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Analysis of the expression and function of Notch-related factors in endometrial carcinoma

Research Project

Project/Area Number 23592442
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionShinshu University

Principal Investigator

TAKATSU Akiko  信州大学, 医学部附属病院, 助教 (90447730)

Co-Investigator(Kenkyū-buntansha) SUZUKI Akihisa  信州大学, 医学部附属病院, 特任研究員 (10547095)
SHIOZAWA Tanri  信州大学, 医学部, 教授 (20235493)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsNotch シグナル / 子宮内膜癌 / Notch 阻害薬 / Notch1 / Notch3 / JAG1 / DLL4 / Notchシグナル経路 / 遊走能 / 浸潤能 / γ-secretase阻害剤 / 浸潤
Research Abstract

The expression of Notch receptors (Notch1 and 3) and Notch ligands (JAG1 and DLL4) was examined immunohistochemically in 37 normal and 76 malignant endometrial tissue samples. For each section, immunohistochemical staining was scored using a positivity index (PI, full score; 200). The PIs for Notch1 (mean 90.4), Notch3 (mean 95.6), JAG1 (mean 95.5) and DLL4 (mean 88.2), were significantly higher in endometrial carcinoma than normal endometrium. Patients with tumours showing high expression of both Notch1 and JAG1 had a poor prognosis compared with those having double-negative carcinomas (P = 0.015). The addition of a Notch inhibitor, DAPT, did not inhibit proliferation, but decreased invasion and motility of endometrial carcinoma cell lines. In conclusion, the Notch1-JAG1 axis may enhance the invasive properties of endometrial carcinomas, whichsuggests the Notch pathway may be a promising target for the treatment of this malignancy.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (22 results)

All 2013 2012 2011

All Journal Article (12 results) (of which Peer Reviewed: 10 results) Presentation (10 results)

  • [Journal Article] Lipocalin2 enhances the matrix metalloproteinase-9 activity and invasion of extravillous trophoblasts under hypoxia2013

    • Author(s)
      Kobara H, Miyamoto T, Suzuki A, Asaka R, Yamada Y, Ishikawa K, Kikuchi N, Ohira S, Shiozawa T
    • Journal Title

      Placenta

      Volume: 34 Pages: 1036-43

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clonality analysis suggests that STK11 gene mutations are involved in progression of lobular endocervical glandular hyperplasia (LEGH) to minimal deviation adenocarcinoma (MDA)2013

    • Author(s)
      Takatsu A, Miyamoto T, Fuseya C, Suzuki A, Kashima H, Horiuchi A, Ishii K, Shiozawa T
    • Journal Title

      Virchows Arch

      Volume: 462 Pages: 645-51

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical expression of core 2β1,6-N-acetylglucosaminyl transferase 1 (C2GnT1) in endometrioid-type endometrial carcinoma : a novel potential prognostic factor2013

    • Author(s)
      Miyamoto T, Suzuki A, Asaka R, Ishikawa K, Yamada Y, Kobara H, Nakayama J, Shiozawa T
    • Journal Title

      Histopathology.

      Volume: 62(7) Pages: 986-93

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clonality analysis suggests that STK11 gene mutations are involved in progression of lobular endocervical glandular hyperplasia (LEGH) to minimal deviation adenocarcinoma (MDA).2013

    • Author(s)
      Takatsu A, Miyamoto T, Fuseya C, Suzuki A, Kashima H, Horiuchi A, Ishii K, Shiozawa T
    • Journal Title

      Virchows Arch

      Volume: 462(6) Issue: 6 Pages: 645-51

    • DOI

      10.1007/s00428-013-1417-1

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Placental mesenchymal dysplasia: chronological observation of placental images during gestation and review of the literature.2013

    • Author(s)
      Ohira S, Ookubo N, Tanaka K, Takatsu A, Kobara H, Kikuchi N, Ohya A, Kanai M, Shiozawa T
    • Journal Title

      Gynecol Obstet Invest

      Volume: 75(4) Issue: 4 Pages: 217-23

    • DOI

      10.1159/000350661

    • NAID

      120007107419

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical expression of core 2 β1,6-N-acetylglucosaminyl transferase 1 (C2GnT1) in endometrioid-type endometrial carcinoma: a novel potential prognostic factor.2013

    • Author(s)
      Miyamoto T
    • Journal Title

      Histopathology

      Volume: Feb 9 [Epub ahead of print] Issue: 7 Pages: 986-93

    • DOI

      10.1111/his.12107

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lipocalin2 enhances the matrix metalloproteinase-9 activity and invasion of extravillous trophoblasts under hypoxia.2013

    • Author(s)
      Kobara H, Miyamoto T, Suzuki A, Asaka R, Yamada Y, Ishikawa K, Kikuchi N, Ohira S, Shiozawa T.
    • Journal Title

      Placenta

      Volume: 34(11) Issue: 11 Pages: 1036-43

    • DOI

      10.1016/j.placenta.2013.08.004

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Involvement of pelvic inflammation-related mismatch repair abnormalities and microsatellite instability in the malignant transformation of ovarian endometriosis2012

    • Author(s)
      Fuseya C, Horiuchi A, Hayashi A, Suzuki A, Miyamoto T, Hayashi T, Shiozawa T
    • Journal Title

      Hum Pathol

      Volume: 43 Pages: 1964-72

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of Notch signalling molecules and their involvement in the invasiveness of endometrial carcinoma cells2012

    • Author(s)
      Mitsuhashi Y, Horiuchi A, Miyamoto T, Kashima H, Suzuki A, Shiozawa T
    • Journal Title

      Histopathology.

