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Exploration of diagnostic and therapeutic targets through array-based analyses for genomic and epigenomic alterations in esophageal squamous-cell carcinoma

Research Project

Project/Area Number 18591457
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionTokyo Medical and Dental University

Principal Investigator

IMOTO Issei  Tokyo Medical and Dental University, Medical Research Institute, Associate Professor (30258610)

Co-Investigator(Kenkyū-buntansha) INAZAWA Johji  Tokyo Medical and Dental University, Medical Research Institute, Professor (30193551)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsesophageal cancer / array-CGH / expression analysis / tissue-microarray / molecular target / DNA methylation / gene amplification / homozygous deletion / アレイCGH法
Research Abstract

By constructing the array-based system for genomic, epigenomic, and mRNA and protein expression changes, we tried to identify diagnostic and/or therapeutic target genes necessary and sufficient to develop "personalized medicine" for esophageal squamous-cell carcinoma (ESCC).
(1) Investigation of genomic copy-number aberrations using CGH-array in ESCC In cell lines as well as primary tumor samples of ESCC, we performed array-CGH analyses using bacterial artificial chromosome (BAC)-arrays and oligo-arrays to explore novel copy-number alterations in cancer genome. Among series of genes locating within the identified amplified and homozygously deleted regions, we determined several target genes, which are associated with the pathogenesis of ESCC through these alterations. In addition to the ESCC, we also analyzed several types of cancers, such as ovarian cancer, hepatocellular carcinoma, and oral cancers, and identified several targets, which may be useful for diagnosis/prediction of progno … More sis and molecular targeting therapy.
(2) Evaluation of clinicopathological and biological significance of candidate targets in cancer cells Possible cancer-associated genes identified from amplified and homozygously deleted regions, we performed expression analyses in mRNA and protein levels using quantitative methods, such as array-based methods and real-time PCR system. In candidate tumor-suppressor genes (TSGs), we also analyzed the involvement of epigenetic alterations, such as alterations in DNA methylation and histone codes, in cancer cells. To evaluate biological significance of target genes as oncogenes or TSGs, we transfected expression plasmids or siRNAs for those genes, and analyzed cell growth, cell cycle, apoptotic cell death, and/or invasive phenotype.
(3) Identification of TSGs through direct exploration of epigenetic alterations in cancer In order to identify epigenetically silenced genes directly, we applied BAMCA (BAC-array based methylated CpG island amplification) method to cancer DNA, and explored abnormally methylated region. From identified possibly hypermethylated regions in ESCC cell lines, we identified several candidate TSGs and determined their clinicopathological and biological significance in ESCC. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (23 results)

All 2007 2006 Other

All Journal Article (15 results) (of which Peer Reviewed: 6 results) Presentation (3 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Promoter hypermethylation contributes to frequent inactivation of a putative con-ditional tumor suppressor gene connective tissue growth factor in ovarian cancer.2007

    • Author(s)
      Kikuchi R, et. al.
    • Journal Title

      Cancer Res 67

      Pages: 7095-105

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] PRTFDC1, a possible tumor-suppressor gene, is frequently silenced in oral squamous-cell carcinomas by aberrant promoter hypermethylation.2007

    • Author(s)
      Suzuki E, et. al.
    • Journal Title

      Oncogene 26

      Pages: 7921-32

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Epigenetic silencing of prostaglandin E receptor 2 (PTGER2) is associated with progression of neuroblastomas.2007

    • Author(s)
      Sugino Y, et. al.
    • Journal Title

      Oncogene 26

      Pages: 7401-13

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Promoter hypermethylation contributes to frequent inactivation of a putative conditional tumor suppressor gene connective tissue growth factor in ovarian cancer2007

    • Author(s)
      Kikuchi R, et. al.
    • Journal Title

      Cancer Res 67

      Pages: 7095-105

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] PRTFDCI, a possible tumor-suppressor gene, is frequently silenced in oral squamous-cell carcinomas by aberrant promoter hypenmethylation2007

    • Author(s)
      Suzuki E, et. al.
    • Journal Title

      Oncogene 26

      Pages: 7921-32

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Epigenetic silencing of prostaglandin E receptor 2(PTGER2) is associated with progression of neuroblastomas2007

    • Author(s)
      Sugino Y, et. al.
    • Journal Title

      Oncogene 26

      Pages: 7401-13

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Promoter hypermethylation contributes to frequent inactivation of a putative con-ditional tumor suppresser gene connective tissue growth factor in ovarian cancer.2007

