| Project/Area Number |
20590935
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
FUJIMORI Yoshihiro Hyogo College of Medicine, 医学部, 准教授 (20229058)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Takashi 兵庫医科大学, 医学部, 教授 (10155781)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 中皮腫 / アポトーシス / 幹細胞 / 癌幹細胞 |
|---|
| Research Abstract |
Malignant mesothelioma is an aggressive tumor of serosal surfaces which is refractory to current treatment options. We analyzed cytological and molecular characteristics of mesothelioma cells to identify the stem cells that initiate its tumorogenesis. We first analyzed the apoptosis of mesothelioma cells induced by arsenic trioxide (As_2O_3), which is used clinically to treat acute promyelocytic leukemia. We found that As_2O_3 inhibited cell viability of a mesothelioma cell line, NCI-H2052. As_2O_3 induced apoptosis of NCI-H2052 cells, which was accompanied by activation of JNK1/2, ERK1/2 and caspase-3. As_2O_3 induced apoptosis of NCI-H2052 cells mainly through JNK1/2 activation, and ERK1/2 was involved in As_2O_3-induced apoptosis when JNK1/2 was inactivated. On the other hands, we found that PP2, a selective SFK inhibitor, induced apoptosis through a caspase-8 pathway in NCI-H28 cells which are resistant to As_2O_3. Fyn-deficiency is prerequisite for caspase-8-dependent apoptosis induced by SFK inhibitors in mesothelioma cells. In our search for cancer stem cells, we found that mesothelioma cells expressed CD318, which play a role in mesotheiloma.
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