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Basic research for oral cancer therapy by anti-cancer drugs and apoptosis-inducing factor

Research Project

Project/Area Number 09557171
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Surgical dentistry
Research InstitutionShowa University

Principal Investigator

NAGUMO Masao  Showa university, School of Dentistry, Professor, 歯学部, 教授 (70013993)

Co-Investigator(Kenkyū-buntansha) KAMIJO Ryutaro  Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (70233939)
IWASE Masayasu  Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (50193743)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥8,000,000 (Direct Cost: ¥8,000,000)
KeywordsCDDP / 5-Fu / NO donors / apoptosis / ICAM-1 / caspase / Fas / Fas L / TNF-alpha / 5-FU / FasL / SNP / 可溶性Fas / IFN-γ
Research Abstract

We investigated the effects of anti-cancer drugs (CDDP, 5-Fu) , IFN-y or NO donors(SNP, SNAP, NOC) on induction of apoptosis mainly in NA cells which had been established from a squamous cell carcinoma of the tongue. Further the effects of these agents on the expression of c-myc and c-myb, adhesion molecules including ICAM-1, Fas/Fas ligand, and soluble Fas were also studied in NA cells. The results obtained were as follows :
1. When NA cells were treated with NO donors, apoptosis of NA cells was induced together with the inhibition of the expression of c-myc and c-myb mRNA.
2. CDDP and 5-Eu induced apoptosis of NA cells and it was suggested that FLICE (caspase 8) might be concerned in the induction of apoptosis of NA cells. However, synergistic -effect was not observed when NA cells were treated both with these anti-cancer drugs.
3. ICAM-1 expression on NA cells was enhanced by the treatment of CDDP or 5- Eu, and simultaneous treatment with CDDP and 5-Eu exhibited synergistic effect on the induction of ICAM-1.
4. Apoptosis was induced when NA cells were treated with IEN-gamma or anti-Fas antibody (CH11). Then, membrane binding Fas was not altered, whereas soluble Eas in the medium was decreased.
5. The expression of Fas and Fas ligand on HL-60 cells, a leukemia cell line, was enhanced by the treatment with IEN-gamma or TNF-alpha, while the expression of bcl-2 protein and its mRNA was reduced by the treatment.
These results indicate that apoptosis is induced both by anti-cancer drugs or NO donors and that the induction of apoptosis is enhanced by IFN-gamma or TNF-alpha.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] 滝沢邦生 他: "cisplatin, s-flaorourocil併用による癌細胞の細胞接着因子発現誘導とT細胞の抗腫瘍効果誘導" Proceding of the Japanese Cancer Association (56th Annual Meeting). 88(Sup). 375-375 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa K.et al: "Induction of soluble Fas release from cancer cells by inteferon-γ" Molecular Biology of the cell.8. 248-248 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohashi M.et al: "Upregulation of Fas/Fos ligand expression by IFN-γ or TNF-α on HL-60 cells." Molecular Biology of the Cell. 8. 249-249 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 岩瀬正泰 他: "口腔癌における5-Fu, 白金化合物併用化学療法の副作用の検討" 日本口腔外科学会雑誌. 43(12). 912-914 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwase M.et al: "Clinical trial of recombinant granulocyte colony-stlmulating factor for chemotherapy-inducod neutrapenia in potients with oral cancer" J Oral Maxillofac Surg. 55. 836-840 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa K.et al: "Synergistic induction of ICAM-1 expression by cisplatin and 5-fluorounacil in a cancer cell line via a NF-κB independent pathuay" Brit Journal of Cancer. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa M.et al: "Induction of adhesion molecules on cancer cells and anti-tumor effect of T cells by CDDP and/or 5-Fu." Proc Jpn Cancer Assoc. 88. 375-375 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa K.et al: "Induction of soluble Fas release from cancer cells by interferon-gamma." Molecular Biology of the Cell. 8. 248-248 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohashi O.et al: "Upregulation of Fas/Fas ligand expression by IFN-gamma or TNF-alpha on HL-60 cells." Molecular Biology of the Cell.8. 248-248 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwase M.et al.: "Side effects of combination in patients with chemotherapy with fluorouracil and platinum compounds in in oral cancer." Jpn J Oral Maxillo-fac Surg. 43. 912-914 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwase M.et al.: "Clinical trial of recombinant granulocyte colony stimulating factor for chemotherapy-induced neutropenia in patients with oral cancer." J Oral Maxillo-fac Surg. 55. 836-840 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa K.et al: "Synergistic induction of ICAM-1 expression by cisplatin and 5-fluorouracil in a cancer cell line via NF-kB independent pathway." Brit J Cancer. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 滝沢邦生 他: "Cisplatin,5-fluorouracil併用による癌細胞の細胞接着因子発現誘導とT細胞の抗腫瘍効果誘導" Proceeding of the Japanese cancer Association (56th Ammual Muting). 88(Sup). 375-375 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takizawa K,et al: "Induction of socuble Fosrelease from cancercells by interferox-r" Molecular Biology of the Call.8. 248-248 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohashi M.et al: "Upregulation of Fos/Fasligand expression by IFN-γ_<61> TNF-α on HL-60 cells" Molecular Biology of the Cell.8. 249-249 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 岩瀬正泰 他: "口腔癌における5-Fu,白金化合物併用化学療法の副作用の検討" 日本口腔外科学会雑誌. 43(12). 912-914 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Iwase M.et al: "Clinical trial of recombinant Granulocyte colony-stimulating factor for chcmotherapy-induced neutropenia inpatient with oral cancer." J Oral Maxillofac Suig. 55. 836-840 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takizawa K.et al: "Synergistic induction of ICAM-1 expression by cisplantin and 5-fluorouracil in a cancer cell line via a NF-κBindependent pathway" British Journal of Cancer. in press. (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sumitani K, et al: "Cytofoxic effect of Sodium nitroprusside on concer cells : Inuoluement of apotosis and suppresion of C-MYC and C-MYB proto-oncogene expression" Anticoncer Research. 17(2). 865-872 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 滝沢邦生,他: "cisplacin,5-fluorouracil併用による癌細胞の細胞接着分子発現誘導とT細胞の抗腫瘍効果誘導" Proceeding of the Japanese Concer Association. 375-375 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takizawa K, et al.: "Synergislic induction of the expression of cell odhesion moleales by cisplatin and 5-fluorouracil in & human cancer cell line." Proceeding of 13th international Conference on Oral and Moillofacial Surgery. (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takizawa K, et al.: "Induclion of Soluble Fas release from cancer cells by ihtirferon-γ." Molewlar Biology of the Cell. 8. 248-248 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohashi M, et al.: "Upregulation of Fas/Fas ligand expression by IFN-γ or TNF-2 on HL-60 cells" Molocular Biology of the Cell. 8. 249-249 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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