{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T11:06:13Z","timestamp":1763809573011},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2016,8,12]],"date-time":"2016-08-12T00:00:00Z","timestamp":1470960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0160979","type":"journal-article","created":{"date-parts":[[2016,8,12]],"date-time":"2016-08-12T13:38:56Z","timestamp":1471009136000},"page":"e0160979","update-policy":"http:\/\/dx.doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"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"],"prefix":"10.1371","volume":"11","author":[{"given":"Elena","family":"Navarro-Villar\u00e1n","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Tinoco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Granada","family":"Jim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheila","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jize","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Aliseda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda A.","family":"Rodr\u00edguez-Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ra\u00fal","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu\u00eds M.","family":"Mar\u00edn-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel A.","family":"G\u00f3mez-Bravo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco J.","family":"Padillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 M.","family":"\u00c1lamo-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Muntan\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2016,8,12]]},"reference":[{"issue":"7","key":"ref1","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1053\/j.gastro.2007.04.061","article-title":"Hepatocellular carcinoma: epidemiology and molecular carcinogenesis","volume":"132","author":"HB El-Serag","year":"2007","journal-title":"Gastroenterology"},{"issue":"1","key":"ref2","first-page":"11","article-title":"Cancer statistics, 2013","volume":"63","author":"R Siegel","year":"2013","journal-title":"CA: a cancer journal for clinicians"},{"issue":"1","key":"ref3","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10456-011-9243-z","article-title":"Foretinib demonstrates anti-tumor activity and improves overall survival in preclinical models of hepatocellular carcinoma","volume":"15","author":"H Huynh","year":"2012","journal-title":"Angiogenesis"},{"issue":"4","key":"ref4","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1053\/j.gastro.2003.12.049","article-title":"Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance","volume":"126","author":"A Sangiovanni","year":"2004","journal-title":"Gastroenterology"},{"issue":"4","key":"ref5","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1053\/j.gastro.2015.12.041","article-title":"Evidence-Based Diagnosis, Staging, and Treatment of Patients With Hepatocellular Carcinoma","volume":"150","author":"J Bruix","year":"2016","journal-title":"Gastroenterology"},{"issue":"12","key":"ref6","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1093\/ndt\/15.12.1916","article-title":"Clinical and mechanistic differences between FK506 (tacrolimus) and cyclosporin A","volume":"15","author":"WY Almawi","year":"2000","journal-title":"Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association\u2014European Renal Association"},{"issue":"6","key":"ref7","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1124\/mol.55.6.1094","article-title":"Inhibition of cyclic AMP response element-binding protein\/cyclic AMP response element-mediated transcription by the immunosuppressive drugs cyclosporin A and FK506 depends on the promoter context","volume":"55","author":"G Siemann","year":"1999","journal-title":"Molecular pharmacology"},{"issue":"6","key":"ref8","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1053\/jlts.2001.24645","article-title":"mTOR inhibitors: an overview","volume":"7","author":"P Neuhaus","year":"2001","journal-title":"Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society"},{"issue":"6","key":"ref9","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.cell.2004.12.040","article-title":"The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation","volume":"120","author":"I Beuvink","year":"2005","journal-title":"Cell"},{"issue":"13","key":"ref10","doi-asserted-by":"crossref","first-page":"4573","DOI":"10.1158\/0008-5472.CAN-10-4322","article-title":"Combination of PI3K\/mTOR inhibitors: antitumor activity and molecular correlates","volume":"71","author":"M Mazzoletti","year":"2011","journal-title":"Cancer research"},{"issue":"7","key":"ref11","doi-asserted-by":"crossref","first-page":"731","DOI":"10.2174\/0929867003374723","article-title":"FK506, an immunosuppressant targeting calcineurin function","volume":"7","author":"FJ Dumont","year":"2000","journal-title":"Current medicinal chemistry"},{"issue":"5","key":"ref12","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1097\/SLA.0b013e3181896278","article-title":"Liver transplantation for hepatocellular carcinoma under calcineurin inhibitors: reassessment of risk factors for tumor recurrence","volume":"248","author":"M Vivarelli","year":"2008","journal-title":"Ann Surg"},{"issue":"6","key":"ref13","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/j.jhep.2013.07.012","article-title":"Reduced exposure to calcineurin inhibitors early after liver transplantation prevents recurrence of hepatocellular carcinoma","volume":"59","author":"M Rodriguez-Peralvarez","year":"2013","journal-title":"Journal of hepatology"},{"issue":"4","key":"ref14","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1002\/hep.23437","article-title":"Sirolimus-based immunosuppression is associated with increased survival after liver transplantation for hepatocellular carcinoma","volume":"51","author":"C Toso","year":"2010","journal-title":"Hepatology"},{"issue":"6","key":"ref15","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1016\/j.transproceed.2009.05.012","article-title":"Causes and predisposing factors of de novo tumors in our series of liver transplant recipients","volume":"41","author":"Aguilar L Tallon","year":"2009","journal-title":"Transplantation proceedings"},{"issue":"16","key":"ref16","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1136\/vr.116.16.431","article-title":"Guidelines on the recognition of pain, distress and discomfort in experimental animals and an hypothesis for assessment","volume":"116","author":"DB Morton","year":"1985","journal-title":"Vet