The translational potential of microRNAs as biofluid markers of urological tumours

MicroRNAs (miRNAs) are secreted by cells in vesicles, bound in a ribonucleoprotein complex or as free molecules. These miRNA secretion pathways are dysregulated in cancer, making miRNAs attractive candidate molecules for liquid biopsies. A number of studies have investigated the regulation of miRNA secretion into blood and urine and suggested that miRNAs are noninvasive diagnostic, prognostic and surveillance markers in urological carcinomas, and research in this area has increased over the past 5 years. However, methodological and analytical pitfalls exist and require addressing to enable future translation of the laboratory findings regarding miRNAs as biomarkers into clinical practice in bladder cancer, kidney cancer, prostate cancer and testicular cancer

The miRNA-kallikrein axis of interaction: a new dimension in the pathogenesis of prostate cancer

Kallikrein-related peptidases (KLKs) are a family of serine proteases that were shown to be useful cancer biomarkers. KLKs have been shown to be dysregulated in prostate cancer (PCa). microRNAs (miRNAs) are short RNA nucleotides that negatively regulate gene expression and have been reportedly dysregulated in PCa. We compiled a comprehensive list of 55 miRNAs that are differentially expressed in PCa from previous microarray analysis and published literature. Target prediction analyses showed that 29 of these miRNAs are predicted to target 10 KLKs. Eight of these miRNAs were predicted to target more than one KLK. Quantitative real-time (qRT)-PCR demonstrated that there was an inverse correlation pattern in the expression (normal vs. cancer) between dysregulated miRNAs and their target KLKs. In addition, we experientially validated the miRNA-KLK interaction by transfecting miR-331-3p and miR-143 into a PCa cell line. Decreased expression of targets KLK4 and KLK10, respectively, and decreased cellular growth were observed. In addition to KLKs, dysregulated miRNAs were predicted to target other genes involved in the pathogenesis of PCa. These data show that miRNAs can contribute to KLK regulation in PCa. The miRNA-KLK axis of interaction projects a new element in the pathogenesis of PCa that may have therapeutic implications

The International Society of Sport Psychology (ISSP) Ethical Code for Sport Psychology Practice

The International Society of Sport Psychology (ISSP) aims to be the leading international and inclusive organization focused on the development of sport psychology in all regions and cultural areas of the world, promoting professional impact in the global community through research and practice. As a global organization, ISSP encompasses professionals that render services to individuals, groups and the society at large, who ought to have ethics to guide their engagement in rendering services. Such code of ethics will protect the members’ interest so as to comply with their underlying practice as well as it will contribute to guarantee the protection of the clients

Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17

Background: Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. Methods: We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings: Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40·0% (95% uncertainty interval [UI] 39·4–40·7) to 50·3% (50·0–50·5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46·3% (95% UI 46·1–46·5) in 2017, compared with 28·7% (28·5–29·0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88·6% (95% UI 87·2–89·7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664–711) of the 1830 (1797–1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76·1% (95% UI 71·6–80·7) of countries from 2000 to 2017, and in 53·9% (50·6–59·6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation: Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation

Cytotoxic activity of sunitinib and everolimus in Caki-1 renal cancer cells is accompanied by modulations in the expression of apoptosis-related microRNA clusters and BCL2 family genes

Sunitinib and everolimus are two of the antineoplastic agents indicated for the management of metastatic renal cancer. Although both of the above compounds were primarily designed as antiangiogenic factors, preclinical studies claim that these drugs can also trigger apoptosis. Herein, we sought to evaluate the cytotoxic activity of sunitinib and everolimus against renal cancer cells Caki-1 and moreover to assess their impact on the expression levels of three BCL2 family members and three apoptosis-related microRNA clusters upon incubation with the drugs or following recovery from treatment. The cytotoxic effect of sunitinib and everolimus on Caki-1 cells' viability was estimated by the MTT assay, while cleaved PARP, assayed via Western Blotting, served as a marker of programmed cell death. As for the expression levels of the BCL2 family members BCL2, BAX and BCL2L12 and those of the mature microRNAs of the miR-183/96/182, miR-143/145, and miR-15a/16 clusters, they were quantified via real-time PCR. Our results showed that both agents induced a time- and dose-dependent decrease in cell viability and promoted cleavage of PARP. In parallel, significant modulations were observed in the expression levels of miR-145, miR-15a, and miR-16 in case of sunitinib, whereas BCL2, BAX, miR-145 and miR-15a expression was strongly affected by everolimus. Overall, our data support the notion that sunitinib and everolimus are able to directly induce cell death in renal cancer cells and simultaneously affect the expression levels of their apoptosis-related microRNAs and BCL2 family members upon this process. © 2015 Elsevier Masson SAS

Gemcitabine impacts differentially on bladder and kidney cancer cells: distinct modulations in the expression patterns of apoptosis-related microRNAs and BCL2 family genes

Bladder and renal cancer are two representative cases of tumors that respond differentially to gemcitabine. Previous studies have shown that gemcitabine can trigger apoptosis in various cancer cells. Herein, we sought to investigate the impact of gemcitabine on the expression levels of the BCL2 family members BCL2, BAX, and BCL2L12 and the apoptosis-related microRNAs miR-182, miR-96, miR-145, and miR-16 in the human bladder and kidney cancer cell lines T24 and Caki-1, respectively. Cancer cells’ viability as well as the IC50 doses of gemcitabine were estimated by the MTT assay, while the detection of cleaved PARP via Western blotting was used as an indicator of apoptosis. Furthermore, T24 and Caki-1 cells’ ability to recover from treatment was also monitored. Two different highly sensitive quantitative real-time RT-PCR methodologies were developed in order to assess the expression levels of BCL2 family genes and microRNAs. Exposure of cancer cells to gemcitabine produced the IC50 values of 30 and 3 nM for Caki-1 and T24 cells, correspondingly, while cleaved PARP was detected only in Caki-1 cells. T24 cells demonstrated the ability to recover from gemcitabine treatment, whereas Caki-1 cells’ recovery capability was dependent on the initial time of exposure. BCL2 and BAX were significantly modulated in treated Caki-1 cells. Instead, T24 cells exhibited alterations only in the latter, as well as in all studied microRNAs. Therefore, according to our data, bladder and renal cancer cells’ response to gemcitabine is accompanied by distinct alterations in the expression levels of their apoptosis-related genes and microRNAs. © 2015, International Society of Oncology and BioMarkers (ISOBM)

MicroRNAs in clinical oncology: At the crossroads between promises and problems

MicroRNAs (miRNAs) are small RNAs that do not code for proteins, but function by controlling protein expression of other genes. miRNAs have been shown to control cell growth, differentiation and apoptosis. Shortly after their discovery, miRNAs have been found to be associated with cancer. Earlier reports have shown that human cancers frequently show a distorted expression profile of miRNAs. In this review, the biogenesis of miRNAs and potential mechanisms of their dysregulation and involvement in cancer pathogenesis are discussed. The current literature on potential applications of miRNAs in the field of clinical oncology from diagnostic to prognostic and predictive applications at the tissue, and more recently, serum levels, is reviewed. The potential therapeutic applications of miRNAs and RNAi in the field of cancer are summarised. Finally, some of the potential challenges that face the transition of miRNAs from a research setting into a clinical application are highlighted, with a future prospective of the incorporation of miRNAs in cancer patient management