1999 Fiscal Year Final Research Report Summary
Mechanisms of cisplatin resistance and its reversal in urogential carcinoma
| Project/Area Number |
09671635
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KOGA Hirofumi Kyushu University, Graduate School of Medical Science, Assistant, 大学院・医学系研究科, 助手 (20271108)
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| 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)
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| Project Period (FY) |
1997 – 1999
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| Keywords | urogential carcinoma / renal cell carcinoma / chemotherapy / drug resistance / cisplatin / metallothionein / gluthatione / overcome of drug resistance |
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| 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.
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