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Basic study on treatment of hepatocellular carcinoma targetted of Gal-9 exosomes

Research Project

Project/Area Number 16K09361
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionKagawa University

Principal Investigator

Masaki Tsutomu  香川大学, 医学部, 教授 (30335848)

Co-Investigator(Kenkyū-buntansha) 谷 丈二  香川大学, 医学部, 協力研究員 (00596075)
小原 英幹  香川大学, 医学部附属病院, 講師 (10612476)
岩間 久和  香川大学, 総合生命科学研究センター, 准教授 (20398035)
森 宏仁  香川大学, 医学部附属病院, 講師 (20568844)
藤田 浩二  香川大学, 医学部附属病院, 病院助教 (50749421)
森下 朝洋  香川大学, 医学部附属病院, 助教 (60423430)
野村 貴子  香川大学, 医学部, 助教 (70645415)
米山 弘人  香川大学, 医学部, 助教 (80294750)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords肝細胞癌 / Gal-9 / Gal-9 / Gal-9
Outline of Final Research Achievements

Proteins,DNAs,mRNAs,microRNAs,etc.are contained in the 50 to 1000 nm exosome (extracellular secretory vesicle organ). Therefore,exosomes can be a delivery cargo that transmits information sources from cell to cell.We examined the effect on microRNA in exosomes of Gal-9 Small RNA in culture solution of Gal-9 non-added,added Gal-9 sensitive cells(Li-7,HLE,HLF)and resistant cells(HuH-7,HepG2,Hep3B)Total RNA was extracted.By the addition of Gal-9,miR-34 can be detected as a Gal-9 sensitive cell(Li-7,HLE,HLF)by comprehensive analysis of the exosomal microRNA using a microRNA oligo chip.MiR-34 was increased in serum exosomes as liver progressive disease.Furthermore,miR-34 showed migratory effects when it was transfected with miR-34,and further,it was confirmed that cyclin D1 induced from the G1 phase to the S phase of the cell cycle was attenuated.From this,it was found that Gal-9 increases miR-34 in exosomes and is involved in the suppression of cell proliferation.

Academic Significance and Societal Importance of the Research Achievements

50~1000nmのエクソソーム(細胞外分泌小胞器官)内には、タンパク質、DNA,mRNA,microRNAなどが内包されている。こうした情報伝達物質は、細胞の起源によって異なるものの、100~300種類の以上のタンパク質、100種類以上のmicroRNAが内包されている。それ故に、エクソソームは情報源を細胞から細胞へ伝搬するデリバリーカーゴ(cargo)となりうる。今回の研究において、Gal-9がエクソソーム内にあるmicroRNA-34によって、抗腫瘍効果をもたらすことが明らかにされ、近い将来において、Gal-9がエクソソームを標的とした新薬剤となり得ると考える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (21 results)

All 2018 2017 2016

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (11 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Human microRNAs preferentially target genes with intermediate levels of expression and its formation by mammalian evolution.2018

    • Author(s)
      Iwama H, Kato K, Imachi H, Murao K, Masaki T.
    • Journal Title

      PLoS One

      Volume: 13(5)

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNAs as possible biomarkers for hepatocellular carcinoma.2018

    • Author(s)
      Morishita A, Masaki T.
    • Journal Title

      Hepatol Res

      Volume: 48 Pages: 499-501

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum miRNAs Predicting Sustained HBs Antigen Reduction 48 Weeks after Pegylated Interferon Therapy in HBe Antigen-Negative Patients.2018

    • Author(s)
      Fujita K, Mimura S, Iwama H, Nakahara M, Oura K, Tadokoro T, Nomura T, Tani J, Yoneyama H, Morishita A, Oryu M, Himoto T, Nishitsuji H, Shimotohno K, Omata M, Masaki T.
    • Journal Title

      Int J Mol Sci

      Volume: 19(7)

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fibrosis Staging Using Direct Serum Biomarkers is Influenced by Hepatitis Activity Grading in Hepatitis C Virus Infection.2018

    • Author(s)
      Fujita K, Kuroda N, Morishita A, Oura K, Tadokoro T, Nomura T, Yoneyama H, Arai T, Himoto T, Watanabe S, Masaki T.
    • Journal Title

      J Clin Med

      Volume: 7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] icroRNA profile of hepatic epithelioid hemangioendothelioma: A case report.2017

    • Author(s)
      Morishita A, Iwama H, Yoneyama H, Sakamoto T, Fujita K, Nomura T, Tani J, Miyoshi H, Fujihara S, Nishiyama N, Kobara H, Mori H, Yamamoto N, Okano K, Suzuki Y, Ibuki E, Haba R, Himoto T, Masaki T.
    • Journal Title

      Oncol Lett

      Volume: 13(3) Issue: 3 Pages: 1655-1659

    • DOI

      10.3892/ol.2017.5643

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic potential of the antidiabetic drug metformin in small bowel adenocarcinoma.2017

    • Author(s)
      Chiyo T, Kato K, Iwama H, Fujihara S, Fujita K, Tadokoro T, Ohura K, Samukawa E, Yamana Y, Kobayashi N, Matsunaga T, Nishiyama N, Ayaki M, Yachida T, Morishita A, Kobara H, Mori H, Masaki T.
    • Journal Title

      Int J Oncol

      Volume: 50(6) Issue: 6 Pages: 2145-2153

    • DOI

      10.3892/ijo.2017.3971

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of galectin-9 on apoptosis, cell cycle and autophagy in human esophageal adenocarcinoma cells.2017

