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 effectiveness of the intraperitoneal administration of cis-diamminedichloroplatinum (II) for peritoneal carcinomatosis by gastric cancers was evaluated through experimental and clinical studies. In experimental studies, the effect of sodium thiosulfate (STS) on cytotoxic activity of DDP was evaluated by MTT assay using human gastric cancer cell lines. The cytotoxic activity of DDP was reduced by 50% with 100-fold STS in the area under the curve (AUC), whereas 10-fold STS in AUC did not reduce the cytotoxicity of DDP. In clinical studies, patients were treated with one of three protocols: Group A was treated by the intraperitoneal injection (ip) of DDP at a dose of 70 mg/m2, and group B or C was treated by ip DDP at a dose of 110 mg/m2 with or without STS rescue. The pharmacodynamics and the adverse effects of treatments were evaluated between these three protocols. In group C, the means of AUC of STS were 2.43-, 10.8- and 86.8-fold those of total platinum in the peritoneal cavity, plasma, and urine, respectively. There were 1/5, 1/2 and 2/2 partial responses in peritoneal carcinomatosis patients treated with A, B and C. Renal toxicity was not observed in the patients treated with DDP and STS rescue. STS does not seem to reduce the antitumor activity of DDP in peritoneal cavity and plasma, while the renal cytotoxicity was reduced by STS rescue. The result led us to conclude that intraperitoneal DDP treatment combined with STS rescue would be useful chemotherapy against peritoneal carcinomatosis by gastric cancer.
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PMID:[Intraperitoneal administration of cis-diamminedichloroplatinum (II) for peritoneal carcinomatosis caused by gastric cancers]. 837 38

Intraperitoneal (IP) cisplatin administered at the time of intraabdominal malignancies such as gastric cancer may prevent or delay intraabdominal recurrence. Perioperative IP cisplatin raises concerns regarding systemic toxicity and retardation of wound healing. Systemic cisplatin toxicity may be reduced by administering its antidote, sodium thiosulfate (STS). A preclinical study of IP cisplatin in rats undergoing a small intestinal anastomosis was carried out. All animals that had received only cisplatin died in the postoperative period as a consequence of cisplatin toxicity. Tensile strength of the intestinal anastomoses was determined on the tenth postoperative day in the surviving animals. Animals that had received intravenous (IV) cisplatin with STS had significantly lower tensile strengths than both those receiving IP cisplatin with STS and STS alone. This study demonstrates the safety of perioperative cisplatin with STS protection by the avoidance of systemic toxicity and minimizing the cisplatin-related retardation of wound healing.
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PMID:Intraperitoneal cisplatin with sodium thiosulfate protection in rats with intestinal anastomoses. 846 90

Patients (459) with chronic gastritis, ulcers, polyposis and different types of gastric cancers were examined by endoscopic fluorescent technique using a special drug based on the sodium salt of fluorescein (F1). Eighty-five percent of gastric cancers showed positive fluorescence. The F1 distribution in the stomach of the rat with induced gastric cancer was examined. In all cases the level of F1 fluorescence in the tumor was higher than in the adjacent normal tissues of the stomach. Thus, all the obtained results confirm the selective accumulation of F1 in tumors of the stomach.
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PMID:Fluorescent diagnostics of human gastric cancer and sodium fluorescein accumulation in experimental gastric cancer in rats. 849

