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Analysis of the mechanisms of expression and function of endostatin, a novel anti-cancer medicine derived from basement membrane collagen.

Research Project

Project/Area Number 14571130
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

YAMAGUCHI Noriko  Tokyo Med. & Dent. Univ., Medical Research Institute, Instructor, 難治疾患研究所, 助手 (90251553)

Co-Investigator(Kenkyū-buntansha) HORI Hisae  Tokyo Med. & Dent. Univ., Medical Research Institute, Instructor, 難治疾患研究所, 助手 (80014190)
OKABE Satoshi  Tokyo Med. & Dent. Univ., Graduate School, Associate Professor, 大学院・医歯学総合研究科, 講師 (60242187)
AOYAGI Masaru  Tokyo Med. & Dent. Univ., Graduate School, Associate Professor, 大学院・医歯学総合研究科, 助教授 (40134704)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsAngi ogenesis / Cancer / Endostatin / Rheumatoid arthritis / コラーゲン
Research Abstract

Endostatin is an endogenous angiogenesis inhibitor and showed quite strong anti-cancer activity. In mouse tumor model, endostatin inhibits tumor progression, tumor metastasis and induces tumor regression The final goal of this research is to elucidate the functional mechanisms of endostatin on molecular level, then to contribute the development of new anti-cancer drugs. During 2002 to 2003, we achieved those progression described below.
It was reported that serum level of endostatin Was positively correlated to the progression of cancer. Therefore, we measured angiogenesis inhibitory activity of endostatin-related proteins in human serum. Four endostatin-related fragments were isolated from human serum by anti-endostatin immuno-affinity colum. Recombinant proteins for four fragments revealed inhibitory activities in endothelial cell migration assay. We detected 25kDa fragment reacted with anti-endostatin antibody in the homogenates of human glioma tissues. The levels of tissue endostatin (25kDa fragment) and malignancy grades in gliomas showed the positive correlation. Also, we discovered that endostatin has inhibitory activity against some matrix metalloproteinases through the examination of functional study of endostatin. Angiogenesis inhibitors were considered to be a potential therapy of rheumatod arthritis. We estimated the efficacy of endostatin in two different animal models of rhematoid arthritis and endostatin was proved to be a promising medicine for rhematoid arthritis.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Morimoto T. et al.: "Increased levels of tissue endostatin in human malignant gliomas."Clin.Cancer Res.. 8. 2933-2938 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsumo H, et al.: "Treatment with the angiogenesis inhibitor endostatin : A novel therapy in rheumatiol arthritis."J.Rheumatol.. 29. 890-895 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 山口典子, 二宮善文: "基底膜コラーゲンのフラグメントによる血管新生阻害"Connective Tissue. 34. 165-173 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Furumatsu T. et al.: "Endostatin inhibits adhesion of endothelial cells to collagen I via α_2β_1 integrin, a possible cause of prevention of chondrosarcoma growth."J.Biochem.. 131. 619-626 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kurosaka D et al.: "Arthritis-inhibiting effect of systemic administration of endostatin in passive murine collagen-induced arthritis."Ann.Rheum.Dis.. 62. 677-679 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 山口典子: "XVII型コラーゲンの機能と遺伝子異常症"細胞(The Cell). 35. 136-139 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morimoto T., Aoyagi M., Tamaki M., Yoshino Y., Hon H., Duan L., Yano T., Shibata M., Ohno K., Hirakawa K., Yamaguchi N.: "Increased levels of tissue endostatin in human malignant gliomas."Clin. Cancer Res.. 8. 2933-2938 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsuno H., Yudoh K., Uzuki M., Nakazawa F., Sawai T., Yamaguchi N., Olsen B.R., Kimura T.: "Treatment with the angiogenesis inhibitor endostatin: A novel therapy in rheumatoid arthritis."J.Rheumatol.. 29. 890-895 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamaguchi N., Ninomiya Y.: "Antiangiogenesis activity of fragments derived from basement membrane collagens."Connective Tissue. 34. 165-173 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Furumatsu T., Yamaguchi N., Nishida K., Kawai A., Kunisada T., Namba M., Inoue H., Ninomiy Y.: "Endostatin inhibits adhesion of endothelial cells to collagen I via α_2β_1 integrin, a possible cause of prevention of chondrosarcoma growth."J.Biochemistry. 131. 