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Model for human tumor sngiogenesis using NOD/SCID mice

Research Project

Project/Area Number 13670190
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionKeio University

Principal Investigator

YAMADA Taketo  Keio university, School of Medicine, Instructor, 医学部, 専任講師 (60230463)

Co-Investigator(Kenkyū-buntansha) HOZUMI Nobumichi  Science University of Tokyo, Research Institute for Biological Sciences Professor, 生命科学研究所, 教授 (60051744)
秦 順一  国立成育医療研究センター, 研究所, 所長(研究職) (90051614)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordshuman cancer / leukemia / NOD / SCID mice / angiogenesis / angiopoietin / tek tyrosine kinase / 腫瘍血管新生 / アンギオポエチン / VEGF / 骨髄ストローマ細胞 / レトロウイルスベクター / 腫瘍血管
Research Abstract

Angiogenesis is a crucial event for cancer. We examined human tumor angiogenesis using transplantation of human bone and human breast carcinoma (MB-231) or neuroblastoma (SK-N-DZ) cells into subcutaneous tissue of NOD/SCID mice. Human vessels were observed by immunohistochemical stainings with anti-human CD31 and CD34 antibodies. As a result, human tumor angiogenesis was observed in all transplanted human cancer tissues. Expression vectors (Tek-Fc or Flt-Fc) containing Tek/Tie-2 or Flt-1-extracellular domain and human immunoglobulin Fc domain were transferred into MB-231 or SK-N-DZ cells. Clones with Tek-Fc, Flt-Fc, or neor were inoculated into human bone transplanted-NOD/SCID mice. As a result, tumors which formed by not only the Flt-Fc clones but also the Tek-Fc clones were smaller than tumors formed by neor clones. The tumor vessel density in the tumors of Flt-Fc clones was significantly decreased compared with the tumors of neor clones. In the other hand, the deformity of tumor vessels and the decreased density of vessel were observed in the tumors of Tek-Fc clones. It is obscure whether tumor angiogenesis in hematological malignancies is essential for the tumor development. We examined whether human tumor angiogenesis was generated in these tumors by the inoculation of human leukemia/lymphoma or myeloma cells into the transplanted human bone. As a result, the microvessels in tumors of the leukemia or myeloma cells were formed by human endothelia, which expressed human CD31 and CD34. The microvessel density of the tumors was significantly higher than one of the transplanted human bones without leukemic or myeloma cells (p<0.01). The in vivo models for human tumor angiogenesis were established using the transplantation of human bone and human cancer cells into NOD/SCID mice. These models may be useful for the development of new cancer therapies.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Yuasa H: "Analysis of human TIE2 function on hematopoietic stem cells in umbilical cord blood"Biochem Biophys Res Commun. 298. 731-737 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishimura N: "Various amplification of direct PCR using Blood Samples"Clinical Laboratory. 48. 377-384 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakimoto T: "Thalidomide for the Treatment of Refractory Multiple Myeloma : Association of Plasma Concentrations of Thalidomide and Angiogenic Growth Factors with Clinical Outcome"Jpn J Cancer Res. 93. 1029-1036 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhao C: "Exogenous expression of heat shock protein 90kDa retards the cell cycle and impairs the heat shock response"Experimental Cellular Research. 275. 200-214 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato N: "Elevated level of basic fibroblast growth factor in multiple myeloma correlates with increased disease activity"Jpn J Cancer Res. 93. 459-466 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukao T: "Selective loss of gastrointestinal mast cells and impaired immunity to intestinal parasites in Pik3rl deficient mice"Nature Immunology. 3. 295-304 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yuasa H, Takakura N, Shimomura T, Suenobu S, Yamada T, Nagayama H, Oike Y, Suda T: "Analysis of human TIE2 function on hematopoietic stem cells in umbilical cord blood"Biochem Biophys Res Commun. 298(5). 731-737 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishimura N, Nakayama T, Tonoike H, Kojima K, Shirasaki Y, Kondo K, Yamada T: "Various amplification of direct PCR using Blood Samples"Clinical Laboratory. 48. 377-384 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakimoto T, Hattori Y, Okamoto S, Sato N, Kamata T, Yamaguchi M, Morita K, Yamada T, Takayama N, Uchida H, Shimada N, Tanigawara Y, Ikeda Y: "Thalidomide for the treatment of refractory multiple myeloma : Association of plasma concentrations of thalidomide and angiogenic growth factors with clinical outcome"Jpn J Cancer Res. 93. 