RESUMEN
Protein glycosylation, the attachment of carbohydrates onto proteins, is a fundamental process that alters the biological activity of proteins. Changes to glycosylation states are associated with many forms of cancer including breast cancer. Through immunohistological analysis of breast cancer patient tumors, we have discovered the expression of an atypical glycan-polysialic acid (polySia)-in breast cancer. Notably, we have identified polySia expression in not only tumor cells but also on tumor-infiltrating lymphocytes (TILs) and our study reveals ST8Sia4 as the predominant polysialyltransferase expressed. Evaluation of ST8Sia4 expression in tumor cells identified an association between high expression levels and poor patient outcomes whereas ST8Sia4 expression in infiltrating stromal cells was associated with good patient outcomes. Investigation into CD56, a protein known to be polysialylated, found CD56 and polySia expression on breast tumor cells and TILs. CD56 expression did not positively correlate with polySia expression except in patient tumors which expressed HER2. In these HER2 expressing tumors, CD56 expression was significantly associated with HER2 expression score. Evaluation of CD56 tumor cell expression identified a significant association between CD56 expression and poor patient outcomes. By contrast, CD56 expression on TILs was significantly associated with good clinical outcomes. Tumors with CD56+ TILs were also consistently polySia TIL positive. Interestingly, in tumors where TILs were CD56 low-to-negative, a polySia+ lymphocyte population was still identified and the presence of these lymphocytes was a poor prognostic indicator. Overall, this study provides the first detailed report of polySia and CD56 in breast cancer and demonstrates that the prognostic significance is dependent on the cell type expression within the tumor.
RESUMEN
The Opioid Awareness and Support Team (OAST) at the Memorial University Faculty of Medicine is a novel student-led initiative designed to supplement medical student learning related to opioid use disorder and the opioids crisis. OAST has focused on grounding educational initiatives related to opioid use disorder in the local community context, working with community partners, and bringing in individuals with lived experience. We present initial findings from an Opioid Education Day that suggest student-led supplemental education for medical students can improve student knowledge surrounding opioid use.
L'équipe d'aide et de sensibilisation aux opioïdes (OAST) est une initiative des étudiants de la faculté de médecine de l'Université Memorial qui apporte un complément à la formation que reçoivent les étudiants sur le trouble lié à l'usage d'opioïdes. L'OAST s'est efforcée d'inscrire les initiatives éducatives liées à la crise des opïodes dans un contexte local en collaboration avec des partenaires communautaires et de faire participer des personnes ayant une expérience de terrain. Nous présentons les résultats préliminaires d'une journée de sensibilisation aux opioïdes qui suggèrent que cette activité éducative menée par les étudiants en médecine peut améliorer les connaissances des apprenants sur la consommation d'opioïdes.
RESUMEN
Metastatic disease is the principal cause of prostate-cancer-related mortality. Our ability to accurately recapitulate the spread of prostate cancer to bone - the most common site of metastasis - is critical to the development of novel metastasis-directed therapies. Several translational models of prostate cancer bone metastasis have been developed, including animal models, cell line injection models, 3D in vitro models, bone implant models, and patient-derived xenograft models. The use of these models has led to numerous advances in elucidating the molecular mechanisms of metastasis and innovations in targeted therapy. Despite this progress, current models are limited by a failure to holistically reproduce each individual element of the metastatic cascade in prostate cancer bone metastasis. In addition, factors such as accurate recapitulation of immunobiological events and improvements in tumour heterogeneity require further consideration. Knowledge gained from historical and currently used models will improve the development of next-generation models. An introspective appraisal of current preclinical models demonstrating bone metastases is warranted to narrow research focus, improve future translational modelling, and expedite the delivery of urgently needed metastasis-directed treatments.