As more high-quality studies of mTOR inhibitors in different malignancies and clinical settings become available, further analyses could be preformed to confirm the trends observed here. Third, the process by which investigators attribute FAE causality is a variable practice since FAEs were not the primary end point of any of the included studies. In addition, a continuity correction of 0.5 subjects with an event is used, which may have slightly overestimated the actual event rate of GS 6201 individual trials. Fourthly, although FAEs are prospectively collected for each individual study, this analysis is retrospective, and there are potentially important differences among the studies, including differing tumor types, dosage and administration schedule of mTOR inhibitors, periods of study conduct and study investigators. All of these would increase the clinical heterogeneity among included trials, which also made the interpretation of a metaanalysis more problematic. Additionally, our study includes a mixed population of patients treated mTOR inhibitors-based combination therapy or mTOR inhibitors alone, and patients received placebo or non-placebo therapy were also included in our study. Therefore, the treatment design is not the same in all arms, and it might be another source of heterogeneity. Finally, it is not an individual patient data analysis, and meta-analyses based on published data tend to overestimate treatment effects compared with individual patient data analyses. In addition, it precludes a more comprehensive analysis such as adjusting for baseline factors and other differences that existed between the trials from which the data were pooled. In summary, our study demonstrates that the use of mTOR inhibitors seems to increase the risk of FAEs in patients with GT 2016 advanced solid tumors, but one should be cautious when interpreting these results due to the limitations of our study. Additionally, as this class of drugs gains greater clinical use, clinicians should be aware of the risks of FAEs with the administration of mTOR inhibitors in solid cancer, and closely monitoring is recommended during the therapy. As the role of monoclonal antibodies in biology and medicine becomes increasingly important, so does the precise evaluation of the epitopes being recognized by the antibodies. There are many methods allowing to precisely define amino acid residues that are involved in antibody binding, such as evaluation of binding of the antibody to synthetic peptides or to recombinant peptides expressed either in bacteria on in eukaryotic cells. Recently, saturation transfer difference spectroscopy NMR has been increasingly used in epitope-antibody studies, although majority of antibodies evaluated by this method bind carbohydrate antigens. In this paper we used a variety of methods, including STD-NMR, to precisely define the peptidic epitope of 2C3 MAb.
Mutagenesis and kinetic data have demonstrated the importance of conserved SDHC
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