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Innovative histopathological diagnosis and therapy in osteosarcoma

Research Project

Project/Area Number 19K07413
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionShiga University of Medical Science

Principal Investigator

Suzuko Moritani  滋賀医科大学, 医学部, 准教授 (20283559)

Co-Investigator(Kenkyū-buntansha) 茶野 徳宏  滋賀医科大学, 医学部, 准教授 (40346028)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsRAB39A / RXRB / osteosarcoma / RDH10 / ovarian cancer / carbohydrate / cancer stem cell / PEPCK / 骨肉腫 / がん幹細胞 / 分子標的阻害
Outline of Research at the Start

骨肉腫治療へ高用量抗がん剤が適用されるようになり約30年が経過するが、その後、治療成績に大きな改善は見られないままである。未だ1/3の症例は肺転移、死亡に至る。肺転移、死亡を規定する分子マーカー、治療標的も分かっていない。我々は、骨肉腫のがん幹細胞を規定する新規分子経路RAB39A-RXRBを同定している。
本研究では、骨肉腫コホートに於けるRAB39A, RXRB分子の病理診断マーカーとしての可能性を免疫組織化学的手法にて明らかにし、また、RNAiを用いたRAB39A, RXRB分子の標的阻害実験により骨肉腫に対する治療学的意義を証明する。

Outline of Final Research Achievements

In osteosarcomas, RAB39A-RXRB pathway wasn't a clinicopathological biomarker. On the other hand, targeted RAB39A inhibition showed strong anticancer effects in many osteosarcomas, indicating that this molecular inhibition has broadly therapeutic applicability in osteosarcomas.
We further searched for molecules supporting RXRB-cancer stem pathway and identified RDH10, which is important for maintaining carbohydrate storage in ovarian cancer stem cells. Inhibiting RDH10-PEPCK-RXRB molecular pathway can reduce the cancer stem cell function in ovarian cancers, suggesting the molecular inhibition of this pathway will become a novel therapeutic target for ovarian cancers.

Academic Significance and Societal Importance of the Research Achievements

骨肉腫に於いてはRAB39A-RXRB経路は臨床病理学的なバイオマーカーとはなりませんでしたが、RXRBがん幹細胞経路を支援する分子探索を更に実施することで、RDH10分子を新規に同定しました。
RDH10分子は、骨肉腫ではなく、卵巣がんに於いて、がん幹細胞機能の維持に極めて重要であり、RDH10-PEPCK-RXRBの分子経路を阻害することで、卵巣がん幹細胞のcarbohydrate貯蔵能を抑制し、がん幹細胞機能を強く阻害できることが明らかになりました。本経路の阻害は、卵巣がんに対する新たな治療標的となり得ると考えられます。

Report

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

    (15 results)

All 2021 2020 2019

All Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 10 results) Book (1 results)

  • [Journal Article] Antioxidants and Therapeutic Targets in Ovarian Clear Cell Carcinoma2021

    • Author(s)
      Amano Tsukuru、Murakami Atsushi、Murakami Takashi、Chano Tokuhiro
    • Journal Title

      Antioxidants

      Volume: 10 Issue: 2 Pages: 187-187

    • DOI

      10.3390/antiox10020187

    • NAID

      120006956951

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Histopathological explanation of the MRI target sign in extra-axial schwannomas2021

    • Author(s)
      Ishizawa Michihito、Okabe Hidetoshi、Matsumoto Keiji、Morimoto Shigeru、Hukuda Sinsuke、Chano Tokuhiro
    • Journal Title

      Journal of Orthopaedic Science

      Volume: 26 Issue: 4 Pages: 660-665

    • DOI

      10.1016/j.jos.2020.06.009

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Single short retention instillation of pirarubicin prevents intravesical recurrence of low-risk non muscle invasive bladder cancer2021

    • Author(s)
      Susumu Kageyama, koki Maeda, Shigehisa Kubota, Tetsuya Yoshida, Takashi Osafune, Yutaka Arai, Hiroki Soga, Zenkai Nishikawa, Yuji Sano, Keita Takimoto, Chul Jang Kim, Tokuhiro Chano, Akihiro Kawauchi
    • Journal Title

      in vivo

      Volume: 35 Issue: 2 Pages: 1141-1145

    • DOI

      10.21873/invivo.12360

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Linking oxidative stress and ovarian cancers2021

    • Author(s)
      Amano Tsukuru、Chano Tokuhiro
    • Journal Title

      Cancer; Oxidative Stress and Dietary Antioxidants; Book; Second Edition

      Volume: Chapter 8 Pages: 77-86

    • DOI

      10.1016/b978-0-12-819547-5.00008-0

    • ISBN
      9780128195475
    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] A risk stratification model based on four novel biomarkers predicts prognosis for patients with renal cell carcinoma2020

