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Novel heterogeneity analyses for extracellular vesicles in micro volume bio-fluids

Research Project

Project/Area Number 22K18394
Research Category

Grant-in-Aid for Challenging Research (Pioneering)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionNagoya University

Principal Investigator

Yokoi Akira  名古屋大学, 医学部附属病院, 病院講師 (30737135)

Co-Investigator(Kenkyū-buntansha) 安井 隆雄  東京科学大学, 生命理工学院, 教授 (00630584)
Project Period (FY) 2022-06-30 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2024: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2023: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2022: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Keywordsがん微小環境 / エクソソーム / 細胞外小胞 / Heterogeneity / 卵巣がん / ナノテクノロジー / heterogeneity
Outline of Research at the Start

EVシートによる微量体液中EV解析手法とがん患者体液中EVにおけるheterogeneityの概念の提唱という本研究目的の達成のため、検討事項の明確化、連携体制の構築を行う。がん患者および疾患モデルマウスの体液を対象として、EVシート用いてEVを回収し、治療標的としての妥当性を評価・検討する。研究チームとしての強みを生かしつつ連携を密にし、研究成果の最大化を図る。

Outline of Final Research Achievements

The objective of this study was to enable analysis of extracellular vesicles (EVs) from extremely small amounts of body fluid, which have been difficult to recover with conventional techniques. By using a method for collecting trace amounts of body fluid using special cellulose nanofiber paper (CNF paper), we were able to clarify differences in the molecular profiles of EVs depending on the site of collection, such as tumor surface, visceral peritoneum, mural peritoneum, and diaphragm, from the concept of a single fluid, such as blood or ascites, as the source of EVs (Nat Commun. 2023). By analyzing EV heterogeneity from a new perspective of in vivo location information, a new mechanism of progression in ovarian cancer will be elucidated, which will lead to clinical application in the future.

Academic Significance and Societal Importance of the Research Achievements

特殊なセルロースナノファイバー紙(CNF紙)を用いた微量体液の回収手法は、EV研究のみならず産業界においても大きなインパクトを有する。現在、製紙会社と共同で量産タイプの開発を進めており、抽出操作が煩雑だった従来のEV回収法に比べて本技術は画期的である。さらに、臓器表面におけるEV分子プロファイルの直接評価を可能とする点で極めて新規性が高く、新たなEV研究領域の創出に貢献している。現在、複数の疾患領域における臨床医との共同研究を展開中である。

Report

(5 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Comments on the Screening Results   Research-status Report
  • Research Products

    (36 results)

All 2025 2024 2023 2022

All Journal Article (16 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 12 results) Presentation (19 results) (of which Int'l Joint Research: 6 results,  Invited: 15 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Understanding the impact of spatial immunophenotypes on the survival of endometrial cancer patients through the ProMisE classification2025

    • Author(s)
      Hattori Satomi、Yoshikawa Nobuhisa、Liu Wenting、Matsukawa Tetsuya、Kubokawa Mei、Yoshida Kosuke、Yoshihara Masato、Tamauchi Satoshi、Ikeda Yoshiki、Yokoi Akira、Shimizu Yusuke、Niimi Kaoru、Kajiyama Hiroaki
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: 74 Issue: 2

    • DOI

      10.1007/s00262-024-03919-8

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemotherapeutic hormesis induced by the tumor microenvironment in refractory ovarian cancer2025

    • Author(s)
      Chang Xuboya、Tamauchi Satoshi、Nakagawa Atsushi、Xinyuan Wang、Yoshida Kosuke、Yokoi Akira、Yoshikawa Nobuhisa、Kajiyama Hiroaki
    • Journal Title

      Scientific Reports

      Volume: 15 Issue: 1

    • DOI

      10.1038/s41598-024-84290-7

    • Related Report
      2024 Annual Research Report
  • [Journal Article] Extracellular vesicles display distinct glycosignatures in high-grade serous ovarian carcinoma2025

    • Author(s)
      Bienes Kristina Mae、Yokoi Akira、Kitagawa Masami、Kajiyama Hiroaki、Thaysen-Andersen Morten、Kawahara Rebeca
    • Journal Title

