Inhibition of triple negative breast cancer-associated inflammation and progression by N- acylethanolamine acid amide hydrolase (NAAA).

Triple-negative breast cancer (TNBC) is associated with high mortality due to the high expression of pro-inflammatory cytokines and lack of targeted therapies. N-acylethanolamine acid amidase (NAAA) is an N-terminal cysteine hydrolase that promotes inflammatory responses through the deactivation of Palmitoylethanolamide (PEA), an endogenous bioactive lipid mediator. Here, we examined NAAA expression in TNBC cells (MDA-MB-231 and MDA-MB-BrM2 cells) and the effects of NAAA inhibition on TNBC tumor growth, using a selective NAAA inhibitor AM11095 (IC = 20 nM).

Inhibition of triple negative breast cancer-associated inflammation, tumor growth and brain colonization by targeting monoacylglycerol lipase.

While the prevalence of breast cancer metastasis in the brain is significantly higher in triple negative breast cancers (TNBCs), there is a lack of novel and/or improved therapies for these patients. Monoacylglycerol lipase (MAGL) is a hydrolase involved in lipid metabolism that catalyzes the degradation of 2-arachidonoylglycerol (2-AG) linked to generation of pro- and anti-inflammatory molecules. Here, we targeted MAGL in TNBCs, using a potent carbamate-based inhibitor AM9928 (hMAGL IC = 9 nM) with prolonged pharmacodynamic effects (46 h of target residence time).

Use of behavioural contracting to increase adherence with rehabilitation treatments on an inpatient brain injury unit: a case report.

Background: This systematic, single-subject case study presents a 37-year old male with a severe traumatic brain injury who exhibited agitation and poor adherence with rehabilitation treatment on an inpatient traumatic brain injury unit. Attempts to address presumed awareness issues were unsuccessful. Medication trials also failed to produce an observable response in the patient's behaviour.

Comparison of two T-state structures of regulatory-chain mutants of Escherichia coli aspartate transcarbamoylase suggests that His20 and Asp19 modulate the response to heterotropic effectors.

Asp19 and His20 of Escherichia coli aspartate transcarbamoylase (EC 2.1.3.