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Original Article
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Volume 352:1317-1323 March 31, 2005 Number 13
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Sirolimus for Kaposi's Sarcoma in Renal-Transplant Recipients
Giovanni Stallone, M.D., Antonio Schena, M.D., Barbara Infante, M.D., Salvatore Di Paolo, M.D., Antonella Loverre, Ph.D., Giulio Maggio, M.D., Elena Ranieri, Ph.D., Loreto Gesualdo, M.D., Francesco Paolo Schena, M.D., and Giuseppe Grandaliano, M.D.

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ABSTRACT

Background Recipients of organ transplants are susceptible to Kaposi's sarcoma as a result of treatment with immunosuppressive drugs. Sirolimus (rapamycin), an immunosuppressive drug, may also have antitumor effects.

Methods We stopped cyclosporine therapy in 15 kidney-transplant recipients who had biopsy-proven Kaposi's sarcoma and began sirolimus therapy. All patients underwent an excisional biopsy of the lesion and one biopsy of normal skin at the time of diagnosis. A second biopsy was performed at the site of a previous Kaposi's sarcoma lesion six months after sirolimus therapy was begun. We examined biopsy specimens for vascular endothelial growth factor (VEGF), Flk-1/KDR protein, and phosphorylated Akt and p70S6 kinase, two enzymes in the signaling pathway targeted by sirolimus.

Results Three months after sirolimus therapy was begun, all cutaneous Kaposi's sarcoma lesions had disappeared in all patients. Remission was confirmed histologically in all patients six months after sirolimus therapy was begun. There were no acute episodes of rejection or changes in kidney-graft function. Levels of Flk-1/KDR and phosphorylated Akt and p70S6 kinase were increased in Kaposi's sarcoma cells. The expression of VEGF was increased in Kaposi's sarcoma cells and even more so in normal skin cells around the Kaposi's sarcoma lesions.

Conclusions Sirolimus inhibits the progression of dermal Kaposi's sarcoma in kidney-transplant recipients while providing effective immunosuppression.


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From the Division of Nephrology, Department of Emergency and Transplantation (G.S., A.S., B.I., S.D., F.P.S., G.G.), and the Division of Plastic Surgery (G.M.), University of Bari, Bari; and the Division of Nephrology, Departments of Biomedical Sciences (A.L., L.G.) and Clinical Pathology (E.R.), University of Foggia, Foggia (L.G.) — both in Italy.

Address reprint requests to Dr. Grandaliano at the Division of Nephrology, Department of Emergency and Transplantation, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy, or at g.grandaliano{at}nephro.uniba.it.

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Related Letters:

Kaposi's Sarcoma after Renal Transplantation
Kanitakis J., Edey M. M., Gutiérrez-Dalmau A., Campistol J. M., Stallone G., Schena A., Grandaliano G.
Extract | Full Text | PDF  
N Engl J Med 2005; 353:846-847, Aug 25, 2005. Correspondence

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