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Title: Differential Antitumoral Properties and Renal-Associated Tissue Damage Induced by Tacrolimus and Mammalian Target of Rapamycin Inhibitors in Hepatocarcinoma: In Vitro and In Vivo Studies.
Authors: Navarro-Villarán, Elena
Tinoco, José
Jiménez, Granada
Pereira, Sheila
Wang, Jize
Aliseda, Sara
Rodríguez-Hernández, María A
González, Raúl
Marín-Gómez, Luís M
Gómez-Bravo, Miguel A
Padillo, Francisco J
Álamo-Martínez, José M
Muntané, Jordi
metadata.dc.contributor.authoraffiliation: [Navarro-Villarán,E; Pereira,S; Aliseda,S; Rodríguez-Hernández,MA; González,R] Institute of Biomedicine of Seville (IBIS), "Virgen del Rocío"-"Virgen Macarena" University Hospital/CSIC/University of Seville, Seville, Spain. [Tinoco,J; Jiménez,G; Wang,J; Marín-Gómez,LM; Gómez-Bravo,MA; Padillo,FJ; Álamo-Martínez,JM; Muntané,J] Department of General Surgery, "Virgen del Rocío"-"Virgen Macarena" University Hospital/CSIC/University of Seville/IBIS/CSIC/University of Seville, Seville, Spain. [Gómez-Bravo,MA; Padillo,FJ; Álamo-Martínez,JM; Muntané,J] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
Keywords: Calcineurina;Carcinoma hepatocelular;División celular;Línea celular;Everolimus;Rechazo del injerto;Hiperbilirrubinemia;Hipertensión portal;Inmunosupresión;Recurrencia neoplásica loca
metadata.dc.subject.mesh: Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Phosphoric Monoester Hydrolases::Phosphoprotein Phosphatases::Calcineurin
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, Hepatocellular
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Cycle::Cell Division
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line
Medical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immune System Processes::Transplantation Immunology::Host vs Graft Reaction::Graft Rejection
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Hyperbilirubinemia
Medical Subject Headings::Diseases::Digestive System Diseases::Liver Diseases::Hypertension, Portal
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunosuppression
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver Neoplasms
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Digestive System Surgical Procedures::Liver Transplantation
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, Nude
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Lactones::Macrolides::Sirolimus
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Lactones::Macrolides::Tacrolimus
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Lactones::Macrolides::Sirolimus::Everolimus
Medical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Neoplasm Recurrence, Local
Issue Date: 12-Aug-2016
Publisher: Public Library of Science
Citation: Navarro-Villarán E, Tinoco J, Jiménez G, Pereira S, Wang J, Aliseda S, et al. Differential Antitumoral Properties and Renal-Associated Tissue Damage Induced by Tacrolimus and Mammalian Target of Rapamycin Inhibitors in Hepatocarcinoma: In Vitro and In Vivo Studies. PLoS ONE. 2016; 11(8):e0160979
Abstract: Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with potential portal hypertension and/or bilirubinemia, but without vascular-associated diseases. The patients are receiving immunosuppressive therapy to reduce graft rejection, but differential side effects have been related to calcineurin and mTOR inhibitor administration regarding tumor recurrence and nephrotoxicity. The in vitro studies showed that Tacrolimus exerted a more potent pro-apoptotic effect than Everolimus (Huh 7>Hep 3B>HepG2), being sirolimus only active in Hep3B cell line. Tacrolimus and Everolimus exerted potent antiproliferative properties in Huh 7 and Hep3B in which cells Sirolimus was inactive. Interestingly, Tacrolimus- and Everolimus-dependent G0/G1 cell accumulation occurred as a consequence of drastic reduction in S, as well as in S and G2+M phases, respectively. The in vivo studies support data on the more effective antitumoral properties of Everolimus, eventual risk of pro-angiogenic tumoral properties and nephrotoxicity of Tacrolimus, and pro-proliferative properties of Sirolimus in tumors developed in nude mice.
Description: Journal Article;
metadata.dc.identifier.doi: 10.1371/journal.pone.0160979
ISSN: 1932-6203 (Online)
Appears in Collections:01- Artículos - Hospital Virgen del Rocío
01- Artículos - Hospital Virgen Macarena
01- Artículos - IBIS. Instituto de Biomedicina de Sevilla

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