Abstract
Despite its known anticancer benefits, monotherapy with sirolimus is not sufficient to achieve optimal immunosuppression to prevent rejection. However, there is no published prospective study to compare the anticancer effect between various immunosuppressive combinations. Therefore, we analyzed the anticancer effects of various immunosuppressive regimens in order to provide experimental evidence for selecting an optimal immunosuppressive regimen after liver transplantation for hepatocellular carcinoma (HCC). The Huh7 cell line was used as a model for HCC in both in vitro and in vivo mouse experiments. The immunosuppressant regimens tested were: tacrolimus, sirolimus, MMF, sirolimus plus tacrolimus, and sirolimus plus MMF. 3-(4 5-Dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide assays showed that the sirolimus plus MMF combination appeared to be synergistic in its cell suppressive effects, achieving statistically significant lowest cell viability. In vitro western blot analysis showed that there were lower levels of expression of phosphorylated mammalian target of rapamycin, p70S6K and p4EBP1, transforming growth factor-β and pSmad3 expression in the cells treated with sirolimus, MMF and sirolimus plus MMF. Finally, in the ...Continue Reading
References
Sep 11, 1998·Nature·Y ZhangR Derynck
Jan 12, 1999·Transplantation·M D VuH Chen
Mar 10, 1999·Transplantation·C J WatsonR Calne
Jul 6, 2000·Immunopharmacology·A C Allison, E M Eugui
Oct 25, 2000·Transplantation·I L DodgeX C Li
Nov 21, 2000·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·G J ChangR Hirose
Oct 22, 2002·Lancet·J G O'GradyUNKNOWN UK and Republic of Ireland Liver Transplant Study Group
Apr 11, 2003·Transplant International : Official Journal of the European Society for Organ Transplantation·Daniela KniepeissKarl-Heinz Tscheliessnigg
Mar 17, 2004·Transplantation·Fuad S ShihabTakeshi F Andoh
Jun 30, 2004·Transplantation·Markus GubaEdward K Geissler
Sep 18, 2004·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Norman M KnetemanDavid L Bigam
Apr 20, 2005·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Marco VivarelliAntonio Daniele Pinna
Aug 27, 2005·Oncogene·Lopa MishraStephen W Byers
May 15, 2007·Transplantation·Christian TosoNorman M Kneteman
Mar 8, 2008·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Michael A ZimmermanIgal Kam
Oct 25, 2008·Annals of Surgery·Marco VivarelliAntonio Daniele Pinna
May 23, 2009·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·S RamirezX Forns
Dec 16, 2010·Nature Reviews. Molecular Cell Biology·Roberto ZoncuDavid M Sabatini
Oct 4, 2011·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Wenhua LiangXiaoshun He
May 23, 2012·Transplant Immunology·Tingting WuYong Zhao
Jul 27, 2012·The New England Journal of Medicine·Sylvie EuvrardUNKNOWN TUMORAPA Study Group