Rec"},{"issue":"11","key":"ref17","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1038\/sj.bjc.6605642","article-title":"Guidelines for the welfare and use of animals in cancer research","volume":"102","author":"P Workman","year":"2010","journal-title":"Br J Cancer"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0091-679X(08)61707-0","article-title":"Assays of cell viability: discrimination of cells dying by apoptosis","volume":"41","author":"Z Darzynkiewicz","year":"1994","journal-title":"Methods Cell Biol"},{"issue":"7","key":"ref19","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1111\/j.1600-6143.2006.01360.x","article-title":"Cyclosporin versus Tacrolimus as Primary Immunosuppressant After Liver Transplantation: A Meta-Analysis","volume":"6","author":"VC McAlister","year":"2006","journal-title":"American Journal of Transplantation"},{"issue":"10","key":"ref20","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1056\/NEJMoa021744","article-title":"Chronic Renal Failure after Transplantation of a Nonrenal Organ","volume":"349","author":"AO Ojo","year":"2003","journal-title":"New England Journal of Medicine"},{"issue":"4","key":"ref21","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1002\/hep.23437","article-title":"Sirolimus-based immunosuppression is associated with increased survival after liver transplantation for hepatocellular carcinoma","volume":"51","author":"C Toso","year":"2010","journal-title":"Hepatology"},{"issue":"1","key":"ref22","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.jhep.2011.06.012","article-title":"The use of Sirolimus should be restricted in liver transplantation","volume":"56","author":"O Massoud","year":"2012","journal-title":"Journal of hepatology"},{"issue":"8","key":"ref23","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.1016\/j.transproceed.2008.08.028","article-title":"Tacrolimus-induced apoptotic signal transduction pathway","volume":"40","author":"SJ Choi","year":"2008","journal-title":"Transplantation proceedings"},{"issue":"2","key":"ref24","first-page":"269","article-title":"Effects of tacrolimus on proliferation, apoptosis, and fluorouracil sensitivity of liver cancer cell line of SMMC-7721","volume":"4","author":"XW Cao","year":"2005","journal-title":"Hepatobiliary & pancreatic diseases international: HBPD INT"},{"issue":"10","key":"ref25","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.3748\/wjg.v11.i10.1420","article-title":"Sirolimus inhibits growth of human hepatoma cells alone or combined with tacrolimus, while tacrolimus promotes cell growth. World journal of gastroenterology","volume":"11","author":"G Schumacher","year":"2005","journal-title":"WJG"},{"issue":"4","key":"ref26","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/0092-8674(94)90540-1","article-title":"G1 phase progression: cycling on cue","volume":"79","author":"CJ Sherr","year":"1994","journal-title":"Cell"},{"issue":"24","key":"ref27","doi-asserted-by":"crossref","first-page":"2820","DOI":"10.1038\/sj.onc.1203585","article-title":"Calcineurin regulation of the mammalian G0\/G1 checkpoint element, cyclin dependent kinase 4","volume":"19","author":"S Baksh","year":"2000","journal-title":"Oncogene"},{"issue":"2","key":"ref28","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/mc.22265","article-title":"Cyclosporine A and tacrolimus inhibit urothelial tumorigenesis","volume":"55","author":"T Kawahara","year":"2016","journal-title":"Molecular carcinogenesis"},{"issue":"1","key":"ref29","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/S0006-291X(03)00340-1","article-title":"The immunosuppressive agent tacrolimus induces p21WAF\/CIP1WAF1\/CIP1 via TGF-beta secretion","volume":"303","author":"AK Khanna","year":"2003","journal-title":"Biochemical and biophysical research communications"},{"issue":"11","key":"ref30","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1038\/nrm2510","article-title":"Cyclin-dependent kinases and cell-cycle transitions: does one fit all?","volume":"9","author":"H Hochegger","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"40","key":"ref31","doi-asserted-by":"crossref","first-page":"4789","DOI":"10.1038\/onc.2012.498","article-title":"RAD001 (everolimus) induces dose-dependent changes to cell cycle regulation and modifies the cell cycle response to vincristine","volume":"32","author":"PO Saunders","year":"2013","journal-title":"Oncogene"},{"issue":"5","key":"ref32","first-page":"1627","article-title":"Metformin and the mTOR inhibitor everolimus (RAD001) sensitize breast cancer cells to the cytotoxic effect of chemotherapeutic drugs in vitro","volume":"32","author":"H Liu","year":"2012","journal-title":"Anticancer research"},{"issue":"7","key":"ref33","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1111\/j.1582-4934.2008.00364.x","article-title":"RAD001 (everolimus) inhibits tumour growth in xenograft models of human hepatocellular carcinoma","volume":"13","author":"H Huynh","year":"2009","journal-title":"Journal of cellular and molecular medicine"},{"issue":"8B","key":"ref34","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1111\/j.1582-4934.2009.00692.x","article-title":"Sorafenib and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma","volume":"13","author":"H Huynh","year":"2009","journal-title":"Journal of cellular and molecular medicine"},{"issue":"3","key":"ref35","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0092-8674(00)80116-6","article-title":"The immunophilin FKBP12 functions as a common inhibitor of the TGF beta family type I receptors","volume":"86","author":"T Wang","year":"1996","journal-title":"Cell"},{"issue":"3","key":"ref36","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1093\/cvr\/cvn079","article-title":"FK506 can activate transforming growth factor-beta signalling in vascular smooth muscle cells and promote proliferation","volume":"79","author":"A Giordano","year":"2008","journal-title":"Cardiovascular research"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0160979","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T09:56:37Z","timestamp":1568282197000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0160979"}},"subtitle":[],"editor":[{"given":"Matias A","family":"Avila","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,8,12]]},"references-count":36,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2016,8,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0160979","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,12]]}}}