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Establishment of Quantitative Method for Measurement of MMPs in Blood and Bile, and Its Clinical Application

Research Project

Project/Area Number 10357023
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Laboratory medicine
Research InstitutionUniversity of Tokyo

Principal Investigator

KUBOTA Shunichiro  University of Tokyo, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (00260480)

Co-Investigator(Kenkyū-buntansha) HORI Hisae  Tokyo Medical & Dental University, Medical Research Institute, Assistant Professor, 難治疾患研究所, 助手 (80014190)
YAMAMOTO Kazuhiko  University of Tokyo, Hospital, Professor, 医学部付属病院, 教授 (80191394)
SEYAMA Yousuke  University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (90010082)
YOSHIMOTO Masataka  Cancer Institute Hospital, Department of Breast Surgery, Chief, 外科, 副部長(研究職)
HATTORI Shunji  Nippi Biomatrix Institute, Chief Researcher, 主任研究員
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥30,300,000 (Direct Cost: ¥30,300,000)
Fiscal Year 2000: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1999: ¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 1998: ¥16,000,000 (Direct Cost: ¥16,000,000)
KeywordsMMP-2 / MMP-9 / ECM / Telomelase / Collagen / Merosin / Clinical Status / Clinical Samples / 胆汁 / 胃癌 / 大腸癌 / エンドスタチン / VEGF / ODC / 癌 / MMP / 筋ジストロフィー症
Research Abstract

