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)

X-Prolyl dipeptidyl-aminopeptidase (no EC no. assigned) activity in normal and pathological human sera was assayed with several newly synthesized X-proline p-nitroanilides as chromogenic substrates. Normal values for 88 healthy subjects (15 to 81 years old), with glycylproline p-nitroanilide as substrate at pH 8.7, were 54.9 +/- 1.5 (SE) (range, 25.7 - 96.0) mumol/min per liter of serum at 37 degrees C. The results suggest that the enzyme activities with all X-proline p-nitroanilides were increased in patients with hepatitis and decreased in patients with gastric cancer. On Sephadex G-200 column chromatography, normal human sera showed a single peak of enzyme activity with glycylproline p-nitroanilide as the substrate, which coincided with the peak with glycylproline beta-naphthylamide but was different from the peaks with leucine beta-naphthylamide. Sera from patients with hepatitis or liver cirrhosis showed an increase in the normal peak and the appearance of another new peak with glycylproline p-nitroanilide as substrate.
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PMID:X-Prolyl dipeptidyl-aminopeptidase activity, with X-proline p-nitroanilides as substrates, in normal and pathological human sera. 94 33

Exposure to nitrate and propensity for endogenous nitrosation were examined in 80 healthy males, aged 25-40 years, residing in areas of Italy with long-standing high (Florence) and low (Cagliari) rates of gastric cancer. Nitrate exposure was assessed by measurement of urinary nitrate excretion over 12 hr, and endogenous nitrosation was assessed using the N-nitrosoproline test (NPRO-test). Our hypothesis was whether the geographic variation in cancer rate correlated with nitrate exposure or nitrosating ability. Exposure to background sources of NPRO was significantly higher in the high-risk subjects (phi = 0.04) whereas no differences were found in exposure to nitrate or in urinary NPRO levels after L-proline loading (test NPRO levels). The regional difference in test NPRO was almost completely accounted for by background NPRO exposure. Examination of individual rather than grouped data revealed that exposure to nitrate was a major factor in NPRO formation. No other factors studied (age, dietary-questionnaire-assessed intake of anti-oxidant vitamins) had a significant effect. Geographical variation in gastric cancer risk did not, therefore, correlate with either nitrate exposure or propensity for endogenous nitrosation of L-proline.
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PMID:Nitrate and N-nitrosoproline excretion in two Italian regions with contrasting rates of gastric cancer: the role of nitrate and other factors in endogenous nitrosation. 154 7

The N-nitrosoproline (NPRO) test has been used in studies in which populations at high risk of cancer have been compared with equivalent populations at lower risk, to examine whether the geographical variation in cancer risk correlates with propensity for endogenous nitrosation, as assessed by the NPRO test. The usual method employed has been to determine NPRO in 12- or 24-h urine samples, after ingestion of L-proline, in a representative sample of the general population. We present results from one such geographical study conducted in two regions of Italy (Florence and Cagliari) with an approximately three-fold variation in gastric cancer mortality. The nonsignificant difference in mean NPRO excretion between the two populations was insufficient to explain the difference in cancer risk. The fact that there are appreciable international differences in formation of NPRO suggests, firstly, that nitrosation may be of relevance to cancer risk in some countries but not in others and, secondly, that variations within one country may not be large enough for significant geographical differences to be evident. Multivariate analysis of individual, rather than grouped, results from our Italian study made it possible to quantify the relevance of different factors to NPRO formation: a major factor is exposure to nitrate. Important relationships may be missed by analysing only grouped data.
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PMID:The N-nitrosoproline test as a measure of cancer risk in geographical comparison studies: results from Italy and an overall comparison. 185 39

The hypothesis that endogenous chemical nitrosation in the normal stomach in early life could play a crucial role in inducing chronic atrophic gastritis/intestinal metaplasia in later life was tested by applying the N-nitrosoproline (NPRO) test to 12-h urine samples from about 50 children (aged 8-14 years) living in high- and low-risk areas for stomach cancer. The median values of NPRO and the sum of four nitrosamino acids analysed were 0.28-0.84 micrograms/12 h and 0.75-1.75 micrograms/12 h, respectively. The NPRO level after proline intake was significantly higher in children from a high-risk area than in those from a low-risk area (p less than 0.04), and markedly reduced after ingestion of ascorbic acid and proline (p less than 0.05). Urinary nitrate level was lower than that of adults. NPRO levels on the day of proline intake, however, correlated well with nitrate levels (p less than 0.001), indicating that children in a high-risk area in Costa Rica have high endogenous nitrosation potential. Blood samples were also collected from about 300 children (aged 7-20 years) and analysed for antibodies against Campylobacter pylori, a suspected gastritis-causing bacteria. About 71% of children in both high- and low-risk areas for stomach cancer had antibodies. In addition, raw and cooked beans, which are consumed very frequently in Costa Rica, were collected from families in both areas and analysed for levels of nitrite/nitrate, total N-nitroso compounds and genotoxicity in the SOS chromotest.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exposure to N-nitrosamines and other risk factors for gastric cancer in Costa Rican children. 185 42

