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Mucosal remodeling and genetic instability of stromal cells in ulcerative colitis-associated tumorigenesis

Research Project

Project/Area Number 16590293
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionKITASATO UNIVERSITY

Principal Investigator

OKAYASU Isao  Kitasato University, School of Medicine, Professor, 医学部, 教授 (20014342)

Co-Investigator(Kenkyū-buntansha) YOSHIDA Tsutomu  Kitasato University, School of Medicine, Assistant Professor, 医学部, 講師 (90316943)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsulcerative colitis / carcinogenesis / genetic instability / stromal cells / colorectal cancer / colorectal adenoma / chronic inflammation / remodeling / 発がん / 大腸がん / マイクロダイセクション
Research Abstract

In order to clarify both epithelial and stromal genetic instability in colorectal tumorigenesis in patients of ulcerative colitis (UC), the laser-captured microdissection-PCR-GeneScan method was applied to investigate genetic instability in both epithelial and stromal elements of early UC-associated lesions (regenerative mucosa and dysplasia) and carcinomas using multiple microsatellite markers, chiefly close to NCI-recommended standard markers, chromosome 17 (Chr.17) markers and tumor suppressor genes (TSG). In epithelium, although loss of heterozygosity (LOH) for Chr.17 markers increased along with histological progression, the frequencies of LOH or microsatellite instability (MSI) for TSG markers were found to be almost constantly elevated in both stromal and epithelial components of all lesion types. On the other hand, genetic instability of NCI-recommended standard markers was not found to be significantly correlated with UC-associated tumorigenesis and no frame shift mutations were detected using seven mononucleotide repeat markers.
In comparison, sporadic colorectal adenomas and carcinomas were analyzed with the same method as UC-associated lesions. Frequencies of epithelial alterations showed a step-up increase in tumor progression from adenoma with low-grade dysplasia and adenoma with high-grade dysplasia to carcinoma. Frequencies of stromal LOH or MSI were almost constant in adenomas and invasive carcinomas.
In conclusion, the results indicate the presence of genetic alterations in stroma from an early stage of carcinogenesis, accompanied by stepwise increasing genetic instability of epithelia with progression to carcinoma. In particular, genetic instability in the stroma, especially regarding TSG markers, may play an important role in early phase UC-associated tumorigenesis.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (21 results)

All 2006 2005 2004

All Journal Article (21 results)

  • [Journal Article] Disruption of the p53-p53R2 repair system in ulcerative colitis contributes colon tumorigenesis2006

    • Author(s)
      Yoshida T, 他6名, Okayasu I
    • Journal Title

      Int J Cancer 118

      Pages: 1395-1403

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bottom-up cell proliferation with cyclin A and p27Kip1 expression in ulcerative colitis-associated dysplasia2006

    • Author(s)
      Mikami T, Yoshlda T, 他3名, Okayasu I
    • Journal Title

      Pathol Int 56

      Pages: 10-16

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Epithelial and stromal genetic instability contributes to genesis of colorectal adenomas2006

    • Author(s)
      Ishiguro K, Yoshida T, 他3名, Okayasu I
    • Journal Title

      Gut in press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Disruption of the p53-p53R2 repair system in ulcerative colitis contributes to colon tumorigenesis2006

    • Author(s)
      Yoshida T, Haga S, Numata Y, Yamashita K, Mikami T, Ogawa T, Ohkusa T, Okayasu I.
    • Journal Title

      Int J Cancer 118

      Pages: 1395-1403

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bottom-up cell proliferation with cyclin A and p27Kip1 expression in ulcerative colitis-associated dysplasia2006

    • Author(s)
      Mikami T, Yoshida T, Shiraishi H, Tokuyama W, Motoori T, Okayasu I.
    • Journal Title

      Pathol Int 56

      Pages: 10-16

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Epithelial and stromal genetic instability contributes to genesis of colorectal adenomas2006

    • Author(s)
      Ishiguro K, Yoshida T, Yagishita H, Numata Y, Okayasu I.
    • Journal Title

      Gut (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Disruption of the p53-p53R2 repair system in ulcerative Colitis Contributes to colon tumorigenesis2006

