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Investigation of cancer extracellular vesicles for their revealing heterogeneity

Research Project

Project/Area Number 20K22806
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0901:Oncology and related fields
Research InstitutionNagoya University

Principal Investigator

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

Project Period (FY) 2020-09-11 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsエクソソーム / 細胞外小胞 / がん微小環境 / 卵巣がん / リキッドバイオプシー
Outline of Research at the Start

本研究は、未だ明らかにされていないがん細胞由来細胞外小胞の多様性と、臨床応用へ向けた特性を明らかにすることを目的とする。研究代表者は、予後不良の卵巣がんを対象とし、血液、腹水、腫瘍組織等を用いて、細胞外小胞(Extracellular Vesicle: EV)抽出方法の検討、EV表面タンパク質のプロテオーム解析、EV関連核酸(RNAおよびDNA)の次世代シーケンスによる解析等を行うことで、臨床検体ベースの取り扱いの最適化、および特異マーカーの同定を行う。本研究で明らかになる知見は今後急速に進むと予想されるEVトランスレーショナル研究において、極めて重要な意義をもつ。

Outline of Final Research Achievements

Extracellular vesicles (EVs) were extracted from bio-fluids of ovarian cancer patient and fresh tumor tissue and profiled for both protein and nucleic acids (DNA, miRNA). Ovarian cancer-specific proteins have been identified and are in the process of being published and patent pending. We have also identified DNA profiles associated with response rates to therapeutic drugs in ovarian cancer patients, and we will submit a patent application and prepare the manuscript. The data from sequencing and LC-MS/MS indicated that EVs of different sizes have different characteristics, and that it is appropriate to analyze small EVs as targets for body fluid diagnostics, and that they have different biological functions.

Academic Significance and Societal Importance of the Research Achievements

エクソソーム研究は、世界的にみて、現在最も注目を集めている研究分野の一つであり、世界中で多くの研究者が未だ明らかにされていないエクソソームの機能を明らかにしたいと熱を帯びている。本研究において主に対象とする卵巣がんは、極めて悪性度の高いがんであり、患者予後が悪く、サブタイプ等の多様性から、臨床に還元できる研究成果が得られにくいがん種である。しかし、その反面、臨床応用を目指した基礎的研究を行う意義は高いと言える。本研究により同定した卵巣がんにおけるEVの特性は、需要の極めて高い、エクソソーム研究、卵巣がん研究の双方の発展に寄与する極めて重要な位置づけとなる。

Report

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

    (31 results)

All 2022 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (19 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 19 results,  Open Access: 19 results) Presentation (9 results) (of which Invited: 5 results) Book (1 results) Remarks (1 results)

  • [Int'l Joint Research] UT MD Anderson Cancer Center(米国)

    • Related Report
      2021 Annual Research Report
  • [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
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy2022

    • Author(s)
      Uno Kaname、Yoshikawa Nobuhisa、Tazaki Akira、Ohnuma Shoko、Kitami Kazuhisa、Iyoshi Shohei、Mogi Kazumasa、Yoshihara Masato、Koya Yoshihiro、Sugiyama Mai、Tamauchi Satoshi、Ikeda Yoshiki、Yokoi Akira、Kikkawa Fumitaka、Kato Masashi、Kajiyama Hiroaki
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 4513-4513

    • DOI

      10.1038/s41598-022-08503-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Is adjuvant chemotherapy necessary for young women with early-stage epithelial ovarian cancer who have undergone fertility-sparing surgery?: a multicenter retrospective analysis2022

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

      BMC Women's Health

      Volume: 22 Issue: 1 Pages: 80-80

    • DOI

      10.1186/s12905-022-01642-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peritoneal restoration by repurposing vitamin D inhibits ovarian cancer dissemination via blockade of the TGF-β1/thrombospondin-1 axis2022

    • Author(s)
      Kitami Kazuhisa、Yoshihara Masato、Tamauchi Satoshi、Sugiyama Mai、Koya Yoshihiro、Yamakita Yoshihiko、Fujimoto Hiroki、Iyoshi Shohei、Uno Kaname、Mogi Kazumasa、Ikeda Yoshiki、Yokoi Akira、Yoshikawa Nobuhisa、Nishino Kimihiro、Niimi Kaoru、Nawa Akihiro、Enomoto Atsushi、Kajiyama Hiroaki
    • Journal Title

      Matrix Biology

      Volume: 109 Pages: 70-90

    • DOI

      10.1016/j.matbio.2022.03.003

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ChrXq27.3 miRNA cluster functions in cancer development2021

    • Author(s)
      Yoshida Kosuke、Yokoi Akira、Yamamoto Yusuke、Kajiyama Hiroaki
    • Journal Title

