Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenocarcinoma of the stomach represents a significant problem worldwide. The only known curative treatment of gastric cancer is complete surgical resection of the stomach tumor with surrounding lymph node-bearing areas. However, as many as 50% to 90% of patients undergoing gastric tumor resection relapse and die of cancer. Adjuvant chemotherapy has been used to prevent recurrence of gastric cancer after surgical resection. Single agents including thiotepa and fluorodeoxyuridine have no benefit as adjuvant therapy. Likewise, combination chemotherapy including 5-fluorouracil (5-FU) plus methyl-CCNU, 5-FU plus Adriamycin plus mitomycin C (FAM), and mitomycin C plus 5-FU plus cytosine arabinoside do not result in overall improved survival. Combined modality irradiation plus fluorinated pyrimidine, however, has resulted in long-term survival of patients with known residual gastric cancer. The newest clinical trial in postoperative gastric cancer being performed in the United States will test 5-FU plus leucovorin plus irradiation in a prospectively randomized study in patients with resected stage IB through stage IV stomach cancer. This surgical study, designed with excellent prospective quality control, is actively accruing patients and will be completed in 1.5 to 2.0 years.
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PMID:Adjuvant treatment of gastric cancer. 775 27

Effect of utilization of purine and pyrimidine in the culture medium by human gastric cancer cells (KATO III) was evaluated. Nucleosides mixture solution (OG-VI), consisting of inosine, guanosine 5' monophosphate (5'GMP), cytidine, uridine and thymidine (4: 4: 4: 3: 1 in molar ratio) was used and their levels in the culture medium was measured by HPLC after 3 day culture. Purine, inosine and 5' GMP, in the medium almost decreased and purine base, xanthine and hypoxanthine levels increased, but changes in pyrimidine level were minimal. 5-FU decreased purine and increased pyrimidine consumption. Addition of nucleosides mixture did not enhance the cellular proliferation, but inhibited growth when given in higher concentrations. Nucleoside mixture solution enhanced growth inhibition by 5-FU and it is a potential biochemical modulator of 5-FU metabolism in human cancer cells.
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PMID:[Effect of 5-FU on the utilization of purine and pyrimidine by human gastric cancer cells (KATO III)]. 775 82

The effect of the nucleotides and a nucleotide mixture (OG-VI), consisting of inosine, guanosine 5'-monophosphate (5'-GMP), cytidine, uridine, thymidine (TdR) (4:4:4:3:1 in molar ratio), and TdR co-administration on proliferation of KATO III human gastric cancer cells in culture was evaluated. Consumption of purine and pyrimidine by cancer cells and changes in cell number with OG-VI or TdR were compared with the control culture medium (Williams E) after 72 hour-culture. Addition of OG-VI or TdR did not enhance the cellular proliferation, but inhibited growth when given in higher concentrations (0.3-3 mM inosine, 0.3-3 mM 5'-GMP, 0.22-2.2 mM uridine, 74-740 microM TdR). Consumption rate of TdR in the medium was less in the TdR group, 33.7%, than in the OG-VI group, 72.2% (p < 0.05). This suggests that TdR metabolism is modulated by other nucleosides and nucleotide included in OG-VI. Under the coadministration of 5-fluorouracil (FUra), addition of OG-VI or TdR suppressed cellular proliferation (p < 0.05). The inhibition rate of cellular proliferation in the OG-VI group was slightly higher than the TdR group, but there was no statistically significant difference between the two groups. The combination of FUra with OG-VI or TdR enhances the antitumor effect of FUra. It is concluded that the OG-VI does not enhance the tumor cell proliferation and it is a potential biochemical modulator of FUra metabolism in human cancer cells.
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PMID:Effect of nucleosides and a nucleotide mixture on proliferation of human gastric cancer cells (KATO III). 782 35

