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Study on the Clinical and Molecular Pathological Significance of Autonomic Nerve Interactions in the Tumor Microenvironment of Salivary Duct Carcinoma

Research Project

Project/Area Number 21K09616
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionInternational University of Health and Welfare

Principal Investigator

TADA Yuichiro  国際医療福祉大学, 医学部, 准教授 (70292430)

Co-Investigator(Kenkyū-buntansha) 長尾 俊孝  東京医科大学, 医学部, 主任教授 (90276709)
赤澤 宏平  新潟大学, 医歯学総合病院, 教授 (10175771)
川北 大介  名古屋市立大学, 医薬学総合研究院(医学), 准教授 (70584506)
伏見 千宙  国際医療福祉大学, 大学病院, 講師 (20623531)
高橋 秀聡  横浜市立大学, 附属病院, 助教 (50727196)
平井 秀明  東京医科大学, 医学部, 助教 (00770744)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords唾液腺導管癌 / 癌免疫微小環境 / 自律神経 / 交感神経 / 副交感神経 / 腫瘍神経学 / がん微小環境 / ノルアドレナリン / TH発現 / VAChT発現 / 癌微小環境
Outline of Research at the Start

唾液腺導管癌組織内における自律神経の臨床病理学的および分子病理学的意義を明らかにし、将来的にはそれに基づく本腫瘍の新たな治療法の開発を目指す研究である。
全国9施設の共同研究により集積された唾液腺導管癌症例の病理組織標本を用いて、交感神経系マーカーであるTH、副交感神経系マーカーであるVAChT1CとCHAT、および、神経成長因子マーカーであるBDNF、β-NGF、CNTF、GDNF、LIFを用いて、癌組織内での発現を評価する。これらの結果と過去の先行研究で収集した臨床情報、各種バイオマーカーの発現、癌免疫微小環境との相関を解析し、予後との関連や治療における神経関連マーカーの意義を解析する。

Outline of Final Research Achievements

This study elucidated the clinical and molecular pathological significance of autonomic nerve interactions in the tumor microenvironment of salivary duct carcinoma (SDC). Immunohistochemical staining (S100, TH, VAChT, CHAT) was utilized to evaluate autonomic nerve markers, and the results were statistically analyzed concerning prognosis. The findings revealed that autonomic nerves in SDC tumor tissue significantly impact patient prognosis, highlighting the importance of interactions between sympathetic and parasympathetic nerves. These results were presented at the Japan Salivary Gland Society meeting and are currently under submission to an English journal.

Academic Significance and Societal Importance of the Research Achievements

本研究は、唾液腺導管癌(SDC)の癌微小環境における自律神経相互作用の臨床的・分子病理学的意義を明らかにした。免疫組織化学染色を用いて自律神経マーカー(S100、TH、VAChT、CHAT)を評価し、予後との関連を統計解析した。これにより、自律神経の存在がSDCの予後に与える影響を示し、特に交感神経と副交感神経の相互作用の重要性を明らかにした。これらの成果は、SDCの新たな治療法開発の基盤となる可能性があり、予後改善に寄与することが期待される。

Report

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

    (24 results)

All 2024 2023 2022 2021

All Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (12 results) (of which Int'l Joint Research: 4 results,  Invited: 7 results) Book (1 results)

  • [Journal Article] Brain metastases in patients with salivary duct carcinoma: A retrospective study2024

    • Author(s)
      Fushimi Chihiro、Takahashi Hideaki、Kawakita Daisuke、Kano Satoshi、Tsukahara Kiyoaki、Ozawa Hiroyuki、Okami Kenji、Sakai Akihiro、Yamazaki Keisuke、Okada Takuro、Hanazawa Toyoyuki、Sato Yuichiro、Imanishi Yorihisa、Shimizu Akira、Matsuki Takashi、Nagao Toshitaka、Tada Yuichiro
    • Journal Title

      Cancer Medicine

      Volume: 13 Issue: 5

    • DOI

      10.1002/cam4.7037

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 特集 新たに注目される頭頸部癌治療 分子標的治療薬 アンドロゲン遮断療法2023

    • Author(s)
      多田 雄一郎
    • Journal Title

      JOHNS

      Volume: 39 Issue: 11 Pages: 1364-1370

    • DOI

      10.24479/ohns.0000000846

    • ISSN
      0910-6820
    • Year and Date
      2023-11-01
    • Related Report
      2023 Annual Research Report
  • [Journal Article] 増刊号 豊富な処方例でポイント解説! 耳鼻咽喉科・頭頸部外科処方マニュアル 15 頭頸部がん 唾液腺がん2023

