Cyclin-dependent kinase 5 (CDK5) is a unique member of the cyclin-dependent kinase family. CDK5 is activated by binding with its regulatory proteins, mainly p35, and its activation is essential in the development of the central nervous system (CNS) and neurodegeneration. Recently, it has been reported that CDK5 plays important roles in regulating various biological and pathological processes, including cancer progression. Concerning prostate cancer, the androgen receptor (AR) is majorly involved in tumorigenesis, while CDK5 can phosphorylate AR and promotes the proliferation of prostate cancer cells. Clinical evidence has also shown that the level of CDK5 is associated with the progression of prostate cancer. Interestingly, inhibition of CDK5 prevents prostate cancer cell growth, while drug-triggered CDK5 hyperactivation leads to apoptosis. The blocking of CDK5 activity by its small interfering RNAs (siRNA) or Roscovitine, a pan-CDK inhibitor, reduces the cellular AR protein level and triggers the death of prostate cancer cells. Thus, CDK5 plays a crucial role in the growth of prostate cancer cells, and AR regulation is one of the important pathways. In this review paper, we summarize the significant studies on CDK5-mediated regulation of prostate cancer cells. We propose that the CDK5–p35 complex might be an outstanding candidate as a diagnostic marker and potential target for prostate cancer treatment in the near future.

Objective To assess the effect of surgical experience on peri‐operative, functional and oncological outcomes during the first 50 Retzius‐sparing robot‐assisted radical prostatectomy (RsRARP) cases performed by surgeons naïve to this novel approach. Materials and Methods We retrospectively evaluated the initial cases operated by 14 surgeons in 12 different international centres. Pre‐, peri‐ and postoperative features of the first 50 patients operated by each surgeon in all the participating centres were collected. The effect of surgical experience on peri‐operative, functional and oncological outcomes was firstly evaluated after stratification by level of surgical experience (initial [≤25 cases] and expert [>25 cases]) and after using locally weighted scatterplot smoothing to graphically explore the relationship between surgical experience and the outcomes of interest. Results We evaluated 626 patients. The median follow‐up was 13 months in the initial group and 9 months in the expert group (P = 0.002). Preoperative features overlapped between the two groups. Shorter console time (140 vs 120 min; P = 0.001) and a trend towards lower complications rates (13 vs 5.5%; P = 0.038) were observed in the expert group. The relationship between surgical experience and console time, immediate urinary continence recovery and Clavien–Dindo grade ≥2 complications was linear, without reaching a plateau, after 50 cases. Conversely, a non‐linear relationship was observed between surgical experience and positive surgical margins (PSMs). Conclusions In this first report of a multicentre experience of RsRARP during the learning curve, we found that console time, immediate urinary continence recovery and postoperative complications are optimal from the beginning and further quickly improve during the learning process, while PSM rates did not clearly improve over the first 50 cases.

Seeding of ureteral grafts with autologous bladder cells does not promote success in two largeanimal models using different xenogenic acellular matrices. However, muscle and urothelium regeneration occurs with ureteral acellular matrix in the dog. Urothelium-seeded de-epithelialized Monti bowel segments may be an acceptable substitute for long proximal ureteral segments. Further technical refinements are required to replace the bowel mucosa completely with normal urothelium.

Arecoline is the primary alkaloid in betel nuts, which are known as a risk factor for oral submucosal fibrosis and oral cancer. Lung cancer is a severe type of carcinoma with high cell motility that is difficult to treat. However, the detailed mechanisms of the correlation between Arecoline and lung cancer are not fully understood. Here, we investigated the effect of Arecoline on migration in lung cancer cell lines and its potential mechanism through the muscarinic acetylcholine receptor 3 (mAChR3)-triggered EGFR/Src/FAK pathway. Our results indicate that different concentrations of Arecoline treatment (10 µM, 20 µM, and 40 µM) significantly increased the cell migration ability in A549 and CL1-0 cells and promoted the formation of the filamentous actin (F-actin) cytoskeleton, which is a crucial element for cell migration. However, migration of H460, CL1-5, and H520 cell lines, which have a higher migration ability, was not affected by Arecoline treatment. The EGFR/c-Src/Fak pathway, which is responsible for cell migration, was activated by Arecoline treatment, and a decreased expression level of E-cadherin, which is an epithelial marker, was observed in Arecoline-treated cell lines. Blockade of the EGFR/c-Src/Fak pathway with the inhibitors of EGFR (Gefitinib) or c-Src (Dasatinib) significantly prevented Arecoline-promoted migration in A549 cells. Gefitinib or Dasatinib treatment significantly disrupted the Arecoline-induced localization of phospho-Y576-Fak during focal adhesion in A549 cells. Interestingly, Arecoline-promoted migration in A549 cells was blocked by a specific mAChR3 inhibitor (4-DAMP) or a neutralizing antibody of matrix metalloproteinase (MMP7 or Matrilysin). Taken together, our findings suggest that mAChR3 might play an essential role in Arecoline-promoted EGFR/c-Src/Fak activation and migration in an A549 lung cancer cell line.

Laparoscopic surgery seems to be unable to sustain peritoneal immune responses, which may mask reliable clinical signs and symptoms of peritonitis associated with bowel injury.

endoscopic tools were assessed. Specifications, purchase prices and repair costs were obtained from each manufacturer. The field of view and screen image size of each ureteroscope were also compared. RESULTSThe ACMI DUR-8 Elite and the Storz 11278AU had improvements of 79 ∞ and 144 ∞ , respectively, from their respective older models. Although the tip deflection of all ureteroscopes was compromised by inserting different endoscopic tools, these new instruments were less affected. With a 3 F basket inside the working channel, the ACMI DUR-8 Elite and the Storz 11278AU had only 0.7% and 2.8% loss of upward tip deflection, compared with their older models, at 9.6% and 5.0%, respectively. However, the flow rates of these new instruments were decreased. CONCLUSIONThe new flexible ureteroscopes have significantly better active tip deflection than previous models, both with and without endoscopic instrumentation inserted. However, improved flexibility is at the expense of decreased flow rates and higher purchase costs.

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