Development of new therapeutic approach for multiple myeloma targeted against biological properties of bone marrow microenvironment
| Project/Area Number |
24591409
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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 | Saitama Medical University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
OKUDA Akihiko 埼玉医科大学, 医学部, 教授 (60201993)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 多発性骨髄腫 / 分子標的療法 / 骨髄微小環境 / 細胞死 / NF-κB / 幹細胞 / JAK/STAT / 前駆細胞 / Wnt/β-カテニン |
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| Outline of Final Research Achievements |
In the present study, new NF-κB inhibitor TM-233 was synthesized from natural compound 1'-acetoxychavicol acetate (ACA) having NF-κB inhibitory activity. TM-233 has more potent NF-κB inhibitory activity than that of ACA and induced cell death of myeloma cells via production of reactive oxygen species (ROS). TM-233 phosphorylated JAK2 and STAT3 and obstructed the shift to a nucleus of NF-κB p65. In addition, TM-233 induced cell death of bortezomib-resistant myeloma cells through inhibition of β-ring β1, β2, and β5 in the proteasome. TM-233 may become the new therapeutic agent for the multiple myeloma having potent NF-κB inhibitory activity in the bone marrow microenvironment.
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] TM-233, a novel analog of 1'-acetoxychavicol acetate, induces cell death in myeloma cells by inhibiting both JAK/STAT and proteasome activities.2015
Author(s)
Sagawa M, Tabayashi T, Kimura Y, Tomikawa T, Nemoto-Anan T, Watanabe R, Tokuhira M, Ri M, Hashimoto Y, Iida S, Kizaki M.
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Journal Title
Cancer Sci.
Volume: 106
Issue: 4
Pages: 438-446
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Phytohemagglutinin-induced IL2 mRNA in whole blood can predict bortezomib-induced peripheral neuropathy for multiple myeloma patients．2013
Author(s)
Watanabe T, Mitsuhashi M, Sagawa M, Ri M, Suzuki K, Abe M, Ohmachi K, Nakagawa Y, Nakamura S, Chosa M, Iida S, and Kizaki M.
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Journal Title
Blood Cancer Journal
Volume: 3
Issue: 10
Pages: e150-e150
DOI
Related Report
Peer Reviewed
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[Presentation] Interim analysis of clinical trial of MPB followed by bortezomib maintenance therapy for elderly patients with newly diagnosed multiple myeloma.2013
Author(s)
Tokuhira M, Takezako N, Nakazato T, Sasaki M, Handa T, Ikuta K, Ikezoe T, Matsumoto M, Aotsuka N, Taguchi J, Shimomura S, Chin K, Ichikawa K, Usuki K, Ohyashiki K, Nara M, Kishi K, Kuroda Y, Nakamura Y, Kizaki M, et al.
Organizer
International Myeloma Workshop
Place of Presentation
Kyoto (ICC), Japan
Related Report
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[Presentation] TM-233 exerts anti-myeloma activity bortezomib-resistance in human multiple myeloma cells by targeting NF-κB and JAK/STAT dual-signaling pathways.2013
Author(s)
Sagawa M, Tomikawa T, Anan T, Tabayashi T, Watanabe R, Tokuhira M, Ri M, Hashimoto Y, Iida S, and Kizaki M
Organizer
55th Amecican Society of Hematology Annual Meeting
Place of Presentation
New Orleans (Ernest N. Morial Convention Center), LA, USA
Related Report
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[Book] 中外医学社2012
Author(s)
金倉譲、他
Total Pages
594
Publisher
EBM血液疾患の治療2013-2014
Related Report
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