We have established quantitative method for the measurement of MMPs, especially MMP-2 and MMP-9 in blood and bile. We applied this method to clinical samples, and found the following new results.
(1)MMP-9 levels in blood was significantly elevated in gastric cancer patients, compared to normal healthy subjects. In stage IV gastric cancer patients MMP-9 level was the highest among stages I, II, III and IV.We examined the correlation between MMP-9 level and the survival of gastric cancer patients, and found that the level of MMP-9(>410)was a good indicator for predicting the survival of gastric cancer patients.
(2)We for the first time established a method for measuring MMP-2 and MMP-9 in bile. Further, we have found that activated MMP-2 and proMMP-9 activities were good markers for predicting liver metastasis in colon cancer patients.
Immunohistochemical analysis using anti-MMP-2 antibody was performed in various cancer tissue sections and we found that MMP-2 expressed in 59% cases out of 80 various cancer including colon, uterus, lung, liver brain, soft tissue and esophagus. We for the first time found that MMP-2 expression was transcriptionally controlled by ODC in cancer cells using gel shift and promotor assays. As ODC is now considered to be a protooncogene and expresses in various cancer, the results suggest that suppressing ODC expression is a reasonabale approach to treat cancer and metastasis.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Ito, S.et al: "Human rhabdomyosarcoma retain insulin-regulated giucose transport activity"Arch Biochem Biophy. 373・1. 287-290 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inoue, K.et al: "Cholestanol induces apotosis of cerebellar neuronal cells"B B R C. 256. 198-203 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hattori, S.et al: "Alkali-treated collagen retained the triple helical conformation"J.Biochem. 125. 676-684 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujisaki, H & Hattori, S: "Gelatin-binding IgG from normal serum"Connective Tissue. 31. 155-160 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki, Y et al: "Interaction of collagen molecules from the aspect of fibril formation"J.Biochem. 126. 54-67 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inoue, K et al.: "Cholestanol induces apoptosis of corneal endothelial and lens epithelial cells."Invest.Ophthalmol.Vis.. 41. 991-997 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubota, S.: "Ornithine decarboxylase and cancer(review)."Cancer J.. 11. 294-297 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nemoto, T.et al.: "Convenient method for analyzing differential expressing gene in theplural cells."Biomages. 8. 91-96 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubota, S., & Seyama, Y.: "Overexpression of vacuolar ATPase 16kDa subunit in 10T1/2 fibroblasts enhances invasion with concomitant induction of matrix metalloproteinase-2."Biochem.Biophys.Res.Commun.. 278(2). 390-394 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nemoto, T.et al.: "p53 independent G1 arrest induced by DL-a-difluromethylornithine."Biochem.Biophys.Res.Commun.. 280. 848-854 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishibashi, Y.et al.: "Anti-alpha integrin antibody induces secretion and activation of 72kDa progelatinase by human fibroblasts."Biochem.Mol.Biol.Int.. 51. 1-7 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito, H.et al.: "Calreticulin is directly involved in anti-a3 integrin antibody-mediated secretion and activation of matrix metalloprotease-2."Biochem.Biophys.Res.Commun.. 283(2). 297-302 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sato, K.et al.: "Laminin 5 promotes activation and spoptosis of the T cells expressing α3β1 integrin"Exp.Cell Res.. 247. 451-460 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 久保田俊一郎: "血液・尿化学検査-その数値をどう読むか-"日本臨床社. 789 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 服部俊治: "バイオインダストリー ; コラーゲンの構造と応用展開"シーエムシー. 75 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubota, S.: "Ornithine decarboxylase and cancer(review)"Cancer J.. 11. 294-297 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sato, K.et al.: "Laminin 5 promotes activation and spoptosis of the T cells expressing α3β1 integrin."Exp.Cell Res.. 247. 451-460 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubota S.: "Polyamine and ODC"Nippon Rinsho. Suppl. 570-574 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujisaki, H.& Hattori, S.: "Gelatin-binding immunoglobulins in normal bovine serum."Connective Tissue. 31. 155-160 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hattori, S.et al.: "Alkali-treated collagen retained the triple helical conformation and the ligand activity for the cell adhesion via α2β1 integrin."J.Biochem.. 125. 676-684 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki, Y.et al.: "Interaction of collagen molecules from the aspect of fibril formation."J.Biochem.. 126. 54-67 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inoue, K.et al.: "Cholestanol induces apoptosis of corneal endothelial and lens epithelial cells."Invest.Ophthalmol.Vis.Sci.. 41. 991-997 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nemoto, T.et.al.: "Convenient method for analyzing differential expressing gene in the plural cells."Bioimages. 8. 91-96 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubota, S., & Seyama, Y.: "Overexpression of vacuolar ATPase 16kDa subunit in 10T1/2 fibroblasts enhances invasion with concomitant induction of matrix metalloproteinase-2."Biochem.Biophys.Res.Commun.. 278. 390-394 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nemoto, T.et al.: "p53 independent G1 arrest induced by DL-α-difluoromethylornithine."Biochem.Biophys.Res.Commun.. 280. 848-854 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishibashi, Y.et al.: "Anti-alpha integrin antibody induces secretion and activation of 72kDa progelatinase by human fibroblasts."Biochem.Mol.Biol.Int.. 51. 1-7 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito, H.et al.: "Calreticulin is directly involved in anti-a3 integrin antibody-mediated secretion and activation of matrix metalloprotease-2. Biochem."Biophys.Res.Commun.. 283(2). 297-302 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nemoto,T.,Kamei,S.,Seyama,Y.,Kubota,s.: "p53 independent G1 arrest induced by DL=α=difluoromethylornithine."Biochem.Biophys.Res.Commun.. 280. 848-854 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nemoto,T.,Kamei,S.,Seyama,Y.,Kubota,S.: "Convenient method for analyzing differential expressing gene in the plural cells."Bioimages. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishibashi,Y.,Ito,H.,Seyama,Y.,Kubota,S.: "Anti-alpha integrin antibody induces secretion and activation of 72 kDa progelatinase by human fibroblasts"Biochem.Mol.Biol.Int.. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Kubota,S.,Seyama,Y.: "Overexpression of vacuolar ATPass 16 kDa subunit in 10T1/2 fibroblasts enhanoesinvasion with concomitant induction of matrix metalloproteinese-2"Biochem.Biophys.Res.Commun.. 278. 390-394 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kubota,S. et al.: "Effects of para-nonylphenol on 92kDa gelatinase secretion by human peripheral lymphocytes and U937 cells in vitro."Biochem.Biophys.Res.Commun.. 279. 270-274 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Kubota: "Omithine decarboxylase and Cancer" The Cancer J. 11. 294-297 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Kubota: "A Novel Arg^<362>Ser Mutation in the Sterol 27-Hydroxylase Gene (CY27)" Biochemistry. 37(43). 15050-15056 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 服部俊治: "コラーゲン" 高分子. 47. 394-397 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Hori: "The complete cDNA coding sequence for the bovine pro a 2(1) chain of type 1 procollagen" Matrix Biology. 17. 85-88 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Hattori: "Differential regulation of MMP-2 and MMP-9Gelatinases in cultured human keratinocytes" Dermatology. 197. 1-5 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 服部俊治: "細胞外マトリックス研究法" コラーゲン技術研究会, 122 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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