Expression of the tumor suppressor miR-34a was reduced in HN5-ER LY294002 ic50 cells and increasing its expression abrogated Axl expression and reversed erlotinib resistance. Finally, analysis of 302 HNC patients revealed that high tumor Axl mRNA expression

was associated with poorer survival (HR = 1.66, P = 0.007). In summary, our results identify Axl as a key mediator of acquired erlotinib resistance in HNC and suggest that therapeutic inhibition of Axl by small molecule drugs or specific miRNAs might overcome anti-EGFR therapy resistance. (C) 2013 AACR.”
“Anthracycline antibiotics such as daunomycin (Dauno) and doxorubicin (Dox) are well-known clinically used cancer chemotherapeutics, which, among other mechanisms, bind to DNA, thereby triggering a cascade of biological responses leading to cell death. However, anthracyclines are cardiotoxic, and drug resistance

develops rapidly, thus limiting their clinical use. We report here the synthesis and DNA-binding affinity of a novel class of functional anthracycline mimetics consisting of an aromatic moiety linked to a carbohydrate (1-12). In the targets, the aromatic core consists of a 2-phenylbenzo[b]furan-3-yl, DMH1 purchase 2-phenylbenzo[b]thiophen-3-yl, 1-tosyl-2-phenylindol-3-yl, or 2-phenylindol-3-yl group that is bound to one of three aminosugars (daunosamine, acosamine, or 4-amino-2,3,4,6-tetradeoxy-alpha-L-hexopyranoside) via a propargyl linker. The DNA binding affinity of these twelve compounds has been evaluated by using both direct and indirect fluorescence measurements. Compared to Dauno and Dox, the DNA binding affinity of these analogues is weaker. However, both aromatic and aminosugar motifs are critical to DNA binding, with more in. uence coming from the structural features of the aromatic portion.”
“Lysergic acid diethylamide (LSD) is a potent hallucinogenic drug that strongly affects animal and human behavior. Although adult zebrafish (Danio rerio) are emerging as a promising neurobehavioral selleck products model, the effects of LSD on zebrafish have not been investigated previously. Several behavioral paradigms

(the novel tank, observation cylinder, light-dark box, open field, T-maze, social preference and shoaling tests), as well as modern video-tracking tools and whole-body cortisol assay were used to characterize the effects of acute LSD in zebrafish. While lower doses (5-100 mu g/L) did not affect zebrafish behavior, 250 mu g/L LSD increased top dwelling and reduced freezing in the novel tank and observation cylinder tests, also affecting spatiotemporal patterns of activity (as assessed by 3D reconstruction of zebrafish traces and ethograms). LSD evoked mild thigmotaxis in the open field test, increased light behavior in the light-dark test, reduced the number of arm entries and freezing in the T-maze and social preference test, without affecting social preference.