Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured the dihydropyrimidine dehydrogenase (DPD) activity considered to regulate the sensitivity of pyrimidine fluoride anti-cancer drugs in 50 cases of urothelial cancer (preoperative therapy group 10 cases, non-therapy group 40 cases). The association of DPD activity with pathological factors and TS activity as well as the influence of UFT oral administration on the DPD activity in tumors and blood were studied. The DPD activity in cancer tissue tended to be higher than that in the mucous membranes of the non-tumor region, but the difference was not significant. The DPD activity was high in infiltrative cancer (p < 0.05) but was not associated with atypia. The TS activity and DPD activity were manifested independently. The DPD activity in cancer tissue was significantly higher after UFT administration, with levels of 76.7 +/- 71.0 pmol/mg/min before administration and 220.6 +/- 129.1 pmol/mg/min after (p < 0.05). The DPD activity in peripheral blood was elevated after administration, but no significant difference was found. Since DPD activity is found in urothelial cancer tissue, 5-FU stable to DPD should preferably be used. It is also suggested that using a more potent DPD inhibitor in combination will produce higher anti-tumor effects.
 ...
PMID:[Dihydropyrimidine dehydrogenase activity in urothelial cancer--influence of UFT administration on DPD activity]. 1172 80

Between 1998 and 2001, 82 colorectal cancers were resected in our hospital. The activities of TS and DPD were evaluated. TS activities in tumor tissues were significantly higher than in normal tissue, but the DPD activities had no significant difference between them. TS and DPD showed a correlation between normal and tumor tissues in stage III or IV patients. The TS value of patients with recurrence tended to be higher than that of patients with no recurrence. Especially in stage I or II patients with recurrence, who were administered 5-FU before recurrence, the TS value was significantly higher than in non-treated patients. In stage III or IV patients, it was considered that DPD prevention was important for 5-FU to effectively prevent TS. The TS value might be a new prospective risk factor for recurrence. Moreover, TS and DPD would be the index of biological malignancy.
 ...
PMID:[Activities of thymidylate synthase and dihydropyrimidine dehydrogenase in patients with colorectal cancer]. 1179 81

We have assessed pyrimidine nucleoside phosphorylase (PyNPase) and dihydropyrimidine dehydrogenase (DPD) activity to compare the chemosensitivity of 5-fluorouracil (5-FU) and doxifluridine (5'-DFUR). Tumor samples were prepared from fresh surgical specimens of 28 patients with advanced colon carcinoma. The activity levels of the two enzymes were assessed as indicators of chemosensitivity to 5'-DFUR and 5-FU. PyNPase activity was analyzed using the HPLC method, and DPD activity was assessed according to the methods of Naguib et al. (1985). A histoculture drug response assay (HDRA) was conducted according to the methods described by Furukawa et al. (1992). The mean and standard deviation of PyNPase activity in the tumor tissue was 110 +/- 48.6 &mgr;g 5-FU/mg protein/h, which was statistically higher than the corresponding value obtained in normal tissue (60 +/- 43.1 &mgr;g 5-FU/mg protein/h) (P < 0.005). When chemosensitivity to the two drug forms was compared in 16 samples obtained from 16 cases with colon cancer, 1 specimen was sensitive to both drug forms, 3 specimens were exclusively sensitive to 5'-DFUR, 5 specimens were exclusively sensitive to 5-FU, and the other 7 specimens were insensitive to both drugs, without significance. High PyNPase activity was associated with a high chemosensitivity to 5'-DFUR, and high DPD activity correlated with a low chemosensitivity to 5-FU. However, the converse relationship was not found. We suggest that the activity of PyNPase and DPD represents a reliable indicator for the chemosensitivity of colon cancer to 5'-DFUR and 5-FU, respectively.
 ...
PMID:Pyrimidine nucleoside phosphorylase and dihydropyrimidine dehydrogenase indicate chemosensitivity of human colon cancer specimens to doxifluridine and 5-fluorouracil, respectively. 1181 May 6

