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Comprehensive genomic and epigenetic analysis of ESCC to construct new therapeutic modality

Research Project

Project/Area Number 24300341
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Clinical oncology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

KAWANO Tatsuyuki  東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (00186115)

Co-Investigator(Kenkyū-buntansha) INAZAWA Johji  東京医科歯科大学, 難治疾患研究所, 教授 (30193551)
EISHI Yoshinobu  東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (70151959)
OMURA Ken  東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (10334434)
Co-Investigator(Renkei-kenkyūsha) KOZAKI Ken-ichi  東京医科歯科大学, 難治疾患研究所, 准教授 (50270715)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2014: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywords食道扁平上皮癌 / ゲノム解析 / エピゲノム解析 / マイクロRNA / 全エクソンシーケンス / Field cancerization / heterogeneity / メチル化
Outline of Final Research Achievements

Esophageal squamous cell carcinoma (ESCC) is one of the cancers with poor prognosis, and there are no effective molecular targeted drugs to ESCC yet. To clarify valuable biomarkers or therapeutic targets, we analyzed ESCC clinical samples mainly using a technique of genomic or epigenetic analysis. Whole-exome sequencing revealed some common mutations between two distinct tumors in the same patient, which might explain the mechanism of field cancerization. A comprehensive analysis of methylation status revealed several differentially methylated regions (DMRs) which relate to lymph node metastasis. This might be a novel diagnostic tool to predict lymph node metastasis in ESCC patients. Moreover, we identified tumor-suppressor microRNA which expression was often down-regulated in ESCC clinical samples. This microRNA might be a novel therapeutic agent in ESCC. Though it requires further investigations, we expect that these findings contribute to improve the prognosis of ESCC patients.

Report

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

    (16 results)

All 2014 2013 2012 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (11 results)

  • [Journal Article] The impact of miRNA-based molecular diagnostics and treatment of NRF2-stabilized tumors.2014

    • Author(s)
      Yamamoto S, Inazawa J, et al.
    • Journal Title

      Mol Cancer Res.

      Volume: 12 Issue: 1 Pages: 58-68

    • DOI

      10.1158/1541-7786.mcr-13-0246-t

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Esophageal Squamous Cell Carcinoma Developed 11 Years After Allogeneic Bone Marrow Transplantation for Acute Lymphatic Leukemia.2013

    • Author(s)
      Miyawaki Y, Inazawa J, et al.
    • Journal Title

      Jpn J Clin Oncol.

      Volume: 43 Issue: 1 Pages: 69-73

    • DOI

      10.1093/jjco/hys184

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genomic copy-number alterations of MYC and FHIT genes are associated with survival in esophageal squamous-cell carcinoma.2012

    • Author(s)
      Miyawaki Y, Inazawa J, et al.
    • Journal Title

      Cancer Sci.

      Volume: 103 Issue: 8 Pages: 1558-1566

    • DOI

      10.1111/j.1349-7006.2012.02329.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osteoplastic bone metastasis in esophageal squamous eel cancer : report of a case2012

    • Author(s)
      Nakajima Y
    • Journal Title

      Surgery Today

      Volume: 42(Epub 2011 Nov 18.) Pages: 376-381

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A pilot trial of S-1 plus irinotecan chemotherapy of esophageal adenocar cinoma.2012

    • Author(s)
      Nakajima Y
    • Journal Title

      Hepatogastroenterology

      Volume: 59 Pages: 2182-2185

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Identification of Mir-634 as novel tumor-suppressor microRNA in human cancers2014

    • Author(s)
      藤原直人、井上純、河野辰幸、小崎健一、稲澤譲治
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜, 横浜
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] MicroRNAを用いたNRF2活性化癌に対する診断治療戦略2014

    • Author(s)
      藤原直人、井上純、山本信佑、中島康晃、小村健、河野辰幸、小崎健一、稲澤譲治
    • Organizer
      第69回日本消化器外科学会総会
    • Place of Presentation
      郡山総合体育館, 福島
    • Year and Date
      2014-07-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] MicroRNA-634 induces caspase-dependent apoptosis by targeting anti-apoptotic and mitochondria-related genes in human cancer cells2014

    • Author(s)
      Naoto Fujiwara, Jun Inoue, Tatsuyuki Kawano, Ken-ichi Kozaki, Johji Inazawa
    • Organizer
      AACR annual meeting 2014
    • Place of Presentation
      San Diego Convention Center, San Diego, U.S.A
    • Year and Date
      2014-04-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Exploring target gene(s) within chromosome 19-amplification detected in a subclone from metastatic tumors in mouse transplantable OSCC2014

    • Author(s)
      Tomoki Muramatsu, Ken-ichi Kozaki, Seiya Imoto, Rui Yamaguchi, Hitoshi Tsuda, Tatsuyuki Kawano, Satoru Miyano, Johji Inazawa
    • Organizer
      AACR annual meeting 2014
    • Place of Presentation
      San Diego Convention Center, San Diego, U.S.A
    • Year and Date
      2014-04-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Genome-wide screening of DNA methylation markers to predict the presence of lymph node metastasis in esophageal squamous cell carcinoma2014

    • Author(s)
      Ken-ichi Kozaki, Hiroaki Nagata, Kousuke Tanimoto, Naoto Fujiwara, Seiya Imoto, Daisuke Ichikawa, Satoru Miyano, Tatsuyuki Kawano, Eigo Otsuji, Johji Inazawa
    • Organizer
      AACR annual meeting 2014
    • Place of Presentation
      San Diego Convention Center, San Diego, U.S.A
    • Year and Date
      2014-04-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] 食道扁平上皮癌の術後予後因子として遺伝子MYCおよびFHITにおけるゲノムコピー数異常の意義2012

    • Author(s)
      宮脇豊
    • Organizer
      日本癌学会学術総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-20
    • Related Report
      2012 Annual Research Report
  • [Presentation] 食道扁平上皮癌におけるDNAメチル化関連遺伝子の統合的スクリーニング.2012

    • Author(s)
      永田啓明
    • Organizer
      日本癌学会学術総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-20
    • Related Report
      2012 Annual Research Report
  • [Presentation] 食道扁平上皮癌におけるリンパ節転移予測マーカー同定を目指した網

    • Author(s)
      永田 啓明、河野 辰幸、稲澤 譲治 他
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] NRF2 活性化癌に対するMicroRNA を基盤とした診断・治療

    • Author(s)
      山本 信祐、河野 辰幸、小村 健、稲澤 譲治 他
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 食道癌におけるLAPTM5 遺伝子の発現低下

    • Author(s)
      ヌイラン ミシェル、河野 辰幸、稲澤 譲治 他
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 複数癌種における、MicroRNA-634 による細胞死誘導機構

    • Author(s)
      藤原 直人、河野 辰幸、稲澤 譲治 他
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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