Thymidine phosphorylase profiles in nonmalignant and malignant pancreatic tissue. Potential therapeutic role of capecitabine on tumoral and endothelial cells and tumor-infiltrating macrophages.
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.
Passantino
L
L
Faculty of Veterinary Medicine, University of Bari, Bari, Italy.
Patruno
R
R
Valerio
P
P
Penna
A
A
Mazzone
F
F
Zito
A F
AF
Catalano
V
V
Pellecchia
A
A
Jirillo
E
E
Ranieri
Girolamo
G
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*
D003841:Deoxycytidine; D000069287:Capecitabine; D013939:Thymidine Phosphorylase; D005472:Fluorouracil