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Elucidation of the mechanism of HPV-associated oropharyngeal tumor carcinogenesis through the interaction between tumor-associated nerves and the cancer microenvironment.

Research Project

Project/Area Number 20K18259
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionYokohama City University

Principal Investigator

HATANO Takashi  横浜市立大学, 附属病院, 助教 (40807583)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords中咽頭癌 / ヒト乳頭腫ウイルス / オルガノイド / 腫瘍関連神経 / 癌微小環境 / 唾液腺腫瘍 / ヒト乳頭腫ウイルス関連中咽頭癌 / 頭頸部癌 / HPV / マイクロRNA / 神経新生
Outline of Research at the Start

頭頸部癌の中でもヒトパピローマウイルス(HPV)感染を主因とするHPV関連中咽頭癌の罹患数は著しく増加傾向を示している。HPV関連中咽頭癌の発癌および進展機序の詳細は不明な点が多くあるが,近年癌微小環境における癌細胞と神経細胞の相互作用が癌の進展に関連することが明らかになってきた。本研究では,HPV関連中咽頭癌発癌機構における,エクソソームを介した腫瘍関連神経の癌微小環境との相互作用の詳細を明らかにすることで,HPV関連中咽頭癌の中に依然として存在する予後不良群に対する新たな治療法開発へつなげることが期待される。

Outline of Final Research Achievements

Recently, it has become clear that the interaction between cancer cells and neurons in the cancer microenvironment is associated with cancer progression and drug resistance. The purpose of this study is to elucidate the details of the interaction between the cancer microenvironment and tumor-associated nerves in HPV-associated oropharyngeal cancer carcinogenesis. During the period of this study, we narrowed down the microRNAs involved in tumor-associated neurogenesis and established a salivary gland adenoid cystic carcinoma organoid model associated with nerve invasion as a basis for studying tumor-associated neurogenesis.

Academic Significance and Societal Importance of the Research Achievements

癌微小環境における癌細胞と神経細胞の相互作用が癌の進展や薬剤耐性に関連することが明らかになってきており,HPV関連中咽頭癌における癌微小環境と腫瘍関連神経との相互作用の詳細が明らかになれば,HPV関連中咽頭癌の発癌機構の解明や予後不良因子の同定へ寄与することとなり,HPVの有無によりわけられている中咽頭癌の分類をより詳細に層別化することが可能となる可能性がある。今回の研究成果として,今後のオルガノイドモデル作製の成果は今後の中咽頭癌オルガノイドモデル作製の素地となり,研究をすすめる技術的基盤となるものと考える。

Report

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

    (15 results)

All 2023 2022 2021 2020

All Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (6 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Establishment of experimental salivary gland cancer models using organoid culture and patientderived xenografting.2023

    • Author(s)
      Aizawa Y, Takada K, Aoyama J, Sano D, Yamanaka S, Seki M, Kuze Y, Ramilowski JA, Okuda R, Ueno Y, Nojima Y, Inayama Y, Hatakeyama H, Hatano T, Takahashi H, Nishimura G, Fujii S, Suzuki Y, Taniguchi H, Oridate N
    • Journal Title

      Cell Oncol.

      Volume: 46 Issue: 2 Pages: 409-421

    • DOI

      10.1007/s13402-022-00758-6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Real-world Therapeutic Outcomes of the Pembrolizumab Regimen as First-line Therapy for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: A Single-center Retrospective Cohort Study in Japan2022

    • Author(s)
      SANO DAISUKE、TOKUHISA MOTOHIKO、TAKAHASHI HIDEAKI、HATANO TAKASHI、NISHIMURA GOSHI、ICHIKAWA YASUSHI、ORIDATE NOBUHIKO
    • Journal Title

      Anticancer Research

      Volume: 42 Issue: 9 Pages: 4477-4484

    • DOI

      10.21873/anticanres.15948

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A risk factor for newly diagnosed secondary cancer in patients with early-stage laryngeal, oropharyngeal, or hypopharyngeal cancer: sub-analysis of a prospective observation study2021

    • Author(s)
      Nishimura Goshi、Sano Daisuke、Arai Yasuhiro、Takahashi Hideaki、Hatano Takashi、Kitani Yosuke、Takada Kentaro、Wada Takashi、Hiiragi Yohei、Oridate Nobuhiko
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 27 Issue: 3 Pages: 488-494

    • DOI

      10.1007/s10147-021-02080-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pathogenic Role of Immune Evasion and Integration of Human Papillomavirus in Oropharyngeal Cancer2021

    • Author(s)
      Hatano Takashi、Sano Daisuke、Takahashi Hideaki、Oridate Nobuhiko
    • Journal Title

