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:	Laura Ochoa-Callejero, Laura Pérez-Martínez, Susana Rubio-Mediavilla, José A Oteo, Alfredo Martínez, José R Blanco
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9483bbcf38d94b9ca0c397d5de1c2366
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spelling	oai:doaj.org-article:9483bbcf38d94b9ca0c397d5de1c23662021-11-18T08:02:06ZMaraviroc, a CCR5 antagonist, prevents development of hepatocellular carcinoma in a mouse model.1932-620310.1371/journal.pone.0053992https://doaj.org/article/9483bbcf38d94b9ca0c397d5de1c23662013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23326556/?tool=EBIhttps://doaj.org/toc/1932-6203Chronic 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.Laura Ochoa-CallejeroLaura Pérez-MartínezSusana Rubio-MediavillaJosé A OteoAlfredo MartínezJosé R BlancoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53992 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Laura Ochoa-Callejero Laura Pérez-Martínez Susana Rubio-Mediavilla José A Oteo Alfredo Martínez José R Blanco Maraviroc, a CCR5 antagonist, prevents development of hepatocellular carcinoma in a mouse model.
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.
format	article
author	Laura Ochoa-Callejero Laura Pérez-Martínez Susana Rubio-Mediavilla José A Oteo Alfredo Martínez José R Blanco
author_facet	Laura Ochoa-Callejero Laura Pérez-Martínez Susana Rubio-Mediavilla José A Oteo Alfredo Martínez José R Blanco
author_sort	Laura Ochoa-Callejero
title	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_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_sort	maraviroc, a ccr5 antagonist, prevents development of hepatocellular carcinoma in a mouse model.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9483bbcf38d94b9ca0c397d5de1c2366
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Maraviroc, a CCR5 antagonist, prevents development of hepatocellular carcinoma in a mouse model.

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