Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MG7-Ag is a human gastric-carcinoma-associated antigen with a high specificity. So far it is remained unclear whether MG7-Ag is correlated with the in vivo cellular immune response of patients with gastric cancer. In this study, we detected the expression of the T cell receptor (TCR) repertoire of T cell subpopulations and cytokines in tumor-infiltrating lymphocytes (TIL), peripheral blood lymphocytes (PBL), and residue benign mucosal lymphocytes (NML) of patients with gastric cancer using semiquantitative RT-PCR. Our data showed that the expanded clones in CD8(+) NML and TIL and CD4+ NML and PBL in MG7-Ag-positive patients were significantly fewer than those of MG7-Ag-negative patients (p = 0.0360; p = 0.0026; p = 0.0065 p = 0.0109, respectively). The levels of IL-8 in CD8(+) TIL and TNF in CD4(+) TIL from the MG7-Ag-positive group were significantly higher than those from the MG7-Ag-negative group (p = 0.0302; p = 0.0177, respectively). Taken together, the results demonstrated a weaker T cell immune response and more proinflammatory cytokine secretion in MG7-Ag-positive patients with gastric cancer than in MG7-Ag-negative ones. This likely contributes to the poor prognosis in MG7-Ag-positive gastric-cancer patients.
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PMID:Expression of MG7-Ag in patients with gastric cancer correlates with weaker T cell immune response and more proinflammatory cytokine secretion. 1660 93

Helicobacter pylori is present in the stomach of more than half of the world population. Based on compelling epidemiological evidences, it was classified by the World Health Organization as a type I gastric carcinogen. It is generally believed that gastric cancer development is a multi-step progression from chronic gastritis to atrophy, intestinal metaplasia, dysplasia, and cancer. Individuals infected with H. pylori have at least a 2-fold increase in risk of gastric cancer development though only a small proportion of infected individuals will ultimately develop this malignancy. The exact mechanisms underlying how H. pylori triggers or causes gastric cancer remain elusive. Certain H. pylori genotypes like cagA, vacA s1 or babA1 are considered to be of higher virulent potential. Apart from the bacterial factors, the host response to chronic H. pylori infection may also attribute to the cancer risk. It was found that individuals who carry pro-inflammatory cytokine gene polymorphism have a substantial increase in risk of cancer development. The combination of bacterial and host genotypes may have a synergistic effect on cancer development. Despite the strong causal link between chronic H. pylori infection and gastric cancer, the role of H. pylori eradication in preventing gastric cancer remains controversial. More long-term data may be necessary to clarify this controversy.
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PMID:Helicobacter pylori and gastric neoplasia. 1662 59

IL-18 is a pleiotropic cytokine that is produced by many cancer cells. A recent report suggested that IL-18 plays a key role in regulating the immune escape of melanoma and gastric cancer cells. Thrombospondin (TSP-1) is known to inhibit angiogenesis in several cancers but some studies have reported that it stimulates angiogenesis in some cancers such as gastric cancer. IL-18 and TSP-1 are related to tumor proliferation and metastasis. This study investigated the relationship between IL-18 and TSP-1 in gastric cancer. RT-PCR and ELISA showed that after the cells had been treated with IL-18, the level of TSP-1 mRNA expression and TSP-1 protein production by IL-18 increased in both a dose- and time-dependent manner. The cells were next treated with specific inhibitors in order to determine the signal pathway involved in IL-18-enhanced TSP-1 production. IL-18-enhanced TSP-1 expression was blocked by SP600125, a c-Jun N-terminal kinase (JNK) specific inhibitor. In addition, Western blot showed that IL-18 enhanced the expression of phosphorylated JNK. Overall, these results suggest that IL-18 plays a key role in TSP-1 expression involving JNK.
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PMID:IL-18 enhances thrombospondin-1 production in human gastric cancer via JNK pathway. 1665 Aug 13

