSF and IL-3 that induces a neuroprotective phenotype of microglia leading to amelioration of (6-OHDA)-induced Parkinsonism of rats2011

    • Author(s)
      Choudhry, E., et al
    • Journal Title

      Brain and Behavior

      Volume: 1 Issue: 1 Pages: 26-43

    • DOI

      10.1002/brb3.11

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Subcutaneous injection containing IL-3 and GM-CSF ameliorates stab wound-induced brain injury in rats2011

    • Author(s)
      Nishihara, T., et al
    • Journal Title

      Experimental neurology

      Volume: 229 Issue: 2 Pages: 507-516

    • DOI

      10.1016/j.expneurol.2011.04.006

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Contributions of TGFβ1 on insidious glioma cell invasions in the experimental glioma and exploration of the source of the TGFβ12014

    • Author(s)
      Haruna Yaguchi, Kohei Shiota, Takefumi Shimoda, Hajime Yano, Kana Sugimoto, Hisaaki Takahashi, and Junya Tanaka
    • Organizer
      第91回日本生理学会
    • Place of Presentation
      鹿児島市
    • Related Report
      2013 Final Research Report
  • [Presentation] Exploration of the mechanism of TGFβ1 production from glioma associated macrophage-like cells in experimental glioma2014

    • Author(s)
      Noriko Nomura, Haruna Yaguchi, Kohei Shiota, Takefumi Shimoda, Hajime Yano, Kana Sugimoto, Hisaaki Takahashi, and Junya Tanaka
    • Organizer
      第91回日本生理学会
    • Place of Presentation
      鹿児島市
    • Related Report
      2013 Final Research Report
  • [Presentation] Suppression of draining lymph node metastasis of oral squamous cell carcinoma by inhibition of the factors secreted from primary tumor site at pre-metastatic phase2014

    • Author(s)
      Hajime Yano, Teppei Kaminota, Noriko Nomura, Yusuke Kobayashi, Yui Kirino, Kana Sugimoto, Hisaaki Takahashi, and Junya Tanaka
    • Organizer
      第91回日本生理学会
    • Place of Presentation
      鹿児島市
    • Related Report
      2013 Final Research Report
  • [Presentation] Suppression of draining lymph node metastasis of oral squamous cell carcinoma by  inhibition of the factors secreted from primary tumor site at pre-metastatic phase2014

    • Author(s)
      Hajime Yano, Teppei Kaminota, Noriko Nomura, Yusuke Kobayashi, Yui Kirino, Kana Sugimoto, Hisaaki  Takahashi, and Junya Tanaka
    • Organizer
      第 91 回日本生理学会
    • Place of Presentation
      鹿児島市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Exploration of the mechanism of TGFβ1 production from glioma associated macrophage-like cells in experimental glioma2014

    • Author(s)
      Noriko Nomura, Haruna Yaguchi, Kohei Shiota, Takefumi Shimoda, Hajime Yano, Kana Sugimoto, Hisaaki Takahashi, and Junya Tanaka
    • Organizer
      第 91 回日本生理学会
    • Place of Presentation
      鹿児島市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Contributions of TGFβ1 on insidious glioma cell invasions in the experimental glioma and exploration of the source of the TGFβ12014

    • Author(s)
      Haruna Yaguchi, Kohei Shiota, Takefumi Shimoda, Hajime Yano, Kana Sugimoto, Hisaaki Takahashi, and Junya   Tanak
    • Organizer
      第 91 回日本生理学会
    • Place of Presentation
      鹿児島市
    • Related Report
      2013 Annual Research Report
  • [Presentation] グリオーマ潜行性浸潤モデルの構築とNHE1阻害による潜行性浸潤抑制2013

    • Author(s)
      矢口明那、下田健文、塩田浩平、矢野元
    • Organizer
      第23回日本病態生理学会
    • Place of Presentation
      東京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 神経膠腫病巣内に浸潤する脳マクロファージ様細胞におけるナトリウムイオン/プロトン交換輸送体1の役割の解析2013

    • Author(s)
      矢野元、野村倫子、矢口明那、下田健文、塩田浩平
    • Place of Presentation
      東京都
    • Related Report
      2013 Final Research Report
  • [Presentation] Na^+/H^+ Exchanger 1 (NHE1) as a molecular target to suppress glioblastoma invasion2013

    • Author(s)
      Haruna Yaguchi, Takefumi Shimoda, Kohei Shiota, Kana Sugimoto, Hisaaki Takahashi, Hajime Yano and Junya Tanaka
    • Organizer
      第90回日本生理学会
    • Place of Presentation
      東京都
    • Related Report
      2013 Final Research Report
  • [Presentation] Exploration of the mechanism of TGFβ1 production from glioma associated macrophage-like cells in experimental glioma2013

