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)

Rhus verniciflua Stokes (RVS) is a traditional medicine used in Korea, Japan and China to treat various diseases including catharsis, diaphoretic gastritis and stomach cancer. However, the effects of RVS on allergic inflammatory diseases are unknown to date. This study showed the antiallergic inflammatory effects of RVS on human mast cells (HMC-1) which were stimulated by phorbol myristate acetate (PMA) and calcium ionophore A23187. RVS inhibited the expressions of TNF-alpha, IL-6 and IL-8 that were stimulated by treatment with both PMA and A23187. Among the mitogen-activated protein kinases (MAPKs), extracts of RVS suppressed the phosphorylation of ERK and p38, whereas RVS increased the phosphorylation of JNK in HMC-1. Consistent with the regulation of MAPKs, it was found that RVS inhibited the nuclear translocation of nuclear factor (NF)-kappaB via inhibition of the phosphorylation of IkappaB-alpha, which are important processes in controlling inflammatory responses. Taken together, these results suggest that RVS modulates the expressions of signal molecules related to allergic inflammatory responses mainly through the ERK signaling pathway, suggesting that RVS could be used as a treatment for mast cell-derived allergic inflammatory diseases.
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PMID:Early antiallergic inflammatory effects of Rhus verniciflua Stokes on human mast cells. 1965 91

Interleukin (IL)-8 has been implicated in a wide range of diseases. The polymorphism of IL-8 gene, which may affect the production level of the cytokine, may be associated with cancer cachexia. To test this hypothesis, we investigated the potential influence of the polymorphisms of the IL-8 gene, -251 A/T and +781 C/T, on susceptibility to cachexia from patients with gastric cancer in a Chinese population, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A significantly increased frequency of +781 T allele was noted in patients with cachexia (OR = 1.765, 95% CI: 1.192-2.615, P = 0.004). The +781 TT genotypes were observed to be associated with a significantly increased risk of cachexia (OR = 2.156, 95% CI: 1.056-4.400, P = 0.033), and the difference was enhanced beyond the level of statistical significance when logistic regression was applied (OR = 3.500, 95% CI: 1.406-8.710, P = 0.007). Haplotype analysis revealed that A(251)T(781) haplotype (defined by SNPs at positions -251 and +781) was associated with a significantly increased risk of cachexia as compared with the T(251)C(781) haplotype (OR = 1.69; 95% CI: 1.08-2.62; P = 0.022). These results suggest that the genetic polymorphisms of proinflammatory cytokine IL-8 may contribute to the pathogenesis of cachexia in gastric cancer patients.
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PMID:Association of interleukin-8 gene polymorphism with cachexia from patients with gastric cancer. 1992 72

A strong association between persistent infection, chronic inflammation and cancer has been described. Helicobacter pylori is the main cause of gastric cancer, with 900,000 new cases yearly. Helicobacter colonization triggers the gastric epithelial cells to secret IL-8, a chemoattractant of immune cells, which persistently infiltrate the infected tissue. High levels of inflammatory cytokines are found, leading to loss of local homeostasis due to altered cell proliferation and apoptosis. It is not known how this local inflammatory response leads to cancer but the expression of mutagenic O2 and N2 free radicals might directly contribute to the irreversible mucosal genomic damage. Epstein Barr Virus is another pathogen associated with gastric cancer. We review here our current knowledge of inflammatory mechanisms at the site of infection that could be important to the development of cancer and that could be shared by other pathogens. This is of great importance since around 25% of cancers are associated with infection.
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PMID:[Infection, inflammation and gastric cancer]. 1993 56

