Abnormalities in TCR signal transduction in T cell non-Hodgkin's lymphoma as a basis for a new classification system.
| Project/Area Number |
18390111
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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 |
Human pathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
WATANABE Toshiki The University of Tokyo, Graduate School of Frontier Sciences, Professor (30182934)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Takaomi The University of Tokyo, Graduate School of Frontier Sciences, Research Associate (80293447)
HORIE Ryouichi Kitasato University, Facutly of Medicine, Associate Professor (80229228)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,710,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2007: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2006: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | Cancer / Signal transduction / T-lymphocytes / Virus / ウイルス |
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| Research Abstract |
This project was aimed at a systematic characterization of abnormalities in T-cell receptor (TCR) signal transduction pathway in T-cell non-Hodgkin's lymphomas, which will provide novel basis for a new classification and new modalities for molecularly targeted therapies. NF-kB pathway was first focused because of its general significance in T-cell growth and other functions. It was revealed that overexpression of NIK in ATL cells as well as Hodgkin's lymphoma. A new NF-kB inhibitor, DHMEQ, was shown to be effective for overcoming the drug resistance when used in combination with conventional cytotoxic drugs. Comprehensive analysis of copy number abnormalities (allelo-karyotyping) of ATL cells revealed characteristic chromosomal aberrations in ATL cells, which may provide basis of new classification of ATL based the genotype. The results also revealed more than 100 potential target genes, some of which are now under investigation as to their roles in transformation and proliferation of ATL cells. Expression profiling of ATL cells demonstrated overexpression of Ezrin, which connect membrane structure and cyto-skeleton, and is involved in regulation of cell motility and migration. Our results showed that Ezrin overexpression is involved in enhanced migration of ATL cells. An RT-PCR array system was established based on the expression profiling results of ATL cells, which can specifically detect ATL cells in PBMC. Furthermore, it was shown that the "ATL-type score" calculated from the results of array PCR showed a possibility to dissect "asymptomatic carriers" into high and low risk groups for ATL development. The possibility is now being tested using cohort samples.
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Report
(3 results)
Research Products
(126 results)
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[Journal Article] 「研究成果報告書概要(欧文)」より2008
Author(s)
Saitoh Y, Yamamoto N, Dewan MDZ, Sugimoto H, Martinez VJ, Iwasaki Y, Matsubara K, Qi X, Saitoh T, Imoto I, Inazawa J, Utsunomiya A, Watanabe T, Masuda T, Yamamoto N, Yamaoka S.
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Journal Title
Blood 111
Pages: 5118-5129
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[Journal Article] Integration of HIV-1 caused STAT3-associated B cell lymphoma in an AIDS patient2007
Author(s)
Katano H, Sato Y, Hoshino S, Tachikawa N, Oka S, Morishita Y, Ishida T, Watanabe T, Rom WN, Mori S, Sata T, Weiden, MD, Hoshino Y.
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Journal Title
Microbes and Infection 9
Pages: 1581-1589
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] IκBα independent induction of NF-κB and its inhibition by DHMEQ in Hodgkin-Reed-Sternberg cells.2007
Author(s)
Watanabe M, Dewan Md.Z, Taira M, Shoda M, Honda M, Sata T, Higashihara M, Kadin ME, Watanabe T, Yamamoto N, Umezawa K, Horie R
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Journal Title
Laboratory Investigation 87
Pages: 372-382
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[Presentation] Interaction of Histone Methylase SETDB1 and HTLV-1 Tax2007
Author(s)
Suzuki Shoko, Yamamoto K, Ishida T, Tokunaga C, Kurokawa N, Soejima A.
Organizer
The 30th the Annual Meeting of the Molecular Biology Society of Japan, the 80th the Annual meeting of the Japanese Biochemical Society
Place of Presentation
Yokohama
Year and Date
2007-12-11
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Molecular Allelo-Karyotyping of adult T-cell Leukemia Using High SNP Genotyping Microarray2007
Author(s)
Muto S, Yamamoto G, Nannya Y, Sanada M, Utsunomiya A, Yamada Y, Kamihira S, Yamaguchi Y, Watanabe T, Ogawa S
Organizer
The American Society of Hematology 49th Annual Meeting and Exposition
Place of Presentation
Atlanta, USA
Year and Date
2007-12-08
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Functional analysis of Blimp-1 in cell cycle control2007
Author(s)
Wang L, Hangaishi A, Yamamoto G, et. al.
Organizer
The 69th Annual Meeting of the Japanese Society of Hematology, the 49th Annual Meeting of the Japanese Society of clinical Hematology
Place of Presentation
Yokohama, Japan
Year and Date
2007-10-11
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia : Result of a single center study2007
Author(s)
Koh H, Koh KR, Hagihara K, Nakane T, Takeoka Y, Kanashima H, Sakamto E, Nakane M, Ichihara H, Terada Y, Nakamae H, Ohata K, Yamane T, Watanabe T, Hino M.
Organizer
Presentations in 13th International Conference on Human Retrovirology : HTLV and Related Viruses
Place of Presentation
Hakone, Japan
Year and Date
2007-05-24
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Molecular allelo-karyotyping of adult T-cell leukemia using high SNP genotyping microarrays2007
Author(s)
Muto S, Yamamoto G, Nannya Y, Sanada M, Dabaghmanesh N, Ishida T, Utsunomiya A, Yamada Y, Kamihira S, Yamaguchi K, Ogawa S, Watanabe T.
Organizer
Presentations in 13th International lonference on Human Retrovirology : HTLV and Related Viruses
Place of Presentation
Hakone, Japan
Year and Date
2007-05-22
Description
「研究成果報告書概要(欧文)」より
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[Presentation] HTLV-1 uveitis and viral load in PBMC (JSPFAD study)2007
Author(s)
Iwanaga Y, Futagami Y, Miyanaga M, Shimizu K, Miyata K, Watanabe T, Mochizuki M.
Organizer
Presentations in 13th International Conference on Human Retrovirology : HTLV and Related Viruses
Place of Presentation
Hakone, Japan
Year and Date
2007-05-22
Description
「研究成果報告書概要(欧文)」より
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[Book] HTLV-1と疾患2007
Author(s)
渡邉俊樹、上平憲、山口一成(編)
Total Pages
263
Publisher
文光堂
Description
「研究成果報告書概要(和文)」より
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