UMLS:C0024623 - FACTA Search

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Query: UMLS:C0024623 (gastric cancer)
36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter pylori (H. pylori) infection in the stomach is etiologically closely associated with chronic active gastritis, peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. In this study, we examined the antibody responses and cytokine profiles of three strains of mice (BALB/c, C3H/He, and C57BL/6) infected with H. pylori. Following this, correlations between host-immune reactions and intensity of inflammation were analyzed. H. pylori (ATCC43504) was intragastrically administered once a week to the mice from 4 weeks of age, and they were sacrificed at the ages of 4 and 7 months. In these mice, we examined the histology of the stomach, antibody titers against H. pylori, and serum levels of cytokines (IL-4, IL-10, TNF-alpha, IL-2 and Interferon-gamma). In BALB/c mice, inflammation of the stomach was minimal. Inflammation was observed in 63.6% of C57BL/6 mice and 33.3% of C3h/He mice. In C57BL/6 and C3H/He mice, all the cytokines tended to increase. In contrast, BALB/c mice were inactive in cytokine production except for IL-2. Two C3H/He mice developed severe inflammation with lymph follicles; one showed a response largely typical of Th-1, and the other showed a response largely typical of Th-2. Although a definite correlation was not shown between Th-1/Th-2 response evaluated by cytokine production and intensity of inflammation, it appears that in H. pylori-induced inflammation both cell-mediated (Th-1) and humoral (Th-2) immunity play a role in pathogenesis.
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PMID:Antibody and cytokine responses in Helicobacter pylori-infected various mouse strains. 954 93

Persons of blood group O are at increased risk of peptic ulcers. Enhanced binding of Helicobacter pylori to epithelial cells of persons of blood group O has been demonstrated. Release of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha by human leukocytes from 40 donors (10 from each ABO blood group) was measured after incubation in vitro with outer membrane protein preparations of H. pylori. Isolates DU (from a patient with a duodenal ulcer), GC (from a patient with gastric cancer), NE (from a patient with normal endoscopic findings), and NCTC 11637 bound in significantly higher numbers to group O leukocytes. Bacterial binding correlated with release of IL-6 and TNF-alpha but not of IL-10. Group O cells released significantly more IL-6 in response to DU, NE, and NCTC 11637, and the cells released more TNF-alpha in response to DU and NCTC 11637. Increased density of colonization of epithelial cells and higher inflammatory responses to H. pylori of persons of blood group O might contribute to increased susceptibility to peptic ulceration.
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PMID:Increased inflammatory responses of persons of blood group O to Helicobacter pylori. 1075 28

p53 is a tumor suppressor gene that is mutated in many human malignancies, including gastric cancer. It remains unclear why patients with germ-line p53 mutations (i.e., Li-Fraumeni syndrome) are not at increased risk for gastric adenocarcinoma, despite the fact that they show a high rate of many other tumors. Furthermore, the precise relationship between germ-line p53 mutations and the response to chronic bacterial infections (such as Helicobacter spp.) has not been investigated. To assess the role of germ-line p53 deletions in modulating the progression to gastric cancer, p53(+/-) and wild-type (WT) C57BL/6 mice were infected with H. felis. The gastric pathology and immune response in these two groups of mice were analyzed for up to 15 months postinfection. The gastric fundus and antrum were evaluated independently using a 0-4 scale to score inflammation, parietal and chief cell loss, mucus metaplasia, and helicobacter colonization. Nonparametric statistical analysis was performed to determine the effects of p53(+/-), infection status, and postinoculation (p.i.) time on inflammation, preneoplastic changes, invasive lesions, and helicobacter colonization. mRNA expression for gammaIFN, interleukin (IL)-1, IL-10, and IL-4 was quantified by PCR. Sera were also evaluated for H. felis antibody by ELISA. Antral inflammation increased significantly with time in infected mice. There was a significant, protective effect on the development of preneoplastic fundic lesions and invasive carcinoma attributable to the deletion of one p53 allele (P < 0.05). Submucosal invasive foci were observed in 9 of 11 WT-infected mice ranging from 13 to 15 months p.i.; invasion of adjacent submucosal blood vessels by glandular epithelia also was present in 5 of these mice. None of these lesions were observed in 33 p53(+/-) mice, infected or not, at any time p.i. p53(+/-) mice had significantly higher helicobacter colonization consistent with a Th2 host response. In sera from WT mice, IgG2a, considered a proinflammatory Th1 response, continued to rise throughout the 15-month study (P < 0.004). In contrast, IgG2a levels of the p53(+/-) mice were 50-60% lower than those of the WT mice at each time point (P range, <0.012 to 0.002) and did not progress in magnitude between 12 and 15 months of chronic H. felis infection (P = 0.167). mRNA levels for gammaIFN and IL-1 were significantly up-regulated in WT mice infected with H. felis (P < 0.05) but were slightly elevated or were at background levels in p53(+/-) mice. IL-10 and IL-4 mRNA expression was not significantly different from control samples. Our results support the hypothesis that germ-line deletion of one p53 allele results in a down-regulated Th1 response to gastric helicobacter infection, possibly because of T-cell senescence, which may indirectly protect against the development of gastric cancer and other epithelial-derived neoplasms associated with chronic inflammation.
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PMID:Germ-line p53-targeted disruption inhibits helicobacter-induced premalignant lesions and invasive gastric carcinoma through down-regulation of Th1 proinflammatory responses. 1183 May 22