5-Phenethyl-2'-deoxyuridine (PEUdR) augmented 5-fluoro-2'-deoxyuridine (FUdR) cytotoxicity up to 100-fold in several human gastric cancer cell lines. PEUdR also potentiated 5-fluorouracil (5-FU) cytotoxicity about 5-fold. In contrast, PEUdR reversed 5-fluorouridine (FUR) cytotoxicity in all cell lines studied. PEUdR was not cytotoxic up to 200 microM. PEUdR inhibited the incorporation of [3H]thymidine and [14C]uridine into acid-insoluble fractions, and also inhibited uptake of [3H]thymidine into KATO III cells. Thus, PEUdR inhibits pyrimidine nucleoside transport and salvage enzymes, which potentiates the cytotoxicity of FUdR and reverses the effect of FUR in human gastric cancer cells. These results may contribute to more effective cancer chemotherapy with FUdR and 5-FU.
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PMID:Augmentation of 5-fluoro-2'-deoxyuridine cytotoxicity by 5-phenethyl-2'-deoxyuridine in human gastric cancer cells in culture. 794 45

We compared the survival time and drug toxicity between patients with stage IV gastric cancer who were over and under 65 years. All had undergone gastric resection followed by treatment with mitomycin C and a fluorinated pyrimidine. There were no differences in prognostic factors or doses of drugs prescribed between the two groups, nor were there differences in survival rates or toxicities. As advanced chronological age is not sufficient justification to limit or withhold treatment with anticancer drugs, postoperative chemotherapy should be designed for patients with gastric cancer, regardless of age.
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PMID:Postgastrectomy anticancer chemotherapy for stage IV gastric cancer equally tolerable for patients under and over age 65. 847 23

5-fluorouracil (5-FU), although a widely used chemotherapeutic agent, has a limited effect in the treatment of human solid tumors due to their resistance to the cytotoxic effects of 5-FU. Escherichia coli uracil phosphoribosyltransferase (UPRT) is a pyrimidine salvage enzyme that catalyzes the synthesis of UMP from uracil and 5-phosphoribosyl-alpha-1-diphosphate. The present study demonstrates that adenovirus-mediated transduction of E. coli UPRT gene results in marked sensitization of colon, gastric, liver, and pancreas cancer cell lines to low concentration of 5-FU in vitro. The in vitro bystander effect was observed when only 10% of the hepatoma Hep3B cells were infected with UPRT-expressing adenovirus. In addition, 5-FU treatment of human hepatoma or gastric cancer xenografts in nude mice transduced with UPRT was demonstrated to result in significant in vivo antitumor effects. The adenovirus vector transduction of the UPRT gene followed by 5-FU administration is representative of a new chemosensitization strategy for cancer gene therapy.
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PMID:Adenovirus-mediated transduction of Escherichia coli uracil phosphoribosyltransferase gene sensitizes cancer cells to low concentrations of 5-fluorouracil. 958 37

We analyzed the pyrimidine metabolite in the urine of a patient with severe mucositis and hand and foot syndrome, who was administered 5-fluorouracil for recurrence of gastric cancer. From our analysis, it was suggested that the patient had decreased dihydropyrimidine dehydrogenase activity. Dihydropyrimidine dehydrogenase activity is usually measured in peripheral blood mononuclear cells, but this time it was estimated from the analysis of uracil, dihydrouracil, thymine, and dihydrothymine in the urine. We concluded that urinary analysis of the pyrimidine metabolism is effective as screening for the prediction and prevention of 5-fluorouracil toxicity.
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PMID:[A case of gastric cancer with decreased dihydropyrimidine dehydrogenase activity]. 967 86

It has been hypothesized that intratumoral thymidylate synthase (TS) gene expression might be used to select therapy for patients with disseminated colorectal cancer. We recently reported the results of a clinical trial in 46 patients with disseminated or recurrent colorectal cancer testing whether expression of TS within the primary tumor, as assessed by quantitative polymerase chain reaction (PCR) methodology, would predict the responsiveness of that cancer of fluoropyrimidine-based therapy. This trial demonstrated that intratumoral TS/beta-actin messenger RNA (mRNA) ratio can accurately predict which metastatic colorectal tumors will be resistant to a leucovorin-modulated 5-FU infusion and which have a high likelihood of responding to such a regimen. Results of other studies of adjuvant therapy in gastric cancer and colorectal cancer also indicated that TS expression within the tumor is predictive of response of 5-FU-based therapy. It may be possible to use this parameter prospectively to decide which patients should receive fluorinated pyrimidine therapy: Patients whose tumors express low TS levels would be likely to benefit from such therapy, whereas limited preliminary data suggest that patients whose tumors express high TS levels may benefit from irinotecan (CPT-11[Camptosar]).
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PMID:Thymidylate synthase as a predictor of response. 972 90