Several recent case-control studies of gastric cancer have demonstrated the protective effect of consumption of vegetables. According to Correa's model of gastric carcinogenesis, the initiating agent is N-nitroso compounds either ingested or formed in vivo. In our study of endogenous nitrosation, we measured intragastric formation of N-nitroso compounds in 285 individuals by the nitrosation of proline; in this presentation we analysed the effect of consumption of vegetables on urinary excretion of N-nitrosoproline (NPRO). When adjustment was made for the dominating determinants of NPRO excretion (total nitrate intake and tobacco smoking), a marked difference in the effects of consumption of raw and cooled vegetables was seen: consumption of cooked vegetables increased endogenous nitrosation of proline, while consumption of raw vegetables had only a marginal effect. We suggest that the difference between raw and cooked vegetables is due to destruction of ascorbate in the cooking of the vegetables. The lack of a protective effect of consumption of raw vegetables on the rate on endogenous nitrosation of proline indicates, however, that the determinants of nitrosation of proline and the determinants of gastric cancer risk may be different.
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PMID:Urinary excretion of N-nitrosoproline in relation to consumption of raw and cooked vegetables in a Danish rural population. 185 43

Etiological factors for gastric cancer, among others, involve consumption of smoked, salted, and pickled fish of certain types. Their chemical nature is not yet fully established but probably involves diazo phenols, and their formation can be prevented either by omitting the salting and pickling process, or by using vitamins C and E on the food prior to salting, pickling, or smoking. Both preventive approaches would limit the formation of mutagenic and carcinogenic diazo phenols. Sugimura and associates discovered new types of mutagens as heterocyclic amines that are formed during frying or broiling of meats and fish. In rats, these amines induce cancer specifically in organs such as breast, colon, or pancreas, associated with Western-type nutrition where promotional elements such as dietary fat play an enhancing role. Thus, inhibition of the formation of these new carcinogens during cooking would remove the genotoxic components from the diet. Mixing 10% soy protein with ground meat prior to frying prevents the formation of these mutagens presumably by affording a lower surface temperature. More effective is the addition of tryptophan, proline, or mixtures thereof, which specifically blocks the formation of these mutagens/carcinogens, probably by competing for reactive intermediary aldehydes, so that these cannot interact with the normal essential target, creatinine. Thus, we have available practical, yet science-based, mechanistically understood procedures to prevent the formation of carcinogens associated with important types of cancer prevalent in many countries.
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PMID:Prevention of formation of important mutagens/carcinogens in the human food chain. 218 63

Urine samples were collected from 96 inhabitants of a high-risk rural area and a low-risk urban area for stomach cancer in Poland, according to the following protocol: (1) when they were undosed; (2) after ingestion of proline 3 times a day; and (3) after ingestion of proline together with vitamin C 3 times a day. The samples were analyzed for N-nitrosamino acids and nitrates, as indices of exposure to preformed and endogenously formed N-nitrosamines. The median values of N-nitrosoproline (NPRO) and N-nitrosothiazolidine 4-carboxylic acid (NTCA) excreted in the urine of undosed subjects were not different between the two areas; but N-nitrososarcosine and 3-(N-nitroso-N-methylamino)propionic acid levels were 3- to 4-fold higher in subjects of the high-risk area. After intake of proline, the NPRO level increased (p less than 0.02) only in subjects in the high-risk area; intake of vitamin C tended to inhibit this increase in NPRO and lowered the levels of other nitrosamino acids. The urinary level of nitrates was 1.4-fold, but significantly higher among subjects in the high-risk area than among those in the low-risk area; nitrate levels were not correlated with the amounts of cured meat or types of vegetables consumed. Urinary nitrate levels and excretion of NPRO, NTCA and the sum of all nitrosamino acids analyzed showed positive, though modest, correlations. These results indicate a higher potential for endogenous nitrosamine formation, possibly by intragastric nitrosation among subjects in the high-risk rural area.
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PMID:Urinary excretion of N-nitrosamino acids and nitrate by inhabitants of high- and low-risk areas for stomach cancer in Poland. 258 63

