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Attempt to establishment of early diagnosis and prediction of therapeutic response in pancreatobiliary neoplasms

Research Project

Project/Area Number 15K08349
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionKagoshima University

Principal Investigator

HIGASHI Michiyo  鹿児島大学, 医歯学域附属病院, 准教授 (60315405)

Co-Investigator(Kenkyū-buntansha) 横山 勢也  鹿児島大学, 医歯学域医学系, 助教 (20569941)
Research Collaborator MATSUO KEI  鹿児島大学, 大学院医歯学総合研究科, 技術職員
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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords病理学 / 膵胆道腫瘍 / ムチン抗原 / 予後因子 / MUC1 / MUC4 / MUC16 / メチル化 / MUC / methylation / prognosis / 膵胆道系腫瘍 / 病理
Outline of Final Research Achievements

We had reported that expression profiles of mucins are closely associated with biological behavior of human pancreatobiliary neoplasms. We evaluated the methylation status of MUC1 and MUC4 promoter regions in pancreatic tissue samples by the methylation specific electrophoresis (MSE) method. We show that the DNA methylation status of the promoters of MUC1 and MUC4 in pancreatic tissue correlates with the expression of MUC1 and MUC4 mRNA. In addition, the expression of several DNA methylation/demethylation factors show a significant correlation with MUC1 and MUC4 methylation status. Furthermore, CAIX expression significantly correlates with the expression of MUC1 and MUC4. Interestingly, our results indicate that low methylation of MUC1 and/or MUC4 promoters correlates with decreased overall survival. Analysis of epigenetic changes in mucin genes may be of diagnostic utility and one of the prognostic predictors for patients with PDAC.

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 Int'l Joint Research (4 results) Journal Article (12 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 12 results,  Open Access: 10 results,  Acknowledgement Compliant: 2 results) Presentation (5 results) (of which Invited: 2 results)

  • [Int'l Joint Research] University of Nebraska Medical Center(米国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] University of Ulm(Germany)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] University of Nebraska Medical Center(米国)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] University of Ulm(Germany)

    • Related Report
      2015 Research-status Report
  • [Journal Article] 集学的治療で完全奏効が得られた肝転移を伴うcStage IV膵体部癌の1例2018

    • Author(s)
      伊地知, 徹也 蔵原, 弘 前村, 公成 又木, 雄弘 川崎, 洋太 迫田, 雅彦 飯野, 聡 上野, 真一 新地, 洋之 東, 美智代 夏越, 祥次
    • Journal Title

      日本消化器外科学会雑誌

      Volume: 50 Pages: 897-904

    • NAID

      130006210157

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical expression of mucin antigens in gallbladder adenocarcinoma: MUC1-positive and MUC2-negative expression Is associated with vessel invasion and shortened survival2017

    • Author(s)
      Hiraki, T. Yamada, S. Higashi, M. Hatanaka, K. Yokoyama, S. Kitazono, I. Goto, Y. Kirishima, M. Batra, S. K. Yonezawa, S. Tanimoto, A.
    • Journal Title

      Histol Histopathol

      Volume: 32 Pages: 585-596

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] TET1-mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer2017

    • Author(s)
      Yokoyama, S. Higashi, M. Tsutsumida, H. Wakimoto, J. Hamada, T. Wiest, E. Matsuo, K. Kitazono, I. Goto, Y. Guo, X. Hamada, T. Yamada, S. Hiraki, T. Yonezawa, S. Batra, S. K. Hollingsworth, M. A. Tanimoto, A.
    • Journal Title

      Genes & cancer

      Volume: 8 Issue: 3-4 Pages: 517-527

    • DOI

      10.18632/genesandcancer.139

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diagnostic efficacy of liquid-based cytology for solid pancreatic lesion samples obtained with endoscopic ultrasound-guided fine-needle aspiration: Propensity score-matched analysis2017

    • Author(s)
      Hashimoto, S. Taguchi, H. Higashi, M. Hatanaka, K. Fujita, T. Iwaya, H. Nakazawa, J. Arima, S. Iwashita, Y. Sasaki, F. Nasu, Y. Kanmura, S. Ido, A.
    • Journal Title

      Digestive endoscopy

      Volume: 29 Issue: 5 Pages: 608-616

    • DOI

      10.1111/den.12827

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assessment of tumor characteristics based on glycoform analysis of membrane-tethered MUC12017

    • Author(s)
      Matsuda, A. Higashi, M. Nakagawa, T. Yokoyama, S. Kuno, A. Yonezawa, S. Narimatsu, H.
    • Journal Title

      Lab Invest

      Volume: 97 Issue: 9 Pages: 1103-1113

    • DOI

      10.1038/labinvest.2017.53

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Assessment of tumor characteristics based on glycoform analysis of membrane-tethered MUC12017

    • Author(s)
      Atsushi Matsuda, Michiyo Higashi, Tomomi Nakagawa, Seiya Yokoyama, Atsushi Kuno, Suguru Yonezawa, and Hisashi Narimatsu
    • Journal Title

