Elevated expression of P-glycoprotein in kidney and urinary bladder cancers.

A monoclonal antibody, MRK16, recognizing specifically an epitope of P-glycoprotein (P-GP), a highly active efflux transporter of chemotherapeutic agents, was used to determine the degree of expression of P-GP in the normal human kidney and urinary bladder, and in kidney and urinary bladder cancers. P-glycoprotein was localized in the microvilli of the epithelial cells of the proximal renal tubules by immunoelectron microscopy, and detected immunohistochemically in 6 of 20 untreated kidney cancers and 11 of 31 untreated urinary bladder cancers. Some of the cancerous tissues were further examined with regard to P-GP expression by immunoprecipitation. In urinary bladder cancers, the degree of P-GP expression seemed to be somewhat correlated with tumor grading. These results indicate that our method to detect the degree of expression of P-GP by MRK16 may be applicable for the diagnosis of clinical multidrug resistant urinary cancers.

Expression of c-erbB-2 gene product in urinary bladder cancer.

Expression of the c-erbB-2 gene product and the epidermal growth factor receptor (EGF-R) was investigated in 54 cases of human bladder cancer immunohistologically and by Western blot analysis. For detection of the c-erbB-2 product, two specific antibodies, a rabbit polyclonal antibody directed to the intracellular domain and a murine monoclonal antibody recognizing an epitope in the extracellular domain, were used. Seventeen cases of bladder cancer were stained by the anti-c-erbB-2 polyclonal antibody, while 20 cases were stained by the monoclonal antibody, with good correlation on both stainings (p less than 0.01). There were four c-erbB-2 positive cases in 26 G1 tumors, four in 15 G2 tumors, and nine in 13 G3 tumors. There were also eight erbB-2 positive cases in nine muscle-invasive tumors, nine of 45 superficial tumors, four of five with lymph node metastasis, and seven of 14 without metastasis, as revealed by staining with the polyclonal antibody. Thus, the c-erbB-2 gene product was more frequently expressed in high grade tumors (p less than 0.01), in high stage tumors (p less than 0.01), and nodal metastatic tumors (N.S. by Chi-square test). Twenty-two of the 54 tumors were stained by an anti-EGF-R monoclonal antibody, 528 IgG. The expression of EGF-R was independent of histological grading, tumor stage, and nodal status, and no correlation was observed between expression of the c-erbB-2 product and EGF-R. The c-erbB-2 product may be applicable as a tumor marker for evaluation of malignant potential, invasiveness, and probably metastatic potential of human bladder cancer.

[Immunological diagnosis of multidrug resistant cancer in urological malignancies].

A monoclonal antibody, MRK16, recognizing specifically an epitope of P-glycoprotein (P-GP) was used to determine the degree of expression of P-GP in kidney and urinary bladder cancers. Immunohistochemistry, immunoelectronmicroscopy, and immunoprecipitation were used for this study. Expression of P-GP was found in 6 of 20 kidney cancers treated without anticancer drugs. Also expression of P-GP was found in 17 of 47 urinary bladder cancers. 11 of 31 in primary cases, 0 of 5 in recurrent cases treated without anticancer drugs, and 6 of 11 in recurrent cases treated with anticancer drugs were positively expressed. These results indicate that a certain proportion of kidney and urinary bladder cancers intrinsically acquired multidrug resistance, and also that prior administration of anticancer drugs may induce P-GP in initially negative tumors. We also succeeded to detect MDR1 mRNA by means of in situ hybridization. From our present data, our methods to detect P-GP and MDR1 mRNA appeared to be very useful from the point of clinical application.

[Recurrence of upper urinary tract calculi].

Treatment of upper urinary tract stones has changed greatly. The recurrence of calculi after the discharge was studied in the 634 patients with urolithiasis admitted to our department during the 9 years up to the end of 1984. The recurrence rate in the 325 cases followed for more than 3 months after the disappearance of the original stones, was 15.6% after 2 years, 27.6% after 5 year and 51.4% after 8 years. In recurrent stone formers, the rate of recurrence thereafter was greater than that of primary stone formers. The growth of calculi was rapid in the renal stone former concomitant with urinary tract infection together with a past history of renal surgery. In relation to the composition of the stone, uric acid calculi tended to recur more often than calculi composed of other substances. In view of recurrence, pyelolithotomy is preferred to renal parenchymal incision.

[Two cases of synchronous bilateral renal tumors].

Case 1: A 56-year-old man visited us complaining of gross hematuria. Because of his refusal to undergo a surgical operation, we performed embolization and chemotherapy, which were ineffective and he died of cancerous cachexia. Case 2: A 59-year-old female with microscopic hematuria was referred to our clinic. Left partial nephrectomy and right radical nephrectomy were done in a two-stage operation at a 3 month interval. She is now well without sign of recurrence at 9 months after the last operation.

Familial pheochromocytoma in a child with multiple recurrence including a lesion in the intrathoracic region.

Familial pheochromocytomas were removed from the bilateral adrenal glands and the abdominal cavity of a 10-year-old female. Due to the existence of an accessory adrenal gland, it was possible to discontinue steroid supplement. The disease relapsed, however, when she was 15 years old. After removing the ectopic pheochromocytomas from the abdominal cavity and thorax, she was free from symptoms for 2 years and 6 months.

Measurement of androgen receptor in cytosols from normal, benign hypertrophic and cancerous human prostates.

The binding of R 1881 in cytosols from the normal, benign hypertrophic and cancerous human prostates was examined in the presence of molybdate and triamcinolone acetonide. The addition of 10 mM Na2MoO4 resulted in an increase in the stability of the binder without any change in Kd. Triamcinolone acetonide added to the incubation of cytosol with R 1881 modified the inhibition pattern by other steroids, and the binding in the presence of triamcinolone acetonide exhibited the characteristics of androgen receptor. The complex of cytosol and R 1881 formed in the incubation in the presence of triamcinolone acetonide was sedimented at 8.5S. Kd of the binding to R 1881 of the normal and pathological prostates was almost identical, but maximum binding sites of the androgen receptor were larger in benign hypertrophic and cancerous prostates than in normal tissues. For the assay of binding capacity in needle biopsy specimens, one point determinations were performed using 2.5 nM R 1881 as the ligand. The number of binding sites obtained by this method were well correlated with those obtained by the Scatchard plot in various prostatic tissues.