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APPROARCH AT MOLECULAR LEVEL FOR MECHANISMS OF MULTIDRUG-RESISTANCE AND ENHANCEMENT OF ANTICANCER DRUGS WITH HYPERTHERMIA

Research Project

Project/Area Number 11670890
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

KAWASAKI Shoji  Okayama Univ., Medical School, Professor, 医学部, 教授 (20034952)

Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsadriamycin / multidrug resistance / hyperthermia / Ehrlich ascites tumor cells / anticancer drugs / ion channel / MGMT / alkylating agent / WAF1 / wortmannin / 分化度 / 喉頭癌 / アントシアニジン / Caイオン / Calcein
Research Abstract

It is an important problem that tumor cells treated with anticancer drugs expressed multidrug resistance. Therfore, resistant mechanisms of varius mammalian cells were studied, MDR1 gene concerning resistance to adriamycin were appeared in our established cells of Ehrlich ascites tumor. Its resistance related to eflux pump of p-gp which is in cellular membrane, and the penetration of adriamycin into cells was affected by both of ion channels of Na^+/H^+ and Cl^-/HCO_3. Heating showed marked enhancement of cell killing effects of adriamycin. Abtitumor effects of adriamycin were tested on in vivo with or without treatment of mild hyperthermia. However, antitumor effects were shown not so much. On the other hand, efflux of adriamycin was inhibited with cepharanthine, that is, cepharanthine enhanced a killing effect of adriamycin. Antitumor effects of adriamycin were affected with intraa- and extracellure pH. Intracellular accumulation of adriamycin was small amount at acidic condition. It was depended to slow infflux of adriamycin. It is concluded that antitumor effects of adriamycin were not so large enhancement with hyperthermia as it is low pH condition in tumor and hyperthermia induced low pH more than without treatment. On the othe hand, those cells showed the other unknown resistant mechanisims to adriamycin. It is indicated that adriamysin-resistant cells of Ehrlich ascites tumor have at least two expression processes of resistance to adriamycin. There are many mechanisms on resistant to anticancer drugs. Hyperthermia enhanced markedly killing effects of alkylating agents in vitro and in vivo. The sensitivity to alkylating agents related to 06-methylguanine-DNA methyltransferase(MGMT). As MGMT expression was depressed by methylation, it is investigated that relationship between level of methylation and killing effect of alkylating agent in several human squarmous carcinoma cells. Methylation of MGMT is closely related to the sennsitivity for alkylating agents.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Asaumi J, Higuchi Y, Matsuzaki H, Murakami J, Kawasaki S et al.: "Thermochemotherapy of a human salivary adenocarcinoma cell line"Oncol Rep. 9. 365-369 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shibuya K, Kawasaki S et al.: "Effect of wortmannin on the suppression of thermotolerance in tsAF8 cells"Oncol Rep. 9. 81-84 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ando Y, Kuroda M, Kawasaki S et al.: "The effect of calcium on Fas-mediated apoptosis and secondary necrosis of Jurkat cells"Int J Mol Med. 7. 243-247 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawasaki S, et al.: "Thermotherapy for Neoplasia, Inflamation, and Pain"Springer. 424-432 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Asaumi J, Higuchi Y, Matsuzaki H, Murakami J, Kawasaki S, Kuroda M, Shibuya K, Konouchi H, Hisatomi M, Wakasa T, Kishi K, and Hiraki Y: "Thermochemotherapy of a human sailvary adenocarcmoma cell line."Oncol Rep.. 9 (2). 365-369 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shibuya K, Kawasaki S, Kuroda M, Takemoto M, Asaumi J, and Hlraki Y: "Effect of wortmannin on the suppression of thermotolerance in tsAF8 cells."Oncol Rep.. 9 (1). 