Although AIMP1 (previously known as p43) is one of three auxiliary proteins bound to a macromolecular aminoacyl tRNA complex, it is also secreted as a cytokine controlling both angiogenesis and immune responses. Here we show that systemically administered purified recombinant human AIMP1 had anti-tumor activity in mouse xenograft models. In Meth A-bearing Balb/c mice, tumor volume increased about 28 fold in the vehicle treatment group, while an increase of about 16.7 fold was observed in the AIMP1-treated group. We also evaluated the anti-tumor activity of AIMP1 in combination with a sub-clinical dose of the cytotoxic anti-tumor drug, paclitaxel. The growth of NUGC-3 human stomach cancer cells was suppressed by 84% and 94% by the combinations of 5 mg/kg paclitaxel + 25 mg/kg AIMP1 (p = 0.03), and 5 mg/kg paclitaxel + 50 mg/kg AIMP1 (p = 0.02), respectively, while 5 mg/kg paclitaxel alone suppressed growth by only 54% (p = 0.02). A similar cooperative effect of AIMP1 and paclitaxel was observed in a lung cancer xenograft model. These results suggest that AIMP1 may be useful as a novel anti-tumor agent.
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PMID:Antitumor activity of the novel human cytokine AIMP1 in an in vivo tumor model. 1668 15

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that has recently been implicated in carcinogenesis. Helicobacter pylori, which is closely linked to gastric cancer, induces the gastric epithelium to produce proinflammatory cytokines, including MIF. MIF can bind to CD74, which we have previously shown to be highly expressed on the surface of gastric epithelial cells (GEC) during H. pylori infection. In this study, we sought to investigate the role of the H. pylori-induced MIF on epithelial proliferation and procarcinogenic events. Upon establishing a role for the H. pylori CagA virulence factor in MIF production, MIF binding to CD74 on GEC was confirmed. rMIF and H. pylori were shown to increase GEC proliferation, which was decreased when cagA- strains were used and when CD74 was blocked by mAbs. Apoptosis was also decreased by MIF, but increased by cagA- strains that induced much lower amounts of MIF than the wild-type bacteria. Furthermore, MIF binding to CD74 was also shown to decrease p53 phosphorylation and up-regulate Bcl-2 expression. This data describes a novel system in which an H. pylori virulence factor contributes to the production of a host factor that in turn up-regulates procarcinogenic events by the gastric epithelium.
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PMID:Helicobacter pylori CagA-dependent macrophage migration inhibitory factor produced by gastric epithelial cells binds to CD74 and stimulates procarcinogenic events. 1670 39

Recently, we were able to show that Helicobacter pylori-positive gastric cancer (GC) patients have a significantly better survival after the complete resection of their tumor compared to H. pylori-negative GC patients. H. pylori is known to polarize an immune response towards a type 1 cytokine profile and tumor-specific type 1 cytokine responses are associated with protection from tumor challenge and T-cell-mediated tumor regression. Therefore, we hypothesized that the improved survival in H. pylori-positive patients may be secondary to the induction of a GC-specific type 1 T cell response. To characterize the anti-tumor immune response in GC patients we analyzed tumor-infiltrating lymphocytes (TIL) isolated from primary tumors. The CD3+ T cell population contained 50% CD4+ (range 0.4-81%) and 39% CD8+ cells (range 22-53%). The number of B cells (CD19+, P = 0.03) was significantly increased and the number of T cells (CD3+, P = 0.02) significantly decreased in intestinal compared to diffuse type of tumors. Four tumor cell lines were established from primary GCs and three from lymph node metastases. T cell cultures were established from isolated TIL from four H. pylori-positive and one H. pylori-negative GC patients and tested for tumor-specific cytokine secretion. Eight of ten T cell cultures derived from H. pylori-positive patients secreted both IFN-gamma and IL-5 after restimulation with autologous tumor cells. The only tumor-specific TIL line expressing a dominant IL-5 response was derived from an H. pylori-negative patient.
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PMID:Characterization of immune responses in gastric cancer patients: a possible impact of H. pylori to polarize a tumor-specific type 1 response? 1676 89

