Detection of Extracellular Vesicle-Derived RNA as Potential Prostate Cancer Biomarkers: Role of Cancer-type SLCO1B3 and ABCC3.

Extracellular vesicles (EVs) provide a minimally invasive liquid biopsy source of tumor-specific markers for patients who have already undergone prostatectomies. Our laboratory has previously demonstrated enrichment of the cancer-type solute carrier organic anion transporter family 1B3 (ct-SLCO1B3) and the ATP Binding Cassette Subfamily Member C (ABCC3) in castration-resistant cell lines (CRPC). However, their expression in EVs has yet to be explored. Our study demonstrated that ct-SLCO1B3 and ABCC3 are highly detectable in CRPC cell line-derived EVs. We also showed that ct-SLCO1B3 and ABCC3 were detectable in a CRPC xenograft mouse model, both intratumorally and in plasma-derived EVs. Our results provide evidence for EV-contained ct-SLCO1B3 and ABCC3 as novel, EV-based tumor markers for prostate cancer progression.

Development of a national proficiency test for SARS-CoV-2 detection by PCR in Colombia.

Background: Proficiency testing (PT) is a tool for ensuring the validity of results of testing laboratories and is essential when laboratories are working with assays authorised for emergency use or implementing novel techniques for detecting emerging pathogens. Methods: In collaboration with the National Health Institute of Colombia and with international support, we developed a qualitative PT for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR). A proficiency test item (PTI) based on reference material (research grade) produced by the National Institute of Standards and Technologies (NIST) was prepared and characterised using three positive samples with varying concentrations of SARS-CoV-2 ribonucleic acid (RNA) and two negative (control) samples. Tests were distributed to 121 laboratories across the national network of public health laboratories in Colombia. Results: Positive samples had varying concentrations of SARS-CoV-2 RNA and were quantified by digital PCR (RT-ddPCR) assays for the E gene of SARS-CoV-2. We tested the ability of laboratories to detect low and high levels of viral RNA using samples with SARS-CoV-2 RNA concentrations of 1417 ± 216, 146 ± 28, and 14 ± 10 copies /uL (expanded uncertainty, k = 2, 95% confidence level) We also performed a semiquantitative analysis of instrumental responses (Ct values) reported by participating laboratories and homogeneity, stability, and characterisation studies of the produced materials to determine the adequacy of these materials and methods for use in the qualitative PT scheme. The PT evaluated reports for individual target genes from each laboratory; 98.3% of laboratories had satisfactory performance and the remaining 1.7% of laboratories had unsatisfactory performance for the detection of at least one of the reported genes. Conclusions: This PT scheme identified the potential metrological weaknesses of laboratories in the detection of SARS-CoV-2 by RT-PCR and may facilitate improvements in the quality of measurements from the perspective of public health surveillance.

Diversity on demand: multi-ancestry meta-analysis improves genetic risk prediction in prostate cancer.

Several genome-wide association studies have been conducted to identify genetic risk factors associated with prostate cancer, but their ability to discover new genetic variants and their applicability across ancestry groups have been limited by their lack of genetic diversity, owing to an underrepresentation of non-European populations. A recent meta-analysis published in Nature Genetics by Conti et al. has used a multi-ancestry approach to identify 86 new genetic loci associated with prostate cancer risk, refine leads in known risk regions, and develop a genetic risk score that is transferable across population groups. The findings of this study represent a significant advancement in genetic risk prediction for prostate cancer and their incorporation into standard screening protocols may lead to significant improvements in clinical outcomes.

Fixation of vascular grafts with increased glutaraldehyde concentration enhances mechanical properties without increasing calcification.

Our objective was to study the effect of glutaraldehyde (GLU) concentration, heat, and photooxidation on mechanical properties and calcification of bovine pericardium grafts in an in vivo model. Fresh pericardia were treated as follows: 0.625% GLU for 7 days (standard); 0.625%, 1%, and 3% GLU at 4 degrees C for 20 days and 50 degrees C for additional 20 days; irradiation in cross-linking medium with metilene blue at 0 degrees C for 8 hours. Tissues were subjected to tensile mechanical tests (n = 76). Fixed patches were subcutaneously implanted in mice for 50 days (n = 16 per treatment). Calcification was assessed by atomic absorption spectrophotometry (n = 55) and von Kossa staining (n = 28). Analysis of variance and Tukey's test were used for statistical analysis. The 3% GLU and 3% GLU + heat treatments showed an enhancement of the mechanical properties above standard treatment. No significant difference was found in calcification between treatments. The 3% GLU treatment enhances the mechanical properties of the tissue above standard treatment without increasing calcification and without applying heat; therefore it is recommended for high-strength applications. Supplementary treatments to decrease calcification could be combined with this methodology to obtain a high-strength-low-calcification biomaterial for manufacturing of long-term cardiovascular grafts.