title: 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), 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.
authors.affiliation: Faculty of Veterinary Medicine, University of Bari, Bari, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Passantino
authors.forename: R
authors.initials: R
authors.lastname: Patruno
authors.forename: P
authors.initials: P
authors.lastname: Valerio
authors.forename: A
authors.initials: A
authors.lastname: Penna
authors.forename: F
authors.initials: F
authors.lastname: Mazzone
authors.forename: A F
authors.initials: AF
authors.lastname: Zito
authors.forename: V
authors.initials: V
authors.lastname: Catalano
authors.forename: A
authors.initials: A
authors.lastname: Pellecchia
authors.forename: E
authors.initials: E
authors.lastname: Jirillo
authors.forename: Girolamo
authors.initials: G
authors.lastname: Ranieri
mesh_terms: D000368:Aged; D000069287:Capecitabine; D002465:Cell Movement / Q000276:immunology*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D013939:Thymidine Phosphorylase / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D013939:Thymidine Phosphorylase; D005472:Fluorouracil