      BBA Advances

      Volume: 7 Pages: 100140-100140

    • DOI

      10.1016/j.bbadva.2025.100140

    • Related Report
      2024 Annual Research Report
  • [Journal Article] Single‐Nucleus RNA Sequencing and Spatial Transcriptomics for Squamous Cell Carcinoma Arising From Ovarian Mature Teratoma2025

    • Author(s)
      Kosuke Yoshida、Akira Yokoi、Hironori Suzuki、Satoshi Tamauchi、Masami Kitagawa、Eri Inami、Jun Nakayama、Yutaro Mori、Koji Okamoto、Yutaka Suzuki、Hiroshi Yoshida、Tomoyasu Kato、Hiroaki Kajiyama、Yusuke Yamamoto
    • Journal Title

      Cancer Science

      Volume: 116(5) Issue: 5 Pages: 1339-1351

    • DOI

      10.1111/cas.70022

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety assessments and clinical features of PARP inhibitors from real-world data of Japanese patients with ovarian cancer2024

    • Author(s)
      Uekusa Ryosuke、Yokoi Akira、Watanabe Eri、Yoshida Kosuke、Yoshihara Masato、Tamauchi Satoshi、Shimizu Yusuke、Ikeda Yoshiki、Yoshikawa Nobuhisa、Niimi Kaoru、Suzuki Shiro、Kajiyama Hiroaki
    • Journal Title

      Scientific Reports

      Volume: 14 Issue: 1

    • DOI

      10.1038/s41598-024-63600-z

    • Related Report
      2024 Annual Research Report
  • [Journal Article] Update on the oncologic and obstetric outcomes of medroxyprogesterone acetate treatment for atypical endometrial hyperplasia and endometrial cancer2024

    • Author(s)
      Tamauchi Satoshi、Nakagawa Atsushi、Yoshida Kosuke、Yoshihara Masato、Yokoi Akira、Yoshikawa Nobuhisa、Niimi Kaoru、Kajiyama Hiroaki
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: - Issue: 9 Pages: 1614-1621

    • DOI

      10.1111/jog.16038

    • Related Report
      2024 Annual Research Report
  • [Journal Article] Elucidation of the role of XBP1 in the progression of complete hydatidiform mole to invasive mole through RNA-seq2024

    • Author(s)
      Shibata Mayu、Yoshida Kosuke、Yokoi Akira、Suzuki Hironori、Yamamoto Yusuke、Kitagawa Masami、Asano-Inami Eri、Yasui Yuko、Nishiko Yuki、Yoshihara Masato、Tamauchi Satoshi、Yoshikawa Nobuhisa、Nishino Kimihiro、Yamamoto Eiko、Niimi Kaoru、Kajiyama Hiroaki
    • Journal Title

      Gynecologic Oncology

      Volume: 190 Pages: 189-199

    • DOI

      10.1016/j.ygyno.2024.08.023

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating serum miRNAs predict response to platinum chemotherapy in high‐grade serous ovarian cancer2024

    • Author(s)
      Suzuki Kazuhiro、Yokoi Akira、Matsuzaki Juntaro、Yoshida Kosuke、Yamamoto Yusuke、Kato Tomoyasu、Ishikawa Mitsuya、Ochiya Takahiro、Kajiyama Hiroaki
    • Journal Title

      Cancer Medicine

      Volume: 13 Issue: 22

    • DOI

      10.1002/cam4.70251

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Amniotic fluid‐derived small extracellular vesicles for predicting postnatal severe outcome of congenital diaphragmatic hernia2024

    • Author(s)
      Matsuo Seiko、Yokoi Akira、Yoshida Kosuke、Kitagawa Masami、Asano‐Inami Eri、Miura Mayo、Yasui Takao、Tano Sho、Ushida Takafumi、Imai Kenji、Kajiyama Hiroaki、Kotani Tomomi
    • Journal Title

      Journal of Extracellular Biology

      Volume: 3 Issue: 6

    • DOI

      10.1002/jex2.160

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spatial exosome analysis using cellulose nanofiber sheets reveals the location heterogeneity of extracellular vesicles2023

    • Author(s)
      Yokoi Akira、Yoshida Kosuke、Koga Hirotaka、Kitagawa Masami、Nagao Yukari、Iida Mikiko、Kawaguchi Shota、Zhang Min、Nakayama Jun、Yamamoto Yusuke、Baba Yoshinobu、Kajiyama Hiroaki、Yasui Takao
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 6915-6915

