Thymidine Phosphorylase Profiles in Nonmalignant and Malignant Pancreatic Tissue. Potential Therapeutic Role of Capecitabine on Tumoral and Endothelial Cells and Tumor-Infiltrating Macrophages

Abstract

The drug capecitabine (CAP) is a thymidine Pi-deoxyribosyltransferase (TP) activated oral fluorpyrimidine that generates 5-fluorouracil (5-FU), prefentially, within tumors. Here, in 38 patients with pancreatic cancer we analyzed immunohistochemical TP expression in pancreatic cancer tissue (PCT) and adjacent nonmalignant pancreatic tissue (ANMPT). In addition, a correlation with the main clinical pathological features was made. Furthermore, TP-positive macrophages (MØ) isolated from neoplastic tissue were determined. The mean of TP-positive epithelial cells and endothelial cells in terms of microvessel density was significantly higher in PCT than in ANMPT. Because pancreatic cancer is sensitive to 5-FU, TP-activated oral CAP in tumoral andendothelial cells and tumor infiltrating MØ could increase the concentration of 5-FU at tumor site, thus resulting in an enhanced antitumor activity.

Key Words :

• Capecitabine
• 5-Fluorouracile
• Immunohistochemistry
• Pancreatic cancer
• Platelet-derived endothelial cell growth factor
• Thymidine phosphorylase