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Induction of differentiation of human myelogenous leukemic cells and signal transduction

Research Project

Project/Area Number 04671369
Research Category

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

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionShowa University

Principal Investigator

TAKEDA Ken  Shouwa Universiy Associate School of Medicine Professor, 医学部, 助教授 (80054013)

Co-Investigator(Kenkyū-buntansha) IWAMOTO Sanju  Showa University Assistant Scool of Medicine, 医学部, 助手 (50176567)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Keywordsmyeloid leukemia / differentiation / TNF / TNF receptor / signal transduction / ADP-ribosylation / ML-1 / macrophage / ヒト骨髄性白血病 / レチノイン酸 / GM-CSF / 顆粒球 / 細胞死 / ML-1細胞 / マクロファージ / エンテロトキシン
Research Abstract

Human myelogenous leukemic cells can be induced to differentiate into the monocyte/macrophage pathway by protein inducers called differentiation inducing factors. We have succeeded in purifing one of these factors from leukocyte conditioned medium and identified it as TNF.TNF interacts with target cells by binding to two receptors, 55 kDa and 75 kDa. We examined the functions of these two TNF receptors in induction of differentiation of ML-1 cells. Differentiation was monitored by assessing the appearance and accrual of various cellular markers that are usually associated with maturation of the monocytic elements. 1) The ratio of 55 kDa/75 kDa TNF receptors of ML-1 cells was 1/4.2) Bothe TNF receptors were involved in induction of differentiation of ML-1 cells. Stimulation of either receptor type alone could induce differentiation, but simultaneous stimulation of both receptors induced it more effectively.
We also clarified that TNF synergistically induced differentiation of ML-1 cells in combination with certain bacterial toxins such as choleratoxin and enterotoxin. They acted via ADP-ribosylation of GTP-binding proteins that were coupled to certain effectors other than adenylate cyclase.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Takeda,K. et al: "Lymphotoxin and TNF differ greatly in capacity to induce differentiation of ML 1" Cells.Biochem.Mol.Biol.Internatl.32. 1109-1119 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Iwamoto,S.et al: "Lymphotoxin lacks effects on 75 kDa receptors in cytotoxicity on U-937 cells." Biochem.Biophys.Res.Commun.199. 70-77 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hori,M. et al: "Down regulation of c-myc expression by tumor necrosis factor in combination with TGF or IFN-r with concomitant inhibition" J.Interferon Res.14. 49-55 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeda,K. et al: "Roles of two tumor necrosis factor receptors in induction of differentiation of ML-1 cells." Anticancer Res.13. 883-886 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 武田 健、巌本三寿: "TNFの骨髄性白血病細胞分化誘導" 造血因子. 3. 233-239 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 武田 健、巌本三寿、竹田 稔: "サイトカインによる分化誘導療法" 医学のあゆみ. 169. 123-126 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 武田 健: "癌に対する生体防御機構" 共和出版, 165(101-114) (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 武田 健、他: "臨床免疫、増刊号「サイトカインのすべて」" 科学評論社, 616(269-276) (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeda, K., Iwamoto, S., and Takeda, M.: "Lymphotoxin and TNF differ greatly in capacity to induce differentiation of human myeloblastic leukemia ML-1 cells." Biochem.Mol.Biol.Internatl. 32. 1109-1119 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Iwamoto, S., Shibuya, I., Takeda, K., and Takeda, M.: "Lymphotoxin lacks effects on 75 kDa receptors in cytotoxicity on U-937 cells." Biochem.Biophys.Res.Commun.199. 70-77 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hori, M., Kamijo, R., Takeda.K., and Nagumo, M.: "Down regulation of c-myc expression by tumor necrosis factor-alpha in combination with transforming growth factor-beta or interferon-gamma with concomitant inhibition of proliferation in human cell lines." J.Interferon Res.14. 49-55 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeda, K., Iwamoto, S., and Takeda, M.: "Roles of two tumor necrosis factor receptors in induction of differentiation of ML-1 cells." Anticancer Res.13. 883-886 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeda, K.and Iwamoto, S.: "TNF induces differentiation human myelogenous leukemic cells." Zouketsu Inshi. 3. 233-239 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeda, K., Iwamoto, S.and Takeda, M.: "Cytokine and differentiation therapy of cancer." Igakunoayumi. 169. 123-126 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeda.K.: "Kyouwa Shuppan" "Defense System for Cancer". 165. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeda, K., Iwamoto, S.and Takeda, M.: "Clinical Imuunology" "All of Cytokines". 616. (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeda,K.,et al.: "Roles of two tumor necrosis factor receptors in induction of differentiation of ML-1 cells." Anticancer Res.13. 883-886 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takeda,K. et al: "Lymphotoxin and TNF differ greatly in capacity to induce differentiation of human myeloblastic leukemia" Biochem.Mol.Biol.Internatl.32. 1109-1119 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Iwamoto,S.,et al: "Lymphotoxin lacks effects on 75 kDa receptors in cytotoxicity on U-937 cells." Biochem.Biophys.Res.Commun.199. 70-77 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hori,M. et al: "Down regulation of c-myc expression by tumor necrosis factor in combination with TGF--------" J.Interferon Res.14. 49-55 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 武田 健、他: "サイトカインによる分化誘導療法、" 医学のあゆみ. 169. 123-126 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 武田 健: "TNFとリンホトキシン" 現代医療. 26. 3903-3908 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 武田 健、他: "臨床免疫、増刊号「サイトカインのすべて」" 科学評論社, 616,(269-276) (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takeda,K.et al.: "Roles of two tumor necrosis factor receptors in induction of differentiation of ML-1 cells." Anticancer Res.13. 883-886 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Iwamoto,S.et al.: "Lymphotoxin lacks effects on 75kDa receptors in cytotoxicity on U-937 cells." Biochem.Biophys.Res.Commun.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Hori,M.et al.: "Down regulation of c-myc expression by TNF in combination with TGF-beta or IFN-gamma with concomitant inhibition of proliferation in human cell lines." J.Interferon Res.in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] 武田,健: "サイトカインによる分化誘導療法" 医学のあゆみ. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 武田,健: "癌に対する生体防御機構" 共和出版, 171 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 武田,健: "動物培養細胞マニュアル" 共立出版, 368 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 武田 健、巌本 三寿: "分化誘導促進因子TNFの骨髄性白血病細胞 分化誘導因子" 造血因子. 3. 233-239 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 武田 健、巌本 三寿、竹田 稔: "TNFとリンホトキシン-構造と作用の違いとレセプター" 別冊医学のあゆみ「サイトカイン-基礎から臨床応用まで」. 66-70 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Iwamot,S.,Takeda,K.Ueda,T.and Yasuhara,H.: "Oxygen Radicals" Elsevier Science, 811-814 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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