| Project/Area Number |
14571506
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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, Department of Urology, Graduate School of Medical Sciences, Associate Professor, 大学院・医学研究院, 助教授 (20271108)
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| Co-Investigator(Kenkyū-buntansha) |
NAITO Seiji Kyushu University, Department of Urology, Graduate School of Medical Sciences, Professor, 大学院・医学研究院, 教授 (40164107)
YOKOMIZO Akira Kyushu University, Kyushu University Hospital, Research Associate, 病院・助手 (60346781)
OKUMURA Koji Kyushu University, Department of Urology, Graduate School of Medical Sciences, Research Associate, 大学院・医学研究院, 助手 (40325519)
TSUNODA Toshiyuki Kyushu University, Kyushu University Hospital, Research Associate, 病院・医員
TADA Yasuhiro Kyushu University, Kyushu University Hospital, Research Associate, 病院・医員
猪口 淳一 九州大学, 大学病院, 医員
平田 晃 九州大学, 大学病院, 医員
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | urogenital cancer / cisplatin / drug resistance / microarray / bladder cancer / IP3R1 / MDR1 / MRP / IP_3R1 / 耐性遺伝子 / 抗癌剤 / 薬剤耐性 / 耐性克服 |
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| Research Abstract |
1.To investigate the molecules that regulate the acquisition of cisplatin resistance, we performed cDNA microarrays using two pairs of parental and cisplatin-resistant bladder cancer cell lines. We found a markedly reduced expression of inositol 1,4,5-trisphosphate receptor typel (IP3R1), endoplasmic reticulum membrane protein, in cisplatin-resistant cells. The suppression of IP3R1 expression using small interfering RNA in parental cells prevented apoptosis and resulted in decreased sensitivity to cisplatin. Contrarily, overexpression of IP3R1 in resistant cells induced apoptosis and increased sensitivity to cisplatin. These results suggest that cisplatin-induced downregulation of IP3R1 expression was closely associated with the acquisition of cisplatin resistance in bladder cancer cells.
2.Overexpression of the P-glycoprotein/multidrug resistance 1(MDR1) and multidrug resistance-associated protein(MRP) gene is associated with drug resistance to some chemotherapeutic agents including doxorubicin. We determined the expressions of MDR1,MRP1,MRP2,and MRP3 gene in bladder cancer before and after the treatment using doxorubicin and investigated the correlation between the expressions of these genes and drug responses to doxorubicin. We showed that the each level of MDR1,MRP1,MRP2,and MRP3 gene expression after the treatment using doxorubicin was higher than that of gene expression before the treatment. We also found the significant correlation of MDR1,MRP1,and MRP3 mRNA levels with resistance to doxorubicin. These data suggest that MDR1,MRP1,and MRP3 mRNA levels were correlated with the response to doxorubicin.
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