    • Author(s)
      岩城 翔、川北 大介、多田 雄一郎
    • Journal Title

      耳鼻咽喉科・頭頸部外科

      Volume: 95 Issue: 5 Pages: 317-320

    • DOI

      10.11477/mf.1411203373

    • ISSN
      0914-3491, 1882-1316
    • Year and Date
      2023-04-30
    • Related Report
      2023 Annual Research Report
  • [Journal Article] Systemic therapy for salivary gland carcinoma2023

    • Author(s)
      TADA Yuichiro
    • Journal Title

      Japanese Journal of Oral and Maxillofacial Surgery

      Volume: 69 Issue: 4 Pages: 178-184

    • DOI

      10.5794/jjoms.69.178

    • ISSN
      0021-5163, 2186-1579
    • Year and Date
      2023-04-20
    • Related Report
      2023 Annual Research Report
  • [Journal Article] 唾液腺癌に対する新たな薬物療法2023

    • Author(s)
      多田 雄一郎
    • Journal Title

      Nippon Jibiinkoka Tokeibugeka Gakkai Kaiho(Tokyo)

      Volume: 126 Issue: 2 Pages: 88-99

    • DOI

      10.3950/jibiinkotokeibu.126.2_88

    • ISSN
      2436-5793, 2436-5866
    • Year and Date
      2023-02-20
    • Related Report
      2023 Annual Research Report
  • [Journal Article] Prognostic value and clinicopathological roles of the tumor immune microenvironment in salivary duct carcinoma2023

    • Author(s)
      Hirai Hideaki、Nakaguro Masato、Tada Yuichiro、Saigusa Natsuki、Kawakita Daisuke、Honma Yoshitaka、Kano Satoshi、Tsukahara Kiyoaki、Ozawa Hiroyuki、Okami Kenji、Yamazaki Keisuke、Fushimi Chihiro、Kondo Takahito、Imanishi Yorihisa、Sakai Akihiro、Togashi Takafumi、Hanazawa Toyoyuki、Matsuki Takashi、Nagao Toshitaka
    • Journal Title

      Virchows Archiv

      Volume: 483 Issue: 3 Pages: 367

    • DOI

      10.1007/s00428-023-03598-3

    • URL

      https://pure.teikyo.jp/en/publications/3dae8340-e282-467e-9456-dc9d57ca4812

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of novel prognostic and predictive biomarkers in salivary duct carcinoma via comprehensive molecular profiling2022

    • Author(s)
      Kohsaka S, Tada Y, Okami K, et al.
    • Journal Title

      NPJ Precis Oncol.

      Volume: 6 Issue: 1 Pages: 82-82

    • DOI

      10.1038/s41698-022-00324-1

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma2022

    • Author(s)
      Kawakita Daisuke、Nagao Toshitaka、Takahashi Hideaki、Kano Satoshi、Honma Yoshitaka、Hirai Hideaki、Saigusa Natsuki、Akazawa Kohei、Tani Kaori、Ojiri Hiroya、Tsukahara Kiyoaki、Ozawa Hiroyuki、Okami Kenji、Kondo Takahito、Togashi Takafumi、Fushimi Chihiro、Shimura Tomotaka、Matsuki Takashi、Tada Yuichiro
    • Journal Title

      Therapeutic Advances in Medical Oncology

      Volume: 14 Pages: 175883592211195-175883592211195

    • DOI

      10.1177/17588359221119538

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 病理診断と頭頸部個別化治療のかかわり2022

    • Author(s)
      多田 雄一郎, 櫛橋 幸民, 平井 秀明
    • Journal Title

      耳鼻咽喉科

      Volume: 1 Pages: 676-692

    • Related Report
      2022 Research-status Report
  • [Journal Article] The Role of the EZH2 and H3K27me3 Expression as a Predictor of Clinical Outcomes in Salivary Duct Carcinoma Patients: A Large-Series Study With Emphasis on the Relevance to the Combined Androgen Blockade and HER2-Targeted Therapy2022

    • Author(s)
      Saigusa N, Hirai H, Kohsaka S, et al.
    • Journal Title

      Front Oncol

      Volume: 11 Pages: 779882-779882

    • DOI

      10.3389/fonc.2021.779882

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Predictive and Prognostic Biomarker Identification in a Large Cohort of Androgen Receptor-Positive Salivary Duct Carcinoma Patients Scheduled for Combined Androgen Blockade2021

    • Author(s)
      Lassche Gerben、Tada Yuichiro、van Herpen Carla M. L.、Jonker Marianne A.、Nagao Toshitaka、Saotome Takashi、Hirai Hideaki、Saigusa Natsuki、Takahashi Hideaki、Ojiri Hiroya、van Engen-Van Grunsven Adriana C. H.、Schalken Jack A.、Fushimi Chihiro、Verhaegh Gerald W.
    • Journal Title

