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)

Incorporation of uracil and uridine into ribonucleic acid (RNA) was compared among the ascitic and solid forms of Ehrlich mouse tumor, Morris hepatoma, Rhodamine sarcoma, gastric cancer and ulcer from human patients, and several normal rat tissues. Of these cells tested, the cells of Ehrlich ascites and solid tumors, human gastric cancer and ulcer, and certain tissues of a normal rat showed a considerably high activity. Furthermore, Ehrlich ascites tumor cells indicating a high incorporation activity was also high in activities of both phosphorylase and kinase for uridine, while Rhodamine sarcoma as a representative having a low incorporation activity was considerably low in these two enzymic activities. RNA synthesis from uridine phosphates by Rhodamine sarcoma was maintained to a fairly high extent contrary to its low activities of the phosphorylase and the kinase. Consequently, the low utilization of uracil and uridine by certain tumors was suggested to be due to the extremely low activities of both enzymes.
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PMID:Incorporation characteristics of uracil, uridine, and orotic acid into ribonucleic acid of neoplastic cells. 19 18

Formation of ribothymidine by the ribose exchange reaction between thymine and uridine with the cell-free extract of mouse Ehrlich ascites tumor cells was demonstrated. Since phosphate ions appear to be not required for this reaction, perhaps it proceeds by the mechnism of direct exchange of nucleoside N-ribosyltransferase. The transfer activity was found in the precipitates when the crude extract was fractionated with 30-60% saturated ammonium sulfate. Ribothymidine formation was also demonstrated between thymine and ribonucleosides other than uridine with this tumor extract. Production of ribothymidine from thymine and uridine was detected also by the use of extracts from lung, brain, and regenerating liver of normal rats, and from newborn rats (whole body). An extract of Rhodamine sarcoma exhibited the ribose exchange activity, while that of human gastric cancer did not.
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PMID:Formation of ribothymidine from thymine and ribonucleosides by the cell-free extract of tumors and rat tissues. 34 Apr 51

Up to 19--20 fractions of separate RNA species and groups have been revealed in malignant tumors of the stomach and mucous membrane of patients with stomach cancer, ulcer and polyposis of the stomach by means of the method of analytical and preparative electrophoresis in 2.5% polyacrylamide gel. A more intensive incorporation of 14C uridine both into the nuclear and separate fractions of cytoplasmic RNA was observed in stomach tumors in comparison with the stomach mucous membrane of man. Pepsinogen-pepsin was synthesized by bound polysoms of the stomach mucous membrane. In stomach malignant tumors of man the polysomes were not capable of synthesizing this enzyme. Fractions of messenger RNA with sedimentation constants 16S-17S, possessing the ability to stimulate pepsinogen-pepsin synthesis in vitro, have been isolated from cytoplasmic RNA of a pig stomach mucous membrane.
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PMID:Realization of genetic information programming the synthesis of pepsinogen-pepsin in the mucous membrane and tumors of the stomach in man. 79 Feb 10

The effects of abdominal surgery on protein, RNA, and de novo purine nucleotide synthesis in lymphocytes, and modification of these changes by postoperative amino acid supply, were investigated in 24 patients undergoing cholecystectomy (n = 12) or removal of gastric cancer (n = 12). Mono-nuclear cells were isolated from the peripheral venous blood and incubated with radioactive tracers in vitro. Protein and RNA synthesis, as measured using [14C] glycine and [3H]uridine, respectively, increased postoperatively. Nucleotide synthesis determined by the incorporation of radioactivity from [14C] glycine into nucleotides increased simultaneously. The concentration of 5-phosphoribosyl 1-pyrophosphate (PRPP) estimated by the incorporation of [14C]adenine into nucleotides also increased. These changes were greater and of longer duration in patients with cancer operation than in those with cholecystectomy. In neither case were they affected by the amount of amino acid intake, or increases in energy intake. These results suggest that abdominal surgery stimulates protein and ribonucleic acid (RNA) synthesis in lymphocytes. Increased RNA synthesis may be ensured by increased synthesis of nucleotides, and increased PRPP concentrations appear to regulate the rate of nucleotide synthesis. The responses are apparently dependent upon the severity of surgery, but unrelated to the amount of amino acid supplied postoperatively.
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PMID:Stimulation of protein, RNA, and nucleotide synthesis in lymphocytes after abdominal surgery is not affected by postoperative amino acid supply. 171 2

