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Relationship between PI3K-Akt pathway activation and recurrence of early glottic cancer

Research Project

Project/Area Number 19K18731
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Makino Takuma  岡山大学, 大学病院, 助教 (50648706)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsMACC1 / recurrence / glottic cancer / サイトカイン / がん遺伝子 / 早期声門癌 / 再発 / 頭頸部癌
Outline of Research at the Start

Metastasis-associated with colon cancer 1は、PI3K/AKTシグナル経路を介してさまざまな悪性腫瘍の病態に関与している。しかし、頭頸部癌とMetastasis-associated with colon cancer 1の関連については報告がない。本研究では、頭頸部癌患者を対象に、PI3K/AKTシグナル経路に関する因子の網羅的な解析を行うとともに、検出された因子と治療効果などの臨床因子との関連を検討する。また、頭頸部癌モデルマウスを用いて、AKTの関連因子の発現を調べる。以上により、頭頸部癌に対する新規治療法やバイオマーカーの確立を目指す。

Outline of Final Research Achievements

The transcriptional target of MACC1 is c-Met, the gene that encodes HGF. MACC1 is involved in the signal transduction of PI3K-Akt pathways. Moreover, the involvement of MACC1 in the inactivation of apoptosis-inducing factors and in cell cycle promotion in malignancies is thought to contribute to cancer infiltration and metastasis. MACC1 has been reported to be an independent indicator of poor prognoses in some kinds of cancer due to disease metastasis or recurrence. However, a relationship between MACC1 and head and neck cancer has not been previously reported.
Johan et al. reported that the radioresistance of head and neck cancers is linked to PI3K-Akt pathway activation. As the PI3K-Akt pathway is assumed to be activated in MACC1-positive patients, we believe that MACC1 expression increase the risk of radioresistance. In the present study, we confirmed that MACC1 expression, in early stage glottic cancers, makes patients significantly more likely to experience recurrence after RT.

Academic Significance and Societal Importance of the Research Achievements

早期声門癌においてMACC1が陽性であれば、RT、CRT後に有意に再発を来たしやすいことを確認した。MACC1陽性例は放射線抵抗性が高かったことが再発を来しやすい一因ではないかと考えられた。本検討において再発症例はRT単独症例のみでCRT症例では認められなかった。これは化学療法を追加したことで、放射線治療抵抗性があるものの治療強度が上がり根治し得た可能性が考えられた。
MACC1陽性の声門癌ではより放射線抵抗性が強いことが推察されるため、治療強度を上げたCRTを行うことで再発を防げる可能性も考えられ、今後のさらなる検討が必要と考えられた。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (22 results)

All 2022 2021 2020 2019

All Journal Article (17 results) (of which Peer Reviewed: 10 results,  Open Access: 1 results) Presentation (5 results)

  • [Journal Article] 特集 新たに薬事承認・保険収載された薬剤・医療資材・治療法ガイド 《頭頸部》 セツキシマブサロタロカンナトリウムを用いた頭頸部イルミノックス治療2022

    • Author(s)
      牧野 琢丸
    • Journal Title

      耳鼻咽喉科・頭頸部外科

      Volume: 94 Issue: 1 Pages: 59-64

    • DOI

      10.11477/mf.1411202898

    • ISSN
      0914-3491, 1882-1316
    • Year and Date
      2022-01-20
    • Related Report
      2021 Research-status Report
  • [Journal Article] Midline involvement and perineural invasion predict contralateral neck metastasis that affects overall and disease-free survival in locally advanced oral tongue squamous cell carcinoma2022

    • Author(s)
      Maki Akamatsu,Takuma Makino,Shinya Morita,Yohei Noda,Shin Kariya,Tomoo Onoda,Mizuo Ando,Yoshihiro Kimata,Kazunori Nishizaki,Mitsuhiro Okano,Aiko Oka,Kengo Kanai,Yoshihiro Watanabe,Yorihisa Imanishi
    • Journal Title

      Front Oncol

      Volume: 12 Pages: 1010252-1010252

    • DOI

      10.3389/fonc.2022.1010252

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Candidemia in patients with head and neck cancer: mortality and a novel risk factor2022