This paper describes the characteristics of exotoxins produced by Helicobacter pylori, and in particular the vacuolating toxin (VacA) and the cytotoxin-associated protein (CagA). The possible association between infection by strains of certain phenotypic or genomic types and the seriousness of gastroduodenal diseases is discussed. Helicobacter pylori induces various morphological changes in cells in vitro, but only infection by strains which induce cytovacuolation has been studied at present. In its native form, VacA is a protein aggregate made of subunits with a mass of 95 kDa. In vitro it stimulates a cellular v-type ATPase present on the endosomes and creates an acidic environment inside the vacuoles. It also alters in vitro a K(+)-dependent phosphatase activity and could impair the flux of sodium through the cells. Purified VacA causes ulceration in mice; experimental infection in mice with strains which also express the CagA protein causes gastric erosions, vacuolation and epithelial and stromal polymorphonuclear (PMN) cell infiltration. In vivo vacuolation can be observed in gastric cells from patients infected with type I (VacA-CagA positive) H. pylori. CagA is a protein of 128-140 kDa molecular weight, noncytotoxic and highly immunogenic. It is coexpressed in approximately 70% of cytotoxin-producing strains. In CagA positive strain infection, increased levels of interleukin-8 (IL-8) are secreted by the colonized gastric mucosa. Patients infected by cytotoxic strains and/or patients with anti-CagA antibodies are more likely to have active gastritis, and are more likely to develop peptic ulcer or gastric cancer. The different outcomes of infection could be determined by host factors, diet, or by the age at which infection is acquired.
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PMID:Helicobacter pylori exotoxins and gastroduodenal diseases associated with cytotoxic strain infection. 873 Feb 63

A high serum alpha-fetoprotein (AFP) level was found in a patient with endometrial adenocarcinoma of the uterus, which appeared to be hepatoid on histological examination. The AFP of this unusual patient was purified by immunoaffinity chromatography and characterized. The electrophoretic profiles on sodium dodecyl sulfate-polyacrylamide get electrophoresis both before and after glycopeptidase F treatment were indistinguishable from those of a hepatoma AFP. This indicates that the patient's AFP was also composed of a single polypeptide chain of Mr 67,000 and an N-linked sugar chain of Mr 3,000. Amino acid sequence analyses of this AFP, and of AFP from hepatoma and umbilical cord serum indicated that the N-terminal sequences were essentially the same. The sequence, Arg-Thr-Leu-His-Arg-Asn-Glu-Tyr-Gly-Ile, was slightly different from previous reports, but matched that deduced from the cDNA sequence. AFP isoforms due to microheterogeneity of the sugar chain were analyzed by lectin affinity electrophoresis using a series of lectins. The AFP isoform profiles were distinct from those of proteins derived from cord serum, hepatoma, yolk sac tumor and gastric cancer. The reverse-transcription of RNA from the tumor tissue followed by a polymerase chain reaction using primers with AFP-specific sequences gave a product of the size and nucleotide sequence expected for AFP. mRNAs possessing the requisite sequences for albumin and transferrin syntheses were also detected in the tumor. The expression of these hepatocyte-specific proteins supported the hepatoid nature of this tumor.
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PMID:Biochemical characterization of alpha-fetoprotein and other serum proteins produced by a uterine endometrial adenocarcinoma. 876 25

The customary salting and pickling of fish in high risk gastric cancer regions were modeled to explore the relevant causative chemicals. The fish Sanma hiraki was treated with sodium chloride and sodium nitrite at pH 3. Previously, it had been found that an extract of the treated fish was mutagenic in Salmonella typhimurium TA 1535 without S9 and also that it induced glandular stomach cancer upon gavage to rats. We now demonstrate that the mutagenicity was enhanced by preincubation of the raw meat for several days before salt-nitrite treatment. HPLC techniques showed that three mutagens were present in the fish extract. One of the mutagens was found to be stable over the pH range of 1.0-9.0. This mutagen was purified by silica gel solid phase extraction, followed by a series of reverse phase HPLC steps, and was characterized by low and high resolution MS, NMR, and FT-IR. While N-nitroso compounds were generally believed to be associated with gastric carcinogenesis, it was unexpectedly found that the mutagen has the novel structure 2-chloro-4-methylthiobutanoic acid (CMBA). Based on the structure, it seemed likely that methionine might be the precursor, and this was, indeed, proven. Both salt and nitrite are essential factors for forming this mutagen. The yield of CMBA was linear for chloride concentrations from 0 to 800 mM NaCl. Of 20 amino acids reacted with nitrite and chloride at pH 3, only methionine generated a mutagen for S. typhimurium TA 1535. Tryptophan gave a product mutagenic in S. typhimurium TA 100 and TA 98, but not TA 1535, and in the case of tyrosine, the mutagen was active only for TA 100. These results suggest an important role for salt in gastric carcinogenesis and provide new approaches for exploring the formation of mutagens/carcinogens for specific target organs.
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PMID:Gastric carcinogenesis: 2-chloro-4-methylthiobutanoic acid, a novel mutagen in salted, pickled Sanma hiraki fish, or similarly treated methionine. 892 17

