Epigenetic and oncogenic regulation of SLC16A7 (MCT2) results in protein over-expression, impacting on signalling and cellular phenotypes in prostate cancer

Monocarboxylate Transporter 2 (MCT2) is a major pyruvate transporter encoded by the SLC16A7 gene. Recent studies pointed to a consistent overexpression of MCT2 in prostate cancer (PCa) suggesting MCT2 as a putative biomarker and molecular target. Despite the importance of this observation the mechanisms involved in MCT2 regulation are unknown. Through an integrative analysis we have discovered that selective demethylation of an internal SLC16A7/MCT2 promoter is a recurrent event in independent PCa cohorts. This demethylation is associated with expression of isoforms differing only in 5'-UTR translational control motifs, providing one contributing mechanism for MCT2 protein overexpression in PCa. Genes co-expressed with SLC16A7/MCT2 also clustered in oncogenic-related pathways and effectors of these signalling pathways were found to bind at the SLC16A7/MCT2 gene locus. Finally, MCT2 knock-down attenuated the growth of PCa cells. The present study unveils an unexpected epigenetic regulation of SLC16A7/MCT2 isoforms and identifies a link between SLC16A7/MCT2, Androgen Receptor (AR), ETS-related gene (ERG) and other oncogenic pathways in PCa. These results underscore the importance of combining data from epigenetic, transcriptomic and protein level changes to allow more comprehensive insights into the mechanisms underlying protein expression, that in our case provide additional weight to MCT2 as a candidate biomarker and molecular target in PCa.

Construcción del protocolo de procedimiento clínico del examen electrorretinograma cromático de la clínica de optometria de La Universidad de La Salle

Tesis (Optometra). -- Universidad de La Salle, Facultad de Ciencias de La Salud. Programa de Optometria, 2014

How are Canadian universities training and supporting undergraduate medical, physiotherapy and occupational students for global health experiences in international low-resource settings?

Abstract : OBJECTIVES : Canadian medical (MD), physiotherapy (PT) and occupational therapy (OT) students increasingly show an interest in global health experiences (GHEs). As certain moral hazards can occur as a result of student GHEs, a growing consensus exists that universities must have an established selection process, in-depth pre-departure training (PDT), adequate onsite supervision and formal debriefing for their students. This study aimed at identifying current practices in Canadian MD, PT and OT programs and discussing areas for improvement by comparing them with recommendations found in the literature. METHODS : Canadian MD, PT and OT programs (n = 45) were invited to answer an online survey about their current practices for GHE support and training. The survey included 24 close-ended questions and 18 open-ended questions. Descriptive statistics and a thematic analysis were performed on the data and results were discussed with recommendations found in the literature. RESULTS : Twenty-three programs responded to the survey. Student selection processes varied across universities; examples included using academic performance, interviews and motivation letters. All but 1 MD program had mandatory PDT; content and teaching formats varied, as did training duration (2-38 hours). All but 1 MD program had onsite supervision; local clinicians were frequently involved. Debriefing, although not systematic, covered similar content; debriefing was variable in duration (1-8 hours). CONCLUSIONS : Many current practices are encouraging but areas for improvement exist. Integrating global health content into the regular curriculum with advanced study option in global health for students participating in GHEs could help universities standardize support and training.