To evaluate the antitumor efficacy against metastatic breast cancer of fluoropyrimidines alone and combined with other chemotherapeutic agents, we developed a murine model of breast cancer metastatic to the lung by orthotopically implanting MDA-MB-435S breast tumors into mice. MDA tumor cells greatly metastasized to lung tissue only after the orthotopically implanted tumors were surgically removed. Measurement of the expression of enzymes involved in 5-FU metabolism showed significantly higher activity of dihydropyrimidine dehydrogenase (DPD) and lower activity of thymidylate synthase (TS) in the MDA metastases than in the orthotopically implanted tumors. Based on the enzymatic properties of metastatic tumors, the minimum toxic doses of UFT (17.5 mg/kg/day) as a DPD-inhibitory fluoropyrimidine (DIF), and of 5'-DFUR (120 mg/kg/day) as a non-DIF, were orally administered to mice with pulmonary metastasis of the breast tumor. The results showed that UFT significantly inhibited the growth of pulmonary metastases of the breast tumors, but 5'-DFUR did not. UFT seemed to inhibit the growth of the pulmonary metastases of the breast tumors in combination with paclitaxel (50 mg/kg) more than in combination with 5'-DFUR, although the antitumor efficacy of neither combination was significantly different from that of paclitaxel alone. These results suggest that combination of DIF with other chemotherapeutic drugs, such as taxanes, is required to attain high antimetastatic and antitumor efficacy against breast tumor metastases, based on the molecular characteristics of the metastatic tumors.
 ...
PMID:[Antimetastatic and antitumor effects of fluoropyrimidines alone and combined with taxanes in a murine model of breast cancer metastatic to the lung]. 1181 85

Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) levels in transitional cell carcinoma of the bladder resected from 38 patients were examined by ELISA. TP levels in high-grade and invasive cancer were significantly higher than those in low-grade and superficial cancer, respectively. No significant differences in the DPD levels were observed among grades and stages, but the DPD/TP ratio was significantly lower in grade 3 tumor than in grade 1. These results demonstrated that 5'-deoxy-5-fluorouridine seemed to be useful for managing patients with grade 3 cancer. The present study also suggested that we might be able to exclude cases of bladder cancer in which 5-fluorouracil group medicines would be inappropriate candidates in treatment options by measuring both TP and DPD levels in the tumor.
 ...
PMID:Thymidine phosphorylase and dihydropyrimidine dehydrogenase in bladder cancer. 1183 4

The rate-limiting enzyme to catabolize 5-fluorouracil (5-FU) is dihydropyrimidine dehydrogenase (DPD), which expression in cancerous tissue is reported to have a relation with anti-tumor effect for 5-FU. In this study, we evaluated the immunohistochemical expression in gastric cancer using two different kinds of anti-human DPD antibody, KM1915 and KM1919. However, recognition of both antibody was mimetic in human gastric cancer, and strong expression of DPD was observed in the interstitial tissue when using KM1919. There is a positive relationship between immunohistochemical expression by KM1915 and mRNA expression in human gastric cancer. Immunohistochemical study with KM1915 might be a clinically useful method to evaluate the expression of DPD in paraffin-embedded materials.
 ...
PMID:[Dihydropyrimidine dehydrogenase expression in gastric cancer using anti-human dihydropyrimidine dehydrogenase monoclonal antibody]. 1186 31

We measured the activity of orotate phosphoribosyl transferase (OPRT), the amount of thymidylate synthase (TS) enzyme, and the activity of dihydropyrimidine dehydrogenase (DPD) for individual tissue types in order to study the contribution of these substances to the effects of the pyrimidine fluoride anticancer drug 5-fluorouracil (5-FU). We also studied the correlation between these 3 enzymes and clinical pathophysiologic characteristics (age, sex, extent of tumor invasion, extent of metastasis to the lymph nodes, lymphatic invasion and the venous invasion of the colorectal wall). Sixty-eight patients with colorectal carcinoma who had undergone surgical resection in our department were studied. There was a significant (p < 0.01) elevation of OPRT activity in the tumor tissue compared with regions of normal tissue. OPRT activity levels in the tumor tissue were lowest in patients with mucinous carcinoma while TS enzyme levels showed the highest activity in tumor tissue in poorly differentiated adenocarcinoma. DPD also showed high activity levels in tumor tissue in poorly differentiated adenocarcinoma and mucinous carcinoma. It is possible that the expression of enzymes with respect to the antitumor effects of 5-FU is a factor contributing to the poor prognosis for patients with poorly differentiated adenocarcinoma and mucinous carcinoma. In the present study of clinical pathophysiologic characteristics, we found that metastasis to the lymph nodes was associated with a significant reduction in the OPRT tumor/normal (T/N) ratio. Our results indicate that it may be possible to predict lymphatic metastasis by determining the T/N ratio for OPRT before surgery.
 ...
PMID:[Correlation between clinical pathophysiologic factors and expression of orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) in colorectal cancer]. 1191 31

