Screening of therapeutic agent for Ph-positive ALL using patient-derived xenograft cells
Project/Area Number |
15K09472
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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 | Nagoya University |
Principal Investigator |
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | PDX / PDXスクリーニング / ドラッグリポジショニング / 白血病 / 悪性リンパ腫 / スクリーニング / Ph陽性ALL / 微小環境 / 酸化ストレス / 薬剤スクリーニング / reactive oxygen species / 急性リンパ性白血病 |
Outline of Final Research Achievements |
We developed a high-throughput drug screening system using PDX cells and performed drug screening using the PDX cells of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). We performed a screening of 3440 compounds using leukemia cells from the PDX mice (PDX-cell screening). The profiles of drugs selected by PDX-cell screening were markedly different from those by screening using the Ph+ ALL cell line. We found that verteporfin, an FDA-approved drug, exhibited strong PDX cell-specific cytotoxicity. Although verteporfin is a photosensitizer activated by photoirradiation, its cytotoxic effects were mediated by the light-independent production of reactive oxygen species; therefore, its anti-leukemic effects were also exerted in vivo without photoirradiation. Furthermore, it exhibited synergistic effects with dasatinib, an ABL kinase inhibitor. These results indicated the potential of verteporfin as a new anti-leukemic reagent.
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] YM155 induces apoptosis through proteasome-dependent degradation of MCL-1 in primary effusion lymphoma.2017
Author(s)
Kojima Y, Hayakawa F, Morishita T, Sugimoto K, Minamikawa Y, Iwase M, Yamamoto H, Hirano D, Imoto N, Shimada K, Okada S, Kiyoi H
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Journal Title
Pharmacol Res.
Volume: in press
Pages: 242-251
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Emetine elicits apoptosis of intractable B-cell lymphoma cells with MYC rearrangement through inhibition of glycolytic metabolism.2017
Author(s)
Aoki T, Shimada K, Sakamoto A, Sugimoto K, Morishita T, Kojima Y, Shimada S, Kato S, Iriyama C, Kuno S, Harada Y, Tomita A, Hayakawa F, Kiyoi H.
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Journal Title
Oncotarget.
Volume: 8
Issue: 8
Pages: 13085-13098
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Malignant lymphoma with cardiac involvement2017
Author(s)
Terakura S, Onji M, Iriyama C, Goto T, Ushijima Y, Shimada K, Ishikawa Y, Nishida T, Hayakawa F, Murata M, Kiyoi H
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Journal Title
Rinsho Ketsueki
Volume: 58
Issue: 3
Pages: 239-242
DOI
NAID
ISSN
0485-1439, 1882-0824
Related Report
Peer Reviewed
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[Journal Article] Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults2016
Author(s)
Takahiko Yasuda, Shinobu Tsuzuki, Masahito Kawazu, Fumihiko Hayakawa, Shinya Kojima, Toshihide Ueno, Naoto Imoto, Shinji Kohsaka, Akiko Kunita, Koichiro Doi, Toru Sakura, Toshiaki Yujiri, Eisei Kondo, Katsumichi Fujimaki, Yasunori Ueda, Yasutaka Aoyama, Shigeki Ohtake, Junko Takita, Eirin Sai, Masafumi Taniwaki, et al.
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Journal Title
Nature genetics
Volume: in press
Issue: 5
Pages: 409-417
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Development and analysis of patient derived xenograft mouse models in intravascular large B-cell lymphoma. Leukemia.2016
Author(s)
Shimada K, Shimada S, Sugimoto K, Nakatochi M, Suguro M, Hirakawa A, Hocking TD, Takeuchi I, Tokunaga T, Takagi Y, Sakamoto A, Aoki T, Naoe T, Nakamura S, Hayakawa F, Seto M, Tomita A, Kiyoi H
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Journal Title
Leukemia
Volume: in press
Issue: 7
Pages: 1568-1579
DOI
Related Report
Peer Reviewed
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[Presentation] High expression of MEF2D-fusion protein by escaping from the regulation by microRNA2017
Author(s)
Daiki Hirano, Fumihiko Hayakawa, Takahiko Yasuda, Naoyuki Tange, Hideyuki Yamamoto, Yuki Kojima, Takanobu Morishita, Naoto Imoto, Shinobu Tsuzuki, Hiroyuki Mano, Tomoki Naoe, Hitoshi Kiyoi
Organizer
59th annual meeting of american society of hematology
Related Report
Int'l Joint Research
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[Presentation] High expression of MEF2D-fusion protein by escaping from the regulation by microRNA2017
Author(s)
平野大希, 早川文彦, 安田貴彦, 山本秀行, 小島勇貴, 森下喬允, 井本直人, 都築忍, 間野博行, 直江知樹, 清井仁
Organizer
第79回日本血液学会学術集会
Related Report
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