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1999 Fiscal Year Final Research Report Summary

Mechanisms of cisplatin resistance and its reversal in urogential carcinoma

Research Project

Project/Area Number 09671635
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

KOGA Hirofumi  Kyushu University, Graduate School of Medical Science, Assistant, 大学院・医学系研究科, 助手 (20271108)

Co-Investigator(Kenkyū-buntansha) HASEGAWA Shuji  Kyushu University, Faculty of Medicine, Assistant, 医学部, 医員
KOTOH Shuji  Kyushu University, Faculty of Medicine, Assistant, 医学部, 助手 (80294940)
NAITO Seiji  Kyushu University, Graduate School of Medical Science, Professor, 大学院・医学系研究科, 教授 (40164107)
Project Period (FY) 1997 – 1999
Keywordsurogential carcinoma / renal cell carcinoma / chemotherapy / drug resistance / cisplatin / metallothionein / gluthatione / overcome of drug resistance
Research Abstract

1. The mechanisms of acquired resistance to cisplatin was examined using newly established cisplatin resistant bladder cancer cell lines. Multiple mechanisms, including decreased drug accumulation, increased intracellular glutathione and increased expression of glutathione S-transferase π and γ-glutamylcysteine synthetase genes, contributed to the acquisition of cisplatin resistance.
2. The mechanisms of intrinsic resistance to cisplatin in human bladder cancer cell lines was investigated. It was revealed that accumulation of intracellular platinum was correlated with intrinsic resistance.
3. We performed the prospective randomized study to examined whether verapamil, a chemosensitizing agent of P-glycoprotein-mediated multidrug resistance, could enhance the prophylactic effect of doxorubicin on intravesical recurrence after transurethral resection of superficial bladder cancer. We found that intravesical instillation of verapamil and doxorubicin had a significantly greater beneficial effect than that of doxorubicin alone for preventing recurrence.
4. We screened newly synthesized dihydropyridine and imidazothiazole derivatives to determine whether they might be able to overcome multidrug resistance, and found several useful agents.
5. We established a cisplatin resistant germ cell tumor cell line from human testicular germ cell tumor cell line and also established an useful model of lymphnode metastasis by injecting the cells into orthotopic site (testis) of node mice.

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] 長谷川周二: "副腎皮質癌の1例-抗癌剤耐性を含めた検討-"西日泌尿. 59. 132-135 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 内藤誠二: "尿路性器癌における抗癌剤感受性規定因子の分子生物学的解析"第17回浜松カンファランス.泌尿器科学の最近の進歩 Recent Advances in Urology. 17-22 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kotoh S: "Enhanced expression of r-glatamylcysteine synthetase and gluthatione S-transferase gene in cisplatin-resistant bladder cancer cells with maltidrug resistance pheno type."J Urol. 157. 1054-1058 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Naito S: "Prophylactic intravesical instillation chemotherapy against recarrence after a transurethral resiction of supertiion bladdre cancer Ia randamized controlled trial of doxorubicin plas rersus doxorubicin alone."Cancer Chemother Pharmacol. 42. 367-372 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Naito S: "Development of novel reversal agents, imidazothiazole derivatives, targeting MDR1-and MRP-mediated maltidrug resistance"Oncol Res. 10. 123-132 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Naito S: "Mechanisms of drug resistance in chemotherapy for oragenital carcinama"Int. J. Urol. 6. 427-439 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Naito S: "Molecular analysis of mechanisms regulating drag sensitivity and the development of new strotegi in chemo tharapy for genitouriuary carcinomas."World J Surg. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaga H: "Accumulation of intracellular plantinum is correlated with intrinsic cisplation resistance in human bladder cancer cell lines."Int J Oncol. (accepted).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kotoh S: "Enhanced expression of g-glutamylcystein synthetase and glutathione S-transferase genes in cisplastin-resistant bladder cancer cells with multidrug resistance phenotype"The Journal of Urology. 157(3). 1054-1058 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hasegawa S: "Adrenocortical carcinoma : a case report and analysis of anticancer drug resistance"The Nishinihon Journal of Urology. 59(2). 132-135 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Naito S: "Prophylactic intraversical instillation chemotherapy against recurrence after a transurethral resection of superficial bladder cancer : a randomized controlled trial of doxorubicin plus verapamil versus doxorubicin alone"Cancer Chemotherapy Pharmacology. 42(5). 367-372 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Naito S: "Development of novel reversal agents, imidazothiazole derivatives, targeting MDR1-"Oncology Research. 10(3). 123-132 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Naito S: "Mechanisms of drug resistance in chemotherapy for urogential carcinomas"The International Journal of Urology. 6(9). 427-439 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Naito S: "Molecular analysis of mechanisms regulating drug sensitivity and the development of new strategies in chemotherapy for genitourinary carcinomas"The World Journal of Surgery. (accepted).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koga H: "Accumulation of intracellular platinum is correlated with intrinsic cisplastin resistance in human bladder cancer cell lines"International Journal of Urology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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