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1997 Fiscal Year Final Research Report Summary

Analysis of signal transduction in human glioma cells transfected with cytokine gene

Research Project

Project/Area Number 07457312
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionNagoya University

Principal Investigator

YOSHIDA Jun  Nagoya University, School of Medicine Neurosurgery, Professor, 医学部, 教授 (40158449)

Co-Investigator(Kenkyū-buntansha) HAGIWARA Masatoshi  Tokyo medical and dental university, Medical Research Institute, Professor, 難治疾患研究所, 教授 (10208423)
WAKABAYASHI Toshihiko  Nagoya University, School of Medicine Neurosurgery, Assistant Professor, 医学部, 講師 (50220835)
Project Period (FY) 1995 – 1997
KeywordsBRAIN TUMOR / INTERFERON / TNF / GENE / LIPOSOME / NF-kappaB / PHOSPHORYLATION / SIGNAL TRANSDUCTION
Research Abstract

Our aim is analysis of mechanisms of antitumor activity induced by cytokine gene transfection into human glioma cells.
To clarify the underlying mechanisms involved in the different susceptibility to cytokines, we examined the degrees of phosphorylation or NF-kappaB complex when cytokines (interferon-beta (IFN-beta) or tumor necrosis factor-alpha (TNF-alpha)) were exogenously added to human glioma cells. These results suggest that the different NF-kB complex induced by cytokines in human glioma cells might be related to the varying degrees of susceptibility of tumor cells to cytokines.
To elucidate the mechanisms underlying the antitumor activity of cytokine gene transfection using cationic liposomes, we observed morphological changes under video-enhanced contrast differential interference contrast microscopy. Cells harboring the intranuclear human IFN-beta gene underwent morphological changes characterized by bled formation and cytoplasmic boiling such as apoptosis. On the other hand, exogenously added cytokines did not induce the changes at all.
In in vivo experiments using C57BL/6 mouse, we confirmed the activation of cellular immunity when liposomes, containing mouse IFN-beta gene were injected into the experimental glioma.

