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Development of therapy on central nervous system diseases using "Lipo-signal"

Research Project

Project/Area Number 13470291
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

MIZUNO Masaaki  Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70283439)

Co-Investigator(Kenkyū-buntansha) MIYACHI Shigeru  Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (00293697)
WAKABAYASHI Toshihiko  Nagoya University Hospital, Associate Professor, 医学部附属病院, 助教授 (50220835)
YOSHIDA Jun  Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40158449)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2002: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2001: ¥9,400,000 (Direct Cost: ¥9,400,000)
KeywordsBRAIN DISEASE / LIPO-SIGNAL / CELL THERAPY / GENETIC ANALYSIS
Research Abstract

"Lipo-signal" is a way to increase and transduce some kinds of signals by combining a lot of biological materials with lipsomes. In this study, we basically studied a development of therapy on central nervous system (CNS) diseases using "Lipo-signal"
Subject 1 : Development of a new immunotherapy for brain tumors using "Lipo-signal"
(1) Lipo-signal, which consisted of small unilamellar vesicle-type liposomes and cell-extracts from cultured glioma cells, induced a specific immune response for the tumor cells in vitro and in vivo. In an experimental mouse melanoma, it induced a strong immune response, even in a lot of metastatic lesions.
(2) Expressions of CD80 and CD86 on dendritic cells (DCs) significantly increased by co-culture DCs with Lipo-signal mentioned above.
Subject 2 : Development of a new regenerative medicine using "Lipo-signal"
Lipo-signal, which consisted of small unilamellar vesicle-type liposomes and biological materials such as VEGF, FGF, NGF, GDNF, and bcl-2, promoted neuronal development of neural stem cells.
Subject 3. Administration of "Lipo-signal"
(1) Intravascualr approach : We injected Lipo-signal into CNS vessels through intravascular catheter and investigated the transfer to brain. Unfortunately, little lipo-signal transferred into brain, but the transfer significantly increased by lactocerebroside-conjugated lipo-signal. Lactocerebroside-conjugated lipo-signal may play a role as a carrier to CNS.
(2) Intracellular dynamics : Lipid entered into the cells through endocytsis and reached to the perinuclear region within 1 h.Thereafter, some were decomposed and others bound to host chromosome during cell division.
From these findings, it is suggested that "Lipo-signal" may play a role on development of new therapy for CNS diseases.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Nakanishi T, et al.: "Significant antitumoral activity of cationic liposomes containing human interferon-β gene against human renal cell carcinoma"Clin. Cancer Res,. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ryuke T, et al.: "Growth inhibition of subcutaneous mouse melanoma and induction of natural killer cells by liposome-mediated interferon-beta gene therapy"Melanoma Res. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yosbida J, et al.: "Antitumor effect of an experimental intracranial human glioma by adeno-associated virus vector containing the human interferon-β gene"Jpn J Cancer Res. 93. 223-228 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ogawa H, et al.: "Reduction of α-galactosyl xenoantigen by expression of endo-β-galactosidase C in pig endothelial cells"Xenotransplantation. 9. 290-296 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizuno M, et al.: "Cationic liposomes conjugation to recombinant adenoviral vectors containing herpes simplex virus thymidine kinase gene followed by ganciclovir treatment reduces viral antigenicity and maintains antitumor activity in mouse subcutaneous glioma model"Cancer Gene Ther. 9. 825-829 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nobayashi M, et al.: "Repeated cationic liposome-mediated gene transfer enhanced transduction efficiency against murine melanoma cell lines"J. Dermatol Sci. 29. 206-213 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aoki H, et al.: "Dendritic cells pulsed with tumor extract-cationic liposomes complex increase the induction of cytotoxic T lymphocytes in mouse brain tumor"Cancer Immunol Immunother. 50. 463-468 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okamoto K, et al.: "Process of apoptosis induced by TNF-α in murine fibroblast Ltk-cell: Continuous observation with video enhanced contrast microscopy"Apoptosis. 7. 77-86 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kageshita T, et al.: "Growth inhibition of human malignant melanoma transfected with the human interferon-β gene by means of cationic liposomes"Melanoma Res. 11. 337-342 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida T, et al.: "Rat glioma cell death induced by cationic liposome-mediated transfer for the herpes simplex virus thymidine kinase gene followed by ganciclovir treatment"J Surgcal Oncol. 76. 19-25 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakanishi H, Mizutani Y, Kawauchi A, Ukimura O, Shiraishi T, Hatano M, Mizuno M, Yoshida J, Miki T: "Significant antitumoral activity of cationic liposomes containing human interferon-βgene against humanrenal cell carcinoma"Clin.Cancer Res. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ryoke Y, Mizuno M, Natsume A, Suzuki O, Nobayashi M, Kageshita T, Matsumoto K, Saida T, Yoshida J: "Growth inhibition of subcutaneous mouse melanoma and induction of natural killer cells by liposome-mediated interferon-beta gene therapy"Melanoma Res. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida J, Mizuno M, Nakahara N and Colosi P: "Antitumor effect of an experimental intracranial human glioma by adeno-associated virus vector containing the human interferon-β gene"Jpn J Cancer Res. 93. 