title: Sirolimus for Kaposi's sarcoma in renal-transplant recipients.
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.
authors.affiliation: Division of Nephrology, Department of Emergency and Transplantation, University of Bari, Bari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stallone
authors.forename: Antonio
authors.initials: A
authors.lastname: Schena
authors.forename: Barbara
authors.initials: B
authors.lastname: Infante
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Paolo
authors.forename: Antonella
authors.initials: A
authors.lastname: Loverre
authors.forename: Giulio
authors.initials: G
authors.lastname: Maggio
authors.forename: Elena
authors.initials: E
authors.lastname: Ranieri
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Schena
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grandaliano
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D001706:Biopsy; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000209:etiology; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D011518:Proto-Oncogene Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020123:Sirolimus