619-626 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Akagi A., Tajima S., Ishibashi A., Matsubara Y., Takehana M., Kobayashi S., Yamaguchi N.: "Type XVI collagen is expressed in factor XIIIa+ monocyte-derived dermal dendrocytes and constitutes a potential substrate for factor XIIIa."J.Invest.Dermatol.. 118. 267-274 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto S, Momose T, Aoyagi M, Ohno K.: "Spontaneous intracerebral hematomas expanding during the early stage of hemorrhage without re-bleeding.Report of three cases."J.Neurosurg.. 97. 455-460 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto M, Akazawa K, Aoyagi M, Yamamoto N, Yamamoto K.: "Changes in elastin-binding protein in fibroblasts derived from cardinal ligaments of patients with prolapsus uteri."Cell Biol.Int.. 26. 441-449 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto S; Yoshida Y, Aoyagi M, Hirakawa K, Hamada H.: "Reduced transduction efficiency of adenoviral vectors expressing human p53 gene by repeated transfection into glioma cells in vitro."Clin.Cancer Res.. 8. 913-921 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto S, Ohno K, Aoyagi M, Ichinose S, Hirakawa K.: "Cacific deposits on degraded shunt catheters: long-term follow-up of V-P shunts and late complications in three cases."Child's Nerv.Syst.. 18. 19-25 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nemoto T., Hon H., Yoshimoto M., Seyama Y., Kubota S.: "Overexpression of ornithine decarboxylase enhances endothelial proliferation by suppressing endostatin expression."Blood. 15. 1478-1481 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hori H., Hattori S., Inouye S., Kimura A., Irie S., Miyazawa H., Sakaguchi M.: "Analysis of the major epitope of α2 chain of bovine type I collagen in children with bovine gelatin allergy."Journal of Allergy and Clinical Immunology. 110. 652-658 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katsube K., Shimokawa R., Hon H., Hamagaki M., Shiraki S., Takagi M.: "FBN1 gene point mutation in an autopsy case with myxomatous degeneration of the cardiovascular system."Oral Med.Pathol.. 8. 83-89 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kurosaka D., Yoshida K., Yasuda J., Yokoyama T., Kingetu I., Yamaguchi N., Joh K., Matsushima M., Saito S., Yamada A.: "Arthritis-inhibiting effect of systemic administration of endostatin in passive murine collagen-induced arthritis."Ann.Rheum.Dis.. 62. 677-679 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamaguchi N.: "The function and the genetic disorders of type XVIII collagen."The Cell. 35. 136-139 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Duan L, Aoyagi M, Tamaki M, Yoshino Y, Morimoto T, Wakimoto T, Nagasaka Y, Hirakawa K, Ohno K, Yamamoto K.: "Impairment of both apoptotic and cytoprotective signalings in glioma cells resistant to the combined use of cisplatin and tumor necrosis factor-α."Clin.Cancer Res.. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arai T, Ohno K, Takada Y, Aoyagi M, Hirakawa K.: "Neonatal craniopharyngioma and inference of tumor inception time: case report and review of the literature."Surg.Neurol.. 60. 254-259 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hara M, Aoyagi M, Yamamoto M, Maehara T, Takada Y, Nojiri T, Ohno K.: "Rapid shrinkage of remnant central neurocytoma after gamma-knife radiosurgery: A case report."J.Neuro.-Oncol.. 62. 269-273 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 山口 典子: "XVIII型コラーゲンの機能と遺伝子異常症"細胞(The Cell). 35. 136-139 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kurosaka D.: "Arthritis-inhibiting effect of systemic administration of endostatin in passive murine collagen-induced arthritis."Ann.Rheum.. 62. 677-679 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Morikoto T: "Increased levels of tissue endostatin in human malignant gliomas"Clin. Cancer Res.. 8. 2933-2938 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuno H.: "Treatment with the angiogenesis inhibitor endostatin : A novel therapy in rheumatoid arthritis"J. Rheumatol.. 29. 890-895 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Furumatsu T.: "Endostatin inhibits adhesion of endothelial cells to collagen I via α_2β_1 integrin, a possible cause of prevention of chondrosarcoma growth"J. Biochem. (Tokyo). 131. 619-626 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山口 典子: "基底膜コラーゲンのフラグメントによる血管新生阻害"Connective Tissue. 34. 165-173 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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