LXR-inverse agonism stimulates immune-mediated tumor destruction by enhancing CD8 T-cell activity in triple negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype that is untreatable with hormonal or HER2-targeted therapies and is also typically unresponsive to checkpoint-blockade immunotherapy. Within the tumor microenvironment dysregulated immune cell metabolism has emerged as a key mechanism of tumor immune-evasion. We have discovered that the Liver-X-Receptors (LXRα and LXRβ), nuclear receptors known to regulate lipid metabolism and tumor-immune interaction, are highly activated in TNBC tumor associated myeloid cells.

Perampanel in routine clinical use across Europe: Pooled, multicenter, observational data.

Objective: To pool observational data on the routine use of perampanel to obtain information on real-world outcomes and data in populations typically underrepresented in clinical trials.

Methods: Individual-level data of people with epilepsy treated with perampanel at 45 European centers were merged into a single dataset. Prespecified outcomes were: 1-year retention rate, 1-year seizure freedom rate (duration ≥6 months), and incidence of treatment-emergent adverse events (TEAEs).

Rev-Erb co-regulates muscle regeneration via tethered interaction with the NF-Y cistrome.

Objective: The loss of skeletal muscle mass and strength are a central feature of traumatic injury and degenerative myopathies. Unfortunately, pharmacological interventions typically fail to stem the long-term decline in quality of life. Reduced Rev-Erb-mediated gene suppression in cultured C2C12 myoblasts has been shown to stimulate myoblast differentiation.

Incidental findings in pediatric research.

The approach to incidental research findings in children emerges by considering the child-parent relationship and balancing divergent interests and preferences. Incidental findings with clear and proximate clinical importance should be disclosed to both. We recommend that particularly sensitive or private information (e.

Effects of GCP-II inhibition on responses of dorsal horn neurones after inflammation and neuropathy: an electrophysiological study in the rat.

N-Acetylaspartylglutamate (NAAG) is a peptide neurotransmitter present in the brain and spinal cord. It is hydrolysed by glutamate carboxypeptidase II (GCPII); thus, the GCP-II inhibitor 2-[phosphono-methyl]-pentanedioic acid (2-PMPA) protects endogenous NAAG from degradation, allowing its effects to be studied in vivo. We recorded the effect of spinal 2-PMPA (50-1000 microg) on the electrical-evoked activity of dorsal horn neurones in normal and carrageenan-inflamed animals, and in the spinal nerve ligation (SNL) model of neuropathy and sham-operated animals.