  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Wakabayashi T et al: "Antitumor activity of recombinant human tumor necrosis factor-α (rH-TNFα) and liposome-entrapped rH-TNFα." Neurologia medico-chiruugica. 37. 739-746 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohta S et al: "Augmentation of anti-Fas antibody-mediated apoptosis on human glioma cells by liposomes associated with the anbtibody." J Neuro-Oncology. 35. 7-11 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Muro Y et al: "Low Frequency of Autoantibies against Ki-67 Antigen in Japanese Patients with Systemic Autoimmune." Journal of Autoimmunity. 10. 499-503 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe Y et al: "Characterization of a Serum Response Factor-Like Protein in Saccharomyces cerevisiae,Rlml,Which Has Transcriptional Activity Regulated by the Mpkl (Slt2) Mitogen-Activated Protein Kinase Pathway" Mol Cell Biol. 17. 2615-2623 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida J et al: "Cytolysis of malignant glioma cells by lymphokine-activated killer cells combined with anti-CD3/antiglioma bifunctional antibody and tumor necrosis factor-α." J Surg Oncol. 62. 177-182 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida J: "Molecular neurosurgery using gene therapy to treat malignant glioma" Nagoya J.Med.Science. 59. 97-105 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mizuno M et al: "Tumor Necrosis Factor-α gene transfer augments anti-fas antibody-mediated apoptosis in Human glioma cells." Jpn.J.Cancer Res. 87. 543-547 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okada H et al: "Suppression of CD44 expression decreases migration and invasion of human glioma cell." Int J Cancer. 66. 255-260 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okamoto S et al: "Monoclonal antibody against the fusion junction of a deletion-mutant epidermal growth factor receptor." British J Cancer. 73. 1366-1372 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okada H et al: "Gene therapy against an experimental glioma using adeno-associated virus vectors." Gene Therapy. 3. 957-964 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mizuno M et al: "Repeated exposure to cationic immunoliposomes activates effective gene transfer to human glioma cells." Neurologia medico-chirurgica. 36. 141-144 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida J: "Simple preparation and characterization of cationic liposomes associated with a monoclonal antibody against glioma-associated antigen (immunoliposomes)." J Liposome Res. 5. 981-995 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mizuno M,Yoshida J,Takaoka T,and Sugita K.: "Reinforced cytotoxixity of lymphokine-activated killer cells toward glioma cells by transfection of the killer cells with the gamma-interferon gene." Jpn J Cancer Res. 86. 95-100 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Harada K,Yoshida J,Mizuno M and Uozumi T.: "Growth inhibition of intracerebral rat glioma by transfection-induced human interferon-beta." J Surgical Oncology. 55. 105-109 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida J and Mizuno M.: "Simple preparation and characterization of cationic liposomes associated with a monoclonal antibody against glioma-associated antigen (immunoliposomes)." J Liposome Res. 5. 981-995 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida J,Mizuno M,Seo H,Ishikawa T and Kakumu S.: "Inhibition of hepatitis B virus replication by interferon-beta produced in situ by gene delivery." Environ Med. 39. 33-36 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mizuno M and Yoshida J.: "Repeated exposure to cationic immunoliposomes activates effective gene transfer to human glioma cells." Neurologia medico-chirurgica. 36. 141-144 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sadamoto T,Yoshida J,Wakabayashi T,Mizuno M,Harada K,Kurisu K,Uozumi T and Sugita K.: "New approach for the treatment of medulloblastoma by transfection with glial fibrillary acidic protein gene." Surgical Oncology. 5. 69-75 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okada H,Miyamura K,Itoh T,Hagiwara M,Wakabayashi T,Mizuno M,Colosi P,Kurtzman G,Yoshida J.: "Gene therapy against an experimental glioma using adeno-associated virus vectors." Gene Therapy. 3. 957-964 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida J.: "Molicular neurosurgery using gene therapy to treat malignant glioma." Nagoya J.Med.Science. 59. 97-105 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okada H,Yoshida J,Sokabe M,Wakabayashi T,Hagiwara M.: "Suppression of CD44 expression decreases migration and invasion of human glioma cell." Int.J.Cancer. 66. 255-260 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida J,Wakabayashi T,Mizuno M,Takaoka T,Okamoto S,Okada H,Harada K,Yagi K.: "Cytokine gene therapy of malignant glioma by means of DNA/liposomes." Brain Tumor Res. 423-434 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okamoto S,Yoshikawa K,Obata Y,Shibuya M,Aoki S,Yoshida J,Takahashi T.: "Monoclonal antibody against the fusion junction of a deletion-mutant epidermal growth factor receptor." British.J.Cancer. 73. 1366-1372 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mizuno M,Yoshida J.: "Tumor Necrosis Factor-alpha gene transfer augments anti-fas antibody-mediated apoptosis in human glioma cells." Jpn.J.Cancer Res.87. 543-547 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida J,Takaoka T,Mizuno M,Momota H,Okada H.: "Cytolysis of malignant glioma cells by lymphokine-activated killer cells combined with anti-CD3/antiglioma bifunctional antibody and tumor necrosis factor-alpha." J Surg Oncol. 62. 177-182 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wakabayashi T,Yoshida J,Takaoka T,Sadatomo T,Mizuno M,Kimura S.: "Enzyme immunoassay of glioma cell tenascin secretion and augmentation by tumor necrosis factor-alpha." Neurologia medico-chiruugica. 37. 392-398 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wakabayashi T,Yoshida J,Takaoka T,Sadamoto T,Mizuno M,Kimura S.: "Antitumor activity of recombinant human tumor necrosis factor-alpha (rH-TNFalpha) and liposome-entrapped rH-TNFalpha." Neurologia medico-chiruugica. 37. 739-746 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohta S,Mizuno M,Takaoka T,Yoshida J.: "Augmentation of anti-Fas antibody-mediated apoptosis on human glioma cells by liposomes associated with the anbtibody." J Neuro-Oncology. 35. 7-11 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Muro Y,Kano T,Sugiura K and Hagiwara M.: "Low Frequency of Autoantibies against Ki-67 Antigen in JapanesePatient with Systemic Autoimmune." Journal of Autoimmunity. 10. 499-503 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagai Y,Kojima T,Muro Y,Hachiya T,Nishizawa Y,Wakabayashi T,Hagiwara M.: "Identification of a novel nuclear speckle-type protein" SPOP.FEBS Letters. 418. 23-26 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe Y,Takaetsu G,Hagiwara M,Irie K and Matsumoto K.: "Characterization of a Serum Response Factor-Like Protein in Saccharomyces cerevisiae, Rlml, Which Has Transcriptional Activity Regulated by the Mpk1 (Slt2) Mitogen-Activated Protein Kinase Pathway." Mol Cell Biol. 17 (5). 2615-2623 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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