No abstract

We report what is to our knowledge the largest known series of collecting duct carcinoma. Since advanced or recurrent collecting duct carcinoma is resistant to standard treatment modalities, new treatment strategies are needed for advanced collecting duct carcinoma.

We investigated the presence of beta-adrenoceptor subtypes in human urinary bladder urothelium and examined whether beta-adrenoceptors in the urothelium modulate the relaxation responses of isolated human detrusor strips to a beta-adrenoceptor agonist. Expression of beta1-, beta2-, and beta3-adrenoceptor mRNA in urothelium and detrusor smooth muscle was determined by reverse transcription-polymerase chain reaction, and the distribution of beta1-, beta2-, and beta3-adrenoceptors in human urinary bladder urothelium were examined by immunohistochemistry. Paired human longitudinal detrusor strips with and without an intact urothelium were suspended in organ baths to construct concentration-response curves to isoproterenol. The possible involvement of urothelium-derived nitric oxide (NO) in this response was examined in additional experiments with urothelium-intact strips in the presence of NG-nitro-L-arginine methylester (L-NAME). Results confirmed the expression of beta1-, beta2-, and beta3-adrenoceptors in the human urinary bladder urothelium. Further, the presence of the urothelium caused a parallel rightward shift of the concentration-response curve to isoproterenol with a significant reduction in potency (pEC50). L-NAME failed to exert any significant effect on the relaxation response to isoproterenol in the urothelium-intact strips. These results confirm the presence of beta1-, beta2-, and beta3-adrenoceptors in human urinary bladder urothelium. Further, they suggest that urothelial beta-adrenoceptors induce the release of a urothelium-derived factor which inhibits the beta-adrenoceptor agonist-induced relaxation of the human detrusor smooth muscle and that this inhibitory mechanism might not involve NO.

Following maximum androgen blockade with an alternative nonsteroidal antiandrogen is effective for advanced prostate cancer that has relapsed after initial maximum androgen blockade. Even a partial response to second line maximum androgen blockade was associated with improved survival. Our data support the notion that responders to second line regimens are androgen independent but still hormonally sensitive.