We report a case of nephrotic syndrome with thymic neuroendocrine tumor. A 50-year-old woman was admitted with generalized edema. 24-hour urine collection revealed proteinuria of 20 gram daily and creatinine clearance of 28 mL/min. During examination, a thymic mass was found, which is unresectable due to metastasis to the lung. Biopsy of the thymus and the kidney revealed large cell neuroendocrine carcinoma of thymus origin and minimal change disease, respectively. Despite high dose steroid therapy, massive proteinuria continued for about 30 days. However, when the patient was given a chemotherapy (cyclophosphamide, adriamycin, vincristine), proteinuria began to decrease dramatically. The carcinoma showed the partial response after six cycles of chemotherapy. This is the first report on remission of malignancy-related nephrotic syndrome after chemotherapy, especially for thymic neuroendocrine tumor.
Biopsy ; Carcinoma, Neuroendocrine ; Creatinine ; Doxorubicin ; Edema ; Female ; Humans ; Kidney ; Lung ; Middle Aged ; Neoplasm Metastasis ; Nephrosis, Lipoid ; Nephrotic Syndrome ; Neuroendocrine Tumors ; Proteinuria ; Thymus Gland ; Thymus Neoplasms ; Urine Specimen Collection

By using differential display, we identified one of the genes encoding the multi-subunit complex protein V-ATPase, c subunit gene (ATP6L), and showed alterations of the gene expression by oxidative stresses. Expression of the ATP6L gene in Neuro-2A cells was increased by the treatment with H2O2 and incubation in hypoxic chamber, implying that the expression of the ATP6L gene is regulated by oxidative stresses. To examine mechanisms involved in the regulation of the gene expression by oxidative stresses, the transcriptional activity of the rat ATP6L promoter was studied. Transcription initiation site was determined by primer extension analysis and DNA sequencing, and promoter of the rat ATP6L and its deletion clones were constructed in reporter assay vector. Significant changes of the promoter activities in Neuro-2A cells were observed in two regions within the proximal 1 kbp promoter, and one containing a suppressor was in -195 to -220, which contains GC box that is activated by binding of Sp1 protein. The suppression of promoter activity was lost in mutants of the GC box. We confirmed by electrophoretic mobility shift and supershift assays that Sp1 protein specifically binds to the GC box. The promoter activity was not changed by the H2O2 treatment and incubation in hypoxic chamber, however, H2O2 increased the stability of ATP6L mRNA. These data suggest that the expression of the ATP6L gene by oxidative stresses is regulated at posttranscriptional level, whereas the GC box is important in basal activities of the promoter.
Animals ; Clone Cells ; Gene Expression* ; Hydrogen Peroxide ; Oxidative Stress* ; Rats ; RNA, Messenger ; Sequence Analysis, DNA ; Transcription Initiation Site ; Vacuolar Proton-Translocating ATPases*