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Identification and Cloning for cisplatin Resistance gene

Research Project

Project/Area Number 06671641
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionNagoya University

Principal Investigator

KIKKAWA Fumitaka  Nagoya University, 医学部, 講師 (40224985)

Co-Investigator(Kenkyū-buntansha) TAMAKOSHI Koji  Nagoya University, 医学部, 助手 (30262900)
岡崎 勝男  名古屋大学, 医学部, 助手 (20252231)
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Keywordscisplatin / glutathione / drug resistance
Research Abstract

We established cisplatin resistant ovarian cancer cell line (NOS2CR), Which showed about 50-fold resistant to cisplatin compared with parental cell line (NOS2). By SDS-PAGE,2 bands were clearly augmented, 1 was weakened, and 1 was disappeared in NOS2CR.However, it was difficult to identify proteins corresponding to these bands due to contamination of other bands. Detoxification by glutathione was one of the mechanisms for cisplatin resistance. Thus, glutathione binding proteins were eluted by glutathion column and were electrophoresed. Several bands were appeared and disappeared in NOS2CR.We analyzed amino-acid sequence, but the most clear band was glutathione-S-transferase, which is a key enzyme of glutathione cycle. Other bands could not be analyzed in an ordinary way, suggesting that proteins were modified. On the other hand, carboplatin and aqupla are also available for cancer treatment. We further established carboplatin resistant cell line (NOS2CBR) and examined the sensitivity against platinum and other anticancer drugs, which were used for cancer treatment. These cell lines showed cross resistance to platinum anticancer drugs, suggesting that the same mechanisms were acquired in both resistant cell lines.

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] H. Oguchi: "Glutathione related enzymes in cis-diamminedichloroplatinvm (II) -sensitive and-resistant human ovarian carcinoma cells." Anticancer Res.14. 193-200 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M. Kojima: "Potentiation of cis-diammine (1,1-cyclobutanedicar boxy-lato) platinom (II) by amphotericin Bin BALBlc nude mice bearing human ovarian carcinoma cells." Jpn. J. Cancer. Res. 85. 1159-1164 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T. Misawa: "Establishment and characterization of aeguired resistnce to platinon anticancer drugs in human ovarian carcinoma cells." Jpn. J. Cancer. 86. 88-94 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N. H. Obata: "Ca^<2+>/calmodulin-dependent protein kinase II inhibitor, on adriamycin-resistance of human ovarian cancer cells." Biochem. Biochm. Biophys. Res. Commun.215. 566-571 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A. O. Sawamura: "Transfection of human cytochrome P-450 reductase cDNA and its effect on the sensitivity to toxins." Oncoloyy. 53. 406-411 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y. Wakahara: "The combination Effects of the Anti-Fas Antibody and Chemotherapevtiv Drugs in Ovarian cancer cells in vitra" Oncoloyy. 54. 48-54 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Oguchi, F.Kikkawa, M.Kojima, O.Maeda, K.Mizuno, N.Suganuma, M.Kawai, and Y.Tomoda: "Glutathione related enzymes in cisdiamminedichloroplatinum (11)-sensitive and -resistant human ovarian carcinoma cells." Anticancer Res.14. 193-200 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Kojima, F.Kikkawa, H.Oguchi, K.Tamakoshi, O.Maeda, N.Suganuma, and Y.Tomoda: "Potentiation of cis-diammine (1,1-cyclobutanedicarboxy-lato) platinum (11) by amphotericin B in BALB/c nude mice bearing human ovarian carcinoma cells." Jpn.J.Cancer Res.85. 1159-1164 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Misawa, F.Kikkawa, O.Maeda, N.H.Obata, K.Higashide, N.Suganuma, and Y.Tomoda: "Establishment and characterization of acquired resistance to platinum anticancer drugs in human ovarian carcinoma cells." Jpn.J.Cancer Res.86. 88-94 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.H.Obata, K.Okazaki, O.Maeda, F.Kikkawa, Y.Tomoda, and H.Hidaka: "Effect of KN-62, Ca^<2+>/calmodulin-dependent protein kinase 11 inhibitor, on adriamycin-resistance of human ovarian cancer cells." Biochem.Biochm.Biophys.Res.Commun.215. 566-571 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.O.Sawamura, T.Aoyama, K.Tamakoshi, K.Mizuno, N.Suganuma, F.Kikkawa, Y.Tomoda: "Transfection of human cytochrome P-450 reductase cDNA and its effect on the sensitivity to toxins." Oncology. 53. 406-411 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Wakahara, A.Nawa, T.Okamoto, A.Hayakawa, F.Kikkawa, N.Suganuma, F.Wakahara, Y.Tomodaa: "The Combination Effect of the Anti-Fas Antibody and Chemotherapeutic Drugs in Ovarian Cancer Cells in vitro." Oncology. 54. 48-54 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 三澤俊哉: "新規白金誘導体ACT-078とCDDP,cBDCAとの交叉耐性に関する検討" 癌と化学療法. 22. 569-571 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.H.Obata: "Ca^<2+>/calmodulin-dependent protein kinase II inhibitor,on adriamycin-resistance of human ovarian cancer cells." Biochem.Biochm.Biophys Res. Commun.215. 566-571 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] A.O.Sawamura: "Transfection of human cytochrome P-450 reductase cDNA and its effect on the sensitivity to toxins." Oncology. 53. 406-411 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Wakahara: "The combination on Effect of the Anti-Fas Antibody and Chemotherapevtio Drugs in Ovarian Cancer cells in vitro." Oncology. 54. 48-54 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Misawa: "Establishment and Charization of Acquired Resistance to Platinum Anticancer Drugs in human Ovarian Carcinoma Cells." J.J.Concer Res.86. 88-94 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] N.Kato: "Suppression of Gelatinace Prodaction with Decreased Invasiveness of Choriocarcinoma Cells by Human Recombinant Interferon Beta" Am.J.Obstet.Gynecol. 172. 601-606 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Tamakoshi: "Clinical Value of a new serum tumor marker,OA125II,in gynecologic disease:comparision with CA125." Gynecol.Obstet.Invest.39. 125-129 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Tamakoshi: "Characterization of extracellular matrix-degrading proteinase and its inhibitor in gynecologic cancer tissues with clintcally different metastaric forms" Cancer.

    • Related Report
      1995 Annual Research Report
  • [Publications] M.Kojima: "Sensitisation of Human Ovarian Carcinoma cells to Cis-diamminedichloroplatinum(II)by Amphotericin B in vitro and in vivo." Eur.J.Cancer. 30. 773-778 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] F.Kikkawa: "Effect of new platinum anticancer drugs in human cisdiamminedichloroplatinum (II) Sensitive and resistant ovarian carcinoma cells:" J.Exp.Clin.Cancer Res. 12. 233-240 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] F.Kikkawa: "Potentiating effect of amphotericin B on five platinum anticancer drugs in human cis-diamminedichloroplatinum (II) sensitive and resistant ovarian carcinoma cells." Anticancer Res.13. 891-896 (1993)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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