Document Detail

Pyrimidine nucleoside phosphorylase and dihydropyrimidine dihydrogenase activities as predictive factors for the efficacy of doxifluridine together with mitomycin C as adjuvant chemotherapy in primary colorectal cancer.
MedLine Citation:
PMID:  17629045     Owner:  NLM     Status:  MEDLINE    
BACKGROUND/AIMS: Pyrimidine Nucleoside Phosphorylase (PyNPase) converts 5'-deoxy-5-fluorouridine (5'-DFUR, doxifluridine) to 5-fluorouracil (5-FU). While this reaction is taking place Dihydropyrimidine Dihydrogenase (DPD) catalyzes 5-FU to inactive molecules. Mitomycin C (MMC) elevates the PyNPase level in tumor cells. METHODOLOGY: We investigated 17 colorectal cancer patients' PyNPase and DPD activities in tumor and normal tissues using an enzyme-linked immunosorbent assay (ELISA) to assess their clinical significance as indicators for selecting colorectal cancer patients for 5'-DFUR together with MMC as adjuvant chemotherapy. RESULTS: Six of 17 patients developed experienced a recurrence. Tumor DPD activity of the 6 patients who had a recurrence were higher than those of the 11 patients with no recurrence (p = 0.047). On the other hand, there were no significant differences in both the PyNPase and the PyNPase/DPD (P/D) ratio between the group with recurrence and the group without recurrence. For survival analyses, we designed the cut-off value of tumor PyNPase, DPD and P/D ratio as their median value and classified patients into a higher group and a lower group, but there were no significant differences between the groups. CONCLUSIONS: The DPD activity in the tumor may be a useful indicator for selecting patients likely respond to 5'-DFUR together with MMC as adjuvant chemotherapy. If tumor DPD is high, we had better select a different anticancer drug.
Masanori Nishioka; Hidenori Miyamoto; Nobuhiro Kurita; Jun Higashijima; Kouzou Yoshikawa; Tomohiko Miyatani; Mitsuo Shimada
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Hepato-gastroenterology     Volume:  54     ISSN:  0172-6390     ISO Abbreviation:  Hepatogastroenterology     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-07-16     Completed Date:  2007-08-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8007849     Medline TA:  Hepatogastroenterology     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1089-93     Citation Subset:  IM    
Department of Digestive and Pediatric Surgery, Institute of Health Biosciences The University of Tokushima Graduate School, Tokushima, Japan.
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MeSH Terms
Antineoplastic Protocols
Chemotherapy, Adjuvant
Colorectal Neoplasms / drug therapy*,  enzymology,  mortality
Dihydrouracil Dehydrogenase (NADP) / analysis*
Floxuridine / therapeutic use*
Middle Aged
Mitomycin / therapeutic use*
Pentosyltransferases / analysis*
Survival Analysis
Treatment Outcome
Reg. No./Substance:
3094-09-5/doxifluridine; 50-07-7/Mitomycin; 50-91-9/Floxuridine; EC Dehydrogenase (NADP); EC 2.4.2.-/Pentosyltransferases; EC phosphorylase

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