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The role of mTOR and HSP90 against oral cancer induced angiogenesis

Research Project

Project/Area Number 23890124
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Surgical dentistry
Research InstitutionOkayama University

Principal Investigator

OKUI Tatsuo  岡山大学, 岡山大学病院, 医員 (40610928)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsHSP90 / mTOR / 口腔癌 / 血管新生 / 癌血管新生
Research Abstract

From surgically resected lower gingival squamous cell carcinoma samples, CD31 and VEGFR2 were highly expressed in vascular endothelial cells, and VEGF-A was expressed in tumor cells. The combination treatment of HSP90 inhibitor and mTOR inhibitor significantly inhibited VEGF induced cell proliferation, tube formation of human umbilical vein endothelial cells (HUVEC) more than the single treatment of them. Gelatin zymography showed that the combination treatment inhibited the activation of MMP-2 induced by VEGF in HUVEC more than the single treatment of them. Immunohistochemical analysis of mice xenografted with SAS oral squamous cell carcinoma cells showed a significant reduction in CD31-positive tumor vasculature in HSP90 inhibitor and mTOR inhibitor-administrated mouse tumor sections compared with the single treatment of them. Furthermore, the combination treatment of them suppressed both VEGFR2 and MMP-2 expression compared with both the control and the single treatments.

Report

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

    (9 results)

All 2013 2012 2011 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] Novel HSP90 inhibitor NVP-AUY922 enhances the anti-tumor effect of temsirolimus against oral squamous cell carcinoma2013

    • Author(s)
      Okui T, Shimo T, Fukazawa T, Mohammad Monsur Hassan N, Honami T, Ibaragi S, Takaoka M, Naomoto Y, Sasaki A
    • Journal Title

      Curr Cancer Drug Targets

      Volume: 13(3) Pages: 289-99

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel HSP90 Inhibitor NVP-AUY922 Enhances the Anti-tumor Effect of Temsirolimus Against Oral Squamous Cell Carcinoma.2013

    • Author(s)
      (Okui T), Shimo T, Fukazawa T, Mohammad Monsur Hassan N, Honami T, Ibaragi S, Takaoka M, Naomoto Y, Sasaki A.
    • Journal Title

      Current cancer drug targets

      Volume: 13 Pages: 289-299

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-tumor effect of a novel FAK inhibitor TAE226 against human oral squamous cell carcinoma.2012

    • Author(s)
      Kurio N, Shimo T, Fukazawa T, Okui T, Hassan NM, Honami T, Horikiri Y, Hatakeyama S, Takaoka M, Naomoto Y, Sasaki A.
    • Journal Title

      Oral Oncol

      Volume: 48(11) Issue: 11 Pages: 1159-70

    • DOI

      10.1016/j.oraloncology.2012.05.019

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hypoxia-induced up-regulation of angiogenin, besides VEGF, is related to progression of oral cancer.2012

    • Author(s)
      Kishimoto K, Yoshida S, Ibaragi S, Yoshioka N, Okui T, Hu GF, Sasaki A
    • Journal Title

      Oral Oncol.

      Volume: 48(11) Issue: 11 Pages: 1120-7

    • DOI

      10.1016/j.oraloncology.2012.05.009

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sonic hedgehog signaling promotes growth of oral squamous cell carcinoma cells associated with bone destruction.2012

    • Author(s)
      Honami T, Shimo T, Okui T, Kurio N, Hassan NM, Iwamoto M, Sasaki A
    • Journal Title

      Oral Oncol

      Volume: 48(1) Issue: 1 Pages: 49-55

    • DOI

      10.1016/j.oraloncology.2011.08.026

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma2011

    • Author(s)
      Okui T, Shimo T, Hassan NM, Fukazawa T, Kurio N, Takaoka M, Naomoto Y, Sasaki A
    • Journal Title

      Anticancer Res

      Volume: 31(4) Pages: 1197-204

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Antitumor Effect of Novel HSP90 Inhibitor NVP-AUY922 against Oral Squamous Cell Carcinoma2011

    • Author(s)
      Tatsuo okui, et al
    • Journal Title

      Anti cancer research

      Volume: 31 Pages: 1197-1204

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 新規HSP90阻害薬NVP-AUY922はTemsirolimusの抗腫瘍効果を増強する2011

    • Author(s)
      奥井達雄
    • Organizer
      第56回日本口腔外科学会総会学術集会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2011-10-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] Antitumor effect of temsirolimus against oral squamous cell carcinoma associated with bone destruction

    • Author(s)
      奥井達雄
    • Organizer
      岡山歯学会総会
    • Place of Presentation
      岡山
    • Related Report
      2012 Annual Research Report
    • Invited

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Published: 2011-09-05   Modified: 2019-07-29  

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