The gram-negative bacterial pathogen Helicobacter pylori is a major cause of peptic ulcer disease and a risk factor for gastric cancer in humans. Adapted H. pylori strains, such as strain SS1, are able to infect mice and are a useful model for gastric colonization and vaccination studies. In this study we used a streptomycin-resistant derivative of H. pylori SS1 to analyze the colonization behavior and the success of vaccination in wild-type (wt) and various knockout mice of the BALB/c and C57BL/6J genetic backgrounds. We here report that BALB/c interleukin-4 knockout (IL-4(-/-)) mice are weakly overcolonized compared to the wt strain but that the IL-12(-/-) knockout results in a strong overcolonization (500%). Unexpectedly, in the C57BL/6J background the same knockouts behaved in diametrically opposed manners. The IL-4(-/-) mutation caused a 50% reduction and the IL-12(-/-) knockout caused a 95% reduction compared to the wt colonization rate. For C57BL/6J mice we further analyzed the IL-18(-/-) and Toll-like receptor 2 knockout mutations, which showed reductions to 66 and 57%, respectively, whereas mice with the IL-10(-/-) phenotype were hardly infected at all (5%). In contrast, the tumor necrosis factor receptor knockout (p55(-/-) and p55/75(-/-)) mice showed an overcolonization compared to the C57BL/6J wt strain. With exception of the low-level infected C57BL/6J IL-10(-/-) and IL-12(-/-) knockout mice, all knockout mutants were accessible to a prophylactic vaccination and their vaccination behavior was comparable to that of the wt strains.
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PMID:Colonization of C57BL/6J and BALB/c wild-type and knockout mice with Helicobacter pylori: effect of vaccination and implications for innate and acquired immunity. 1254 May 59

A host's immune-defense system is suppressive by many factors in patients with cancer. We have previously shown one possible mechanism behind the T-cell dysfunction, whereby H(2)O(2) secreted from macrophages in tumor-draining lymph node (MTDL) induced T-cell dysfunction with down-regulation of TCR zeta molecules. In the present study, we analyzed how MTDL affect T cells, with a particular focus on T-cell apoptosis, by co-culturing MTDL with autologous peripheral blood T cells in gastric cancer. Moreover, we characterized the MTDL according to surface marker, oxygen-burst capacity and intracellular cytokine status. T-cell apoptosis was significantly induced in comparison to T-cell alone control in patients with advanced disease, concomitant to the elevated caspase activity and following impaired T-cell function. In patients with early disease, no significant difference was seen in the proportions of T cells that underwent apoptosis between T cells plus MTDL and T cells alone. Moreover, the addition of a selective scavenger of H(2)O(2), catalase inhibited the apoptosis of T cells co-cultured with MTDL in patients with advanced disease. In the characterization of MTDL, the production of H(2)O(2) in MTDL from advanced disease was significantly higher than that in early disease. The amounts of intracellular IL-10 and IL-12 in MTDL in advanced disease were significantly higher than those in early disease. These results indicated that MTDL induced apoptosis of autologous T cells and this T-cell dysfunction was mediated by H(2)O(2) derived from MTDL. Furthermore, the characteristics of MTDL including the capacity of oxygen-burst and intracellular cytokine production were different depending on the disease progression.
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PMID:Macrophages in tumor-draining lymph node with different characteristics induce T-cell apoptosis in patients with advanced stage-gastric cancer. 1258 34

