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Apoptosis induction therapy for pancreatic cancer cells by isoprenoids

Research Project

Project/Area Number 10670491
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionSapporo Medical University

Principal Investigator

TERUI Takeshi  Sapporo Medical University, 医学部, 助手 (50281233)

Co-Investigator(Kenkyū-buntansha) NIITSU Yoshiro  Sapporo Medical University, Prof., 医学部, 教授 (10045502)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordspancreatic cancer / isoprenoid / apoptosis / caspase / G protein
Research Abstract

Geranylgeraniol (GGO) and farnesol (FO), synthetic isoprenoids, which are the side chain of vitamine K2, have been noted for their growth inhibitory-effect on hematological cells. However, the precise mechanisms of their functions are still unclear.
We investigated the effect of GGO and FO on the proliferation of sex pancreatic cancer cell lines (Panc-1, MIAPaCa-2, AsPC-I, BxPC-3, 1B2C6, KP4) and fresh cancer cells, which were isolated from ascitis of three pancreatic cancer patients. GGO inhibited the proliferation of all these cancer cells at 20-70μM of IC50 and FO did at 20-60μM of IC50. GGO and FO stimulated DNA fragmentation of treated cells. Therefore, we studied on the signal transudation of apoptosis induced by GGO and FO. P53 is not to be implicated to apoptosis by GGO and FO, because all cell lines have deletion or mutation on p53 gene. We studied whether caspse family (ICE and CPP32) was involved in the effect of GGO or FO by using ICE and CPP32 inhibitors. Effect of GGO and FO were not affected by both inhibitors. Pancreatic cancer cells were inoculated in nude mise to study the effect of GGO and FO diminished the cancer tumors without obvious side effects.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Sato T, et al: "An apoptosis-inducing gene therapy for pancreatic cancer with a combination of 55-kDa receptor gene transfection and mutein TNF administration"Cancer Res. 58. 1677-1683 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hirayama Y, et al: "Concentrations of thrombopoietin in bone marrow in normalsubjexts and in patients with idiopathic thrombocytopenic purpura, apalastic anemia, and essential thrombocythemia correlate with its mRNA"Blood. 92. 46-52 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kobayashi D, et al: "Suppression of Intracellular resistance factors by adriamycin augments heat-induced apoptosis via interleukin-1β-convertingenzyme activation in pancreatic carcinoma cells"Int J Cancer. 76. 552-555 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Niitsu Y, et al: "A proof of glutathione S-transferase-π-related multidrug resistance by transfer of antisense gene to cancer cells and sense gene to bone marrow stem cell"Chem Biol Interact. 24. 325-332 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takayama T, et al: "Aberant crypt foci of the colon as precursors of adenoma and cancer"New Eng Med. 339. 1277-1284 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sakamaki S, et al: "Transforming growth factor-β1(TGF-β1)induces thrombopoietin frombone marrow stromal cells, which stimulates the expression of TGF-β receptor on megakaryocytes"Blood. 94. 1961-1970 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] SATO,T., et al: "An apoptosis-inducing gene therapy for pancreatic cancer with a combination of 55-kDa receptor gene transaction and mutein TNF administration"Cancer Res.. 58. 1677-1683 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] KOBAYASHI,D., et al: "Suppression of Intracellular resistance factors by adriamycin augments heat-induced apoptosis via interleukin-1β-converting enzyme activation in pancreatic carcinoma cells"Int J Cancer. 76. 552-555 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] HIRAYAMA,Y., et al: "Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura, aplastic anemia, and essential thrombocythemia correlate with its mRNA expression of bone marrow stromal cells"Blood.. 92. 46-52 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] NIITSU,Y., et al: "A proof of glutathione S-transferase-π-related multidrug resistance by transfer of antisense gene to cancer cells and sense gene to bone marrow stem cell"Chem Biol. Interact.. 24. 325-332 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] TAKAYAMA,T., et al: "Aberant crypt foci of the colon as precursors of adenoma and cancer."New Eng J Med. 339. 1277-1284 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] SAKAMAKI,Saga Prefectural Cancer Registry., et al: "Transforming growth factor-β1(TGF-β1) induces thrombopoietin from bone marrow stromal cells, which stimulates the expression of TGF-β receptor on megakaryocytes and, in turn, renders them susceptible to suppression by TGF-β itself with high specificity."Blood. 94. 1961-1970 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sato T,et al: "An apoptosis-inducing gene therapy for pancreatic cancer with a combination of 55-kDa receptor gene transfection and mutein TNF administration."Cancer Res.. 58. 1677-1683 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirayama Y,et al: "Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura,aplastic anemia,and essential thrombocythemia correlate with its mRNA"Blood.. 92. 46-52 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kobayashi D,et al: "Suppression of Intracellular resistance factors by adriamycin augments heat-induced apoptosis via interleukin-1β-converting enzyme activation in pancreatic carcinoma cells."Int J Cancer.. 76. 552-555 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Niitsu Y,et al: "A proof of glutathione S-transferase-π-related multidrug resistance by transfer of antisense gene to cancer cells and sense gene to bone marrow stem cell."Chem Biol Interact.. 24. 325-332 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takayama T.,et al: "A berant crypt foci of the colon as precursors of adenoma and cancer."New Eng J Med.. 339. 1277-1284 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sakamaki S1,et al: "Transforming growth factor-β1(TGF-β1)induces thrombopoietin from bone marrow stromal cells,which stimulates the expression of TGF-βreceptor on megakaryocytes"Blood.. 94. 1961-1970 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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