    • Author(s)
      Noriko Nomura, Haruna Yaguchi, Kohei Shiota, Takefumi Shimoda, Hajime Yano, Kana Sugimoto, Hisaaki Takahashi, and Junya Tanaka
    • Organizer
      第90回日本生理学会
    • Place of Presentation
      東京都
    • Related Report
      2013 Final Research Report
  • [Presentation] An attempt of anti-metastasis therapy based on analyses of pre-metastatic microenvironmental reconstruction in target lymph node upon squamous cell carcinoma metastasis2013

    • Author(s)
      Kohei Shiota, Alejandro Mayorca Guilliani, Haruna Yaguchi, Takefumi Shimoda, Kana Sugimoto, Hisaaki Takahashi, Hajime Yano and Junya Tanaka
    • Organizer
      第90回日本生理学会
    • Place of Presentation
      東京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 神経膠腫病巣内に浸潤する脳マクロファージ様   細胞における ナトリウムイオン/プロトン交換輸送体 1 の役割の解析2013

    • Author(s)
      矢野元、野村倫子、矢口明那、下田健文、塩田浩平
    • Organizer
      第 23 回日本病態生理学会
    • Place of Presentation
      東京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] グリオーマ潜行性浸潤モデルの構築と NHE1 阻害による潜行   性浸潤抑制2013

    • Author(s)
      矢口明那、下田健文、塩田浩平、矢野元
    • Organizer
      第 23 回日本病態生理学会
    • Place of Presentation
      東京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] Na+/H+ Exchanger 1 (NHE1) as a molecular target to suppress glioblastoma invasion2013

    • Author(s)
      Haruna Yaguchi, Takefumi Shimoda, Kohei Shiota, Kana Sugimoto, Hisaaki Takahashi, Hajime Yano and Junya Tanaka
    • Organizer
      第 90 会日本生理学会大会
    • Place of Presentation
      東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] Analysis of the mode of action of 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) on the inhibition of glioma cell invasion2013

    • Author(s)
      Takefumi Shimoda, Haruna Y, Kohei S, Hajime Y, Kana S, Hisaaki T and Junya T
    • Organizer
      第 90 会日本生理学会大会
    • Place of Presentation
      東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] Expression of Sodium ion / proton exchanger 1(NHE1) in macrophage-like cells recruited into the ischemic brain.2013

    • Author(s)
      Noriko Nomura, Yusuke Kobayashi, Mika Horiuchi, Kohei Shiota, Hajime Yano, Kana Sugimoto, Hisaaki Takahashi, and Junya Tanaka
    • Organizer
      第 90 会日本生理学会大会
    • Place of Presentation
      東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] Suppressive control of N-cadherin mediated cell-cell adhesion by a chondroitin sulfate proteoglycan, NG22013

    • Author(s)
      Mika Horiuchi, Noriko Nomura, Yusuke Kobayashi, Tomohiro Kawamura, Kohei Shiota, Hajime Yano, Kana Sugimoto, Hisaaki Takahashi and Junya Tanaka
    • Organizer
      第 90 会日本生理学会大会
    • Place of Presentation
      東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] A possible anti-metastasis therapy based on analyses of pre-metastatic microenvironmental reconstruction in target lymph nodes upon squamous cell carcinoma metastasis2013

    • Author(s)
      Kohei Shiota, Alejandro Mayorca Guiliani, Hajime Yano, Kana Sugimoto, Hisaaki Takahashi and Junya Tanaka
    • Organizer
      第 90 会日本生理学会大会
    • Place of Presentation
      東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] ナトリウムイオン/プロトン交換輸送体1(NHE1)を標的とした神経膠腫細胞浸潤抑制治療の試み2012

    • Author(s)
      矢口明那、下田健文、塩田浩平、矢野元杉本香奈、高橋寿明、田中潤也
    • Organizer
      第64回日本生理学会中四国地方会
    • Place of Presentation
      高知市
    • Related Report
      2013 Final Research Report
  • [Presentation] 神経膠腫細胞浸潤抑制における5-(N-ethyl-N-isopropyl)- amiloride (EIPA)の作用機序の解析2012

    • Author(s)
      下田健文、矢口明那、塩田浩平、矢野元杉本香奈、高橋寿明、田中潤也
    • Organizer
      第64回日本生理学会中四国地方会
    • Place of Presentation
      高知市
    • Related Report
      2013 Final Research Report
  • [Presentation] 扁平上皮がんのリンパ節転移に先立転移標的組織構築改変とがん細胞浸潤性の関連について2012

    • Author(s)
      塩田浩平、矢野元、Alejandro Mayorca Guiliani,杉本香奈、高橋寿明、田中潤也
    • Organizer
      第22回日本病態生理学会
    • Place of Presentation
      大分市
    • Related Report
      2013 Final Research Report
  • [Presentation] Sodium / Proton exchanger 1 (NHE1) as a molecular target for “anti-invasion therapy” of malignant gliomas2012

