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1990 Fiscal Year Final Research Report Summary

Studies on the Mechanism of Cytotoxic Action of Antitumor Cytokines Using Liposomal Membrane Systems

Research Project

Project/Area Number 01580165
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 物質生物化学
Research InstitutionThe University of Tokushima

Principal Investigator

YOSHIMURA Tetsuro  Institute for Enzyme Research, University of Tokushima, Associate Professor, 酵素科学研究センター, 助教授 (30035472)

Co-Investigator(Kenkyū-buntansha) MAEZAWA Shigenori  Institute for Enzyme Research, University of Tokushima, Research Associate, 酵素科学研究センター, 助手 (70173698)
SONE Saburo  School of Medicine, University of Tokushima, Assistant Professor, 医学部附属病院, 講師 (40145024)
Project Period (FY) 1989 – 1990
KeywordsCytotoxic action / Membrane action / Antitumor cytokine / Liposome / Phosphatidylserine / Macrophage / Intracellular behavior / Liposome-bound cytokine
Research Abstract

Studies on the Mechanism of Membrane Action of Antitumor Cytokines Using Liposomal Membrane Systems : TNF and IFN show cytotoxic action on tumor cells. We first examined the effect of membrane lipid composition on the membrane actions of these cytokines, found that membrane Phosphatidylserine (PS) modulates their membrane actions, and suggested that the PS content in the cellular membranes of tumor cells might be responside for their sensitivity to cytokines. We next examined the relationship between the bound state and membrane activity of the two cytokines, and found that the extent of penetration of these cytokines into membranes is correlated with their membrane activities, which could result in the difference in their antitumor activities.
Studies on the Mechanism of Cytotoxic Action of Antitumor Cytokines by the Procedure to Introduce Liposomes into Tumor Cells : To achieve this project smoothly, we first prepared liposomes containing effective fluorescent probes and used macrophage cell systems. We then examined the intracellular behavior of the liposomes in single macrophage cells using a fluorescence microscope, and established the systems to detect and kinetically analyze endocytosis and intracellular fate of liposomes. We have studied the principal pathway and reaction for expression of the cytotoxic actions of cytokines by applying the systems to tumor cells.
Studies on the Mechanism of Action of Antitumor Cytokines Using Liposome-Bound Cytokine Preparation : We have already found that IL-4 inhibits production of TNF and IL-1 in human blood monocytes and suppresses monocyte activation to tumoricidal state, and that liposome-encapsulated IL-4 expresses similar effects. Therefore, we have prepared liposome-bound IL-4 and studied the mechanism of these IL-4 effects.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Tetsuro Yoshimura: "Role of Phosphatidylserine in Membrane Actions of Tumor Necrosis Factor and Interferons α and γ" Biochemistry International. 20. 697-705 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉村 哲郎: "サイトカインの膜作用" 免疫薬理. 8. 38 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tetsuro Yoshimura: "Kinetic Analysis of Endocytosis and Intracellular Fate of Liposomes in Single Macrophage Cells"

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chikamasa Yamashita: "Potential Value of Cetylmannosideーmodified Liposomes as Carriers of Macrophage Activators to Human Blood Monocytes" Japan Journal of Cancer Research. (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tetsuro Yoshimura: "Membrane Perturbation as a Possible Cytotoxic Mechanism of TNF and Interferons.in Tumor Necrosis Factor: Structure,Mechanism of Action,Role in Disease and Ther." Karger,Basel, 7 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 寺田 弘: "ライフサイエンスにおけるリポソ-ム ー実験マニュアルー" SpringerーVerlag, Tokyo, (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshimura, T., and Sone, S.: "Role of Phosphatidylserine in Membrane Actions of Tumor Necrosis Factor and Interferons alpha and gamma" Biochemistry Int.20-4. 697-705 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshimura, T.: "Membrane Actions of Cytokines" Immunopharmacol. & Ther. 8-1. 38 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshimura, T., Sone, S., and Ogura, T.: "Membrane Perturbation as a Possible Cytotoxic Mechanism of TNF and Interferons. in Tunor Necrosis Factor : Structure, Mechanism of Action, Role in Disease and Therapy" Karger, Basel. 70-76 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terada, H., and Yoshimura, T.,: "Liposomes in life Sciences -Laboratory Manual-" Springer-Verlag, Tokyo. (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamashita, C., Sone, S., Ogura, T., and Kiwada, H.: "Potential Value of Cetylmannoside-modified Liposomes as carriers of Macrophage Activators to Human Blood Monocytes" Jpn. J. Cancer Res.(1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshimura, T., Shono, M., and Hong, K.: "Kinetic Analysis of Endocytosis and Intracellular Fate of Liposomes in Single Macrophage Cells"

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

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Published: 1993-08-12  

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