Ersible EGFR inhibitor were 324 674 effects of EGF adversely quickly Chtigt. Not only phosphorylated EGFR levels, but also the downstream Rtige ERK and AKT BCR-ABL Signaling Pathway p p levels were dose-dependent on a fast Ngigen way located in very low concentrations. In both cell lines maintained pY 1068 EGFR, ERK and AKT p p-levels in the presence of the inhibitor at concentrations ranging from 1 to 3 EGFR/HER2/HER4 LM, the Best Account a Change of about 100 times in drug development sensibility t, which corresponded to the observations of the MTT assay. For the inhibitor GW583340, a treatment almost micromolar YOUR BIDDING inhibits the phosphorylation of EGFR, but not its downstream signaling effector Akt in both cell lines.
Completely for AG1478, the maximum concentration of 3 SM YOUR BIDDING inhibited phosphorylation of EGFR, but both ERK and AKT phosphorylation maintained in high concentrations in the two cells. Taken together, these results showed that, contrary to the general TKI, the irreversible EGFR inhibitors 324 674 k Can effectively and precisely regulate the EGFR signaling pathway is blocked EGFR phosphorylation and downstream events of his work in very low concentrations. 4th Discussion EGFR is the cell surface Chen-receptor of the family of the epidermal growth factor. After activation by its ligand, erf EGFR leads a transition from an inactive monomer, a compound homodimer and this dimerization is a prerequisite for the start of the kinase activity of t. Consequently, EGFR autophosphorylation occurs, triggering sen A subsequent series of downstream events, including normal MAPK, Akt and activation of the JNK pathway.
The activation of these pathways is closely linked to tumor proliferation, migration, angiogenesis, stromal invasion and resistance to apoptosis linked. Blocking the tyrosine kinase activity of t of the EGFR optimal strategy in cancer therapy. Discoveries led to the development and approval of several EGFR inhibitors such as, for example rpern inhibitors of therapeutic monoclonal antibodies. These therapeutic antique block Ligandenbindungsdom the body Ne of extracellular Ren, The binding of signaling molecules, which then prevents activating k Nnte tyrosine kinase. For the treatment of b Sartigen human tumors, is another type of tyrosine kinase inhibitor is a small molecular compound that alters the intracellular Ren tyrosine kinase Dom ne of the receptor target.
Obviously there are big differences between the s mode of action of anti-EGFR mAbs and EGFR-TKI. In general, the antique Body-dependent Independent Cytotoxicity t, the ideal group of patients receive anti-EGFR therapies, therapeutic Antique Body are those in which EGFR on the surface Surface-expressed by tumor cells, but little or no expression in the serum. In contrast, patients who are well to therapy with EGFR-TKI-set, such as EGFR phosphorylation with proliferation of cancer cells and metastasis. Therefore, the involvement of EGFR activation by ITC is a promising strategy for new and selective anticancer therapies. Use as a research model of the human lines of C Lon adenocarcinoma HT29 and SW480, with their respective expression patterns of EGFR, we examined and the effect of the inhibitor in comparison 324,674 irreversible EGFR, EGFR inhibitor AG1478 classical reversible, Dual EGFR / HER-2 inhibitor, GW583340 and pan EGFR / deregulated cell growth independent ngig