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1996 Fiscal Year Final Research Report Summary

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)
Project Period (FY) 1994 – 1996
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.

  • Research Products

    (12 results)

All Other

All Publications (12 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-03-09  

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