      Cancers

      Volume: 13 Issue: 14 Pages: 3527-3527

    • DOI

      10.3390/cancers13143527

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Chemotherapy for AR+/HER2+ Parotid Cancer2023

    • Author(s)
      TADA Yuichiro
    • Organizer
      The 7th World Congress of the International Federation of Head and Neck Oncologic Societies
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Comprehensive Genomic Profiling of Salivary Gland Carcinomas in the Japanese Population; analysis of National Cancer Center,Center for Cancer Genomics and Advanced Therapeutics database2023

    • Author(s)
      Sho Iwaki, Daisuke Kawakita, Takuma Matoba, Hiroshi Inagaki, Yuichiro Tada, Toshitaka Nagao, Shinichi Iwasaki
    • Organizer
      The 7th World Congress of the International Federation of Head and Neck Oncologic Societies
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Precision Medicine 新世紀: 唾液腺導管癌2023

    • Author(s)
      多田雄一郎
    • Organizer
      第47回 日本頭頸部癌学会総会・学術講演会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 唾液腺導管癌における自律神経(交感神経・副交感神経)の臨床・分子病理学的意義2022

    • Author(s)
      梶原 真奈美, 高橋 秀聡, 川北 大介, 平井 秀明, 内海 由貴, 浦野 誠, 中黒 匡人, 佐藤 由紀子, 塚原 清彰, 加納 里志, 大上 研二, 小澤 宏之, 富樫 孝文, 岡田 拓朗, 多田 雄一郎, 長尾 俊孝
    • Organizer
      第66回日本唾液腺学会総会・学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 頭頸部がんの新たな治療戦略 唾液腺癌に対する新たな薬物療法2022

    • Author(s)
      多田雄一郎
    • Organizer
      第123回日本耳鼻咽喉科頭頸部外科学会 総会・学術講演会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 唾液腺癌に対するアンドロゲン遮断療法2022

    • Author(s)
      多田雄一郎
    • Organizer
      第32回日本頭頸部外科学会総会ならびに学術講演会
    • Related Report
      2022 Research-status Report
  • [Presentation] Yatagarasu: A single-arm, open-label, phase 2 study of apalutamide (APA) plus goserelin (GOS) for patients (pts) with far locally advanced or recurrent/metastatic (fLA/RM) and androgen receptor (AR)-expressing salivary gland carcinoma (SGC).2022

    • Author(s)
      Yoshitaka Honma, Nobuya Monden, Keisuke Yamazaki, Satoshi Kano, Hironaga Satake, Shigenori Kadowaki, Toshitaka Nagao, Tomohiko Nakatogawa, Koji Fujii, Yosuke Koroki, Junya Aoyama, Shohei Ouchi, Tetsuro Ogawa, Sharon McCarthy, Sabine D. Brookman-May, Suneel Mundle, Jinhui Li, Yuichiro Tada
    • Organizer
      ASCO annual meeting 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 頭頸部 唾液腺癌 唾液腺癌の治療 唾液腺導管癌に対する抗HER2治療、抗AR治療2022

    • Author(s)
      多田 雄一郎
    • Organizer
      第41回 日本画像医学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Predictive and prognostic biomarker identification in a large cohort of androgen receptor-positive salivary duct carcinoma patients scheduled for combined androgen blockade.2021

    • Author(s)
      Gerben Lassche, Yuichiro Tada, Carla M. Van Herpen, Marianne A. Jonker, Diederick Keizer, Wim Verhaegh, Toshitaka Nagao, Takashi Saotome, Hideaki Hirai, Natsuki Saigusa, Adriana C. van Engen - van Grunsven, Jack A. Schalken, Chihiro Fushimi, Gerald W. Verhaegh.
    • Organizer
      2021 American Society of Clinical Oncology Annual Meeting
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 唾液腺研究の新機軸:基礎から臨床まで 唾液腺癌の分子標的治療2021

    • Author(s)
      多田 雄一郎
    • Organizer
      第65回 日本唾液腺学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 唾液腺癌の診断と治療 Up to data 唾液腺癌に対する全身治療2021

    • Author(s)
      多田 雄一郎
    • Organizer
      第66回 日本口腔外科学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 唾液腺腫瘍細胞病理の新展開-基礎から臨床まで- 唾液腺癌の治療2021

    • Author(s)
      多田 雄一郎
    • Organizer
      第62回 日本臨床細胞学会 春期大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Book] 口腔癌 6章 唾液腺癌2023

    • Author(s)
      桐田 忠昭、原田 浩之
    • Total Pages
      724
    • Publisher
      医歯薬出版
    • ISBN
      9784263423158
    • Related Report
      2023 Annual Research Report

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

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