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Glycan expression profile of schirrhous gastric cancer

Research Project

Project/Area Number 20K09097
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Akashi Yoshimasa  筑波大学, 医学医療系, 准教授 (50709722)

Co-Investigator(Kenkyū-buntansha) 小田 竜也  筑波大学, 医学医療系, 教授 (20282353)
下村 治  筑波大学, 医学医療系, 講師 (60808070)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsスキルス胃癌 / 糖鎖 / レクチン / rBC2LCN / シアリル化糖鎖 / 薬物治療 / ゲノム / バイオマーカー / rBC2 / レクチン薬物複合体 / 胃癌ゲノム型 / 胃癌 / リキッドバイオプシー
Outline of Research at the Start

大規模ゲノム解析を基に胃癌はゲノム型で4つに分類されるようになったが, 予後不良なスキルス胃癌はゲノム安定型に含まれゲノム解析に基づく新規治療法は期待しにくい。所属教室では癌細胞表面抗原を覆う糖鎖に着目し膵癌特異的糖鎖の同定から, その糖鎖に結合するレクチンを薬剤キャリアとした新規抗癌治療薬の開発を進めてきた。本研究では胃癌の糖鎖プロファイルという視点からゲノム型分類を再考察する。また、細胞表面の糖鎖は多く体液中に遊離する事から、標的糖鎖を血清等から検出するリキッドバイオプシーを試みる。さらに、糖鎖標的レクチンによる難治性スキルス胃癌に対する新規治療開発を目指す.

Outline of Final Research Achievements

Schirrhous type of gastric cancer is classified as a genomic stable (GS) subtype with few genetic alterations in a comprehensive large-scale whole genome analysis, and has a poor prognosis due to the lack of efficacy targeting drugs that target membrane proteins on the surface of cancer cells and tumor immunostimulating therapy. In this study, we focused on carbohydrate chains in the outermost layer of cancer cells and identified 11 lectins with high affinity to scirrhous gastric cancer cells and 8 lectins with low affinity by comprehensive lectin microarray. Among the high-affinity lectins, the rBC2LCN lectin can be administered to living animals and showed anti-tumor effects in murine scirrhous gastric cancer models by using a lectin-drug complex, indicating the possibility of sugar chain-targeted drug therapy.

Academic Significance and Societal Importance of the Research Achievements

未だ有効な薬物治療がなく予後が不良なスキルス胃癌に対して、従来の薬剤とは異なるがん細胞表面糖鎖を標的とした新規薬物治療が、有効である可能性を示すことができた。膵癌に対する先行研究を元に臨床応用に向けたレクチン薬物複合体の製剤開発が進んでおり、将来的にスキルス胃癌に対して新たな治療オプションとなる可能性があり、その治療成績を向上させることができるかもしれない。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (4 results)

All 2022 2020

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Glycan expression profile of signet ring cell gastric cancer cells and potential applicability of rBC2LCN-targeted lectin drug conjugate therapy2022

    • Author(s)
      Yang Yu、Akashi Yoshimasa、Shimomura Osamu、Tateno Hiroaki、Saito Sayoko、Hiemori Keiko、Miyazaki Yoshihiro、Furuta Tomoaki、Kitaguchi Daichi、Kuroda Yukihito、Pakavarin Louphrasitthiphol、Oda Tatsuya
    • Journal Title

      Gastric Cancer

      Volume: 25 Issue: 5 Pages: 896-905

    • DOI

      10.1007/s10120-022-01312-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lectin drug conjugate therapy for colorectal cancer2020

    • Author(s)
      Kitaguchi Daichi、Oda Tatsuya、Enomoto Tsuyoshi、Ohara Yusuke、Owada Yohei、Akashi Yoshimasa、Furuta Tomoaki、Yu Yang、Kimura Sota、Kuroda Yukihito、Kurimori Ko、Miyazaki Yoshihiro、Furuya Kinji、Shimomura Osamu、Tateno Hiroaki
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 12 Pages: 4548-4557

    • DOI

      10.1111/cas.14687

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Glycan expression profile of signet ring cell gastric cancer2022

    • Author(s)
      明石義正, Yang Yu, 下村治, 小川光一, 榎本剛史, 大原佑介, 大和田洋平, 宮崎貴寛, 橋本真治, 高橋一広, 土井愛美, 古屋欽司, 馬上頌子, 小田竜也
    • Organizer
      第94回 日本胃癌学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Glycan expression profile of signet gastric cancer and potential applicability of lectin drug conjugate2022

    • Author(s)
      Yoshimsa Akashi, Yu Yang, Osamu Shimomura, Yoshihiro Miyazaki, Tatsuya Oda, et al.
    • Organizer
      第94回日本胃癌学会
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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