Plos One
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The androgen receptor (AR) is the most highly expressed steroid receptor in breast cancer with 75-95% of estrogen receptor (ER)-positive and 40-70% of ER-negative breast cancers expressing AR. Though historically breast cancers were treated with steroidal androgens, their use fell from favor because of their virilizing side effects and the emergence of tamoxifen. Nonsteroidal, tissue selective androgen receptor modulators (SARMs) may provide a novel targeted approach to exploit the therapeutic benefits of androgen therapy in breast cancer. ⋯ 1. AR stimulation inhibits paracrine factors that are important for MSC interactions and breast cancer invasion and metastasis. 2. SARMs may provide promise as novel targeted therapies to treat AR-positive triple-negative breast cancer.
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Microtubules depolymerization caused by the CK1 inhibitor IC261 may be not mediated by CK1 blockage.
The ubiquitously expressed serine/threonine specific casein kinase 1 (CK1) family plays important roles in the regulation of various physiological processes. Small-molecule inhibitors, such as the CK1δ/ε selectively inhibitor IC261, have been used to antagonize CK1 phosphorylation events in cells in many studies. Here we present data to show that, similarly to the microtubule destabilizing agent nocodazole, IC261 depolymerizes microtubules in interphase cells. ⋯ In addition, FACS analysis revealed that IC261 could induce apoptosis independent of cell cycle arrest. In summary this study provides additional and valuable information about various IC261-induced effects that could be caused by microtubule depolymerization rather than by inhibition of CK1. Data from studies that have used IC261 as an inhibitor of CK1 should be interpreted in light of these observations.
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Meta Analysis
Terlipressin versus norepinephrine in the treatment of hepatorenal syndrome: a systematic review and meta-analysis.
Hepatorenal syndrome (HRS) is a severe and progressive functional renal failure occurring in patients with cirrhosis and ascites. Terlipressin is recognized as an effective treatment of HRS, but it is expensive and not widely available. Norepinephrine could be an effective alternative. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of norepinephrine compared to terlipressin in the management of HRS. ⋯ Norepinephrine seems to be an attractive alternative to terlipressin in the treatment of HRS and is associated with less adverse events. However, these findings are based on data extracted from only four small studies.
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Review Meta Analysis
Predictors of extubation failure in neurocritical patients identified by a systematic review and meta-analysis.
Prediction of extubation failure, particularly in neurocritical patients, is unique and controversial. We conducted a systematic review and meta-analysis to identify the risk factors for extubation failure in these patients. ⋯ Besides pneumonia, atelectasis, and the duration of mechanical ventilation, other factors that should be taken into consideration in the prediction of extubation failure when neurocritical patients are weaned from tracheal intubation include neurologic abilities (Glasgow Coma Scale score and following commands), the secretion texture, and the presence of a gag reflex.
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Review Meta Analysis
Recipient-related clinical risk factors for primary graft dysfunction after lung transplantation: a systematic review and meta-analysis.
Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors. Herein, we carried out a systematic review and meta-analysis of published literature to identify recipient-related clinical risk factors associated with PGD development. ⋯ Our analysis identified several recipient related risk factors for development of PGD. The identification of higher-risk recipients and further research into the underlying mechanisms may lead to selective therapies aimed at reducing this reperfusion injury.