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)

Dyspepsia may result from over-indulgence in alcohol and food, or from anxiety and emotional problems. It may also indicate a peptic ulcer, oesophagitis or less commonly, gallstones or gastric cancer. Investigation by endoscopy or barium studies is always indicated when an organic lesion is suspected. Reassurance, tranquillizers and antispasmodics help patients with functional dyspepsia. Antacids given hourly between meals are important in the treatment of all symptomatic peptic ulcers. Cimetidine causes rapid symptomatic relief of duodenal ulcer symptoms, and most ulcers will heal with six weeks' therapy. Gastric ulcer can be treated with carbenoxolone, but this drug is avoided in the elderly and in patients with cardiac failure or hypertension. Anticholinergic drugs are of value in duodenal ulcer, especially for night pain, but they should not be used in patients over the age of 50. Special diets are of no value. For the heartburn of oesophagitis, weight reduction and a regime of regular antacid therapy remain the important measures.
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PMID:The treatment of dyspepsia. 92 13

In attempts to avoid the side-effects derived from a scald on the peritoneo-serosal surface during intraperitoneal hyperthermic perfusion (IPHP) for advanced gastric cancer, a randomized study using cimetidine, a histamine H2-receptor antagonist, was carried out on 18 patients with advanced gastric cancer. Cimetidine, 50 mg/kg, was administered intravenously and immediately before IPHP. The background characteristics of the patients and the types of surgical treatment used were almost the same between each group of patients, whether or not cimetidine was given. The perfusion time in the cimetidine and control groups was 123 +/- 9 and 117 +/- 9 min, respectively. The inflow and outflow temperatures of the perfusate were 46.3 +/- 0.4 and 44.2 +/- 0.1 degrees C in the cimetidine group, respectively, whereas in the control group the temperatures were 46.0 +/- 0.3 and 44.1 +/- 0.2 degrees C, respectively. In the nine patients who were given cimetidine, the histamine concentrations in the peripheral blood increased significantly, compared to those in the nine controls; this resulted from the release of histamine into the circulating blood. Higher concentrations of protein were observed in the post-hyperthermic intraperitoneal exudate of the control group for 3-24 h after IPHP and, consequently, post-hyperthermic hypoproteinaemia was remarkable in the control group. These data suggest that when pre-IPHP cimetidine was prescribed for patients with gastric cancer treated with IPHP, the peritoneo-serosal surface was protected from scald injury and the side-effects of IPHP were reduced.
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PMID:Prevention of scald injury on the peritoneo-serosal surface in advanced gastric cancer patients treated with intraperitoneal hyperthermic perfusion. 191 49

The effect of cimetidine, a histamine type 2 receptor antagonist, on lymphocyte responses to phytohemagglutinin (PHA) was studied in 58 gastric cancer patients. Cimetidine significantly enhanced lymphocyte responses to PHA in certain gastric cancer patients. The degree of enhancement was associated with tumor load. A significant inverse correlation was observed between the degree of enhancement and that of the original lymphocyte responses to PHA. The degree of enhancement significantly correlated with the proportions of OKT3 and OKT8 positive cells. A determination of the degree of enhancement in selected gastric cancer patients revealed it to fall to a low level after a certain period following curative gastric resection. These data appear to favor the in vivo therapeutic administration of cimetidine to advanced gastric cancer patients.
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PMID:Cimetidine-mediated augmentation of lymphocyte responses to phytohemagglutinin in gastric cancer patients. 292 18

Over a period of 1 year 83 patients, admitted to Nottingham hospitals with gastric neoplasms, were interviewed in order to identify the extent of delay in diagnosis and the possible causes. The mean age was 71 (S.D. +/- 10) and there was a male preponderance of 1.8:1. The median delay from onset of symptoms to diagnosis was 22 weeks (IQR 14-35). Delay by the patient after the onset of symptoms before seeking medical help was 4 weeks (IQR 2-12). Family doctor delay was 7 weeks (IQR 3-14) and this was caused by trial of medication and radiological investigations. The hospital delay of 3 weeks (IQR 2-7) was due to patients waiting for multiple out-patient investigations, inadequate investigation of iron-deficiency anaemia, failure to follow-up gastric ulcers and difficulty in getting histological confirmation of clinically suspicious lesions. Seventeen (20%) patients were treated with a H2-receptor antagonist (Cimetidine). There was no significant difference in the delay caused by Cimetidine when compared with that due to antacids (Mann-Whitney U = 232, P greater than 0.5), and there was no difference in survival between these patients and those not treated with Cimetidine (chi 2 = 1.9, P less than 0.1). In this study only one of 80 patients had an early gastric cancer, which supports the view that gastric carcinoma is asymptomatic in its early stages and mass screening of the population would be the only way to detect carcinoma at this stage in its development. Family doctor delay can be reduced by immediate referral of patients to hospital for investigation prior to commencing medication. Hospital delay can be improved by avoiding duplication of investigations, fully investigating iron-deficiency anaemia and following up gastric ulcers with endoscopy and biopsy till fully healed.
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PMID:Gastric cancer--delay in diagnosis and its causes. 342 34

