Randomized Trial of Neuroprotective Effects of Erythropoietin in Patients Receiving Adjuvant Chemotherapy for Breast Cancer: Positron Emission Tomography and Neuropsychological Study

摘要

Animal Research Study Amendment An amendment to the study was initiated in April 2005 to include animal experiments. As per published literature, proinflammatory cytokines play a role in the pathogenesis of cognitive dysfunction. The experiments were designed to assess the cytokines before and after chemotherapy in a rat model. We have established an experimental animal model to study chemotherapy-induced cognitive dysfunction observed in the clinical setting. In this model administration of four weekly doses of clinical chemotherapeutics, i.e., the combination of adriamycin and cytoxan, results in impaired memory function in rats. This study was completed in February 2007 and the results of the study was sent to DOD with the report on September 2007. The study results were published in the Journal Met Brain Dis (23:325-333).After completion of Task 4, we initiated Task 5 as described below. We proposed to further characterize the mechanisms of this cognitive dysfunction by molecular genomics approach. We analyzed global gene expression in the hippocampi from treated vs. control rats using the microarray methodology. This analysis allowed us to identify genes whose expression is altered by the chemotherapeutic treatment. Subsequently, expression of these genes was analyzed by real time RT-PCR to confirm the microarray results, to precisely quantify the differential expression of these genes, and to further streamline the selection of putative genes that underscore the memory impairment. This study will provide important information for future, more clinically oriented endeavors to determine the correlation between the polymorphism of these genes and the susceptibility of patients to chemotherapy- induced cognitive dysfunction.