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Twenty cases (3.3%) of hypercalcemia of more than 11.0 mg/dl associated with urogenital malignancy were observed in 610 inpatients during the past 5 years and 6 months (Jan. 1978-June 1983). Incidences were 10 (16.1%) out of 62 cases of renal cell carcinoma, 6 (1.9%) out of 321 cases of bladder cancer, 3 (6.7%) out of 45 cases of renal pelvic and ureteral cancer, and one (1.1%) out of 95 cases of prostatic cancer. As treatment, surgery (radical nephrectomy) and anti-cancer chemotherapy were effective in 3 cases (2 renal cell carcinomas and one renal pelvic cancer). Conservative therapy with hydration combined with either indomethacin, steroid or eel calcitonin was effective in 11 cases, and s-Ca level was decreased by 3.7 mg/dl on the average. Eighteen patients were in the terminal stage of malignancy when hypercalcemia was observed, and died 5 days to 9 months (mean; 2 months) after the onset of hypercalcemia.

The human MDR1 gene encoding P-glycoprotein, an energy-dependent drug-efflux pump, was initially isolated from a multidrug-resistant KB carcinoma cell. When a 3 kb genomic sequence isolated from normal human tissue including the major downstream promoter and the first and second exons of the MDR1 gene was compared to the equivalent fragment from KB cells, the MDR1 gene from KB carcinoma cells was found to have a point mutation in the first exon. Although this mutation does not affect the downstream promoter sequence or the coding sequence of the MDR1 gene, it creates a single base mismatch between the 5' KB genomic fragment previously used for RNase protection analysis of MDR1 RNA expression in normal tissues and thereby reduces the sensitivity of this assay. Using the DNA fragment from normal tissues rather than KB cells, we have reanalyzed MDR1 mRNA levels in 12 renal carcinomas and 4 colon adenocarcinomas. By this RNase protection assay, MDR1 RNA levels are as high in these tumors as in the multidrug-resistant cell line, KB-8-5. The ribonuclease protection assay indicated that the major downstream promoter was mainly used in these clinical samples including two samples of RNA from metastatic renal cancer. This assay appears to be a very sensitive and specific assay for detecting MDR1 mRNA levels and mRNA initiation sites in clinical samples.