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Regulatory mechanisms for microenvironment and metastasis of cancers with glycosphigolipids via extracellular vesicles

Research Project

Project/Area Number 17K19616
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Tumor biology and related fields
Research InstitutionChubu University

Principal Investigator

FURUKAWA Koichi  中部大学, 生命健康科学部, 教授 (80211530)

Project Period (FY) 2017-06-30 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywordsエクソソーム / 糖脂質 / ガングリオシド / インテグリン / GD3 / 細胞膜 / EGF受容体 / 細胞外顆粒 / 癌微小環境 / エキソソーム / 微小環境 / 癌転移 / 脂質ラフト
Outline of Final Research Achievements

Using cancer-associated glycolipid-expressing cell lines and their normal counterparts (control), secreted amounts of exosomes and levels of contained glycolipids and associated membrane proteins were analyzed. Consequently, in multiple cell line systems, exosomes derived from GD3-expressing cell lines expressed much higher amounts of integrin isoforms than those from individual GD3-negative controls. There were no definite differences in the integrin expression levels in the cell lysates between GD3-positive and GD3-negative cell lines. In the analysis of EGF receptor levels as measured similarly, they showed increase in GD3-expressing cell lines in both cell lysates and secreted exosomes. Now, we are analyzing composition of glycosphingolipids in exosomes, and also their functions.

Academic Significance and Societal Importance of the Research Achievements

癌関連糖脂質が、腫瘍マーカーとしてのみならず、癌細胞の悪性形質に重要な役割を果たすことが示されてきたが、本研究では、癌関連糖脂質を発現する細胞由来の細胞外分泌顆粒であるエクソソームが、接着受容体であるインテグリンを著明に多く含んでいることが判明した。このことから、癌細胞の浸潤、転移等の悪性形質において、細胞膜表面のみならず、癌関連糖脂質とインテグリンがエクソソームにおいても会合して、悪性形質に重要な役割を果たしていることが示唆された。とくに転移の予防においてエクソソームが標的になりうることを示唆する結果である。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (47 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (16 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 16 results,  Open Access: 11 results) Presentation (26 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results) Book (2 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] ハーバード大学(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] リール大学(フランス)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Novel molecular mechanisms for roles of gangliosides in the nervous system elucidated by genetic engineering.2020

    • Author(s)
      Furukawa, K., Ohmi, Y., Yesmin, F., Tajima, O., Kondo, Y., Pu Zhang, P., Hashimoto, N., Ohkawa, Y., Bhuiyan, R.H., Furukawa, K.
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 21 Issue: 6 Pages: 1906-1906

    • DOI

      10.3390/ijms21061906

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Elucidation of the enigma of glycosphingolipids in the regulation of inflammation and degeneration — Great progress over the last 70 years —2019

    • Author(s)
      Koichi Furukawa, Yuhsuke Ohmi, Yuji Kondo, Robiul H. Bhuiyan, Orie Tajima, Yuki Ohkawa, Keiko Furukawa
    • Journal Title

      Proceedings of the Japan Academy, Series B

      Volume: 95 Issue: 3 Pages: 136-149

    • DOI

      10.2183/pjab.95.011

    • NAID

      130007608536

    • ISSN
      0386-2208, 1349-2896
    • Year and Date
      2019-03-11
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] New era of research on cancer‐associated glycosphingolipids.2019

    • Author(s)
      Koichi Furukawa, Yuhsuke Ohmi, Yuki Ohkawa, Robiul H. Bhuiyan, Pu Zhang, Orie Tajima, Noboru Hashimoto, Kazunori Hamamura, Keiko Furukawa.
    • Journal Title

      Cancer Science

      Volume: - Issue: 5 Pages: 1-8

    • DOI

      10.1111/cas.14005

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The ceramide moiety of disialoganglioside (GD3) is essential for GD3 recognition by the sialic acid-binding lectin SIGLEC7 on the cell surface.2019

    • Author(s)
      Hashimoto N, Ito S, Tsuchida A, Bhuiyan RH, Okajima T, Yamamoto A, Furukawa K, Ohmi Y, Furukawa K.
    • Journal Title

      J Biol Chem.

