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

In 68 subjects the activities of Cu/Zn-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were investigated in gastric mucosa. The patients were classified according to the histological finding into following groups: 12 with normal finding (N), 16 with superficial gastritis (SG), 13 with mild atrophic gastritis (MAG), 19 with severe atrophic gastritis (SAG) and 8 with gastritis after partial gastrectomy (PGG). The comparison of groups SG, MAG, SAG and PGG with the group N revealed the following changes: in SG increased SOD and GSH-Px, in MAG and SAG no significant changes, and in PGG increase in SOD, CAT and GSH-Px were observed. It was supposed that increased enzymatic activities were caused by higher concentration of active oxygen species produced by phagocytizing leukocytes in inflamed gastric mucosa. Administration of vitamin E resulted in significant reduction of SOD and CAT activities, on the other hand GSH-Px activity significantly increased. The explanation of this effect of vitamin E requires further studies. A prolonged interaction of active oxygen species with chemical carcinogens (N-nitroso- or diazonium compounds, PAH) can exhibit a significant promoting effect on the development of intestinal type of gastric cancer from its precancerous conditions, above all after partial gastrectomy.
 ...
PMID:Gastric mucosal antioxidant activity in patients at increased risk of gastric cancer. 827 61

Glutathione S-transferases (GSTs) are a family of isoenzymes that play an important role in protecting cells against cytotoxic and carcinogenic agents. The distribution and levels of GST Alpha and Pi in normal and malignant gastric tissue of 34 patients with gastric cancer were examined immunohistochemically. Expression of GST Alpha and Pi was observed in 47 and 100 percent of the tumors, respectively. In normal mucosa both enzyme classes were present in 100 percent of the specimens. Mucous cells showed staining for GST Alpha and Pi in 88 and 97 percent, parietal cells in 93 and 67 percent, and chief cells in 82 and 30 percent, respectively. No correlation was observed between the amount or pattern of GST Alpha or Pi in carcinomas and the clinical and pathological characteristics of the patients. So it can be concluded that both GST Alpha and Pi cannot be considered as prognostic factors for gastric cancer.
 ...
PMID:Immunohistochemical determination of glutathione S-transferases in gastric carcinomas and in adjacent normal gastric epithelium. 868 99

This study characterizes glutathione (GSH) S-transferase (GST) isoenzymes of the liver and forestomach of the female A/J mouse and compares their specificities in catalyzing the conjugation of GSH with 7beta,8alpha-dihydroxy-9alpha,10alpha-oxy-7,8,9, 10-tetrahydrobenzo[a] pyrene (anti-BPDE), the ultimate carcinogenic metabolite of benzo[a]pyrene (BP). The GST activity in female A/J mouse liver was expressed by a minimum of seven isoenzymes which arose from different homo- or heterodimeric combinations of at least two alpha class (designated as alpha1 and alpha4), four micro class (micro1 to micro4), and one pi class GST subunit. The GST isoenzyme composition of A/J mouse forestomach appeared to be different from that of the liver. For example, while GST isoenzymes containing micro3 and micro4 type subunits were selectively expressed in the liver, an alpha class heterodimeric GST isoenzyme (containing alpha2 and alpha3 subunits) was expressed in the forestomach but could not be detected in the liver. The (+)-anti-BPDE appeared to be a better substrate than the (-)-enantiomer for all GSTs, except for isoenzymes containing the alpha4 type GST subunit. The murine pi class GST isoenzyme displayed relativey higher specific activity toward (+)-anti-BPDE compared to other GSTs. The specific activities of mouse GSTs toward (+)-anti-BPDE were in the order of pi > micro > alpha. These results suggest that the pi class GST isoenzyme may play an important role in providing protection against BP-induced cancer. Therefore, it seems logical to postulate that the ability of a chemoprotector to increase the expression of GST pi may be an important determinant of its effectiveness against BP-induced cancer. To test the validity of this contention, we have determined the effects on hepatic and forestomach GST isoenzyme/subunit expression of three naturally occurring organosulfides (OSCs) from garlic, which significantly differ in their effectiveness against BP-induced forestomach cancer. Treatment of mice with diallyl sulfide (DAS) and diallyl trisulfide (DATS), which are potent inhibitors of BP-induced fore- stomach cancer in mice, resulted in a significant increase in hepatic and forestomach GST activity toward anti-BPDE. On the contrary, this activity was not increased in either organ by dipropyl sulfide (DPS), which is ineffective against BP-induced forestomach cancer. The chemopreventive efficacy of these OSCs correlated with their ability to increase the expression of GST pi. For example, DAS treatment resulted in approximate increases of 1.7- and 2.2-fold in hepatic and forestomach GST pi expression, respectively, over the control. Treatment of mice with DATS, which is a relatively more potent inhibitor of BP-induced forestomach cancer than DAS, resulted in about 3.8- and 3.2-fold increases, respectively, in hepatic and forestomach GST pi expression over the control. On the contrary, the expression of hepatic and forestomach GST pi was increased only marginally (10-20%) upon DPS administration. In conclusion, the results of the present study suggest that induction of GST pi can be used as a bioassay for screening potential inhibitors of BP-induced cancer.
 ...
PMID:Glutathione S-transferases of female A/J mouse liver and forestomach and their differential induction by anti-carcinogenic organosulfides from garlic. 895 67

