The association of N-palmitoylethanolamine with the FAAH inhibitor URB597 impairs melanoma growth through a supra-additive action

<p>Abstract</p> <p>Background</p> <p>The incidence of melanoma is considerably increasing worldwide. Frequent failing of classical treatments led to development of novel therapeutic strategies aiming at managing advanced forms of this skin cancer. Additionally, the implication of the endocannabinoid system in malignancy is actively investigated.</p> <p>Methods</p> <p>We investigated the cytotoxicity of endocannabinoids and their hydrolysis inhibitors on the murine B16 melanoma cell line using a MTT test. Enzyme and receptor expression was measured by RT-PCR and enzymatic degradation of endocannabinoids using radiolabeled substrates. Cell death was assessed by Annexin-V/Propidium iodine staining. Tumors were induced in C57BL/6 mice by s.c. flank injection of B16 melanoma cells. Mice were injected i.p. for six days with vehicle or treatment, and tumor size was measured each day and weighted at the end of the treatment. Haematoxylin-Eosin staining and TUNEL assay were performed to quantify necrosis and apoptosis in the tumor and endocannabinoid levels were quantified by HPLC-MS. Tube formation assay and CD31 immunostaining were used to evaluate the antiangiogenic effects of the treatments.</p> <p>Results</p> <p>The <it>N</it>-arachidonoylethanolamine (anandamide, AEA), 2-arachidonoylglycerol and <it>N</it>- palmitoylethanolamine (PEA) reduced viability of B16 cells. The association of PEA with the fatty acid amide hydrolase (FAAH) inhibitor URB597 considerably reduced cell viability consequently to an inhibition of PEA hydrolysis and an increase of PEA levels. The increase of cell death observed with this combination of molecules was confirmed in vivo where only co-treatment with both PEA and URB597 led to decreased melanoma progression. The antiproliferative action of the treatment was associated with an elevation of PEA levels and larger necrotic regions in the tumor.</p> <p>Conclusions</p> <p>This study suggests the interest of targeting the endocannabinoid system in the management of skin cancer and underlines the advantage of associating endocannabinoids with enzymatic hydrolysis inhibitors. This may contribute to the improvement of long-term palliation or cure of melanoma.</p

Validation of an Adapted French Form of the Career Adapt-Abilities Scale in four Francophone Countries

This study presents the validation of a French version of the Career Adapt-Abilities Scale in four Francophone countries. The aim was to re-analyze the item selection and then compare this newly developed French-language form with the international form 2.0. Exploratory factor analysis was used as a tool for item selection, and confirmatory factor analysis (CFA) verified the structure of the CAAS French-language form. Measurement equivalence across the four countries was tested using multi-group CFA. Adults and adolescents (N=1,707) participated from Switzerland, Belgium, Luxembourg, and France. Items chosen for the final version of the CAAS French-language form are different to those in the CAAS international form 2.0 and provide an improvement in terms of reliability. The factor structure is replicable across country, age, and gender. Strong evidence for metric invariance and partial evidence for scalar invariance of the CAAS French-language form across countries is given. The CAAS French-language and CAAS international form 2.0 can be used in a combined form of 31 items. The CAAS French-language form will certainly be interesting for practitioners using interventions based on the life design paradigm or aiming at increasing career adapt-ability