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2002 Fiscal Year Final Research Report Summary

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
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.

  • Research Products

    (20 results)

All Other

All Publications (20 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2004-04-14  

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