2012 Fiscal Year Final Research Report
Targeting tyrosine kinases for autophagy induction along with cytoprotective effect in hematopoietic progenitor cells
Project/Area Number |
22591050
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Tokyo Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Tomohisa 東京医科大学, 医学部, 講師 (40408240)
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Project Period (FY) |
2010 – 2012
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Keywords | オートファジー / チロシンキナーゼ / メシル酸イマチニブ / 小胞体ストレス / 白血病 |
Research Abstract |
Treatment with imatinib mesylate (IM), which is used for targeting therapy for chronic myelogenous leukemia, exhibited an effect of an increased viable cell number of non-BCR-ABL-expressing cell lines by inhibiting spontaneous apoptosis along with autophagy induction. IM attenuated the cytotoxic effects of cytosine arabinoside,tunicamycin, and bortezomib as well as inhibiting cell death with serum-deprived culturein an autophagy-dependent manner. In contrast to autophagy-dependent cytoprotection in response to IM, combined treatment with autophagy inhibitor such as clarithromycin, and proteasome inhibitor, bortezomib potently enhanced endoplasmic reticulum (ER)-stress mediated apoptosis in breast cancer cells and myeloma cells. These lines of evidence suggest that manipulation of autophagy can induce cytoprotective effect via attenuationof ER-stress loading in various kinds of cells including hematopoietic progenitor cells.
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Research Products
(30 results)
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[Journal Article]2013
Author(s)
Klionsky DJ, Abdalla FC, Abeliovich H, Miyazawa K, et al
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Journal Title
Autophagy.
Volume: 8
Pages: 445-544
DOI
Peer Reviewed
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[Journal Article] Selectively induced apoptosis in human neutrophils in thepresence of oxidative phenoxazines, 2-amino-4,4α-dihydryo-4α-7H-phenoxazine-3-one and 2-aminophenoxazine-3-one, preceded by decrease of intracellular pH, depolarization of the mitochond2011
Author(s)
Tabuchi T, Che XF, Hiraishi K, Adachi M, Miyano K, Sumimoto H, Tabuchi T, Miyazawa K, Tomoda A
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Journal Title
JPharmacol Sci
Volume: 117
Pages: 139-48
Peer Reviewed
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[Presentation]2010
Author(s)
森谷昇太,宮澤啓介,川口寛裕,大友理,車暁芳,内藤宗和,伊藤正裕,友田〓夫
Organizer
第33回日本分子生物学会・第83回日本生化学会合同大会
Place of Presentation
神戸
Year and Date
20101207-10
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