      Journal of Experimental & Clinical Cancer Research

      Volume: 40 Issue: 1

    • DOI

      10.1186/s13046-021-01910-0

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of Concurrent Chemoradiotherapy as Primary Treatment in Patients with Metastatic Cervical Cancer2021

    • Author(s)
      Hattori Satomi、Yoshikawa Nobuhisa、Mogi Kazumasa、Yoshida Kosuke、Yoshihara Masato、Tamauchi Satoshi、Ikeda Yoshiki、Yokoi Akira、Nishino Kimihiro、Niimi Kaoru、Suzuki Shiro、Kajiyama Hiroaki
    • Journal Title

      Current Oncology

      Volume: 28 Issue: 3 Pages: 1663-1672

    • DOI

      10.3390/curroncol28030155

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabolome analysis reveals a diversity of cancer tissues in advanced epithelial ovarian cancer2021

    • Author(s)
      Yoshida Kosuke、Yoshikawa Nobuhisa、Kitami Kazuhisa、Tamauchi Satoshi、Ikeda Yoshiki、Yokoi Akira、Nishino Kimihiro、Niimi Kaoru、Kajiyama Hiroaki
    • Journal Title

      Cancer Cell International

      Volume: 21 Issue: 1

    • DOI

      10.1186/s12935-021-02014-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Is cystectomy an option as conservative surgery for young patients with borderline ovarian tumor? A multi‐institutional retrospective study2021

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

      International Journal of Gynecology & Obstetrics

      Volume: 157 Issue: 2 Pages: 437-443

    • DOI

      10.1002/ijgo.13844

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD63-mediated cloaking of VEGF in small extracellular vesicles contributes to anti-VEGF therapy resistance2021

    • Author(s)
      Ma Shaolin、Mangala S、Hu W、Bayaktar E、Yokoi A、Hu W、Pradeep S、Lee S、Piehowski PD.、Villar-Prados A、Wu S.、McGuire M.、Lara Olivia D.、Rodriguez C、LaFargue Christopher J.、Jennings B.、Rodland D.、Liu Tao、Kundra V、Ram Prahlad T.、Ramakrishnan Sundaram、Lopez Gabriel、Coleman RL.、Sood AK.
    • Journal Title

      Cell Reports

      Volume: 36 Issue: 7 Pages: 109549-109549

    • DOI

      10.1016/j.celrep.2021.109549

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exosomes and extracellular vesicles: Rethinking the essential values in cancer biology2021

    • Author(s)
      Yokoi Akira、Ochiya Takahiro
    • Journal Title

      Seminars in Cancer Biology

      Volume: 74 Pages: 79-91

    • DOI

      10.1016/j.semcancer.2021.03.032

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adjuvant taxane plus platinum chemotherapy for stage I ovarian clear cell carcinoma with complete surgical staging: are more than three cycles necessary?2021

    • Author(s)
      Ukai Mayu、Suzuki Shiro、Yoshihara Masato、Yokoi Akira、Yoshikawa Nobuhisa、Kajiyama Hiroaki、Kikkawa Fumitaka
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 27 Issue: 3 Pages: 609-618

    • DOI

      10.1007/s10147-021-02075-8

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular microRNA profiling for prognostic prediction in patients with high‐grade serous ovarian carcinoma2021

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

      Cancer Science

      Volume: 112 Issue: 12 Pages: 4977-4986

    • DOI

      10.1111/cas.15154

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical effects of cervical conization with positive margins in cervical cancer2021

    • Author(s)
      Nagao Yukari、Yokoi Akira、Yoshida Kosuke、Sumi Masanori、Yoshihara Masato、Tamauchi Satoshi、Ikeda Yoshiki、Yoshikawa Nobuhisa、Nishino Kimihiro、Niimi Kaoru、Kajiyama Hiroaki
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1

    • DOI

      10.1038/s41598-021-02635-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gain-of-function p53 protein transferred via small extracellular vesicles promotes conversion of fibroblasts to a cancer-associated phenotype2021

    • Author(s)
      Ma Shaolin、McGuire Michael H.、Mangala Lingegowda S.、Lee Sanghoon、Stur Elaine、Hu Wen、Bayraktar Emine、Villar-Prados Alejandro、Ivan Cristina、Wu Sherry Y.、Yokoi Akira、Dasari Santosh K.、Jennings Nicholas B.、Liu Jinsong、Lopez-Berestein Gabriel、Ram Prahlad、Sood Anil K.
    • Journal Title