Nitrosocimetidine (NC) and 1-methyl-2-nitro-1-nitrosoguanidine (MNNG) are closely related N-nitrosamidines. NC is the nitrosated derivative of cimetidine (Tagamet), an orally administered compound used extensively in the treatment of gastric ulcers. MNNG is a potent carcinogen capable of initiating tumors close to the site of administration and used experimentally to produce stomach cancer. It has become evident that the primary metabolic fate of both of these agents is denitrosation. We have discovered an activity in the cytosol fraction of hamster liver which is capable of denitrosating these nitrosamidines with an efficiency approaching 100%. The activity is heat sensitive and requires reduced glutathione as a cofactor. Inhibition of the denitrosating activity with compounds which inhibit in parallel the conjugation of glutathione with 1-chloro-2,4-dinitrobenzene (CDNB) provides evidence that the activity is glutathione transferase. One molecule of reduced glutathione is consumed in each denitrosation event. Nitrite is formed as denitrosation proceeds with a yield equivalent to 25-50% of the denitrosated product produced. Glutathione disulfide is a minor reaction product, representing 3% of the denitrosation product yield in the MNNG case and 12% in the NC case. Thus far in our survey of N-nitrosamines, N-nitrosamides and N-nitrosamidines, only the nitrosamidines appear to be vulnerable to the cytosolic denitrosating activity. In an attempt to evaluate the importance of the glutathione-dependent reaction in the intact hamster, we have depleted glutathione by pretreatment with the commonly used agents diethyl maleate (DEM) and L-buthionine-S,R-sulfoximine (L-BSO). Nitroso compound was administered i.v. and the circulating blood levels of intact and denitrosated compound 5 min after dosing quantified. NC- and MNNG-derived methylation of organ DNA was also monitored. Pretreatment had no effect on the cytosolic denitrosating or CDNB-conjugating activities. L-BSO pretreatment had no apparent effect on the denitrosative metabolism of NC or MNNG. With DEM pretreatment we obtained clear indications of a decreased rate of denitrosation and observed a 10-fold increase in MNNG-derived liver DNA methylation. The differential effects of these pretreatments are taken as an indication that DEM-sensitive processes other than those requiring glutathione dominate N-nitrosamidine denitrosation in the hamster.
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PMID:Evidence for cytosolic glutathione transferase-mediated denitrosation of nitrosocimetidine and 1-methyl-2-nitro-1-nitrosoguanidine. 367 6

Cimetidine has been shown to have low acute toxicity in dogs and rodents. Repeated-dose studies of up to 24 months' duration in rodents at doses up to 950 mg day-1 kg-1 showed few adverse effects. Liver weight was consistently increased at the highest dose and testis, prostate and seminal vesicle weights were reduced in a dose- and time-related fashion. Cimetidine was not carcinogenic in the rat. In tests of up to 1 year's duration in dogs two animals receiving 504 mg day-1 kg-1 had to be killed before the end of the study. They had degenerative changes in the liver and renal tubular nephrosis. These and other dogs at 504 mg day-1 kg-1 had elevated serum transaminases. No such changes were seen at 366 mg day-1 kg-1 or less. Prostate weights were reduced in a dose- and time-related fashion. In a 7-year study in dogs, specifically designed for the purpose, no changes of the stomach mucosa were seen during regular biopsy. Although shown to be a mild anti-androgen, cimetidine produced no significant adverse effects in reproductive studies. The large body of evidence that cimetidine is not a risk for gastric cancer is reviewed. Over 30 million patients have so far been treated with cimetidine and the prediction from the animal studies that it would be an extremely safe therapeutic agent has been borne out in practice.
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PMID:Toxicology of cimetidine. 398 2