    • Author(s)
      Uraguchi Kensuke、Makino Takuma、Kariya Shin、Noda Youhei、Marunaka Hidenori、Doi Akira、Kozakura Kenichi、Takao Soshi、Ando Mizuo
    • Journal Title

      Supportive Care in Cancer

      Volume: 30 Issue: 7 Pages: 5921-5930

    • DOI

      10.1007/s00520-022-07010-9

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] COVID-19症例に対する気管切開術施行時におけるシングルユース軟性鼻咽喉鏡の使用経験2022

    • Author(s)
      秋定 直樹, 假谷 伸, 牧野 琢丸, 大道 亮太郎, 梶原 壮平, 安藤 瑞生
    • Journal Title

      耳鼻咽喉科・頭頸部外科

      Volume: 94 Pages: 391-395

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 外耳道癌治療中に発症した胆道感染症例2022

    • Author(s)
      秋定 直樹, 牧野 琢丸, 森本 光作, 佐藤 明日香, 駿河 有莉, 梶原 壮平, 浦口 健介, 大道 亮太郎, 安藤 瑞生
    • Journal Title

      頭頸部外科

      Volume: 31 Pages: 301-305

    • NAID

      130008130435

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 【新たに薬事承認・保険収載された薬剤・医療資材・治療法ガイド】頭頸部 セツキシマブサロタロカンナトリウムを用いた頭頸部イルミノックス治療2022

    • Author(s)
      牧野 琢丸
    • Journal Title

      耳鼻咽喉科・頭頸部外科

      Volume: 94 Pages: 59-64

    • Related Report
      2022 Annual Research Report
  • [Journal Article] 【頸部リンパ節を見直す】頸部リンパ節腫脹 鑑別の手順 頸部リンパ節腫脹の視診と触診について2022

    • Author(s)
      牧野 琢丸
    • Journal Title

      JOHNS

      Volume: 38 Pages: 268-270

    • Related Report
      2022 Annual Research Report
  • [Journal Article] 【咽頭癌-最新の治療戦略】転移・再発咽頭癌に対するがん光免疫療法(頭頸部アルミノックス治療)2022

    • Author(s)
      牧野 琢丸
    • Journal Title

      医学と薬学

      Volume: 79 Pages: 1599-1603

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Cytopathological Findings of Secretory Carcinoma of the Salivary Gland and the Diagnostic Utility of Giemsa Staining2021

    • Author(s)
      Egusa Yuria、Nishimura Midori Filiz、Baba Satoko、Takeuchi Kengo、Makino Takuma、Tachibana Tomoyasu、Nishikori Asami、Fujita Azusa、Yanai Hiroyuki、Sato Yasuharu
    • Journal Title

      Diagnostics

      Volume: 11 Issue: 12 Pages: 2284-2284

    • DOI

      10.3390/diagnostics11122284

    • NAID

      120007183233

    • Related Report
      2021 Research-status Report
  • [Journal Article] A case of biliary tract infection during treatment for carcinoma of the external auditory canal2021

    • Author(s)
      Akisada Naoki、Makino Takuma、Morimoto Kosaku、Sato Asuka、Suruga Yuri、Kajihara Sohei、Uraguchi Kensuke、Omichi Ryotaro、Ando Mizuo
    • Journal Title

      JOURNAL OF JAPAN SOCIETY FOR HEAD AND NECK SURGERY

      Volume: 31 Issue: 3 Pages: 301-305

    • DOI

      10.5106/jjshns.21-005

    • NAID

      130008130435

    • ISSN
      1349-581X, 1884-474X
    • Related Report
      2021 Research-status Report
  • [Journal Article] Fertility Preservation Therapy Provided for Childhood, Adolescent, and Young Adult Cancer Patients2021

    • Author(s)
      Akisada Naoki、Makino Takuma、Monden Nobuya、Sugaya Akiko、Kataoka Yuko、Nakatsuka Mikiya、Ando Mizuo
    • Journal Title

