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Analysis of extracellular vesicles using patient derived xenograft

Research Project

Project/Area Number 19K09838
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionOsaka Medical and Pharmaceutical University

Principal Investigator

Tomohito Tanaka  大阪医科薬科大学, 医学部, 講師 (90411363)

Co-Investigator(Kenkyū-buntansha) 林 正美  大阪医科薬科大学, 医学部, 准教授 (00551748)
大道 正英  大阪医科薬科大学, 医学部, 教授 (10283764)
田中 良道  大阪医科薬科大学, 医学部, 講師 (10625502)
恒遠 啓示  大阪医科薬科大学, 医学部, 講師 (70388255)
佐々木 浩  大阪医科薬科大学, 医学部, 講師 (80432491)
古形 祐平  大阪医科薬科大学, 医学部, 助教 (80829953)
寺井 義人  大阪医科薬科大学, 医学部, 非常勤講師 (90278531)
Project Period (FY) 2019-04-01 – 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 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords細胞外小胞 / PDX / マイクロRNA / PDX / 臨床腫瘍直接移植モデル / EVs / 腫瘍直接移植モデル / Te-EVs / エクソソーム / 卵巣癌 / 子宮頸癌
Outline of Research at the Start

癌細胞が小胞を放出していることが明らかになり注目を集めている。これらは細胞外小胞と呼ばれ、細胞間の免疫応答や血液凝固など様々なプロセスに関与している。細胞外小胞の中には抗腫瘍免疫における応答や、炎症を抑制する免疫寛容性などを誘導する様々な物質が含まれており、癌細胞の増殖や浸潤・転移に関わっていると考えられる。本研究では子宮頸癌、子宮内膜癌および卵巣癌において細胞外小胞が関与する癌細胞の増殖や浸潤・転移のメカニズムについて臨床腫瘍検体をマウスに直接移植したPatient-derived xenograft (PDX) modelを用いて解明することを目的としている。

Outline of Final Research Achievements

This study aimed to identify cancer-specific miRNAs as novel ovarian clear cell carcinoma (OCC) biomarkers using tissue-exudative extracellular vesicles (Te-EVs). Te-EVs were collected from four patients with OCC on one side and a normal ovary on the other side. Microarray analysis was performed to identify cancer-specific miRNAs in Te-EVs. Serum samples obtained before and after surgery from patients with OCC and atypical endometrial hyperplasia (AEH) (controls) were compared. Thirty-seven miRNAs were > 2-fold upregulated on the OCC side compared with the normal ovarian side. The levels of six EV miRNAs were significantly decreased in postoperative OCC serum compared to those in preoperative OCC serum. In contrast, no significant change was observed between the pre and post-operative values in the control group. We identified OCC tissue-specific miRNAs in the EVs secreted by OCC tissues. These EV miRNAs have potential for use as biomarkers for the early diagnosis.

Academic Significance and Societal Importance of the Research Achievements

本研究では癌が放出する細胞外小胞内の癌特異的マイクロRNAを同定した。さらに、細胞外小胞自体が転移や浸潤に影響を与えていることを確認した。これらの癌組織から放出された細胞外小胞をターゲットにして、癌の早期発見や、新薬の開発の可能性が示唆された。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (29 results)

All 2023 2022 2021 2020 2019 Other

All Journal Article (16 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 16 results,  Open Access: 16 results) Presentation (11 results) (of which Int'l Joint Research: 1 results) Remarks (2 results)

  • [Journal Article] Boron uptake of boronophenylalanine and the effect of boron neutron capture therapy in cervical cancer cells2023

    • Author(s)
      Terada Shinichi、Tsunetoh Satoshi、Tanaka Yoshimichi、Tanaka Tomohito、Kashiwagi Hideki、Takata Takushi、Kawabata Shinji、Suzuki Minoru、Ohmichi Masahide
    • Journal Title

      Applied Radiation and Isotopes

      Volume: 197 Pages: 110792-110792

    • DOI

      10.1016/j.apradiso.2023.110792

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Effect of Maternal Coagulation Parameters on Fetal Acidemia in Placental Abruption2022

