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Study for therapeutic strategy using the target protein expressionsystem based on protein stabilization/destabilization in the cancertracing mechanism

Research Project

Project/Area Number 23659880
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionKyushu University

Principal Investigator

SAKAI Hidetaka  九州大学, 歯研究院, 教授 (80136499)

Co-Investigator(Kenkyū-buntansha) KIYOSHIMA Tamotsu  九州大学, 大学院・歯学研究科, 准教授 (20264054)
NAGATA Kengo  九州大学, 大学院・歯学研究科, 助教 (90189134)
WADA Hiroko  九州大学, 大学院・歯学研究科, 助教 (70380706)
KOBAYASHI Ieyoshi  九州大学, 大学院・歯学研究科, 准教授 (40243951)
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords腫瘍治療 / PETトレーサ / 遺伝子/蛋白調節 / PETトレーサー / 遺伝子/蛋白調節 / 遺伝子/蛋白発現調節
Research Abstract

We studied regulations of gene/protein expression in oral squamous cell carcinoma (OSCC) cells stimulated by exogenous factors and drug-resistance of the OSCC cells in order to develop the anti-cancer therapeutic strategy using the target protein expression system based on protein stabilization/destabilization in the cancer tracing mechanism. The OSCC cells downregulated the keratinocyte differentiation-related genes and upregulated the expression of SERPINB3/4 (SCCA1/2), well-known SCC markers, following treatment with IL-22. These results indicate that IL-22 and IL-6 differentially activate the STAT-signalingpathway depending on the type of OSCC. When the OSCC cells with resistance to the V-ATPase inhibitor were treated with combination with SAHA, these cells indicated the change in STAT signaling pathway and became more susceptible to the V-ATPase inhibitor. Together these findings suggest V-ATPase could be an attractive target against OSCCs. In addition, combination with other reagents such as SAHA could help V-ATPase inhibitors to induce apoptosis in the V-ATPase inhibitor-resistant OSCC cells via change in STAT-signal pathway. Together, the regulation of STAT-signaling pathway may be a pivotal target for development of the tumor specific expression system. The accumulation of these data could lead to the development of new perspectives on this disease, and potentially new therapies with few side effects, thereby improving the treatment of patients with OSCC

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (27 results)

All 2013 2012 2011

All Journal Article (11 results) (of which Peer Reviewed: 5 results) Presentation (16 results)

  • [Journal Article] Immunohistochemical Expression of Thymosin β4 in Ameloblastomas and Odontomas.2013

    • Author(s)
      Kiyoshima T., Nagata K., Wada H., Fujiwara H., Shiotsuka M., Kihara M., Hasegawa K.,Someya H., and Sakai H.
    • Journal Title

      Histol. Histopathol.

      Volume: 28(6) Pages: 775-86

    • Related Report
      2012 Final Research Report
  • [Journal Article] Parotid gland myoepithelioma with remarkable cystic formation: A case report.2013

    • Author(s)
      Kakehashi H., Kawano S., Kiyoshima T., Shimizu M., Moriyama M., Matsubara R., Kiyosue T., Goto Y., Shiratsuchi H., Nakamura S.
    • Journal Title

      J. Oral Maxillofac. Surg. Med. Pathol.

      Volume: 25 Issue: 2 Pages: 183-188

    • DOI

      10.1016/j.ajoms.2012.05.018

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical Expression of Thymosin β4 in Ameloblastomas and Odontomas.2013

    • Author(s)
      Kiyoshima T., Nagata K., Wada H., Fujiwara H., Shiotsuka M., Kihara M., Hasegawa K., Someya H., and Sakai H.
    • Journal Title

      Histol. Histopathol.