A new class of 5-halogenated pyrimidine analogs substituted at the 6-position was evaluated as competitive inhibitors of thymidine phosphorylase (TPase). The most potent member of the series was 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidine dio ne hydrochloride (TPI), which has an apparent K(i) value of 1.7 x 10(-8) M. TPI selectively inhibited the activity of TPase, but not that of uridine phosphorylase, thymidine kinase, orotate phosphoribosyltransferase, or dihydropyrimidine dehydrogenase. In vitro inhibition studies of TPI using a thymidine analogue, 5-trifluoromethyl-2'-deoxyuridine (F(3)dThd), as the substrate demonstrated that F(3)dThd phosphorolytic activity was inhibited markedly by TPI (1 x 10(-6) M) in extracts from the liver, small intestine, and tumors of humans, from the liver and small intestine of cynomolgus monkeys, and from the liver of rodents, but not from the liver or small intestine of dogs or the small intestine of rodents, suggesting that the distribution of TPase differs between humans and animal species, and that TPI could contribute to the modulation of TPase in humans. When F(3)dThd or 5-iodo-2'-deoxyuridine (IdUrd) was coadministered to mice with TPI at a molar ratio of 1:1, the blood levels of F(3)dThd (or IdUrd) were about 2-fold higher than when F(3)dThd (or IdUrd) was administered alone. In monkeys, the maximum concentration (C(max)) and the area under the concentration-time curve (AUC) after oral F(3)dThd alone were 0.23 microg/mL and 0.28 microg. hr/mL, respectively, but markedly increased to 15.18 microg/mL (approximately 70-fold) and 28.47 microg. hr/mL (approximately 100-fold), respectively, when combined with equimolar TPI. Combined oral administration of TPI significantly potentiated the antitumor activity of F(3)dThd on AZ-521 human stomach cancer xenografts in nude mice. In conclusion, TPI may contribute not only to inhibition of TPase-mediated biological functions but also to potentiation of the biological activity of various 2'-deoxyuridine and thymidine derivatives by combining with them.
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PMID:Structure and activity of specific inhibitors of thymidine phosphorylase to potentiate the function of antitumor 2'-deoxyribonucleosides. 1073 23

Pyrimidine nucleoside phosphorylase (PyNPase) is a general term for enzymes which phosphorolyse pyrimidine class nucleosides; convert 5'-deoxy-5-fluorouridine (5'-DFUR), a fluoropyrimidine class anticancer drug, to an active type of 5-fluorouracil (5-FU); and demonstrate higher concentrations in tumor tissue. These findings have attracted attention from the standpoint of drug delivery systems. With regard to immunohistochemical staining studies, PyNPase expression correlated with cancer proliferation and metastasis. However, few have shown a relation between PyNPase assay and prognosis. We measured PyNPase value in tumor tissue of operative specimens from 60 gastric cancer patients. The results showed that the PyNPase value in tumor tissue was significantly higher (1.9 times) than in normal mucosa. There was no correlation between the PyNPase level in tumor tissue and clinicopathologic factors. However, many patients with relatively early gastric cancer had high enzyme levels, indicating that PyNPase may influence cancer proliferation and metastasis as well as prognosis. By detecting such a factor as PyNPase, and clinically applying the results, 5'-DFUR is promising for the treatment of patients with respect to prognosis.
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PMID:[Correlation between pyrimidine nucleoside phosphorylase (PyNPase) and clinicopathological factors in patients with gastric cancer]. 1092 87


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