A correlation between cimetidine and gastric cancer has been suggested. Nitrosation of cimetidine in the presence of nitrite and HCl and mutagenic activity as well as DNA damage in mammalian cells displayed by nitrosocimetidine, as these phenomena occur in vitro, were the supporting hypothesis. Previous studies have shown that liver DNA damage was a well correlated index of potential carcinogenic activity of N-nitroso compounds and that such a damage was found after long-term simultaneous oral administration of aminopyrine and nitrite in rats. In this work, liver DNA fragmentation was investigated by three different techniques: DNA alkaline elution, DNA alkaline denaturation followed by hydroxylapatite chromatography and a new viscometric method markedly more sensitive than the above mentioned ones in detecting DNA damage. Evidence of DNA damage was not gained in any of the groups of rats treated with high single or successive oral daily doses of cimetidine (250 mg/kg) along with nitrite (80 mg/kg) in approximately equimolar amounts. Cimetidine and nitrite given alone were also ineffective. The lowering of gastric pH, obtained with fasting and histamine administration before giving cimetidine and nitrite combination in a single dose, did not favor the induction of liver DNA fragmentation neither in the above condition nor even when the amount of cimetidine was lowered to 125 mg/kg in order to obtain an approximately 2-fold molar amount of nitrite.
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PMID:Absence of DNA damage in liver of rats given high doses of cimetidine and sodium nitrite. 706 84

Cimetidine has demonstrated a survival benefit in a randomized trial as adjuvant therapy for gastric cancer. We have demonstrated expression of histamine receptors on colon cancer cell lines and inhibition of their growth with cimetidine. Cimetidine also activates suppressor T cells and stimulates cell-mediated immunity. We therefore performed a randomized controlled clinical trial to determine the effect of cimetidine 400 mg given twice daily in conjunction with chemotherapy vs chemotherapy alone. Thirty-eight patients were randomized and 35 patients were eligible for further analysis. Both groups were well matched for pre-treatment characteristics. There was no difference in overall response. There was, however, a significantly increased rate of CEA response in the cimetidine group. Four of 11 patients (36%) in the cimetidine group had a CEA response compared to none of eight in the control. Meaningful comparisons of overall survival cannot yet be made. This study demonstrates that cimetidine has encouraging activity in increasing CEA response in patients with metastatic colorectal cancer treated with chemotherapy. This observation needs to be extended in a larger randomized study, which is currently underway.
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PMID:A randomized trial of cimetidine with 5-fluorouracil and folinic acid in metastatic colorectal cancer. 758 98

The modulation effects of cimetidine on the production of IL-2 and IFN-gamma by the peripheral blood mononuclear cells in 31 patients with gastric cancer and 32 normal subjects were studied. Their T lymphocyte subsets were also assayed. The IL-2 and IFN-gamma activity in patients were significantly lower than that in normal subjects (P < 0.01). Cimetidine could significantly promote IL-2 and IFN-gamma production. There was a significant negative correlation between OKT8 subsets and the activity of IL-2 and IFN-gamma (P < 0.01). The results showed that cimetidine could be used as an adjunct in the treatment of advanced neoplasm.
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PMID:[Modulation effect of cimetidine on the production of IL-2 and interferon-gamma in patients with gastric cancer]. 780 62

Since pretreatment with cimetidine results in the prevention of scald injury on the peritoneo-serosal surface caused by intraperitoneal hyperthermic perfusion (IPHP) for advanced gastric cancer, the diverse influence of IPHP on patients who were either given or not given cimetidine was studied both during and after IPHP treatment. Cimetidine 50 mg/kg was injected intravenously into 12 patients immediately prior to IPHP. There were no statistical background differences between the cimetidine and control groups (those not given cimetidine). The inflow and outflow temperatures of the hyperthermic perfusate in the control and cimetidine groups were 46.1 +/- 0.1 degree C and 44.1 +/- 0.1 degree C and 46.3 +/- 0.1 degree C and 44.2 +/- 0.04 degree C, respectively. Either the pre-IPHP hypothermia or IPHP in the control group resulted in a considerable increase in serum noradrenaline and adrenaline. The intravenous administration of cimetidine led to a stransient but moderate drop in the mean blood pressure as well as a delayed appearance of high concentrations of noradrenaline and adrenaline, induced by high concentrations of circulating histamine released with cimetidine. These results suggest that the sympathetic nervous responses were activated either by hypothermia or hyperthermia. The transient hypotension and delayed increases of both serum catecholamines were attributed to a marked increase in circulating histamine, released with the intravenous cimetidine.
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PMID:Metabolic changes in cimetidine treatment for scald injury on the peritoneo-serosal surface in far-advanced gastric cancer patients treated by intraperitoneal hyperthermic perfusion. 832 32


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