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)

The author has studied the effects of alpha-difluoromethylornithine (alpha DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase; human fibroblast interferon (IFN beta); and their combination on human gastric cancer cell growth in vitro. alpha DFMO (from 0.1 to 4 mmol/l) inhibited cell growth in a dose-dependent manner. Both alpha DFMO (0.1 mmol/l) and higher doses of IFN beta (100 and 1000 IU/ml) caused only limited inhibition of cell growth. When alpha DFMO (0.1 mmol/l) was administered in combination with IFN beta (100 and 1000 IU/ml), synergistic antiproliferative activity was observed 7 days after continuous exposure. Although the mechanisms by which this effect occurs are unclear, it appears to be associated with direct inhibition of tumor cell proliferation, possibly by modulation of polyamine metabolism.
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PMID:Synergistic antiproliferative activity of human fibroblast interferon in combination with alpha-difluoromethylornithine against human gastric cancer cells in vitro. 156 61

A clone of human gastric cancer cells (AGS-6) and the parental line (AGS-P) from which it was isolated were used in cell survival studies to determine whether pretreatment for 24, 48 or 72h with alpha-difluoromethylornithine (DFMO, 5mM) would increase the cell's sensitivity to 5-Fluorouracil (5FU), Adriamycin (Adria), 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (MeCCNU), or Bleomycin (Bleo). Generally, the AGS parental cells were most sensitive to the anticancer agents after exposures to DFMO. However, there was no way to predict in advance from DFMO-induced changes in ornithine decarboxylase (ODC), polyamine or cell kinetics values, how long an exposure to DFMO was required before sensitization to an anticancer agent occurred. The degree of potentiation for a single drug was variable from time to time during exposure to DFMO, and broad differences in the sensitizations were demonstrated among the four anticancer drugs. The AGS-6 clone exhibited little or no increased sensitivity as a result of pretreatment with DFMO, even though the DFMO-induced reductions in ODC and polyamine values in these cells were similar to those produced in the more sensitive parental line.
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PMID:Schedule dependent potentiation of antitumor drug effects by alpha-difluoromethylornithine in human gastric carcinoma cells in vitro. 169 47

The induction of ornithine decarboxylase (ODC), a key enzyme of polyamine biosynthesis, is an early and obligatory event in the tumor-promoting step in animal models. The enzyme activity is also elevated in some human premalignant lesions. We determined the ODC activity in human gastric cancer tissue and in the mucosa of cancer-bearing stomach. We concluded that gastric cancer tissue had significantly elevated ODC levels over those of mucosa (157.8 versus 45.7, respectively; P less than 0.05). Among mucosa of the stomach, that of the pyloric gland had higher ODC activity than that of the fundic gland (42.8 versus 21.6, respectively; P less than 0.05). Moreover, mucosa from the cancer-bearing stomach had high ODC activity compared with gastric mucosa without cancer. ODC activity in cancer tissue and mucosa from cancer-bearing stomach was activated by GTP. In rat experiments, the properties of ODC induced by gastric carcinogen were analyzed. Transiently induced ODC by a single gastric intubation of N-methyl-N'-nitro-N-nitrosoguanidine was not activated by GTP whereas constitutively expressed ODC of N-methyl-N'-nitro-N-nitrosoguanidine-induced cancer-bearing stomach was activated by GTP. These results suggest that some tumor-promoting stimuli may be concerned in human gastric carcinogenesis and that mucosal ODC activity may be a useful marker for assessing the risk of gastric malignancy.
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PMID:Increased mucosal ornithine decarboxylase activity in human gastric cancer. 199 84

In order to predict the chemopreventive activity of garlic on gastric cancer, the effect of diallyl sulfide (DAS), a natural extract of the garlic, on MNNG-induced nuclear aberration (NA) and ornithine decarboxylase (ODC) activity in Wistar rat glandular stomach mucosa was studied. The results showed that NA and ODC activity were positively correlated to MNNG dose given 24 and 6 hr after oral intubation with MNNG. Oral or parenteral pretreatment with DAS significantly and dose-dependently inhibited MNNG-induced NA and ODC. These data suggest that DAS has the potential to inhibit MNNG-induced gastric cancer, supporting the epidemiological evidence of the chemopreventive effect of garlic on gastric cancer.
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PMID:[Protective effect of diallyl sulfide, a natural extract of garlic, on MNNG-induced damage of rat glandular stomach mucosa]. 207 38

