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Micro RNA expression in serrated pathway and its association with a potential target therapy

Research Project

Project/Area Number 24590429
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MITOMI Hiroyuki  獨協医科大学, 医学部, 教授 (90181940)

Co-Investigator(Kenkyū-buntansha) SAITO Tsuyoshi  順天堂大学, 医学部人体病理病態学講座, 准教授 (80439736)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsマイクロRNA / 広基性鋸歯状腺腫/ポリープ / 鋸歯状発癌経路 / 大腸ポリープ / 遺伝子メチル化 / 発癌 / 大腸 / Wntシグナル / 広基性鋸歯状ポリープ / 鋸歯状腺癌 / 発癌経路
Outline of Final Research Achievements

Sessile serrated adenoma/polyp (SSA/P) is considered as an early precursor in the serrated pathway leading to colorectal cancer development. To clarify WNT signaling activation and expression of microRNAs (20a/21/93/181b) in this pathway, we performed β-catenin immunostaining and methylation specific PCR for AXIN2, MCC and secreted frizzled-related proteins in SSA/Ps, SSA/Ps with high-grade dysplasia (SSA/P+HGD) and SSA/Ps with submucosal carcinoma (SSA/P+SM-Ca). Nuclear β-catenin immunolabelings and the methylation of AXIN2 or MCC showed stepwise increment from SSA/Ps through SSA/P+HGD to SSA/P+SM-Ca. A stepwise increment of miR21 and a stepwise decrement of miR20a/93/181b expressions were seen in this sequence. There were significant correlations of those miR expressions with AXIN2 or MCC methylation in this pathway. Our results point toward a potential target therapy of those miRs and methylated genes such as RNA-interference drug or demethylase in malignant progression of SSA/P.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (30 results)

All 2015 2014 2013 2012

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (18 results) (of which Invited: 6 results)

  • [Journal Article] A case of Krukenberg carcinoma metastasized from colon cancer resembling mucinous cystadenocarcinoma of the ovary2014

    • Author(s)
      Shiono S, Saito T, Fujii H, Arakawa A, Nakamura T, Yao T
    • Journal Title

      Int J Clin Exp Pathol

      Volume: 7 Issue: 1 Pages: 394-401

    • DOI

      10.1038/modpathol.2014.41

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distinct profile of HIF1α, PTCH, EphB2 or DNA repair protein expression and BRAF mutation in colorectal serrated adenoma.2014

    • Author(s)
      Morimoto T, Mitomi H, Saito T, Takahashi M, Murakami T, Sakamoto N, Yao T, Watanabe S:
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: 印刷中 Issue: 6 Pages: 1192-1199

    • DOI

      10.1111/jgh.12553

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Downregulation of sFRP-2 by epigenetic silencing activates the β-catenin/Wnt signaling pathway in esophageal basaloid squamous cell carcinoma.2014

    • Author(s)
      Saito T, Mitomi H, Imamhasan A, Hayashi T, Mitani K, Takahashi M, Kajiyama Y, Yao T:
    • Journal Title

      Virchows Arch

      Volume: 464 Issue: 2 Pages: 135-143

    • DOI

      10.1007/s00428-014-1538-1

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of p53 genetic alteration associated with protein overexpression in malignant transformation of giant-cell tumor of bone.2013

    • Author(s)
      Okubo T, Saito T, Mitomi H, Takagi T, Torigoe T, Suehara Y, Yao T, Kaneko K.
    • Journal Title

      Virchows Arch

      Volume: 63 Issue: 1 Pages: 67-77

    • DOI

      10.1007/s00428-013-1435-z

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protein expression and methylation of DNA repair genes hMLH1, hMSH2, MGMT and BRCA1 and their correlation with clinicopathological parameters and prognosis in basal-like breast cancer.2013

    • Author(s)
      Alkam Y, Mitomi H, Nakai K, Himuro T, Saito T, Takahashi M, Arakawa A, Yao T, Saito M:
    • Journal Title

      Histopathology

      Volume: 63 Issue: 5 Pages: 713-725

    • DOI

      10.1111/his.12220

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Alteration in the Wnt/β-catenin signaling pathway in gastric neoplasias of fundic gland (chief cell predominant) type.2013

    • Author(s)
      Hidaka Y, Mitomi H, Saito T, Takahashi M, Lee SY, Matsumoto K, Yao T, Watanabe S:
    • Journal Title

