17ß-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer.

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor-positive (ER+) BC, we hypothesized that 17ß-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17ß-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2. Additionally, miR-149-5p downregulation promotes hnRNPA1 expression, responsible for the loading of let-7's miRNAs into EVs. In multiple patient cohorts, we observed increased levels of let-7a-5p and let-7d-5p in EVs derived from the blood of premenopausal ER+ BC patients, and elevated EV levels in patients with high BMI, both conditions associated with higher levels of 17ß-estradiol. In brief, we identified a unique estrogen-driven mechanism by which ER+ BC cells eliminate tumor suppressor miRNAs in EVs, with effects on modulating tumor-associated macrophages in the microenvironment.

Assessing visualization in robotic-assisted surgery: demystifying a misty lens.

Despite major technological advancements in robotic-assisted laparoscopic surgery (RAS), there remain shortcomings yet to be addressed. This study assesses the prevalence of suboptimal vision in minimally invasive RAS and corresponding factors regarding related surgical conditions. 45 minimally invasive robotic surgeries, performed using Da Vinci XI, were observed across three surgical subspecialties: general, urology, and OB/GYN. Lens occlusion events were monitored and defined as the presence of a visual distortion caused by debris deposition on the scope lens. Lens occlusions and cleanings, and "active instrumentation" were recorded. Descriptive statistics summarized duration-based variables, and one-factor ANOVA compared the presence of active instrumentation. Cases averaged 127 ± 76 min. Active instrumentation ANOVA during lens occlusions demonstrated significant variation between categories (F7, 256 = 11.63, p = 2.558e-13). Post hoc Tukey HSD found electrocautery devices were active significantly more during occlusion events (37.9%) than other instruments. On average, lens cleaning occurred every 36.5 ± 39.8 min despite lens occlusion occurring every 24.5 ± 15.7 min. Of the operative time observed, 41.4% ± 28.1% was conducted with visual distortion. 1.16% ± 0.97% of time observed was spent cleaning. Although only 1.16% of operative time was spent cleaning, surgeons experienced suboptimal conditions for nearly 35× the time it would take the clear lens, potentially indicating a tendency to avoid cleaning the lens to disrupt surgery. Future research may examine the impact of occluded visualization and lens cleaning on other aspects of surgery.