2012 Fiscal Year Final Research Report
Proteomics analysis of a mechanism of sinusoidal endothelial cell injury after receiving oxaliplatin-based chemotherapy in colorectal liver metastases.
| Project/Area Number |
22591509
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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 |
Digestive surgery
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
NAKANO Hiroshi 聖マリアンナ医科大学, 医学部, 医学部 (10241035)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 大腸癌肝転移術前化学療法 / oxaliplatin-based chermotherapy / sinusoidal obstruction syndrome / プロテオミクス / glutathione S-transferase M1 / sphingosine 1 phosphate |
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| Research Abstract |
Oxaliplatin-based chemotherapy in patients with colorecatl liver metastases has been shown to be significantly associated with sinusoidal obstruction syndrome (SOS). In the present study, our proteomics study using 2-Dimensional electrophoresis and LC/MS/MS showed that Peroxiredoxin6、Aldehyde dehydrogenase 2、 α-methylacetyl-CoA racemase、Protein disulfide-isomerase A3、60-S-acid ribosomal protein P0、and Glutathione S-transferase M1 (GST-M1) significantly differed as compared with the control sinusoidal cells. Among them, GST-M1 significantly decreased in human sinusoidal endothelial cells after the administration of oxaliplatin. In addition, an administration of sphingosine 1 phosphate (S1P), which has a protective effect on sinusoidal endothelial injury, significantly attenuate the oxaliplatin-induced sinusoidal injury and showed the maintenance of GST-M1 concentration. These results suggests thatGST-M1 and S1P have a crucial role of oxaliplatin-induced sinusoidal endothelial inj.
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