Profound variation in dihydropyrimidine dehydrogenase activity in human blood cells: major implications for the detection of partly deficient patients

Dihydropyrimidine dehydrogenase (DPD) is responsible for the breakdown of the widely used antineoplastic agent 5-fluorouracil (5FU), thereby limiting the efficacy of the therapy. To identify patients suffering from a complete or partial DPD deficiency, the activity of DPD is usually determined in peripheral blood mononuclear cells (PBM cells). In this study, we demonstrated that the highest activity of DPD was found in monocytes followed by that of lymphocytes, granulocytes and platelets, whereas no significant activity of DPD could be detected in erythrocytes. The activity of DPD in PBM cells proved to be intermediate compared with the DPD activity observed in monocytes and lymphocytes. The mean percentage of monocytes in the PBM cells obtained from cancer patients proved to be significantly higher than that observed in PBM cells obtained from healthy volunteers. Moreover, a profound positive correlation was observed between the DPD activity of PBM cells and the percentage of monocytes, thus introducing a large inter- and intrapatient variability in the activity of DPD and hindering the detection of patients with a partial DPD deficiency. © 1999 Cancer Research Campaig

Assessing the Advantages, Limitations and Potential of Human Primary Prostate Epithelial Cells as a Pre-clinical Model for Prostate Cancer Research

Choosing an appropriate cell model(s) is the first decision to be made before starting a new project or programme of study. Here, we address the rationale that can be behind this decision and we summarize the current cell models that are used to study prostate cancer. Researchers face the challenge of choosing a model that recapitulates the complexity and heterogeneity of prostate cancer. The use of primary prostate epithelial cells cultured from patient tissue is discussed, and the necessity for close clinical-academic collaboration in order to do this is highlighted. Finally, a novel quantitative phase imaging technique is described, along with the potential for cell characterization to not only include gene expression and protein markers but also morphological features, cell behaviour and kinetic activity