Anti-pan-AKT polyclonal antibody

The influence of chia (Salvia hispanica L.) flour and oil on glucose metabolism (GM) in insulin resistant (IR) Wistar rats and the effect of chia hydrolyzed phenolics extract (CHPE) on GM in IR HepG2 cells were evaluated. In vivo study: animals were divided into four groups: AIN-93M, high-fat and high-fructose (HFHF), HFHF with chia flour (14.7%) or chia oil (4%). In vitro study: IR HepG2 cells were treated with CHPE (80 ppm). In vivo, chia flour and oil reduced adiposity and increased AMPK mRNA. Chia oil improved glucose tolerance, increased AKT1[pS473] protein level, mRNA of insulin receptor, FOXO1 and glycolysis enzymes. In vitro, CHPE decreased gluconeogenesis enzymes mRNA. Chia flour and oil decreased adiposity, but only chia oil was able to improve glucose tolerance and restore energy fuel system in liver of rats fed HFHF diet. CHPE decreased mRNA levels of gluconeogenesis enzymes.

Head and neck squamous cell carcinomas (HNSCCs) frequently harbor alterations in the PI3K/AKT/mTOR signaling axis, particularly in the PIK3CA gene. PI3K-targeted agents have therefore gained considerable preclinical and clinical interest as emerging therapies for HNSCC. Identification of predictive biomarkers of response would advance the clinical application of PI3K-targeted drugs for patients, in order to achieve maximal benefit. To date, studies of drug biomarkers have largely focused on screening cell lines, with much more limited in vivo testing, usually only as validation. This approach has rarely enabled accurate predictions of clinical efficacy. Recently, clinical trials of PDX models (PDX clinical trials) have been introduced as a preclinical approach to interrogate interpatient response heterogeneity. Already, PDX clinical trial responses have been demonstrated to correlate closely with patient outcomes. Here, using both an HNSCC specific, 28-cell line panel and a PDX clinical trial of 80 xenografts derived from 20 unique HNSCC tumors, we systematically examine patterns of response to PI3K inhibition in HNSCC. We find EGFR, AKT1 and CSMD1 copy number aberrations, but not PIK3CA mutations, to be associated with responsiveness to PI3K-targeted drugs. Further, we reveal PI3K alpha inhibition to be almost globally tumoristatic in HNSCC xenografts regardless of PIK3CA mutational status, emphasizing its potential as a stabilizing neoadjuvant therapy for HNSCC patients.