• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Establishment of a new innovative treatment strategy for uterine carcinosarcoma

Research Project

Project/Area Number 19K09753
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionOkayama University

Principal Investigator

KEIICHIRO NAKAMURA  岡山大学, 医歯薬学域, 准教授 (90359886)

Co-Investigator(Kenkyū-buntansha) 増山 寿  岡山大学, 医歯薬学域, 教授 (30314678)
小川 千加子  岡山大学, 大学病院, 講師 (50583035)
松原 侑子  岡山大学, 医歯薬学総合研究科, 非常勤研究員 (50835139)
松岡 敬典  岡山大学, 大学病院, 助教 (60835057)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords子宮体部癌肉腫 / RNA編集 / 癌肉腫 / TCGA / 革新的新規治療戦略 / microRNA / ゲノム解析
Outline of Research at the Start

子宮体癌はThe Cancer Genome Atlas(TCGA)による網羅的ゲノム解析から4つのサブタイプに分類でき,我々は以前から遺伝子解析を鋭意遂行し,臨床病理学的特徴と遺伝子変異の照合を行い,ゲノム解析を推進してきた。しかしながらゲノム解析結果からわかるようにゲノム変異情報だけによって構成されるPrecision Medicineには限界があり,より細やかなPersonalized Medicineへ繋ぐためにはゲノム変異だけでなく,癌特性に大きな影響を及ぼすmicroRNAを新たに加味し,革新的新規治療戦略の構築を試みる。

Outline of Final Research Achievements

Adenosine-to-inosine (A-to-I) RNA editing is a recently described epigenetic modification, which is believed to constitute a key oncogenic mechanism in human cancers. ADAR1 showed significant association with worse histology, and lymph vascular space involvementin EC. The level of AZIN1 RNA editing was also significantly associated with worse histology. ADAR1 expression was significantly correlated with AZIN1 RNA editing level. Multivariate analysis indicated that higher ADAR1 expression along with AZIN1 RNA editing is an independent predictor of prognosis in EC patients. Knockdown of ADAR1 led to increased MDA-5, RIG-I, PKR, and IRF-7 expression, which in turn resulted in increased levels of Bak and apoptosis in EC cells. High ADAR1 expression along with AZIN1 RNA editing could be a predictor of worse prognosis in EC. ADAR1 could be a potential therapeutic target in EC patients.

Academic Significance and Societal Importance of the Research Achievements

子宮体癌症例を解析した結果,ADAR1およびantizyme inhibitor 1(AZIN1)の発現レベル上昇は組織型に関連しており,ADAR1とAZIN1 RNAレベルがいずれも上昇していた症例は予後不良であった。 ADAR1 ノックダウンによりインターフェロン経路に作用し,Bakとアポトーシスが増加を認め,当研究は子宮体癌におけるRNA編集の意義について検討した初めての独創的な研究であり,子宮体癌バイオマーカーとなりうることだけでなく,新たな治療ターゲットとなりうることを示し,癌肉腫に特に有効なことが認められた。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (4 results)

All 2022 2020 2019

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results)

  • [Journal Article] ADAR1 and AZIN1 RNA editing function as an oncogene and contributes to immortalization in endometrial cancer2022

    • Author(s)
      Nakamura K, Shigeyasu K, Okamoto K, Matsuoka H, Masuyama H.
    • Journal Title

      Gynecol Oncol.

      Volume: 166(2) Issue: 2 Pages: 326-333

    • DOI

      10.1016/j.ygyno.2022.05.026

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The presence of chronic diseases contributes to the occurrence risk factors for gynecological cancers in Japan.2020

    • Author(s)
      Okamoto K, Nakamura K, Matsuoka H, Matsubara Y, Haraga J, Ogawa C, Masuyama H.
    • Journal Title

      Mol Clin Oncol.

      Volume: 12(4) Pages: 336-342

    • DOI

      10.3892/mco.2020.1989

    • NAID

      120007004833

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histologic Appearance and Immunohistochemistry of DNA Mismatch Repair Protein and p53 in Endometrial Carcinosarcoma: Impact on Prognosis and Insights Into Tumorigenesis.2019

    • Author(s)
      Saijo M, Nakamura K, Ida N, Nasu A, Yoshino T, Masuyama H, Yanai H.
    • Journal Title

      Am J Surg Pathol.

      Volume: 43(11) Issue: 11 Pages: 1493-1500

    • DOI

      10.1097/pas.0000000000001353

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pre-treatment psoas major volume is a predictor of poor prognosis for patients with epithelial ovarian cancer.2019

    • Author(s)
      Matsubara Y, Nakamura K, Matsuoka H, Ogawa C, Masuyama H.
    • Journal Title

      Mol Clin Oncol.

      Volume: 11(4) Pages: 376-382

    • DOI

      10.3892/mco.2019.1912

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2019-04-18   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi