The accepted androgen receptor (AR) role is to promote proliferation and survival of prostate epithelium and thus prostate cancer progression. While growth-inhibitory, tumor-suppressive AR effects have also been documented, the underlying mechanisms are poorly understood. Here, we for the first time link AR anti-cancer action with cell senescence in vitro and in vivo. First, AR-driven senescence was p53-independent. Instead, AR induced p21, which subsequently reduced ΔN isoform of p63. Second, AR activation increased reactive oxygen species (ROS) and thereby suppressed Rb phosphorylation. Both pathways were critical for senescence as was proven by p21 and Rb knock-down and by quenching ROS with N-Acetyl cysteine and p63 silencing also mimicked AR-induced senescence. The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose localization to senescence-associated chromatin foci was increased by AR activation. All these pathways contributed to growth arrest, which resolved in senescence due to concomitant lack of p53 and high mTOR activity. This is the first demonstration of senescence response caused by a nuclear hormone receptor.

Until more precise plasma and tissue data are available, we recommend that fosfomycin prophylaxis be given 1-4 h prior to prostate biopsy. We do not recommend fosfomycin prophylaxis for subjects with known organisms with MICs >4 mg/L.

Adenocarcinoma arising in urinary bladder or prostatic urethra is uncommon. When they occur, the tumor can be mistaken for metastatic lesions, especially from the colon. Here we report the fifth case of a primary urothelial-type adenocarcinoma arising in the prostate which showed enteric differentiation. The patient was a 55 year-old male whose prostatic needle core biopsy showed a high grade adenocarcinoma which was initially thought to be metastatic colon cancer. A follow-up colonoscopy was unremarkable. Subsequent prostatectomy revealed a high grade adenocarcinoma which was positive for cytokeratins 7 and 20, carcinoembryonic antigen, CDX2, and high molecular weight cytokeratin, and negative for prostate specific antigen, prostate specific acid phosphatase and AMACR. A diagnosis of urothelial-type adenocarcinoma of the prostate was rendered. We review the literature regarding this entity, and discuss the differential diagnosis, emphasizing utility of immunohistochemistry in making the diagnosis. Finally, we speculate on the behavior of these rare tumors.

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BackgroundWe evaluated the effectiveness of targeted antimicrobial prophylaxis in transrectal ultrasound guided prostate biopsy (TRUSP).MethodsA prospective, non-randomized cohort study was conducted. Rectal swab cultures plated on non-selective blood agar and on selective MacConkey agar supplemented with ciprofloxacin identified ciprofloxacin-susceptible and –resistant gram-negative bacteria (CS-GNB and CR-GNB). Patients with CS-GNB received ciprofloxacin while those with CR-GNB received directed prophylaxis. Infectious complications were defined clinically and microbiologically within 30 days after TRUSP. Data were derived at 7 and 30 days post procedure by questionnaires and electronic medical records. We hypothesized that there would be no difference in the infectious outcomes among the CS and CR groups.ResultsFrom November 1, 2012 to March 31, 2015, 510 men completed the study; 430 (84.3%) had CS-GNB and 80 (15.7%) had CR-GNB. 484 (94.9%) completed the study per protocol, while 26 (5.1%) had an intention-to-treat (ITT) analysis. Of the 484, 475 (98.1%) had no infections, nine (1.9%) had infections, six of which (1.2%) were culture-proven (CP). The nine infections were as follows: five (1.0%) uncomplicated UTIs, one (0.2%) complicated UTI, and three (0.6%) urosepsis. One case of uncomplicated UTI and two cases of urosepsis were not CP, but were diagnosed clinically. ITT outcomes were similar. The infection rates were not statistically different between the CS-and CR-GNB patients (p-value = 0.314; 95% CI 0.8–3.3). The four patients with complicated UTIs or sepsis were hospitalized for a mean of 2.6 days and discharged without sequelae. Of the nine infections, three were antimicrobial prophylaxis failures (two ciprofloxacin and one amikacin); three were likely due to failure of the collection or processing of the rectal swab or increasing bacterial resistance between the time of swab collection and biopsy, and three developed clinical infections with no isolate recovered.ConclusionsTargeted antimicrobial prophylaxis follows the principles of antimicrobial stewardship and achieved a low rate of infectious complications with limited morbidity and no sequelae. This individualized method of prophylaxis may be widely applied. Further studies are needed to explore reasons for targeted prophylaxis failure and to determine comparative efficacy of non-ciprofloxacin-containing targeted prophylaxis regimens.Trial registrationClinicalTrials.gov. NCT01659866. Registered 9 July 2012. First patient enrolled 1 November 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-017-2470-1) contains supplementary material, which is available to authorized users.