Individuals with atrophic gastritis (AG), especially atrophic body gastritis (ABG), are at increased risk of developing gastric cancer. Serum concentrations of pepsinogens (PG) have been proposed as markers for ABG. The aim of this study was to determine the risk factors for AG and ABG and the potential of using serum PG concentrations to detect ABG in a dyspeptic population in Costa Rica, which is one of the countries with the highest incidence and mortality rates of gastric cancer in the world. Seven biopsy specimens, a fasting blood sample and a questionnaire concerning sociodemographic factors were obtained from 501 consecutive dyspeptic patients. The serum PGI level and the PGI/PGII ratios were significantly lower in patients with ABG than in other groups (P<0.000). A cut-off point of 3.4 led to a sensitivity of 91.2% in identifying ABG, a negative predictive value of 98.1%, but a positive predictive value of only 11.2%. Helicobacter pylori were present in 93% of the patients and all those with peptic ulcers were positive. AG was associated with increased age, lower body mass index, high alcohol intake and low fruit consumption. ABG was associated with age, alcohol consumption and PGI/PGII<3.4. In dyspeptic patients with a high prevalence of H. pylori infection, serum PG levels provide an assessment of ABG but it is necessary to introduce other serological and genetic markers in order to achieve a better specificity. Those markers could be serum antibodies to H. pylori-CagA, cytokine gene polymorphisms or others.
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PMID:Association of serum pepsinogen with atrophic body gastritis in Costa Rica. 1682 Sep 94

Important new data were published during the past year on the relationship of Helicobacter infection and gastric neoplasias. In the pathogenesis of gastric cancer, a thrilling new hypothesis was put forward based on animal experiments. Helicobacter infection induces gastric mucosal damage and bone marrow-derived cells (mobilized into peripheral blood and attracted to the inflamed mucosa) replace the areas of damaged gastric tissue and turn into neoplastic proliferation. Several studies focused on mechanisms related to the development of gastric malignancy in infected individuals with particular attention to inflammatory cytokine gene polymorphisms. Some new evidence is also reported to suggest that Helicobacter infection increases the risk of neoplasias outside the stomach in the liver and colon.
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PMID:Helicobacter and digestive malignancies. 1692 9

Gastric trefoil peptides mediate mucosal repair by stimulating cell migration, inhibiting apoptosis and inflammation, and likely augmenting the barrier function of mucus. One of these, tff1, is a gastric-specific tumor suppressor gene, which when repressed is associated with gastric cancer progression. IL-6 family cytokines play an important role in maintaining gastric homeostasis by regulating tff1 and other mediators of mucosal proliferation, inflammation, angiogenesis, and apoptosis. In this review the signaling cascades downstream of the common IL-6 cytokine family coreceptor gp130 that contribute to control of this homeostasis are described, as are the pathological outcomes of imbalancing these pathways.
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PMID:Differentiation of the Gastric Mucosa IV. Role of trefoil peptides and IL-6 cytokine family signaling in gastric homeostasis. 1693 52

Proinflammatory cytokine gene polymorphisms have been demonstrated to associate with gastric cancer risk, of which IL1B-31T/C and -511C/T changes have been well investigated due to the possibility that they may alter the IL1B transcription. The signal transduction target upon interleukin 1 beta (IL1beta) stimulation, the nuclear factor of kappa B (NFkappaB) activation, supports cancer development, signal transduction in which is mediated by FS-7 cell-associated cell surface antigen (FAS) signaling. Based on recent papers describing the prognostic roles of the polymorphisms and the NFkappaB functions on cancer development, we sought to determine if Japanese gastric cancer patients were affected by the IL1B -31/-511 and FAS-670 polymorphisms. A case-control study was conducted on incident gastric adenocarcinoma patients (n=271) and age-gender frequency-matched control subjects (n=271). We observed strong linkage disequilibrium between the T allele at -511 and the C allele at -31 and between the C allele at -511 and the T allele at -31 in IL1B in both the cases and controls (R (2)=0.94). Neither IL1B-31, -511 nor FAS-670 polymorphisms showed significantly different risks of gastric adenocarcinoma. Though FAS-670 polymorphisms did not show any significant difference, the proportion of subjects with IL1B-31TT (or IL1B-511CC) increased according to stage (trend P=0.019). In particular, subjects with stage IV had a two times higher probability of having either IL1B-31TT (or IL1B-511CC) genotype compared with stage I subjects. These observations suggest that IL1B-31TT and IL1B-511CC are associated with disease progression.
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PMID:A polymorphism of C-to-T substitution at -31 IL1B is associated with the risk of advanced gastric adenocarcinoma in a Japanese population. 1700 6


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