Our study used protein array technology to analyze the expression status of various activated receptor tyrosine kinases (RTKs) in gastric carcinoma; then, we sought to discover an effective therapeutic receptor tyrosine kinase for this disease and investigated the anti-tumor mechanism of the therapeutic RTK. In addition to the expressions of activated RTKs in human gastric cancer and adjacent normal mucosa, the expression of activated RTKs in gastric cancer cell lines, MKN74, MKN45, MKN7 and MKN1, were also studied. The RTKs activated in gastric cancer tissue are EGFR, ErbB2, FGFR1, FGFR2alpha insulin R, and EphA4. Among the RTKs activated in gastric cancer tissues, EGFR and ErbB2 were also activated in all gastric cell lines examined in this study. A subsequent in vitro experiment using subcutaneous gastric cancer-bearing athymic nude mice demonstrated that the ErbB2-targeting drug trastuzumab markedly suppressed the growth of gastric cancer. Moreover, using an angiogenesis protein array, the expressions of Ang I, FGF-alpha, FGF-beta TGF-beta and IL-8 in MKN74 xenograft tumors were found to be significantly reduced by treatment with trastuzumab, indicating that trastuzumab may inhibit the expression of angiogenic molecules in MKN74 cells in vivo. These data suggest that ErbB2 is activated in gastric cancer, and the ErbB2-targeting drug trastuzumab may be related to the reduction of Ang 1, FGFalpha, FGFbeta, TGFalpha and IL-8.
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PMID:Use of protein array to investigate receptor tyrosine kinases activated in gastric cancer. 1995 38

Background. Interleukin (IL)-8 has been implicated in the development of cancer cachexia. The polymorphism of IL-8 gene, which may affect the production level of IL-8, may be associated with cancer cachexia. Methods. The serum IL-8 level in our study was examined by radioimmunoassay. We also analyzed single nucleotide polymorphisms (SNPs) -251 A/T and +781 C/T of IL-8 gene, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results. The serum levels of IL-8 were significantly elevated in patients with low-third gastric cancer compared with controls, and were further up-regulated in patients with cachexia than those without (Z = -3.134, P = .002). A significantly increased frequency of +781 T allele was noted in patients with cachexia (OR = 2.247, 95% CI: 1.351-3.737, P = .002). The +781 TT genotype was observed to be associated with a significantly increased risk of cachexia (OR = 3.167, 95% CI: 1.265-7.929, P = .011), and with odds ratio of 3.033 (95% CI: 1.065-8.639, P = .038) for cachexia after adjusting for potential confounding factors. Meanwhile, haplotype analysis indicated a borderline positive association between T(251)T(781) haplotype and cachexia as compared with the T(251)C(781) haplotype (OR = 4.92, 95% CI: 1.00-24.28; ,P = .053). Conclusions. IL-8 appears to be associated with cachexia from patients with low-third gastric cancer.
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PMID:Association of interleukin-8 with cachexia from patients with low-third gastric cancer. 2003 40

Helicobacter pylori produces a vacuolating cytotoxin, VacA, and most virulent H. pylori strains secrete VacA. VacA binds to two types of receptor-like protein tyrosine phosphatase (RPTP), RPTPalpha and RPTPbeta, on the surface of host cells. VacA bound to RPTPbeta, relocates and concentrates in lipid rafts in the plasma membrane. VacA causes vacuolization, membrane anion-selective channel and pore formation, and disruption of endosomal and lysosomal activity in host cells. Secreted VacA is processed into p33 and p55 fragments. The p55 domain not only plays a role in binding to target cells but also in the formation of oligomeric structures and anionic membrane channels. Oral administration of VacA to wild-type mice, but not to RPTPbeta knockout mice, resulted in gastric ulcers, in agreement with the clinical effect of VacA. VacA with s1/m1 allele has more potent cytotoxic activity in relation to peptic ulcer disease and appears to be associated with human gastric cancer. VacA activates pro-apoptotic Bcl-2 family proteins, and induces apoptosis via a mitochondria-dependent pathway. VacA can disrupt other signal transduction pathways; VacA activates p38 MAPK, enhancing production of IL-8 and PGE(2), and PI3K/Akt, suppressing GSK-3beta activity. VacA has immunomodulatory actions on T cells and other immune cells, possibly contributing to the chronic infection seen with this organism. H. pylori virulence factors including VacA and CagA, which is encoded by cytotoxin-associated gene A, along with host genetic and environmental factors, constitute a complex network to regulate chronic gastric injury and inflammation, which is involved in a multistep process leading to gastric carcinogenesis.
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PMID:Pleiotropic actions of Helicobacter pylori vacuolating cytotoxin, VacA. 2004 46

