The activity t is the use of TKI 3-Methyladenine therapy is very effective in these tumors, because the mutant kinase hEGFR Dom ne are directly involved in tumor initiation, cell survival and maintenance of tumors. Cetuximab is a humanized monoclonal antibody Body be edited with the binding of EGF or other ligands to the extracellular Re cathedral Ne of EGFR st Ren. To determine the efficacy of cetuximab monotherapy in an in vivo model, we treated Mice injected intraperitoneally with bitransgenic tumor with 1.0 mg of cetuximab every other day. After 1 week of treatment, they underwent Mice were re-imaged and sacrificed for histological analysis. Targeting of cetuximab in lung tumors entered Born hEGFR of kinase-Dom Ne mutant expression was positive by fluorescence immunostaining Staining with antibodies Rpern against human IgG-FITC compared with negative F Staining in tumors treated with placebo best CONFIRMS. In contrast to erlotinib-treated or treated HKI 272 M Mice was measured by the treatment with cetuximab is less effective than erlotinib in the MRI imaging after 1 week of treatment. Histological analysis of lungs from M Mice treated with erlotinib or HKI best 272 for 1 week Preferential dramatic reduction in tumor burden in the imaging analysis seen. In addition, treated, as opposed to the group with cetuximab for 1 week, lungs treated with erlotinib or HKI 272 v Llig normal and microscopically Similar in the M Mice observed after withdrawal of doxycycline. In areas likely sentieren repr Remnants of tumors with erlotinib or HKI 272, a significantly lower number of Ki-67 positive cells were visible tumors were treated in comparison to M Mice cetuximab. TUNEL positive F Staining was also featured in areas residual tumor, which suggests that the treatment are connected by either erlotinib or HKI 272 resolution and high results in the tumor with an apoptotic process.
In contrast, tumors treated with cetuximab receive for 1 week pathological characteristics Resemble those of untreated animals with high Ki-67-F Staining and TUNEL-F Low coloration. consistent with these results, reduced treatment with erlotinib or HKI 272 for 1 week, both total EGFR and EGFR activation in the lung similar as to the distance observed by doxycycline, w While the effects of 1 week after treatment with cetuximab on EGFR and total assets were much smaller. Thus, these data indicate that inhibition of EGFR leads to rapid tumor regression pharmacologically effective with decreased proliferation and increased tumor Hte associated apoptosis of tumor cells. Than 1 week of treatment with cetuximab was not as effective as erlotinib or HKI 272, we have attempted to determine the relative efficacy of these agents for long-term treatment. For this purpose, we performed the treatment using either erlotinib or cetuximab for 4 weeks. Interestingly, after 2 weeks of treatment with cetuximab, we began a pc monitor Rkere decrease in tumor mass, and after 4-w Weeks of treatment one allm Hliche narrowing of 94% 6 4% of the tumors Similar to that of the permanent tumor response at 4 weeks erlotinibdevelopment of lung adenocarcinomas with BAC features in a hnlichen time seen hnlicher histology. In addition in our mouse model showed no significant differences between these two mutants in their R Ability to observe, EGFR activation.