[Effect of preoperative oral 5'-DFUR on PyNPase level in gastrointestinal malignant tumor tissues].
OBJECTIVE
Pyrimidine nucleoside phosphorylase (PyNPase) exists mainly in tumor tissues.5'-deoxy-5-fluorouridine(5'-DFUR) can decrease its level in tumor tissues. However, the effect of preoperative oral 5'-DFUR on PyNPase level in the different time after administration has not been reported. This study was designed to investigate the suitable duration of preoperative chemotherapy through observing the changes of PyNPase levels in gastrointestinal malignant tumors after preoperative oral administration of 5'- DFUR in different duration.


METHODS
Seventy-three patients with gastrointestinal malignant tumors were divided into four groups by the duration of preoperative oral 5'-DFUR (600-1,200 mg x d(-1)): group A, three days, 27 cases; group B, one week, 22 cases; group C, two weeks, 15 cases; group D, two months, 9 cases. Meanwhile, group E, control group, had 24 inpatients with gastrointestinal malignant tumors at the same term. All the above-mentioned patients did not receive the other chemotherapy or radiotherapy. The changes of PyNPase levels in tumor tissues of different groups were tested using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC), etc.


RESULTS
(1)Under electron microscope, there were many irrecoverable, lethal changes in tumor cells of group C. The outlines of the tumor cells were normal under light microscope, and more fibroconnective tissues were seen only in the stroma of group D. (2)The expressing levels of PyNPase mRNA and protein production in tumor tissues reduced obviously in group A (0.79+/-0.08, 19.26+/-1.65), and decreased most obviously in group C (0.43+/-0.07,5.91+/-1.45) comparing with group E (0.95+/-0.09, 29.34+/-1.82). However, there was no significant difference between group C and group D (0.42+/-0.04, 5.36+/-1.19) for the levels of PyNPase mRNA and protein production. The correlation coefficient between the levels of PyNPase mRNA and protein in tumor tissues of different group was r=0.92(P< 0.0001).


CONCLUSIONS
5'-DFUR by oral administration before operation might destroy gastrointestinal malignant tumor cells. As the duration prolonged, the content of PyNPase in tumor tissues decreased progressively, being lowest level in two weeks after chemotherapy. So two-week duration might be suitable for the treatment.
Wang
Wen-Jian
WJ
Department of General Surgery, The First Affiliated Hospital, Sun Yat-sen University of Medical Sciences, Guangzhou, Guangdong, PR China. w166w@yahoo.com.cn
Shi
De
D
Wang
Shen-Ming
SM
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000627:therapeutic use*; D005770:Gastrointestinal Neoplasms / Q000201:enzymology* / Q000628:therapy / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010430:Pentosyltransferases / Q000032:analysis*; D057845:Pyrimidine Phosphorylases
D005467:Floxuridine; D010430:Pentosyltransferases; D057845:Pyrimidine Phosphorylases; C025034:doxifluridine