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)

In laboratory rodents, concentrations of reduced glutathione (GSH) are exceedingly high (up to 7 to 8 millimolar) in the glandular gastric tissue compared to concentrations in other portions of the gastrointestinal tract or to those of most other organs. Gastric GSH varies diurnally, with the highest levels occurring in the late afternoon or early evening. Starvation, treatment with diethyl maleate, or cold-restraint stress all caused marked decreases in stomach GSH, whereas treatment with cobaltous chloride caused an increase in the GSH concentrations. The physiological significance of the high gastric GSH is unknown, but because this endogenous compound may strongly modulate (decrease or increase) the macromolecular binding of certain chemicals capable of inducing stomach tumors, the possible role of glutathione in the pathogenesis of chemically induced gastric cancer should be considered.
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PMID:High concentrations of glutathione in glandular stomach: possible implications for carcinogenesis. 57 89

Recent prospective epidemiological studies have shown an association between a low prediagnostic serum selenium (Se) concentration and the risk of cancer. Se concentrations in whole blood and plasma, and the activity of red cell and plasma glutathione peroxidase (GSH-Px) were measured in patients with breast cancer, gastric cancer and colorectal cancer. The observed whole blood and plasma Se concentrations of healthy persons were 99.5 and 78.5 micrograms/L, respectively. Red cell and plasma GSH-Px activities of this group were: 21.0 U/g Hb and 256 U/L plasma. In all investigated cancer patients significantly lower whole blood and plasma Se concentrations, and significantly lower red cell and plasma GSH-Px activities were found, as compared with the values of healthy controls. Low Se concentrations of blood components may be indicative of increased cancer risk.
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PMID:Blood selenium concentrations and glutathione peroxidase activities in patients with breast cancer and with advanced gastrointestinal cancer. 182 38

Many antineoplastic agents alter the reduced glutathione (GSH) status of liver and tumor tissue by inhibiting cellular GSH-linked enzymes. Thus, intracellular GSH plays an important role in a wide variety of antineoplastic interventions regarding therapeutic efficacy and toxicity. Mean GSH values were 0.791 +/- 0.072 mg/m wet weight (ww) and 0.719 +/- 0.047 mg/g ww in gastric cancer tissue and nontumorous glandular mucosa, respectively. Whereas, the average GSH level of normal gastric mucosa was 1.709 +/- 0.135 mg/g, the mean GSH level of normal liver biopsies was 2.378 +/- 0.260 mg/g. The GSH values of normal liver tissue were higher than the hepatocellular GSH concentrations of patients with gastric adenocarcinoma and of another group of tumor-bearing patients who had received chemotherapy preoperatively. These results suggest that the GSH levels of tumor and liver may influence the efficacy and/or toxicity of chemotherapeutic agents.
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PMID:Liver glutathione contents in patients with gastric adenocarcinomas. 232 Dec 74

The purpose of these studies is to evaluate the anticancerous effects of tegafur suppository and Glutathione (GSH) as enhanced drug and compare the difference of the histopathological effects and tissue concentration of 5-FU and FT-207 in gastric and colon cancer. Thirty three patients with gastric cancer and 17 with colon cancer were treated by tegafur suppository at a dose of 1,500 mg/day and GSH, 1,200 mg/day intravenously. These patients were clinically divided into two groups, one of which was treated with tegafur suppository (Group A) and another administered with suppository and GSH (Group B). Five-fluorouracil was measured by GC-MF method and FT-207 was also done by HPLC method. After surgery, relationship between tissue concentration of 5-FU and histopathological effects were investigated. In gastric cancer, 5-FU concentration in cancer tissue was significantly kept high level in cancer tissue in patients treated with tegafur and GSH (Group B). However, there was no same results in colon cancer. These results seemed to be the difference of organ specificity. According to histopathological studies, well differentiated adenocarcinoma including papillary carcinoma were markedly effective compared to poorly differentiated adenocarcinoma in both cancer. This difference of anticancerous effect was supposed to be microangiographically different of microvascular architecture and quantity of anticancerous agents in tumor.
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PMID:[The effect of tegafur suppository and glutathione in patients with gastric and colonic cancer with special reference to the histopathological anticancer effect]. 311 14

This study was carried out to determine the relationships between blood trace metal concentrations and the clinical status of patients with cerebrovascular disease, gastric cancer and diabetes mellitus. The concentrations of blood trace metals were determined by flameless atomic absorption spectrophotometry. The concentrations were compared to clinical parameters such as blood biochemical parameters, CBC, etc. The contribution of blood trace elements to these three diseases and the possibilities for prophylaxis of these three diseases are discussed. The results obtained were as follow: 1. Patients with cerebrovascular disease showed generally lower concentrations than normal subjects, while the gender difference of the blood metal concentrations showed a pattern similar to that of normal subjects. In some combination, significant correlations were observed between blood metal concentrations and clinical biochemical parameters. 2. As the stage of gastric cancer advanced, blood copper concentrations increased. In all gastric cancer patients the blood copper concentration had a positive correlation with platelet counts, CEA and LDH, and a negative correlation with hemoglobin concentrations, hematocrit value and catalase. Plasma copper concentrations had a significant positive correlation with catalase. Corpuscular zinc concentrations had a significant positive correlation with platelet counts, CEA, ALP and LDH, and a significant negative correlation with hemoglobin concentration and GSH-Px. Corpuscular manganese concentrations had a significant positive correlation with CEA and LDH. 3. The blood copper concentration of patients with diabetes mellitus showed a distribution pattern similar to that of healthy subjects. Therefore, copper is not considered to be an important factor in diabetes mellitus. Diabetic patients treated by insulin injection showed increased blood zinc concentrations. Chromium, which is contained in GTF (glucose tolerance factor), showed lower blood concentrations in patients with severe complications, such as retinopathy or nephropathy. Therefore, it appears that chromium plays an important role in advancing diabetes mellitus.
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PMID:[Studies on the relationships between blood trace metal concentrations and the clinical status of patients with cerebrovascular disease, gastric cancer and diabetes mellitus]. 344 33

Selenium (Se) compounds have shown an inhibitory effect on chemically induced tumours in several laboratory models and there is an inverse epidemiological relationship between Se status and certain types of cancer. Little is known about the influence of Se on the development of stomach cancer. Three different forms of dietary Se, selenomethionine, sodium selenite, and high-selenium yeast were investigated as possible inhibitors of benzo(a)pyrene-induced forestomach tumours in mice. The effects of sodium selenite in combination with vitamin E, and of Se-deficiency were also studied. None of the dietary modifications had any effect on tumour incidence or number. Marked elevations of whole-blood glutathione peroxidase (GSH-Px) activities were observed in animals supplemented with all Se-compounds. High-selenium yeast caused the largest increase of GSH-Px activity followed by sodium selenite and selenomethionine. The results indicate that the inhibitory effect of Se on carcinogenesis may be specific with respect to organ site or tumour cell examined.
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PMID:Effects of dietary selenium compounds on benzo (a)-pyrene-induced forestomach tumours and whole-blood glutathione peroxidase activities in C3H mice. 375 57

The gamma-glutamyl-transferase activity, the total glutathione content, the GSH-peroxidase activity, and the GSH S-transferase activity using an aryl substrate were estimated in the S9 fraction of gastric biopsy specimens taken from patients with normal stomach morphology (n = 24), acute gastritis (n = 15), chronic-atrophic gastritis (n = 10), gastric ulcer (n = 9), and carcinoma of the stomach (n = 12). The total glutathione content of normal gastric mucosal specimens was significantly higher than that of human liver biopsy specimens, whereas the GSH-peroxidase and the GSH S-aryltransferase activities were much lower than those found in the liver. Specimens of gastric ulcer had significantly lower enzyme activities of GSH-peroxidase and GSH-aryltransferase, whereas gastric cancer tissue had significantly lower concentrations of total glutathione. The intraindividual comparison of tumorous and non-tumorous tissue showed a consistent decrease of total glutathione as well as of GSH-aryltransferase activity in carcinomatous tissue.
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PMID:Glutathione and GSH-dependent enzymes in the human gastric mucosa. 670 2

Thirty patients with gastric cancer were clinically studied by rectal administration of FT-207 suppository at a dose of 1500mg per day as a preoperative adjuvant chemotherapy. Eighteen of thirty patients were divided into two groups, 13 patients of which were only administrated with tegafur (FT-207) suppository (Group A) and 5 patients were administrated with glutathione (GSH) at a dose of 1200mg daily with FT-207 suppository (Group B): The tissue concentration of FT-207 and 5-FU in normal and cancer tissues was measured following the resection of the stomach. In addition, we studied anticancer effect of FT-207 suppository on the basis of our original pathological criteria. Experimental results revealed that 5-FU concentration in serum was reached to maximum at 3 to 4 hours following administration in both groups. The serum concentration in most cases of the former group was decreased to the lower level of the effective concentration for 8 hours, however the latter could be kept the effective concentration for more than 10 hours. The correlation between the tissue concentration and total dose was analyzed. 5-FU concentration, which was active substance of FT-207, in cancer tissue was higher than in normal one, especially in Borrmann II type cancer, but the difference of concentration was not found between group A and B. The correlation between total dose and anticancer effect was also analyzed. Histopathological effect in group A showed a mild change, such as necrosis of cancer nest. On the other hand, group B revealed a markedly effective change like scarring formation. As the result, administration of FT-207 suppository with GSH was clinically and histopathologically effective procedure as preoperative adjuvant chemotherapy.
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PMID:[Evaluation of pre-operative chemotherapy using FT-207 suppositories combined with glutathione--with special reference to histopathological antitumor effect]. 682 Aug 99

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.
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PMID:Gastric mucosal antioxidant activity in patients at increased risk of gastric cancer. 827 61

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.
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PMID:Glutathione S-transferases of female A/J mouse liver and forestomach and their differential induction by anti-carcinogenic organosulfides from garlic. 895 67


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