F-receptors by reactions of receptor tyrosine Syk Inhibitors kinase, which phosphorylates RSS output receptors. The subsystem has a power that feeds the STS input signal, and includes PI3K/PTEN/AKT and RAF / MEK / ERK signaling pathways and output signals are phosphorylated AKT and ERK STS. This process makes glicht To the properties of the signal response of ovarian cancer cells to compare Similar properties to other cells is obtained by comparing the different cell lines in signaling and signal transduction both systems. We conduct the relationship between the sensitivities of these subsystems and their contribution to the sensitivity of the SN rate applied. We analyze the sensitivity of the output signal to AKT inhibition of HER2 with a calculation model for the signaling and activation modeling PI3K/PTEN/AKT identified mutations in the development of cancer and drug resistance. In particular, we consider: the loss of PTEN activity t, PI3K, AKT mutations, HER2 overexpression of AKT and cytochrome P450 inhibitor overproduction of GSK3 and CK2 kinase phosphorylation of PTEN controlled slow. We use the sensitivity Tsanalyse themechanisms SN of Change in the sensitivity due to the sensitivity to the contact resistance for mutations of activation and action of active ingredients aufzukl Ren.
By in silico and in vitro experiments, we also study the inhibition of the combination of SN to determine: 1 How acquired mutations that prevent the action of the drug and buy Cidofovir escape oncogene dependence to dependence, 2 As and sensitivity to inhibitors of RTK recovery through a combination of drugs with mutations in the activation SN.We examine these questions using the example of the loss of PTEN leads to resistance, and pertuzumab evaluate in silico and in vitro efficacy of inhibition of drug targets upstream and downstream of PTEN pathwaysTo pr gene, the receptor signaling system, RSS, we examined the dose-dependent dependence Independent phosphorylation of the HER2 protein on two external signals, the ligand and drugs and the concentration of HER2 receptors that lines.We vary in different cancer cells, the dose- PACT calculated on the same external signals to the reactions of the RSS and SN Silibinin compare whole. The theoretical and experimental dependencies are PHER2 of the concentration of HRG, pHER2 and pertuzumab, pHER2, are presented in Fig. 2A and B.
The calculation of the dose-response curve showed a switch pHER2 behavior pHER2 signal HRG stimulation: RTK activation from 10% to 100% in a narrow range of concentrations of HRG and our experimental data showed a pHER2 signal S saturation was at 1 nM HRG achieved. The best fit of the dose-response function by pHER2 Hill, which characterizes the slope of this switch, since the transition is a Hill coefficient of n2, indicating cooperativity t in the formation of ligand / receptor complex and HER2/HER3 heterodimerization . The EC50 of the dose-theoretical Dependence obtained is consistent with the experimental EC503 nM. The dose-response to HRG PACT, PACT showed Similar behavior as a switch for pHER2. Maximum activation of AKT signaling narrowrange occurswithin a HRG concentration and the S Saturation is reached at a concentration equal to0.1 nM HRG. Thus k can Both the RSS and SN-S mode HRG Ttigungskonzentration of 1 nM. The dose dependence dependencies.