    • Author(s)
      Kohei Shiota, Hajime Yano, Kana Sugimoto, Hisaaki Takahashi, Junya Tanaka.
    • Organizer
      The 3rd Symposium of the INTERNATIONAL SOCIETY FOR PROTON DYNAMICS IN CANCER
    • Place of Presentation
      京都市
    • Related Report
      2012 Research-status Report
  • [Presentation] Analyses of the modes of action of 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) on inhibition of glioma cell invasions2012

    • Author(s)
      Hajime Yano, Kohei Shiota, Kana Sugimoto, Hisaaki Takahashi, Junya Tanaka.
    • Organizer
      The 3rd Symposium of the INTERNATIONAL SOCIETY FOR PROTON DYNAMICS IN CANCER
    • Place of Presentation
      京都市
    • Related Report
      2012 Research-status Report
  • [Presentation] ナトリウムイオン / プロトン交換輸送体1(NHE1) を標的とした 神経膠腫細胞浸潤抑制治療の試み2012

    • Author(s)
      矢口明那、下田健文、塩田浩平、矢野 元 杉本香奈、高橋寿明、田中潤也
    • Organizer
      第 64 回日本生理学会中四国地方会
    • Place of Presentation
      高知市
    • Related Report
      2012 Research-status Report
  • [Presentation] 神経膠腫細胞浸潤抑制における 5-(N-ethyl-N-isopropyl)- amiloride (EIPA) の作用機序の解析2012

    • Author(s)
      下田健文、矢口明那、塩田浩平、矢野 元 杉本香奈、高橋寿明、田中潤也
    • Organizer
      第 64 回日本生理学会中四国地方会
    • Place of Presentation
      高知市
    • Related Report
      2012 Research-status Report
  • [Presentation] コンドロイチン硫酸プロテオグリカン NG2 による カドヘリン接着の抑制的制御2012

    • Author(s)
      矢野 元、矢口明那、下田健文、塩田浩平、杉本香奈、高橋寿明、田中潤也
    • Organizer
      第 64 回日本生理学会中四国地方会
    • Place of Presentation
      高知市
    • Related Report
      2012 Research-status Report
  • [Presentation] Sodium / Proton exchanger 1 (NHE1) as a therapeutic molecular target for anti-invasion therapy of malignant gliomas2012

    • Author(s)
      Kohei Shiota, Hajime Yano, Kana Sugimoto, Hisaaki Takahashi, Junya Tanaka
    • Organizer
      日本生理学会
    • Place of Presentation
      松本市
    • Related Report
      2011 Research-status Report
  • [Presentation] Analyses of the modes of action of 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) on inhibition of glioma cell invasions2012

    • Author(s)
      Hajime Yano, Kohei Shiota, Kana Sugimoto, Hisaaki Takahashi, Junya Tanaka
    • Organizer
      日本生理学会
    • Place of Presentation
      松本市
    • Related Report
      2011 Research-status Report
  • [Presentation] Possible regulation of cell adhesiveness by a chondroitinsulfate proteoglycan, NG22012

    • Author(s)
      Kawamura Tomohiro, Kohei Shiota, Hajime Yano, Kana Sugimoto, Hisaaki Takahashi, Jyunya Tanaka
    • Organizer
      日本生理学会
    • Place of Presentation
      松本市
    • Related Report
      2011 Research-status Report
  • [Presentation] ナトリウムイオン/プロトン交換輸送体(NHE1)阻害による神経膠腫細胞浸潤抑制の試み2011

    • Author(s)
      塩田浩平、和田愛子、矢野元、杉本香奈、高橋寿明、田中潤也
    • Organizer
      日本病態生理学会
    • Place of Presentation
      東京都
    • Related Report
      2011 Research-status Report
  • [Presentation] ナトリウムイオン / プロトン交換輸送体 1 (NHE1) 細胞内局在と糖鎖修飾の関与の可能性2011

    • Author(s)
      矢野元、塩田 浩平、和田 愛子、杉本 香奈、高橋 寿明、田中 潤也
    • Organizer
      日本病態生理学会
    • Place of Presentation
      東京都
    • Related Report
      2011 Research-status Report
  • [Presentation] ナトリウムイオン/プロトン交換輸送体1(NHE1)阻害による神経膠腫細胞浸潤抑制2011

    • Author(s)
      塩田浩平、矢野元、杉本香奈、高橋寿明、田中潤也
    • Organizer
      グリア研究会
    • Place of Presentation
      名古屋市
    • Related Report
      2011 Research-status Report
  • [Presentation] NG2 による細胞接着性の制御について2011

    • Author(s)
      矢野 元、河村智宏、塩田浩平、杉本香奈、高橋寿明、田中潤也
    • Organizer
      グリア研究会
    • Place of Presentation
      名古屋市
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://hgyano.jimdo.com/

    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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