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Mechanisms of resistance to molecularly targeted drugs for oral squamous cell carcinoma and investigation of countermeasures

Research Project

Project/Area Number 16K11732
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

YAMAZAKI Hiroshi  東海大学, 医学部, 准教授 (00338708)

Co-Investigator(Kenkyū-buntansha) 森 泰昌  国立研究開発法人国立がん研究センター, 中央病院, 医員 (00296708)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords外科系歯学 / 臨床腫瘍学 / 口腔癌 / 口腔扁平上皮癌 / 分子標的薬 / 歯学 / 癌 / 遺伝子
Outline of Final Research Achievements

The expression of mutant epidermal growth factor receptor (EGFRvIII) was investigated in 96 patients with oral squamous cell carcinoma (OSCC) who underwent surgery. Biopsied tissue samples underwent reverse transcription polymerase chain reaction (PCR), Sanger sequencing, and digital PCR testing, as well as next-generation sequencing. The detection of EGFRvIII was not consistent among the cases, but at least 3 (3%) were considered definitely positive. In order to elucidate the functions of EGFRvIII, we used an OSCC cell line, prepared and evaluated cetuximab-resistant and EGFRvIII-transfected OSCC cell lines. We detected no changes in the protein expression of EGFRvIII, or the signal transduction pathway, in either line.

Academic Significance and Societal Importance of the Research Achievements

上皮成長因子受容体(EGFR)の抗体であるセツキシマブ(Cmab)は、局所進行あるいは再発転移口腔癌(OSCC)の標準治療に用いられている。そのため、Cmabに関するバイオマーカーの確立は重要であるが、現在のところ真に有用なバイオマーカーは存在せず、これを発見することはきわめて重要である。Cmabは野生型に対する抗体であり、変異型であるEGFRvⅢへの結合性は低いため、EGFRvⅢを指標としたネガティブセレクションの可能性が示唆されている。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results)

  • [Journal Article] Altered DNA methylation is associated with aberrant stemness gene expression in early stage HNSCC2019

    • Author(s)
      Suzuki Takatsugu、Yamazaki Hiroshi、Honda Kazufumi、Ryo Eijitsu、Kaneko Akihiro、Ota Yoshihide、Mori Taisuke
    • Journal Title

      International Journal of Oncology

      Volume: 55 Pages: 915-924

    • DOI

      10.3892/ijo.2019.4857

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] New PCNT candidate missense variant in a patient with oral and maxillofacial osteodysplasia: a case report2019

    • Author(s)
      Aoyama KI, Kimura M, Yamazaki H, Uchibori M, Kojima R, Osawa Y, Hosomichi K, Ota Y, Tanaka M, Yamada S, Nishimura G.
    • Journal Title

      BMC Medical Genetics

      Volume: 20 Issue: 1 Pages: 126-126

    • DOI

      10.1186/s12881-019-0858-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mandibular pain, trismus, and weight loss in a 75-year-old man.2018

    • Author(s)
      Yamazaki H, Suzuki T, Denda Y, Nakanishi Y, Uchibori M, Kojima R, Kondo Y
    • Journal Title

      Oral Surg Oral Med Oral Pathol Oral Radiol

      Volume: 印刷中 Issue: 6 Pages: 451-456

    • DOI

      10.1016/j.oooo.2017.12.012

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Case of Early Pneumoparotid Presenting with Oral Noises.2018

    • Author(s)
      Yamazaki H, Kojima R, Nakanishi Y, Kaneko A
    • Journal Title

      J Oral Maxillofac Surg

      Volume: 76 Issue: 1 Pages: 67-69

    • DOI

      10.1016/j.joms.2017.05.039

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lateral retropharyngeal lymph node metastasis from squamous cell carcinoma of the upper gingiva: a case report2018

    • Author(s)
      Yamazaki H, Sasaki M, Aoyama K, Suzuki T, Denda Y, Uchibori M, Nakanishi Y, Kojima R, Ota Y
    • Journal Title

      MOLECULAR AND CLINICAL ONCOLOGY

      Volume: 8 Pages: 68-72

    • DOI

      10.3892/mco.2017.1496

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2016-04-21   Modified: 2021-02-19  

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