Influence of pH on the Cytotoxic Activity of Inositol Hexakisphosphate (IP6) in Prostate Cancer

Objectives: In the present study, we investigated whether the pH of IP6 could influence its anti-tumoral activity in vitro. Methods: PC-3 cells were exposed to IP6 at pH 5, pH 7, and pH 12 and we evaluated the metabolic activity (WST-1 assay), cell proliferation (cell count), cell cycle distribution (FACS), and mitochondrial depolarization (JC-1 staining) in vitro. Results: Our results demonstrated that IP6 at pH 5 and pH 12 were more potent at lowering the metabolic activity of PC-3 cells than IP6 at pH 7. Treatment with IP6 at pH 12 also caused the greatest inhibition in cellular proliferation and accumulation of PC-3 cells in sub-G1. Finally, IP6 at pH 12 lead to a reduction in phospho-AKT and phospho-PDK1 and upregulated phospho-ERK. Conclusion: Together, our data strongly suggest that the pH of IP6 effectively modulates its anti-tumoral activity and should be reported in future studies

Securing the appendiceal stump in laparoscopic appendectomy: Evidence for routine stapling?

Background: This metaanalysis aimed to compare endoscopic linear stapling and loop ligatures used to secure the base of the appendix. Methods: Randomized controlled trials on appendix stump closure during laparoscopic appendectomy were systematically searched and critically appraised. The results in terms of complication rates, operating time, and hospital stay were pooled by standard metaanalytic techniques. Results: Data on 427 patients from four studies were included. The operative time was 9 min longer when loops were used (p = 0.04). Superficial wound infections (odds ratio [OR], 0.21; 95% confidence interval (CI), 0.06-0.71; p = 0.01) and postoperative ileus (OR, 0.36; 95% CI, 0.14-0.89; p = 0.03) were significantly less frequent when the appendix stump was secured with staples instead of loops. Of 10 intraoperative ruptures of the appendix, 7 occurred in loop-treated patients (p = 0.46). Hospital stay and frequency of postoperative intraabdominal abscess also were comparable in loop-treated and staple-treated patients. Conclusions: The clinical evidence on stump closure methods in laparoscopic appendectomy favors the routine use of endoscopic staplers

Ebp1 expression in benign and malignant prostate

<p>Abstract</p> <p>Background</p> <p>ErbB3-binding protein 1 (Ebp1) is a member of the <it>PA2G4 </it>family of proliferation-regulated proteins that is expressed in multiple malignant and non-malignant cells. ErbB3 and other members of the EGFR family have been implicated in cancer progression, it however remains unknown whether Ebp1 participate in prostate cancer progression <it>in vivo</it>. Therefore, the present study examines Ebp1 expression in cancerous and non-cancerous prostates tissues. Ebp1 expression was also correlated to known Ebp1 regulated proteins (Androgen receptor (AR), Cyclin D1 & ErbB3) and the proliferation marker Ki67. Furthermore we evaluated whether Ebp1 expression correlated with biochemical recurrence (BCR) following radical prostatectomy.</p> <p>Methods</p> <p>The expression of Ebp1, AR, Cyclin D1, ErbB3 and Ki67 were evaluated by immunohistochemistry using three separate tissue micro-arrays containing normal prostate tissues, non-cancerous tissue adjacent to the primary tumor, hormone-sensitive and hormone-refractory cancerous tissues. Multivariate COX regression analysis was performed with four clinical parameters in order to correlate Ebp1 expression with PCa progression.</p> <p>Results</p> <p>The expression of Ebp1 significantly increased with the progression from normal to hormone sensitive and to hormone refractory PCa. Furthermore, we observed strong correlation between Ebp1 expression and the nuclear expression of AR, Cyclin D1 and ErbB3 in both normal adjacent and cancer tissues. The expression of AR, Cyclin D1 and ErbB3 in normal adjacent tissues correlated with PSA relapse, whereas Ebp1 on its own did not significantly predict PSA relapse. Finally, in a multivariate analysis with a base clinical model (Gleason, Pre-op PSA, surgical margins and P-stage) we identified the multi-marker combination of Ebp1+/Cyclin D1- as an independent predictor of PSA relapse with a hazard ratio of 4.79.</p> <p>Conclusion</p> <p>Although not related to disease recurrence, this is the first <it>in vivo </it>study to report that Ebp1 expression correlates with PCa progression.</p

Wide-field optical spectroscopy system integrating reflectance and spatial frequency domain imaging to measure attenuation-corrected intrinsic tissue fluorescence in radical prostatectomy specimens

