Effects of 5'-DFUR and OK-432 on cytokines and thymidine phosphorylase in tumor tissue of gastric cancer patients.
BACKGROUND
The purpose of the study was to verify whether OK-432 in combination with 5'-DFUR induced thymidine phosphorylase (TdR Pase) and cytokines in gastric cancer patients as well as in vitro.


METHODS
Fifty patients with invasive gastric cancer were randomly assigned, upon admission using by a closed-envelope technique, to either a group receiving 5'DFUR or OK-432 alone, to a group receiving both 5'DFUR and OK-432, or to a non- treated group up. Surgical specimens of the tumor and normal tissues were taken soon after gastrectomy to evaluate TdR Pase activity, IL-1 alpha and TNF-production.


RESULTS
TdR Pase activities were several times higher in tumor than in normal tissues. In normal tissues, TdR Pase activities in the 5'-DFUR + OK-432 group were significantly higher than in the OK-432 group. TdR Pase activity in tumors, however, showed no significant difference between treated group. In the 5'-DFUR + OK-432 group, the level of IL-1 alpha production in tumor was significantly higher compared to the control group. In the 5'-DFUR + OK-432 group, the level of TNF alpha production in tumor was significantly higher than in normal tissue. TNF alpha production in tumor showed no significant difference in each treated group compared to the control. There was a significant correlation between TdR Pase activity and IL-1 alpha production levels in tumor.


CONCLUSIONS
TdR Pase was induced by IL-1 alpha in tumor tissues of gastric cancer patients. OK-432 in combination with 5'-DFUR, however, did not induce TNF alpha and IL-1 alpha, and increase TdR Pase activity in gastric cancer tumors.
Ohwada
S
S
Second Department of Surgery, Gunma University School of Medicine, Japan. sohwada@sb.gunma-u.ac.jp
Ogawa
T
T
Izumi
M
M
Inoue
T
T
Teshigawara
O
O
Ikeya
T
T
Kusaba
T
T
Roppongi
T
T
Iino
Y
Y
Morishita
Y
Y
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis*; D004790:Enzyme Induction; D005467:Floxuridine / Q000008:administration & dosage / Q000627:therapeutic use*; D005743:Gastrectomy; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010844:Picibanil / Q000008:administration & dosage / Q000627:therapeutic use*; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D013939:Thymidine Phosphorylase / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000970:Antineoplastic Agents; D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D005467:Floxuridine; D010844:Picibanil; D013939:Thymidine Phosphorylase; C025034:doxifluridine