223-228 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ogawa H, Kobayashi T, Yokoyama I, Nagatani N, Mizuno M, Yoshida J, Kadomatsu K, Muramatsu H, Nakao A, Muramatsu T: "Reduction of α-galactosyl xenoantigen by expression of endo-β-galactosidase C in pig endothelial cells"Xenotransplantation. 9. 290-296 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizuno M, Ryuke Y, Yoshida J: "Cationic liposomes conjugation to recombinant adenoviral vectors containing herpes simplex virus thymidine kinase gene followed by ganciclovir treatment reduces viral antigenicity and maintains antitumor activity in mouse subcutaneous glioma model"Cancer Gene Ther. 9. 825-829 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nobayashi M, Mizuno M, Kageshita T, Matsumoto K, Saida T, Yoshida J: "Repeated cationic liposome-mediated gene transfer enhanced transduction efficiency against murine melanoma cell lines"Journal of Dermatological Science. 29. 206-213 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aoki H, Mizuno M, Natsume A, Tsugawa T, Tsujimura K, Takahashi T, Yoshida J: "Dendritic cells pulsed with tumor extract-cationic liposomes complex increase the induction of cytotoxic T lymphocytes in mouse brain tumor"Cancer Immunol Immunother. 50. 463-468 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okamoto K, Mizuno M, Nakahara N, Natsume A, Yoshida J, Mori T, Hori S, Kobayashi H: "Process of apoptosis induced by TNF-α in murine fibroblast Ltk- cell : Continuous observation with video enhanced contrast microscopy"Apoptosis. 7. 77-86 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kageshida T, Mizuno M, Ono T, Matsumot K, Saida T, Yoshida J: "Growth inhibition of human malignant melanoma transfected with the human interferon-β gene by means of cationic liposomes"Melanoma Res. 11. 337-342 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida T, Mizuno M, Taniguchi K, Nakayashiki N, Wakabayashi T, Yoshida J: "Rat glioma cell death induced by cationic liposome-mediated transfer for the herpes simplex virus thymidine kinase gene followed by ganciclovir treatment"J Surgical Oncol. 76. 19-25 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakanishi T et al.: "Significant antitumoral activity of cationic liposomes containing human interferon-β gene against human renal cell carcinoma"Clin. Cancer Res. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Ryuke T et al.: "Growth inhibition of subcutaneous mouse melanoma and induction of natural killer cells by liposome-mediated interferon-beta gene therapy"Melanoma Res. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshida J et al.: "Antitumor effect of an experimental intracranial human glioma by adeno-associated virus vector containing the human interferon-β gene"Jpn J Cancer Res. 93. 223-228 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ogaw H et al.: "Reduction of α-galactosyl xenoantigen by expression of endo-β-galactosidase C in pig endothelial cells"Xenotransplantation. 9. 290-296 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mizuno M et al.: "Cationic liposomes conjugation to recombinant adenoviral vectors containing herpes simplex virus thymidine kinase gene followed by ganciclovir treatment reduces viral antigenicity and maintains antitumor activity in mouse subcutaneous glioma model"Cancer Gene Ther. 9. 825-829 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nobayashi M et al.: "Repeated cationic liposome-mediated gene transfer enhanced transduction efficiency against murine melanoma cell lines"J. Dermatol Sci. 29. 206-213 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Aoki H et al.: "Dendritic cells pulsed with tumor extract-cationic liposomes complex increase the induction of cytotoxic T lymphocytes in mouse brain tumor"Cancer Immunol Immunother. 50. 463-468 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okamoto K et al.: "Process of apoptosis induced by TNF-α in murine fibroblast Ltk-cell : Continuous observation with video enhanced contrast microscopy"Apoptosis. 7. 77-86 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukui T, Hayashi Y, Fukuhara H, Yamamoto N, Nishikawa M, Mitsudo K, Tohnai I, Ueda M, Mizuno M, Yoshida J.: "Suicide gene therapy for human oral squamous cell carcinoma with adeno-associated virus vector"Oral Oncol. 7. 187-189 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto N, Hayashi Y, Fukuhara H, Fukui T, Nishikawa M, Mitsudo K, Tohnai I, Ueda M, Mizuno M, Yoshida J.: "Basic research on interferon gene therapy for oral squamous cell carcinoma"Oral Oncol. 7. 492-494 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nishikawa M, Hayashi Y, Yamamoto N, Fukui T, Fukuhara H, Mitsudo K, Tohnai I, Ueda M, Mizuno M, Yoshida J.: "Cell death of human oral squamous cell caricinoma cell line induced by herpes simplex virus thymidine kinase gene and ganciclovir"Oral Oncol. 7. 578-580 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kageshida T, Mizuno M, Ono T, Matsumot K, Saida T, Yoshida J.: "Growth inhibition of human malignant melanoma transfected with the human interferon-b gene by means of cationic liposomes"Melanoma Res,. 11. 337-342 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshida T, Mizuno M, Taniguchi K, Nakayashiki N, Wakabayashi T, Yoshida J.: "Rat glioma cell death induced by cationic liposome-mediated transfer for the herpes simplex virus thymidine kinase gene followed by ganciclovir treatment"J Surgcal Oncol. 76. 19-25 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Aoki H, Mizuno M, Natsume A, Tsugawa T, Tsujimura K, Takahashi T, Yoshida J.: "Dendritic cells pulsed with tumor extract-cationic liposomes complex increase the induction of cytotoxic Tlymphocytes in mouse brain tumor"Cancer Immunol Immunother. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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