| Project/Area Number |
14370787
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Keio University |
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Principal Investigator |
TANIGAWARA Yusuke Keio University, Department of Medicine, Professor, 医学部, 教授 (30179832)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Kunihiko Keio University, Department of Medicine, Associate Professor, 医学部, 助教授 (80327717)
SHIMAZU Motohide Keio University, Department of Medicine, Assistant Professor, 医学部, 講師 (70124948)
TANABE Minoru Keio University, Department of Medicine, Assistant Professor, 医学部, 講師 (50197513)
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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 |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2004: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥8,300,000 (Direct Cost: ¥8,300,000)
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| Keywords | immunosuppressive agents / cardiac transplantation / liver transplantation / small bowel transplantation / biomarker / DNA microarray / protein chip / 心臓移植モデル / 小腸移植モデル / 拒絶反応バイオマーカー / シクロスポリン / 網羅的解析 / 生体肝移植 / シクロスポリンA / CYP3A / 6β-水酸化コルチゾール / コルチゾール / 拒絶反応 / CYP3A5 / TaqMan PCR法 |
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| Research Abstract |
We found gene markers for predicting acute rejection and therapeutic effect of immunosuppressive agents in rat cardiac and liver transplantation. We also identified protein markers to predict acute rejection in rat small bowel transplantation.
Rat cardiac transplantation model :
Profiling of DNA expression followed by quantitative real-time PCR analysis revealed that the expression of six candidate genes (IRF1, PSMB9, TAP1, CTSS, NOS2, PIM1) in peripheral blood were significantly induced by acute rejection. The induction was reversed by cyclosporine administration. A relationship between the cyclosporine trough concentration and the gene expression could be well described by a sigmoid Emax model. The results suggested that the expression of these candidate genes were good predictors for rejection episode and therapeutic effect of immunosuppressive agents.
Rat liver transplantation model :
We found that the expression of four genes in peripheral blood were significantly increased by acute rejection in the DNA microarray analysis followed by quantitative PCR. Immunosuppressive agents reduced the expression of these candidate genes. The results suggested that the expression of these genes in peripheral blood would be a good predictor for acute rejection and therapeutic effect of immunosuppressive drugs.
Rat small bowel transplantation model :
We identified three possible biomarkers (10.1,13.0,14.8 kDa) in peripheral blood that reflected acute rejection after small bowel transplantation. Among them, lysozyme (14.8 kDa) may be useful for detecting acute rejection and for monitoring the pharmacological effects of immunosuppressants, whereas migration inhibitory factor-related protein (MRP)-8 (10.1 kDa) and MRP-14 (13.0 kDa) may be useful for detecting the early stage of allograft rejection.
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