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Novel anti-sulfated glycan antibodies for ovarian cancer pathology diagnosis and photoimmunotherapy

Research Project

Project/Area Number 21H02702
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionUniversity of Fukui

Principal Investigator

Kobayashi Motohiro  福井大学, 学術研究院医学系部門, 教授 (00362137)

Co-Investigator(Kenkyū-buntansha) 赤間 智也  関西医科大学, 医学部, 准教授 (10548788)
長屋 匡信  信州大学, 学術研究院医学系(医学部附属病院), 准教授 (00718033)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Fiscal Year 2023: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2022: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2021: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywords卵巣癌 / 硫酸化糖鎖 / 光免疫療法
Outline of Research at the Start

近赤外線光免疫療法は,がん細胞を特異的に認識する抗体に光吸収体を結合したものを投与した後,近赤外線を当てるだけでがん細胞を選択的に破壊することができる画期的な治療法である。申請者らは最近,ユニークな硫酸化糖鎖を認識する新規抗体を作製し,このユニークな硫酸化糖鎖が予後不良の卵巣癌に選択的に発現していることを見いだした。本研究課題では,この硫酸化糖鎖が卵巣癌の悪性形質に寄与するメカニズムを明らかにするとともに,卵巣癌の病理診断および予後マーカーとしての可能性を検討する。さらに,この新規抗硫酸化糖鎖抗体を近赤外線光免疫療法に応用し,卵巣癌の予後を著しく改善する新規治療法開発の基盤を築く。

Outline of Final Research Achievements

We generated a novel anti-sulfated carbohydrate antibody, 297-11A, which recognizes galactose-sulfated N-acetyllactosamine structures, and performed clinicopathological analysis of ovarian cancer histopathological specimens. The results showed that 297-11A-positive cases were frequently observed in serous carcinomas, and that it was also expressed in normal fallopian tube epithelial secretory cells, which are considered to be the origin of such carcinomas. In addition, we found that progression-free survival was significantly shorter in 297-11A-sulfated glycosylation-positive ovarian cancer patients than in negative patients.

Academic Significance and Societal Importance of the Research Achievements

卵巣漿液性癌は卵管上皮を構成する分泌細胞の過剰増殖を引き金に発生すると考えられているが,漿液性癌細胞に加えて,この分泌細胞も297-11A抗体で陽性に染色されるという今回の結果は,この考えをさらに支持するものである。また,297-11A陽性の患者は陰性の患者よりも無増悪生存期間が有意に短いことから,卵巣癌治療における予後予測や,新規治療開発の標的として有望であると考えられる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (31 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (2 results) Journal Article (15 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 15 results,  Open Access: 5 results) Presentation (14 results) (of which Int'l Joint Research: 4 results)

  • [Int'l Joint Research] 台湾中央研究院(台湾)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] 台湾中央研究院(台湾)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Structural Elucidation and Prognostic Relevance of 297-11A-Sulfated Glycans in Ovarian Carcinoma2024

    • Author(s)
      Inoue Daisuke、Hoshino Hitomi、Chen Ya-Ying、Yamamoto Makoto、Kogami Akiya、Fukushima Mana、Khoo Kay-Hooi、Akama Tomoya O.、Yoshida Yoshio、Kobayashi Motohiro
    • Journal Title

      Laboratory Investigation

      Volume: 104 Issue: 6 Pages: 102057-102057

    • DOI

      10.1016/j.labinv.2024.102057

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Establishment of a human ovarian clear cell carcinoma cell line mutant in PIK3CB but not PIK3CA2024

    • Author(s)
      Hoshino Hitomi、Inoue Daisuke、Shinagawa Akiko、Yoshida Hisato、Shigeto Shohei、Matsuda Kazuyuki、Akama Tomoya O.、Yoshida Yoshio、Kobayashi Motohiro
    • Journal Title

      Human Cell

      Volume: - Issue: 4 Pages: 1184-1193

    • DOI

      10.1007/s13577-024-01058-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of low-sulfated keratan sulfate in non-mucinous ovarian carcinoma2024

    • Author(s)
      Hoshino H, Chen YY, Inoue D, Yoshida Y, Khoo KH, Akama TO, Kobayashi M
    • Journal Title

      Glycobiology

      Volume: 34 Issue: 1

    • DOI

      10.1093/glycob/cwad056

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Paradoxical expression of R-10G-reactive antigen in human testicular embryonal carcinoma2023

    • Author(s)
      Muramoto A, Inamura S, Hoshino H, Terada N, Kobayashi M
    • Journal Title

      J Histochem Cytochem

      Volume: 71 Issue: 10 Pages: 555-563

    • DOI

      10.1369/00221554231199134

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The percentage of PNAd-expressing vessels is correlated with disease severity in eosinophilic chronic rhinosinusitis2023

    • Author(s)
      Kato E, Tsutsumiuchi T, Muramoto A, Tokunaga T, Fujieda S, Kobayashi M
    • Journal Title

