mycophenolic-acid and Neoplasm-Metastasis

Topics: Adult; Female; Humans; Immunosuppression Therapy; Liver Neoplasms; Liver Transplantation; Lung Neoplasms; Mycophenolic Acid; Neoplasm Metastasis; Sirolimus; Tomography Scanners, X-Ray Computed; White People

Polyoma virus nephropathy is recognized as an emerging clinical problem in renal transplantation; however, polyoma in native kidneys is unusual. We report a patient who developed polyoma nephropathy in his native kidneys 15 months after successful lung transplantation. His immunosuppression consisted of tacrolimus, mycophenolate mofetil, and large doses of steroids because of three rejection episodes. When the condition was recognized, cidofovir was an effective treatment (3 doses of 2-3mg/kg); however, his renal function deteriorated nonetheless. Tubulitis and interstitial cell infiltration in his native kidneys were evidence that the changes were in response to viral injury. Polyoma nephropathy of native kidneys is unusual. An earlier course of cisplatin treatment because of metastatic seminoma prior to lung transplantation may have been contributory to pre-existing renal injury. After cidofovir was begun, the polyoma viral load in serum and urine decreased substantially; however, after high-dose steroid treatment of two rejection episodes, each time a significant increase in viral load was seen. We stained biopsies of native kidneys from 30 recipients of other organs. The biopsies were done for various reasons but not because polymoma virus was suspected. We found no additional cases.

Topics: Adult; Antiviral Agents; Biopsy; BK Virus; Cidofovir; Cisplatin; Cytosine; Graft Rejection; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Lung Transplantation; Male; Mycophenolic Acid; Neoplasm Metastasis; Organophosphonates; Polyomavirus; Polyomavirus Infections; Seminoma; Steroids; Tacrolimus

Cultured tumor cell lines, tumor xenografts grown in athymic nude mice, and a murine experimental metastasis model were used to assess the in vitro and in vivo anti-tumor activity of the potent IMP dehydrogenase (IMPDH) inhibitor, mycophenolic acid (MPA), and its morpholinoethyl ester pro-drug, mycophenolate mofetil (MM). The growth of all the cell lines tested was inhibited by MPA in vitro, with EC50 values ranging from less than 0.1 microM to 3.9 microM. Mice were monitored for s.c. tumor outgrowth in the case of human tumor xenograft models or survival time for the murine experimental metastasis model. Treatment with MM p.o. was started 24 hr after tumor challenge or after tumors became palpable. Treatment of athymic nude mice bearing A3.01 (T-lymphoblast), Molt-4 (T-cell leukemia), CaPan-2 (pancreatic adenocarcinoma), CaLu-3 (non-small-cell lung adenocarcinoma), LS174T and T84 (colon adenocarcinoma), and Daudi (B-cell lymphoma) human tumor xenografts with MM significantly inhibited s.c. tumor growth. Treatment of BALB/c mice with MM after i.v. injection of murine RAW117-H10 lymphoma cells in an experimental metastasis assay resulted in increased survival time for treated animals. No significant inhibitory effect on s.c. tumor outgrowth was seen with MM treatment of SK-Hep-1, a human hepatic endothelioma, or Hep-3B, a liver adenocarcinoma, at any of the doses tested.

Topics: Animals; Antineoplastic Agents; Cell Division; Disease Models, Animal; Drug Screening Assays, Antitumor; Female; Humans; IMP Dehydrogenase; Leukemia; Lymphoma; Mice; Mice, Inbred BALB C; Mice, Nude; Mycophenolic Acid; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Transplantation, Heterologous