
<ArticleTitle><prot>Dihydropyrimidine dehydrogenase</prot> activity and <prot>thymidylate synthase</prot> level are associated with response to 5-fluorouracil in human colorectal cancer.</ArticleTitle>
<AbstractText>In the recent studies associated with the modulation of 5-fluorouracil (5-FU) and the development of new antifolates, attentions have been focused on the expression of the target enzymes, <prot>thymidylate synthase</prot> (<prot>TS</prot>) and <prot>dihydropyrimidine dehydrogenase</prot> (<prot>DPD</prot>), that affect tumor sensitivity and resistance to drugs. In order to evaluate predictability of therapeutic efficacy by intratumoral enzyme activity, we investigated the role of <prot>TS</prot> content and <prot>DPD</prot> activity in tumor sensitivity of 5-FU. Surgical specimens were obtained from 51 patients with colorectal cancer and used to measure <prot>TS</prot> content and <prot>DPD</prot> activity. <prot>TS</prot> content and <prot>DPD</prot> activity in tissues were measured by [3H]-FdUMP binding assay and radioenzymatic assay, respectively. The sensitivity to 5-FU in tumor specimens was determined by collagen-gel droplet embedded-drug sensitivity test (CD-DST). The <prot>TS</prot> content and <prot>DPD</prot> activity did not correlate with Dukes' staging. There was no correlation between <prot>TS</prot> content and <prot>DPD</prot> activity in any tumors. Simple linear regression analysis showed that neither <prot>DPD</prot> activity (r = -0.267, p  0.05) nor TS content (r = -0.277, p  0.05) in tumors had a significant correlation with 5-FU effectiveness independently. Four out of 24 patients, highly responsive to 5-FU, showed low levels in both <prot>DPD</prot> and <prot>TS</prot>. The patients with high value in either <prot>DPD</prot> activity or <prot>TS</prot> content proved not to respond to 5-FU. In conclusion, these results demonstrate that both tumor <prot>DPD</prot> activity and <prot>TS</prot> content are the factors predicting 5-FU responsiveness in colorectal cancer.</AbstractText>