The presence of kinins in ascitic tumor fluids from rodents and human patients was identified and quantified. In bioassay, kinin content was found to be 1 to 40 ng/ml, and by enzyme immunoassay, 0.6 to 2.5 ng/ml. In particular, a high kinin content, 40 ng/ml, was found in the ascites of a gastric cancer patient by bioassay. Purification of this kinin in the ascites from the gastric cancer patient was performed by ethanol precipitation, gel filtration and reversed-phase high-performance liquid chromatography (HPLC). Two peaks (peak A and peak B) showed kinin activity. Peak A did not correspond to either bradykinin or other known kinins, such as lysyl-bradykinin and T-kinin, whereas peak B corresponded to bradykinin. Peak A contained 8 amino acid residues from bradykinin minus one proline plus an additional hydroxyproline. Sequence analysis of peak A showed that the proline at the third amino acid residue of bradykinin was replaced by hydroxyproline. The retention time of peak A on reversed-phase HPLC was exactly the same as that of synthetic hydroxyprolyl3-bradykinin (Hyp3-bradykinin) but was distinguishable from des-Pro3-bradykinin. Thus, these results demonstrate for the first time the presence of Hyp3-bradykinin in mammalian system.
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PMID:Quantification, isolation and structural determination of bradykinin and hydroxyprolyl-bradykinin in tumor ascites. 264 May 67

A high molecular weight, mucous glycoprotein (MG) from the pleural fluid of lung adenocarcinoma was purified by the DEAE-cellulose, gel-filtration and wheat germ agglutinin affinity chromatography. Protein portion of the molecule was composed of amino acids rich in serine, threonine and proline, but methionine and tyrosine concentrations were relatively low. About 65% of the weight, was composed of galactose, galactosamine, glucosamine, fucose and sialic acid. The gel-filtration pattern on Sepharose 4B revealed Mr greater than 10(6) Da. The SDS-PAGE pattern revealed a main band at the position of the Mr about 350 kDa under the reducing condition. Rabbit antibody against this molecule recognized mainly the peptide portion, and the radioimmunoassay (RIA) using the double antibody method was developed by this antibody. Serum MG level was low in healthy subjects and in benign diseases (0.8 +/- 0.7 U/ml; mean +/- SD and 1.1 +/- 2.3 U/ml, respectively). Thus, 3 U/ml was used as the cut-off value. The mean of serum MG levels and positive rates in malignant diseases were significantly high; 4.4 U/ml and 32.3% in lung cancer, 20.1 U/ml and 77.5% in pancreas cancer 11.6 U/ml and 64.3% in gastric cancer, 12.9 U/ml and 57.1% in hepatoma, 12.3 U/ml and 77.8 in colon cancer. Other malignancies such as ovarial and uterus cancer showed also high levels. Elevated values in these malignancies were observed frequently in patients with metastasis. On the other hand, the false positive cases were found in 10% of benign diseases. Determination of MG seems to be useful for the detection of several kinds of malignancies, but it is not adequately sensitive as a screening method for early cancer detection.
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PMID:Clinical significance of mucin-like high molecular weight glycoprotein originated from lung cancer as tumor marker. 274 68

Intragastric nitrosation has been implicated in the pathogenesis of gastric cancer and in precancerous conditions such as pernicious anaemia and the post-gastrectomy state. Intragastric nitrosation was assessed in at-risk patients by N-nitrosoproline (NPRO) excretion using both a conventional and a modified test. Twenty-four hour urinary excretion of NPRO was measured after oral administration of sodium nitrate (300 mg) and L-proline (500 mg) as an indirect indicator of intragastric nitrosation. In the conventional test no differences in intragastric nitrosation were found between at-risk patients and controls. In the modified test the loading dose of sodium nitrate was omitted and urinary NPRO levels were found to be significantly increased in Polya partial gastrectomy patients (P = 0.003) and post-vagotomy patients (P = 0.03) compared to controls. In pernicious anaemia patients NPRO levels were also higher than in controls but just failed to reach statistical significance. This study has confirmed that hypochlorhydria results in increased intragastric nitrosation, thus facilitating the formation of potentially carcinogenic N-nitroso compounds.
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PMID:Use of a modified N-nitrosoproline test to show intragastric nitrosation in patients at risk of gastric cancer. 276 71


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