      Am J Rhinol Allergy

      Volume: 37 Issue: 1 Pages: 43-50

    • DOI

      10.1177/19458924221129903

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distinct sulfated glycans expressed in intrahepatic cholangiocarcinoma: a potential target for new therapy2023

    • Author(s)
      Hoshino H, Kobayashi M
    • Journal Title

      Immunotherapy

      Volume: 15 Issue: 7 Pages: 503-516

    • DOI

      10.2217/imt-2022-0220

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vascular E-selectin expression detected in formalin-fixed, paraffin-embedded sections with an E-selectin monoclonal antibody correlates with ulcerative colitis activity2022

    • Author(s)
      Murahashi M, Kogami A, Muramoto A, Hoshino H, Akama TO, Mitoma J, Goi T, Hirayama A, Okamura T, Nagaya T, Kobayashi M
    • Journal Title

      J Histochem Cytochem

      Volume: 70 Issue: 4 Pages: 299-310

    • DOI

      10.1369/00221554221085336

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sulfated Glycans Recognized by S1 Monoclonal Antibody can Serve as a Diagnostic Marker for Malignant Pleural Mesothelioma2022

    • Author(s)
      Koki Nakashima, Yasuhiro Sakai, Hitomi Hoshino, Yukihiro Umeda, Hiroto Kawashima, Yoshitaka Sekido, Tamotsu Ishizuka, Motohiro Kobayashi
    • Journal Title

      Lung

      Volume: 200 Issue: 3 Pages: 531-534

    • DOI

      10.1007/s00408-022-00531-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bronchiolitis obliterans syndrome after hematopoietic stem cell transplant diagnosed using ultrathin bronchoscopy2022

    • Author(s)
      Sato M, Waseda Y, Sonoda T, Tanizawa A, Itoh H, Kobayashi M, Takemura T, Ishizuka T
    • Journal Title

      Am J Respir Crit Care Med

      Volume: 206 Issue: 1 Pages: e1-e3

    • DOI

      10.1164/rccm.202109-2073im

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful treatment with lenvatinib in a patient with thymic carcinoma presenting with cardiac tamponade: a case report and review of literature2022

    • Author(s)
      Nakashima K, Azuma T, Ohta R, Fujii Y, Sato M, Igarashi K, Kadowaki M, Umeda Y, Waseda Y, Anzai M, Kobayashi M, Ishizuka T
    • Journal Title

      Anticancer Drugs

      Volume: 33 Pages: 761-764

    • DOI

      10.1097/cad.0000000000001332

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cholesterol crystal embolism in multiple organs after transarterial chemoembolization for hepatocellular carcinoma: An autopsy case report.2022

    • Author(s)
      Yamashita J, Nosaka T, Takahashi K, Naito T, Ofuji K, Matsuda H, Ohtani M, Hiramatsu K, Kobayashi M, Nakamoto Y.
    • Journal Title

      Medicine (Baltimore)

      Volume: 101(39) Issue: 39 Pages: e30769-e30769

    • DOI

      10.1097/md.0000000000030769

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression and Clinical Significance of Spi-B in B-cell Acute Lymphoblastic Leukemia2022

    • Author(s)
      Yuzuru Ariga, Shulin Low, Hitomi Hoshino, Tsutomu Nakada, Tomoya O Akama, Akifumi Muramoto, Mana Fukushima, Takahiro Yamauchi, Yusei Ohshima, Motohiro Kobayashi
    • Journal Title

      J Histochem Cytochem

      Volume: 70 Issue: 10 Pages: 683-694

    • DOI

      10.1369/00221554221130383

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Apical membrane expression of distinct sulfated glycans is a characteristic feature of ductules and their reactive and neoplastic counterparts2021

    • Author(s)
      Hoshino H, Akama TO, Uchimura K, Fukushima M, Muramoto A, Uehara T, Nakanuma Y, Kobayashi M
    • Journal Title

      J Histochem Cytochem

      Volume: 69 Issue: 9 Pages: 555-573

    • DOI

      10.1369/00221554211035730

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The conspicuousness of high endothelial venues in angioimmunoblastic T-cell lymphoma is due to increased cross-sectional area, not increased distribution density2021

    • Author(s)
      Kogami A, Fukushima M, Hoshino H, Komeno T, Okoshi T, Murahashi M, Akama TO, Mitoma J, Ohtani H, Kobayashi M
    • Journal Title

      J Histochem Cytochem

      Volume: 69 Issue: 10 Pages: 645-657

    • DOI

      10.1369/00221554211048551

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of non-small cell lung cancer presenting anti-amphiphysin antibody-positive paraneoplastic neurological syndrome2021

    • Author(s)
      Nakashima K, Fujii Y, Sato M, Igarashi K, Kobayashi M, Ishizuka T
    • Journal Title

      Respir Med Case Rep

      Volume: 34 Pages: 101525-101525

    • DOI

      10.1016/j.rmcr.2021.101525

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 低硫酸化ケラタン硫酸を発現する明細胞卵巣癌細胞株の樹立2024

