title: Effectiveness of a combination therapy using calcineurin inhibitor and mTOR inhibitor in preventing allograft rejection and post-transplantation renal cancer progression.
abstract: Calcineurin inhibitors (CNIs) may promote post-transplantation cancer through altered expression of cytokines and chemokines in tumor cells. We found that there is a potential cross-talk among CNI-induced signaling molecules and mTOR. Here, we utilized a murine model of post-transplantation cancer to examine the effect of a combination therapy (CNI + mTOR-inhibitor rapamycin) on allograft survival and renal cancer progression. The therapy prolonged allograft survival; and significantly attenuated CNI-induced post-transplantation cancer progression, with down-regulation of mTOR and S6-kinase phosphorylation. Also, rapamycin inhibited CNI-induced over-expression of the angiogenic cytokine VEGF, and the chemokine receptor CXCR3 and its ligands in post-transplantation tumor tissues.
authors.affiliation: Division of Nephrology and Transplantation Research Center, Boston, MA, USA.
authors.forename: Aninda
authors.initials: A
authors.lastname: Basu
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Pallavi
authors.initials: P
authors.lastname: Banerjee
authors.forename: Evelyn
authors.initials: E
authors.lastname: Flynn
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.forename: Dipak
authors.initials: D
authors.lastname: Datta
authors.forename: Ondrej
authors.initials: O
authors.lastname: Viklicky
authors.forename: Martin
authors.initials: M
authors.lastname: Gasser
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Waaga-Gasser
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Soumitro
authors.initials: S
authors.lastname: Pal
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000494:pharmacology; D065095:Calcineurin Inhibitors; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D016030:Kidney Transplantation; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D054367:Receptors, CXCR3 / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014180:Transplantation; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D065095:Calcineurin Inhibitors; D018925:Chemokines; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D054367:Receptors, CXCR3; D042461:Vascular Endothelial Growth Factor A; D058570:TOR Serine-Threonine Kinases; D019703:Calcineurin; D020123:Sirolimus