Development of a novel therapy against myeloma stem cells in a bone marrow hypoxic niche
Project/Area Number |
26461436
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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 | Kyoto Pharmaceutical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
横田 明日美 京都大学, 医学研究科, 研究員 (00571556)
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Research Collaborator |
SHIMAZAKI CHIHIRO 地域医療機能推進機構京都鞍馬口医療センター, 院長
TAKADA TESTUYA 京都薬科大学, 薬学部, 大学院生
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 多発性骨髄腫 / がん幹細胞 / 骨髄微小環境 / 低酸素環境 / TGF-β / C7orf24 |
Outline of Final Research Achievements |
The prognosis of patients with multiple myeloma (MM) has been improved by the emergence of new molecular targeting agents including proteasome inhibitors and immunomodulating agents. Nevertheless, MM remains incurable at present because it is likely that MM stem cells are resistant to these targeting agents. Thus, it is important to further investigate the biology of MM stem cells to cure the MM patients. We have established the hypoxia-adapted MM cells (MM-HA) that can survive under hypoxic conditions (O2 1%) for more than six months and these MM-HA cells have cancer stem cell-like characters. In this project, we clarified further characters of HA-MM cells. HA-MM cells have significantly higher plating efficiencies in a clonogenic replating assay. Moreover, the inhibition of TGF-β/Smad signaling reduced plating efficiencies, suggesting that TGF-β/Smad signal could be a novel target against MM-stem cells.
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] CG13250, a novel bromodomain inhibitor, suppresses proliferation of multiple myeloma cells in an orthotopic mouse model.2017
Author(s)
Natsuki Imaysohi, Makoto Yoshioka, Jay Chauhan, Susumu Nakata, Yuki Toda, Steven Fletcher, Jeffrey Strovel, Kazuyuki Takata, and Eishi Ashihara.
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 484
Issue: 2
Pages: 262-268
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Monocarboxylate transporter 4, associated with the acidification of synovial fluid, is a novel therapeutic target for inflammatory arthritis.2015
Author(s)
Fujii W, Kawahito Y, Nagahara H, Kukida Y, Seno T, Yamamoto A, Kohno M, Oda R, Taniguchi D, Fujiwara H, EjimaA, Kishida T, Osam Mazda, Ashihara E.
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Journal Title
Arthritis Rheum
Volume: 67
Issue: 11
Pages: 2888-2896
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Isopentenyl pyrophosphate secreted from zoledronate-stimulated myeloma cells, activates the chemotaxis of γδT cells.2015
Author(s)
Eishi Ashihara, Tatsuya Munaka, Shinya Kimura, Saori Nakagawa, Yoko Nakagawa, Masaki Kanai, Hideyo Hirai, Hirohisa Abe, Takashi Miida, Susumu Yamato, Shuichi Shoji, Taira Maekawa
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Journal Title
Biochem Biophys Res Commun
Volume: 463
Issue: 4
Pages: 650-655
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pharmacological assessment of methamphetamine-induced behavioral hyperactivity mediated by dopaminergic transmission in planarian Dugesia japonica2014
Author(s)
N. Tashiro, K. Nishimura, K. Daido, T. Oka, M. Todo, A. Toshikawa, J. Tsushima, K. Takata, E. Ashihara, K. Yoshimoto, K. Agata and Y. Kitamura
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Journal Title
Biochem Biophys Res Commun
Volume: 449
Issue: 4
Pages: 412-8
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] A novel BRD4 inhibitor CA2 suppresses MM cell proliferation in an orthotopic myeloma mouse model.2016
Author(s)
Natsuki Imaysohi, Makoto Yoshioka, Susumu Nakata, Jay Chauhan, Yoko Kado, Yuki Toda, Steven Fletcher, Jeffrey Strovel, Kazuyuki Takata, and Eishi Ashihara.
Organizer
American Society of Hematology (ASH) 58th Annual Meeting
Place of Presentation
San Diego, USA
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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[Presentation] Monitoring of lenalidomide levels for prediction of its toxicity and efficacy in myeloma patients.2016
Author(s)
Yoko Kado, Fumiaki Kitazawa, Masayuki Tsujimoto, Shin-ichi Fuchida, Akira Okano, Mayumi Hatsuse, Satoshi Murakami, Kumi Ueda, Takatoshi Kokufu, Ryosuke Irie, Tohko Sakashita, Mizuki Yamamoto, Tetsuya Minegaki, Kohshi Nishiguchi, Eishi Ashihara and Chihiro Shimazaki.
Organizer
第78回日本血液学会学術集会.
Place of Presentation
横浜
Year and Date
2016-10-13
Related Report
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[Presentation] Novel bromodomain inhibitors suppress proliferation of multiple myeloma cells.2015
Author(s)
Ashihara E, Oki R, Imayoshi N, Yoshioka M, Strovel JW, Honjo A, Sakai Y, Takada T, Chauhan J, Raje M, Flecher S, Takata K.
Organizer
The 57th Annual Meeting of American Society of Hematology.
Place of Presentation
Orlando, USA
Year and Date
2015-12-05
Related Report
Int'l Joint Research
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[Presentation] Prediction of the lenalidomide toxicity and its therapeutic efficacy in Japanese multiple myeloma patients by measuring its plasma concentration.2015
Author(s)
Kado Y, Kitazawa F, Tsujimoto M, Fuchida AI, Okano A, Hatsuse M, Murakami S, Ueda K, Kokufu T, Ozawa S, Ito K, Morishita S, Takada T, Minegishi T, Nishiguchi K, Ashihara E, Shimazaki C.
Organizer
The 57th Annual Meeting of American Society of Hematology.
Place of Presentation
Orlando, USA
Year and Date
2015-12-05
Related Report
Int'l Joint Research
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[Presentation] Monocarboxylate transporter (MCT) 4, associated with the decrease of synovial fluid pH, is a novel therapeutic target of rheumatoid arthritis.2014
Author(s)
Fujii W, Ashihara E, Nagahara H, Kukida Y, Kasahara A, Sagawa R, Sagawa T, Seno T, Yamamoto A, Kohno M, Oda R, Tokunaga E, Kubo, Kawahito Y.
Organizer
Annual European Congress of Rheumatology 2014 (The biology of rheumatoid arthritis)
Place of Presentation
Paris (France)
Year and Date
2014-06-11 – 2014-06-14
Related Report
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