    • DOI

      10.1038/s41467-023-42593-9

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel therapeutic strategies targeting UCP2 in uterine leiomyosarcoma2023

    • Author(s)
      Nagao Yukari、Yokoi Akira、Yoshida Kosuke、Sugiyama Mai、Watanabe Eri、Nakamura Kae、Kitagawa Masami、Asano-Inami Eri、Koya Yoshihiro、Yoshihara Masato、Tamauchi Satoshi、Shimizu Yusuke、Ikeda Yoshiki、Yoshikawa Nobuhisa、Kato Tomoyasu、Yamamoto Yusuke、Kajiyama Hiroaki
    • Journal Title

      Pharmacological Research

      Volume: 189 Pages: 106693-106693

    • DOI

      10.1016/j.phrs.2023.106693

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypoalbuminemia for the prediction of survival in patients with stage IVB cervical cancer2022

    • Author(s)
      Yoshikawa Nobuhisa、Yoshihara Masato、Tamauchi Satoshi、Ikeda Yoshiki、Yokoi Akira、Kajiyama Hiroaki
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 9 Pages: 0273876-0273876

    • DOI

      10.1371/journal.pone.0273876

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preoperative serum microRNAs as potential prognostic biomarkers in ovarian clear cell carcinoma2022

    • Author(s)
      Suzuki Kazuhiro、Yokoi Akira、Yoshida Kosuke、Kato Tomoyasu、Ochiya Takahiro、Yamamoto Yusuke、Kajiyama Hiroaki
    • Journal Title

      Journal of Gynecologic Oncology

      Volume: 34 Issue: 3

    • DOI

      10.3802/jgo.2023.34.e34

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Survival benefits of retroperitoneal lymphadenectomy for optimally-resected advanced ovarian high-grade serous carcinoma: a multi-institutional retrospective study2022

    • Author(s)
      Ikeda Yoshiki、Yoshihara Masato、Tamauchi Satoshi、Yokoi Akira、Yoshikawa Nobuhisa、Kajiyama Hiroaki
    • Journal Title

      Journal of Gynecologic Oncology

      Volume: 33 Issue: 4

    • DOI

      10.3802/jgo.2022.33.e40

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant activation of cell cycle-related kinases and the potential therapeutic impact of PLK1 or CHEK1 inhibition in uterine leiomyosarcoma2022

    • Author(s)
      Yoshida Kosuke、Yokoi Akira、Yamamoto Tomofumi、Hayashi Yusuke、Nakayama Jun、Yokoi Tsuyoshi、Yoshida Hiroshi、Kato Tomoyasu、Kajiyama Hiroaki、Yamamoto Yusuke
    • Journal Title

      Clinical Cancer Research

      Volume: - Issue: 10 Pages: 2147-2159

    • DOI

      10.1158/1078-0432.ccr-22-0100

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Drug library screening identifies histone deacetylase inhibition as a novel therapeutic strategy for choriocarcinoma2022

    • Author(s)
      Watanabe Eri、Yokoi Akira、Yoshida Kosuke、Sugiyama Mai、Kitagawa Masami、Nishino Kimihiro、Yamamoto Eiko、Niimi Kaoru、Yamamoto Yusuke、Kajiyama Hiroaki
    • Journal Title

      Cancer Medicine

      Volume: 12 Issue: 4 Pages: 4543-4556

    • DOI

      10.1002/cam4.5243

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Extracellular vesicles derived from vaginal bacteria initiate the progression of early-phase ovarian carcinoma at fallopian tubes2025

    • Author(s)
      Akira Yokoi, Eri Inami, Kosuke Yoshida, Yukari Nagao, Masami Kitagawa, Hiroaki Kajiyama
    • Organizer
      SGO Annual Meeting on Women's Cancer
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] EVシートによる新しいバイオマーカー戦略創出2025

    • Author(s)
      横井暁
    • Organizer
      第9回 Liquid Biopsy 研究会
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] Spatial exosome analysis reveals the location heterogeneity of exosomal miRNAs in ovarian cancer patients2024