Using male Wister rats, the ornithine decarboxylase (ODC) activity in the fundic mucosa has been determined from the duodenal juice with bile of a reflux model. The activity at 24 hours postoperatively presented a value approximately 18 times higher than the preoperative level. Though this level declined subsequently, it still was approximately two times higher four weeks later. The ODC activity in the corporal mucosa of humans was compared in 25 normal persons, in 21 patients with a gastric adenoma in 29 patients with a gastric cancer, in 20 patients who had undergone a Billroth I operation and in 20 patients who had undergone a Billroth II operation. No differences in ODC activity were observed among those with a gastric adenoma, a gastric cancer, and normal cases but significantly higher values were seen in cases with a remnant stomach, particularly those who had undergone Billroth II reconstructive surgery. Further, this activity tended to be especially high from 5 to 15 years postoperatively in cases with a gastric remnant.
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PMID:[The ornithine decarboxylase activity of the gastric remnant mucosa: the effect of the duodenal juice with bile on the gastric mucosa]. 231 91

In previous investigations using models for gastrointestinal cancer, the anticarcinogenic effects of diallyl sulfide (DAS), an organosulfur compound present in garlic, was established. In this study, we conducted experiments to determine whether DAS modulates two biomarkers, nuclear aberrations (NA) and ornithine decarboxylase (ODC) activity, in the glandular stomach mucosa of the Wistar rat. N-methyl-N'-nitro-N-nitrosoguanidine (MN-NG) induced dose-related NA and ODC activity in the glandular stomach 24 h and 6 h, respectively, after oral intubation with the carcinogen. Either oral or parenteral pretreatment with DAS significantly reduced the MNNG induction of NA or ODC. Furthermore, the suppressions were observed to be dose dependent. These data suggest that DAS may potentially inhibit MNNG-induced gastric cancer. In view of recent epidemiologic evidence linking reduced risk for gastric cancer with increased consumption of allium vegetables, it is clear that DAS has pluripotent effects as an anticarcinogen, although studies addressing a mechanism of action have yet to be reported.
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PMID:Effect of diallyl sulfide on MNNG-induced nuclear aberrations and ornithine decarboxylase activity in the glandular stomach mucosa of the Wistar rat. 263 29

The present study has investigated the question of whether or not hydrocortisone as a gene regulator plays a role in the expression of carcinogenic and cocarcinogenic actions of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and NaCl at the gastric epithelium. The interaction of local hydrocortisone, MNNG and NaCl was studied in vitro and in vivo using Swiss/ICR mice of both sexes. MNNG inhibited specific hydrocortisone binding with the cytoplasmic receptor from the glandular stomach of mouse. The intake of both excess NaCl and MNNG induced an increase in hydrocortisone turnover in the glandular stomach of mouse. Likewise, administration of either excess NaCl or MNNG increased the activity of ornithine decarboxylase in the glandular stomach of mouse. Long-term use of a salt-rich diet and MNNG drink induced an irreversible reduction in water consumption without affecting NaCl consumption, a dissociation of the hydrocortisone effect. The aforementioned MNNG effect on water turnover was more marked in female than in male mice. It is suggested that NaCl and MNNG produce a state of corticosteroid stimulation and androgen depression at the glandular stomach epithelium of mouse--a reproduction of the hormonal markers of gastric cancer.
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PMID:Interaction between N-methyl-N'-nitro-N-nitrosoguanidine and 2 steroid hormones in the glandular stomach of mouse. I. Acceleration of hydrocortisone turnover by use of a salt-rich diet and the carcinogen. 277 56