The sensitivity to 5-fluorouracil (5-FU) was examined in 40 well differentiated and 50 poorly differentiated gastric cancer tissues and 15 normal tissues, using the in vitro succinate dehydrogenase inhibition (SDI) test. The tissue phosphorylating and degrading activities of 5-FU were compared in each type of tumor and in the normal tissues. Decreases in succinate dehydrogenase (SD) activity were more apparent in the poorly differentiated cancer tissues than in the well differentiated cancer tissues (p less than 0.005), and than in the normal tissues (p less than 0.001), exposed to 5-FU. The rate of sensitivity to 5-FU was higher in the poorly differentiated than in the well differentiated tissues and than in the normal tissues. The phosphorylating activities of 5-FU, in pathways involving uridine (Urd) phosphorylase and Urd Kinase, and thymidine (dThd) phosphorylase and dThd Kinase, were 1.7 fold higher in the poorly differentiated than in the well differentiated tissues and several fold higher than in the normal tissues (p less than 0.05-p less than 0.001). The degrading activity of 5-FU was similar in both types of tumor and in the normal tissues. Our findings show that 5-FU is actively metabolized to 5-FU-nucleotides in poorly differentiated tissues after incorporation into the tumor cells. 5-FU seems to have an increased susceptibility in cases of poorly differentiated gastric carcinoma.
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PMID:5-Fluorouracil is converted to F-nucleotides more extensively and is more cytotoxic in poorly differentiated than in well differentiated human gastric carcinoma. 238 81

In tissues obtained from patients undergoing gastrectomy, the activities of 12 enzymes involved in pyrimidine nucleotide synthesis: cytidine triphosphate (CTP) synthetase, deoxycytidine monophosphate (dCMP) deaminase, thymidine monophosphate (dTMP) kinase, uridine (Urd), deoxycytidine (dCyd) and thymidine (dThd) kinases, Urd, deoxyuridine (dUrd) and dThd phosphorylases, cytidine (Cyd) and dCyd deaminases, and DNA polymerase were examined in the eight-well-differentiated and 12 poorly differentiated gastric cancer tissues and the ten normal tissues. These cases were clinically advanced and serosal invasions were evident. Activities of these enzymes were higher in the poorly differentiated tissues than the well differentiated type and in the normal tissues. Significant differences were noted between the poorly differentiated and well-differentiated types, in dTMP kinase (P less than 0.02), dThd kinase (P less than 0.05), dThd phosphorylase (P less than 0.01), and DNA polymerase (P less than 0.05). The authors' findings show that the level of pyrimidine nucleotide synthesis, in both de novo and salvage pathways, is higher in the poorly differentiated gastric cancer tissues than in the well-differentiated type and suggest that antitumor drugs have an increased susceptibility in cases of poorly differentiated gastric carcinoma.
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PMID:Pyrimidine nucleotide synthesis is more extensive in poorly differentiated than in well-differentiated human gastric carcinoma. 291 Apr 29

Reversed-phase high-performance liquid chromatography (HPLC) has been used to determine the level of nucleic acid metabolites in perchloric acid extracts of gastrointestinal mucosa. By comparing the levels of these compounds in the normal portion with the levels in the neoplastic portion of mucosa resected from patients with malignant cancer, it was found that uracil was significantly elevated in the neoplastic colorectal mucosa (adenocarcinoma) of eight patients with colorectal cancer (P less than 0.01, statistically significant with the paired t test). The mean level of uracil in neoplastic colorectal mucosa was 2.7-fold higher than that in normal mucosa. However, in neoplastic gastric mucosa, only one out of four patients with gastric cancer showed elevated uracil. In neoplastic mucosa, the levels of hypoxanthine and uridine for colorectal cancer, and inosine for gastric cancer, were also significantly higher than those in normal mucosa (P less than 0.05, with the paired t test). The urinary modified nucleosides were prefractionated with a boronate affinity gel column, and their levels determined by the same HPLC method. No significant differences in the concentrations of pseudouridine, 1-methylguanosine, N2-methylguanosine or N2,N2-dimethylguanosine were observed in pre- and post-operative urines from patients with colorectal cancer and normal urines.
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PMID:Reversed-phase liquid chromatographic investigation of nucleosides and bases in mucosa and modified nucleosides in urines from patients with gastrointestinal cancer. 405 38

Reversed-phase high-performance liquid chromatography (HPLC) was used to determine the levels of nucleosides, bases and their metabolites in perchloric acid extracts of gastrointestinal mucosa. By comparing the levels of these compounds in the normal portion with the neoplastic portion of mucosa resected from malignant cancer patients, it was found that there was significant elevation of the uracil level in the neoplastic mucosa of all eight patients with colorectal cancer (2.7-fold in normal mucosa), but only in the neoplastic mucosa of one out of four patients with gastric cancer. The levels of hypoxanthine and uridine in the colorectal cancer mucosa samples and the inosine in gastric cancer samples were also significantly higher than those in normal mucosa. The urinary modified nucleosides were prefractionated with a boronate affinity gel column, and their levels were determined by the same HPLC method. There was no significant difference in the concentrations of pseudouridine, 1-methylguanosine N2-methylguanosine and N2,N2-dimethylguanosine between urine samples taken before and after surgery from eight patients with malignant colorectal cancer. Contrary to other reports, no significant differences in modified nucleoside levels were observed between urine samples from patients with colorectal cancer and those from normal subjects.
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PMID:Reversed-phase high-performance liquid chromatographic investigation of mucosal nucleosides and bases and urinary modified nucleosides of gastrointestinal cancer patients. 406 57

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


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