Analysis of pathophysiology of EBV-positive T- or NK-lymphoproliferative diseases and development of new treatment strategy
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 |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Tokyo Medical and Dental University |
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 |
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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Report
(4 results)
Research Products
(74 results)
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[Journal Article] High-resolution genomic copy number profiling of primary intraocular lymphoma by single nucleotide polymorphism microarrays.2014
Author(s)
Wang L, Sato-Otsubo A, Sugita S, Takase H, Mochizuki M,Usui Y, Goto H, Koyama T , Akiyama H, Miura O, Ogawa S, Arai A.
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Journal Title
Cancer Science
Volume: 未定
Issue: 5
Pages: 592-599
DOI
Related Report
Peer Reviewed
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[Journal Article] Recurrence of chronic active Epstein-Barr virus infection from donor cells after achieving complete response through allogeneic bone marrow transplantation2012
Author(s)
Arai A, Imadome K, Wang L, Wu N, Kurosu T, Wake A, Yamamoto H, Ota Y, Harigai M, Fujiwara S, Miura O
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Journal Title
Int Medicine
Volume: 51(7)
Pages: 777-82
NAID
Related Report
Peer Reviewed
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[Journal Article] ZNF385B is characteristically expressed in germinal center B cells and involved in B-cell apoptosis2012
Author(s)
Iijima K, Yamada H, Miharu M, Imadome K, Miyagawa Y, Akimoto S, Kobayashi K, Okita H, Nakazawa A, Fujiwara S, Fujimoto J, Kiyokawa N.
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Journal Title
Eur J Immunol.
Volume: 42(12)
Issue: 12
Pages: 3405-3415
DOI
Related Report
Peer Reviewed
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[Journal Article] CD4^+T cells have a critical role in the proliferation of EBV-infected T and NK cells2011
Author(s)
Imadome K, Yajima M, Arai A, Nakagawa-Nakazawa A, Kawano F, Ichikawa S, Shimizu N, Yamamoto N, Morio T, Ohga S, Nakamura H, Ito M, Miura O, Komano J, Fujiwara S
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Journal Title
PLOS Pathogen
Volume: (in press)
Issue: 10
Pages: 1-14
DOI
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Peer Reviewed
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[Presentation] Four cases of Helicobacter cinaedi bacteremia complicating hematological malignancies2012
Author(s)
Shinya Ishida、, Masahide Yamamoto, 、Daisuke Watanabe, Yusuke Nakamura, Toshikage Nagao, Tehtsuya Kurosu, Tehtsuya Fikuda, Naomi Murakami, Shuji Tohda, Ayako Arai, Osamu Miura
Organizer
第74回日本血液学会総会
Place of Presentation
京都
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[Presentation] EBV induces AID expression in T or NK cells leading to mutagenesis and development of lymphoma
Author(s)
Masato Horino, Ken-Ichi Imadome, Kohsuke Imai, Ludan Wang, Go Matsuda, Kasumi Hamazaki, Honami Komatsu, Morito Kurata, Tetsuya Kurosu, Shigeyoshi Fujiwara, Osamu Miura, Ayako Arai,
Organizer
第75回 日本血液学会総会
Place of Presentation
札幌市、ロイトン札幌
Related Report
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[Presentation] Epstein&Barr virus Induces Activation-Induced Cytidine Deaminase Expression in T or NK Cells Leading to Mutagenesis and Development of Lymphoma
Author(s)
Ayako Arai, Masato Horino, Ken-Ichi Imadome, Kohsuke Imai, Ludan Wang, Go Matsuda, Kasumi Hamazaki, Honami Komatsu, Morito Kurata, Tetsuya Kurosu, Shigeyoshi Fujiwara, Osamu Miura
Organizer
55th Annual meeting of American Journal of Hematology
Place of Presentation
New Orleans, U.S.A.
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