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Cancer Lett. 2012 Aug 28;321(2):179-86. doi: 10.1016/j.canlet.2012.02.004. Epub 2012 Feb 14.

Effectiveness of a combination therapy using calcineurin inhibitor and mTOR inhibitor in preventing allograft rejection and post-transplantation renal cancer progression.

Author information

1
Division of Nephrology and Transplantation Research Center, Boston, MA, USA.

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.

PMID:
22343319
PMCID:
PMC3356500
DOI:
10.1016/j.canlet.2012.02.004
[Indexed for MEDLINE]
Free PMC Article

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