    • Author(s)
      Akira Yokoi, Kosuke Yoshida, Yusuke Yamamoto, Takao Yasui , Hiroaki Kajiyama
    • Organizer
      AACR Annual Meeting 2024
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tailored cellulose nanofiber sheets capture and preserve small extracellular vesicles from micro-volume body fluids and reveal the unknown profiles of extracellular vesicles.2024

    • Author(s)
      Akira Yokoi, Kosuke Yoshida, Masami Kitagawa, Takao Yasui, Hiroaki Kajiyama
    • Organizer
      Annual Meeting of International Society for Extracellular Vesicles 2024
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腟内細菌由来細胞外小胞による卵巣がん超早期進展機構の解明2024

    • Author(s)
      横井 暁, 稲見 恵理, 吉田 康将, 長尾 有佳里, 北川 雅美, 梶山 広明
    • Organizer
      第23回日本婦人科がん分子標的研究会
    • Related Report
      2024 Annual Research Report
  • [Presentation] EVシートを活用した新しい細胞外小胞トランスレーショナル研究2024

    • Author(s)
      横井暁
    • Organizer
      慈恵医科大学 先端医学推進拠点群 エクソソーム医学研究センター シンポジウム
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] Spatial Exosome Analysis Reveals the Location Heterogeneity of EV-miRNAs in Cancer Patients2024

    • Author(s)
      横井暁
    • Organizer
      Asia Pacific Societies for Extracellular Vesicles (APSEV) 2024
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] エクソソームを標的とした新しいがん診療バイオマーカーの創出2024

    • Author(s)
      横井暁
    • Organizer
      第62回日本癌治療学会学術集会
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] 最新!体液中エクソソームの応用性と可能性2024

    • Author(s)
      横井暁
    • Organizer
      BioJapan / 再生医療JAPAN / healthTECH JAPAN
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] 空間的腹水中エクソソーム解析による新しい卵巣がん進展メカニズム解析2023

    • Author(s)
      横井 暁
    • Organizer
      第65回日本婦人科腫瘍学会
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] Malignant Mechanisms of Intercellular Communication in Gynecologic Cancers2023

    • Author(s)
      Akira Yokoi
    • Organizer
      8th Biennial Meeting of Asian Society of Gynecologic Oncology (ASGO 2023)
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Translational Research for Extracellular Vesicles in Ovarian Carcinoma2023

    • Author(s)
      Akira Yokoi
    • Organizer
      第65回日本婦人科腫瘍学会
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] 卵巣がんにおける細胞外小胞エクソソームの包括的機能解析2023

    • Author(s)
      横井 暁
    • Organizer
      第75回 日本産科婦人科学会学術講演会
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] 革新的エクソソーム回収テクノロジーを利用した新しいLiquid Biopsy戦略2023

    • Author(s)
      横井 暁
    • Organizer
      第8回 Liquid, Biopsy 研究会
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] EVシートによる生体内微量腹水中エクソソーム解析2023

    • Author(s)
      横井 暁、吉田 康将、北川 雅美、梶山 広明、山本 雄介、安井 隆雄
    • Organizer
      第7回 Liquid Biopsy 研究会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 卵巣がん細胞由来核酸搭載エクソソームの機能解析と臨床応用2022

    • Author(s)
      横井 暁
    • Organizer
      第74回日本産科婦人科学会学術講演会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Comprehensive analyses of ovarian cancer exosomes for clinical applications2022

    • Author(s)
      Akira Yokoi
    • Organizer
      ASGO 2022 7th International Workshop on Gynecologic Oncology
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] DNA損傷応答/分裂期のチェックポイント 子宮平滑筋肉腫に対するPLK1/CHEK1阻害剤2022

    • Author(s)
      横井 暁、吉田 康将、山本 雄介、加藤 友康、落谷 孝広、梶山 広明
    • Organizer
      第7回日本肉腫学会年次学術集会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Novel exsome analyses for micro volume ascites in ovarian cancer dissemination2022

    • Author(s)
      横井 暁, 安井 隆雄, 吉田 康将, 北川 雅美, 梶山 広明
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] 対象液体に含まれる対象物質を分離する方法2022

    • Inventor(s)
      安井隆雄、横井暁
    • Industrial Property Rights Holder
      東海国立大学機構
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2022 Research-status Report

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Published: 2022-07-05   Modified: 2026-01-16  

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