RESUMO
We report a rare case of the development of various tumors over a 16-year period after renal transplantation. A 56-year-old woman underwent renal transplantation using a US kidney. Immunosuppressive treatment consisted of a triple regimen of methylprednisolone, azathioprine, and mizoribine. Left breast cancer was diagnosed 9 years after the renal transplantation, then colon cancers and meningeal epidermal meningioma were diagnosed, 10 years and 12 years post-transplant, respectively. During the investigations for the breast and colon cancers, a p53 gene mutation was detected. A deterioration of renal function was found 16 years after the transplant and graft biopsy confirmed chronic rejection. We suggest that the effects of the immunosuppressive drugs combined with the p53 gene abnormality accelerated tumor development in this patient.
Assuntos
Neoplasias da Mama/etiologia , Neoplasias do Colo/etiologia , Genes p53 , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Mutação , Neoplasias Primárias Múltiplas , Azatioprina/administração & dosagem , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/etiologia , Carcinoma Ductal de Mama/genética , Neoplasias do Colo/genética , Neoplasias do Colo/cirurgia , Pólipos do Colo/etiologia , Pólipos do Colo/cirurgia , Quimioterapia Combinada , Feminino , Rejeição de Enxerto , Hemangioma/patologia , Humanos , Neoplasias Hepáticas/secundário , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Ribonucleosídeos/administração & dosagemRESUMO
Metastasis to the liver remains an important problem in the treatment of patients with gastrointestinal cancer. We examined the mechanism and effect on liver metastasis of in vivo interleukin-2 (IL-2) gene transfer to the liver. RCN-9 cells derived from F344 rat colon adenocarcinoma were injected into syngeneic rats via the ileocecal vein to induce liver tumors. A total of 2.5x10(9) pfu of adenovirus vector harboring the human IL-2 gene (AdCMVhIL-2), or 2.5x10(9) pfu of control vector encoding beta-galactosidase was administered before RCN-9 cell challenge. On day 14, mean tumor weight was 4.0+/-2.4 g in the control group, whereas IL-2-transduced livers had no tumors. Survival of AdCMVhIL-2-treated rats was significantly longer than that of control rats (P<.01). Flow cytometry demonstrated that the proportion of natural killer (NK) cells had increased among sinusoidal cells collected from IL-2-transduced livers. These cells were highly cytotoxic to RCN-9 cells in vitro in the presence of a physiological high concentration of recombinant IL-2. Preventative effects of IL-2 transduction of the liver against liver metastasis were lost after depletion of NK cells by treatment with anti-asialo GM1 antibodies. Our results indicate that IL-2 gene transfer to the liver prevents liver metastasis by continuously providing physiological high concentrations of IL-2 in the liver, thereby activating sinusoidal NK cells.
