1995 Fiscal Year Final Research Report Summary
Chemosensityivity and drug resistance in urogenital carcinoma
| Project/Area Number |
05671322
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
NAITO Seiji Kyushu University Faculty of Medicine Associate Professor, 医学部, 助教授 (40164107)
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| Co-Investigator(Kenkyū-buntansha) |
HASEGAWA Shuji Kyushu University Faculty of Medicine Senior resident, 医学部, 医員
KOTOH Shuji Kyushu University Faculty of edicine Senior resident, 医学部, 医員
KOGA Hirofumi Kyushu University Faculty of Medicine Assistant, 医学部, 助手 (20271108)
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| Project Period (FY) |
1993 – 1995
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| Keywords | urogenitral cancer / drug resistance / MDR 1 / metallothionein / multridrig resistance / P-glycoprotein / multidrug resistancej-associated protein / DNAトポイソメラーゼ |
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| Research Abstract |
1.Renal cell carcinoma(RCC)was resistant to cisplatin, adriamycin(ADM)and vinblastine as compared with testicular tumor or transitional cell carcinoma of the unrinary tract on chemosensitivity test (succinate dehydrogenase inhibition test), reflecting the clinical features well. The expression of P-glycoprotein, encoded by the multidrug resistance(MDR)1 gene was considered to be mainly responsible for the intrinsic MDR phenotype of RCCs.
2. The expression of metallothionein was considered to be one of the important factors responsible for the cisplatin resistance of bladder carcinoma.
3.Not only P-glycoprotein-mediated classical MDR but also non-P-glycoprotein-mediated atypical MDR,which may be induced by the overecpression of multidrug resistance-associated protein(MRP)and/or decreased expression of DNA topoisomerase II,may develop in bladder carcinoma treated with chemotherapy including ADM.
4.The mechanism of cisplatin resistance in bladder carcinoma is multifactorial and many factors including decreased intracellular concentration of cisplatin, increased detoxification associated with increased intracellular level of glutathione(GSH)or increased ecpression of glutathione S-transferase pi mRNA were considered to be involved. Buthionine sulfoximine increased the cisplatin sesitivity of cisplatin-resistant bladder cancer by decreasing the inatracellular GSH.
5.A prospective randomized trial was conducted to compare the prophylactic effect of intravesical instillation of ADM plus verapamil with that of ADM alone for postoperative recurrrence of superficial bladder cancer, and the significance of verapamil was suggested.
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