• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The study of the regulatory mechanisms of cancer bone destruction metabolism and immunity in Hedgehog signaling

Research Project

Project/Area Number 18H02999
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionHealth Sciences University of Hokkaido

Principal Investigator

SHIMO Tsuyoshi  北海道医療大学, 歯学部, 教授 (40362991)

Co-Investigator(Kenkyū-buntansha) 佐々木 朗  岡山大学, 医歯薬学域, 教授 (00170663)
吉田 祥子  岡山大学, 歯学部, 客員研究員 (00616047)
青山 絵理子  岡山大学, 医歯薬学域, 助教 (10432650)
國定 勇希  岡山大学, 医歯薬学域, 助教 (10779416)
滝川 正春  岡山大学, 医歯薬学域, 教授 (20112063)
奥井 達雄  島根大学, 学術研究院医学・看護学系, 准教授 (40610928)
長塚 仁  岡山大学, 医歯薬学域, 教授 (70237535)
高畠 清文  岡山大学, 医歯薬学域, 助教 (70736537)
久保田 聡  岡山大学, 医歯薬学域, 教授 (90221936)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Keywords癌 / 骨破壊 / 口腔癌 / 顎骨破壊 / 破骨細胞 / 血管新生 / ヘッジホッグ / 癌骨破壊 / Hedgehog
Outline of Final Research Achievements

Hedgehog downstream signaling molecules deployed from a comprehensive pathway analysis in the cancer bone destruction microenvironment (Shimo et al. PlosOne 2016) are associated with prognosis in gingival cancer patients with Stage IV jaw bone invasion (Yoshida, Shimo et al. Diagnostics (Basel) 2021).
In addition, tumor vascular endothelial cells in patients with Stage II introverted tongue cancer showed significantly enhanced expression of Hedgehog signaling and a positive correlation with tumor-associated macrophage (TAM) accumulation (Takabatake, Shimo et al. Int J Mol Sci 2019). We also analyzed the histological and genetical effect of Gli-1 and Gli-2 dual inhibitor on the in vitro study and in vivo cancer bone destruction mouse model.

Academic Significance and Societal Importance of the Research Achievements

口腔癌の顎骨浸潤は,化学療法の効果が期待できず,高線量の放射線療法では放射線性顎骨壊死のリスクが高いため外科療法が選択される。しかしながら,機能温存の観点から問題点も多く,顎骨切除症例における歯肉癌骨髄浸潤は予後に独立して寄与し(Yoshida, Shimo et al. Anticancer Res 2018),癌を取り巻く微小環境が薬剤耐性獲得に関与することから癌骨破壊微小環境は新たな治療標的となる可能性がわかってきた。癌骨破壊微小環境で活性化されるHedgehogシグナルを起点とした癌免疫の統合的な解析が必須である。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (20 results)

All 2022 2021 2020 2019

All Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Expression of Neurokinin B Receptor in the Gingival Squamous Cell Carcinoma Bone Microenvironment2021

    • Author(s)
      Shoko Yoshida, Tsuyoshi Shimo, Kiyofumi Takabatake, Yurika Murase, Kyoichi Obata, Tatsuo Okui, Yuki Kunisada, Soichiro Ibaragi, Hitoshi Nagatsuka, Akira Sasaki
    • Journal Title

      Diagnostics (Basel, Switzerland)

      Volume: 11 Pages: 1044-1044

    • NAID

      120007116755

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression and Role of IL-1β Signaling in Chondrocytes Associated with Retinoid Signaling during Fracture Healing2020

    • Author(s)
      Shimo Tsuyoshi、Takebe Hiroaki、Okui Tatsuo、Kunisada Yuki、Ibaragi Soichiro、Obata Kyoichi、Kurio Naito、Shamsoon Karnoon、Fujii Saki、Hosoya Akihiro、Irie Kazuharu、Sasaki Akira、Iwamoto Masahiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 7 Pages: 2365-2365

    • DOI

      10.3390/ijms21072365

    • NAID

      120007127458

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hedgehog Signaling in Organogenesis and the Tumor Microenvironment2020

    • Author(s)
      Shimo Tsuyoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 8 Pages: 2788-2788

    • DOI

      10.3390/ijms21082788

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sonic Hedgehog Signaling and Tooth Development2020

    • Author(s)
      Hosoya Akihiro、Shalehin Nazmus、Takebe Hiroaki、Shimo Tsuyoshi、Irie Kazuharu
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 5 Pages: 1587-1587

    • DOI

      10.3390/ijms21051587

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sonic Hedgehog Regulates Bone Fracture Healing2020

    • Author(s)
      Takebe Hiroaki、Shalehin Nazmus、Hosoya Akihiro、Shimo Tsuyoshi、Irie Kazuharu
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 2 Pages: 677-677

    • DOI

      10.3390/ijms21020677

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High-mobility group box 1 induces bone destruction associated with advanced oral squamous cancer via RAGE and TLR42020

