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Feasibility of MARCO(Mitochondrial antisense RNA for cytochrome C Oxidase) for the treatment of leukerniaz

Research Project

Project/Area Number 11470207
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionTeikyo University School of Medicine (2000-2002)
The University of Tokyo (1999)

Principal Investigator

SHIRATUJI Naoki  Department of medicine, Associated Professor, 医学部, 助教授 (00206301)

Co-Investigator(Kenkyū-buntansha) GOTO Moritaka  Univ. of Nagoya, Department of Medicine, Assistant Professor, 医学部, 助手
MATSUDA Satoru  Univ. of Nagoya, Department of Medicine, Associate Professor, 医学部, 助教授 (50242110)
佐藤 典治  東京大学, 医科学研究所, 助教授 (90162461)
大井 淳  東京大学, 医科学研究所, 教務職員 (20302606)
井関 徹  東京大学, 医科学研究所, 助手 (10232365)
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1999: ¥6,100,000 (Direct Cost: ¥6,100,000)
Keywordsmitochondria / antisense RNA / cytochrome C oxidase / gene therapy / Adenovirus / liposome / 抗腫瘍効果 / 白血病
Research Abstract

The plasmid which expressed MARCO: mitochondrial antisense RNA for cytochrome C oxidase was constructed with CMV promoter, and was introduced into murine leukemia cell line MOPC (B cell), EL-4 (T cell), and WEHI-3B (myelomonocytic) with liposomal delivery. The efficiency of the introduction of MARCO to each cell line was approximately 10 %. Cell-death was observed significantly in a time dependent manner in in vitro system. In in vivo system there were also observed elongated survival for 4 weeks when MARCO was administered to the tumor-burden mice for 3 days intra peritoneally, and intra venously. When MARCO was administered to the tumor-burden mice for 14 days with liposomal delivery, there were observed 3 months' elongated survival compared with the mock-transfected mice. There were also observed dose-dependency on the amount of the administered MARCO. The adverse effects were observed leukocytopenia for a transient period ( after 12 to 24 hours after the administration), and no other effects were observed to main organs which was determined with pathological findings. Also, recombinant Adenovirus which expressed MARCO was constructed with cosmid shattle vector originated from Adenovirus. The efficiency of the introduction to MOPC, EL-4, and WEHI-3B cells was approximately 50%. However, in in vitro, and in vivo study, cell-death effects were less than that observed with liposomal administration of MARCO. These data indicated that gene therapy using MARCO is feasible against leukemias, especially with liposomal delively. On the next step, we intend to use RNAi for the gene therapy against leukemias.

Report

(5 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] A.Tomonari, et al.: "Second allogeneic stem cell transplantation for leukemia relapse after first allogeneic transplantation"International Journal of Hematology. 75. 318-323 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Tomonari, et al.: "Acquired pulmonary alveolar proteinosis after umbilical cord blood transplantation for acute myeloid leukemia"American Journal of Hematology. 70. 154-157 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oshima K, et al.: "SHPS-1 : a budding molecule against cancer dissemination"Cancer Research. 62. 3929-3933 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Tomonari, et al.: "Using related donors other than genotypically HLA-matched siblings in allogeneic hematopoietic stem cell transplantation for hematologic disease"International Journal of Hematology. 76. 354-359 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Tomonari, et al.: "Acute myelogeneous leukemia M5b developed during clinical remission of castleman disease"International Journal of Hematology. 77. 274-276 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Asano, et al.: "Impaired selectin-ligand biosynthesis and reduced inflammatory responses in β-1,4-galactosyltransferase-I-deficient mice"Blood. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A,Tomunari, et al: "Second allogeneic stem cell transplantation for leukemia velapse after first allogeneic transplantation"International Journal of Hematology. 75. 318-323 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Tomonari, et al: "Acquired pulmonary alveolar proteinosis after umbilical card blood transplantation for acute myelold lenkemia"Amrican Journal of Hematology. 70. 154-157 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oshima,K, et al: "SHPS-1 : a budding molecule ageinst cancer dissemination"Cancer Research. 62. 3929-3933 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Tomonari, et al: "Using related donors other than genetically HLA-matched siblings in allogeneic hematopoietic stem cell transplantation for hematologic disease"International Journal of Hematology. 76. 354-359 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Tomonari, et al: "A cute myelogeneous leukemia M56 developed during clrurcal remission of castleman dicease"International Journal of Hematology. 77. 274-276 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Asano, et al: "Impared selection ligand biosynthesis and reduced inflammatony responses in B-1, 4-galactosy transferase-2-defficient mice"Blood. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Tomonari, et al.: "second allogeneic stem cell transplantation for leukemia relapse after first allogeneic transplantation"International Journal of Hematology. 75. 318-323 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] A.Tomonari, et al.: "Acquired pulmonary alveolar proteinosis after umbilical cord blood transplantation for acute myeloid leukemia"American Journal of Hematology. 70. 154-157 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Oshima K, et al.: "A Budding Molecule against Cancer Dissemination"Cancer Research. 62. 3929-3933 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] A.Tomonari, et al.: "Using related donors other then genetypically HLA-matched siblings in allogeneic hematopoietic stem cell transplantation for hematologic disease"International Journal of Hematology. 76. 354-359 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T. Yamamoto, etal: "P73 is highly expressed in mycepithelial cells"International Journal of Oncology. 19. 271-276 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S. Matsuda, etal: "Cloning and sequencing of a novel human gene"Journal of Human Genetics. 46. 483-486 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] J. ooi etal: "unrelated cerd blood from splantation for adult patients"British Journal of Haematology. 114. 834-386 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] A. Tomonari: "Severe autoimmune throwbocytopenia after allo-BMT"International Journal of Hematology. 74. 228-232 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Utako Machida, et al: "Refractory Facial Cellulitis Following Cosmetic Rhinoplasty After Cord-blood Stem Cell Transplantation"International Journal of Hematology. 72. 98-100 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hidenori Hase, et al: "TCR-VβRepertoire Analysis with RT-PCR was useful for the Early Detection of Pulmonary Relapsed Tcell Lymphoma After Autologous PBSCT"American Journal of Hematology. 64. 124-127 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nozomi Yusa, et al: "Transcription factor Sp3 activates the liver/bone/kidney-type alkaline phosphatase promoter in hematopoietic cells"Journal of Leukocyte Biology. 68. 772-777 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H. Hase: "TRC-Vbrepertoir analysis with RT-PCR was useful for the early detection of pulmonary relapsed T cell lymphuma after auto PBSCT"Am.J. Hematol. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] N. Yusa: "Transcription factor SP3 binds to the promoter region of the alkaline phosphatase gene"J. Biol. Chem.. (in Press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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