| Project/Area Number |
23591375
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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 |
Hematology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ARAI Ayako 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (70359678)
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| Co-Investigator(Kenkyū-buntansha) |
IMADOME Ken-ichi 国立成育医療研究センター, 母児感染研究部, 室長 (70392488)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | T,NK細胞リンパ腫 / EBウイルス / NF-ｋB / 血液腫瘍学 / マウスモデル / EBV陽性T、NK細胞リンパ増殖症 / Epstein-Barr Virus / AID / FOX-p3 / Simvastatin / integrin / 炎症性サイトカイン産生 / CD137 / NF-κB / 慢性活動性EBウイルス感染症 |
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| Research Abstract |
We performed the research in order to elucidate the molecular mechanisms of EBV-positive T or NK lymphoproliferative diseases (EBV-T/NK-LPDs) development, and to establish the new treatment strategy for the disorders. First, we established the xenograft model of EBV-T/NK-LPDs and published the results in 2011. In addition, we performed in vitro EBV infection assay and found that EBV induced NF-kB-mediated anti-apoptotic signals in T and NK cells. NF-kB was constitutively activated in EBV-positive T- or NK-cells, not only in the cell lines, but in patients cells. Suppression of NF-kB by proteasome inhibitor bortezomib induces anti-tumor effects on EBV-T/NK-LPD not only in vitro but also in vivo. NF-kB may contribute to the development of EBV-T/NK-neoplasms and represents an attractive therapeutic target for the diseases. We reported the results at EHA meeting in 2013, and we have submitted the manuscript to the journal in 2014.
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