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Liver-directed gene therapy using space-mediated and remote -controlled method

Research Project

Project/Area Number 14370351
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionNagoya University

Principal Investigator

NAKAO Akimasa  Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (70167542)

Co-Investigator(Kenkyū-buntansha) MIZUNO Masaaki  Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70283439)
TACHIBANA Katsuro  Fukuoka University, School of Medicine, Assistant Professor, 医学部, 講師 (40271605)
SUZUKI Haruhiko  Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (90283431)
YOSHIKAWA Kazuhiro  Aichi Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (60109759)
YOSHIOKA Kentaro  Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (60201852)
福田 吉秀  名古屋大学, 医学部附属病院, 講師 (40181284)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2002: ¥7,200,000 (Direct Cost: ¥7,200,000)
Keywordsspace medicine / remote control / gene therapy / regeneration / liver
Research Abstract

Many kinds of gene therapy project have been tried for various diseases such as congenital metabolic ones, cardiovascular ones, and malignancies all over the world, however, the effectiveness has not been clearly identified due to the immature development of gene transferred vector, In this study, we investigated the effect of space-mediated and remote-controlled method in liver-directed gene therapy as a novel strategy. The ultrasound-mediated gene transfer with echo-contrast agents has been performed to analyze the transduction efficiency by LacZ or EGFP cDNA and to measure the anti-tumor effect by IFNbeta cDNA, In addition, using the hepatic metastasis model of murine colon cancer and the subcutaneous xenograft model of human hepatoma cells, in vivo anti-tumor effect of IFNbeta gene therapy by ultrasound with echo-contrast agent was examined. The results demonstrated that the ultrasound-mediated gene therapy with echo-contrast agents was applicable for hepatic cancer treatment. Next we investigated the effect of hyperbaric oxygen (HBO)-mediated gene transfer to the cold-preserved donor organ in the transplantation. Under the low temperature and short transfection period, the transgene expression by adneovirus-mediated gene transfer was significantly lower than that under the normal condition. The addition of HBO in the transfection period augmented the transgene expression compared to the simple method. We investigated the basic study about the remote-controlled gene therapy using micro and nanorobotics. The results demonstrated that the cavitation effect by the ultrasound was feasible for the remote-controlled gene therapy using micro and nanorobotics. It is concluded that the space-mediated and remote-controlled method are hopeful strategies in liver-directed gene therapy.

Report

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

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Hayakawa A.: "Activation of caspase-8 is critical for sensitivity to cytotoxic anti-Fas antibody-induced apoptosie in human ovarian cancer cells"Apoptosis. 7. 107-113 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakashima I.: "Redox control of T-cell death."Antioxid Redox Signal.. 4. 353-356 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimazui T: "Detection of cadherin-6 mRNA by nested RT-PCR as a potential marker for circulating cancer cells in renal cell carcinoma."Int. Oncol. 23(4). 1049-1054 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takasu S: "Radioimmunoscintigraphy of intracranial glioma xenograft with a technetium-99m-labeled mouse monoclonal antibody specifically recognizing type III mutant epidermal growth factor receptor"J Neurooncol. 63(3). 247-256 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimizu K: "Induction of antigen specific cellular immunity by vaccination with peptides from-MN/CA IX in renal cell carcinoma."Oncol Rep.. 10(5). 1307-1311 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ito A: "Heat shock protein 70 expression induces antitumor immunity during intracellular hyperthermia using magnetite nanoparticles."Cancer Immunol Immunother,. 52(2). 80-88 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hayakawa A., Wu J., Kawamoto Y., Zhou YW., Tanuma S., Nakashima I., Suzuki H.: "Activation of caspase-8 is critical for sensitivity to cytotoxic anti-Fas antibody-induced apoptosis in human ovarian cancer cells."Apoptosis. 7. 107-113 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakashima I., Suzuki H., Kato M., Akhand AA.: "Redox control of T-cell death."Antioxid Redox Signal.. 4. 353-356 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimazui T, Yoshikawa K, Uemura H, Kawamoto R, Kawai K, Uchida K, Hirao Y, Saga S, Akaza H.: "Detection of cadherin-6 mRNA by nested RT-PCR as a potential marker for circulating cancer cells in renal cell carcinoma."Int.Oncol.. 23(4). 1049-1054 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takasu S, Takahashi T, Okamoto S, Oriuchi N, Nakayashiki N, Okamoto K, Muramatsu H, Hayashi T, Nakahara N, Mizuno M, Wakabayashi T, Higuchi T, Endo K, Kozaki K, Miyaishi O, Saga S, Ueda R, Yoshida J, Yoshikawa K.: "Radioimmunoscintigraphy of intracranial glioma xenograft with a technetium-99m-labeled mouse monoclonal antibody specifically recognizing type III mutant epidermal growth factor receptor."J Neurooncol. 63(3). 247-256 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimizu K, Uemura H, Yoshikawa M, Yoshida K, Hirao Y, Iwashima K, Saga S, Yoshikawa K.: "Induction of antigen specific cellular immunity by vaccination with peptides from MN/CA IX in renal cell carcinoma."Oncol Rep.. 10(5). 1307-1311 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ito A, Shinkai M, Honda H, Yoshikawa K, Saga S, Wakabayashi T, Yoshida J, Kobayashi T.: "Heat shock protein 70 expression induces antitumor immunity during intracellular hyperthermia using magnetite nanoparticles."Cancer Immunol Immunother. 52(2). 80-88 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimazui T: "Detection of cadgerin-6 mRNA by nested RT-PCR as a potential marker for circulating cancer cells in renal cell carcinoma."Int.Oncol. 23(4). 1049-1054 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takasu S: "Radioimmunoscintigraphy of intracranial glioma xenograft with a technetium-99m-labeled mouse monoclonal antibody specifically recognizing type III mutant epidermal growth receptor."J Neurooncol. 63(3). 247-256 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimizu K: "Induction of antigen specific cellular immunity by vaccination with peptides from MN/CA IX in renal cell carcinoma."Oncol Rep.. 10(5). 1307-1311 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ito A: "Heat shock protein 70 expression induces antitumor immunity during intracellular hyperthermia using magnetite nanoparticles."Cancer Immunol Immunother. 52(2). 80-88 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hattori A: "AVAQ 594-597 deletion of the TfR2 gene in a Japanese family with hemochromatosis."Hepatol Res.. 26(2). 154-156 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arao M: "Prevalence of diabetes mellitus in Japanese patients infected chronically with hepatitis C virus."J Gastroenterol. 38(4). 355-360 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 八木斎和: "空間制御法を用いた肝癌遺伝子治療の検討"日本外科系連合会雑誌. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Hayakawa A.: "Activation of caspase-8 is critical for sensitivity to cytotoxic anti-Fas antibody-induced apoptosis in human ovarian cancer cells"Apoptosis. 7. 107-113 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akhand AA: "Evidence of both extra^-and intracellular cysteine targets of protein modification for activation of RET kinase"Biochem Biophys Res Commun.. 292. 826-831 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakashima I.: "Redox control of T-cell death"Antioxid Redox Signal. 4. 353-356 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akhand AA.: "Redox-linked cell surface-oriented signaling for T-cell death"Antioxid Redox Signal. 4. 445-454 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] N.kashima I: "Redox-linked signal transduction pathways for protein tyrosine kinase activation"Antioxid Redox Signal. 4. 517-431 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hayakawa A: "Activation of caspase-8 is critical for sensitivity to cytotoxic anti-Fas antibody-induced apoptosis in human ovarian cancer cells"Apoptosis. 7. 107-113 (2002)

    • Related Report
      2002 Annual Research Report

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

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