It was previously reported that monocytes/macrophages play an important role in mediating T-cell dysfunction in tumor-bearing hosts, in which monocytes/macrophages were found to induce the loss of T-cell functions concomitantly with induction of defects in T-cell signaling molecules. These observations encouraged us to investigate monocyte status in cancer-bearing hosts. We characterized peripheral blood monocytes in gastric cancer patients with advanced disease (n = 14), in those with early disease (n = 17) and in healthy individuals (n = 14), based on surface marker, oxygen-burst capacity, and intracellular cytokine status (IL-10 and IL-12). To clarify which mediators induced the characteristic differences of monocytes in cancer-bearing hosts, healthy donor-derived monocytes were co-incubated with the patients' plasma. Intracellular IL-10 and IL-12 status on monocytes in advanced disease was significantly increased in comparison with early disease or healthy individuals, while there were no differences in the surface marker or oxygen-burst capacity of monocytes. The plasma from the patients with advanced disease could induce increased intracellular IL-10 and IL-12 status in healthy monocytes. The phenomenon was significantly inhibited with neutralizing mAbs specific for VEGF.
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PMID:[Study of monocyte intracellular cytokine and heterogeneity of monocytes in a gastric cancer patient]. 1461 35

Helicobacter pylori (HP) infection elevates the risk of gastric diseases including peptic ulcer and gastric cancer. The infection induces inflammatory cytokines, which could work both for and against lifetime infection in the human stomach. Genetic polymorphisms of the cytokines and other related ligands, receptors, and enzymes may influence persistent HP infection. This paper summarizes studies done on the associations between anti-HP antibody seropositivity and polymorphism genotypes. To date, the associations with the polymorphisms of fucosyl transferase 2 (FUT2 or secretor gene), FUT3 (Lewis gene), interleukin 1A (IL-1A), IL-1B, IL-1RN, IL-8, IL-10, myeloperoxidase (MPO), and tumor necrosis factor A (TNF-A) and TNF-B have been reported. Polymorphisms of other related genes, CD14, CXC chemokine receptor 2 (CXCR2), IL-1RI, nuclear factor KB2 (NF-KB2), and Toll-like receptor 4 (TLR4), have the potential to influence persistent infection. Unpublished results from our datasets are reported here for all these polymorphisms except TLR4. Gene-environment interactions between these genotypes and smoking are reviewed. An effect on OR due to the involvement of unexposed subjects is demonstrated to elucidate a disadvantage in the studies done in areas where the majority of the population is not exposed to HP.
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PMID:Persistent Helicobacter pylori infection and genetic polymorphisms of the host. 1472 87

Experimental infection with Helicobacter pylori in Mongolian gerbils results in chronic gastritis and gastric cancer. To investigate epithelial cell proliferation, apoptosis, and mucosal cytokine responses in gastritis, Mongolian gerbils were infected with the H pylori SS1 strain. At 4 weeks post-infection, gastritis was predominantly within the antrum, but extended to the corpus in approximately 50% of gerbils by 36 weeks. Epithelial cell proliferation and apoptosis in glandular epithelial cells were increased with infection. Antral cell proliferation, but not apoptosis, correlated significantly with gastric inflammation. In female gerbils, H pylori significantly increased expression of transcripts for IFN-gamma and IL-12p40, but not TGF-beta or IL-10, in the gastric mucosa. Significantly reduced IFN-gamma and IL-12p40 responses were observed in male gerbils infected with H pylori, but epithelial proliferative and apoptotic responses were comparable to those of females. These studies demonstrate that the female gerbil cytokine response to H pylori has a Th1 profile and that there are gender differences in the magnitude of the gastric cytokine responses to H pylori. The absence of a down-regulatory cytokine response may account for the more severe gastritis observed with H pylori infection in gerbils than in mice.
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PMID:Gastric mucosal cytokine and epithelial cell responses to Helicobacter pylori infection in Mongolian gerbils. 1474 2