    • Author(s)
      Sugimoto Atsuko、Tanaka Tomohito、Ashihara Keisuke、Daimon Atsushi、Nunode Misa、Nagayasu Yoko、Fujita Daisuke、Tanabe Akiko、Kamegai Hideki、Taniguchi Kohei、Komura Kazumasa、Ohmichi Masahide
    • Journal Title

      Journal of Clinical Medicine

      Volume: 11 Issue: 24 Pages: 7504-7504

    • DOI

      10.3390/jcm11247504

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer-Specific miRNAs Extracted from Tissue-Exudative Extracellular Vesicles in Ovarian Clear Cell Carcinoma2022

    • Author(s)
      Maruoka Hiroshi、Tanaka Tomohito、Murakami Hikaru、Tsuchihashi Hiromitsu、Toji Akihiko、Nunode Misa、Daimon Atsushi、Miyamoto Shunsuke、Nishie Ruri、Ueda Shoko、Hashida Sousuke、Terada Shinichi、Konishi Hiromi、Kogata Yuhei、Taniguchi Kohei、Komura Kazumasa、Ohmichi Masahide
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 24 Pages: 15715-15715

    • DOI

      10.3390/ijms232415715

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypoxia regulates tumour characteristic <scp>RNA</scp> modifications in ovarian cancers2022

    • Author(s)
      Monoe Yuya、Miyamoto Shunsuke、Jingushi Kentaro、Tanimoto Masaya、Tanaka Tomohito、Taniguchi Kohei、Komura Kazumasa、Ohmichi Masahide、Tsujikawa Kazutake
    • Journal Title

      The FEBS Journal

      Volume: 290 Issue: 8 Pages: 2085-2096

    • DOI

      10.1111/febs.16688

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Robot‐assisted modified radical hysterectomy with removal of lymphatic vessel using indocyanine green: A new method2022

    • Author(s)
      Tanaka Tomohito、Nishie Ruri、Ueda Shoko、Hashida Sousuke、Miyamoto Shunsuke、Terada Shinichi、Kogata Yuhei、Taniguchi Kohei、Komura Kazumasa、Ohmichi Masahide
    • Journal Title

      The International Journal of Medical Robotics and Computer Assisted Surgery

      Volume: 18 Issue: 6

    • DOI

      10.1002/rcs.2451

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Postsurgical urodynamic study of total laparoscopic nerve‐sparing radical hysterectomy for uterine cervical cancer2022

    • Author(s)
      Terada Shinichi、Terai Yoshito、Tanaka Yoshimichi、Tanaka Tomohito、Tsunetoh Satoshi、Ohmichi Masahide
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 48 Issue: 11 Pages: 2863-2871

    • DOI

      10.1111/jog.15371

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Validation of a Patient-Derived Xenograft Model for Cervical Cancer Based on Genomic and Phenotypic Characterization2022

    • Author(s)
      Shunsuke Miyamoto, Tomohito Tanaka, Kensuke Hirosuna, Ruri Nishie, Shoko Ueda, Sousuke Hashida, Shinichi Terada, Hiromi Konishi, Yuhei Kogata, Kohei Taniguchi, Kazumasa Komura, Masahide Ohmichi
    • Journal Title

      Cancers (Basel)

      Volume: 14 Issue: 12 Pages: 2969-2969

    • DOI

      10.3390/cancers14122969

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endometrial Cancer Patient-Derived Xenograft Models: A Systematic Review2022

    • Author(s)
      Tanaka Tomohito、Nishie Ruri、Ueda Shoko、Miyamoto Shunsuke、Hashida Sousuke、Konishi Hiromi、Terada Shinichi、Kogata Yuhei、Sasaki Hiroshi、Tsunetoh Satoshi、Taniguchi Kohei、Komura Kazumasa、Ohmichi Masahide
    • Journal Title

      Journal of Clinical Medicine

      Volume: 11 Issue: 9 Pages: 2606-2606

    • DOI

      10.3390/jcm11092606

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of Prognosis between Minimally Invasive and Abdominal Radical Hysterectomy for Patients with Early-Stage Cervical Cancer2022