      Microorganisms

      Volume: 9 Issue: 5 Pages: 891-891

    • DOI

      10.3390/microorganisms9050891

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] FosL1 Regulates Regional Metastasis of Head and Neck Squamous Cell Carcinoma by Promoting Cell Migration, Invasion, and Proliferation2021

    • Author(s)
      Hiroshi Hyakusoku, Kae Sawakuma, Daisuke Sano, Hideaki Takahashi, Takashi Hatano, Kaname Sato, Yasuhiro Isono, Shoko Shimada, Kentaro Takada, Tatsu Kuwahara, Yoshihiro Aizawa, Nobuhiko Oridate
    • Journal Title

      Anticancer research

      Volume: 41 Issue: 7 Pages: 3317-3326

    • DOI

      10.21873/anticanres.15119

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Validation of the risk factors for primary control of early T-stage laryngeal, oropharyngeal, and hypopharyngeal squamous cell carcinoma by transoral surgery: a prospective observational study2021

    • Author(s)
      Nishimura Goshi、Sano Daisuke、Arai Yasuhiro、Takahashi Hideaki、Hatano Takashi、Kitani Yosuke、Takada Kentaro、Wada Takashi、Hiiragi Yohei、Oridate Nobuhiko
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 26 Issue: 11 Pages: 1995-2003

    • DOI

      10.1007/s10147-021-01992-y

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Establishment of PDX‐derived salivary adenoid cystic carcinoma cell lines using organoid culture method2020

    • Author(s)
      Takada Kentaro、Aizawa Yoshihiro、Sano Daisuke、Okuda Ryo、Sekine Keisuke、Ueno Yasuharu、Yamanaka Shoji、Aoyama Jun、Sato Kaname、Kuwahara Tatsu、Hatano Takashi、Takahashi Hideaki、Arai Yasuhiro、Nishimura Goshi、Taniguchi Hideki、Oridate Nobuhiko
    • Journal Title

      International Journal of Cancer

      Volume: 148 Issue: 1 Pages: 193-202

    • DOI

      10.1002/ijc.33315

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] めずらしい腫瘍に対するアプローチ 病理がめずらしい 肉腫2020

    • Author(s)
      高田 顕太郎, 波多野 孝, 荒井 康裕, 西村 剛志, 折舘 伸彦
    • Journal Title

      JOHNS

      Volume: 36 Pages: 1499-1502

    • Related Report
      2020 Research-status Report
  • [Journal Article] 経口的ロボット手術の導入 横浜市立大学における初期経験2020

    • Author(s)
      佐野 大佑, 波多野 孝, 折舘 伸彦
    • Journal Title

      頭頸部外科

      Volume: 30 Pages: 139-140

    • NAID

      130007945962

    • Related Report
      2020 Research-status Report
  • [Presentation] ヒトHER2陽性唾液腺導管癌由来オルガノイドによるin vitro/in vivoでの薬効評価(Drug evaluation using patient-derived organoid of HER2-positive salivary duct carcinoma in vitro and in vivo)2022

    • Author(s)
      青山 準, 野島 雄介, 相澤 圭洋, 高田 顕太郎, 鬼島 菜摘, 平井 友梨, 波多野 孝, 高橋 秀聡, 佐野 大佑, 藤井 誠志, 折舘 伸彦
    • Organizer
      日本癌学会総会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] μオピオイド受容体を標的とした治療の開発2022

    • Author(s)
      高橋 秀聡, 佐野 大佑, 波多野 孝, 木谷 洋輔, 柊 陽平, 大平 彩菜, 折舘 伸彦
    • Organizer
      日本頭頸部癌学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ウイルス感染と頭頸部腫瘍 HPV関連中咽頭癌発癌におけるHPVの免疫逃避機構および組み込み機構の役割2021

    • Author(s)
      波多野 孝, 佐野 大佑, 高橋 秀聡, 折舘 伸彦
    • Organizer
      日本耳鼻咽喉科免疫アレルギー感染症学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 根治治療としてCRTを施行した中咽頭扁平上皮癌症例の予後予測におけるF-NLRの有用性2020

    • Author(s)
      波多野 孝, 高橋 秀聡, 佐野 大佑
    • Organizer
      日本癌治療学会学術集会
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 癌細胞のp53喪失は癌微小環境における神経の成長と再プログラムを通じて癌の進展を促す2020

    • Author(s)
      高橋 秀聡, 佐野 大佑, 波多野 孝, 佐藤 要, 桑原 達, 相沢 圭洋, 青山 準, 折舘 伸彦
    • Organizer
      日本癌学会学術集会
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 頭頸部扁平上皮癌における再発、転移病変腫瘍径のニボルマブ治療効果予測に対する有用性について2020

    • Author(s)
      佐野 大佑, 波多野 孝, 高橋 秀聡, 西村 剛志, 折舘 伸彦
    • Organizer
      日本耳鼻咽喉科学会学術総会・学術講演会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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