    • Author(s)
      Kikuchi R, et. al.
    • Journal Title

      Cancer Res 67

      Pages: 7095-105

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PRTFDC1, a possible tumor-suppressor gene, is frequently silenced in oral squamous-cell carcinomas by aberrant promoter hyermethylation.2007

    • Author(s)
      Suzuki E, et. al.
    • Journal Title

      Oncogene 26

      Pages: 7921-32

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic silencing of prostaglandin E receptor 2 (PTGER2)is associated with progression of neuroblastomas.2007

    • Author(s)
      Sugino Y, et. al.
    • Journal Title

      Oncogene 26

      Pages: 7401-13

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RGC32, a novel p53-inducible gene, is located on centrosomes during mitosis and results in G2/M arrest.2007

    • Author(s)
      Saigusa K, Imoto I, Inazawa J, et al.
    • Journal Title

      Oncogene 26・8

      Pages: 1110-21

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A novel amplification target, DUSP26, promotes anaplastic thyroid cancer cell growth by inhibiting p38 MAPK activity.2007

    • Author(s)
      Yu W, Imoto I, Inazawa J, et al.
    • Journal Title

      Oncogene 26・8

      Pages: 1178-1187

    • Related Report
      2006 Annual Research Report
  • [Journal Article] PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma.2006

    • Author(s)
      Kozaki K, Imoto I, Inazawa J, et al.
    • Journal Title

      Cancer Sci 97・12

      Pages: 1351-8

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genetic or epigenetic silencing of low density lipoprotein receptor-related protein 1B expression in oral squamous cell carcinoma.2006

    • Author(s)
      Nakagawa T, Inazawa J, Imoto I, et al.
    • Journal Title

      Cancer Sci 97・10

      Pages: 1070-4

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genomic loss and epigenetic silencing of very-low-density lipoprotein receptor involved in gastric carcinogenesis.2006

    • Author(s)
      Takada H, Imoto I, Inazawa J, et al.
    • Journal Title

      Oncogene 25・49

      Pages: 6554-62

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Frequent silencing of the candidate tumor suppressor PCDH20 by epigenetic mechanism in non-small-cell lung cancers.2006

    • Author(s)
      Imoto I, Inazawa J, et al.
    • Journal Title

      Cancer Res 66・9

      Pages: 4617-26

    • Related Report
      2006 Annual Research Report
  • [Presentation] RGC32, a novel p53-inducible tumor-suppressor gene, is located on centrosomes during mitosis and results in G2/M arrest.2007

    • Author(s)
      Imoto I, et. al.
    • Organizer
      98th annual meeting of American Association for Cancer Research
    • Place of Presentation
      Los Angeles, U.S.A.
    • Year and Date
      2007-04-16
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] RGC32, a novel p53-inducible tumor-suppressor gene, is located on centrosomesduring mitosis and results in G2/M arrest.2007

    • Author(s)
      Imoto I, et. al.
    • Organizer
      98th annual meeting of American Association for Cancer Research
    • Place of Presentation
      LosAngeles, U.S.A
    • Year and Date
      2007-04-16
    • Related Report
      2007 Annual Research Report
  • [Presentation] RGC32, a novel p53-inducible tumor-suppressor gene, is located on centrosomes during mitosis and results in G2/M arrest2007

    • Author(s)
      Imoto I, et. al.
    • Organizer
      98th annual meeting of American Association for Cancer Research
    • Place of Presentation
      Los Angeles, U. S. A.
    • Year and Date
      2007-04-06
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] アレイCGH診断活用ガイドブック2007

    • Author(s)
      井本 逸勢
    • Publisher
      医薬ジャーナル社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.cghtmd.jp/CGHDatabase/index_j.jsp

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.cghtmd.jp/CGHDatabase/index_j.jsp

    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] 食道癌の判別方法2007

    • Inventor(s)
      稲澤譲治、他
    • Industrial Property Rights Holder
      東京医科歯科大学、他
    • Industrial Property Number
      2007-111033
    • Filing Date
      2007-04-19
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 食道癌の判別方法2007

    • Inventor(s)
      稲澤譲治、他
    • Industrial Property Rights Holder
      東京医科歯科大学、他
    • Filing Date
      2007-04-19
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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