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Development of new oral cancer treatments focused on mTOR inhibition leading to the anti-aging prevention and the healthy life-span extension

Research Project

Project/Area Number 15K11292
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionYamaguchi University

Principal Investigator

HARADA Koji  山口大学, 大学院医学系研究科, 助教 (60253217)

Research Collaborator FERDOUS Tarannum  
MINAMI Haruyasu  
FUJIWARA Rieko  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsmTOR阻害剤 / ラパマイシン / 5-FU / 老化防止 / 健康寿命延長 / 口腔癌 / 口腔扁平上皮癌 / Rapamycin / 5-FU / 併用療法 / リンパ管新生抑制 / 細胞老化抑制 / mTOR阻害 / アポトーシス / 健康寿命
Outline of Final Research Achievements

We investigated the combined effect one of mTOR inhibitors (rapamycin, everolimus or temsirolimus) and any of conventional anticancer agents (5-FU, CDDP, DOC, PTX, C-mab or radiation). Rapamycin in combination with 5-FU exerted maximum growth inhibitory effects on OSCC cell lines and nude mice tumors. Immunohistochemical staining showed that the expressions of p16, VEGF and podoplanin were down-regulated, and the expressions of PI3K, Akt , p27, and p21 were up-regulated on nude mice tumors treated with rapamycin and 5-FU.
These findings suggested that the combined therapy of rapamycin and 5-FU might be an new oral cancer treatments focused on mTOR inhibition leading to the anti-aging prevention and the healthy life-span extension.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (21 results)

All 2018 2017 2016 2015 Other

All Journal Article (11 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 11 results,  Open Access: 6 results,  Acknowledgement Compliant: 6 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Elemental diet inhibits pro-inflammatory cytokine production in keratinocytes through the suppression of NFκB activation.2018

    • Author(s)
      Koji Harada, Tarannum Ferdous, Yoichi Mizukami, Katsuaki Mishima
    • Journal Title

      Oncology reports

      Volume: in press Pages: 361-368

    • DOI

      10.3892/or.2018.6440

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PD-L1 expression in malignant salivary gland tumors.2018

    • Author(s)
      Koji Harada, Tarannum Ferdous, Yoshiya Ueyama
    • Journal Title

      BMC Cancer

      Volume: 18 Issue: 1 Pages: 156-156

    • DOI

      10.1186/s12885-018-4069-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low carbonyl reductase 1 expression is associated with poor prognosis in patients with oral squamous cell carcinoma2018

    • Author(s)
      Ryota Yamanouchi, Koji Harada, Tarannum Ferdous, Yoshiya Ueyama
    • Journal Title

      Mol Clin Oncol.

      Volume: 8 Pages: 400-406

    • DOI

      10.3892/mco.2018.1548

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic strategies with oral fluoropyrimidine anticancer agent, S-1 against oral cancer.2017

    • Author(s)
      Koji Harada, Tarannum Ferdous, Yoshiya Ueyama
    • Journal Title

      Jpn Dent Sci Rev.

      Volume: 53 Issue: 3 Pages: 61-77

    • DOI

      10.1016/j.jdsr.2016.11.001

    • NAID

      210000183430

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Calreticulin is a novel independent prognostic factor for oral squamous cell carcinoma.2017

    • Author(s)
      Koji Harada, Takanori Takenawa, Tarannum Ferdous, Yasuhiro Kuramitsu, Yoshiya Ueyama
    • Journal Title

      Oncology Letters

      Volume: 13 Issue: 6 Pages: 4857-4862

    • DOI

      10.3892/ol.2017.6062

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Induction of artificial cancer stem cells from tongue cancer cells by defined reprogramming factors.2016

    • Author(s)
      Harada K, Ferdous T, Cui D, Kuramitsu Y, Matsumoto T, Ikeda E, Okano H, Ueyama Y.
    • Journal Title

      BMC Cancer

      Volume: 16 Issue: 1 Pages: 548-548

    • DOI

      10.1186/s12885-016-2416-9

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Gimeracil Exerts Radiosensitizing Effects on Oral Squamous Cell Carcinoma Cells In Vitro and In Vivo.2016

    • Author(s)
      Harada K, Ferdous T, Ueyama Y.
    • Journal Title

      Anticancer Res

      Volume: 36 Issue: 11 Pages: 5923-5930

    • DOI

      10.21873/anticanres.11179

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] METFORMIN IN COMBINATION WITH 5-FLUOROURACIL SUPPRESSES TUMOR GROWTH BY INHIBITING WARBURG EFFECT IN HUMAN ORAL SQUAMOUS CELL CARCINOMA2016

    • Author(s)
      Koji Harada, Tarannum Ferdous, Toyoko Harada, Yoshiya Ueyama
    • Journal Title