      Volume: 294 Issue: 28 Pages: 10833-10845

    • DOI

      10.1074/jbc.ra118.007083

    • NAID

      120007168785

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cholera toxin B induces interleukin-1β production from resident peritoneal macrophages through the pyrin inflammasome as well as the NLRP3 inflammasome2019

    • Author(s)
      Orimo T, Sasaki I, Hemmi H, Ozasa T, Fukuda-Ohta Y, Ohta T, Morinaka M, Kitauchi M, Yamaguchi T, Sato Y, Tanaka T, Hoshino K, Katayama KI, Fukuda S, Miyake K, Yamamoto M, Satoh T, Furukawa K, Kuroda E, Ishii KJ, Takeda K, Kaisho T
    • Journal Title

      International Immunology

      Volume: 印刷中 Issue: 10 Pages: 657-668

    • DOI

      10.1093/intimm/dxz004

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deficiency of GD3 Synthase in Mice Resulting in the Attenuation of Bone Loss with Aging2019

    • Author(s)
      Yo S, Hamamura K, Mishima Y, Hamajima K, Mori H, Furukawa K, Kondo H, Tanaka K, Sato T, Miyazawa K, Goto S, Togari A
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 10 Issue: 11 Pages: 2825-2825

    • DOI

      10.3390/ijms20112825

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TNFα-signal and cAMP-mediated signals oppositely regulate melanoma- associated ganglioside GD3 synthase gene in human melanocytes.2019

    • Author(s)
      Takeuchi R, Kambe M, Miyata M, Jeyadevan U, Tajima O, Furukawa K, Furukawa K.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 14740-14740

    • DOI

      10.1038/s41598-019-51333-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of enzyme activity of mutated B4GALNT1 gene products found in patients with hereditary spastic paraplegia induces relatively mild neurological disorders: Similarity with phenotypes of B4galnt1 knockout mice.2018

    • Author(s)
      Robiul H. Bhuiyan, Yuhsuke Ohmi, Yuki Ohkawa, Pu Zhang, Maiko Takano, Noboru Hashimoto, Tetsuya Okajima, Keiko Furukawa, Koichi Furukawa
    • Journal Title

      Neuroscience

      Volume: 397 Pages: 94-106

    • DOI

      10.1016/j.neuroscience.2018.11.034

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of malignant properties of human glioma cells by ganglioside GD3/GD2.2018

    • Author(s)
      Taiji Iwasawa, Pu Zhang, Yuki Ohkawa, Hiroyuki Momota, Toshihiko Wakabayashi, Yuhsuke Ohmi, Robiul H. Bhuiyan, Keiko Furukawa, Koichi Furukawa
    • Journal Title

      Int. J. Oncol.

      Volume: 52 Pages: 1255-1266

    • DOI

      10.3892/ijo.2018.4266

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gangliosides in inflammation and neurodegeneration.2018

    • Author(s)
      Furukawa K, Ohmi Y, Tajima O, Ohkawa Y, Kondo Y, Shuting J, Hashimoto N, Furukawa K
    • Journal Title

      Prog Mol Biol Transl Sci.

      Volume: 156 Pages: 265-287

    • DOI

      10.1016/bs.pmbts.2018.01.009

    • ISBN
      9780128123416
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genome-wide CRISPR screens for Shiga toxins and Ricin reveal Golgi proteins critical for glycosylation.2018

    • Author(s)
      Songhai Tian, Khaja Muneeruddin, Mei Yuk Choi, Liang Tao, Robiul H. Bhuiyan, Yuhsuke Ohmi, Keiko Furukawa, Koichi Furukawa, Sebastian Boland, Scott A. Shaffer, Rosalyn M. Adams, Min Dong
    • Journal Title

      PLoS Biol.

