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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
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥3,800,000 (Direct Cost: ¥3,800,000)
KeywordsBRAIN TUMOR / INTERFERON / TNF / GENE / LIPOSOME / NF-kappaB / PHOSPHORYLATION / SIGNAL TRANSDUCTION / NF-κB
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.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (46 results)

All Other

All Publications (46 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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [Publications] Watanabe Y et al: "Characterization of a Serum Response Factor-Like Protein in Saccharomyces cerevisiae,Rlm1,Which Has Transcriptional Activity Regulated by the Mpk1(Slt2) Mitogen-Activated Protein Kinase Pathway" Mol Cell Biol. 17. 2615-2623 (1997)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshida J: "Molecular neurosurgery using gene therapy to treat malignant glioma" Nagoya J.Med.Science. 59. 97-105 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mizuno M.,Yoshida J.: "Tumor Necrosis Factor-α gene transfer augments anti-fas antibody-mediated apoptosis in Human glioma cells." Jpn.J.Cancer Res.87. 543-547 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshida J.,Takaoka T.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)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okada H.,Yoshida J.at al.: "Suppression of CD44 expression decreases migration and invasion of human glioma cell." Int.J.Cancer. 66. 255-260 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sadatomo T.,Yoshida J.et al.: "New approach for the treatment of medulloblastoma by transfection with glial fibrillary acidic protein gene." Surgical Oncology. 5. 69-75 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Harada K,Yoshida J et al.: "Growth inhibition of intracerebral rat glioma by transfection-induced human interferon-β" J Surgical Oncology. 55. 105-109 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshida J,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)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshida J,Mizuno M et al.: "Inhibition of hepatitis B virus replication by interferon-β produced in situ by gene delivery." Environ Med. 39. 33-36 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mizuno M,Yoshida J: "Repeated exposure to cationic immunoliposomes activates effective gene transfer to human glioma cells" Neurologia medico-chirurgica,. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Mizuno M,Yoshida J: "Tumor necrosis factor-α gene transfer augments anti-Fas antibody-mediated apoptosis in human glioma cells" Jpn J Cancer Res,. (in press).

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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