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Study on the DNA methylation status of oral mucosa affected by the betel quid chewing habit using the swab samples in south Asia

Research Project

Project/Area Number 26305035
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section海外学術
Research Field Surgical dentistry
Research InstitutionGifu University

Principal Investigator

SHIBATA Toshiyuki  岐阜大学, 大学院医学系研究科, 教授 (50226172)

Co-Investigator(Kenkyū-buntansha) 加藤 恵三  岐阜大学, 医学部附属病院, 講師 (40397336)
米本 和弘  岐阜大学, 医学部附属病院, 助教 (80422731)
安彦 善裕  北海道医療大学, 歯学部, 教授 (90260819)
牧田 浩樹  岐阜大学, 大学院医学系研究科, 講師 (50345790)
Project Period (FY) 2014-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords口腔 / 粘膜病変 / メチル化異常 / 東南アジア / 口腔がん / 擦過標本 / 嚙みタバコ / 噛みタバコ / 噛タバコ
Outline of Final Research Achievements

To reveal the DNA methylation status of oral mucosa affected by the betel quid chewing habit using the swab samples in south Asia, we carried out the analysis of lesions in in betel quid chewers. Firstly, we evaluated the swab sample accuracy using swab and tissue samples in promoter region of p16 and MGMT so on. DNA methylation status was well correlated between swab and tissue samples. Then, we analyzed DNA methylation status of Taiwan swab samples using pyrosequencing method focused on p16 and MGMT. 10% samples of oral cancer patients indicated positive. Furthermore, we examined the methylation positive of p16 in cancer patients and detected it in high ratio (almost 100%). These results possibly suggested the usefulness of p16 analysis as a biomarker in oral cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究では,口腔癌の発生機序におけるDNAメチル化異常の関与を明らかとするために,噛みタバコの習慣による口腔癌・前癌病変の多発する東南アジアを含むフィールドでDNAメチル化異常を口腔粘膜擦過標本にて検証した(最終的な目標は,前癌病変(状態)を擦過標本で検出することを遠望している)。その結果,癌病変の擦過標本で組織標本と同等の(相関性のある)DNAメチル化異常が検出された。また,種々のDNAメチル化異常はp53遺伝子変異を観察する前段階で観察され,口腔粘膜の擦過標本のDNAメチル化異常の検索が,口腔癌・口腔前癌病変の早期発見に有用と考えられた。

Report

(6 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (19 results)

All 2019 2018 2017 2016 2015 2014 2012

All Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 10 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Invited: 1 results)

  • [Journal Article] Pathobiological role of cleft palate transmembrane protein 1 family proteins in oral squamous cell carcinoma.2019

    • Author(s)
      Inoue K, Hatano K, Hanamatsu Y, Saigo C, Kito Y, Bunai K, Shibata T, Takeuchi T.
    • Journal Title

      J Cancer Res Clin Oncol.

      Volume: 145 Issue: 4 Pages: 851-859

    • DOI

      10.1007/s00432-019-02843-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TMEM207 hinders the tumour suppressor function of WWOX in oral squamous cell carcinoma2018

    • Author(s)
      Bunai Katsuaki、Okubo Hiroshi、Hano Kimika、Inoue Keisuke、Kito Yusuke、Saigo Chiemi、Shibata Toshiyuki、Takeuchi Tamotsu
    • Journal Title

      J Cell Mol Med.

      Volume: 22 Issue: 2 Pages: 1026-1033

    • DOI

      10.1111/jcmm.13456

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sirtuin 1 and oral cancer (Review)2018

    • Author(s)
      Islam Shajedul、Abiko Yoshihiro、Uehara Osamu、Chiba Itsuo
    • Journal Title

      Oncology Letters

      Volume: in press

    • DOI

      10.3892/ol.2018.9722

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Current mouse models of oral squamous cell carcinoma: Genetic and chemically induced models2017

    • Author(s)
      Ishida Kazuhisa、Tomita Hiroyuki、Nakashima Takayuki、Hirata Akihiro、Tanaka Takauji、Shibata Toshiyuki、Hara Akira
    • Journal Title

      Oral Oncol.

      Volume: 73 Pages: 16-20

    • DOI

      10.1016/j.oraloncology.2017.07.028

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Promotion of cell proliferation by the proto-oncogene DEK enhances oral squamous cell carcinogenesis through field cancerization2017

    • Author(s)
      Nakashima, T. Tomita, H. Hirata, A. Ishida, K. Hisamatsu, K. Hatano, Y. Kanayama, T. Niwa, A. Noguchi, K. Kato, K. Miyazaki, T. Tanaka, T. Shibata, T. Hara, A.
    • Journal Title

      Cancer Med

      Volume: 6 Issue: 10 Pages: 2424-2439

    • DOI

      10.1002/cam4.1157

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transforming growth factor-β1 suppresses bone morphogenetic protein-2-induced mesenchymal-epithelial transition in HSC-4 human oral squamous cell carcinoma cells via Smad1/5/9 pathway suppression.2017

    • Author(s)
      Chiba, T., Ishisaki, A., Kyakumoto, S., Shibata, T., Yamada, H., and Kamo, M.
    • Journal Title

      Oncol. Rep.