      Volume: 16(11) Issue: 11 Pages: 1-31

    • DOI

      10.1371/journal.pbio.2006951

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differential roles of gangliosides in malignant properties of melanomas.2018

    • Author(s)
      Ohmi Y, Kambe M, Ohkawa Y, Hamamura K, Tajima O, Takeuchi R, Furukawa K, Furukawa K
    • Journal Title

      PLOS One

      Volume: 13(11) Issue: 11 Pages: e0206881-e0206881

    • DOI

      10.1371/journal.pone.0206881

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inflammatory reactions in microenviron- ments, leading to melanomagenesis2018

    • Author(s)
      Koichi Furukawa, Maiko Miyata, Mariko Kambe, Rika Takeuchi, Robiul H. Bhuiyan, Pu Zhang, Yuhsuke Ohmi, Keiko Furukawa
    • Journal Title

      J. Clin. Cell. Immunol.

      Volume: 5:508 Issue: 03 Pages: 1-3

    • DOI

      10.4172/2155-9899.1000508

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ASC amino acid transporter 2, defined by enzyme-mediated activation of radical sources, enhances malignancy of GD2-positive small-cell lung cancer.2018

    • Author(s)
      Nobutoshi Esaki, Yuki Ohkawa, Noboru Hashimoto, Yuhsuke Tsuda, Yuhsuke Ohmi, Robiul H. Bhuiyan, Norihiro Kotani, Koichi Honke, Atsushi Enomoto, Masahide Takahashi, Keiko Furukawa, Koichi Furukawa.
    • Journal Title

      Cancer sci.

      Volume: 109 Issue: 1 Pages: 141-153

    • DOI

      10.1111/cas.13448

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glycosylation is involved in malignant properties of cancer cells2017

    • Author(s)
      Kazunori Hamamura and Koichi Furukawa
    • Journal Title

      Cancer Translational Medicine

      Volume: 3 Issue: 6 Pages: 209-213

    • DOI

      10.4103/ctm.ctm_28_17

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Glycolipids: Essential regulator of neuro-inflammation, metabolism and gliomagenesis.2017

    • Author(s)
      Koichi Furukawa, Yuhsuke Ohmi, Shuting Ji, Pu Zhang, Robiul H. Bhuiyan, Yuki Ohkawa, Orie Tajima, Noboru Hashimoto, Keiko Furukawa
    • Journal Title

      Biochim. Biophys. Acta

      Volume: 1861 Issue: 10 Pages: 2479-2484

    • DOI

      10.1016/j.bbagen.2017.06.007

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Regulation of cell signals by glycosphingolipids via cluster formation on the cell surface2019

    • Author(s)
      Koichi Furukawa, Yuki Ohkawa, Kei Kaneko, Noboru Hashimoto, Zhang Pu, Robiul H. Bhuiyan, Yuhsuke Ohmi, Keiko Furukawa
    • Organizer
      International Symposium on Bio-CHAINs from Single Molecules to Highly Organized Systems. co-organized by G-CHAIN and CREST exosome project
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 糖鎖とシグナル伝達 (Sugar chains and signal transduction)2019

    • Author(s)
      古川鋼一
    • Organizer
      第17回糖鎖科学コンソーシアムシンポジウム(JCGG) Symposium ~糖鎖研究と他領域との統合~
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Hydroxylation of ceramide modifies sensitivity of GD3-positive cancer cells to the killing of natural killer cells2019

    • Author(s)
      Koichi Furukawa, Noboru Hashimoto, Akihito Yamamoto, Paul Crocker, Yusuke Ohmi, Robiul H. Bhuiyan, Keiko Furukawa
    • Organizer
      International Symposium on Glycoconjugates (IGO GLYCO25)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] シアル酸結合レクチンSiglec7のガングリオシドGD3認識に対するセラミド構造の影響2019

    • Author(s)
      橋本 登、伊藤静香、土田明子、Roubiul H. Bhuiyan、岡島徹也、山本朗仁、古川圭子、大海雄介、古川鋼一
    • Organizer
      第38回日本糖質学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 大腸癌におけるGb3の機能解析2019