1029-1036 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhao C, Hashiguchi A, Kondoh K, Du W, Hata J, Yamada T: "Exogenous expression of heat shock protein 90kDa retards the cell cycle and impairs the heat shock response"Experimental Cellular Research. 275. 200-214 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato N, Hattori Y, Du W, Yamada T, Kamata T, Kakimoto T, Okamoto S, Kawamura C, Kizaki M, Shimada N, Ote Y, Hata J, Ikeda Y: "Elevated level of basic fibroblast growth factor in multiple myeloma correlates with increased disease activity"Jpn J Cancer Res.. 93. 459-466 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukao T, Yamada T, Tanabe M, Terauchi Y, Ohta T, Takeuchi T, Hata J, Kadowaki T, Koyasu S: "Selective loss of gastrointestinal mast cells and impaired immunity to intestinal parasites in Pik3rl deficient mice"Nature Immunology. 3(3). 295-304 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yuasa H, Takakura N, Shimomura T, Suenobu S, Yamada T, Nagayama H, Oike Y, Suda T: "Analysis of human TIE2 function on hematopoietic stem cells in umbilical cord blood"BBRC. 298. 731-737 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kakimoto T, Hattori Y, Okamoto S, Sato N, Kamata T, Yamaguchi M, Morita K, Yamada T., Tanigawara Y, Ikeda Y: "Thalidomide for the treatment of refractory multiple myeloma : Association of plasma concentrations of thalidomide and angiogenic growth factors with clinical outcome"Jpn J Cancer Res. 93. 1029-1036 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Zhao C, Hashiguchi A, Kondoh K, Du W, Hata J, Yamada T: "Exogenous expression of heat shock protein 9OkDa retards the cell cycle and impairs the heat shock response"Experimental Cellular Research. 275. 200-214 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sato N, Hattori Y, Du W, Yamada T, Kamata T, Kakimoto T, Okamoto S, Hata J, Ikeda Y: "Elevated level of basic fibroblast growth factor in multiple myeloma correlates with increased disease activity"Jpn J Cancer Res. 93. 459-466 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamaoka T, Yoshino K, Yamada T, Yano M, Matsui T, Yamaguchi T, Moritani M, Hata J: "Transgenic expression of FGF8 and FGF10 induces transdifferentiation of pancreatic islet cells into hepatocytes and exocrine cells"BBRC. 292. 138-143 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukao T, Yamada T, Tanabe M, Terauchi Y, Ohta T, Takeuchi T, Hata J, Kadowaki T, Koyasu S: "Selective loss of gastrointestinal mast cells and impaired immunity to intestinal parasites in Pik3rl deficient mice"Nature Immunology. 3. 295-304 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukao T, Yamada T, Tanabe M, Terauchi Y, Ohta T, Takeuchi T, Hata J, Kadowaki T, Koyasu S: "Selective loss of gastrointestinal mast cells and impaired immunity to intestinal parasites in Pik3rl deficient mice"Nature Immunology. 3(3). 295-304 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinoda K, Nakamura Y, Matsushita K, Shimoda K, Okita H, Fukuma M, Yamada T, Ohde H, Oguchi Y, Hata J, Umezawa A: "Light-induced apoptosis is accelerated in transgenic retina overexpressing human EAT/mcl-1,an anti-apoptotic bcl-2-related gene"British Journal of Ophthalmology. 85. 1237-1243 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kitamura K, Nagao M, Yamada T, Sunaga M, Hata J, Watanabe S: "Dioxins in bile in relation to those in the human liver and blood"J Toxicological Sciences. 26(5). 327-336 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Minh TB., Watanabe M, Tanabe S, Yamada T, Hata J, Watanabe S: "Specific accumulation and elimination kinetics of of tris(4-chlorophenyl)methane, tris(4-chlorophnyl)methanol and other persistent organochlorines in humans from Japan"Environmental Health Perspectives. 109(9). 927-935 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujita T, Yamada T, Hashiguchi A, Fukushima S, Fujimoto J, Hata J.: "Augmentation of megakaryocytopoiesis by the hematopoietic microenvironment of human granulocyte colony-stimulating factor transgenic mice"Exp Hematol. 29. 1010-1018 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Muto A, Kizaki M, Kawamura C, Matsushita H, Fukuchi Y, Umezawa A, Yamada T, Hata J, Hozumi N, Yamato K, Ito M, Ueyama Y, Ikeda Y: "A novel differentiation-inducing therapy for acute promyelocytic leukemia with a combination of arsenic trioxide and GM-CSF"Leukemia. 15. 1176-1184 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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