    • Author(s)
      Akashi E, Fujihara S, Morishita A, Tadokoro T, Chiyo T, Fujikawa K, Kobara H, Mori H, Iwama H, Okano K, Suzuki Y, Niki T, Hirashima M, Masaki T.
    • Journal Title

      Oncol Rep

      Volume: 38(1) Issue: 1 Pages: 506-514

    • DOI

      10.3892/or.2017.5689

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Galectin-9 ameliorates fulminant liver injury.2017

    • Author(s)
      Tadokoro T, Morishita A, Sakamoto T, Fujihara S, Fujita K, Mimura S, Oura K, Nomura T, Tani J, Yoneyama H, Iwama H, Himoto T, Niki T, Hirashima M, Masaki T
    • Journal Title

      Mol Med Rep

      Volume: 16(1) Issue: 1 Pages: 36-42

    • DOI

      10.3892/mmr.2017.6606

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Galectin-9: An anticancer molecule for gallbladder carcinoma.2016

    • Author(s)
      Tadokoro T, Morishita A, Fujihara S, Iwama H, Niki T, Fujita K, Akashi E, Mimura S, Oura K, Sakamoto T, Nomura T, Tani J, Miyoshi H, Yoneyama H, Himoto T, Hirashima M, Masaki T.
    • Journal Title

      Int J Oncol

      Volume: 48 Issue: 3 Pages: 1165-1174

    • DOI

      10.3892/ijo.2016.3347

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Galectin-9 suppresses the proliferation of gastric cancer cells in vitro.2016

    • Author(s)
      Takano J, Morishita A, Fujihara S, Iwama H, Kokado F, Fujikawa K, Fujita K, Chiyo T, Tadokoro T, Sakamoto T, Nomura T, Tani J, Miyoshi H, Yoneyama H, Kobara H, Mori H, Niki T, Hirashima M, Masaki T.
    • Journal Title

      Oncol Rep

      Volume: 35 Issue: 2 Pages: 851-860

    • DOI

      10.3892/or.2015.4452

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 慢性肝疾患における血清ガレクチン9濃度の診断的意義の検討2018

    • Author(s)
      藤田浩二、樋本尚志、正木 勉
    • Organizer
      第104回日本消化器病学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ソラフェニブ抵抗性肝細胞癌に対する新規治療薬としてのマイクロRNAの有効性2018

    • Author(s)
      森下朝洋、谷 丈二、正木 勉
    • Organizer
      第22回日本肝臓学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] miR-762はDAA治療経過中のゲノタイプ1型HCV排除に際して血清中に増加する2018

    • Author(s)
      米山弘人、森下朝洋、藤田浩二、野村貴子、坂本鉄平、田所智子、大浦杏子、谷 丈二、出口章広、樋本尚志、三村志麻、正木 勉
    • Organizer
      第22回日本肝臓学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] C型肝炎起因性肝細胞癌におけるバイオマーカーとしての血清miR-125a-5pの有用性2018

    • Author(s)
      大浦杏子、田所智子、藤田浩二、三村志麻、坂本鉄平、野村貴子、森下朝洋、米山弘人、正木 勉
    • Organizer
      第22回日本肝臓学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 食道腺癌におけるガレクチン9の増殖抑制効果の検討2018

    • Author(s)
      明石瑛美子、藤原新太郎、森下朝洋、田所智子、千代大翔、正木 勉
    • Organizer
      第60回日本消化器病学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 膵臓癌に対する術前化学放射線療法におけるmicroRNAの網羅的解析を用いた治療効果判定の検討2018

    • Author(s)
      加藤清仁、鎌田英紀、波間大輔、山名浩喜、辻真一郎、山下拓磨、小林聖幸、藤森崇行、正木 勉
    • Organizer
      第60回日本消化器病学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 炎症性腸疾患の診断、鑑別における血清microRNA のバイオマーカーとしての同定2018

    • Author(s)
      谷内田達夫、藤森絢子、小林伸也、千代大翔、西山典子、小原英幹、森 宏仁、岩間久和、舛形 尚、正木 勉
    • Organizer
      第110回日本消化器病学会四国支部例会・第121回日本消化器内視鏡学会四国支部例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Serum Concentration of Galectin-9 Correlates to Liver Fibrosis.2017

    • Author(s)
      Fujita K, Morishita A, Yoneyama H, Niki T, Nishimoto N, Himoto T, Masaki T.
    • Organizer
      APASL STC 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Galectin-9による食道扁平上皮癌のアポトーシスの誘導と作用機序2017

    • Author(s)
      千代大翔、藤原新太郎、森下朝洋、藤田浩二、山名佳美、大浦杏子、寒川英里、田所智子、小林伸也、松永多恵、西山典子、綾木麻紀、谷内田達夫、小原英幹、森 宏仁、正木 勉
    • Organizer
      第103回日本消化器病学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Nonalcoholic Steatohepatitis(NASH)進展および発癌抑制に対するGalectin-9の有効性と機序についての検討2017

    • Author(s)
      森下朝洋、田所智子、正木 勉
    • Organizer
      第53回日本肝臓学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Serum galectin-9 levels are correlated to liver fibrosis regardless of chronic inflammation or hepatocellular carcinoma2017

    • Author(s)
      Fujita K, Niki T, Himoto T, Masaki T.
    • Organizer
      AASLD2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2023-03-16  

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