Cytotoxic activity of sodium ascorbate against a human glioblastoma T98G cell line was concentration-dependently inhibited by serum in the RPMI1640 medium. The inhibitory effect of sera from pancreatic or stomach cancer patients was significantly higher than that of fetal bovine serum (FBS), with or without heat-inactivation. The cytotoxic activity of sodium ascorbate almost completely disappeared in 60-80% of patient sera. ESR spectroscopy revealed that both patient sera and FBS increased the ascorbyl radical intensity, but to significantly lower extents, as compared with that attained by RPMI1640 medium. The present study suggests the importance of re-evaluating the efficacy of not only ascorbate but also other chemotherapeutic drugs under more physiological conditions.
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PMID:Inhibition of cytotoxic activity of ascorbate by human cancer patient sera. 906 88

To explore the causes of the threefold variation in mortality rate from gastric cancer in Japan, we studied the geographic correlations between nutrient consumption and the disease in five Public Health Center districts including the regions with the highest and lowest mortality rates in the country. In the winters of 1989-1991, a three-day weighed food record was collected from 207 men and the wives of 165 of the men sampled from the five districts. The average daily consumption of selected nutrients was computed and correlated with the age-adjusted mortality rates from gastric cancer. Partial rank correlation coefficients adjusted for sex and other nutrients were 0.45, -0.80, -0.20, and -0.07 for sodium, carotene, ascorbic acid, and retinol, respectively. The results suggest that variation in gastric cancer mortality in Japan may be partly accounted for by the regional differences in consumption of sodium, carotene, and possibly ascorbic acid.
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PMID:Nutrient consumption and gastric cancer mortality in five regions of Japan. 910 62

Helicobacter pylori appears to play a major role in the development of gastric cancer in humans. The mechanism behind the carcinogenic or co-carcinogenic effects of H. pylori has not been established. Ammonia, generated by urea from H. pylori, has been studied as a possible cause. However, the ammonia-monochloramine system has been shown to play a more important role in H. pylori-associated mucosal injury. Therefore, the effects of combined administration of monochloramine and methionine, singly or together, on the development of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in inbred Wistar rats. After receiving oral MNNG and regular chow pellet for 25 weeks, rats received regular chow pellets or chow pellets containing 20% ammonium acetate, and normal tap water or water containing 30 mM sodium hypochlorite, with or without a subcutaneous injection of methionine, until the end of the experiment (week 52). Treatment with both ammonium acetate and sodium hypochlorite, which produce monochloramine, significantly increased the incidence of gastric cancers in week 52, whereas the concomitant administration of methionine with ammonium acetate and sodium hypochlorite significantly attenuated such enhanced gastric carcinogenesis. Spectrophotometric examination revealed that methionine scavenged monochloramine. Our findings suggest that H. pylori-associated gastric carcinogenesis may be mediated by monochloramine.
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PMID:Attenuation by methionine of monochloramine-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. 953 64

A 67-old man was referred to our hospital because of dyspnea on exertion and severe hypoxia. He had been given, tegafur and OK 432 for seven years following an operation for gastric cancer. Pulmonary hypertension was noted by right heart catheterization. The findings of a transbronchial lung biopsy resulted in a diagnosis of pulmonary veno-occlusive disease. Pulmonary hemodynamic studies were performed for five different agents: nifedipine, beroprast sodium (PGI2), nitroglycerin, theophylline, and isosorbide dinitrate. However, none of these agents showed significant effects on pulmonary arterial pressure or pulmonary vascular resistance. Treatment with glucocorticoid relieved the patient's symptoms without any apparent effect on pulmonary hemodynamics. The long-term administration of anticancerous agents (tegafur) were thought to have caused pulmonary veno-occlusive disease to develop in this patient.
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PMID:[Pulmonary veno-occlusive disease developed in a man given long-term treatment with anticancerous agents]. 986 89


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