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dc.contributor.author
Piccioni, Flavia Valeria
dc.contributor.author
Malvicini, Mariana
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García, Mariana Gabriela
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Rodriguez, Andrés
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Atorrasagasti, María Catalina
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Kippes, Néstor Fabián
dc.contributor.author
Piedra Buena, Ignacio T.
dc.contributor.author
Rizzo, Manglio Miguel
dc.contributor.author
Bayo Fina, Juan Miguel
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Aquino, Jorge Benjamin
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Viola, Manuela
dc.contributor.author
Passi, Alberto
dc.contributor.author
Alaniz, Laura Daniela
dc.contributor.author
Mazzolini Rizzo, Guillermo Daniel
dc.date.available
2019-07-15T20:45:59Z
dc.date.issued
2012-03
dc.identifier.citation
Piccioni, Flavia Valeria; Malvicini, Mariana; García, Mariana Gabriela; Rodriguez, Andrés; Atorrasagasti, María Catalina; et al.; Antitumor effects of hyaluronic acid inhibitor 4-methylumbelliferone in an orthotopic hepatocellular carcinoma model in mice; Oxford Univ Press Inc; Glycobiology; 22; 3; 3-2012; 400-410
dc.identifier.issn
0959-6658
dc.identifier.uri
http://hdl.handle.net/11336/79589
dc.description.abstract
Liver cirrhosis is characterized by an excessive accumulation of extracellular matrix components, including hyaluronan (HA). In addition, cirrhosis is considered a pre-neoplastic disease for hepatocellular carcinoma (HCC). Altered HA biosynthesis is associated with cancer progression but its role in HCC is unknown. 4-Methylumbelliferone (4-MU), an orally available agent, is an HA synthesis inhibitor with anticancer properties. In this work, we used an orthotopic Hepa129 HCC model established in fibrotic livers induced by thioacetamide. We evaluated 4-MU effects on HCC cells and hepatic stellate cells (HSCs) in vitro by proliferation, apoptosis and cytotoxicity assays; tumor growth and fibrogenesis were also analyzed in vivo. Our results showed that treatment of HCC cells with 4-MU significantly reduced tumor cell proliferation and induced apoptosis, while primary cultured hepatocytes remained unaffected. 4-MU therapy reduced hepatic and systemic levels of HA. Tumors systemically treated with 4-MU showed the extensive areas of necrosis, inflammatory infiltrate and 2-3-fold reduced number of tumor satellites. No signs of toxicity were observed after 4-MU therapy. Animals treated with 4-MU developed a reduced fibrosis degree compared with controls (F1-2 vs F2-3, respectively). Importantly, 4-MU induced the apoptosis of HSCs in vitro and decreased the amount of activated HSCs in vivo. In conclusion, our results suggest a role for 4-MU as an anticancer agent for HCC associated with advanced fibrosis.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Oxford Univ Press Inc
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
4-Methylumbelliferone
dc.subject
Liver Cancer
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Liver Fibrosis
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Otras Medicina Básica
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Antitumor effects of hyaluronic acid inhibitor 4-methylumbelliferone in an orthotopic hepatocellular carcinoma model in mice
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-07-10T19:05:49Z
dc.journal.volume
22
dc.journal.number
3
dc.journal.pagination
400-410
dc.journal.pais
Reino Unido
dc.journal.ciudad
Oxford
dc.description.fil
Fil: Piccioni, Flavia Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina
dc.description.fil
Fil: Malvicini, Mariana. Universidad Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.description.fil
Fil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina
dc.description.fil
Fil: Rodriguez, Andrés. Universidad Austral; Argentina
dc.description.fil
Fil: Atorrasagasti, María Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad Austral; Argentina
dc.description.fil
Fil: Kippes, Néstor Fabián. Universidad Austral; Argentina
dc.description.fil
Fil: Piedra Buena, Ignacio T.. Universidad Austral; Argentina
dc.description.fil
Fil: Rizzo, Manglio Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina
dc.description.fil
Fil: Bayo Fina, Juan Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina. Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica; Argentina
dc.description.fil
Fil: Aquino, Jorge Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina
dc.description.fil
Fil: Viola, Manuela. Universitá degli Studi dell’Insubria; Italia
dc.description.fil
Fil: Passi, Alberto. Universitá degli Studi dell’Insubria; Italia
dc.description.fil
Fil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina
dc.description.fil
Fil: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina
dc.journal.title
Glycobiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1093/glycob/cwr158
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/glycob/article/22/3/400/2000144
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