      International Journal of Oncology

      Volume: in press

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Efficacy of elemental diet on prevention for chemoradiotherapy-induced oral mucositis in patients with oral squamous cell carcinoma2016

    • Author(s)
      Koji Harada, Tarannum Ferdous, Daiju Horinaga, Kenichiro Uchida, Takamitsu Mano, Katsuaki Mishima, SungChul Park, Hideki Hanazawa, Shotaro Takahashi, Atsumi Okita, Misaki Fukunaga, Junko Maruta, Naoko Kami, Keiko Shibuya, Yoshiya Ueyama
    • Journal Title

      Support Care Cancer

      Volume: 24 Issue: 2 Pages: 953-959

    • DOI

      10.1007/s00520-015-2866-7

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] High expression of stathmin 1 is a strong prognostic marker in oral squamous cell carcinoma patients treated by docetaxel-containing regimens2015

    • Author(s)
      Koji Harada, Tarannum Ferdous, Toyoko Harada, Yoshiya Ueyama
    • Journal Title

      Clin Exp Med.

      Volume: - Pages: 1-6

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Osteogenic cell fractions isolated from mouse tongue muscle2015

    • Author(s)
      Harada K, Harada T, Ferdous T, Takenawa T. and Ueyama Y.
    • Journal Title

      Mol. Med. Rep.

      Volume: - Issue: 1 Pages: 31-36

    • DOI

      10.3892/mmr.2015.3350

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 口腔癌化学放射線療法における成分栄養剤エレンタールの有用性に関する基礎的検討2018

    • Author(s)
      原田 耕志、加藤 芳明、南 晴康、清水 香織、木村 智子、村上 尚子、三島 克章
    • Organizer
      第15回日本口腔ケア学会総会・学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト口腔扁平上皮癌の浸潤・転移能獲得につながる因子Tropomyosin 1の同定とその機能解析および臨床的意義の検討2018

    • Author(s)
      原田 耕志、山内 良太、梅田 浩嗣、竹縄 隆徳、三島 克章
    • Organizer
      第72回日本口腔科学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 成分栄養剤エレンタールの口内炎への直接作用の可能性2017

    • Author(s)
      原田 耕志、加藤 芳明、堀永 大樹、内田 堅一郎、眞野 隆充、三島 克章
    • Organizer
      第46回日本口腔外科学会中国四国地方部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 口腔癌における免疫チェックポイント分子の発現とニボルマブの効果予測2017

    • Author(s)
      原田耕志
    • Organizer
      第71回日本口腔科学会学術集会
    • Place of Presentation
      ひめぎんホール(愛媛)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] TS-1併用放射線治療およびcetuximabの継続投与により寛解が得られた進行舌癌の1例2017

    • Author(s)
      眞野隆充、内田堅一郎、原田耕志、山内良太、上山吉哉
    • Organizer
      第35回日本口腔腫瘍学会総会・学術大会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Related Report
      2016 Research-status Report
  • [Presentation] High Expression of FOXM1 is a Strong Prognostic Marker in Oral Squamous Cell Carcinoma Patients Treated by Docetaxel-containing Regimens.2016

    • Author(s)
      Tarannum Ferdous, Koji Harada, Yoshiya Ueyama
    • Organizer
      ESMO 2016
    • Place of Presentation
      The Bella Center (Copenhagen, Denmark)
    • Year and Date
      2016-10-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 口腔扁平上皮癌に対するMetforminと5-FUの併用療法による抗腫瘍効果の検討2016

    • Author(s)
      原田 耕志、上山 吉哉
    • Organizer
      第40回日本頭頸部癌学会
    • Place of Presentation
      ソニックシテイ (埼玉県さいたま市)
    • Year and Date
      2016-06-09
    • Related Report
      2015 Research-status Report
  • [Presentation] 口腔扁平苔癬におけるPD-1およびOsteopontinの役割2016

    • Author(s)
      原田耕志、眞野隆充、上山吉哉
    • Organizer
      第26回日本口腔内科学会
    • Place of Presentation
      さん太ホール (岡山)
    • Related Report
      2016 Research-status Report
  • [Presentation] 口腔扁平上皮癌におけるMetforminと5-FUの併用療法によるWarburg効果阻害を介した抗腫瘍効果の検討2016

    • Author(s)
      原田耕志、上山吉哉
    • Organizer
      第40回日本頭頸部癌学会
    • Place of Presentation
      ソニックシテイ (埼玉)
    • Related Report
      2016 Research-status Report
  • [Remarks] 山口大学医学部附属病院 歯科口腔外科 業績

    • URL

      http://ds.cc.yamaguchi-u.ac.jp/~oms0/custom7.html

    • Related Report
      2017 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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