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The roles of spcific differentiation and cellular senescence in oncogenesis of odontogenic epithelium within the intraosseous microenvironment

Research Project

Project/Area Number 21K09852
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionTohoku University

Principal Investigator

Kumamoto Hiroyuki  東北大学, 歯学研究科, 教授 (70215028)

Co-Investigator(Kenkyū-buntansha) 齋藤 悠  東北大学, 歯学研究科, 助教 (00824450)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords歯原性腫瘍 / 腫瘍発生 / 骨内進展 / 細胞分化 / 細胞老化 / 幹細胞 / 種原性腫瘍
Outline of Research at the Start

歯原性上皮は本来歯の発生に関わる組織であるが、嚢胞や腫瘍への病的変化も稀ではない。これらの病的変化を起こす要因として、細胞死関連因子、細胞周期制御因子、細胞増殖因子、歯の発生制御因子、硬組織関連蛋白など様々な分子や遺伝子の変化が解明されつつあるが、病理発生や病態進展に関わる詳細なメカニズムはあきらかではない。本研究では、歯原性上皮由来の腫瘍細胞における細胞特異的分化または未分化状態および細胞老化に関わる因子について検索し、これらの細胞が骨内微小環境との相互作用によって受ける影響を包括的に解析し、これらの因子が歯原性上皮の病的変化や病態に及ぼす影響について検討する。

Outline of Final Research Achievements

Regulator molecules associated with cell cycle, epithelialcellstemness, and cellular senescence were examined to clarify the role of cell status in oncogenesis of odontogenic epithelium under the intraosseous microenvironment. Cell cycle-related molecules, Cdt1, geminin, and γ-H2A.X, were greater in ameloblastoma than in tooth germ, and Cdt1 in many neoplastic cells, geminin in peripheral neoplastic cells, and γ-H2A.X in central neoplastic cells are redognized. Epithelial stem cell markers, LGR5 and 6, and a cellular senescence-related molecule, SIRT1, were expressed higher in ameloblastoma than in tooth germ. LGR6 showed greater neoplastic cells reactivity than LGR5. SIRT1 tended to show higher expression in older patients.

Academic Significance and Societal Importance of the Research Achievements

正常および腫瘍性の歯原性組織における細胞周期関連分子、上皮幹細胞関連分子、細胞老化関連分子を検索し、腫瘍化による歯原性上皮細胞の特異的な状況や特徴的な腫瘍組織所見・臨床病態との関連を見出した。これらによって、歯原性腫瘍を包括する骨内微小環境下での歯原性上皮の増殖や分化に関わる歯原性上皮の最奥動態・活性状況について、検討することができた。これらの因子は、歯原性上皮が関わる様々な病変の診断や予後判定、治療に応用しうると考えられる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (22 results)

All 2024 2023 2022 2021

All Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 1 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Primary Oral Mixed Neuroendocrine?Non-neuroendocrine Neoplasm (MiNEN): A Rare Case Report and Review of the Literature2024

    • Author(s)
      Sripodok Pawat、Kouketsu Atsumu、Kuroda Kanako、Miyashita Hitoshi、Sugiura Tsuyoshi、Kumamoto Hiroyuki
    • Journal Title

      Head and Neck Pathology

      Volume: 18 Issue: 1 Pages: 13-13

    • DOI

      10.1007/s12105-024-01613-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Immunoexpression of SIRT1, 6, and 7 in oral leukoplakia and oral squamous cell carcinoma2023

    • Author(s)
      Sripodok Pawat、Saito Haruka、Kouketsu Atsumu、Takahashi Tetsu、Kumamoto Hiroyuki
    • Journal Title

      Odontology

      Volume: 112 Issue: 1 Pages: 221-229

    • DOI

      10.1007/s10266-023-00816-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Myeloid‐derived suppressor cells and plasmacytoid dendritic cells are associated with oncogenesis of oral squamous cell carcinoma2023

