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Maraviroc, a CCR5 Antagonist, Prevents Development of Hepatocellular Carcinoma in a Mouse Model

Chronic liver disease may result in a sequential progression through fibrosis, cirrhosis and lead, eventually, to hepatocellular carcinoma (HCC). Hepatic stellate cells (HSC) seem to be responsible for the fibrogenic response through the activation of an autocrine loop involving the chemokine recept...

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Autores principales: Ochoa-Callejero, Laura, Pérez-Martínez, Laura, Rubio-Mediavilla, Susana, Oteo, José A., Martínez, Alfredo, Blanco, José R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541191/
https://www.ncbi.nlm.nih.gov/pubmed/23326556
http://dx.doi.org/10.1371/journal.pone.0053992
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author Ochoa-Callejero, Laura
Pérez-Martínez, Laura
Rubio-Mediavilla, Susana
Oteo, José A.
Martínez, Alfredo
Blanco, José R.
author_facet Ochoa-Callejero, Laura
Pérez-Martínez, Laura
Rubio-Mediavilla, Susana
Oteo, José A.
Martínez, Alfredo
Blanco, José R.
author_sort Ochoa-Callejero, Laura
collection PubMed
description Chronic liver disease may result in a sequential progression through fibrosis, cirrhosis and lead, eventually, to hepatocellular carcinoma (HCC). Hepatic stellate cells (HSC) seem to be responsible for the fibrogenic response through the activation of an autocrine loop involving the chemokine receptor, CCR5. However, the role of CCR5 in HCC remains poorly understood. Since this receptor is also one of the main ports of entry for the human immunodeficiency virus (HIV), several CCR5 inhibitors are being used in the clinic to reduce viral load. We used one of these inhibitors, maraviroc (MVC), in a mouse model of diet-induced HCC to investigate whether this intervention would reduce disease progression. Animals treated with MVC on top of a normal control diet did not present any evidence of toxicity or any morphological change when compared with non-treated mice. Animals treated with MVC presented higher survival, less liver fibrosis, lower levels of liver injury markers and chemokines, less apoptosis, lower proliferation index, and lower tumor burden than their counterparts receiving only the hepatotoxic diet. In addition, MVC inhibits HSC activation markers such as phosphorylation of p38 and ERK, and increases hepatocyte survival. This study suggests that MVC, a well tolerated and clinically characterized drug, may be used as a preventative treatment for HCC. Clinical studies are needed to demonstrate the efficacy of this drug, or other CCR5 inhibitors, in patients with high risk of developing HCC.
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spelling pubmed-35411912013-01-16 Maraviroc, a CCR5 Antagonist, Prevents Development of Hepatocellular Carcinoma in a Mouse Model Ochoa-Callejero, Laura Pérez-Martínez, Laura Rubio-Mediavilla, Susana Oteo, José A. Martínez, Alfredo Blanco, José R. PLoS One Research Article Chronic liver disease may result in a sequential progression through fibrosis, cirrhosis and lead, eventually, to hepatocellular carcinoma (HCC). Hepatic stellate cells (HSC) seem to be responsible for the fibrogenic response through the activation of an autocrine loop involving the chemokine receptor, CCR5. However, the role of CCR5 in HCC remains poorly understood. Since this receptor is also one of the main ports of entry for the human immunodeficiency virus (HIV), several CCR5 inhibitors are being used in the clinic to reduce viral load. We used one of these inhibitors, maraviroc (MVC), in a mouse model of diet-induced HCC to investigate whether this intervention would reduce disease progression. Animals treated with MVC on top of a normal control diet did not present any evidence of toxicity or any morphological change when compared with non-treated mice. Animals treated with MVC presented higher survival, less liver fibrosis, lower levels of liver injury markers and chemokines, less apoptosis, lower proliferation index, and lower tumor burden than their counterparts receiving only the hepatotoxic diet. In addition, MVC inhibits HSC activation markers such as phosphorylation of p38 and ERK, and increases hepatocyte survival. This study suggests that MVC, a well tolerated and clinically characterized drug, may be used as a preventative treatment for HCC. Clinical studies are needed to demonstrate the efficacy of this drug, or other CCR5 inhibitors, in patients with high risk of developing HCC. Public Library of Science 2013-01-09 /pmc/articles/PMC3541191/ /pubmed/23326556 http://dx.doi.org/10.1371/journal.pone.0053992 Text en © 2013 Ochoa-Callejero et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ochoa-Callejero, Laura
Pérez-Martínez, Laura
Rubio-Mediavilla, Susana
Oteo, José A.
Martínez, Alfredo
Blanco, José R.
Maraviroc, a CCR5 Antagonist, Prevents Development of Hepatocellular Carcinoma in a Mouse Model
title Maraviroc, a CCR5 Antagonist, Prevents Development of Hepatocellular Carcinoma in a Mouse Model
title_full Maraviroc, a CCR5 Antagonist, Prevents Development of Hepatocellular Carcinoma in a Mouse Model
title_fullStr Maraviroc, a CCR5 Antagonist, Prevents Development of Hepatocellular Carcinoma in a Mouse Model
title_full_unstemmed Maraviroc, a CCR5 Antagonist, Prevents Development of Hepatocellular Carcinoma in a Mouse Model
title_short Maraviroc, a CCR5 Antagonist, Prevents Development of Hepatocellular Carcinoma in a Mouse Model
title_sort maraviroc, a ccr5 antagonist, prevents development of hepatocellular carcinoma in a mouse model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541191/
https://www.ncbi.nlm.nih.gov/pubmed/23326556
http://dx.doi.org/10.1371/journal.pone.0053992
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