Multiple liver insults synergize to accelerate experimental hepatocellular carcinoma

Multiple liver insults synergize to accelerate experimental hepatocellular carcinoma.

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: Scientific Reports
Volume: 8
Number: 1
Date: 2018
Divisions: Immune Imaging
Liver Enzymes in Metabolism and Inflammation
Liver Injury and Cancer
Depositing User: General Admin
Identification Number: 10.1038/s41598-018-28486-8
ISSN: 2045-2322
Date Deposited: 03 Jan 2021 22:43

The urgent unmet need for hepatocellular carcinoma (HCC) therapies is addressed here by characterising a novel mouse model of HCC in the context of ongoing liver damage and overnutrition. Male C57Bl/6J mice were treated with diethylnitrosamine (DEN) and thioacetamide (TAA), and some were provided with an atherogenic high fat diet (HFD). Inflammation, steatosis, fibrosis, 87 genes, liver lesions and intratumoural leukocyte subsets were quantified up to 24 weeks of age. Adding HFD to DEN/TAA increased fibrosis, steatosis and inflammation, and the incidence of both HCC and non-HCC dysplastic lesions. All lesions contained α-SMA positive fibroblasts. Macrophage marker F4/80 was not significantly different between treatment groups, but the macrophage-associated genes Arg-1 and Cd47 were differentially expressed. Fibrosis, cancer and cell death associated genes were upregulated in DEN/TAA/HFD livers. Fewer Kupffer cells and plasmacytoid dendritic cells were in tumours compared to control liver. In conclusion, combining a hepatotoxin with an atherogenic diet produced more intrahepatic tumours, dysplastic lesions and fibrosis compared to hepatotoxin alone. This new HCC model provides a relatively rapid means of examining primary HCC and potential therapies in the context of multiple hepatotoxins including those derived from overnutrition.

Henderson, James M.
Polak, Natasa
Chen, Jinbiao
Roediger, Ben
Weninger, Wolfgang
Kench, James G.
McCaughan, Geoffrey W.
Zhang, Hui Emma
Gorrell, Mark D.
Last Modified: 03 Jan 2021 22:43

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