    • Author(s)
      Sakamoto Yumi、Okui Tatsuo、Yoneda Toshiyuki、Ryumon Shoji、Nakamura Tomoya、Kawai Hotaka、Kunisada Yuki、Ibaragi Soichiro、Masui Masanori、Ono Kisho、Obata Kyoichi、Shimo Tsuyoshi、Sasaki Akira
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 531 Issue: 3 Pages: 422-430

    • DOI

      10.1016/j.bbrc.2020.07.120

    • NAID

      120006890006

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High mobility group box 1 induces bone pain associated with bone invasion in a mouse model of advanced head and neck cancer2020

    • Author(s)
      Nakamura Tomoya、Okui Tatsuo、Hasegawa Kazuaki、Ryumon Shoji、Ibaragi Soichiro、Ono Kisho、Kunisada Yuki、Obata Kyoichi、Masui Masanori、Shimo Tsuyoshi、Sasaki Akira
    • Journal Title

      Oncology Reports

      Volume: 44 Issue: 6 Pages: 2547-2558

    • DOI

      10.3892/or.2020.7788

    • NAID

      120007004824

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stem cell properties of Gli1-positive cells in the periodontal ligament2020

    • Author(s)
      Hosoya A, Shalehin N, Takebe H, Fujii S, Seki Y, Mizoguchi T, Shimo T, Iijima M, Irie K
    • Journal Title

      J Oral Biosciences

      Volume: 62 Issue: 4 Pages: 299-305

    • DOI

      10.1016/j.job.2020.08.002

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma2019

    • Author(s)
      Takabatake K, Shimo T, Murakami J, Anqi C, Kawai H, Yoshida S, Wathone Oo M, Haruka O, Sukegawa S, Tsujigiwa H, Nakano K, Nagatsuka H.
    • Journal Title

      Int J Mol Sci

      Volume: 20(22) Issue: 22 Pages: 5779-5779

    • DOI

      10.3390/ijms20225779

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ammonium trtrathiomolybdate enhances the anti tumor effect of cisplatin via the suppression of ATPase copper transporting beta in head and neck squamous cell carcinoma2019

    • Author(s)
      Ryumon S., Okui T.,Kunisada Y., Kishimoto K., Shimo T., Hasegawa K., Ibaragi S., Akiyama K., Thi Thu Ha N., Hassan NMM., Sasaki A.
    • Journal Title

      Oncology Reports

      Volume: 42 Pages: 2611-2621

    • DOI

      10.3892/or.2019.7367

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Retinoic Receptor Signaling Regulates Hypertrophic Chondrocyte-specific Gene Expression2019

    • Author(s)
      SHIMO TSUYOSHI、KOYAMA EIKI、OKUI TATSUO、MASUI MASANORI、KUNISADA YUKI、IBARAGI SOICHIRO、YOSHIOKA NORIE、KURIO NAITO、YOSHIDA SHOKO、SASAKI AKIRA、IWAMOTO MASAHIRO
    • Journal Title

      In Vivo

      Volume: 33 Issue: 1 Pages: 85-91

    • DOI

      10.21873/invivo.11443

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 透明化技術とイメージング解析を用いた扁平上皮癌による骨破壊及び骨形成抑制の検討2022

    • Author(s)
      島谷真梨, 志茂剛
    • Organizer
      第76回日本口腔科学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 癌微小環境におけるHedgehogシグナルの局在とその役割の解析2021

    • Author(s)
      Karnoon Shamsoon,平木大地,横関健治,堀江尚弘,藤井彩貴,斎藤隆史,志茂 剛
    • Organizer
      第66回日本口腔外科学会総会・学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Melanoma2021

    • Author(s)
      Karnoon Shamsoon, Hiroaki Takebe, Daichi Hiraki, Mari Shimatani, Saki Fujii, Takashi Saito, Tsuyoshi Shimo
    • Organizer
      北海道医療大学歯学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Gli1陽性歯根膜細胞は抜歯窩治癒過程において歯槽骨形成に寄与する2021

    • Author(s)
      藤井彩貴,志茂 剛
    • Organizer
      第66回日本口腔外科学会総会・学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 悪性黒色腫に対するヘッジホッグシグナル阻害剤GANT61の作用機構の解明2021

    • Author(s)
      平木大地,Karnoon Shamsoon,原田文也,永易裕樹,志茂 剛
    • Organizer
      第66回日本口腔外科学会総会・学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 透明化技術を用いた悪性黒色腫細胞骨浸潤のイメージング解析2021

    • Author(s)
      島谷真梨,志茂 剛
    • Organizer
      第47回日本口腔外科学会北日本支部学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 選択的CAMKK2阻害剤の開発に向けたスクリーニング解析2021

    • Author(s)
      島谷真梨,志茂剛,谷村明彦
    • Organizer
      北医療大歯誌. 40(1):77
    • Related Report
      2021 Annual Research Report
  • [Presentation] Misdiagnosis of gingival cancer as periodontitis - mechanism of cancer induced jaw bone destruction2019

    • Author(s)
      Tsuyoshi Shimo
    • Organizer
      Euro Dentistry, London, UK
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Oral squamous cell carcinoma induced jaw bone destruction2019

    • Author(s)
      Tsuyoshi Shimo
    • Organizer
      International Dental Forum, London, UK
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi