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The technology development using selective amplified gene for chronic granulomatous disease for clinical application.

Research Project

Project/Area Number 16590960
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionJICHI MEDICAL UNIVERSITY

Principal Investigator

TAKATOKU Masaaki  JICHI MEDICAL UNIVERSITY, School of Medicine, Assistant Professor, 医学部, 講師 (20285787)

Co-Investigator(Kenkyū-buntansha) UEDA Masuzu  JICHI MEDICAL UNIVERSITY, School of Medicine, Instructor, 医学部, 助手 (60364501)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsgene therapy / CGD / SAG / iBMT / 造血幹細胞移植
Research Abstract

1.Gene transduction and Transplantation experiment to the target cells.
1)The optimization of the transplantation preconditioning.
To examine which is better methods for high engraftment efficiency under no preconditioning using intra tail vein bone marrow transplantation (IV-BMT) or intra bone marrow transplantation (iBMT). Our results demonstrated that it was no significant difference of engraftment efficiency between IV-BMT and iBMT. Both methods were also very low-efficiency.
Therefore, we used non-myeloablative irradiation (2Gy) as preconditioning. Then we compared engraftment efficiency with IV-BMT or iBMT. As this result, the engraftments were confirmed in both methods, and also we detected high expression of the treatment gene. (reactive oxygen production rate : IV-BMT 10%,iBMT 30%)
2)in vivo amplification by the selective amplified gene (SAG).
We developed the vector which included treatment gene (GP91^<phox>) in retrovirus vector mounted SAG. The transduced cells were transplanted in the mouse model, and the gene system action was confirmed.
As this result, the engraftment was confirmed in the mouse which did iBMT after non-myeloablative irradiation, and in addition, the peripheral blood cell population which introduced the treatment gene were increased after the Erythropoietin (EPO) administration as molecular switch of SAG. But this increase was the transience, and it was the EPO stimulus dependence.
2.The safety of this system.
We analyzed gene integration site of the retrovirus using the linear amplified mediated polymerase chain reaction (LAM-PCR) method.
The random integration of the vector virus was confirmed without increase bits of the specific integration site as a result of tracking the blood cell in our mouse models.
It will be observed in the long term in future too.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (25 results)

All 2005 2004 Other

All Journal Article (25 results)

  • [Journal Article] Autologous gamete cryopreservation before hemopoietic stem cell transplantation.2005

    • Author(s)
      Nagashima T, Muroi K, Takatoku M, et al.
    • Journal Title

      Med Sci Monit 11

      Pages: 91-94

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Hematopoietic microchimerism in sheep after in utero transplamtation of cultured cynomolgus embryonic stem cells.2005

    • Author(s)
      Sasaki K, Nagao Y, Takatoku M, at. al.
    • Journal Title

      Transplantation 79

      Pages: 32-37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Low-dose total body irradiation causes clonal fluctuation of primate hematopoietic stem and progenitor cells.2005

    • Author(s)
      Laukkanen MO, Kuramoto K, Calmels B, Takatoku M, et al.
    • Journal Title

      Blood 105

      Pages: 1010-5

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Histone Deacetylase Inhibitor Despeptide(FK228) induces apoptosis in leukemic cells by facilitating mitochondrial translocation of Bax,which is enhanced by the proteasome inhibitor Brotezomib.2005

    • Author(s)
      Sutheesophon K, Kobayashi Y, Takatoku M, Ozawa K, Kano Y, Ishii H, Furukawa Y.
    • Journal Title

      Acta Haematol 115

      Pages: 78-90

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Histone Deacetylase Inhibitor Depsipeptide (FK228) induces apoptosis in leukemic cells by facilitating mitochondrial translocation of Bax, which is enhanced by the proteasome inhibitor Bortezomib.2005

    • Author(s)
      Sutheesophon K, Kobayashi Y, Takatoku M, Ozawa K, Kano Y, Ishii H, Furukawa Y.
    • Journal Title

      Acta Haematol 115

      Pages: 78-90

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Autologous gamete cryopreservation before hemopoietic stem cell transplantation.2005

    • Author(s)
      Nagashima T, Muroi K, Kawano-Yamamoto C, Miyoshi T, Ohmine K, Toshima M, Miyazato A, Takatoku M, Nagai T, Mori M, Komatsu N, Ozawa K.
    • Journal Title

      Med Sci Monit 11

      Pages: 91-94

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hematopoietic microchimerism in sheep after in utero transplantation of cultured cynomolgus embryonic stem cells.2005

    • Author(s)
      Sasaki K, Nagao Y, Kitano Y, Hasegawa H, Shibata H, Takatoku M, Hayashi H, Ozawa K, Hanazono Y.
    • Journal Title

      Transplantation 79

      Pages: 32-37

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Low-dose total body irradiation causes clonal fluctuation of primate hematopoietic stem and progenitor cells.2005

    • Author(s)
      Laukkanen MO, Kuramoto K, Calmels B, Takatoku M, von Kalle C, Donahue RE, Dunbar CE.
    • Journal Title

      Blood 105

      Pages: 1010-1015

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hematopoietic microchimerism in sheep after in utero tarnsplamtation of cultured cynomolgus embryonic stem cells.2005

    • Author(s)
      Sasaki K, Nagao Y, Taketoku M, et al.
    • Journal Title

      Transplantation 79

      Pages: 32-37

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hematopoietic microchimerism in sheep after in utero transplantation of cultured cynomolgus embryonic stem cells2005

    • Author(s)
      Sasaki K, Nagao Y, Takatoku M, et al.
    • Journal Title

      Transplantation 79(1)

      Pages: 32-37

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of the esophagus and stomach as a first manifestation of varicella zoster virus infection after allogeneic bone marrow transplantation2004

    • Author(s)
      Takatoku M, Muroi K, Yamamoto CK, Nagata T, Komatsu K, Ozawa K.
    • Journal Title

      Internal Med 43

      Pages: 861-4

    • NAID

      130000085100

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Severe hepatitis and coplete molecular response caused by imatinib mesylate : possible association of its serum concentration with clinical outcomes.2004

    • Author(s)
      Kikuchi S, Muroi K, Takahashi S, Kawano-Yamamoto C, Takatoku M, et al.
    • Journal Title

      Leuk Lymphoma 45

      Pages: 2349-51

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] High-Level in Vivo Gene Marking after Gene-Modified Autologous Hematopoietic Stem Cell Transplantation without Marrow Conditioning in Nonhiman Primates.2004

    • Author(s)
      Ueda K, Hanazono Y, Shibata H, Ueda Y, Ogata S, Nagashima T, Takatoku M, et al.
    • Journal Title

      Mol Ther 10

      Pages: 469-77

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Treatment with a proteasome inhibitor, bortezomib, for thalidomide-resistant multiple myeloma.2004

    • Author(s)
      Takamatsu M, Noborio-Hatano K, Takahashi S, Kikuchi S, et al.
    • Journal Title

      Jpn J Clin Hematol 45

      Pages: 144-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Severe hepatitis and coplete molecular response caused by imatinib mesylate : possible association of its serum concentration with clinical outcomes.2004

    • Author(s)
      Kikuchi S, Muroi K, Takahashi S, Kawano-Yamamoto C, Takatoku M, Miyazato A, Nagao T, Mori M, Komatsu N, Ozawa K.
    • Journal Title

      Leuk Lymphoma 45(11)

      Pages: 2349-2351

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of the esophagus and stomach as a first manifestation of varicella zoster virus infection after allogeneic bone marrow transplantation.2004

    • Author(s)
      Takatoku M, Muroi K, Yamamoto CK, Nagai T, Komatsu N, Ozawa K.
    • Journal Title

      Internal Med 43(9)

      Pages: 861-864

    • NAID

      130000085100

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] High-Level in Vivo Gene Marking after Gene-Modified Autologous Hematopoietic Stem Cell Transplantation without Marrow Conditioning in Nonhuman Primates.2004

    • Author(s)
      Ueda K, Hanazono Y, Shibata H, Ageyama N, Ueda Y, Ogata S, Tabata T, Nagashima T, Takatoku M, Kume A, Ikehara S, Taniwaki M, Terao K, Hasegawa M, Ozawa K.
    • Journal Title

      Mol Ther 10(3)

      Pages: 469-477

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Treatment with a proteasome inhibitor, bortezomib, for thalidomide-resistant multiple myeloma.2004

    • Author(s)
      Takatoku M, Noborio-Hatano K, Takahashi S, Kikuchi S, Mori M, Muroi K, Komatsu N, Ozawa K.
    • Journal Title

      Jpn J Clin Hematol 45(2)

      Pages: 144-148

    • NAID

      10012841869

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Severe hepatitis and complete molecular response caused by imatinib mesylate : possible association of its serum concentration with clinical outcome2004

    • Author(s)
      Kikuchi S, Muroi K, Takatoku M, et al.
    • Journal Title

      Leuk Lymphoma 45(11)

      Pages: 2349-2351

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of the esophagus and stomach as a first manifestation of varicella zoster virus infection after allogeneic bone marrow transplantation2004

    • Author(s)
      Takatoku M, Muroi K, et al.
    • Journal Title

      Intern Med 43(9)

      Pages: 861-864

    • NAID

      130000085100

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Low-dose total body irradiation causes clonal fluctuation of primate hematopoietic stem and progenitor cells2004

    • Author(s)
      Laukkanen MO, Takatoku M, et al.
    • Journal Title

      Blood 105(3)

      Pages: 1010-1015

    • Related Report
      2004 Annual Research Report
  • [Journal Article] High-level in vivo gene marking after gene-modified autologous hematopoietic stem cell transplantation without marrow conditioning in nonhuman primates2004

    • Author(s)
      Ueda K, Hanazono Y, Takatoku M, et al.
    • Journal Title

      Mol Ther 10(3)

      Pages: 469-477

    • Related Report
      2004 Annual Research Report
  • [Journal Article] プロテアソーム阻害剤bortezomibが奏効したサリドマイド抵抗性難治性多発性骨髄腫2004

    • Author(s)
      高徳正昭, ほか7名
    • Journal Title

      臨床血液 45(2)

      Pages: 144-148

    • NAID

      10012841869

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The usefulness of magnetic resonance imaging (MRI) for disseminated Trichosporosis of the gastrocnemius muscles.

    • Author(s)
      Meguro-Hashimoto A, Takatoku M, Ohmine K, et al.
    • Journal Title

      J Infection (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The usefulness of magnetic resonance imaging (MRI) for disseminated Trichosporosis of the gastrocnemius muscles.

    • Author(s)
      Meguro-Hashimoto A, Takatoku M, Ohmine K, Toshima M, Mori M, Nagai T, Muroi K, Ozawa K.
    • Journal Title

      J Infection (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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