      Volume: 60 Pages: 826-37

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of Notch signalling molecules and their involvement in the invasiveness of endometrial carcinoma cells.2012

    • Author(s)
      Mitsuhashi Y, Horiuchi A, Miyamoto T, Kashima H, Suzuki A, Shiozawa T
    • Journal Title

      Histopathology.

      Volume: 30 Issue: 5 Pages: 826-37

    • DOI

      10.1111/j.1365-2559.2011.04158.x

    • Related Report
      2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of pelvic inflammation-related mismatch repair abnormalities and microsatellite instability in the malignant transformation of ovarian endometriosis.2012

    • Author(s)
      Fuseya C, Horiuchi A, Hayashi A, Suzuki A, Miyamoto T, Hayashi T, Shiozawa T.
    • Journal Title

      Hum Pathol.

      Volume: 43 Issue: 11 Pages: 1964-72

    • DOI

      10.1016/j.humpath.2012.02.005

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diagnosis and treatment of endometrial stromal sarcoma2012

    • Author(s)
      Miyamoto T,Shiozawa T.
    • Journal Title

      Nihon Rinsho.

      Volume: 70 Suppl 4 Pages: 447-51

    • Related Report
      2012 Research-status Report
  • [Presentation] 子宮内膜癌におけるポリコーム遺伝子群発現とその臨床病理学的意義の検討2013

    • Author(s)
      石川香織、宮本強、鈴木昭久、山田靖、浅香亮一、塩沢丹里
    • Organizer
      第65回日本産科婦人科学会学術講演会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] T:The expression of lipocalin2 in ovarian carcinoma and endometriosis2012

    • Author(s)
      Yamada Y,Miyamoto T,Asaka R,Ishikawa k,Kobara H,Suzuki A,Shiozawa
    • Organizer
      14th International Gynecologic Cancer Society(IGCS)
    • Place of Presentation
      バンクーバー
    • Related Report
      2013 Final Research Report
  • [Presentation] T:Lipocalin2 enhances the proliferation of endometrial carcinoma cells in nude mice2012

    • Author(s)
      Miyamoto T,Asaka R,Yamada Y,Ishikawa K,Kobara H,Suzuki A,Kashima H,Shiozawa
    • Organizer
      14th International Gynecologic Cancer Society(IGCS)
    • Place of Presentation
      バンクーバー
    • Related Report
      2013 Final Research Report
  • [Presentation] Lipocalin2はヌードマウスでの子宮内膜癌細胞の腫瘍増大を促進する2012

    • Author(s)
      宮本強、浅香亮一、山田靖、石川香織、小原久典、鈴木昭久、鹿島大靖、塩沢丹里
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] Lipocalin2は紫外線照射後およびシスプラチン処理後の子宮内膜癌細胞の生存を促進する2012

    • Author(s)
      宮本強、浅香亮一、鈴木昭久、鹿島大靖、塩沢丹里
    • Organizer
      第64回日本産科婦人科学会学術講演会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] Immunohistochemical expression of Core2β1-6 N-acetylglucosaminyl transferase 1 in the endometrial carcinoma;a novel potential prognostic factor2011

    • Author(s)
      Asaka R,Miyamoto T, Suzuki A,Takatsu A, Kashima H,Nakayama J, Shiozawa T
    • Organizer
      Asian Society of Gynecologic Oncology
    • Place of Presentation
      韓国
    • Related Report
      2013 Final Research Report
  • [Presentation] T:Pre-operative diagnosis and the management of minimal deviation adenocarcinoma and lobular endocervical glandular hyperplasia of the uterine cervix : a multi-center,retrospective study2011

    • Author(s)
      Takatsu A,Imanishi T, Tunoda H,Tanino S,AsakaR,Kashima H,Miyamoto T,Shiozawa
    • Organizer
      Asian Society of Gynecologic Oncology
    • Place of Presentation
      韓国
    • Related Report
      2013 Final Research Report
  • [Presentation] T:Lasr captured microdissection-microarray analysis of the genes innolved in endometrial carcinogenesis : stepwise up-regulation of lipocalin2 expression in normal and neoplastic endometria,and its functional relevance2011

    • Author(s)
      Miyamoto T,Asaka R,Imanishi T,Kashima H,Shiozawa
    • Organizer
      Asian Society of Gynecologic Oncology
    • Place of Presentation
      韓国
    • Related Report
      2013 Final Research Report
  • [Presentation] LEGH(lobular endocervical grandular hyperplasia)は悪性腺腫の前駆病変か?2011

    • Author(s)
      高津亜希子、布施谷千穂、鈴木昭久、宮本強、堀内晶子、塩沢丹里
    • Organizer
      第63回日本産科婦人科学会・総会・学術講演会
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report
  • [Presentation] 子宮内膜癌におけるlipocalin2受容体SLC22A17発現の検討.2011

    • Author(s)
      宮本強、浅香亮一、鈴木昭久、高津亜希子、鹿島大靖、塩沢丹里
    • Organizer
      第63回日本産科婦人科学会・総会・学術講演会大阪
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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