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1988 Fiscal Year Final Research Report Summary

Bioactive Sialoglycosphingolipids(Gangliosides) and Their Related Amphipathic Sialoglycocompounds:Fundamental Studies and Applications of Anti-Leukemic(Differentiation-Inducing) Activities

Research Project

Project/Area Number 61870050
Research Category

Grant-in-Aid for Developmental Scientific Research

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionJichi Medical School

Principal Investigator

SAITO Masaki  Jichi Medical School, Professor, 医学部, 教授 (60012762)

Co-Investigator(Kenkyū-buntansha) ITOH Masayoshi  MECT Manager, 課長
NOJIRI Hisao  Jichi Medical School, Associate, 医学部, 助手 (70180742)
NAKAMURA Mitsuru  Jichi Medical School, Associate, 医学部, 助手 (20198237)
OHTA Masatsugu  Jichi Medical School, Lecturer, 医学部, 講師 (90160514)
KITAGAWA Sei-ichi  Jichi Medical School, Lecturer, 医学部, 講師 (50133278)
Project Period (FY) 1986 – 1988
Keywordsglycosphingolipids / gangliosides / alpha-sialocholesterol / alpha-sialoglyceride / differentiation-induction / HL-60 / シアロコレステロール / シアログリセリド
Research Abstract

We have recently demonstrated that the particular ganglioside molecules play an important role in regulation of differentiation of human myelogenous leukemia cell line HL-60 cells. The ganglio-series ganglioside GM3, which increases characteristically during monocytic differentiation of HL-60 cells induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA), can induce monocytic differentiation of HL-60 cells, whereas neolacto-series gangliosides, which increase characteristically during granulocytic differentiation of HL-60cells induced by retinoic acid (RA) or dimethylsulfoxide (DMSO), can induce granulocytic differentiation of HL-60 cells. These findings raise the possibility that, in addition to gangliosides, certain types of amphipathic compounds containing sialic acid might be capable of inducing the differentiation of HL-60 cells when added to the culture medium. In this context, we investigated the differentiation-inducing activity of sialocholesterols, which are synthetic amphipath … More ic glycocompounds containing sialic acid. We found that alpha-sialo-cholesterol was a potent inducer for granulocytic differentiation of HL-60 cells, and that the differentiation-inducing activity was stereospecific; that is, alpha-sialocholesterol was much more potent than beta-anomer.The differentiation of cells was dependent on the concentration of alpha-sialocholesterol and accompanied with inhibition of cell growth. Another amphipathic sialocompound, alpha-sialoglyceride, was also demonstrated to be considerably potent for inducing human myelogenous leukemia cells. Further studies with various types of synthetic sialocompounds will be needed to elucidate the structure-activity relationships in the differentiation-induction as well as the determination of differentiation-direction in HL-60 cells however, it will be certain that these sialocompounds, alpha-sialocholesterol and alpha-sialoglyceride, are best candidates ever known for anti-leukemic differentiation-inducing drugs amooth natural and synthetic sialocompounds since they were found to be much less toxic than anticipated. Less

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] H.Nojiri;F.Tkadu;Y.Terul;Y.Miura;M.Saito: Proc.Natl.Aca.Scl.USA. 83. 782-786 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Ohta;Y.Furukawa;C.lde;N.Akiyama;T.Utakoji;Y.Miura;M.Saito: Cancer Res.46. 3067-3074 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Furukawa;M.Ohta;T.Kasahara;Y.Miura;M.Saito: Cancer Res.47. 2589-2593 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Naito;l.Kudo;Y.Nakagawa;K.Waku;H.Nojiri;M.Saito;K.lnoue: J.Biochem.102. 155-162 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Nojiri;S.Kitagawa;M.Nakamura;K.Kirito;Y.Enomoto;M.Saito.: J.Biol.Chem.263(16). 7443-7446 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Akashi;F.Takaku;H.Nojiri;Y.Miura;Y.Nagai;M.Saito.: Blood. 72(2). 469-479 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 斎藤政樹: "医科分子生物学" 南江堂, 12 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 斎藤政樹: "Annual Review 血液" 中外医学社, 18 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nojiri,H.;Takaku,F.;Terui,Y.;Miura,Y.; Saito,M.: "Ganglioside GM3:An acidic membrane component that increases during macrophage-like cell differentiation can induce monocytic differentiation of human myeloid and monocytoid leukemic cell lines HL-60 and U937" Proc.Natl.Acad.Sci.USA. 83. 782-786 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohta,M.;Furukawa,Y.;Ida,C.;Akiyama,N.;Utakoji,T.;Miura,Y.; Saito,M.: "Establishment and Characterization of Four Human Monocytoid Leukemia Cell Lines (JDSK-I,-S,-M and -K) with Capabilities of Monocyte-Macrophage Lineage Differentiation and Constitutive Production of Interleukin 1" Cancer Res.46. 3067-3074 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Furukawa; M.Ohta; T.Kasahara; Y.Miura; M.Saito: "Constitutive Prodduction of Interlleukin 1 by Human Monocytic Leukemia Cell Line JOSK-l and the Production Mechanism" Cancer Res.47. 2589-2593 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nojiri; S.Kitagawa; M.Nakamura; K.Kirito; Y.Enomoto; M.Saito: "Neolacto-series Gangliosides lnduce Granulocytic Differentitation of Human Promyelocytic Leukemia Cell Line HL-60" J.Biol.Chem.263. 7443-7446 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Akashi; F.Takaku; H.Nojiri; Y.Miura; Y.Nagai; M.Saito: "Neutral and Sialosyl Glycosphingolipid Composition and Metabolism of Human T-Lymphoblastic Cell Line MOLT-3 Cells: Dinstinctive Changes as Markers Specific for Their Differentiation" Blood. 72. 469-479 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Experimental Hematology Today-1985 M.Saito; H.Nojiri; Y.Miura: Glycosphingolipids as Specific Differentiation-Markers and Differentiation-Inducers for Human Myelogenous Leukemia Cells: A Monosialyl Glycosphingolipid,Ganglioside GM3,is Highly Potent for Induction of Monocytic Differentiation of Human Myeloid and Monocytoid Cell Lines, HL-60 and U937 Cells. Springer-Verlag, New York, 64-74 (1986)

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      「研究成果報告書概要(欧文)」より

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Published: 1990-12-19  

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