Thymidine phosphorylase profiles in nonmalignant and malignant pancreatic tissue. Potential therapeutic role of capecitabine on tumoral and endothelial cells and tumor-infiltrating macrophages

Immunopharmacol Immunotoxicol. 2005;27(1):95-107. doi: 10.1081/iph-51753.


The drug capecitabine (CAP) is a thymidine Pi-deoxyribosyltransferase (TP) activated oral fluorpyrimidine that generates 5-fluorouracil (5-FU), preferentially, 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 (MO) 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 and endothelial cells and tumor infiltrating MO could increase the concentration of 5-FU at tumor site, thus resulting in an enhanced antitumor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Capecitabine
  • Cell Movement / immunology*
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Deoxycytidine / therapeutic use*
  • Endothelial Cells / drug effects
  • Endothelial Cells / enzymology
  • Endothelial Cells / pathology
  • Female
  • Fluorouracil / analogs & derivatives
  • Humans
  • Immunohistochemistry
  • Macrophages / drug effects
  • Macrophages / enzymology*
  • Macrophages / pathology*
  • Male
  • Middle Aged
  • Pancreas / drug effects
  • Pancreas / enzymology
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / enzymology
  • Pancreatic Neoplasms / pathology*
  • Thymidine Phosphorylase / analysis
  • Thymidine Phosphorylase / biosynthesis*


  • Deoxycytidine
  • Capecitabine
  • Thymidine Phosphorylase
  • Fluorouracil