      Practica Oto-Rhino-Laryngologica

      Volume: 114 Issue: 12 Pages: 957-962

    • DOI

      10.5631/jibirin.114.957

    • NAID

      130008123313

    • ISSN
      0032-6313, 1884-4545
    • Related Report
      2021 Research-status Report
  • [Journal Article] Pathological evaluation of radiotherapy and concomitant intraarterial cisplatin for maxillary sinus cancer2020

    • Author(s)
      Makino Takuma、Tachibana Tomoyasu、Kariya Shin、Matsui Yusuke、Matsuzaki Hidenobu、Fujimoto Shohei、Orita Yorihisa、Katsui Kuniaki、Hiraki Takao、Sato Yasuharu、Kanazawa Susumu、Nishizaki Kazunori
    • Journal Title

      Auris Nasus Larynx

      Volume: 47 Issue: 5 Pages: 881-886

    • DOI

      10.1016/j.anl.2020.04.004

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical Significance of Cytoplasmic IgE-Positive Mast Cells in Eosinophilic Chronic Rhinosinusitis2020

    • Author(s)
      Gion Yuka、Okano Mitsuhiro、Koyama Takahisa、Oura Tokie、Nishikori Asami、Orita Yorihisa、Tachibana Tomoyasu、Marunaka Hidenori、Makino Takuma、Nishizaki Kazunori、Sato Yasuharu
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 5 Pages: 1843-1843

    • DOI

      10.3390/ijms21051843

    • NAID

      120006840783

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical characteristics of subglottic cancer: emphasis on therapeutic management strategies for stage II subglottic cancer2020

    • Author(s)
      Komatsubara Yasutoshi、Tachibana Tomoyasu、Orita Yorihisa、Makino Takuma、Kuroda Kazunori、Naoi Yuto、Kataoka Yuko、Sato Yasuharu、Kariya Shin、Nishizaki Kazunori
    • Journal Title

      Acta Oto-Laryngologica

      Volume: 140 Issue: 9 Pages: 765-770

    • DOI

      10.1080/00016489.2020.1767303

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] MACC1 expression is an indicator of recurrence in early-stage glottic cancer2020

    • Author(s)
      Makino Takuma、Orita Yorihisa、Gion Yuka、Tachibana Tomoyasu、Takao Soshi、Marunaka Hidenori、Miki Kentaro、Akisada Naoki、Akagi Yusuke、Yoshino Tadashi、Nishizaki Kazunori、Sato Yasuharu
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: - Issue: 4 Pages: 1-8

    • DOI

      10.1093/jjco/hyz206

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] KRAS mutation in tongue squamous cell carcinoma.2019

    • Author(s)
      Akagi Y
    • Journal Title

      Acta Otolaryngol

      Volume: 139 Issue: 7 Pages: 647-651

    • DOI

      10.1080/00016489.2019.1610574

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Young adult patients with squamous cell carcinoma of the tongue strongly express p16 without human papillomavirus infection2019

    • Author(s)
      Tachibana Tomoyasu、Orita Yorihisa、Gion Yuka、Miki Kentaro、Ikegami Kana、Marunaka Hidenori、Makino Takuma、Akagi Yusuke、Akisada Naoki、Tsumura Munechika、Ito Toshihiro、Yoshino Tadashi、Nishizaki Kazunori、Sato Yasuharu
    • Journal Title

      Acta Oto-Laryngologica

      Volume: 139 Issue: 1 Pages: 80-84

    • DOI

      10.1080/00016489.2018.1541506

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 当科における上顎洞癌治療の検討:RADPLAT後の病理組織学的評価2020

    • Author(s)
      牧野琢丸
    • Organizer
      第30回日本頭頸部外科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 悪性末梢神経鞘腫の1例2020

    • Author(s)
      森田慎也
    • Organizer
      第30回日本頭頸部外科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Nivolmab投与中に生じたACTH単独欠損症の1例2020

    • Author(s)
      野田洋平
    • Organizer
      第30回日本頭頸部外科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 上咽頭明細胞癌の1例2019

    • Author(s)
      浜崎龍平
    • Organizer
      第32回日本口腔・咽頭科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 上顎に発生したエナメル上皮線維肉腫の1例2019

    • Author(s)
      野田洋平
    • Organizer
      第43回頭頸部癌学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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