We studied the serum levels of 1,25-dihydroxyvitamin D [1,25(OH)2D (Vit D)] in patients with renal cell carcinoma (RCC) and the influence of 1,25(OH)2D3 (Vit D3) on gap junctional intercellular communication (GJIC) during carcinogenesis. The serum Vit D levels were measured by a competitive protein-binding assay using the chromatographic method. Using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay, noncytotoxic concentrations of Vit D3 and the tumor promoters N-nitrosodimethylamine (NDMA) and N-ethyl-N-hydroxyethylnitrosamine (EHEN) were tested against cultured human renal proximal tubular cells (HRPTCs). GJIC function was assayed by the scrape-loading dye transfer technique. Cx43 mRNA expression was also examined by the reverse transcriptase-polymerase chain reaction (RT-PCR). Serum Vit D levels in patients with RCC were lower than those in controls (p< 0.001). Patients with T3 to T4 (rapid-growth) tumors had lower levels of Vit D than did patients with T1 to T2 (slow-growth) tumors (p < 0.001). Vit D3 enhanced the GJIC function of HRPTCs (p < 0.05), whereas NDMA and EHEN suppressed it (p < 0.05). When the cells were treated with tumor promoters and Vit D3 simultaneously, the GJIC functions remained at pretreatment levels. We also demonstrated Cx43 mRNA expression in RPTECs treated with EHEN and VitD3 simultaneously. These data suggest that a decrease in the serum Vit D level is one of the risk factors for development and progression of RCC, and Vit D3 may prevent RCC by preserving GJIC during carcinogenesis.
Seventeen cases of renal small cell carcinoma have been reported in the literature. Approximately half of the reported cases show combined features of transitional cell carcinoma. Presented herein is a case of renal small cell carcinoma in a 37-year-old Japanese male who had been treated for 10 years with famotidine for duodenal ulcer. He suffered from sudden-onset chest pain at presentation and myxoma of the right atrium was suspected. He was treated by atriotomy and a tumor was removed from the right atrium and pulmonary artery. Histological examination, however, revealed it to be small cell carcinoma. Accordingly, a radical operation was performed for the removal of a tumor found in the right kidney. Histological examination of the tumor confirmed the presence of renal small cell carcinoma without any features of transitional cell carcinoma. It is reported that long-term administration of an histamine 2 (H2) receptor antagonist may produce carcinoid tumors in rodents and enterochromaffin-like cell hyperplasia in humans. The possible relationship between neuroendocrine carcinoma and H2 receptor antagonist therapy is discussed.
Our experience suggests that aggressive surgery should be considered in selected patients with non-metastatic renal cell carcinoma extending into the vena cava.
Recently it has been known that the active form of vitamin D, 1 alpha, 25-dihydroxyvitamin D (1 alpha, 25-(OH)2D), plays some immunological roles in controlling cell differentiation and carcinogenesis. Moreover, 1 alpha, 25-(OH)2D is said to have some effects in the changes of several numbers of oncogenes. In this study, the serum concentrations of 1 alpha, 25(OH)2D and 25-hydroxyvitamin D (25-(OH)2D) were measured in 30 patients with renal cell carcinoma. The two vitamin D metabolites were separated and purified using high performance liquid chromatography, and each fraction was subjected to competitive protein binding assay using vitamin D deficient rat serum for 25-(OH)2D and chick embryo intestinal receptors for 1 alpha, 25-(OH)2D as the binder. The average concentration of serum 1 alpha, 25-(OH)2D was 28.9 +/- 5.2 pg/ml for controls whereas the average in patients with renal cell carcinoma was 19.7 +/- 5.9 pg/ml. The concentration of 1 alpha, 25-(OH)2D was significantly lower in the patients with renal cell carcinoma compared to in the controls (p less than 0.01). The average concentrations of serum 25-(OH)2D had no significant differences between the two groups. Comparison between the stage I + II and stage III + IV, T1 + T2 and T3 + T4, rapid type and slow type groups showed that the average serum 1 alpha, 25-(OH)2D concentrations was significantly lower in the stage III + IV, T3 + T4, and rapid type groups compared to the other groups (p less than 0.01, p less than 0.05, p less than 0.01). And besides there were no significant correlations between the concentration of serum 1 alpha, 25-(OH)2D and creatinine clearance in patients with renal cell carcinoma. Taken together, it is suggested that the serum concentration of 1 alpha, 25-(OH)2D is in some way correlated with the progression of renal cell carcinoma.
No useful tumor makers for renal cell carcinoma (RCC) have yet been established. In the present study, the serum IAP level was assessed sa a diagnostic and follow-up marker for RCC. The subject were 16 women Based on these results, it was concluded that IAP may be auseful marker for RCC, although it appears valuable for assessing the prognosis than for diagnosis. A more accurate assessment of the prognosis of RCC was possible using a combination of the IAP value and clinical stage.
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