      Hum Pathol

      Volume: 44 Issue: 11 Pages: 2438-2448

    • DOI

      10.1016/j.humpath.2013.06.002

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical analysis of chromogranin A and p53 expression in ulcerative colitis-associated neoplasia: neuroendocrine differentiation as an early event in colitis-neoplasia sequence2013

    • Author(s)
      Shigaki K, Fujimori T (11人中3番目)
    • Journal Title

      Human Pathology

      Volume: 44 Issue: 11 Pages: 2393-2399

    • DOI

      10.1016/j.humpath.2013.06.008

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of polycomb group proteins EZH2 and Bmi-1 during progression of esophageal squamous intraepithelial neoplasia: An association with p16INK4a and p53.2013

    • Author(s)
      Uchida S, Saito T, Mitomi H, Hayashi T, Tomita N, Kajiyama Y, Wada R, Yao T:
    • Journal Title

      Juntendo Medical Journal

      Volume: 59 Pages: 331-339

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Low-grade myofibroblastic sarcoma of the distal femur2012

    • Author(s)
      Saito T, Suehara Y et al.
    • Journal Title

      International Journal of Surgery Case Reports

      Volume: 4 Issue: 2 Pages: 195-199

    • DOI

      10.1016/j.ijscr.2012.11.017

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] MUC5AC/β-catenin expression and KRAS gene alteration in laterally spreading colorectal tumors.2012

    • Author(s)
      2) Nakae K, Mitomi H, Saito T, Takahashi M, Morimoto T, Hidaka Y, Sakamoto N, Yao T, Watanabe S.
    • Journal Title

      World J Gastroenterol.

      Volume: 18 Issue: 39 Pages: 5551-9

    • DOI

      10.3748/wjg.v18.i39.5551

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intraneural lipomatous tumor of the median nerve: Three case reports with a review of literature2012

    • Author(s)
      Okubo T, Suehara Y et al.
    • Journal Title

      International Journal of Surgery Case Reports

      Volume: 3 Issue: 9 Pages: 407-411

    • DOI

      10.1016/j.ijscr.2012.05.007

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical and oncogenetic analyses of the esophageal basaloid squamous cell carcinoma in comparison with conventional squamous cell carcinomas.2012

    • Author(s)
      4) Imamhasan A, Mitomi H, Saito T, Hayashi T, Takahashi M, Kajiyama Y, Yao T.
    • Journal Title

      Hum Pathol.

      Volume: 43 Issue: 11 Pages: 2012-23

    • DOI

      10.1016/j.humpath.2012.02.010

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Clinicopathologic characteristics and molecular associations of WNT/β-catenin signal in the serrated neoplasia pathway of the colorectum.2015

    • Author(s)
      Murakami T, Mitomi H, Sakamoto N, Ritsuno H, Ueyama H, Matsumoto K, Shibuya T, Osada T, Yao T, Watanabe S
    • Organizer
      Digestive Disease Week 2015
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2015-05-16 – 2015-05-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] SSA/P併存早期大腸癌の臨床病理学的検討.2014

    • Author(s)
      村上敬,三富弘之,坂本直人,立之英明,上山浩也,松本健史,澁谷智義,長田太郎,荻原達雄,寺井毅,八尾隆史,渡辺純夫
    • Organizer
      第24回大腸IIc研究会
    • Place of Presentation
      大阪
    • Year and Date
      2014-09-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] 胃底腺(主細胞優位)型胃癌におけるWnt/βカテニンシグナル伝達系の変異とβカテニン核内発現との関連.2013

    • Author(s)
      日高康博、三富弘之、齋藤剛、高橋路子、李世容、松本健史、八尾隆史、渡辺純夫
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Nuclear β-catenin expression in association with mutations in components of the Wnt/β-catenin signaling pathway in gastric adenocarcinoma of fundic gland (chief cell predominant) type.2013

    • Author(s)
      Hidaka Y, Mitomi H, Saito T, Takahashi M, Lee SY, Matsumoto K, Yao T, Watanabe S
    • Organizer
      Digestive Disease Week 2013
    • Place of Presentation
      Orlando, Florida, USA
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 大腸鋸歯状腺腫におけるHIF1α、PTCH、EphB2蛋白やDNA修復遺伝子関連蛋白発現の変化とBRAF・Kras遺伝子変異.2013

