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A novel gene therapy against human leukemias : suppression of protein-tyrosine kinase activities

Research Project

Project/Area Number 05807092
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionJichi Medical School (1994)
The University of Tokyo (1993)

Principal Investigator

MANO Hiroyuki  Jichi Medical School, Dept.Molecular Biology, Assistant professor, 医学部, 講師 (90240704)

Co-Investigator(Kenkyū-buntansha) HONDA Hiroaki  Jichi Medical School, Dept.Molecular Biology, Assistant professor, 医学部, 助手 (40245064)
SAKAI Ryuichi  Jichi Medical School, Dept.Molecular Biology, Associate professor, 医学部, 助手 (40215603)
平井 久丸  東京大学, 医学部(病), 講師 (90181130)
三谷 絹子  東京大学, 医学部(病), 助手 (50251244)
花園 豊  東京大学, 医学部(病), 助手 (70251246)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
KeywordsProtein-tyrosine kinase / Anti-sense / 遺伝子治療 / レトロウィルス
Research Abstract

Protein-tyrosine kinase(PTK)is known to be directly involved in the mechanisms of cell growth or differentiation. As in the case of the Bcr-Abl kinase in chronic myeloid leukemia(CML), activated PTKs have been identified in some human malignancies and shown to participate in the process of oncogenesis. In this study, we have investigated if suppression of such PTK-activities may block the deregulated growth of cancer cells. Tec PTK is known to transduce mitogenic stimuli of cytokines. Addition of antisense oligonucleotides against Tec to culture medium was demonstrated to suppress the cytokine-dependent growth of both leukemia cells and normal bone marrow mononuclear cells. Also, antisense oligonucleotides against Abl could block the growth of CML cell line in a sequence-specific manner.Taken together, suppression of PTK activities should be a novel approach of gene therapy against a broad range of malignancies.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Mano,H. et al.: "Tec protein-tyrosine kinase is involved in IL-3 signaling path way" Blood. 85. 343-350 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Matsuda,T. et al.: "Association and activation of Btk-Tec kinases by gp130,a signal transducer of the IL-6 family of cytokines" Blood. 85. 627-633 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mano,H. et al.: "Tec protein-tyrosine kinase directly associates with Lyu protein-tyrosine kinase through its N-terminal unique domain" Oncogene. 9. 3205-3212 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tang,B. et al.: "Tec kinase associates with c-Kit and is tyrosins phosphorylated and activated following stew cell factor binding" Mol.Cell.Biol.14. 8432-8437 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sato,K. et al.: "Molecular cloning and analysis of the human Tec protein-tryosine kinase." Leukemia. 8. 1663-1672 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mano, H.al.: "Tec protein-tyrosine kinase is involved in IL-3 signaling pathway." Blood. 85. 343-350 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Matsuda, T.et al.: "Association and activation of Btk-Tec kinases by gp130, a signal transducer of the IL-6 family of cytokines." Blood. 85. 627-633 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mano, H.et.al.: "Tec protein -tyrosine kinase directly associates with Lyn protein-tyrosine kinase through its N-terminal unique domain." Oncogene. 9. 3205-3212 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ogawa, S.et al.: "The C-terminal SH3 domain of the mouse c-Crk protein negatively regulates tyrosine-phosphorylation of Crk associated p130 in rat 3YI cells." Oncogene. 9. 1669-1678 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitani, K.et al.: "Molecular analysis of the t(1 ; 19)(q23 ; p13)translocation observed in adult leukemias." Int.J.Hematol.60. 267-271 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitani, K.et al.: "Generation of the AML1-EVI-1 fusion gene in the t(3 ; 21)(q26 ; q22)causes blastic crisis in chronic myelocytic leukemia." EMBO J.13. 504-510 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tang, B.et al.: "Tec kinase associates with c-Kit and is tyrosine phosphorylated and activated following stem cell factor binding." Mol.Cell.Biol.14. 8432-8437 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sato, K.et al.: "Molecular cloning and analysis of the human Tec protein-tyrosine kinase." Leukemia. 8. 1663-1672 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sakai, R.et al.: "A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner." EMBO J.13. 3748-3756 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sugimoto, K.et al.: "Mutations of the p53 gene in myelodysplastic syndrome and MDS-derived leukemia." Blood. 81. 3022-3026 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ogawa, S.et al.: "Detection of the PML/RAR a fusion gene in acute promyelocytic leukemia with a complex translocation involving chromosome 15,17 and 18." Cancer Genet.Cytogenet. 69. 113-117 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sasaki, K.et al.: "Coordinate expression of the alpha and beta chains of human granulocyte macrophage colony-stimulating factor receptor confers ligand-induced morphological transformation in mouse fibroblasts." J.Biol.Chem.268. 13697-13702 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hanazono, Y.et al.: "c-fps/fes protein-tyrosine kinase is implicated in a signaling pathway triggered by granulocyte-macrophage colony-stimulating factor and interleukin-3." EMBO J.12. 1641-1646 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hanazono, Y.et al.: "Erythropoietin induces tyrosine phosphorylation and kinase activity of the c-fps/fes proto-oncogene product in human. erythropoietin-responsive cells." Blood. 81. 3193-3196 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mano, H.et al.: "Expression of a novel form of Tec kinase in hematopoietic cells and mapping of the gene to chromosome 5 near Kit." Oncogene. 8. 417-424 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mano,H.et al.: "Tec protein-tyrosine kinase is involved in IL-3 sigualing pothway" Blood. 85. 343-350 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Matsuda,T.et al.: "Association and activation of Btk.Tec kinase by 8p130,a signal transducer of the IL-6 family of cytokins" Blood. 85. 627-633 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mano,H.et al: "Tec protein-tyrosine kinase directly associates with Lyu protein-tyme kinase through its N-terminal unique domain" Oncogene. 9. 3205-3212 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tang,B.et al.: "Tec Kinase associate with c-Kit and is tyrosine phosphorylated and utlvated tolloming stem cell factor binding" Mol.Cell.Biol.14. 8432-8437 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sato,K.et al.: "Molocular cloning and analysis of the human Tec protein-Tyrosine kinase" Leukemia. 8. 1663-1672 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mano,H.et al.: "Expression of a novel form of Tec kinase in hematopoietic cells and mapping of the gene to chromosome 5 near Kit" Oncogene. 8. 417-424 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sugimoto,K.et al.: "Mutations of the p53 gene in myelodysplastic syndrome and MDS-derived leukemia" Blood. 81. 3022-3026 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hanazono,Y.et al.: "The c-fps/fes tyrosine kinase is involved in a signaling pathway triggered by granulocyte-macrophage colony-stimulating factor and interleukin-3" EMBO J.12. 1641-1646 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sasaki,K.et al.: "Coordinate expression of the α and β chains of human granulocyte-macrophage CSF receptor confers ligand-induced morphological transformation" J.Biol.Chem.268. 13697-13702 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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