Overcoming resistance and pharmacologicaly-directed tailor-made chemotherapy for leukemia
| Project/Area Number |
23501307
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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 |
Clinical oncology
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| Research Institution | University of Fukui |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 白血病 / 化学療法 / 機能薬理 / 耐性克服 / テーラーメイド / ヌクレオシドアナログ / がん化学療法 / テーラーメイド化 / 機能薬理学 / 抗がん薬 / 耐性 / テーラーメイド医療 |
|---|
| Research Abstract |
To establish pharmacologicaly-directed tailor-made chemotherapy for leukemia, the mechanisms of action and resistance of clofarabine were investigated using two newly developed clofarabine-resistant leukemic cell lines.
The resistant cell lines exhibited reduced clofarabine triphosphate production due to decreased mRNA levels of 3 cell membrane transporters and low protein levels of 2 kinases. The cell lines also showed increased Bcl-2 protein levels, suggestive of antiapoptosis. A cytarabine-resisntant leukemic cell line that had been previously develped showed reduction in only one transporter and one kinase, and 1/10 reduced cytarabine triphosphate. This cell line still possessed the sensitivity to clofarabine, which was atttibutable to the capacity to produce clofarabine triphosphate.
Thus, pharmacologically-directed tailor-made chemotherapy will be established using surrogate markers (intracellular triphosphate production and Bcl-2 exression) to overcome resistance of leukemia.
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Report
(4 results)
Research Products
(112 results)
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[Journal Article] Purine analog-like properties of bendamustine underlie rapid activation of DNA damage response and synergistic effects with pyrimidine analogues in lymphoid malignancies.2014
Author(s)
Hiraoka N, Kikuchi J, Yamauchi T, Koyama D, Wada T, Uesawa M, Akutsu M, Mori S, Nakamura Y, Ueda T, Kano Y, Furukawa Y.
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Journal Title
Plos One
Volume: 13
Issue: 3
Pages: e90675-e90675
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Expression of CD56 is an unfavorable prognostic factor for acute promyelocytic leukemia with higher initial white blood cell counts.2014
Author(s)
Ono T, Takeshita A, Kishimoto Y, Kiyoi H, Okada M, Yamauchi T, Emi N, Horikawa K, Matsuda M, Shinagawa K, Monma F, Ohtake S, Nakaseko C, Takahashi M, Kimura Y, Iwanaga M, Asou N, Naoe T; Japan Adult Leukemia Study Group.
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Journal Title
Cancer Sci
Volume: 105
Issue: 1
Pages: 97-104
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Role of hematopoietic stem cell transplantation as salvage treatment for acute promyelocytic leukemia initially treated with all-trans-retinoic acid and chemotherapy2013
Author(s)
Fujita H, Asou N, Iwanaga M, Hyo R, Nomura S, Kiyoi H, Okada M, Tsuzuki M, Matsuda M, Yamauchi T, 他
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Journal Title
Cancer Sci
Volume: 104
Pages: 1339-1339
Related Report
Peer Reviewed
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[Journal Article] Role of hematopoietic stem cell transplantation for relapsed acute promyelocytic leukemia: a retrospective analysis of JALSG-APL97.2013
Author(s)
Fujita H, Asou N, Iwanaga M, Hyo R, Nomura S, Kiyoi H, Okada M, Inaguma Y, Matsuda M, Yamauchi T, Ohtake S, Izumi T, Nakaseko C, Ishigatsubo Y, Shinagawa K, Takeshita A, Miyazaki Y, Ohnishi K, Miyawaki S, Naoe T; Japan Adult Leukemia Study Group.
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Journal Title
Cancer Sci
Volume: 104
Issue: 10
Pages: 1339-1345
DOI
Related Report
Peer Reviewed
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[Journal Article] A high serum uric acid level is associated with poor prognosis in patients with acute myeloid leukemia.2013
Author(s)
Yamauchi T, Negoro E, Lee S, Takai M, Matsuda Y, Takagi K, Kishi S, Tai K, Hosono N, Tasaki T, Ikegaya S, Inai K, Yoshida A, Urasaki Y, Iwasaki H, Ueda T.
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Journal Title
Anticancer Res
Volume: 33
Pages: 3947-3951
Related Report
Peer Reviewed
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[Journal Article] Detectable Wilms' tumor-1 transcription at treatment completion is associated with poor prognosis of acute myeloid leukemia: a single institution's experience.2013
Author(s)
Yamauchi T, Negoro E, Lee S, Takai M, Matsuda Y, Takagi K, Kishi S, Tai K, Hosono N, Tasaki T, Ikegaya S, Yoshida A, Urasaki Y, Iwasaki H, Ueda T.
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Journal Title
Anticancer Res
Volume: 33
Pages: 3335-3340
Related Report
Peer Reviewed
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[Journal Article] Utility of PCR amplification and DNA microarray hybridization of 16S rDNA for rapid diagnosis of bacteremia associated with hematological diseases.2013
Author(s)
Negoro E, Iwasaki H, Tai K, Ikegaya S, Takagi K, Kishi S, Yamauchi T, Yoshida A, Urasaki Y, Shimadzu M, Ueda T.
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Journal Title
Int J Infect Dis
Volume: 17
Issue: 4
Pages: e271-e276
DOI
Related Report
Peer Reviewed
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[Presentation] Higher serum uric acid levels are associated with poorer overall survival in patients with acute myeloid leukemia.2013
Author(s)
山内高弘, 根来英樹, 李 心, 高井美穂子,松田安史, 高木和貴, 田居克規, 細野奈穂子, 池ヶ谷諭史, 浦崎芳正 吉田 明, 岩崎博道, 上田孝典
Organizer
第75回日本血液学会総会
Place of Presentation
北海道、ロイトン札幌（国内発表）
Related Report
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