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PEDF inhibits IL8 production in prostate cancer cells through PEDF receptor/phospholipase A2 and regulation of NFκB and PPARγ.

Interleukin-8 (IL8/CXCL8) has been described as a key effector in prostate cancer progression and resistance to standard chemotherapeutic drugs. In the present study, we investigated the effect of the natural, angio-inhibitory and anti-tumoral Pigment Epithelium-Derived Factor (PEDF) on the expression of IL8 cytokine by prostate cancer cells. Using a cytokine antibody array and ELISA, in addition to IL8 quantitative RT PCR, we showed that PEDF inhibits the production of IL8 in human hormone-refractory prostate cancer cells, and delays the growth of these cells in vitro. IL8 reduction was mimicked in cancer cells treated with PPARγ agonist and NFκB-specific inhibitors. Accordingly, PPARγ expression increased in response to PEDF, whereas RelA/p65 expression and nuclear localization, and NFκB transcriptional activity decreased. NFκB deactivation was reversed by the PPARγ antagonist GW9662 and PPARγ (Leu(468)/Glu(471)) dominant negative suggesting a PPARγ-dependent process. We also investigated PEDF Receptor/PLA2 as key player in this pathway by small interference RNA. PEDFR knock down in prostate cancer cells reversed PEDF-induced PPARγ up-regulation, and NFκB and IL8 inhibition compared to non-targeting control siRNA. We conclude that by binding to PEDFR, PEDF up-regulates PPARγ, leading subsequently to suppressed NFκB-mediated transcriptional activation, reduced production of IL8 and limited proliferation of prostate cancer cells. These results reinforce PEDFs therapeutic potential and imply that blocking IL8 could represent a novel alternative for prostate cancer treatment.

Positive correlation between PEDF expression levels and macrophage density in the human prostate.

In this study, we investigated the capacity of pigment epithelium‐derived factor (PEDF) to modulate the recruitment and the differentiation of monocytes/macrophages both in vitro and in human prostate.

PSA screening and deaths from prostate cancer after diagnosis—a population based analysis

The United States Preventative Health Task Force recently recommended prostate specific antigen (PSA) screening be abandoned, believing the results of prior studies failed to show benefits that outweighed risks. Prior analyses did not include a complete 10 year follow‐up in their analyses.

PEDF increases the tumoricidal activity of macrophages towards prostate cancer cells in vitro

Background Although inflammation and prostate cancer (PCa) have been linked, the molecular interactions between macrophages and PCa cells are poorly explored. Pigment Epithelium-Derived Factor (PEDF) is an anti-angiogenic and anti-tumor factor. We previously showed that PEDF induces macrophages recruitment in vitro, correlates with macrophages density in human prostate, and stimulates macrophages polarization towards the classically activated pathway. Here, we demonstrate that PEDF modulates the interaction between macrophages and PCa cells through a bidirectional signalling leading to tumor cell apoptosis and phagocytosis. Methods RAW 264.7 and THP-1 cells, and BMDMs were grown in vitro as mono- or co-cultures with PC3 or CL1 tumor cells. The effects of PEDF and its derived P18 peptide were measured on macrophages differentiation, migration, and superoxide production, and tumor cell apoptosis and phagocytosis. PEDF receptors (ATP5B, PNPLA2, and LRP6) and CD47 mRNA and protein expression were quantified in macrophages and tumor cells by quantitative RT-PCR, western blot, immunofluorescence and flow cytometry. Results We found that PEDF induced the migration of macrophages towards tumor 3D spheroids and 2D cultures. In co-culture, PEDF increased PCa cells phagocytosis through an indirect apoptosis-dependent mechanism. Moreover, PEDF stimulated the production of superoxide by macrophages. Conditioned media from macrophages exposed to PEDF induced tumor cells apoptosis in contrast to control conditioned media suggesting that ROS may be involved in tumor cells apoptosis. ATP5B and PNPLA2 PEDF receptors on macrophages and CD47 on tumor cells were respectively up- and down-regulated by PEDF. As PEDF, blocking CD47 induced phagocytosis. Inhibiting ATP5B reduced phagocytosis. Inversely, PNPLA2 inhibition blocks differentiation but maintains phagocytosis. CD47-induced phagocytosis was partially reverted by ATP5B inhibition suggesting a complementary action. Similar effects were observed with P18 PEDF-derived peptide. Conclusions These data established that modulating the molecular interactions between macrophages and PCa cells using PEDF may be a promising strategy for PCa treatment.

