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2013 Fiscal Year Research-status Report

Serrated pathway大腸癌関連マイクロRNAの同定と治療への展開

Research Project

Project/Area Number 24590429
Research InstitutionDokkyo Medical University

Principal Investigator

三富 弘之  獨協医科大学, 医学部, 教授 (90181940)

Co-Investigator(Kenkyū-buntansha) 齋藤 剛  順天堂大学, 医学部, 准教授 (80439736)
Keywords広基性鋸歯状腺腫/ポリープ / 大腸 / Wntシグナル
Research Abstract

We performed β-catenin immunostaining, methylation specific PCR for Wnt signaling associated genes such as AXIN2, APC, MCC and secreted frizzled-related proteins (SFRPs) in 27 Sessile serrated adenoma/polyps (SSA/Ps), 14 SSA/Ps with high grade dysplasia (SSA/P-HDs) and 9 SSA/Ps with submucosal carcinoma (SSA/P-CAs), as well as 19 conventional tubular adenomas (ADs), 26 ADs with high grade dysplasia (AD-HDs) and 25 ADs with submucosal carcinoma (AD-CAs). Nuclear β-catenin labeling was significantly lower in the SSA/P series than in their AD counterparts whereas a significant increment was found from SSA/Ps to SSA/P-HDs or SSA/P-CAs. The frequency of SFRP4 methylation was significantly higher in SSA/Ps, SSA/P-HDs and SSA/P-CAs, as compared to corresponding AD series. Although APC was only rarely methylated in all groups, AXIN2 and MCC were more frequently methylated in SSA/P-HDs and SSA/P-CAs than in AD counterparts. Stepwise increment of AXIN2 and MCC methylation was identified from SSA/Ps through SSA/P-HDs to SSA/P-CAs. A significant correlation was seen between nuclear β-catenin expression and methylation of AXIN2 or MCC in the SSA/P series. In conclusion, Wnt/β-catenin signal activation mediated by methylation of SFRP4, MCC and AXIN2 may make different contributions to colorectal neoplasia between the serrated and conventional routes.

Current Status of Research Progress
Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

広基性鋸歯状腺腫早期癌合併例23病変のWntシグナルの関連する遺伝子のメチル化解析にかなりのDNAを使ったため、microRNA 20, 21, 93, 181b発現の検討に用いる残りのDNA量がきわめて少なくなり、その解析が進んでいない状況である.

Strategy for Future Research Activity

1) 広基性鋸歯状腺腫の早期癌化例あるい鋸歯状腺癌例を他施設も含めて当たって症例を再度蒐集する予定である.
2)現時点で、解析可能なDNAが残っている広基性鋸歯状腺腫癌合併例のmicroRNA 20, 21, 93, 181b発現の検討を進める.

  • Research Products

    (13 results)

All 2014 2013

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (6 results) (of which Invited: 6 results)

  • [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 Pages: 印刷中

    • DOI

      10.1111/jgh.12553.

    • 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 Pages: 135-143

    • DOI

      10.1007/s00428-014-1538-1.

    • Peer Reviewed
  • [Journal Article] p53 mutations may be involved in malignant transformation of giant cell tumor of bone through interaction with GPX1.2013

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

      Virchows Arch

      Volume: 463 Pages: 67-77

    • DOI

      10.1007/s00428-013-1435-z.

    • 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 Pages: 713-725

    • DOI

      10.1111/his.12220.

    • 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 Pages: 2438-2448

    • DOI

      10.1016/j.humpath.2013.06.002.

    • Peer Reviewed
  • [Journal Article] Immunohistochemical analysis of chromogranin A and p53 expressions in ulcerative colitis-associated neoplasia: neuroendocrine differentiation as an early event in the colitis-neoplasia sequence.2013

    • Author(s)
      Shigaki K, Mitomi H, Fujimori T, Ichikawa K, Tomita S, Imura J, Fujii S, Itabashi M, Kameoka S, Sahara R, Takenoshita S:
    • Journal Title

      Hum Pathol

      Volume: 44 Pages: 2393-2399

    • DOI

      10.1016/j.humpath.2013.06.008.

    • 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

    • Peer Reviewed
  • [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
    • Year and Date
      20130606-20130608
    • 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
    • Year and Date
      20130606-20130608
    • 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
    • Year and Date
      20130606-20130608
    • 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
    • Year and Date
      20130606-20130608
    • 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
    • Year and Date
      20130606-20130608
    • 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
    • Year and Date
      20130518-20130521
    • Invited

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Published: 2015-05-28  

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