      Laboratory Investigation

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant methylation of MUC1 and MUC4 promoters are potential prognostic biomarkers for pancreatic ductal adenocarcinomas2016

    • Author(s)
      Yokoyama, S. Higashi, M. Kitamoto, S. Oeldorf, M. Knippschild, U. Kornmann, M. Maemura, K. Kurahara, H. Wiest, E. Hamada, T. Kitazono, I. Goto, Y. Tasaki, T. Hiraki, T. Hatanaka, K. Mataki, Y. Taguchi, H. Hashimoto, S. Batra, S. K. Tanimoto, A. Yonezawa, S. Hollingsworth, M. A.
    • Journal Title

      Oncotarget

      Volume: - Issue: 27 Pages: 42553-42565

    • DOI

      10.18632/oncotarget.9924

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Dexamethasone Suppression FDG PET/CT for Differentiating between True- and False-Positive Pulmonary and Mediastinal Lymph Node Metastases in Non-Small Cell Lung Cancer: A Pilot Study of FDG PET/CT after Oral Administration of Dexamethasone2016

    • Author(s)
      Nakajo, M. Nakajo, M. Nakayama, H. Jinguji, M. Nakabeppu, Y. Higashi, M. Nakamura, Y. Sato, M. Yoshiura, T.
    • Journal Title

      Radiology

      Volume: 279 Issue: 1 Pages: 246-253

    • DOI

      10.1148/radiol.2015150883

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pancreatic hamartoma: a case report and literature review.2016

    • Author(s)
      Matsushita D, Kurahara H, Mataki Y, Maemura K, Higashi M, Iino S, et al.
    • Journal Title

      BMC gastroenterology.

      Volume: 16 Issue: 1 Pages: 419-422

    • DOI

      10.1186/s12876-016-0419-2

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Computed tomography and magnetic resonance imaging features of lipid-rich neuroendocrine tumors of the pancreas2015

    • Author(s)
      Fukukura Y, Shindo T, Higashi M, Takumi K, Umanodan T, Yoneyama T, et al.
    • Journal Title

      World journal of gastroenterology : WJG

      Volume: 21 Issue: 34 Pages: 10008-17

    • DOI

      10.3748/wjg.v21.i34.10008

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mucin expression in endoscopic ultrasound-guided fine-needle aspiration specimens is a useful prognostic factor in pancreatic ductal adenocarcinoma.2015

    • Author(s)
      Higashi M, Yokoyama S, Yamamoto T, Goto Y, Kitazono I, Hiraki T, et al.
    • Journal Title

      Pancreas

      Volume: 44 Issue: 5 Pages: 728-34

    • DOI

      10.1097/mpa.0000000000000362

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Pancreatic neuroendocrine tumors: Correlation between the contrast-enhanced computed tomography features and the pathological tumor grade.2015

    • Author(s)
      Takumi K, Fukukura Y, Higashi M, Ideue J, Umanodan T, Hakamada H, et al.
    • Journal Title

      Eur J Radiol.

      Volume: 84 Issue: 8 Pages: 1436-43

    • DOI

      10.1016/j.ejrad.2015.05.005

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 粘膜類表皮癌においてMUC4とMUC6の発現低下から生存期間の短縮が予想される2017

    • Author(s)
      本庄, 希江 山口, 壮亮 平木, 翼 東, 美智代 吉村, 卓也 中村, 典史 野元, 三治 野口, 紘嗣 米澤, 傑 谷本, 昭英
    • Organizer
      日本病理学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Analysis of Mucin expression and DNA methylation in serous adenoma of the pancreas2016

    • Author(s)
      Michiyo Higashi, Seiya Yokoyama, Tsubasa Hiraki , Ikumi Kitazono, Yuko Goto,Tasaki Takashi, Mari Kirishima, Kazuhito Hatanaka, and Akihide Tanimoto
    • Organizer
      日本病理学会第105回総会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-05-12
    • Related Report
      2016 Research-status Report
  • [Presentation] ムチン発現からみたIPMNの悪性度2015

    • Author(s)
      東美智代、横山勢也、北薗育美、後藤優子、田崎貴嗣、平木翼、畑中一仁、蔵原弘、又木雄弘、前村公成、新地洋之、谷本昭英、米澤傑、夏越祥次
    • Organizer
      外科病理学会
    • Place of Presentation
      ホテルアパローム紀ノ国(和歌山県和歌山市)
    • Year and Date
      2015-11-06
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 浸潤性膵管癌におけるEUS-FNAでのムチン発現2015

    • Author(s)
      東美智代、後藤優子、米澤傑
    • Organizer
      肝胆膵外科学会
    • Place of Presentation
      ホテルグランパシフィックLE DAIBA (東京都千代田区)
    • Year and Date
      2015-06-11
    • Related Report
      2015 Research-status Report
  • [Presentation] 膵漿液性腫瘍の病理2015

    • Author(s)
      東美智代
    • Organizer
      日本病理学会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-04-30
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2022-02-16  

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