Akt2 (Phospho-Ser474) ELISA Kit

New polymeric biomaterials and nanomedicines targeting cancer cells are highly required because of their potential clinical applications. Gene therapy enjoys high popularity as advanced therapy due to its high specificity; however, clinical translation is scarce because the lack of efficient and safe delivery methods. Here we address the design and development of a new nanosized targeting system consisting on Cetuximab-conjugated micelles (PM) of Pluronic (R) F127 (F127) and Gelatin for efficient delivery of small interfering RNA (siRNA) into epidermal growth factor receptor (EGFR) overexpressing breast cancer cells. Chemical modification by carboxylation of F127 is required prior to conjugation with Cetuximab and PM development. PM presenting appropriate physicochemical features (< 40nm) and an efficiently modified surface with Cetuximab were generated. Gelatin garnished the system with the cationic groups (zeta = +30mV) essential for the complexation of siRNA, allowing high entrapment efficiency, and an efficient gene silencing of 70% with low cytotoxicity and proper hemocompatibility. Cetuximab-functionalized PM showed higher rate of cell internalization in EGFR expressing cells than non-functionalized PM, making them a new promising tool for targeted breast cancer treatment.

Our study was to explore the potential role of miRNA-200b in modulating tumorigenesis in the model of ulcerative colitis-related colorectal cancer (UCRCC) and, further, to decipher the underlying mechanisms associated with this effect. In this study, we examined a greater number of polyps or adenomas, a higher grade of epithelial dysplasia accompanied with a decrease 'in survival ratio in azoxymethane (AOM)/dextran sulfate sodium (DSS) model mice compared to mice treated with over-expressed miRNA-200b. Surprisingly, enforced miRNA-200b expression significantly suppressed AOM/DSS-induced up-regulation of oncologic markers including A-catenin and CD133. Independent of this, treatment with miRNA-200b obviously attenuated inflammatory responses, as indicated by down-regulating tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-alpha) and blockade of AKT2-mediated NF-kappa B/IL-6/STAT3 signaling pathway. Furthermore, a simultaneous shift in epithelial-mesenchymal transition (EMT) markers such as E-cadherin and N-cadherin were observed to be increased and decreased, respectively. Coupled with the associated influence of over-expressed miRNA-200b were change in colorectal cell morphology shown by Transmission electron microscope (TEM) and a decrease in expression of rho-kinase2 (ROCK2) together with AKT2 phosphorylation (p-AKT2). Moreover, mice which were transfected with negative control of miRNA-200b possessed results that were in line with that obtained from AOM/DSS model mice. Additionally, we demonstrated that the 3'untranslated region (UTR) of AKT2 was a direct target of miRNA-200b through bioinformatics analysis and dual-luciferase assay. Collectively, these findings suggest that miRNA-200b's contribution to tumor-suppressing program was correlated with EMT and inflammatory responses in a AKT2-dependent manner.