    • Author(s)
      Kouketsu Atsumu、Haruka Saito、Kuroda Kanako、Hitoshi Miyashita、Kensuke Yamauchi、Tsuyoshi Sugiura、Takahashi Tetsu、Hiroyuki Kumamoto
    • Journal Title

      Journal of Oral Pathology & Medicine

      Volume: 52 Issue: 1 Pages: 9-19

    • DOI

      10.1111/jop.13386

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case of tenosynovial giant cell tumor secondary to synovial chondromatosis in the temporomandibular joint2023

    • Author(s)
      Morishima Hiromitsu、Nogami Shinnosuke、Igarashi Ayano、Imoto Kazuhiro、Saito Shizu、Chiba Masatoshi、Kumamoto Hiroyuki、Takahashi Tetsu、Yamauchi Kensuke
    • Journal Title

      Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology

      Volume: 35 Issue: 6 Pages: 572-576

    • DOI

      10.1016/j.ajoms.2023.03.009

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glandular odontogenic cyst in mandible: a case report and literature review2022

    • Author(s)
      Odashima K Nogami S Kitamura J Iwama R Yanagisawa Y Kajita T Miyashita H Ymauchi K Kumamoto H Takahashi T
    • Journal Title

      J Oral Maxillofac Surg Med Pathol

      Volume: 34 Issue: 4 Pages: 531-535

    • DOI

      10.1016/j.ajoms.2021.11.006

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Condylar Resorption Following Compressive Mechanical Stress in Rabbit Model - Association of Matrix Metalloproteinases2022

    • Author(s)
      NOGAMI SHINNOSUKE、KATAOKA YOSHIHIRO、YAMAUCHI KENSUKE、YANAGISAWA YUTA、IMOTO KAZUHIRO、KUMASAKA AKIRA、IZUMITA KUNIYUKI、KAJITA TOMONARI、IIKUBO MASAHIRO、KUMAMOTO HIROYUKI、TAKAHASHI TETSU
    • Journal Title

      In Vivo

      Volume: 36 Issue: 5 Pages: 2126-2133

    • DOI

      10.21873/invivo.12938

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biodegradation behaviors of magnesium(Mg)-based alloy nails in autologous bone grafts: In vivo study in rabbit skulls2022

    • Author(s)
      Yanagisawa Yuta、Shimizu Yoshinaka、Mukai Toshiji、Sano Yuya、Odashima Kenji、Ikeo Naoko、Saito Haruka、Yamauchi Kensuke、Takahashi Tetsu、Kumamoto Hiroyuki
    • Journal Title

      Journal of Applied Biomaterials & Functional Materials

      Volume: 20 Pages: 1-14

    • DOI

      10.1177/22808000221095230

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunohistochemical expression levels of cyclin D1 and CREPT reflect the course and prognosis in oral precancerous lesions and squamous cell carcinoma2021

    • Author(s)
      Siril YJ Kouketsu A Saito H Takahashi T Kumamoto H
    • Journal Title

      Int J Oral Maxillofac Surg

      Volume: 50 Issue: 1 Pages: 27-32

    • DOI

      10.1016/j.ijom.2021.03.012

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The accuracy of ultrasound and magnetic resonance imaging for estimating thickness of oral tongue squamous cell carcinoma and influence of biopsy on those findings2021

    • Author(s)
      Nogami Shinnosuke、Yamauchi Kensuke、Kitamura Jun、Miyashita Hitoshi、Kojima Ikuho、Kouketsu Atsumu、Furuuchi Toshi、Iikubo Masahiro、Kumamoto Hiroyuki、Takahashi Tetsu
    • Journal Title

      Oral Science International

      Volume: 19 Issue: 1 Pages: 24-30

    • DOI

      10.1002/osi2.1108

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of different diagnostic imaging techniques for the detection of bone invasion in oral cancers2021