    • Author(s)
      森本崇、三富弘之、齋藤剛、高橋路子、村上敬、坂本直人、八尾隆史、渡辺純夫
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 虫垂原発低異型度粘液性腫瘍及び粘液性嚢胞腺腫の臨床病理学的解析.2013

    • Author(s)
      原貴恵子、林大久夫、アリカムイミティ、森本崇、村上敬、李世容、日高康博、具嶋亮介、三富弘之、八尾隆史
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Wnt signal alteration in esophageal basaloid squamous cell carcinoma.2013

    • Author(s)
      齋藤剛、三富弘之、アブドカディイマムハッサン、林大久夫、三谷恵子、高橋路子、八尾隆史
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Pfetin mutations at the C-terminal region define a subset of GISTs with adverse clinical outcomes.2013

    • Author(s)
      大久保武人、末原義之、三富弘之、三谷恵子、高橋路子、窪田大介、近藤格、川井章、金子和夫、八尾隆史、齋藤剛
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 食道上皮内腫瘍におけるポリコーム蛋白EZH2,Bmi-1発現の検討.2012

    • Author(s)
      1) 内田士郎、三富弘之、齋藤剛、Abdukadir Imamhasan、増田芳雄、和田了、八尾隆史
    • Organizer
      第101回日本病理学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 胃原発のyolk sac like carcinomaの1例.2012

    • Author(s)
      2) 原貴恵子、林大久夫、園上浩司、三富弘之、八尾隆史
    • Organizer
      第101回日本病理学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Immunohistochemical and oncogenetic analyses of the esophageal basaloid squamous cell carcinoma in comparison with conventional squamous cell carcinomas.2012

    • Author(s)
      3) Imamhasan Abdukadir、三富弘之、齋藤剛、林大久夫、荒川敦、内田士郎、福村由紀、三谷恵子、八尾隆史
    • Organizer
      第101回日本病理学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 基底細胞様乳癌におけるDNA修復関連遺伝子蛋白発現の検討.2012

    • Author(s)
      4) アリカムイミティ、三富弘之、中井克也、齊藤光江、霞富士雄、荒川敦、八尾隆史
    • Organizer
      第20回日本乳癌学会総会
    • Place of Presentation
      熊本
    • Related Report
      2012 Research-status Report
  • [Presentation] Basal-like (BL) 乳癌における術前化学療法効果の検討.2012

    • Author(s)
      5) 中井克也、三富弘之、アリカムイミティ、荒川敦、八尾隆史、徳田恵美、齊藤光江、霞富士雄
    • Organizer
      第20回日本乳癌学会総会
    • Place of Presentation
      熊本
    • Related Report
      2012 Research-status Report
  • [Presentation] 当院におけるOSNA (One-Step Nucleic Acid Amplification) 法によるセンチネルリンパ節生検 (SNB) の検討.2012

    • Author(s)
      6) 氷室貴規、三富弘之、園上浩二、堀本 義哉、中井克也、齊藤光江、霞富士雄、荒川敦、八尾隆史
    • Organizer
      第20回日本乳癌学会総会
    • Place of Presentation
      熊本
    • Related Report
      2012 Research-status Report
  • [Presentation] Luminal type乳癌の術前化学療法効果とKi67の発現.2012

    • Author(s)
      7) 堀本義哉、徳田恵美、瀬沼幸司、アリカム イミティ、荒川敦、三富弘之、齊藤 光江
    • Organizer
      第20回日本乳癌学会総会
    • Place of Presentation
      熊本
    • Related Report
      2012 Research-status Report
  • [Presentation] 骨軟部腫瘍におけるDNT3BのgenotypeとDNT3B蛋白発現の解析:DNT3B発現はmutator phenotypeと相関する.2012

    • Author(s)
      8) 齋藤剛、三富弘之、高橋路子、大久保武人、高木辰也、鳥越知明、末原義之、金子和夫、八尾隆史
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] 側方発育型大腸腫瘍ではMUC5AC及びβカテニン発現とK-ras遺伝子が変化する.2012

    • Author(s)
      9) 中江弘三郎、三富弘之、斎藤剛、高橋路子、森本崇、日高康博、坂本直人、八尾隆史、渡辺純夫
    • Organizer
      第20回日本消化器関連学会週間
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] 巨大結腸間膜腫瘤がS状結腸に穿通した血友病患者の1例.2012

    • Author(s)
      10) 高橋里奈、(他15名)、冨木裕一、坂本一博、増田芳雄、三富弘之
    • Organizer
      第67回日本大腸肛門病学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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