A cis-diamminedichloroplatinum (CDDP)-resistant scirrhous gastric cancer cell line, OCUM-2M/DDP, was established by chronic exposure of cells of the parent scirrhous gastric cancer cell line, OCUM-2M, to CDDP at progressively increasing concentrations. The OCUM-2M/DDP cell line had an 11.3-fold higher level of resistance relative to its parent cell line as determined by a succinate dehydrogenase inhibition test. The biological and biochemical characteristics of the resistant and parent cell line were compared. There were differences in the modal chromosome number and DNA index, suggesting that some alterations of the DNA in the CDDP-resistant cells had occurred. Neither the parent nor resistant cell line expressed mdr-1 mRNA. After exposure to CDDP for 4 h, the intracellular platinum content of OCUM-2M cells was significantly higher than that of OCUM-2M/DDP cells (51.9 +/- 1.8 vs 16.4 plus 1.0 ng/mg protein, mean +/- SD, respectively). The GSH levels in OCUM-2M cells and OCUM-2M/DDP cells were 3.5 +/- 1.0 micrograms/mg protein and 16.8 +/- 1.2 micrograms/mg protein, respectively. These levels were also significantly different. These findings suggest that the possible mechanisms of acquired resistance to CDDP in OCUM-2M/DDP cells may be a decrease in intracellular CDDP accumulation and detoxication by GSH. This OCUM-2M/DDP cell line could be used in further investigations of the mechanism of CDDP resistance in gastric cancer.
 ...
PMID:Establishment of a cisplatin-resistant gastric carcinoma cell line OCUM-2M/DDP. 913 37

Thioredoxin (TRX) is a widely distributed Mr 13,000 protein with a redox-active dithiol/disulfide in the active site. The TRX system, consisting of TRX, TRX reductase, and NADPH, has an intracellular reducing capacity. Another reducing capacity, glutathione (GSH), can be associated with cis-diaminedichloroplatinum (cDDP) resistance. Therefore, we examined the involvement of TRX in cDDP resistance using two cell lines designated St/DDP and HT/DDP, which were established from the human gastric cancer cell line St-4 and the colon cancer cell line HT-29. St/DDP and HT/DDP were seven and five times as resistant to cDDP as their parental lines, and the expression of TRX in these variants was increased by 2.5- and 2-fold, respectively. The expression of TRX in the complete revertant cells of St/DDP was reduced as low as that in St-4 cells. TRX reductase activity was also increased in St/DDP and HT/DDP, suggesting that activation of the TRX system was associated with in vitro-acquired cDDP resistance. Because cDDP is the first-line drug against ovarian cancer, we examined the expression of TRX in 11 human ovarian cancer cell lines not treated with cDDP in vitro. Positive correlation between TRX expression and cDDP resistance was observed in these cell lines (r = 0.76, P = 0.007). This correlation was comparable to that between GSH content and cDDP resistance (r = 0.69, P = 0.019). These results suggest a possible involvement of TRX, as well as GSH, in cDDP resistance.
 ...
PMID:Increased expression of thioredoxin/adult T-cell leukemia-derived factor in cisplatin-resistant human cancer cell lines. 981 87

Glutathione transferases (GSTs) have been shown to play an important role in multiple drug resistance in cancer chemotherapy. The inactivation of GST isoforms could lead to an enhanced activity of cytotoxic drugs. Thus, we have developed glutathione phosphono analogs [(S)-gamma-glutamyl-(2RS)-(+/-)-2-amino-(dialkoxyphosphinyl)-ac etylgl ycines], which were previously shown to be inhibitors of GSTP1-1. In the present study, the inhibition characteristics of these analogs, including isoenzyme specificities, type of inhibition, and determination of K(i) values, were determined. The inhibition of class alpha GSTs was competitive towards GSH. A mixed-type, non-competitive inhibition of class mu and pi GSTs was observed. The K(i) values varied between 880 +/- 210 and 0.45 +/- 0.1 microM. The inhibitors were most effective towards class mu GSTs. In order to investigate the potential use of these GST inhibitors in intact cellular systems, two additional approaches were examined. Firstly, the metabolic stability was tested with purified gamma-glutamyl transpeptidase and cell homogenates as well as during incubation of cell lines. No appreciable degradation was observed in any of the tested systems. Secondly, to facilitate cellular uptake, three derivatives were synthesized in which the glycine carboxylic group was esterified. Uptake and a possible intracellular cleavage to the corresponding free acids were monitored by HPLC analysis. The esters were effectively transported into HT29 (colon cancer) and EPG85-257P (gastric cancer) cells, respectively, and readily converted into the more active free acids. In conclusion, the tested inhibitors may be regarded as model compounds for the development of modulating agents in cancer chemotherapy.
 ...
PMID:Phosphono analogs of glutathione: inhibition of glutathione transferases, metabolic stability, and uptake by cancer cells. 1069 62

