Anti-IL17B monoclonal antibody, clone 7H6

Overexpression of IL17RB is associated with poor prognosis and short survival of the breast cancer patients. IL17RB/IL17B signaling triggers a substantial increase in the cell growth, proliferation and migration through the activation of NF-kappa B as well as the up-regulation of the Bcl-2. In this study we designed carboxymethyl dextran (CMD) Chitosan nanoparticles (ChNPs) to encapsulated IL17RB siRNA and doxorubicin (DOX) as an anticancer drug. Then we investigated the efficiency of the simultaneous delivery of drug/siRNA on viability and gene expression of MDA-MB361 cell lines. Furthermore the efficacy of dual agent nanoparticles to induce apoptosis and inhibit migration of breast cancer cells was assessed by Annexin-V and wound healing assays respectively. Our results showed that DOX-siRNA-CMD-ChNPs had about 114 nm size; with polydispersity index and zeta potential about 0.3 and 10.1 mV respectively. Fourier transform infrared spectroscopy (FTIR) confirmed the formation of DOX-siRNA-CMD-ChNPs complex. In addition IL17RB siRNA had significant effect on DOX-induced cytotoxicity in MDA-MB361 cells. Furthermore treatment with dual agent nanoparticles resulted in a significant silencing of NF-kB and Bcl-2 relative gene expression, apoptosis induction and migration inhibition in MDA-MB361 cells. In conclusion, co-delivery of IL17RB siRNA and DOX can be considered as an effective system for the treatment of breast cancer. (C) 2016 Elsevier Masson SAS. All rights reserved.

Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin concentrations has been stratified by sex. Therefore, considering the increasing interest in incorporating the gender perspective into nutritional genomics, our main aim was to carry out a GWAS on total serum bilirubin concentrations in a Mediterranean population with metabolic syndrome, stratified by sex. Our secondary aim was to explore, as a pilot study, the presence of gene-diet interactions at the GWAS level. We included 430 participants (188 men and 242 women, aged 55-75 years, and with metabolic syndrome) in the PREDIMED Plus-Valencia study. Global and sex-specific GWAS were undertaken to analyze associations and gene-diet interaction on total serum bilirubin. Adherence (low and high) to the Mediterranean diet (MedDiet) was analyzed as the dietary modulator. In the GWAS, we detected more than 55 SNPs associated with serum bilirubin at p < 5 x 10(-8) (GWAS level). The top-ranked were four SNPs (rs4148325 (p = 9.25 x 10(-24)), rs4148324 (p = 9.48 x 10(-24)), rs6742078 (p = 1.29 x 10(-23)), rs887829 (p = 1.39 x 10(-23)), and the rs4148324 (p = 9.48 x 10(-24))) in the UGT1A1 (UDP glucuronosyltransferase family 1 member A1) gene, which replicated previous findings revealing the UGT1A1 as the major locus. In the sex-specific GWAS, the top-ranked SNPs at the GWAS level were similar in men and women (the lead SNP was the rs4148324-UGT1A1 in both men (p = 4.77 x 10(-11)) and women (p = 2.15 x 10(-14)), which shows homogeneous genetic results for the major locus. There was more sex-specific heterogeneity for other minor genes associated at the suggestive level of GWAS significance (p < 1 x 10(-5)). We did not detect any gene-MedDiet interaction at p < 1 x 10(-5) for the major genetic locus, but we detected some gene-MedDiet interactions with other genes at p < 1 x 10(-5), and even at the GWAS level for the IL17B gene (p = 3.14 x 10(-8)). These interaction results, however, should be interpreted with caution due to our small sample size. In conclusion, our study provides new data, with a gender perspective, on genes associated with total serum bilirubin concentrations in men and women, and suggests possible additional modulations by adherence to MedDiet.