Analyses of the mechanisms of resistance to monoclonal antibody therapy and exploration of overcoming strategies.
| Project/Area Number |
20591116
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Nagoya University |
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Principal Investigator |
TOMITA Akihiro Nagoya University, 医学部附属病院, 講師 (80378215)
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| Co-Investigator(Renkei-kenkyūsha) |
KIYOI Hitoshi 名古屋大学, 医学部附属病院, 講師 (90314004)
AOKI Ichio 独立行政法人放射線医学研究所, 分子イメージング研究センター, チームリーダー (10319519)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | CD20 / リツキシマブ / 抗体療法 / 分子標的治療 / エピジェネティクス / 薬剤耐性 / 分子イメージング |
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| Research Abstract |
We focused on the phenomenon CD20-negative phenotypic change after performing chemotherapies with rituximab in CD20-positive B-cell lymphoma cells, and the molecular mechanisms of CD20-negative change were analyzed. It appears that aberrant down-regulation of MS4A1 gene expression is closely related to CD20-negative phenotype, and the repression may be introduced by recruitment of Sin3-HDAC1 protein complex to MS4A1 promoter region. CD20-negative phenotype is related to resistance to rituximab therapy. Down-regulated CD20 expression can be partially stimulated by epigenetic drugs resulting in partial restoration of rituximab sensitivity.
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Report
(4 results)
Research Products
(79 results)
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[Journal Article] Clinical significance of nuclear non-phosphorylated beta-catenin in acute myeloid leukaemia and myelodysplastic syndrome.2008
Author(s)
Xu J, Suzuki M, Niwa Y, Hiraga J, Nagasaka T, Ito M, Nakamura S, Tomita A, Abe A, Kiyoi H, Kinoshita T, Naoe T
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Journal Title
Br J Haematol. 140(4)
Pages: 394-401
Related Report
Peer Reviewed
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[Presentation] CD20-Negative Phenotypic Change In B-Cell Lymphoma Cells After Using Rituximab: Possibility of a Particular Clinicopathologic Phenomenon Post- Rituximab Extranodal CD20-Negative Lymphoma2010
Author(s)
冨田章裕, 徳永隆之, 入山智沙子, 島田和之, 平賀潤二, 杉本匠, 清井仁, 中村栄男, 木下朝博士, 直江知樹
Organizer
The American Society of Hematology, 52th Annual Meeting
Place of Presentation
Orlando, FL, USA
Year and Date
2010-12-05
Related Report
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[Presentation] CD20-Negative Phenotypic Change In B-Cell Lymphoma Cells After Using Rituximab : Possibility of a Particular Clinicopathologic Phenomenon Post- Rituximab Extranodal CD20-Negative Lymphoma. (Poster)2010
Author(s)
Akihiro Tomita, Takashi Tokunaga, Chisako Iriyama Kazuyuki Shimada, Junji Hiraga, Takumi Sugimoto, Hitoshi Kiyoi, Shigeo Nakamura, Tomohiro Kinoshita, Tomoki Naoe.
Organizer
The American Society of Hematology, 52th Annual Meeting
Place of Presentation
Orlando, FL, USA
Year and Date
2010-12-05
Related Report
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[Presentation] MS4Al(CD20)Gene Expression Is Down-Regulated by Recruiting the Histone Deacetylase Protein Complex to the Promoter in the CD20-Negative B-Lymphoma Cells After Treatment with Rituximab.2009
Author(s)
Takumi Sugimoto, Akihiro Tomita, Junji Hiraga, Kazuyuki Shimada, Hitoshi Kiyoi, Tomohiro Kinoshita, Tomoki Naoe,
Organizer
The American Society of Hematology, 51th Annual Meeting
Place of Presentation
New Orleans, LA, USA
Year and Date
2009-12-05
Related Report
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