High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression

<p>Abstract</p> <p>Background</p> <p>High expression of the RNA-binding protein RBM3 has previously been found to be associated with good prognosis in breast cancer, ovarian cancer, malignant melanoma and colorectal cancer. The aim of this study was to examine the prognostic impact of immunohistochemical RBM3 expression in prostate cancer.</p> <p>Findings</p> <p>Immunohistochemical RBM3 expression was examined in a tissue microarray with malignant and benign prostatic specimens from 88 patients treated with radical prostatectomy for localized disease. While rarely expressed in benign prostate gland epithelium, RBM3 was found to be up-regulated in prostate intraepithelial neoplasia and present in various fractions and intensities in invasive prostate cancer. High nuclear RBM3 expression was significantly associated with a prolonged time to biochemical recurrence (BCR) (HR 0.56, 95% CI: 0.34-0.93, <it>p </it>= 0.024) and clinical progression (HR 0.09, 95% CI: 0.01-0.71, <it>p = </it>0.021). These associations remained significant in multivariate analysis, adjusted for preoperative PSA level in blood, pathological Gleason score and presence or absence of extracapsular extension, seminal vesicle invasion and positive surgical margin (HR 0.41, 95% CI: 0.19-0.89, <it>p </it>= 0.024 for BCR and HR 0.06, 95% CI: 0.01-0.50, <it>p = </it>0.009 for clinical progression).</p> <p>Conclusion</p> <p>Our results demonstrate that high nuclear expression of RBM3 in prostate cancer is associated with a prolonged time to disease progression and, thus, a potential biomarker of favourable prognosis. The value of RBM3 for prognostication, treatment stratification and follow-up of prostate cancer patients should be further validated in larger studies.</p

Aflatoxin-Induced TP53 R249S Mutation in HepatoCellular Carcinoma in Thailand: Association with Tumors Developing in the Absence of Liver Cirrhosis

Primary Liver Cancer (PLC) is the leading cause of death by cancer among males in Thailand and the 3rd among females. Most cases are hepatocellular carcinoma (HCC) but cholangiocarcinomas represent between 4 and 80% of liver cancers depending upon geographic area. Most HCC are associated with chronic infection by Hepatitis B Virus while a G→T mutation at codon 249 of the TP53 gene, R249S, specific for exposure to aflatoxin, is detected in tumors for up to 30% of cases. We have used Short Oligonucleotide Mass Analysis (SOMA) to quantify free circulating R249S-mutated DNA in plasma using blood specimens collected in a hospital case:control study. Plasma R249S-mutated DNA was detectable at low concentrations (≥67 copies/mL) in 53 to 64% of patients with primary liver cancer or chronic liver disease and in 19% of controls. 44% of patients with HCC and no evidence of cirrhosis had plasma concentrations of R249S-mutated DNA ≥150 copies/mL, compared to 21% in patients with both HCC and cirrhosis, 22% in patients with cholangiocarcinoma, 12% in patients with non-cancer chronic liver disease and 3% of subjects in the reference group. Thus, plasma concentrations of R249S-mutated DNA ≥150 copies/mL tended to be more common in patients with HCC developing without pre-existing cirrhosis (p = 0.027). Overall, these results support the preferential occurrence of R249S-mutated DNA in HCC developing in the absence of cirrhosis in a context of HBV chronic infection

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Nebulization of antimicrobial agents in mechanically ventilated adults in 2017: an international cross-sectional survey

2017 ESCMID practice guidelines reported safety concerns and weak evidence of benefit supporting use of aerosolized antibiotics in mechanically ventilated patients. Our primary goal was to assess current patterns of aerosolized antibiotic prescription in mechanically ventilated patients. A sequential global survey was performed prior to the release of the ESCMID guidelines, from the 1st of February to the 30th of April 2017, using an electronic platform. Responses were analyzed comparing geographical regions. A total of 410 units responded, with 261 (177 from Europe) being eligible for the full survey. 26.8%of units reported not using aerosolized antibiotics. The two major indications amongst prescribing units were ventilator-associated pneumonia and ventilator-associated tracheobronchitis (74.3% and 49.4%, respectively). 63.6% of units indicated prescription solely in response to multi-drug resistant organisms. In comparison with a survey undertaken in 2014, there was a significant reduction in use of aerosolized antibiotics for prophylaxis (50.6% vs 7.7%, p < 0.05) and colonization (52.9% vs 25.3%, p < 0.05). The large majority of units (91.7%) reported only prescribing in patients with positive pulmonary cultures. Asia appeared to be an outlier, with 53.3% of units reporting empirical use. The most commonly used device was the jet nebulizer. The most commonly prescribed drugs were colistin methanesulfonate (57.6%), colistin base (41.9%) and amikacin (31.4%), although there was considerable heterogeneity across geographical areas. A significant gap exists between ESCMID clinical practice recommendations and the use of aerosolized antibiotics in clinical practice. Our findings indicate an urgent need for high-quality education to bring practice into line with evidence-based guidelines