      Volume: 28 Pages: 775-786

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma.2012

    • Author(s)
      Naher L., Kiyoshima T., Kobayashi I., Wada H., Nagata K., Fujiwara H., Ookuma Y.F., Ozeki S., Nakamura S., and Sakai H.
    • Journal Title

      Int. J. Oncol

      Volume: 41(5) Issue: 5 Pages: 1577-86

    • DOI

      10.3892/ijo.2012.1594

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Journal Article] A case of adenosquamous carcinoma of the mandibular gingiva2012

    • Author(s)
      見立英史、大部一成、吉賀大午、川野真太郎、河津俊幸、清島 保、豊嶋健史、北村亮二、中村誠司
    • Journal Title

      Journal of Japanese Society of Oral Oncology

      Volume: 24 Issue: 2 Pages: 55-61

    • DOI

      10.5843/jsot.24.55

    • NAID

      10031168579

    • ISSN
      0915-5988, 1884-4995
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Journal Article] 原発性肝扁平上皮癌の1 剖検例肝臓2012

    • Author(s)
      道免和文、田中博文、春野政虎、藤原弘明、小林家吉、清島 保、下田慎治、坂井英隆
    • Journal Title

      肝臓

      Volume: 53(3) Pages: 183-190

    • Related Report
      2012 Final Research Report
  • [Journal Article] An autopsy case of primary squamous cell carcinoma of the liver2012

    • Author(s)
      道免和文、田中博文、春野政虎、藤原弘明、小林家吉、清島 保、下田慎治、坂井英隆
    • Journal Title

      Kanzo

      Volume: 53 Issue: 3 Pages: 183-190

    • DOI

      10.2957/kanzo.53.183

    • NAID

      10030547369

    • ISSN
      0451-4203, 1881-3593
    • Related Report
      2012 Annual Research Report
  • [Journal Article] Antimicrobial and antifungal effects of tissue conditioners containing a photocatalyst2011

    • Author(s)
      M.Uchimaru, H.Sakai, et al
    • Journal Title

      Dental Materials Journal

      Volume: 30 Issue: 5 Pages: 691-699

    • DOI

      10.4012/dmj.2010-203

    • NAID

      10029480766

    • ISSN
      0287-4547, 1881-1361
    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] The transcription factor FBI-1/OCZF/LRF is expressed in osteoclasts and regulates RANKL-induced osteoclast formation in vitro and in vivo2011

    • Author(s)
      A.Kukita, K.Nagata, et al
    • Journal Title

      Arthritis & Rheumatism

      Volume: 63 Issue: 9 Pages: 2744-2754

    • DOI

      10.1002/art.30455

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] 左側上顎に発生した石灰化嚢胞性歯原性腫瘍の1例2011

    • Author(s)
      藤原弘明、小林家吉、清島 保、永田健吾、和田裕子、大隈由紀子、塩塚真帆、木原槇子、坂井英隆
    • Journal Title

      診断病理

      Volume: 28(2) Pages: 117-121

    • NAID

      10029411792

    • Related Report
      2012 Final Research Report
  • [Journal Article] 左側上顎に発生した石灰化嚢胞性歯原性腫瘍の1例2011

    • Author(s)
      藤原弘明、坂井英隆、他
    • Journal Title

      診断病理

      Volume: 28 Pages: 117-121

    • NAID

      10029411792

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Netrin-1結合部位欠失DCC遺伝子導入による癌細胞のアポトーシス誘導2012

    • Author(s)
      和田裕子、清島保、小林家吉、永田健吾、藤原弘明、塩塚真帆、坂井英隆
    • Organizer
      第101回日本病理学会総会
    • Place of Presentation
      京王プラザホテル(東京)
    • Related Report
      2012 Final Research Report
  • [Presentation] DCC蛋白細胞内ドメインによるアポトーシス誘導機構の解析2012

    • Author(s)
      和田裕子、清島保、藤原弘明、坂井英隆
    • Organizer
      第23回日本臨床口腔病理学会総会
    • Place of Presentation
      東京医科歯科大学(東京)
    • Related Report
      2012 Final Research Report
  • [Presentation] エナメル上皮腫におけるThymosin β4の発現とその役割について2012

