| Project/Area Number |
17K11269
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Matsumoto Yoko 東京大学, 医学部附属病院, 登録研究員 (10466758)
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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 |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | DDS / ABC現象 / ドキシル / PLD / 抗PEG抗体 / 卵巣癌 / ドラッグデリバリーシステム / 化学療法 |
|---|
| Outline of Final Research Achievements |
Polyethylene glycol (PEG) is widely used for modification of drug carriers. Although PEG was supposed to have low immunogenicity, accelerated blood clearance of the PEGylated reagent through production of anti-PEG IgM was reported in animals. To assess the significance of anti-PEG IgM in treatments with PLD, clinical data and blood serum samples of 17 ovarian cancer patients were obtained under approval of our institutional ethics committee. Among 17 patients, five had anti-PEG IgM prior to PLD injections. The initial production of anti-PEG IgM was not detected. In IgM positive patients, anti-PEG IgM was consumed by injection of PLD and significantly decreased (p=0.001), but recovered by next treatment. The concentrations of PLD in blood serum 20 hours after injections and quantities of anti-PEG IgM had no correlations. Disease control rates at 16 weeks and non-hematological grade 3/4 adverse events in IgM positive and negative groups were not significantly distinct.
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| Academic Significance and Societal Importance of the Research Achievements |
近年急速に発展しているDDS技術を用いた医薬品のヒトでの体内動態が、その構造、成分によって影響を受け、理論通りとならない可能性についての研究は少ない。今後益々汎用性が増加する技術であり、繊細な構造が重要となることからも今回のABC現象のような解析は必要不可欠であると考える。また
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