MKP-1/2 ELISA Kit

The RAS-RAF-MEK-ERK cascade is a key oncogenic signal transduction pathway activated in many types of tumours in humans. Sorafenib, the medical treatment of reference against advanced stages of hepatocellular carcinoma (HCC), inhibits the RAF-MEK-ERK cascade in HCC cells. Based on previous studies suggesting that this cascade is an important target of sorafenib in HCC cells, we explored its regulation using mathematical modelling and ordinary differential equations. We analysed the dynamic regulation of the core components of the RAF-MEK-ERK cascade in three human HCC cell lines (Huh7, Hep3B and PLC/PRF5) with heterogeneous responses to sorafenib. In silica predictions derived from our mathematical model suggested that the disappearance of phosphorylated MEK and ERIC proteins catalysed by cellular phosphatases is an essential mechanism underlying the anti-ERIC efficacy of sorafenib in HCC cells. This prediction was experimentally validated using specific inhibitors of the phosphatases PP2A (Protein Phosphatase 2A) and DUSP1/6 (Dual-specificity phosphatases 1/6). These findings highlight an unexpected mode of action of sorafenib on the kinome of HCC cells, and open new perspectives regarding the therapeutic targeting of the RAF-MEK-ERK cascade in this context. (C) 2017 Elsevier B.V. All rights reserved.

Background Roasted coffee beans are broadly consumed in nearly all classes of the population. 2,3-Butanedione is a food flavor that causes obstructive bronchiolitis in microwave popcorn manufacturing workers. It can be naturally produced when coffee is roasted. Objective To determine effects of 2,3-butanedione (diacetyl) and 2,3-pentanedione on workers' health during the coffee roasting process, we performed a toxicogenomics study for differentially expressed genes in lung cells after exposure to the two chemicals. Results Gene selection was performed by clustering, gene ontology/pathway, and data mining using microarray data. Target microRNAs and genes were selected based on the expression of microRNAs and correlation analysis of genes and microRNAs. As a result of expression analysis of target gene miRNAs affected by the two chemicals, it was evaluated that Fosl1, Rb1, Aspn, Dusp1, Rnf19b, Jun, and Hbegf were over-regulated by targeting down-regulated miRNAs mutated by two chemicals. Using OMIM database and KEGG pathway, we found that Terc and Bmpr2 were two changed genes by matching with the KEGG disease pathway database. Conclusion Dosage, duration, exposure, and extrapolations are necessary to reflect effects of diacetyl and 2,3-pentanedione on workers in the coffee roasting process. This study focuses on early biochemical changes, mechanisms, and early biomarker discovery when normal lung cells are exposed to these two chemicals.