The development of a multimodal optical imaging system is presented that integrates endogenous fluorescence and diffuse reflectance spectroscopy with single-wavelength spatial frequency domain imaging (SFDI) and surface profilometry. The system images specimens at visible wavelengths with a spatial resolution of 70 microm, a field of view of 25 cm(2) and a depth of field of approximately 1.5 cm. The results of phantom experiments are presented demonstrating the system retrieves absorption and reduced scattering coefficient maps using SFDI with <6% reconstruction errors. A phase-shifting profilometry technique is implemented and the resulting 3-D surface used to compute a geometric correction ensuring optical properties reconstruction errors are maintained to <6% in curved media with height variations <20 mm. Combining SFDI-computed optical properties with data from diffuse reflectance spectra is shown to correct fluorescence using a model based on light transport in tissue theory. The system is used to image a human prostate, demonstrating its ability to distinguish prostatic tissue (anterior stroma, hyperplasia, peripheral zone) from extra-prostatic tissue (urethra, ejaculatory ducts, peri-prostatic tissue). These techniques could be integrated in robotic-assisted surgical systems to enhance information provided to surgeons and improve procedural accuracy by minimizing the risk of damage to extra-prostatic tissue during radical prostatectomy procedures and eventually detect residual cancer

Associations of fat and muscle mass with overall survival in men with prostate cancer: A systematic review with meta-analysis

Background To systematically review and analyse the associations between fat and muscle mass measures with overall survival in men with prostate cancer. Methods A systematic search was conducted in CINAHL, Cochrane Library, EMBASE, PubMed, and Web of Science databases from inception to December 2020, while abstracts from the American Society of Clinical Oncology (ASCO), Clinical Oncology Society of Australia (COSA), and the American College of Sports Medicine (ACSM) conferences were searched from 2014 to 2020. Eligible articles examined the association of body composition measures, such as fat mass (e.g., fat mass, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT) and muscle mass measures, with overall survival in prostate cancer patients at any treatment stage. The primary endpoint was overall survival. Random-effect meta-analysis was conducted for studies reporting multivariable or univariable analysis assessing the associations of fat mass measures (i.e., fat mass, VAT, SAT, VAT/SAT) and muscle mass measures with overall survival. Results Sixteen cohort studies that comprised 4807 men with prostate cancer were included. Total adiposity (hazard ratio (HR) 0.98, 95% CI: 0.75–1.28, p = 0.888) and VAT (HR 1.03, 95% CI: 0.74–1.43, p = 0.873) were not significantly associated with overall survival, while higher subcutaneous adipose tissue levels were associated with higher survival (HR 0.68, 95% CI: 0.54–0.84, p = 0.001). Greater mortality risk was found in patients with localised (HR 1.91, 95% CI: 1.40–2.62, p \u3c 0.001) and advanced disease (HR 1.43, 95% CI: 1.07–1.92, p = 0.020) presenting with low levels of muscle mass compared to those presenting with high levels. Discussion These results indicate that although overall adiposity should be cautiously interpreted in regards to survival, high muscle mass and SAT, and low VAT/SAT ratio values are associated with overall survival in men with prostate cancer

Optimizing Clinical Benefits of Bisphosphonates in Cancer Patients with Bone Metastases

Malignant bone disease is common in patients with advanced solid tumors or multiple myeloma. Bisphosphonates have been found to be important treatments for bone metastases. A positive benefit-risk ratio for bisphosphonates has been established, and ongoing clinical trials will determine whether individualized therapy is possible

primary lymphomas of the genitourinary tract a population based study

Abstract Objective We performed a population-based analysis focusing on primary extranodal lymphoma of either testis, kidney, bladder or prostate (PGUL). Methods We identified all cases of localized testis, renal, bladder and prostate primary lymphomas (PL) versus primary testis, kidney, bladder and prostate cancers within the Surveillance, Epidemiology, and End Results database (1998–2015). Estimated annual proportion change methodology (EAPC), multivariable logistic regression models, cumulative incidence plots and multivariable competing risks regression models were used. Results The rates of testis-PL, renal-PL, bladder-PL and prostate-PL were 3.04%, 0.22%, 0.18% and 0.01%, respectively. Patients with PGUL were older and more frequently Caucasian. Annual rates significantly decreased for renal-PL (EAPC: −5.6%; p = 0.004) and prostate-PL (EAPC: −3.6%; p = 0.03). In multivariable logistic regression models, older ager independently predicted testis-PL (odds ratio [OR]: 16.4; p Conclusion PGUL rates are extremely low and on the decrease in kidney and prostate but stable in testis and bladder. Relative to primary genitourinary tumors, PGUL are associated with worse CSM for testis-PL and renal-PL but not for bladder-PL and prostate-PL, even after adjustment for other-cause mortality