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Differentiation Therapy for Myeloblastic Leukemia-Establishment of New Strategy

Research Project

Project/Area Number 07672380
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionSCIENCE UNIVERSITY OF TOKYO

Principal Investigator

TAKEDA Ken  Science University of Tokyo, Department of Hygiene Chemistry, Professor, 薬学部, 教授 (80054013)

Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordsretinoic acid / GM-CSF / human myeloblastic leukemia cells / differentiation / granulocytes / cell cycle / oncogene / Bcl-2 / bcl-2 / ヒト骨髄性白血病 / サイトカイン / 細胞死 / レチノイン酸誘導体
Research Abstract

The effects of all-trans retinoic acid (ATRA), either alone in combination with GM-CSF, on the induction of differentiation of a human myeloblastic leukemia cell line, ML-1, were investigated. ATRA alone caused only slight induction of NBT-reducing activity even at a high concentration (10-7M), but when combined with GM-CSF, it led to remarkable increase in the induction NBT reducing activity. Synergistic effect of both agents was also observed on morphological changes, the inhibition of cell proliferation and granulocytic characteristics such as esterase activity and expression of surface antigens. When ATRA pr GM-CSF was used alone, neither parameter was changed substantially for long periods of up to 9 days. However, the combination of both agents induced remarkable morphological changes with segmented nuclei and also suppressed DNA-synthesizing activity. The hypophosphorylated form of pRB during this differentiation process was observed. The expression of cyclin D3 cdc25A was markedly down regulated during differentiation. In contrast, Cdk2, Cdk4, Cdk6 and cyclins (A, D2, E) showed almost the same level of expression of CKIs (p21,p27,p57,p15,p16,p18 and p19) that inhibit cdk activity did not change during differentiation. These data suggest that change to the hypophosphorylated form of pRB is attributable to the repression of cyclin D3 and cdc25A genes.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Oka,Y.et al.: "Retinoic acid combined with GM-CSF induces morpho-logical changes with segmented nuclei in human myeloblastic leukemia ML-1 cells"Anticancer Res.. 17. 1951-1956 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fuaki,F.et al.: "Indentification of the anti-adhesive site burried within the heparin-binding domain of fibronectin"J.Biochem.. 121. 189-192 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Itayasu,T.,et al.: "Phorbol ester induces differentiation of human prostatic cancer cell line TSU-Prl into cells with characteristics of microglia"Anticancer Res.in press. (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kubota,K.et al.: "Tumor necrosis factor and lymphotoxin stimulate human myeloblastic leukemia cell(ML-1) invasion through a reconstituted basement membrane(matrigel)"Cancer Letters. 98. 233-240 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 土屋悟 他: "リンホトキシン-β〜その生理的役割"臨床免疫. 28. 1474-1479 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kuroda,K.et al.: "Novel muteins of human tumor necrosis factor with potent antitumor activity and less lethal toxicity in mice"Int.J.Cancer. 63. 152-157 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 武田鍵: "サイトカイン最新動向"医歯薬出版. 235 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 武田鍵: "サイトカインのすべて"科学評論社. 616 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oka, Y. and Takeda, K.: "Retinoic acid combined with GM-CSF induces morphological changes with segmented nuclei in human myeloblastic leukemia ML-1 cells."Anticancer Res.. 17. 1951-1956 (1977)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fukai, F., Hasebe, S., Ueki, M., et al: "identification of the anti-adhesive site buried with the heparin-binding domain of fibronectin"J. Biochem.. 121. 189-192 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Itayasu, T., Shimizu, T., and Takabe, K.: "Phorbol ester induces differentiation of a human prostatic cancer cell line TSU-Pr1 into cells with characteristics of microglia."Anticancer Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kubota, S., Takeda, K., Yamada, T., et al.: "Tumor necrosis factor and lymphotoxin stimulate human myeloblastic leukemia cell (ML-1) invasion through a reconstituted basement membrane (matrigel) with concomitant induction of 92 kDa gelatinase secretion."Cancer letters. 98. 232-240 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kuroda, K., Miyata, K., Kawagoe, T., Nishimura, K., Shikama, H., Takeda, K., and Kato, M.: "Novel muteins of human tumor necrosis factor with potent antitumor activity and less lethal toxicity in mice."Cancer J.. 63. 1474-1477 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takeda, K.: "TNF and Lymphotoxin"IGAKUNOAYUMI. 174. 1104-1108 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takeda, K: "Lymphotoxin in Cytokines"RINSHO-MENEKI. 27. 269-276 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oka,Y.et al.: "Retinoic acid combined with GM-CSF induces morpho-logical changes with segmented muclei in human myeloblastic leukemia ML-1 cells." Anticancer Res.17. 1951-1956 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fuaki,F.et al.: "Identification of the anti-adhesive site burried within the heparin-binding domain of fibronectin." J.Biochem.121. 189-192 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Itayasu,T., et al.: "Phorbol ester induces differentiation of human prostatic cancer cell line TSU-Prl into cells with characteristics of microglia." Anticancer Res.in press.

    • Related Report
      1997 Annual Research Report
  • [Publications] Kubota,K.: "Tumor necrosis factor and lymphotoxin stimulate human myeloblastic leukemia cell (ML-1) invasion through a reconstituted basement membrane (matrigel)" Cancer Letters. 98. 233-240 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fuaki,F.: "Identification of the anti-adhesive site burried within the hepar in-binding domain of fibronectin." J.Biochem.121. 189-192 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Oka,Y.: "Retinoic acid combined with GM-CSF induces morpho-logical changes with segmented nuclei in human myeloblastic leukemia ML-1 cells." Anticancer Res.17(印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 土屋 悟: "リンホトキシン-β〜その生理的役割は?" 臨床免疫. 28. 1474-1479 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takeda,K.: "Novel muteins of human tumor necrosis factor with potent antitumor activity and less lethal toxicity in mice." Int. J. Cancer. 63. 152-157 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takeda,K.: "Tumor necrosis factor and lymphotoxin stimulate human myeloblastic leukemia cell (ML-1) invasion through a reconstituted basement membrane (matrigel) with comcomitant induction of 92 kDa gelatinase secretion." Cancer Letters. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] 武田 健: "TNFとリンホトキシン" 医学のあゆみ. 174. 1104-1108 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 武田 健: "リンホトキシン" 臨床免疫「サイトカインのすべて」. 27. 269-276 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 土屋 悟、武田 健: "リンホトキシン-β〜その生理的役割は?" 臨床免疫. (印刷中).

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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