β-TrCP Inhibition Reduces Prostate Cancer Cell Growth via Upregulation of the Aryl Hydrocarbon Receptor

Prostate cancer is a common and heterogeneous disease, where androgen receptor (AR) signaling plays a pivotal role in development and progression. The initial treatment for advanced prostate cancer is suppression of androgen signaling. Later on, essentially all patients develop an androgen independent stage which does not respond to anti hormonal treatment. Thus, alternative strategies targeting novel molecular mechanisms are required. beta-TrCP is an E3 ligase that targets various substrates essential for many aspects of tumorigenesis.Here we show that beta-TrCP depletion suppresses prostate cancer and identify a relevant growth control mechanism. shRNA targeted against beta-TrCP reduced prostate cancer cell growth and cooperated with androgen ablation in vitro and in vivo. We found that beta-TrCP inhibition leads to upregulation of the aryl hydrocarbon receptor (AhR) mediating the therapeutic effect. This phenomenon could be ligand independent, as the AhR ligand 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) did not alter prostate cancer cell growth. We detected high AhR expression and activation in basal cells and atrophic epithelial cells of human cancer bearing prostates. AhR expression and activation is also significantly higher in tumor cells compared to benign glandular epithelium.Together these observations suggest that AhR activation may be a cancer counteracting mechanism in the prostate. We maintain that combining beta-TrCP inhibition with androgen ablation could benefit advanced prostate cancer patients

Is radical cystectomy mandatory in every patient with variant histology of bladder cancer

Urothelial carcinomas have an established propensity for divergent differentiation. Most of these variant tumors are muscle invasive but not all. The response of non muscle invasive variant tumors to intravesical immunotherapy with BCG is not established in the literature, and is reported here. Between June 1995 and December 2007, 760 patients (mean age of 67.5 years) underwent transurethral resection of first time bladder tumors in our institution. Histologically variant tumors were found in 79 patients (10.4%). Of these 57 patients (72%) of them had muscle-invasive disease or extensive non-muscle invasive tumors and remaining 22 patients (28%) were treated with BCG immunotherapy. These included 7 patients with squamous differentiation, 4 with glandular, 6 with nested, 4 with micropapillary and 1 patient with sarcomatoid variant. The response of these patients to immunotherapy was compared with that of 144 patients having high-grade conventional urothelial carcinomas. Median follow-up was 46 months. The 2 and 5-year progression (muscle-invasion) free survival rates were 92% and 84.24% for patients with conventional carcinoma compared to 81.06% and 63.16% for patients with variant disease (P=0.02). The 2 and 5-year disease specific survival rates were 97% and 91.43% for patients with conventional carcinoma compared to 94.74 % and 82% for patients with variant disease (P=0.33). 5 patients (22.7%) of variant group and 13 patients (9.03%) of conventional group underwent cystectomy during follow-up (P=0.068)

Enantioselective sorption of alcohols in a homochiral metal–organic framework

Single-crystal X-ray diffraction study reveals the host-guest interactions between a homochiral metal-organic framework and two enantiomers of a chiral alcohol providing the key driving force for the enantioselective sorption of alcohols in the framework.open116568sciescopu

History of Ureteral Stenting Negatively Affects the Outcomes of Extracorporeal Shockwave Lithotripsy. Results of a Matched-pair Analysis

To evaluate the impact of ureteral stenting history to the outcomes of extracorporeal shockwave lithotripsy, we retrospectively analysed patients who underwent shockwave lithotripsy with Dornier Gemini lithotripter between September 2010 and August 2012. Forty seven patients (group A) who had a double J stent which was removed just before the procedure were matched-paired with another 47 patients (group B) who underwent shockwave lithotripsy having no stent history. The correlation between ureteral stenting history and stone-free rates was assessed. Stone-free rates were 68.1% and 87.2% for patients of group A and B, respectively (p=0.026). Postoperative complications were not different between groups. Multivariate analysis revealed that stone size (p=0.007), stone location (p=0.044) and history of ureteral stenting (p=0.046) were independent predictors for stone clearance after shockwave lithotripsy. Ureteral stents adversely affect shockwave lithotripsy outcome, even if they are removed before the procedure. Stenting history should divert treatment plan towards intracorporeal lithotripsy

Is emergency percutaneous antegrade drainage of the upper urinary tract useful for future percutaneous nephrolithotomy access?

Purpose: To compare percutaneous nephrolithotomy (PCNL) operations between patients with a preoperative nephrostomy tube and patients that the renal access was obtained at the time of the surgery. Materials and Methods: We retrospectively evaluated PCNL cases. Patients were divided into two groups. Group 1 – a non-nephrostomy tube (percutaneous nephrostomy, PCN) group and Group 2 – patients with a PCN placed before the procedure. All preoperatively placed PCN's were performed in emergency situations by interventional radiologists (IR). Complications were classified according to the Clavien-Dindo classification. We compared stone characteristics, operation time, complications, efficacy and PCN usability at surgery. Results: Five hundred twenty-seven patients who were submitted to PCNL for renal stones were included in the study. In 73 patients (13.9%) the PCNs were placed before the surgery. Patients and stone characteristics, mean operative time (p=0.830), complications (p=0.859) and stone-free rates (93.0%) were similar between the groups. There was a trend toward higher complication rates in Group 1, but the difference was not statistically significant. Only 21 (29.0%) of preoperatively placed PCNs were used during PCNL for establishing a tract. The reasons for not using PCN tract were: pelvic or infundibular insertion (30.0%) and suboptimal anatomic location (70.0%). Conclusions: Preoperative emergency inserted PCNs by IR usage rates were low during PCNL. Its placement neither affects the incidence of complications nor affects the operation time and outcomes. As such, when emergency renal drainage is indicated, the need for a future definitive PCNL should not influence the decision about the modality of renal drainage

bigartm/bigartm: Beta release 0.9.0

There a some changes besides numerous bug fixes and small improvements: Add support for entire model saving and loading via dump_artm_model and save_artm_model methods of artm.ARTM Basic support for building and installing platform-dependent Python wheels VisARTM documentation is moved to its own website, now there is only link to it IMPORTANT Few Python dependencies were added - scipy (required) and wheel (for building Python package, optional). Please install them with pip install. For more details refer to Release Notes. If you have any questions, please ask [email protected]