    • Author(s)
      Tanaka Tomohito、Ueda Shoko、Miyamoto Shunsuke、Hashida Sousuke、Terada Shinichi、Konishi Hiromi、Kogata Yuhei、Taniguchi Kohei、Komura Kazumasa、Ohmichi Masahide
    • Journal Title

      Current Oncology

      Volume: 29 Issue: 4 Pages: 2272-2283

    • DOI

      10.3390/curroncol29040185

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Patient-Derived Xenograft Models in Cervical Cancer: A Systematic Review2021

    • Author(s)
      Tanaka Tomohito、Nishie Ruri、Ueda Shoko、Miyamoto Shunsuke、Hashida Sousuke、Konishi Hiromi、Terada Shinichi、Kogata Yuhei、Sasaki Hiroshi、Tsunetoh Satoshi、Taniguchi Kohei、Komura Kazumasa、Ohmichi Masahide
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 17 Pages: 9369-9369

    • DOI

      10.3390/ijms22179369

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] γ-H2AX as a potential indicator of radiosensitivity in colorectal cancer cells.2021

    • Author(s)
      Kawashima S, Kawaguchi N, Taniguchi K, Tashiro K, Komura K, Tanaka T, Inomata Y, Imai Y, Tanaka R, Yamamoto M, Inoue Y, Lee SW, Kawai M, Tanaka K, Okuda J, Uchiyama K.
    • Journal Title

      Oncol Lett

      Volume: 20(3) Issue: 3 Pages: 2331-2337

    • DOI

      10.3892/ol.2020.11788

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacokinetic evaluation and antitumor potency of liposomal nanoparticle encapsulated cisplatin targeted to CD24-positive cells in ovarian cancer2020

    • Author(s)
      Ashihara K, Terai Y, Tanaka T, Tanaka Y, Fujiwara S, Maeda K, Tunetoh S, Sasaki H, Hayashi M, Ohmichi M.
    • Journal Title

      Oncol Lett.

      Volume: 19 Pages: 1872-1880

    • DOI

      10.3892/ol.2020.11279

    • NAID

      120006873100

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Protective Effect of Testosterone on the Ovarian Reserve During Cyclophosphamide Treatment2020

    • Author(s)
      Yoo M, Tanaka T, Konishi H, Tanabe A, Taniguchi K, Komura K, Hayashi M, Ohmichi M.
    • Journal Title

      Onco Targets Ther.

      Volume: 13 Pages: 2987-2995

    • DOI

      10.2147/ott.s242703

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum exosomal microRNA-34a as a potential biomarker in epithelial ovarian cancer2020

    • Author(s)
      Maeda K, Sasaki H, Ueda S, Miyamoto S, Terada S, Konishi H, Kogata Y, Ashihara K, Fujiwara S, Tanaka Y, Tanaka T, Hayashi M, Ito Y, Kondo Y, Ochiya T, Ohmichi M
    • Journal Title

      J Ovarian Res.

      Volume: 13 Issue: 1 Pages: 47-47

    • DOI

      10.1186/s13048-020-00648-1

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Diagnostic Accuracy of an Intraoperative Frozen Section Analysis and Imprint Cytology of Sentinel Node Biopsy Specimens from Patients with Uterine Cervical and Endometrial Cancer: aRetrospective Observational Study2020

    • Author(s)
      Tanaka T, Miyamoto S, Terada S, Kogata Y, Fujiwara S, Tanaka Y, Taniguchi K, Komura K, Yamamoto K, Yamada T, Ohmichi M.
    • Journal Title

      Pathol Oncol Res.

      Volume: - Issue: 4 Pages: 2273-2279

    • DOI

      10.1007/s12253-020-00822-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intraperitoneal cytology after laparoscopic radical hysterectomy with vaginal closure without the use of a manipulator for cervical cancer: a retrospective observational study2019

    • Author(s)
      Tanaka T, Miyamoto S, Terada S, Kogata Y, Sasaki H, Tsunetoh S, Yamada T, Ohmichi M
    • Journal Title

      Cancer Manag Res.