    • Author(s)
      Kubota Shigehisa、Yoshida Tetsuya、Kageyama Susumu、Isono Takahiro、Yuasa Takeshi、Yonese Junji、Kushima Ryoji、Kawauchi Akihiro、Chano Tokuhiro
    • Journal Title

      World Journal of Surgical Oncology

      Volume: 18 Issue: 1 Pages: 270-270

    • DOI

      10.1186/s12957-020-02046-9

    • NAID

      120006901558

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Depletion of gamma-glutamylcyclotransferase inhibits cancer cell growth by activating the AMPK?FOXO3a?p21 axis2019

    • Author(s)
      Taniguchi Keiko、Ii Hiromi、Kageyama Susumu、Takagi Hiroko、Chano Tokuhiro、Kawauchi Akihiro、Nakata Susumu
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 517 Issue: 2 Pages: 238-243

    • DOI

      10.1016/j.bbrc.2019.07.049

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Current Position of the Molecular Therapeutic Targets for Ovarian Clear Cell Carcinoma: A Literature Review2019

    • Author(s)
      Amano Tsukuru、Chano Tokuhiro、Yoshino Fumi、Kimura Fuminori、Murakami Takashi
    • Journal Title

      Healthcare

      Volume: 7 Issue: 3 Pages: 94-94

    • DOI

      10.3390/healthcare7030094

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blockade of γ-Glutamylcyclotransferase Enhances Docetaxel Growth Inhibition of Prostate Cancer Cells2019

    • Author(s)
      TAKAGI HIROKO、II HIROMI、KAGEYAMA SUSUMU、HANADA EIKI、TANIGUCHI KEIKO、YOSHIYA TAKU、CHANO TOKUHIRO、KAWAUCHI AKIHIRO、NAKATA SUSUMU
    • Journal Title

      Anticancer Research

      Volume: 39 Issue: 9 Pages: 4811-4816

    • DOI

      10.21873/anticanres.13666

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acid microenvironment promotes cell survival of human bone sarcoma through the activation of cIAP proteins and NF-κB pathway.2019

    • Author(s)
      Avnet S, Chano T, Massa A, Bonuccelli G, Lemma S, Falzetti L, Grisendi G, Dominici M, Baldini N.
    • Journal Title

      Am J Cancer Res

      Volume: 9 Pages: 1127-1144

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Abundance of mitochondrial superoxide dismutase is a negative predictive biomarker for endometriosis-associated ovarian cancers2019

    • Author(s)
      Amano Tsukuru、Chano Tokuhiro、Isono Takahiro、Kimura Fuminori、Kushima Ryoji、Murakami Takashi
    • Journal Title

      World Journal of Surgical Oncology

      Volume: 17 Issue: 1 Pages: 24-24

    • DOI

      10.1186/s12957-019-1565-0

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ADP-ribosylation factor-like 4C is a predictive biomarker of poor prognosis in patients with renal cell carcinoma.2019

    • Author(s)
      Isono T, Chano T, Yoshida T, Makino A, Ishida S, Suzaki M, Kageyama S, Kawauchi A, Yonese J, Yuasa T.
    • Journal Title

      Am J Cancer Res

      Volume: 9 Pages: 415-423

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ADP-ribosylation factor-like 4C predicts worse prognosis in endometriosis-associated ovarian cancers.2019

    • Author(s)
      Wakinoue S, Chano T, Amano T, Isono T, Kimura F, Kushima R, Murakami T.
    • Journal Title

      Cancer Biomark.

      Volume: 24 Issue: 2 Pages: 223-229

    • DOI

      10.3233/cbm-181836

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pro-GA, a Novel Inhibitor of γ-Glutamylcyclotransferase, Suppresses Human Bladder Cancer Cell Growth2019

    • Author(s)
      HANADA EIKI、KAGEYAMA SUSUMU、MURAI RYOSUKE、KUBOTA SHIGEHISA、II HIROMI、NAKATA SUSUMU、KITA HIROKO、KAWAUCHI AKIHIRO、CHANO TOKUHIRO
    • Journal Title

      Anticancer Research

      Volume: 39 Issue: 4 Pages: 1893-1898

    • DOI

      10.21873/anticanres.13297

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preferential Tumor Accumulation of Polyglycerol Functionalized Nanodiamond Conjugated with Cyanine Dye Leading to Near‐Infrared Fluorescence In Vivo Tumor Imaging2019

    • Author(s)
      Yoshino Fumi、Amano Tsukuru、Zou Yajuan、Xu Jian、Kimura Fuminori、Furusho Yoshio、Chano Tokuhiro、Murakami Takashi、Zhao Li、Komatsu Naoki
    • Journal Title

      Small

      Volume: 15 Issue: 48 Pages: 1901930-1901930

    • DOI

      10.1002/smll.201901930

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Book] Chapter 8 - Linking oxidative stress and ovarian cancers. In Cancer2021

    • Author(s)
      Amano T, Chano T
    • Publisher
      Academic Press
    • ISBN
      9780128195475
    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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