Core C: Biomarkers Core The goal of the Biomarkers Core (Core C) is to provide services for clinical correlates to the three projects of this program project grant. This will be achieved through the following specific aims: 1. To perform molecular assays for detecting hypoxic and oxidative damage in human tissues ex vivo, and in the animal models. These will include assays for serum markers of drug activity, and immunocytochemistry for proliferation markers, unique hypoxia and oxidation proteins, and cell death via apoptotic or other routes in Projects 1 and 2, as well as studies of hypoxic and oxidation imaging markers which are developed and validated in Project 3. 2. To develop and validate endpoints for assessment of therapeutic response in translational studies. The specific biomarkers to be analyzed by this core will include serum growth factors regulated by hypoxia, such as vascular endothelial growth factor (VEGF) (Projectl) serum thiols that may be altered by redox- active agents, such as glutathione (Project 2), imaging of animal models for therapeutic response to agents under investigation in Projects 1 and 2 (Project 3), and pharmacodynamic endpoints of hypoxia and redox targeted agents (all projects). Techniques are already in place for standardized sample collection, preparation and preservation, and sample analysis procedures for the assays described in this core. Additionally, we will continue to optimize new methods and assays to support the advancement of novel therapeutic agents into clinical trials. The core will work closely with the Clinical Trial Core (Core D) to coordinate and standardize sample collection and handling, and with the Biometry Core (Core B) to provide accurate raw data for analysis and interpretation. Collaboration between the projects will be facilitated by the standardized application of experimental assays developed within the projects to validation in pre-clinical and translation to clinical endpoints of hypoxia and redox targeted therapeutic agents.
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