Previously we demonstrated an inverse relation between cancer of the gastrointestinal tract and glutathione S-transferase activity of the gastrointestinal mucosa. Chronic infection with H. pylori has been associated with an increased risk of gastric cancer. The aim of this study was to investigate the levels of glutathione and glutathione S-transferase activity in H. pylori-infected and noninfected antral mucosa. Glutathione and glutathione S-transferases were measured in antral biopsies of patients with nonulcer dyspepsia without H. pylori infection (A), with prior H. pylori infection who became H. pylori negative after eradication therapy (B) and with proven H. pylori infection (C). Glutathione concentration and glutathione S-transferase activity in group A were 31.0 (range 6.0-59.6) nmol/mg protein and 810 (range 165-1312) nmol/min/mg protein, in group B 27.0 (range 5.0-53.8) nmol/mg protein and 745 (range 403-1199) nmol/min/mg protein, and in group C 18.5 (range 1.6-55.8) nmol/mg protein and 572 (range 144-1047) nmol/min/mg protein, respectively. The glutathione and glutathione S-transferase values were significantly lower in patients infected with H. pylori than in patients who were H. pylori negative.
 ...
PMID:Antral glutathione concentration and glutathione S-transferase activity in patients with and without Helicobacter pylori. 1074 43

Helicobacter pylori infection has been associated with stimulation of gastric mucosal reactive oxygen species (ROS) production, and it was postulated that ROS production is due to neutrophil infiltration and activation. The aim of this study was to investigate the direct effect of H. pylori on ROS formation in gastric epithelial cells in vitro. The human gastric cancer cell line HM02 was incubated with H. pylori for 24 hr, and the effects on cell number and the intracellular radical scavenger reduced glutathione (GSH) were assessed. H. pylori caused a concentration-dependent reduction of cellular GSH concentrations over a broad bacteria-to-cell ratio (1.4-42) in the absence of cell necrosis. The radical scavengers MnTBAP (a cell permeable superoxide dismutase) and ebselen provided protection against H. pylori-induced decrease in cellular GSH concentrations. We conclude that H. pylori directly decreases cellular GSH concentrations in gastric epithelial cells. We suggest that this effect is caused by the release of ROS by H. pylori.
 ...
PMID:Helicobacter pylori reduces intracellular glutathione in gastric epithelial cells. 1105 18

Adenophora triphylla (AT), an oriental medicinal plant, was extracted using water and several organic solvents and each fraction was assayed for its tumoricidal effects on human Jurkat T cells with 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT). The influence on induction of apoptosis and G1 arrest was also examined. The ethyl acetate fraction showed the most pronounced inhibitory effects on proliferation of Jurkat T cells. Apoptosis was induced in line with up-regulation of FasL, tyrosine phosphorylation and c-fos mRNA levels. Arrest in G1 of the cell cycle was observed in A2780 cells with a wild type p53 gene but not HT-29 cells with a mutant p53 gene. Modifying effects of AT on cell turnover and glutathione(GSH) levels in vivo were also investigated in the stomach of rats given 150 mg/kg of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by gavage and then fed a diet supplemented with 5% or 1% pulverized AT and 0.5% or 0.2% ethylacetate-extracted AT for 42 hours. The 5% AT and both of the ethylacetate fractions caused significant reduction in proliferating cell nuclear antigen (PCNA)-labeling in the glandular stomach epithelium as compared with the value for the MNNG alone group. In addition, the treatments significantly increased the gastric GSH levels. These results suggest that AT could be a chemopreventive agent against gastric cancer.
 ...
PMID:Suppressive effects of Adenophora triphylla extracts on in vitro tumor cell growth and in vivo gastric epithelial proliferation. 1106 47

Glutathione S-transferases are important in the detoxification of a wide range of human carcinogens. Previous studies have shown inconsistent associations between the GSTT1 and GSTM1 null genotypes and stomach cancer risk. We investigated the relationship between these and related genotypes and stomach cancer risk in a population-based case-control study in Warsaw, Poland, where stomach cancer incidence and mortality rates are among the highest in Europe. DNA from blood samples was available for 304 stomach cancer patients and 427 control subjects. We observed a 1.48-fold increased risk for stomach cancer (95% confidence interval 0.97-2.25) in patients with the GSTT1 null genotype but no evidence of increased risk associated with the GSTM1, GSTM3 or GSTP1 genotypes. Furthermore, the stomach cancer risk associated with the GSTT1 null genotype varied by age at diagnosis, with odds ratios of 3.85, 1.91, 1.78 and 0.59 for those diagnosed at ages less than 50, 50-59, 60-69 and 70 years or older, respectively (P trend = 0.01). This was due to a shift in the GSTT1 genotype distribution across age groups among stomach cancer patients only. These results suggest that the GSTT1 null genotype may be associated with increased risk of stomach cancer.
 ...
PMID:Glutathione S-transferase genotypes and stomach cancer in a population-based case-control study in Warsaw, Poland. 1169 73


<< Previous 1 2 3 4 5 6 7 Next >>