    • Author(s)
      Yoshida T, 他6名, Okuyasu I
    • Journal Title

      Int J Cancer 118

      Pages: 1395-1403

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Bottom-up cell proliferation with cyclin A and p27^<Kip1> expression in ulcerative colitis-associated dysplasia2006

    • Author(s)
      Mikami T, Yoshida T, 他3名, Okayasu I
    • Journal Title

      Pathol Int 56

      Pages: 10-16

    • NAID

      10017320958

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Epithelial and stromal genetic instability contributes to genesis of colorectal adenomas2006

    • Author(s)
      Ishiguro K, Yoshida T, 他2名, Okayasu I
    • Journal Title

      Gut (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Significant increase of colonic mutated crypts correlates with agein sporadic cancer and diverticulosis cases, with higher ・・・2006

    • Author(s)
      Okayasu I, 他6名, Yoshida T, Mikami T
    • Journal Title

      Cancer Sci 97・5(in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Significant correlation of morphological remodeling in ulcerative colitis with disease duration and between elevated p53 and...2005

    • Author(s)
      Mitsuhashi J, 他2名, Okayasu I
    • Journal Title

      Pathol Int 55

      Pages: 107-115

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Significant correlation of morphological remodeling in ulcerative colitis with disease duration and between elevated p53 and p2l^<WAF1> expression in rectal mucosa and neoplastic development2005

    • Author(s)
      Mitsuhashi J, Mikami T, Saigenji K, Okayasu I.
    • Journal Title

      Pathol Int 55

      Pages: 107-115

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Significant correlation of morphological remodeling in ulcerative colitis with disease duration and between p53 and p21^<WAF1>2005

    • Author(s)
      Mitsuhashi J, 他2名, Okayasu I
    • Journal Title

      Pathol Int 55

      Pages: 107-115

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Significant correlation of morphological remodeling in ulcerative colitis with disease duration and between elevated p53 and p21^<WAF1> expression in rectalmucosa and neoplastic development2005

    • Author(s)
      Matsuhashi J, Mikami T, Saigenji K Okayasu I.
    • Journal Title

      Pathol Int 55

      Pages: 107-115

    • NAID

      10016474705

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Upregulation of p16I^<NK4A> and Bax in p53 wild/p53-overexpressing crypts in ulcerative colitis-associated tumours2004

    • Author(s)
      Yoshida T, 他3名, Okayasu I
    • Journal Title

      Br J Cancer 91

      Pages: 1081-1088

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Dye spraying and magnifying endoscopy for dysplasia and cancer surveillance in ulcerative colitis2004

    • Author(s)
      Sada M, 他6名, Okayasu I, Mitomi H
    • Journal Title

      Dis Colon Rectum 47

      Pages: 1816-1823

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Upregulation of p16^<1NK4A> and Bax in p53wild/p53-overexpressing crypts in ulcerative colitis-associated tumours2004

    • Author(s)
      Yoshida T, Matsumoto N, Mikami T, Okayasu I.
    • Journal Title

      Br J Cancer 91

      Pages: 1081-1088

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Endoscopy for dysplasia Dye spraying and magnifying and cancer surveillance in ulcerative colitis2004

    • Author(s)
      Sada M, Igarashi M, Yoshizawa S, Kobayashi K, Katsumata T, Saigenji K, Otani Y, Okayasu I, Mitomi H.
    • Journal Title

      Dis Colon Rectum 47

      Pages: 1816-1823

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Upregulation of p16^<INRA> and Bax in p53 wild/p53-overexpressing crypts in ulcerative colitis-associated tumours2004

    • Author(s)
      Yoshida T, Matsumoto N, Mikami T, Okayasu I.
    • Journal Title

      Br J Cancer 91

      Pages: 108-1088

    • Related Report
      2004 Annual Research Report
  • [Journal Article] High microvascular density is correlated with high VEGF, iNOS and COX-2 expression in penetrating growth-type early gastric carcinomas2004

    • Author(s)
      Ichinoe M, Mikami T, Shiraishi H, Okayasu I.
    • Journal Title

      Histopathology 45

      Pages: 612-618

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Dye spraying and magnifying endoscopy for dysplesia and cancer surveillance in ulcerafive colitis2004

    • Author(s)
      Sada H, Igarashi M, 他5名, Okayasu I, Mitomi H
    • Journal Title

      Dis Colon Rectum 47

      Pages: 1816-1823

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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