Tomoshi Okamoto

Prevention of renal cell carcinoma by active vitamin D3.

A bstractWe 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.

Renal small cell carcinoma (neuroendocrine carcinoma) without features of transitional cell carcinoma

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 atrlotomy 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 carcinold tumors in rodents and enterochromaffin‐like cell hyperplasia In humans. The possible relationship between neuroendocrine carcinoma and H2 receptor antagonist therapy is discussed.

Combined effects of intraperitoneal administration of recombinant interleukin-2 and streptococcal preparation OK-432 in murine tumors.

The combined effects of rIL-2 and OK-432 were investigated against a Meth-A tumor, a syngeneic tumor of inbred BALB/c mice. An analysis of the effector cells was also performed. The treatment resulted in an inhibition in vivo of tumor growth and increased survival of the Meth-A tumor-bearing mice. Splenic cells obtained from Meth-A inoculated mice which received combination therapy were not only NK-sensitive YAC-1 and LAK-sensitive EL-4 cells, but also NK-resistant Meth-A cells, as shown in a 4-h 51Cr-release assay. Syngeneic killer cell activity against Meth-A cells was abolished almost completely with anti-Thy 1.2 treatment and about 70% of the activity was abolished with anti-asialo GM1 treatment in a complement-dependent cytotoxic assay. It was not changed by the removal of macrophages and B cells from the splenic cells. Mice which survived for 60 days after the start of therapy rejected Meth-A inoculation when rechallenged, suggesting the establishment of a specific immunity. Combination therapy appeared to be beneficial against Meth-A cells and T-cells appeared to play a determining role in the treated Meth-A bearing mice. It was suggested that more than two populations of killer cells exist in the spleen treated with the combined therapy and they may have the same characteristics as activated T and NK cells with or without specific killer T-cells.

Efficacy of autologous blood transfusion in patients with renal cell carcinoma undergoing radical nephrectomy.

Predeposit autologous boood transfusion was performed in 40 patients with renal cell carcinoma who underwent radical nephrectomy between January 1989 and June 1994. No homologous blood was transfused in 31 cases (77.5%) of which 27 cases (81.8%) prepared for predeposit autologus bloos ≥600ml. The prognosis of 20 patients with the autologous blood transfusion until December 1991 was compared with that of 25 patients with homologous blood transfusion during the same period. Recurrence-free rate of autologous blood transfused patients was significantly (p<0.05) lower than that of homologous blood transfused cases. There was no significant difference of survival rate among autologous and homologous blood transfused cases. Patients transfused with homologous whole blood had significantly (p<0.05) poorer survival than autologous blood transfused cases, in addition to significantly (p<0.01) higher tumor recurrence.These results suggested that autologous blood tranfusion had a potential to improve the prognosis of renal cell carcinoma.