Locoregional administration of the streptococcal preparation OK-432 is effective in treating malignant ascites from gastric cancer. In order to enhance the efficacy, we conducted a pilot study of locoregional immunotherapy for malignant ascites using host-oriented doses of OK-432. Moreover, action mechanisms of OK-432 were further explored in view of the T-helper type 1 (Th1)-Th2 concept. Gastric cancer patients with cytologically determined malignant ascites were locoregionally administered with OK-432. The dose of OK-432 was selected according to the delayed-type hypersensitivity (DTH) reaction levels to OK-432. Cytokine production profiles of ascites cells were determined using whole ascites assay by stimulation with OK-432. IL-10 mRNA expression was analyzed using RT-PCR. It was found that a positive clinical response was observed in 37 of the 51 (73%) patients with the DTH-oriented approach, showing a significantly higher efficacy than traditional dosage methods using empirical doses (31/58, 53%) (p=0.0487). The DTH-oriented administration of OK-432 produced adverse effects such as fever elevation (p<0.0001) and abdominal pain (p=0.0013) to a significantly lesser extent compared with the traditional treatment. Analysis of the action mechanism of OK-432 revealed that the DTH reaction in responders (19+/-6 mm) was stronger than that in non-responders (6+/-4 mm) (p<0.0001). Tumor necrosis factor (TNF)-alpha production of ascites cells was also higher in responders (3943+/-1247 pg/ml) than in non-responders (1217+/-939 pg/ml) (p=0.0002). There was a significant positive correlation (p=0.0085) between the levels of DTH reaction and TNF-alpha production of ascites cells, but not of blood cells. Responders appeared to polarize on the Th1 axis when clinical responses were plotted on Th1-Th2 dimensions according to the cytokine production profiles of TNF-alpha, IFN-gamma, IL-4 and IL-6 of ascites cells. In vitro culture with IL-2 of ascites cells after OK-432 administration demonstrated an almost clonal expansion of CD4+ lymphocytes, which produced TNF-alpha and IFN-gamma, but did not produce IL-4 or IL-6. IL-10 mRNA expression was detectable in ascites cells from non-responders before treatment. These results suggest that the DTH-oriented locoregional administration of OK-432 may be both effective and less toxic in treating malignant ascites from gastric cancer, showing a possibility of the tailored immunotherapy for malignant ascites. Th1 dysfunction exists in the microenvironment of malignant ascites from gastric cancer, in which IL-10 may, in part, play a role. The up-regulation of Th1 responses by OK-432 may result in positive clinical responses. The DTH reaction to OK-432 may be a useful tool not only for predicting clinical response but also for selecting the optimal dose of OK-432.
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PMID:Locoregional immunotherapy of malignant ascites from gastric cancer using DTH-oriented doses of the streptococcal preparation OK-432: Treatment of Th1 dysfunction in the ascites microenvironment. 1501 Aug 36

Our study investigated the ability of peripheral blood mononuclear cells (PBMCs) isolated from patients with different clinical stages of gastric cancer to produce proinflammatory (tumor necrosis factor alpha [TNFalpha], interleukin 12p40 [IL-12p40] and interleukin 6 [IL-6]) and antiinflammatory (interleukin-10 [IL-10]) cytokines after stimulation with lipopolysaccharide (LPS) or tumor cells, and its correlation with IL-1R-associated kinase-1 (IRAK-1) protein expression. The data showed that TNF production by tumor cell-stimulated PBMCs obtained from patients with advanced gastric cancer was significantly depressed in comparison to the control group. The response to LPS was less affected. IL-12p40 production was depressed in all stages of disease, while the release of IL-10 and IL-6 remained unchanged. Depressed tumor cell-induced TNF and IL-12p40 production was associated with diminished IRAK-1 protein expression in PBMC. These findings may suggest that in advanced gastric cancer (at least in some cancer patients) diminished IRAK-1 protein expression may be a novel mechanism responsible for or facilitating downregulation of innate immune response to tumor cells.
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PMID:Depressed tumor necrosis factor alpha and interleukin-12p40 production by peripheral blood mononuclear cells of gastric cancer patients: association with IL-1R-associated kinase-1 protein expression and disease stage. 1552 91

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