25 research outputs found
Solubilization of Proteins in 2DE: An Outline
Protein solubilization for two-dimensional electrophoresis (2DE) has to break
molecular interactions to separate the biological contents of the material of
interest into isolated and intact polypeptides. This must be carried out in
conditions compatible with the first dimension of 2DE, namely isoelectric
focusing. In addition, the extraction process must enable easy removal of any
nonprotein component interfering with the isoelectric focusing. The constraints
brought in this process by the peculiar features of isoelectric focusing are
discussed, as well as their consequences in terms of possible solutions and
limits for the solubilization process
Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials
Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting