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

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• 作者：Aninda Basu^a ; ^c ; ¹ ; Tao Liu^a ; ^c ; ¹ ; ³ ; Pallavi Banerjee^a ; ^c ; Evelyn Flynn^a ; ^c ; David Zurakowski^c ; ^b ; Dipak Datta^a ; ^c ; ⁴ ; Ondrej Viklicky^d ; Martin Gasser^e ; Ana Maria Waaga-Gasser^e ; Jun Yang^a ; ^c ; ² ; ⁵ ; Soumitro Pal^a ; ^c ; ² ; ^{soumitro.pal@childrens.harvard.edu}
• 关键词：Renal cancer ; Angiogenesis ; VEGF ; Chemokine ; Transplantation
• 刊名：Cancer Letters
• 出版年：2012
• 期刊代码：44_03043835
• 类别：med
• 出版时间：28 August, 2012
• 卷：321
• 期：2
• 页码：179-186
• 文件大小：1576 K

摘要

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.