    • Author(s)
      北沢裕昭、田中 祥、藤井 碧、大海雄介、大川祐樹、喬 善楼、田島織絵、古川圭子、古川鋼一
    • Organizer
      第38回日本糖質学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Unique function of ganglioside GD2 in malignant melanomas2019

    • Author(s)
      Farhana Yesmin、Robiul H. Bhuiyan、Yuhsuke Ohmi、Tetsuya Okajima、Keiko Furukawa、Koichi Furukawa
    • Organizer
      第38回日本糖質学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Roles of ganglioside GD3 in the regulation of microenvironment of Gliomas2019

    • Author(s)
      Pu Zhang、Yuki Ohkawa、Robiul H. Bhuiyan、Hiroyuki Momota、Toshihiko Wakabayashi、Akira Kato、Yuhsuke Ohmi、Keiko Furukawa、Tetsuya Okajima、Koichi Furukawa
    • Organizer
      第38回日本糖質学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Roles of ganglioside GD3 in the regulation of microenvironment of gliomas2019

    • Author(s)
      Pu Zhang、Okiru Komine、Yuki Ohkawa、Yuhsuke Ohmi、Robiul H. Bhuiyan、Akira Kato、Keiko Furukawa、Tetsuya Okajima、Toshihiko Wakabayashi、Koichi Furukawa
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Targeting GD2 on cancer cells by an anti-GD2 antibody is promising in a variety of cancers: Challenge by CAR T2019

    • Author(s)
      古川鋼一、赤堀 泰、大海雄介、ファーハナ イエスミン、浦野 健、古川圭子、珠玖 洋
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] TNFa-and cAMP-signals oppositely regulate melanoma associated ganglioside GD3 synthase gene in human melanocytes2019

    • Author(s)
      竹内理香、神戸真理子、宮田麻衣子、ウプル ジャワデワン、田島織絵、古川鋼一、古川圭子
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of new CAR that suppress GD2 expressing tumors2019

    • Author(s)
      赤堀 泰、古川鋼一、藤原 弘、美輪啓志、奥村悟司、王立楠、加藤琢磨、宮原慶裕、瀬尾尚宏、 田中義正、珠玖 洋
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Unique function of ganglioside GD2 in malignant melanomas2019

    • Author(s)
      Farhana Yesmin、Robiul H. Bhuiyan、Yuhsuke Ohmi、Tetsuya Okajima、Keiko Furukawa、Koichi Furukawa
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Roles of asialo-series ganglioside GD1alpha in human cancer cell lines2019

    • Author(s)
      Robiul H. Bhuiyan、Farhana Yesmin、Yuji Kodo、Yuki Ohkawa、Yuhsuke Ohmi、Pu Zhang、Tetsuya Okajima、Keiko Furukawa、Koichi Furukawa
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウスアストロサイト上に発現するガングリオシドの機能解析2019

    • Author(s)
      大海雄介, 北浦洋子, 伊藤多佳子, 伴崚太, 古川圭子, 武田明, 河原敏男, 古川鋼一
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Increased readthrough of premature termination codon of B4GALNT1 gene depending on cell cycle2019

    • Author(s)
      Robiul H. Bhuiyan, Farhana Yesmin, Yuhsuke Ohmi, Yuki Ohkawa, Tetsuya Okajima, Keiko Furukawa, Koichi Furukawa
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Extracellular vesicles secreted from ganglioside GD3-expressing cancer cell lines contain high levels of integrins: Roles of lipid rafts2019

    • Author(s)
      Koichi Furukawa, Iori Kobayashi, Yoshiki Kodama, Yuhsuke Ohmi, Satoko Yamamoto, Yuki Ohkawa, Mariko Kambe, Keiko Furukawa
    • Organizer
      ISEV (International Society for Extracellular Vesicles)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 癌関連スフィンゴ糖脂質による細胞動態の分別的制御に関するタイムラプス解析2018