    • Author(s)
      星野 瞳,井上大輔,吉田寿人,重藤翔平,松田和之,赤間智也,吉田好雄,小林基弘
    • Organizer
      第113回日本病理学会総会,下関
    • Related Report
      2023 Annual Research Report
  • [Presentation] 精巣胎児性癌におけるR-10Gの逆説的発現とその他胚細胞性腫瘍における発現の検討2024

    • Author(s)
      村元曉文,稲村 聡,星野 瞳,寺田直樹,小林基弘
    • Organizer
      第113回日本病理学会総会,下関
    • Related Report
      2023 Annual Research Report
  • [Presentation] 心臓粘液腫―その粘液腫状基質にはケラタン硫酸が存在する―2024

    • Author(s)
      福島万奈,星野 瞳,米元菜採,村元曉文,山中真衣子,加藤久隆,小林基弘
    • Organizer
      第113回日本病理学会総会,下関
    • Related Report
      2023 Annual Research Report
  • [Presentation] 悪性リンパ腫による形質細胞増多症の1剖検例2024

    • Author(s)
      米元菜採,福島万奈,浅野直子,村元曉文,木村純也,八田聡美,山内英暉,松田安史,今村好章,小林基弘
    • Organizer
      第113回日本病理学会総会,下関
    • Related Report
      2023 Annual Research Report
  • [Presentation] Structural elucidation and prognostic relevance of 297-11A-sulfated glycans in ovarian carcinoma2024

    • Author(s)
      Inoue D, Hoshino H, Chen YY, Yamamoto M, Kogami A, Fukushima M, Khoo KH, Akama TO, Yoshida Y, Kobayashi M
    • Organizer
      26th Annual San Diego Glycobiology Symposium, San Diego, CA, USA
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] High PNAd(+)/CD34(+) vessel ratio and M2/M2 macrophage ratio observed in nasal polyp formed in allergic fungal rhinosinusitis2024

    • Author(s)
      Kato E, Muramoto A, Natsumi Y, Fukushima M, Fujieda S, Kobayashi M
    • Organizer
      26th Annual San Diego Glycobiology Symposium, San Diego, CA, USA
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Expression of low-sulfated keratan sulfate in non-mucinous ovarian carcinoma2023

    • Author(s)
      Hoshino H, Chen YY, Inoue D, Yoshida Y, Khoo KH, Akama TO, Kobayashi M
    • Organizer
      International Symposium on Glycoconjugates, Taipei, Taiwan
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Paradoxical expression of R-10G-reactive antigen in human testicular embryonal carcinoma2023

    • Author(s)
      Kobayashi M, Muramoto A, Inamura S, Hoshino H, Terada N
    • Organizer
      Annual Conference of the Society for Glycobiology, Waikoloa, HI, USA
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 血管芽球性T細胞リンパ腫では、なぜ高内皮細静脈が目立つのか2022

    • Author(s)
      小上瑛也,福島万奈,星野 瞳,米野琢哉,大越忠和,村橋将崇,赤間智也,三苫純也,大谷明夫,小林基弘
    • Organizer
      第111回日本病理学会総会,神戸
    • Related Report
      2022 Annual Research Report
  • [Presentation] ALK陽性未分化大細胞リンパ腫7例に関する検討2022

    • Author(s)
      米元菜採,村元曉文,木村純也,八田聡美,樋口翔平,福島万奈,今村好章,小林基弘
    • Organizer
      第111回日本病理学会総会,神戸
    • Related Report
      2022 Annual Research Report
  • [Presentation] Myelolipoma に epithelioid hemangioendothelioma が浸潤していた1例2022

    • Author(s)
      村元暁文,米元菜採,木村純也,八田聡美,伊藤知美,山口愛奈,樋口翔平,福島万奈,小林基弘,今村好章
    • Organizer
      第111回日本病理学会総会,神戸
    • Related Report
      2022 Annual Research Report
  • [Presentation] 297-11A抗体のゴルジ陽性パターンはコンドロイチン6硫酸転移酵素の機能を反映する2022

    • Author(s)
      福島万奈,星野 瞳,山中麻衣子,加藤久隆,赤間智也,小林基弘
    • Organizer
      第111回日本病理学会総会,神戸
    • Related Report
      2022 Annual Research Report
  • [Presentation] ヒト卵巣癌由来細胞株の樹立2022

    • Author(s)
      星野 瞳,井上大輔,赤間智也,吉田好雄,小林基弘
    • Organizer
      第68回日本病理学会秋期特別総会,盛岡
    • Related Report
      2022 Annual Research Report
  • [Presentation] アレルギー性真菌性副鼻腔炎の病態形成に関わる因子の解析2022

    • Author(s)
      加藤永一,村元曉文,福島万奈,小林基弘
    • Organizer
      第68回日本病理学会秋期特別総会,盛岡
    • Related Report
      2022 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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