Epidemiological studies have indicated that the consumption of smoked fish and meat products is associated with an increased risk of stomach cancer. A commercial hickory smoke condensate (HSC) was evaluated for its tumour-initiating and promoting activities in the glandular stomach using short-term methods in vivo. HSC (1 ml of a 10-100% v/v solution/rat) was given orally, either with or without nitrite (25-100 mumols/rat) to male F344 rats. The potential of HSC to act as a glandular stomach carcinogen was revealed by the induction in the pyloric mucosa of the stomach of ornithine decarboxylase (ODC), replicative DNA synthesis (RDS) and DNA single-strand breaks. The administration of HSC with nitrite also induced unscheduled DNA synthesis in the pyloric mucosa, but led to decreased induction of ODC, RDS and DNA single-strand breaks in comparison with treatment with HSC alone. These results suggest that HSC contains substance(s) that have potential tumour-initiating and/or tumour-promoting activities and that reaction with nitrite generates new substance(s) that could act as potential tumour-initiators in the rat glandular stomach.
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PMID:Evidence of potential tumour-initiating and tumour-promoting activities of hickory smoke condensate when given alone or with nitrite to rats. 279 74

We studied the effect of inhibition of polyamine biosynthesis by alpha-difluoromethylornithine on the growth of a human gastric adenocarcinoma (CLEES) xenotransplanted in nude mice. CLEES is a well-differentiated gastric adenocarcinoma of the intestinal type. The doubling time has ranged from 7 to 10 days through 11 passages. Electron microscopic and immunohistochemical studies comparing the original tumor and xenotransplants showed similar structure and similar amounts of carcinoembryonic antigen. Polyamine biosynthesis is required for cell division. alpha-Difluoromethylornithine inhibits ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis. In this study, 48 athymic mice were used in two experiments. In the first experiment, two groups of 12 mice each were inoculated with CLEES tumor cells and received either tap water or a 3% alpha-difluoromethylornithine solution as drinking water. Tumor size was measured twice weekly. Tumor size was significantly decreased from controls by the fourth week of treatment and at all points of analysis thereafter for 7 wk. In the second experiment, alpha-difluoromethylornithine significantly reduced tumor concentrations of the polyamines putrescine and spermidine. In addition, the tumor content of DNA was significantly reduced in treated mice (0.64 +/- 0.16 mg) compared to controls (4.76 +/- 0.92 mg). Our data suggest that inhibition of polyamine biosynthesis may be a useful component of multidrug chemotherapy for human gastric adenocarcinoma. Establishment of tumor lines such as this gastric adenocarcinoma will facilitate further studies on the biological behavior of human gastric cancer and its response to chemotherapeutic manipulation in vivo.
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PMID:Inhibition of human gastric adenocarcinoma xenograft growth in nude mice by alpha-difluoromethylornithine. 313 Jan 88

Tautomycin isolated from Streptomyces spiroverticillatus is an inhibitor of protein phosphatases 1 and 2A. Tautomycin induced hyperphosphorylation of cytokeratin peptides in human keratinocytes (PHK 16-I cells) 30 times less strongly than did okadaic acid. Repeated applications of tautomycin (30 micrograms, 40 nmol/application) did not induce tumor promotion in a two-stage carcinogenesis experiment on mouse skin initiated with 7,12-dimethylbenz[a]anthracene, whereas okadaic acid (1 microgram, 1.2 nmol/application) as a control induced tumor promotion strongly. As for mucosa of rat glandular stomach, tautomycin induced ornithine decarboxylase 4 h after intubation into the stomach. The tumor-promoting activity of tautomycin was next studied in the glandular stomach initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Administration of tautomycin in the diet (1 mg rat-1 day-1), from week 9 to week 52 of the experiment, inhibited rather than enhanced tumor development in the glandular stomach initiated with MNNG. The percentages of tumor-bearing rats of the groups treated with MNNG plus tautomycin, MNNG alone, and tautomycin alone were 20.0%, 40.6%, and 0% respectively in week 52. The reason for the absence of tumor-promoting activity of tautomycin was studied in relation to tumor necrosis factor alpha (TNF alpha), an endogenous tumor promoter. We found that tautomycin neither enhanced TNF alpha mRNA expression in mouse skin nor induced TNF alpha release in a human stomach cancer cell line (KATO III cells), whereas okadaic acid did both. These results indicate that not all inhibitors of protein phosphatases are tumor promoters, and suggest that tumor promotion of the okadaic acid class of compounds is mediated by TNF alpha.
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PMID:Tautomycin: an inhibitor of protein phosphatases 1 and 2A but not a tumor promoter on mouse skin and in rat glandular stomach. 755 47


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