| Project/Area Number |
03670163
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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 |
Human pathology
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| Research Institution | Tokai University |
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Principal Investigator |
TAMAOKI Norikazu Tokai University Professor School of Medicine, 医学部, 教授 (50055860)
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| Co-Investigator(Kenkyū-buntansha) |
OHNISHI Yasuyuki Central Institute Researcher for Experimental Animals, 研究員 (70201382)
NAKAMURA Masato Tokai University Associate Professor school of Medicine, 医学部, 講師 (00164335)
UEYAMA Yoshito Tokai University Associate Professor School of Medicine, 医学部, 助教授 (30072408)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1992: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1991: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Multidrug Resistance / P-giycoprotein / In vivo Chemotherapy / Tumor Xenograft / RT-PCR / MDR1 gene / P糖蛋白 / ヌ-ドマウス / PCR |
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| Research Abstract |
The overexpression of membrane associated P-qlycoprotein (PGp) encoded by the multidrug resistance gene (MDR1) decreases drug accumulation in multidrug resistant cells in vitro. However, it is unclear whether P-Gp is effective for multidrug resistance (MDR) in neoplasms in vivo. We examined the sensitivity of 34 human tumor xenografts to two chemotherapeutic drugs (Vincristine, VCR; doxorubicin, DOX) in vivo. Nude mice bearing human tumor xenografts were treated with clinical equivalent doses of the drugs. Twenty four of the 34(71%) xenografts showed intrinsic MDR both to VCR and DOX. The other 10 xenografts were sensitive in vivo to VCR and DOX. We evaluated the expression of MDR1 gene in the 34 tumor xenografts by polymerase chain reaction and discuss the mechanism(s) of in vivo intrinsic MDR. Thirteen of the 24 xenografts (54%) showed low and various intensity of MDR1 gene transcripts. No MDR1 gene expression was detected in the 10 sensitive tumor xenografts. The expression of P-Gp does not completely explain in vivo mechanisms of intrinsic MDR of tumor xenografts, whereas P-Gp may contribute to the MDR of the restricted number of tumor xenografts in vivo. Alternative mechanisms also contribute to intrinsic MDR of tumor xenografts in vivo.
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