The impact of JNK activity on the cancer stem cells
Project/Area Number |
26830065
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Tumor biology
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Research Institution | Yamagata University |
Principal Investigator |
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Project Period (FY) |
2014-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | がん幹細胞 / 腫瘍発生 / JNK / ROS / 薬剤抵抗性 / Kras / xenograft / 幹細胞性 |
Outline of Final Research Achievements |
In this study, we demonstrated that JNK activity is necessary for maintenance of cancer stem cell (CSC) capacity on pancreatic CSCs as well as glioblastoma and lung CSCs in our previous reports. SP600125, a JNK inhibitor, treatment inhibits self-renewal and tumor-initiating capacity. Moreover, systemic administration of SP600125 reduces tumor-initiating CSCs in vivo. The SP600125 has been used in the overwhelming majority of studies, but the clinical safety profile is unknown. Therefore, we used a novel JNK inhibitor, AS602801 that has been developed for the treatment of inflammatory endometriosis. The AS602801 treatment also inhibits CSC capacity and tumor initiating capacity in vitro and in vivo. Generally chemoresistance associated with CSCs, we show that JNK is critically involved in the resistance of pancreatic CSCs to 5-FU and gemcitabine. The JNK inhibition promotes 5-FU or GEM-induced increase of intracellular reactive oxygen species.
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Report
(3 results)
Research Products
(15 results)
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[Journal Article] Time-staggered inhibition of JNK effectively sensitizes chemoresistant ovarian cancer cells to cisplatin and paclitaxel2016
Author(s)
Seino M, Okada M, Sakaki H, Takeda H, Watarai H, Suzuki S, Seino S, Kuramoto K, Ohta T, Nagase S, Kurachi H, Kitanaka C
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Journal Title
Oncology Reports
Volume: 35
Issue: 1
Pages: 593-601
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] GSKJ4, A Selective Jumonji H3K27 Demethylase Inhibitor, Effectively Targets Ovarian Cancer Stem Cells.2015
Author(s)
Sakaki H, Okada M, Kuramoto K, Takeda H, Watarai H, Suzuki S, Seino S, Seino M, Ohta T, Nagase S, Kurachi H, Kitanaka C.
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Journal Title
Anticancer Res.
Volume: 12
Pages: 6607-14
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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