    • Author(s)
      清島保、永田健吾、和田裕子、藤原弘明、坂井英隆
    • Organizer
      第54回歯科基礎医学会学術大会・総会
    • Place of Presentation
      奥羽大学(福島)
    • Related Report
      2012 Final Research Report
  • [Presentation] V-ATPase阻害剤Concanamycin Aによる口腔扁平上皮の細胞死誘導について2012

    • Author(s)
      吉田寿人、清島保、永田健吾、和田裕子、藤原弘明、坂井英隆
    • Organizer
      第54回歯科基礎医学会学術大会・総会
    • Place of Presentation
      奥羽大学(福島)
    • Related Report
      2012 Final Research Report
  • [Presentation] Netrin-1結合部位欠失DCC遺伝子導入による癌細胞のアポトーシス誘導2012

    • Author(s)
      和田裕子、坂井英隆他
    • Organizer
      第101回日本病理学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] DCC蛋白細胞内ドメインによるアポトーシス誘導機構の解析2012

    • Author(s)
      和田裕子、坂井英隆他
    • Organizer
      第23回日本臨床口腔病理学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] エナメル上皮腫におけるThymosin β4の発現とその役割について2012

    • Author(s)
      清島保、坂井英隆他
    • Organizer
      第54回歯科基礎医学会学術大会・総会
    • Place of Presentation
      郡山(福島)
    • Related Report
      2012 Annual Research Report
  • [Presentation] V-ATPase阻害剤Concanamycin Aによる口腔扁平上皮の細胞死誘導について2012

    • Author(s)
      吉田寿人、坂井英隆他
    • Organizer
      第54回歯科基礎医学会学術大会・総会
    • Place of Presentation
      郡山(福島)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 歯胚形成過程におけるThymosinβ-10 の役割 ~Thymosinβ-4との比較検討~2011

    • Author(s)
      和田裕子、塩塚真帆、清島保、小林家吉、永田健吾、藤原弘明、坂井英隆
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      パシフィコ横浜・会議センター(神奈川)
    • Related Report
      2012 Final Research Report
  • [Presentation] Thymosin beta 4のノックッダウンによる歯原性細胞の変化について2011

    • Author(s)
      小林家吉、清島 保、永田健吾、和田裕子、藤原弘明、坂井英隆
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      パシフィコ横浜・会議センター(神奈川)
    • Related Report
      2012 Final Research Report
  • [Presentation] Soft tissue tumour of the lower lip2011

    • Author(s)
      和田 裕子、清島 保、小林 家吉、藤原弘明、坂井 英隆
    • Organizer
      第22回日本臨床口腔病理学会、第5回アジア口腔病理学会
    • Place of Presentation
      福岡歯科大学主催九州大学(福岡)
    • Related Report
      2012 Final Research Report
  • [Presentation] 癌治療用アポトーシス誘導ベクターの作成と導入の試み2011

    • Author(s)
      古庄 克宏、和田 裕子、清島 保、小林家吉、永田 健吾、藤原 弘明、塩塚 真帆、坂井 英隆
    • Organizer
      第53回歯科基礎医学会学術大会・総会
    • Place of Presentation
      長良川国際会議場(岐阜)
    • Related Report
      2012 Final Research Report
  • [Presentation] 歯胚形成過程におけるThymosinβ-10の役割 ~Thymosinβ-4との比較検討~2011

    • Author(s)
      和田裕子、坂井英隆、他
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] Thymosin beta 4のノックッダウンによる歯原性細胞の変化について2011

    • Author(s)
      小林家吉、坂井英隆、他
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] 癌治療用アポトーシス誘導ベクターの作成と導入の試み2011

    • Author(s)
      古庄 克宏、坂井英隆、他
    • Organizer
      第53回歯科基礎医学会学術大会ならびに総会
    • Place of Presentation
      岐阜
    • Related Report
      2011 Research-status Report
  • [Presentation] Soft tissue tumour of the lower lip2011

    • Author(s)
      和田 裕子、坂井 英隆、他
    • Organizer
      第22回日本臨床口腔病理学会、第5回アジア口腔病理学会
    • Place of Presentation
      福岡
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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