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- W3203929897 abstract "Maraviroc (MVC), a CCR5 antagonist, reduces liver fibrosis, injury and tumour burden in mice fed a hepatocarcinogenic diet, suggesting it has potential as a cancer therapeutic. We investigated the effect of MVC on liver progenitor cells (LPCs) and macrophages as both have a role in hepatocarcinogenesis. Mice were fed the hepatocarcinogenic choline-deficient, ethionine-supplemented diet (CDE) ± MVC, and immunohistochemistry, RNA and protein expression were used to determine LPC and macrophage abundance, migration and related molecular mechanisms. MVC reduced LPC numbers in CDE mice by 54%, with a smaller reduction seen in macrophages. Transcript and protein abundance of LPC-associated markers correlated with this reduction. The CDE diet activated phosphorylation of AKT and STAT3 and was inhibited by MVC. LPCs did not express Ccr5 in our model; in contrast, macrophages expressed high levels of this receptor, suggesting the effect of MVC is mediated by targeting macrophages. MVC reduced CD45+ cells and macrophage migration in liver and blocked the CDE-induced transition of liver macrophages from an M1- to M2-tumour-associated macrophage (TAM) phenotype. These findings suggest MVC has potential as a re-purposed therapeutic agent for treating chronic liver diseases where M2-TAM and LPC numbers are increased, and the incidence of HCC is enhanced." @default.
- W3203929897 created "2021-10-11" @default.
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- W3203929897 date "2021-09-30" @default.
- W3203929897 modified "2023-09-27" @default.
- W3203929897 title "Maraviroc Prevents HCC Development by Suppressing Macrophages and the Liver Progenitor Cell Response in a Murine Chronic Liver Disease Model" @default.
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- W3203929897 doi "https://doi.org/10.3390/cancers13194935" @default.
- W3203929897 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8508380" @default.