Management of pleural injuries during retroperitoneal surgical procedures

PurposeThe necessity of a postoperative chest tube for the treatment of pneumothorax after a radical nephrectomy is controversial.Materials and methodsA five-year retrospective study was performed on 91 patients, having undergone a radical nephrectomy. We examined the existence and length of a pleural rent, presence of a postoperative thoracostomy tube, postoperative pneumothorax, postoperative pneumonia, postoperative atelectasis, pain scores, hemoglobin saturation, and length of hospital stay with univariate and multivariate analysis.ResultsIncidence of a pleural rent occurred in 29 (36%) of open radical nephrectomy cases; 4 of the 29 cases had a postoperative thoracostomy tube. There was no significant difference in hemoglobin saturation levels between cases that had no pleural rent, a pleural rent without a thoracostomy tube, and a pleural rent with a postoperative thoracostomy tube. A pleural rent without a postoperative chest tube had significantly lower rates of pain score, atelectasis, pneumonia, pleural effusion, and length of hospital stay compared to individuals with a postoperative chest tube. Patients with a chest tube had a significantly higher incidence of pain, atelectasis, pneumonia, effusion, and length of hospital stay.ConclusionIatrogenic pleural rents treated without a postoperative chest tube show a significant decrease in postoperative complications of pneumonia and atelectasis, pain score and length of hospital stay. These patients show no significant increases in postoperative complications; therefore, it appears that postoperative chest tube placement after a pleural injury occurs is of no advantage.

Patients Willing to Wait: Arrival Time, Wait Time and Patient Satisfaction in an Ambulatory Urology Clinic

Introduction: We evaluated the relationship of patient satisfaction to arrival and wait times. We also sought to determine factors that patients considered important to the visit experience. Methods: A total of 361 participants completed a survey in clinic to record wait times in various areas of the clinic and then rate satisfaction levels with these times and with the care received. A total of 211 participants ranked 6 factors related to the patient experience in the order considered important. Results: Early, on time and late arriving patients spent 26.0, 15.5 and 17.1 minutes in the waiting room and had a total visit duration of 82.5, 67.9 and 72.0 minutes, respectively. Significant differences existed between these times when the early group was compared with the on time and late groups. Early patients were significantly more satisfied with wait time in the waiting room and total clinic visit time compared to late patients. Receiving treatment or relief from a medical problem was the most important factor valued by this population. Conclusions: Surprisingly, patients with longer waits were more satisfied with the time in the waiting room and overall visit duration, indicating that other variables influence patient satisfaction with perceived wait times. This study provides evidence that wait time might not be as important to patients or impact patient satisfaction as previously thought. On average wait time was ranked fifth in regard to what was important. Longer wait times did not seem to impact patient satisfaction when asked about overall satisfaction with the care received.

Association of prostate volume with incidence and aggressiveness of prostate cancer

Objective The aim of this study was to investigate the possible correlation between prostate volume and aggressiveness and incidence of prostate cancer (PCa). Patients and methods A chart review of a cohort of 448 consecutive prostate biopsy-naive men was performed. These men underwent at least a 12-core biopsy at our institution due to increased prostate-specific antigen serum levels (>4 ng/mL) and/or suspicious findings on digital rectal examination during the period between 2008 and 2013. Transrectal ultrasound was used to determine the prostate volume. Results The positive biopsy rate was 66% for patients with a prostate volume of ≤35 cc and 40% for patients with a prostate volume of ≥65 cc (P<0.001). Of the 110 patients testing positive on biopsy with a volume of ≤35 cc, 10 patients (9.1%) had a Gleason score of ≥8. Of the 27 patients testing positive on biopsy with a volume of ≥65 cc, only 1 patient (3.7%) had a Gleason score of ≥8. Conclusion These results suggest that there may be an association between prostate volume and the incidence and aggressiveness of PCa. The larger the prostate, the lower the positive biopsy rate for PCa and the lower the Gleason score.

A Cost-Benefit Analysis of Medical Scribes and Electronic Medical Record System in an Academic Urology Clinic

Introduction: Electronic medical records have introduced an additional level of complexity to the patient‐provider encounter and medical scribes may offer a solution. We examined how a medical scribe system could support an academic urology clinic. To assess the financial feasibility of this model, we analyzed the additional costs associated with adding medical scribes and we discuss the potential benefits of this system. Methods: We measured total patient wait and interaction times with staff, and estimated the additional staff required to maintain an increased patient load if medical scribes were introduced. We then calculated the average revenue per patient during the most recent 9 months of data to estimate the minimum increase in the number of patient visits needed to offset the additional staffing needs. Results: Mean ± SD total wait time was 23 minutes 28 seconds ± 13 minutes 4 seconds. Average monthly expenses would increase by

Occlusion of bilateral dorsal penile arteries resulting in glans necrosis in an obese male truck driver

17,452.50 for 6 additional staff members, including 1 nursing assistant, 1 patient service specialist, 1 nurse and 3 scribes. There was an average of 666 monthly office visits and average net revenue to the department was

Association of benign prostatic hyperplasia (BPH) volume and prostate cancer: consecutive data from an academic institution in respect to the current scientific view

107.78 per patient visit. The increase in the number of patient visits required to break even would be 162 additional patients per month, representing a 24.3% increase. Additional downstream revenue was considered. Conclusions: A medical scribe system in the example of an academic urology clinic setting could increase patient flow and decrease the burden on medical providers by reducing computer charting. This model is only financially prudent if the increased expenses are offset by additional revenue from increased patient visits.