    • Author(s)
      Kouketsu Atsumu、Miyashita Hitoshi、Kojima Ikuho、Sakamoto Maya、Murata Takaki、Mori Shiro、Nogami Shinnnosuke、Yamauchi Kensuke、Nagai Hirokazu、Kumamoto Hiroyuki、Takahashi Tetsu
    • Journal Title

      Oral Oncology

      Volume: 120 Pages: 105453-105453

    • DOI

      10.1016/j.oraloncology.2021.105453

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] In vivo behaviors of highly flexible paper consisting of ultralong hydroxyapatite nanowires2021

    • Author(s)
      Kashiwada H, Shimizu Y, Yuya Sano, Kensuke Yamauchi, Hong Guang, Hiroyuki Kumamoto, Hidero Unuma, Ying-Jie Zhu
    • Journal Title

      Journal of Biomedical Materials Research Part B Applied Biomaterials

      Volume: in print Issue: 10 Pages: 101-107

    • DOI

      10.1002/jbm.b.34819

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] エナメル上皮腫におけるLGR5/6発言についての検討2024

    • Author(s)
      後藤弓里子 Pawat Sripodok 飯久保正弘 熊本裕行
    • Organizer
      第113回日本病理学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 比較的広範な透過像を示したエナメル上皮腫の臨床的検討2024

    • Author(s)
      五十嵐彩乃 大竹義雄 井本和宏 鈴木飛佳理 岩前有香 野上晋之介 熊本裕行 山内健介
    • Organizer
      第42回日本口腔腫瘍学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 透析患者のエナメル上皮腫内部に異所性石灰化を認めた1症例2024

    • Author(s)
      佐藤舜 柳沢佑太 鈴木飛佳理 野上晋之介 熊本裕行 山内健介
    • Organizer
      第42回日本口腔腫瘍学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Klotho and GATA4 immunoexpression in oral leukolakia and oral carcinoma2024

    • Author(s)
      Sripodok P Kouketsu A Sugiura T Kumamoto H
    • Organizer
      102nd General Session & Exhibition of the IADR
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Expression of SIRT1,6, and 7 in oral leukolakia and oral squamous cell carcinoma2023

    • Author(s)
      Sripodok P Saito H Kouketsu A Takahashi T Kumamoto H
    • Organizer
      第47回日本頭頚部癌学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 下顎骨に生じ再発を認めた腺性歯原性嚢胞の1例2022

    • Author(s)
      小田島健二 野上晋之介 梶田倫功 山内健介 熊本裕行 髙橋哲
    • Organizer
      第76回日本口腔科学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 顎関節滑膜軟骨腫症の臨床・画像所見と併せた病理組織学的検討2022

    • Author(s)
      大竹義雄 野上晋之介 小田島健二 江副祐史 千葉雅俊 山内健介 熊本裕行 髙橋哲
    • Organizer
      第35回日本顎関節学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 歯原性腫瘍の病理診断2022

    • Author(s)
      熊本裕行
    • Organizer
      令和3年度熊本県がん診療連携拠点病院機能強化事業がん診断部会講演会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] エナメル上皮腫における未分化能持続に関連する因子に関する研究2021

    • Author(s)
      黒田佳奈子 纐纈衆 齋藤悠 熊本裕行 髙橋哲
    • Organizer
      第66回日本口腔外科学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 口腔癌における骨髄由来抑制系細胞および形質細胞様樹状細胞に関する臨床病理学的研究2021

    • Author(s)
      纐纈衆 髙橋哲 熊本裕行
    • Organizer
      第39回日本口腔腫瘍学会総会
    • Related Report
      2021 Research-status Report
  • [Book] 新口腔病理学 第3版2021

    • Author(s)
      熊本裕行(下野正基 高田隆 田沼順一 豊澤悟 編)
    • Total Pages
      364
    • Publisher
      医歯薬出版
    • ISBN
      9784263458594
    • Related Report
      2021 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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