      Volume: 11 Pages: 7015-7020

    • DOI

      10.2147/cmar.s210277

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 子宮体がんにおける個別化治療にむけたPDXモデルの検討2022

    • Author(s)
      上田尚子、西江瑠璃、橋田宗祐、宮本瞬輔、寺田信一、古形祐平、藤原聡枝、田中良道、田中智人、大道正英
    • Organizer
      第64回日本婦人科腫瘍学会学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 婦人科癌肉腫におけるPDX(Patient-Derived Xenograft)モデル2022

    • Author(s)
      宮本瞬輔、村上 暉、西江瑠璃、上田尚子、橋田宗祐、寺田信一、古形祐平、藤原聡枝、田中良道、田中智人、恒遠啓示、山田隆司、大道正英
    • Organizer
      第64回日本婦人科腫瘍学会学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 進行婦人科癌患者における腹水・胸水を用いた患者由来がんモデルの作製と検証2022

    • Author(s)
      西江瑠璃、田中智人、村上 暉、上田尚子、橋田宗祐、宮本瞬輔、寺田信一、古形祐平、藤原聡枝、田中良道、恒遠啓示、佐々木浩、山田隆司、大道正英
    • Organizer
      第64回日本婦人科腫瘍学会学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 患者由来がんモデルを用いた難治性婦人科悪性腫瘍の個別化医療の構築2022

    • Author(s)
      西江瑠璃、田中智人、福西智美、小川範子、齊藤駿介、井淵誠吾、村上 暉、上田尚子、橋田宗祐、宮本瞬輔、田中良道、大道正英
    • Organizer
      公益社団法人日本産科婦人科学会第74回学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 子宮頸癌におけるPDOX(Patient-Derived Orthotopic Xenograft)モデル2021

    • Author(s)
      宮本瞬輔、直聖一郎、西江瑠璃、上田尚子、寺田信一、古形祐平、藤原聡枝、田中智人、田中良道、大道正英
    • Organizer
      第73回日本産科婦人科学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 卵巣癌組織から抽出したTe-EVs(tissue-exudative extracellular vesicles)の解析2021

    • Author(s)
      宮本瞬輔、上田尚子、橋田宗助、寺田信一、古形祐平、藤原聡枝、田中良道、田中智人、恒遠啓示、神宮司健太郎、辻川和丈、大道正英
    • Organizer
      第63回日本婦人科腫瘍学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 卵巣癌におけるPDOX (Patient Derived Orthotopic Xenograft) モデル2020

    • Author(s)
      宮本瞬輔、安田奈央、飯藤宰士、大瀧瑠璃、上田尚子、寺田信一、小西博巳、丸岡 寛、古形祐平、田中智人、大道正英
    • Organizer
      第72回日本産科婦人科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 卵巣明細胞癌に対する切除組織培養分泌エクソソームを用いた特異的腫瘍マーカーの開発2020

    • Author(s)
      丸岡 寛、田中智人、小西莉奈、飯藤宰士、石川 渚、大瀧瑠璃、上田尚子、宮本瞬輔、寺田信一、小西博巳、林 正美、大道正英
    • Organizer
      第72回日本産科婦人科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 卵巣癌におけるPDOX(Patient Derived Orthotopic Xenograft)モデル2020

    • Author(s)
      宮本瞬輔 田中智人 大道正英
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 卵巣明細胞癌に対する切除組織培養分泌エクソソームを用いた特異的腫瘍マーカーの開発2020

    • Author(s)
      丸岡寛 田中智人 大道正英
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] A Patient-Derived Orthotopic Xenograft model of Cervical Cancer2020

    • Author(s)
      Miyamoto S., Tanaka T., Ohmichi M.
    • Organizer
      Global Academic Program 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] バイオバンク検体を用いたがんの再発・予後に関する血中、尿中新規バイオマーカーの探索と新規治療法の開発

    • URL

      https://www.osaka-med.ac.jp/deps/gyn/img/images/cmn/information/cresearch_15.pdf#view=Fit

    • Related Report
      2019 Research-status Report
  • [Remarks] 臨床腫瘍組織の直接移植モデルに関する研究

    • URL

      https://www.osaka-med.ac.jp/deps/gyn/img/images/cmn/information/cresearch_15.pdf#view=Fit

    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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