2017 Fiscal Year Final Research Report
The role of blood coagulation and fibrinolysis system in the oxaliplatin-induced liver sinusoidal obstruction syndrome
| Project/Area Number |
16H07357
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Kindai University |
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Principal Investigator |
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| Research Collaborator |
KAJI Hiroshi 近畿大学, 医学部, 教授 (90346255)
Mackman Nigel University of North Carolina at Chapel Hill, Professor
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| Project Period (FY) |
2016-08-26 – 2018-03-31
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| Keywords | 肝類洞閉塞症候群 / 凝固因子 / 線溶因子 / PAI-1 / 組織因子 / TF / オキサリプラチン |
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| Outline of Final Research Achievements |
The objective of this study was to clarify the role of coagulation and fibrinolysis system, especially plasminogen activator inihibitor-1 (PAI-1) and tissue factor (TF), in the diathesis of oxaliplatin-induced liver sinusoidal obstruction syndrome (SOS).
Repeated administration of oxaliplatin to the wild-type mice significantly increased PAI-1 mRNA levels in the liver, whereas TF mRNA levels were decreased. The increase rate of liver PAI-1 mRNA was significantly and negatively correlated with the rate of body weight loss of the mice.The increases of inflammatory cytokines and fibrosis markers in the liver of PAI-1 deficient mice were milder than WT mice. TF-deficient mice showed higher mortality and severe body weight loss compared with WT mice.
Therefore, in the SOS pathogenesis, PAI-1 may play an important role in accelerating liver injury by forming multiple microthrombi in the liver microcirculation, resulting in enhanced inflammation and fibrosis.
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| Free Research Field |
血液学
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