81-84 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ando Y, Kuroda M, Honda O, Asaumi J, Okumura Y, Takeda Y, Akaki S, Kanazawa S, Kawasaki S, and Hiraki Y: "The effect of calcium on Fas-mediated apoptosis and secondary necrosis of"Int J Mol Med.. 7 (3). 243-7 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawasaki S, Asaumi J, Shibuya K, Kuroda M, and Hiraki Y: "Recent Aspects of Elucidzlting the Cellular Basis of Thermochemotherapy."Thermotherapy for Neoplasia, Inflamation, and Pain, Ed. by Kosaka M, Sugahara T, Schmidt KL, and Simon E, Springer. 424-432 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shibuya K, Kawasaki S, Kuroda M, Asaumi J, and Hiraki Y: "Inhibition of thermotolerance observed on tsAF8 celIs."Int J Hyperthermia. 16 (5). 449-456 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Asaumi J, Matsuzaki H, Kawasaki S, Kuroda M, Takeda Y, Kishi K, and Hiraki Y: "Influence of bovine calf serum on the intracellular accumulation and retention of adriamycin"Anticancer Research. 20 (2A). 769-772 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Asaumi J, Kawasaki S. Kuroda M, Takeda Y, Kishi K, and Hiraki Y: "lntracellular accumulation and retention of calcein in Ehrlich ascites tumor cells and their adriamycin-resistant strain."Anticancer Research. 19 (5B). 4311-4314 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuroda M, Inamura K, Tahara S, Kurabayashi Y, Akagi T, Asaumi J, Togami I, Takemoto M, Honda O, Morioka Y, Kawasaki S, and Hiraki Y: "A new experimental system for irradiating tumors in mice using a linear accelerator under specific pathogen-free conditions"Acta Medica Okayama. 53 (3). 111-118 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto M, Kuroda M, Honda O, Ono E, Asaumi JI, Shibuya K, Kawasaki S, Joja I, Takemoto M, Kanazawa S, and Hiraki Y: "Cepharanthin enhances thermosensitivity without a resultant reduction in the"Int J of Oncology. 15 (1A). 95-99 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Asaumi J, Higuchi Y, Matsuzaki H, Murakami J, Kawasaki S et al.: "Thermochemotherapy of a human salivary adenocarcinoma cell line"Oncol Rep. 9. 365-369 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shibuya K, Kawasaki S et al.: "Effect of wortmannin on the suppression of thermotolerance in tsAF8 cells"Oncol Rep. 9. 81-84 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ando Y, Kuroda M, Kawasaki S et al.: "The effect of calcium on Fas-mediated apoptosis and secondary necrosis of Jurkat cells"Int J Mol Med.. 7. 243-247 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawasaki S, et al.: "Thermotherapy for Neoplasia, Inflamation, and Pain"Springer. 424-432 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shibuya K,Kawasaki S,Kuroda M,Asaumi K,Kanazawa S,Hiraki Y: "Effects of PKC inhibitors on suppression of thermotolerance development of tsAS8 cells"Int J Hyperthermia. 17(No2),. 106-113 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ando Y,Kuroda M,Honda O,Asaumi J,Okumura Y,Takeda Y,Akski S,KanazawaS,Kawasaki S,Hiraki Y: "The effect of calcium on Fas-mediated apoptosis and secondary necrosis of Jurkat cells."Int J Mol Med.. 7(3). 243-247 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawasaki S,Asaumi J,Shibuya K,Kuroda M,Hiraki Y: "Recent aspects of elicidating the cellular basis of thermochemotherapy"Thermotherapy for neoplasia, inflammation, and pain. 424-432 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shibuya K,Kawasaki S,Kuroda M,Asaumi J,Hiraki Y: "Inhibition of thermotolerance observed on tsAF8 cells"Int J Hyperthermia.. 16(5):. 449-456. (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Asaumi J,Matsuzaki H,Kawasaki S,Kuroda M,Takeda Y,Kishi K,Hiraki: "Influence of bovine calf serum on the intracellular accumulation and retention of adriamycin"Anticancer Res. 20(2A):. 769-772 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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