    • Author(s)
      古川 圭子, 神戸 真理子, 大海 雄介, 大川 祐樹, 竹内 理香, 田島 織絵, 安藤 弘宗, 古川 鋼一
    • Organizer
      第91回 日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 癌転移におけるエクソソームの役割の解析2018

    • Author(s)
      児玉 佳輝, 章 青, 大海 雄介, Hasan Bhuiyan Robiul, Yesmin Farhana, 山本 聡子, 古川 圭子, 古川 鋼一
    • Organizer
      第91回 日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] グリオーマーの微小環境調節におけるガングリオシドGD3の役割2018

    • Author(s)
      張 璞, 大川 祐樹, 大海 雄介, Robiul H.Bhuiyan, 加藤 彰, 古川 圭子, 岡島 徹也, 若林 俊彦, 古川 鋼一
    • Organizer
      第77回 日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 糖鎖リモデリング癌細胞由来エキソソームの膜分子組成と分泌機構の解析2018

    • Author(s)
      小林 伊織, 大海 雄介, 古川 圭子, ブイヤン ロビウル, 張 璞, 古川 鋼一
    • Organizer
      第77回 日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Regulation of inflammation and malignant tumors by glycosylation2017

    • Author(s)
      Koichi Furukawa
    • Organizer
      Seminar at Academia Sinica, GlycoMedicine Seminar, Taipei
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Regulation of inflammation and malignant tumors by glycosylation2017

    • Author(s)
      Koichi Furukawa
    • Organizer
      Medical Research Seminar at Chang Gung Memorial Hospital (CGMH), Taipei
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Regulation of cell signaling by ganglioside GD3/GD2 in gliomas2017

    • Author(s)
      Koichi Furukawa, Yuki Ohkawa, Kei Kaneko, Noboru Hashimoto, Zhang Pu, Robiul H. Bhuiyan, Yuhsuke Ohmi, Keiko Furukawa
    • Organizer
      GLYCO XXIV, ICC Jeju, Korea
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] GD3発現がん細胞由来の細胞外ベクシルにおけるがん関連分子の組成の解析2017

    • Author(s)
      小林伊織、大川祐樹、西沢裕治、大海雄介、古川圭子、Robiul H Bhuiyan, 張 僕、古川鋼一
    • Organizer
      第82回生化学会中部支部例会
    • Related Report
      2017 Research-status Report
  • [Presentation] がん細胞由来の細胞外ベジクルにおける糖鎖関連分子の組成の解析2017

    • Author(s)
      小林 伊織、古川 鋼一、ブイヤン ロビウル、張 璞、大海 雄介
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] GD3発現がん細胞由来の細胞外ベクシルにおけるがん関連分子の組成の解析2017

    • Author(s)
      小林伊織、大川祐樹、西沢裕治、大海雄介、古川圭子、Robiul H Bhuiyan, 張 僕、古川鋼一
    • Organizer
      第36回日本糖質学会年会
    • Related Report
      2017 Research-status Report
  • [Book] 糖鎖生物学、生命現象と糖鎖情報 神経と糖鎖(II) 神経機能2020

    • Author(s)
      古川鋼一、大海雄介、田島織絵、古川圭子
    • Publisher
      名古屋大学出版会
    • ISBN
      9784815809812
    • Related Report
      2019 Annual Research Report
  • [Book] 糖鎖生物学、生命現象と糖鎖情報 免疫と糖鎖(I) 免疫調節2020

    • Author(s)
      大海雄介、古川鋼一
    • Publisher
      名古屋大学出版会
    • ISBN
      9784815809812
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] GD2結合性分子2019

    • Inventor(s)
      珠玖洋、赤堀泰、三輪啓志、藤原弘、古川鋼一、古川圭子、大海雄介
    • Industrial Property Rights Holder
      三重大学、中部大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-142358
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2017-07-21   Modified: 2023-12-25  

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