| Project/Area Number |
18591554
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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 |
Thoracic surgery
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| Research Institution | Kochi University |
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Principal Investigator |
WARIISHI Seiichiro Kochi University, Kochi Medical School, School Hospital, Lecturer (00403882)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Hironori Kochi University, Kochi Medical School, School Hospital, Lecturer (20335946)
KUME Motohiko Kochi University, Kochi Medical School, School Hospital, Assistant Professor (80346725)
ANAYAMA Takashi Kochi University, Kochi Medical School, Assistant Professor (30403893)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | mesothelioma / molecular targeting / MCI-186 / edaravone / VEGF / anti-cancer effect / NF-kB / 増殖抑制 / シグナル伝達 / アポトーシス / 癌 |
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| Research Abstract |
Malignant mesothelioma is an aggressive but rare malignancy that affects the pleura and peritoneum. Most of cases are believed to derive from exposure to primary asbestos fiber. Recently, biological properties of mesothelioma cells in its growth have been reported : especially, EGFR (Epithelial growth factor receptor) expression on mesotheloma cells and VEGF production and its autocrine proliferation by VEGF. We have shown that MCI-186, a radical scavenger for acute cerebral infarction, inhibits proliferation of cancer cell in several types provably by inhibitions of phosphorylation in EGFR and transcriptional factor, NFkB. In this study, we evaluated possible molecular targeting properties of MCI-186 against mesothelioma cells. MCI-186 suppresses the in vitro proliferation of mesothelioma cell line, MSTO-211H under stimulation by serum or IL-1 beta. Synergistic inhibition was shown by combination with Mitomycin C treatment. VEGF production of the mesothelioma cells was induced by the stimuli with IL-1 beta and this VEGF production was inhibited by MCI-186. The phosphorylation of IkB under IL-1 beta stimulation was significantly inhibited by MCI-186, suggesting that the inhibitory effect of MCI-186 on IL-1 beta induced VEGF production might be brought by the inhibition of NFkB pathway. In addition, in vivo effect of MCI-186 was proven in the therapeutic experiments using tumor bearing nude mice. These results support the possibility of the molecular targeting therapies by MCI-186, especially against protein(s)related to tumor angiogenesis.
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