High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER breast cancer.

CDK4/6 inhibitors combined with endocrine therapy have demonstrated higher antitumor activity than endocrine therapy alone for the treatment of advanced estrogen receptor-positive breast cancer. Some of these tumors are de novo resistant to CDK4/6 inhibitors and others develop acquired resistance. Here, we show that p16 overexpression is associated with reduced antitumor activity of CDK4/6 inhibitors in patient-derived xenografts (n = 37) and estrogen receptor-positive breast cancer cell lines, as well as reduced response of early and advanced breast cancer patients to CDK4/6 inhibitors (n = 89).

Cancer resistance to treatment and antiresistance tools offered by multimodal multifunctional nanoparticles.

Chemotherapeutic agents have limited efficacy and resistance to them limits today and will limit tomorrow our capabilities of cure. Resistance to treatment with anticancer drugs results from a variety of factors including individual variations in patients and somatic cell genetic differences in tumours. In front of this, multimodality has appeared as a promising strategy to overcome resistance.

Optimization of pre-emptive isolations in a polyvalent ICU through implementation of an intervention strategy.

Background: Pre-emptive isolation refers to the application of contact precaution measures in patients with strongly suspected colonization by multiresistant bacteria.

Objective: To assess the impact of an intervention program involving the implementation of a consensus-based protocol of pre-emptive isolation (CPPI) on admission to a polyvalent ICU of a general hospital.

Methods: A comparative analysis of 2 patient cohorts was made: a historical cohort including patients in which pre-emptive isolation was established according to physician criterion prior to starting CPPI (from January 2010 to February 2011), and a prospective cohort including patients in which CPPI was implemented (from March to November 2011).

Kinetic resolution of (R,S)-2-butanol using enzymatic synthesis of esters.

Kinetic resolution of (R,S)-2-butanol using enzymatic synthesis of esters has been studied. (R,S)-2-Butanol is commonly found as a racemic mixture, and the products of its esterification are racemic mixtures too. This work is of great significance in the field of the enzymatic kinetic resolution due to the little information found in literature about the resolution of (R,S)-2-butanol as pure compound.

Adsorption and diffusion parameters of methane and nitrogen on microwave-synthesized ETS-4.

ETS-4 is a titanium silicate developed by Engelhard Corporation, which possesses a small pore network, the size of which can be reduced by heat treatment to improve its kinetic selectivity in nitrogen/methane separation. Most of the reported studies about ETS-4 employ crystals synthesized with conventional heating. Furthermore, information available on the adsorption properties of ETS-4, especially the diffusion properties, is scarce.

Presynaptic modulation of K+-evoked [3H]dopamine release in striatal and frontal cortical synaptosomes of normotensive and spontaneous-hypertensive rats.

Regional differences in presynaptic [3H]dopamine ([3H]DA) release and its modulation by D2 DA-receptors between the frontal cortex and striatum obtained from Wystar-Kyoto (WKY) and spontaneous-hypertensive rats (SHR) have been evaluated using superfused synaptosomes. Synaptosomal tritium content was significantly lower in the frontal cortex than in the striatum in both SHR and WKY (approximately 45% and 48%, respectively), but no differences in tritium content were obtained between strains. However, the 15 mM K+-evoked [3H]DA overflow was lower in the SHR as compared to WKY rats in both brain regions (striatum approximately 23%, frontal cortex approximately 21).

Superfusion of synaptosomes to study presynaptic mechanisms involved in neurotransmitter release from rat brain.

Neurotransmitter release, as the primary way for neuron signaling, represents the target of a staggering number of studies in order to understand complex neural functions. The corpus striatum is a brain area especially rich in neurotransmitters where cholinergic neurons are supposed to play an associative role between different neuronal types, and therefore their activity is modulated by multiple neurotransmitter systems [Trends Neurosci. 17 (1994) 228; Trends Neurosci.

Differential effect of quinpirole and 7-OH-DPAT on the spontaneous [(3)H]-dopamine efflux from rat striatal synaptosomes.

The effect of quinpirole and 7-OH-DAPT, two D(2)-like agonists, were examined using superfused rat striatal synaptosomes to study the autoregulation of spontaneous [(3)H]-dopamine ([(3)H]-DA) release. Basal [(3)H]-DA efflux was Ca(2+)-dependent by approximately 45% and was inhibited by cadmium 10 microM by 24%. Quinpirole (1 nM to 3 microM) inhibited spontaneous [(3)H]-DA efflux in a concentration-dependent manner (pEC(50) = 7.

Microcomputed tomography of kidneys following chronic bile duct ligation.

Background: In hepatic cirrhosis, renal sodium and water retention can occur prior to decreases in renal blood flow (RBF). This may be explained in part by redistribution of the intrarenal microcirculation toward the juxtamedullary nephrons. To appreciate this three-dimensional spatial redistribution better, we examined the intrarenal microcirculatory changes using microcomputed tomography (micro-CT) in rats subjected to chronic bile duct ligation (CBDL).

Three-dimensional microcomputed tomography of renal vasculature in rats.

Current microscopic methods to view renal microvasculature reveal only a very limited portion of the total renal volume. Identification of connectivity for postglomerular vessels in the cortex and the medulla during functional states related to changes in sodium excretion will help better to understand the coupling of renal vasculature to tubular function. The purpose of this study was to investigate the possibility of visualizing the continuity of pre- and postglomerular vasculature using three-dimensional micro-computed tomography (micro-CT).

D2 dopamine receptors and modulation of spontaneous acetylcholine (ACh) release from rat striatal synaptosomes.

1. The effect of two D3/2 dopamine receptor agonists, LY-171555 (quinpirole) and 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) on spontaneous [3H]-acetylcholine ([3H]-ACh) release were investigated in rat striatal synaptosomes. 2.

Effect of 1-aminocyclopropanecarboxylic acid on N-methyl-D-aspartate-stimulated [3H]-noradrenaline release in rat hippocampal synaptosomes.

1. The effect of 1-aminocyclopropanecarboxylic acid (ACPC), a partial agonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor complex that exhibits neuroprotective, anxiolytic and antidepressant-like actions, was investigated in a functional assay for presynaptic NMDA receptors. 2.

Differential contribution of L- and N-type calcium channels on rat hippocampal acetylcholine release.

Bay K 8644, nimodipine and omega-conotoxin GVIA (omega-CgTx) were used to study the different contribution of voltage-sensitive calcium channels (VSCC) to [3H]acetylcholine ([[3H]ACh) release in rat hippocampal synaptosomes. In our experimental conditions, the percentage of calcium-dependent ACh release was approximately 80%. Nimodipine (0.