Addition ally, the combination of the inhibition of EGFR phos phorylation and the inhibition of binding of EGFR to Shc produced a synergistic inhibitory effect on EGFR signaling. promotion info Therefore, Mig6 could be one of the critical factors to explain gefitinib sensitivity at cellular level. We constructed the model by referring to the earlier studies on Mig6 functions. However, the model could be modified and improved when novel mechan ism of Mig6 in the regulation of EGFR or new regula tors associated with the EGFR L858R mutation are identified by further studies. Our results shown in Figures 2 and 3 are consistent with a previously published report that EGFR with the L858R mutation did not have stronger EGFR phosphor ylation upon EGF stimulation when compared to the wild type EGFR in H1299 cells.
On the other Inhibitors,Modulators,Libraries hand, Guha et al and Yun et al observed significantly high phosphorylation Inhibitors,Modulators,Libraries of the L858R mutated EGFR com pared with wild type EGFR expressed in HBEC cells and Sf9 cells. This inconsistency among cell types may be explained by the relative levels of Mig6, which is highly expressed when EGFR kinase is in an active state. Conclusion Overall, the analysis presented in this paper allows understanding of the impacts of cancer related abnorm alities on the EGFR signaling pathway. Also, we demon strate the feasibility of using computational models to predict one of the determinants for the evaluation of drug sensitivities. Despite the fact that a new drug may help prevent the deaths of thousands of patients, there are many instances where the patients become severely ill or die because of serious unwanted side effects.
Hence, in prescribing medications appropriate for indivi dual patients, there is a clear Inhibitors,Modulators,Libraries need for guidance in pre dicting side effects and drug sensitivity. It would be no exaggeration to say that the side effects could not be predicted in advance, since signaling pathways are very complex. We believe that in part such guidance can be predicted by computational modeling of appropriate sig naling pathways. Background The advancement of high throughput data generation has ushered a new era of omic sciences. Whole cell measurements can elucidate the genome sequence as well as detect mRNA, proteins, Inhibitors,Modulators,Libraries and small metabolites under a specific condition. Though these methods provide a broad coverage in determining cellular activities, little integrated functional analysis has been performed to date.
Genome scale network reconstructions are a Inhibitors,Modulators,Libraries common denominator for computational analysis in systems biol ogy as well as an integrative platform for experimental data analysis. There are several applications of reconstructions including 1 contextualization of high throughput data, 2 directing hypothesis driven discov ery, and 3 network property free overnight delivery discovery. Network reconstruction involves elucidating all the known bio chemical transformations in a particular cell or organ ism and formally organizing them in a biochemically consistent format.