Thymidine phosphorylase (TP) converts 5'-deoxy-5-fluorouridine (5'-DFUR, doxifluridine), an intermediate metabolite of capecitabine, to 5-fluorouracil (5-FU). While dihydropyrimidine dehydrogenase (DPD) catalyzes 5-FU to inactive molecules. We investigated TP and DPD levels in tumor tissue to assess their clinical significance as indicators for selecting colorectal cancer patients for 5'-DFUR adjuvant chemotherapy. A total of 88 colorectal cancer patients were classified into Dukes' B and C groups and treated for 2 years with oral 5'-DFUR (800 mg/body/day). During the follow-up period, 20 of the 88 patients developed a recurrence. All the patients were examined retrospectively for primary tumor TP and DPD levels and clinical response to 5'-DFUR. Results showed that: a) median levels of TP and DPD in the primary tumor, measured by enzyme-linked immunosorbent assay (ELISA), were, respectively, 43.6 and 32.3 U/mg protein. Primary tumor TP levels of the 20 patients who had a recurrence were lower than those of the 68 patients with no recurrence (p=0.07); b) although there were no significant differences in clinicopathologic features between high and low median TP level groups, disease-free survival was better in the high TP than in the low TP group (89% vs. 64%, at year 4); and c) of patients classified into 4 groups such as high TP/DPD, high TP but low DPD, low TP but high DPD, and low TP/DPD, patients with high TP but low DPD had the best disease-free survival, whereas the low TP but high DPD group had the worst survival. These results suggest that TP and DPD levels in primary colorectal tumors may be a useful indicator for selecting patients likely to respond to 5'-DFUR adjuvant chemotherapy and probably capecitabine, a prodrug of 5'-DFUR.
 ...
PMID:Thymidine phosphorylase and dihydropyrimidine dehydrogenase levels in primary colorectal cancer show a relationship to clinical effects of 5'-deoxy-5-fluorouridine as adjuvant chemotherapy. 1195 13

Fluoropyrimidines remain the most important drugs in the treatment of breast and colorectal carcinoma, but response rates and survival time have been disappointing. Optimal administration is by continuous intravenous infusion, which makes it cumbersome to use and compromises patient independence. Recently, a number of new agents, including fluorouracil prodrugs and selective dihydropyrimidine dehydrogenase inhibitors, have been studied, with promising results. Capecitabine is the first in a new class of fluoropyrimidines. It is an oral, tumor-activated anticancer drug whose activity mimics that of continuously infused 5-fluorouracil. Capecitabine circumvents dihydropyrimidine dehydrogenase catabolism and appears to be at least as active against metastatic colorectal and breast cancer as conventionally administered intravenous 5-fluorouracil, with significantly less toxicity, an improved quality of life, and lesser cost. Capecitabine may ultimately provide enhanced antitumor activity to fluorouracil-containing regimes for advanced colorectal and breast cancer.
 ...
PMID:Capecitabine: indications and future perspectives in the treatment of metastatic colorectal and breast cancer. 1198 87

Patients with advanced cervical carcinoma were treated with oral fluoropyrimidine (UFT) as neoadjuvant chemotherapy and its antitumor effect was examined. The relationship between thymidylate synthase (TS) or dihydropyrimidine dehydrogenase (DPD) activity in tumor tissue and apoptosis was also investigated. The subjects were 56 patients with advanced cervical carcinoma. The patients received two courses of therapy consisting of UFT at a dose of 600 mg/day for 5 days and 2 days off treatment. The TS and DPD activity in tumor tissue was measured before and after UFT administration by the FdUMP binding assay and a catalytic assay in 38 patients, respectively. Apoptosis was detected by the TUNEL method, and the apoptotic index (AI) was calculated. Tumor tissue activity of TS or DPD was unrelated to clinicopathologic factors or to the activity of the other enzyme. The mean tumor TS and DPD activity before UFT administration was 5.42+/-3.92 pmol/g tissue and 206.54+/-128.58 pmol/mg/min, respectively, and the levels of these enzymes in two patients showing an antitumor effect were below the mean values. The AI increased from 1.10+/-0.57% before UFT to 1.27+/-0.81% afterwards, and the DPD activity before UFT showed an inverse relationship with the AI after UFT (r=-0.6938). In patients with DPD activity below the median value (186.92 pmol/mg/min), UFT administration significantly caused an increase of the AI (p=0.0002). These results indicate that the DPD activity of advanced cervical carcinoma is a determinant of sensitivity to UFT, suggesting an association between UFT therapy and the induction of apoptosis.
 ...
PMID:Tumor dihydropyrimidine dehydrogenase activity in advanced cervical carcinoma. 1216 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>