Role of thymidine phosphorylase and dihydropyrimidine dehydrogenase in tumour progression and sensitivity to doxifluridine in gastric cancer patients |
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Authors: | Terashima M Fujiwara H Takagane A Abe K Araya M Irinoda T Yonezawa H Nakaya T Oyama K Takahashi M Saito K |
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Affiliation: | a Department of Surgery 1, Fukushima Medical University, 1 Hikarigaoka, Fukushima, Fukushima 960-1295, Japan;b Department of Surgery 1, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan |
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Abstract: | This study was designed to investigate the role of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) on tumour progression and sensitivity to 5′-deoxy-5-fluorouridine (5′-DFUR). Tumour tissue was obtained from surgically resected samples from 93 patients with primary gastric cancer. Tumour TP and DPD expression levels were determined by the enzyme-linked immunosorbent assay (ELISA) system and compared with several clinicopathological factors and in vitro sensitivity to 5′-DFUR. DPD showed no correlation with any clinicopathological factors. However, the TP level was significantly correlated with the depth of tumour, lymphatic invasion and venous invasion. In comparison with 5′-DFUR sensitivity, there was a weak inverse correlation between the DPD level and the sensitivity to 5′-DFUR (rs=−0.361). Furthermore, the TP/DPD ratio showed a significant correlation with 5′-DFUR sensitivity (rs=0.634). In a subgroup of patients with postoperative 5′-DFUR administration, the survival rate was significantly better in patients with a high TP/DPD ratio (n=8) than in those with low TP/DPD ratio (n=14) (P=0.0140). These results suggest that sensitivity to 5′-DFUR is predictable by measurement of both TP and DPD levels. |
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Keywords: | Thymidine phosphorylase Dihydropyrimidine dehydrogenase Gastric cancer Drug sensitivity testing Doxyfluridine |
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