| Project/Area Number |
16H05442
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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 |
Neurosurgery
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| Research Institution | Kyorin University |
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Principal Investigator |
Nagane Motoo 杏林大学, 医学部, 教授 (60327468)
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| Co-Investigator(Kenkyū-buntansha) |
市村 幸一 国立研究開発法人国立がん研究センター, 研究所, 分野長 (40231146)
富山 新太 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 病院 脳神経外科, 講師 (40385810)
中村 大志 横浜市立大学, 医学部, 助教 (60771615)
立石 健祐 横浜市立大学, 医学部, 助教 (00512055)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
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| Keywords | 中枢神経系悪性リンパ腫 / PIM1 / BAD / NF-kB / 二次性中枢神経系悪性リンパ腫 / 遺伝子変異解析 / 分子標的治療 / 部位特異的変異導入法 / 脳腫瘍 / 遺伝子解析 / 転移機序 / シグナル伝達 / 分子標的知慮 |
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| Outline of Final Research Achievements |
We performed in vitro analysis of the PIM1 mutation, especially the K115N mutation which was associated with poor prognosis in primary central nervous system lymphoma (PCNSL). The K115N mutation was revealed to drive Bcl-2 associated death promotor (BAD) phosphorylation through augmented cytosolic localization of Pim-1, and its role in the inhibition of cell death was suggested. It was also revealed that activation of the NF-kB pathway is a promising therapeutic target in PCNSL, using originally established cell lines. Genetic analysis with paired samples from CNS and systemic lesions in individual patients revealed potential common genetic alterations favorable for CNS involvement.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果から、PCNSLにほぼ必発するにもかかわらず、その意義が明らかではなかったPIM1 変異の少なくとも一部は、PCNSLの発生に関与する可能性が示唆された。またNF-kB標的治療のproof-of-conceptが示され、今後Pim-1 やNF-kBを治療標的とした新規の治療開発が期待され、難治疾患であるPCNSLの予後改善に貢献しうる成果である。
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