| Project/Area Number |
17H01581
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SATO MASAAKI 東京大学, 医学部附属病院, 講師 (00623109)
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| Co-Investigator(Kenkyū-buntansha) |
高橋 美和子 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 計測・線量評価部, 主幹研究員(任非) (00529183)
伊達 洋至 京都大学, 医学研究科, 教授 (60252962)
中島 淳 東京大学, 医学部附属病院, 教授 (90188954)
本山 秀樹 京都大学, 医学研究科, 助教 (20762264)
青山 晃博 京都大学, 医学(系)研究科(研究院), その他 (60379047)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | 肺移植 / 急性拒絶 / 慢性拒絶 / BOS / RAS / 線維化 / FDG-PET / PET/CT / LPS |
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| Outline of Final Research Achievements |
We tried to elucidate the underlying mechanisms of chronic rejection after lung transplantation and to develop a novel non-invasive strategy using nuclear medicine to monitor the process. We found that a rat lung transplant model is useful to study the mechanisms of the subtypes chronic rejection, BOS and RAS. BOS can be caused by trans-airway stimulation such as infection, aspiration, and air pollution, which provokes innate immunity and results in airway-centered inflammation and fibrosis. Conversely, in RAS, multiple anatomical compartments of the lung are broadly affected for example by rejection due to insufficient immunosuppression. We also found that FDG-PET can detect early rejection in this model. Uptake of FDG was significantly correlated with acute rejection grades as well as the degree of tissue fibrosis of allografts. PET-CT could be a novel tool to detect early rejection and infection in lung transplant recipients.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究成果は、肺移植におけるもっとも重要な予後規定因子となっている慢性拒絶の二つのサブタイプ、BOSとRASのメカニズムに迫るものだった。これに基づき、さらなる検査方法や治療方法の開発に期待がかかる。とくに検査としては、非侵襲的な拒絶モニタリングとしての方法として、FDG-PETが有用である可能性が示唆された。今後は臨床研究として、実際の肺移植患者にこの方法を用いた検討が待たれる。
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