Anaplastic lymphoma kinase (ALK) inhibitor response in neuroblastoma is highly correlated with ALK mutation status, ALK mRNA and protein levels

Background In pediatric neuroblastoma (NBL), high anaplastic lymphoma kinase (ALK) levels appear to be correlated with an unfavorable prognosis, regardless of ALK mutation status. This suggests a therapeutic role for ALK inhibitors in NBL patients. We examined the correlation between levels of ALK, phosphorylated ALK (pALK) and downstream signaling proteins and response to ALK inhibition in a large panel of both ALK mutated and wild type (WT) NBL cell lines. Methods We measured protein levels by western blot and ALK inhibitor sensitivity (TAE684) by viability assays in 19 NBL cell lines of which 6 had a point mutation and 4 an amplification of the ALK gene. Results ALK 220 kDa (p=0.01) and ALK 140 kDa (p= 0.03) protein levels were higher in ALK mutant than WT cell lines. Response to ALK inhibition was significantly correlated with ALK protein levels (p<0.01). ALK mutant cell lines (n=4) were 14,9 fold (p<0,01) more sensitive to ALK inhibition than eight WT cell lines. Conclusion NBL cell lines often express ALK at high levels and are responsive to ALK inhibitors. Mutated cell lines express ALK at higher levels, which may define their superior response to ALK inhibition

The Receptor Tyrosine Kinase Alk Controls Neurofibromin Functions in Drosophila Growth and Learning

Anaplastic Lymphoma Kinase (Alk) is a Receptor Tyrosine Kinase (RTK) activated in several cancers, but with largely unknown physiological functions. We report two unexpected roles for the Drosophila ortholog dAlk, in body size determination and associative learning. Remarkably, reducing neuronal dAlk activity increased body size and enhanced associative learning, suggesting that its activation is inhibitory in both processes. Consistently, dAlk activation reduced body size and caused learning deficits resembling phenotypes of null mutations in dNf1, the Ras GTPase Activating Protein-encoding conserved ortholog of the Neurofibromatosis type 1 (NF1) disease gene. We show that dAlk and dNf1 co-localize extensively and interact functionally in the nervous system. Importantly, genetic or pharmacological inhibition of dAlk rescued the reduced body size, adult learning deficits, and Extracellular-Regulated-Kinase (ERK) overactivation dNf1 mutant phenotypes. These results identify dAlk as an upstream activator of dNf1-regulated Ras signaling responsible for several dNf1 defects, and they implicate human Alk as a potential therapeutic target in NF1

Anaplastic Lymphoma Kinase Is Required for Neurogenesis in the Developing Central Nervous System of Zebrafish

10.1371/journal.pone.0063757PLoS ONE85

New hybrid material based on silica-immobilised conjugated beta-ketoenol-bipyridine receptor and its excellent Cu(II) adsorption capacity

A new hybrid material based adsorbent for the efficient elimination of Cu(II) was synthesized by the immobilization of a new conjugated b-ketoenol-bipyridine ligand receptor onto a silica matrix. The analysis of its surface chemistry was evaluated using a set of suitable techniques. Adsorption studies highlight its surface properties for the excellent removal of Cu2+ (131.82 mg g1) from aqueous solutions using FAAS. The effect of various parameters, such as pH, initial metal concentration, temperature, competitive extraction, thermodynamics and kinetics, on the adsorption of several heavy metals was investigated via metal extraction from real water samples. The adsorption efficiency increases with an increase in pH and follows pseudo-second-order kinetics. Adsorption is rapid, as evidenced by the achievement of equilibrium within 25 min. Adsorption equilibrium data were well fitted to the Langmuir isotherm model and the maximum monolayer adsorption capacity for Cu2+, Zn2+, Cd2+, and Pb2+ was 131.82, 110, 90.75 and 79.71 mg g1, respectively. The removal of metals onto the new adsorbent is endothermic and spontaneous in nature. The adsorbent presents high selectivity for Cu2+, in competitive mode, compared to other metals and recent literature reports

New crosslinked cast films based on poly(vinyl alcohol): Preparation and physico-chemical properties

In this paper, we propose a green route to prepare insoluble poly(vinyl alcohol) (PVOH) cast films with potential application as antimicrobial packaging. First PVOH films were cast from different aqueous solutions and analyzed by Differential Scanning Calorimetry (DSC) and Dynamic Mechanical Analysis (DMA) to determine their physical properties under two storage conditions. In order to obtain insoluble films, PVOH was then crosslinked by citric acid (CTR) as confirmed by Nuclear Magnetic Resonance (NMR) analyses. The crosslinking reaction parameters (curing time, crosslinker content) were studied by comparing the characteristics of PVOH/CTR films, such as free COOH content and glass transition temperature (Tg) value, as well as the impact of the crosslinking reaction on mechanical properties. It was found that for 40 and 10 wt% CTR contents, 120 and 40 min of crosslinking times were necessary to bind all CTR respectively. Brittle films were obtained for 40 wt% CTR whereas 10 wt% CTR content led to ductile films. Finally, films containing hydroxypropyl-β-cyclodextrin (HPβCD), chosen as a potential vector of antimicrobial agent, were prepared. The obtained results show that the incorporation of HPβCD in the PVOH matrix does not mainly influence the physical and mechanical properties of the films

Self-stratifying coatings: A review

International audienc

An inorganic-organic hybrid material made of a silica-immobilized schiffbase receptor and its preliminary use in heavy metal removal

A novel and excellent host for heavy metals was synthesized by chemical immobilization of a (E)-4-((pyridin-2-yl-methylene)amino)phenol Schiff base receptor onto silica particles. The new hybrid material (SPSB) was analyzed and evaluated by elemental analysis, FT-IR spectroscopy, solid-state 13C NMR, scanning electron microscopy, BET surface area and BJH analyses. The surface exhibits good thermal stability determined by thermogravimetry and good chemical stability examined in various acidic and buffer solutions (pH 1–7). The coordination ability of SPSB was found to be most efficient in the pH range 6.5–8 for Hg2+, Cd2+, Pb2+ and Zn2+. Alkali coexisting ions did not interfere with separation and determination. The adsorbent can be regenerated at ease without destruction. Heavy metal removal performance (99 mg g−1) was found to be higher compared to previous literature reports

Self-stratifying epoxy/silicone coatings

International audienc

One pot flame retardant and weathering resistant coatings for plastics: a novel approach

International audienc

RECIFE : modèles et outils pour l'analyse de la capacité ferroviaire

International audienc