| Project/Area Number |
18580317
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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 |
Clinical veterinary science
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| Research Institution | Yamaguchi University |
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Principal Investigator |
MAKAICHI Munekazu Yamaguchi University, Paculty of Agriculture, Professor (60243630)
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| Co-Investigator(Kenkyū-buntansha) |
OKUDA Masaru Yamaguchi Univesity, Faculty of Agriculture, Associate Professor (10325243)
TAURA Yasuho Yamaguchi University, Faculty of Agriculture, Professor (80163153)
UNE Satoshi Yamaguchi University, Faculty of Agricultute, Associate Professor (60294659)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | cancer / mast cell tumor / drug resistance / P-glycoprotein / MDR1 / clinical science / veterinary medicine / 薬剤耐 |
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| Research Abstract |
Multidrug resistance was investigated in canine spontaneous mast cell tumors (MCT). We first investigated the effects of imatinib mesylate on canine mast cell tumors, which has growth inhibition effects on the tumors with c-kit mutation. As the results, imatinib mesylate showed marked anti-tumor effect in two clinical cases of canine MCT, and these two cases had been in tumor-free condition for several months after treatment. However, relapse of the tumor tissue was observed despite of the continuance of chemotherapy. These regrowth tissues were not sensitive to imatinib masylate. These cases strongly suggested the drug resistance might potentially manifest in canine MCT. Furthermore, MDR1 expression was studied in 27 spontaneous cases of MCT. As the results, 18 cases showed MDR1 gene expression, also suggesting the latent presence of drug resistance.
In vitro examination was additionally performed using three cell lines derived from canine MCT. The expression of MDR1 gene was examined in the cell lines, and after that, the functional activity of the P-gp expressing on the cells as a drug-efflux pump was investigated by flowcytometric analysis of rhodamine-123. Of these three cell lines, MDR1 gene was shown to be expressed, and growth inhibition effect of imatinib mesylate on these MDR1-positive cells was reversed with the presence of P-gp inhibitor of verapamil. P-glycoprotein was also observed in two cell lines in western blotting, and shown to be functional based on the flowcytometric analysis.
These findings suggest that the expression of MDR1 and P-gp probably contributed to cellular drug resistance in canine MCTs.
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