      Volume: 37 Issue: 2 Pages: 713-720

    • DOI

      10.3892/or.2016.5338

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Immunohistochemical evaluation of Klotho and DNA methyltransferase 3a in oral squamous cell carcinomas.2017

    • Author(s)
      Adhikari BR, Uehara O, Matsuoka H, Takai R, Harada F, Utsunomiya M, Chujo T, Morikawa T, Shakya M, Yoshida K, Sato J, Arakawa T, Nishimura M, Nagayasu H, Chiba I, Abiko Y.
    • Journal Title

      Med Mol Morphol.

      Volume: - Issue: 3 Pages: 155-160

    • DOI

      10.1007/s00795-017-0156-9

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DNA hypermethylation of extracellular matrix-related genes in human periodontal fibroblasts induced by stimulation for a prolonged period with lipopolysaccharide derived from P. gingivalis2016

    • Author(s)
      Rie Takai, Osamu Uehara, Fumiya Harada, Masafumi Utsunomiya, Takatoshi Chujo, Koki Yoshida, Jun Sato, Michiko Nishimura, Itsuo Chiba, Yoshihiro Abiko
    • Journal Title

      J Periodontal Research

      Volume: 51 Issue: 4 Pages: 508-517

    • DOI

      10.1111/jre.12330

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of epithelial cells derived from periodontal ligament on osteoblast-like cells in a Transwell membrane coculture system.2015

    • Author(s)
      Noro D, Kurashige Y, Shudo K, Takahashi A, Abiko Y, Saitoh M.
    • Journal Title

      Arch Oral Biol.

      Volume: 60 Issue: 7 Pages: 1007-1012

    • DOI

      10.1016/j.archoralbio.2015.02.016

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HBD-2 is downregulated in oral carcinoma cells by DNA hypermethylation, and increased expression of hBD-2 by DNA demethylation and gene transfection inhibits cell proliferation and invasion.2014

    • Author(s)
      Kamino Y, Kurashige Y, Uehara O, Sato J, Nishimura M, Yoshida K, Arakawa T, Nagayasu H, Saitoh M, Abiko Y.
    • Journal Title

      Oncol Rep.

      Volume: 32 Issue: 2 Pages: 462-468

    • DOI

      10.3892/or.2014.3260

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lipopolysaccharide extracted from Porphyromonas gingivalis induces DNA hypermethylation of runt-related transcription factor 2 in human periodontal fibroblasts.2012

    • Author(s)
      Uehara O, Abiko Y, Saitoh M, Miyakawa H, Nakazawa F.
    • Journal Title

      J Microbiol Immunol Infect

      Volume: 12 Issue: 3 Pages: 176-181

    • DOI

      10.1016/j.jmii.2012.08.005

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 口腔扁平上皮癌の浸潤・増殖におけるC1qTNF6の機能解析2018

    • Author(s)
      波野 公香,武内勝章,井上敬介,米本和弘,加藤恵三,柴田敏之
    • Organizer
      第72回 NPO法人日本口腔科学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 膜タンパクTMEM207はWWOXの腫瘍抑制作用を妨げMAPR経路およびHIF1α,GLUT1を亢進する2018

    • Author(s)
      武内勝章,加藤恵三,米本和弘,畠山大二郎,柴田敏之
    • Organizer
      第63回(公社)日本口腔外科学会総会・学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] P16INK4a欠損は浸潤性口腔がんの発症を促進する2018

    • Author(s)
      石田和久,中島教行,井上敬介,武内勝章,加藤恵三,柴田敏之
    • Organizer
      第63回(公社)日本口腔外科学会総会・学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 口腔扁平上皮癌におけるDEK発現の検討2017

    • Author(s)
      中島教行、吉田浩明、米本和弘、加藤惠三、牧田浩樹、柴田敏之
    • Organizer
      第71回NPO法人日本口腔科学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 新規標的遺伝子TMEM207の役割とその機能解析および,in situ PLA 法を用いた病理組織標本上における分子間相互作用の視認化の可能性2017

    • Author(s)
      武内勝章、井上敬介,波野公香,柴田敏之
    • Organizer
      第28回日本臨床口腔病理学会総会・学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 口腔扁平上皮癌における新規標的タンパクTMEM207の役割とその機能解析2017

    • Author(s)
      武内勝章、牧田浩樹、加藤恵三、米本和弘、畠山大二郎、柴田敏之
    • Organizer
      第62回日本口腔外科学会総会・学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 腫瘍性タンパクDEKは扁平上皮がんの腫瘍増殖と悪性への形質転換を促進する2016

    • Author(s)
      中島教行、富田弘之、原明、柴田敏之
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Hypermethylation status of oral cancer and Dental pulp stem cell biology as a new resource for the regenerative medicine2015

    • Author(s)
      Toshiyuki Shibata
    • Organizer
      第27回台湾顎顔面口腔外科学会学術大会
    • Place of Presentation
      台北市(台湾)
    • Year and Date
      2015-03-06 – 2015-03-07
    • Related Report
      2014 Annual Research Report
    • Invited

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Published: 2014-04-04   Modified: 2020-03-30  

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