Enoxacin and its bone-seeking bisphosphonate derivative, bis-enoxacin, have recently captured attention as potential therapeutic agents for the treatment of cancer and bone disease. No differences in growth or survival of 4T1 murine breast cancer cells were detected at a concentration of 50 µM of enoxacin or bis-enoxacin. Growth was perturbed at higher concentrations. Both 50 µM enoxacin and bis-enoxacin stimulated increases in the number of GW/Processing bodies, but there were minimal changes in microRNA levels. Extracellular vesicles (EVs) released from 4T1 cells treated with 50 µM enoxacin or 50 µM bis-enoxacin stimulated proliferation of RAW 264.7 cells, and both significantly inhibited osteoclastogenesis in calcitriol-stimulated mouse marrow. EVs from 4T1 cells treated with enoxacin and bis-enoxacin displayed small reductions in the amount of microRNA (miR)-146a-5p and let-7b-5p. In marked contrast, miR-214-3p, which has been shown to regulate bone remodeling, was increased 22-fold and 30-fold respectively. We conclude that enoxacin and bis-enoxacin trigger the release of EVs from 4T1 cancer cells that inhibit osteoclastogenesis.
Aims and methodWe examined learning outcomes, practice impacts and implementation processes for a training intervention in diagnostic skills delivered to multidisciplinary child and adolescent mental health service practitioners (n = 63).ResultsTraining was viewed positively by most participants and associated with significant increases in practitioner self-efficacy, with the effect sustained at 8-month follow-up. A comparative audit before and after training indicated that clinicians were significantly more likely to assign an Axis I diagnosis following the training intervention. However, absolute rates of Axis I classification remained relatively low (< 40%) both before and after training. Practitioners were moderately successful at following through on personal plans for implementing new learning; inconsistent support for implementation was provided within teams.Clinical implicationsA brief training workshop may have limited effects in changing practitioners' behaviour so that diagnoses are made more promptly and appropriately recorded. Future workforce development initiatives should consider more comprehensive and diversified strategies, including targeted post-training support, if increased self-efficacy following training is to be translated into sustained changes in diagnostic practice.
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