2014 Fiscal Year Final Research Report
Biliary carcinogenesis based upon degradated phospholipids
| Project/Area Number |
24500977
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Eating habits, studies on eating habits
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | Bile / Bile duct / phospholipids / lysolecithin / apoposis / SASP / hepatolithiasis |
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| Outline of Final Research Achievements |
In biliary diseases, biliary lysophosphatidylcholine (LPC) level is increased, LPC exhibited cytotoxicity with significant induction of apoptosis. Here, the influence of LPC on cholangiocytes was focussed in the light of cellular senescence and its contribution to carcinogenesis. Treatment of human cholangiosytes with LPC demonstrated cytotoxicity with significant ROS generation. In keeping with this change, LPC provoked oxidative DNA injury while the gene expressions of DNA repair enzyme remained unchanged. Microarray analysis identified differentially regulated genes in response to LPC, which included the components of senescence-associated secretory phenotype (SASP). Based upon these data, cholangiocyte senescence and SASP caused by LPC via induction of oxidative stress are an important pathogenic mechanism in the development of biliary tract cancer.
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| Free Research Field |
Hepatobiliary diseases
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