      Cell Reports

      Volume: 34 Issue: 6 Pages: 108726-108726

    • DOI

      10.1016/j.celrep.2021.108726

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Extracellular miRNAs as Predictive Biomarkers for Glypican-3-Derived Peptide Vaccine Therapy Response in Ovarian Clear Cell Carcinoma2021

    • Author(s)
      Ukai Mayu、Yokoi Akira、Yoshida Kosuke、Suzuki Shiro、Shibata Kiyosumi、Kikkawa Fumitaka、Nakatsura Tetsuya、Kajiyama Hiroaki
    • Journal Title

      Cancers

      Volume: 13 Issue: 3 Pages: 550-550

    • DOI

      10.3390/cancers13030550

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of the chrXq27.3 miRNA cluster in recurrent ovarian clear cell carcinoma and its impact on cisplatin resistance2021

    • Author(s)
      Yoshida Kosuke、Yokoi Akira、Sugiyama Mai、Oda Shingo、Kitami Kazuhisa、Tamauchi Satoshi、Ikeda Yoshiki、Yoshikawa Nobuhisa、Nishino Kimihiro、Niimi Kaoru、Suzuki Shiro、Kikkawa Fumitaka、Yokoi Tsuyoshi、Kajiyama Hiroaki
    • Journal Title

      Oncogene

      Volume: 40 Issue: 7 Pages: 1255-1268

    • DOI

      10.1038/s41388-020-01595-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The clinical impact of intra‐ and extracellular miRNAs in ovarian cancer2020

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

      Cancer Science

      Volume: 111 Issue: 10 Pages: 3435-3444

    • DOI

      10.1111/cas.14599

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ovarian cancer-associated mesothelial cells induce acquired platinum-resistance in peritoneal metastasis via the FN1/Akt signaling pathway.2020

    • Author(s)
      Yoshihara M, Kajiyama H, Yokoi A, Sugiyama M, Koya Y, Yamakita Y, Liu W, Nakamura K, Moriyama Y, Yasui H, Suzuki S, Yamamoto Y, Ricciardelli C, Nawa A, Shibata K, Kikkawa F
    • Journal Title

      Int J Cancer

      Volume: 146 Issue: 8 Pages: 2268-2280

    • DOI

      10.1002/ijc.32854

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 卵巣がんにおける脂肪系幹細胞由来small extracellular vesiclesの抗腫瘍効果2021

    • Author(s)
      横井 暁, 吉田 康将, 宇野 枢, 梶山 広明
    • Organizer
      日本癌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ドラッグリポジショニングを用いた卵巣がん細胞のエクソソーム分泌抑制剤のスクリーニング2021

    • Author(s)
      吉岡 祐亮, 横井 暁, 落谷 孝広
    • Organizer
      日本癌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 卵巣がん細胞外小胞の機能解析と臨床応用へ向けた基盤研究2021

    • Author(s)
      横井 暁
    • Organizer
      日本婦人科腫瘍学
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 細胞外循環型マイクロRNAによる新しいバイオマーカー戦略2021

    • Author(s)
      横井 暁
    • Organizer
      日本婦人科がん検診診断学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 卵巣がんにおける核酸搭載細胞外小胞の機能解析と臨床応用2020

    • Author(s)
      横井 暁
    • Organizer
      日本癌学会総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 核由来DNA搭載エクソソームを用いた新規リキッドバイオプシー戦略2020

    • Author(s)
      横井 暁
    • Organizer
      日本癌学会総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 卵巣がんにおける核酸搭載細胞外小胞の包括的解析2020

    • Author(s)
      横井 暁
    • Organizer
      日本癌学会総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 血液マイクロRNAによる子宮肉腫と変性筋腫の術前鑑別診断2020

    • Author(s)
      加藤 友康, 横井 暁, 松崎 潤太郎, 山本 雄介, 舘 慶生, 米岡 完, 清水 華子, 植原 貴史, 石川 光也, 滝澤 聡子, 青木 良晃, 加藤 健, 落谷 孝広
    • Organizer
      日本婦人科腫瘍学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Mechanisms of nuclear content loading to exosomes derived from high-grade serous ovarian cancer2020

    • Author(s)
      Akira Yokoi, Alejandro Villar-Prados, Kajiyama Hiroaki, Anil K Sood
    • Organizer
      婦人科腫瘍学会
    • Related Report
      2020 Research-status Report
  • [Book] 実験医学2021

    • Author(s)
      横井 暁
    • Total Pages
      1
    • Publisher
      羊土社
    • Related Report
      2021 Annual Research Report
  • [Remarks] https://researchmap.jp/akirayokoi

    • Related Report
      2021 Annual Research Report

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Published: 2020-09-29   Modified: 2023-01-30  

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