Pro-inflammatory cytokines are produced in the gastric mucosa by inflammatory cells activated by chronic Helicobacter pylori (H. pylori) infection. Polymorphisms of these cytokine genes are associated with individual differences in gastric mucosal cytokine mRNA level, which result in differences in gastric mucosal inflammation, acid inhibition and gastroduodenal disease risk in response to H. pylori infection. Although polymorphisms of interleukin (IL)-1B, IL-1RN and TNF-A have been reported to relate well with gastric cancer and peptic ulcer risk, those of IL-2, IL-4, IL-6 and IL-8 genes are unclear. In combined analyses using data from previous studies, we found that the risk of gastric non-cardia cancer development was significantly associated with IL-4-168 C allele (OR: 0.81, 95% CI: 0.69-1.00) and IL-4-590 T allele carrier status (0.61, 0.53-0.73), and IL-6-174 G/G genotype (2.02, 1.31-3.10). In peptic ulcer development, IL-2-330 G and IL-4-590 T allele carriers had a significantly decreased risk (0.37, 0.27-0.50 and 0.58, 0.34-0.99, respectively). Moreover, IL-2, IL-4, IL-6 and IL-8 gene genotypes prevalence differs among populations. The inflammatory cytokine gene polymorphisms (e.g. IL-4-590 and IL-6-572 for gastric cancer, and IL-4-590, IL-6-572 and IL-8-251 for peptic ulcer) have a more potent influence on development of gastroduodenal diseases in Western than East Asian populations. These cytokine gene polymorphisms, as well as those of IL-1B, IL-1RN and TNF-A, may be used to identify groups at higher risk of gastric cancer and peptic ulcer, and those suitable for their prevention by H. pylori eradication therapy in Western populations.
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PMID:Influence of interleukin polymorphisms on development of gastric cancer and peptic ulcer. 2022 61

Previous studies suggested the relationship between interleukin (IL)-8 -251 A/T gene polymorphism and risk of gastric cancer (GC). However, the currently available results were not consistent. The present study aimed to quantitatively analyse this association using a meta-analysis. Published literature from PubMed, EMBASE and CNKI (China Knowledge Resource Integrated Database) were retrieved. Twelve case-control studies with 3012 cases of GC and 3893 controls were included. Overall, IL-8 -251 A/T polymorphism was not associated with the risk of GC. However, when stratified for ethnicity/country, the results showed that A allele carriers had an increased risk of GC while T allele carriers had a decreased risk of GC in Korean people. When stratified for Helicobacter pylori infection, the results showed that A allele carriers with H. pylori infection had an increased risk of GC while T allele carriers with or without H. pylori infection had a decreased risk of GC. When stratified for tumor location and histological type (Lauren's classification), A allele carriers had an increased risk of intestinal- and diffuse-type of GC and non-cardia cancer, while T allele carriers had a decreased risk of intestinal- and diffuse-type of GC and non-cardia cancer. These results suggest that overall IL-8 -251 A/T gene polymorphism is not associated with the risk of GC and the association may be varied according to histological type, tumor location, H. pylori infection and ethnicity/country. More well-designed studies based on larger population are needed to confirm our results and further evaluate the association between IL-8 -251 A/T gene polymorphism and gastric cancer.
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PMID:Interleukin-8 -251 A/T gene polymorphism and gastric cancer susceptibility: a meta-analysis of epidemiological studies. 2036 44

Previous investigations demonstrated that a standardized extract of ginger rhizome inhibited the growth of Helicobacter pylori in vitro with a minimum inhibitory concentration in the range 0.78 to 12.5 mug/mL. In the present work, the extract was tested in a rodent model of H. pylori-induced disease, the Mongolian gerbil, to examine the effects of the extract on both prevention and eradication of infection. The extract was administered to Mongolian gerbils at a daily dose of 100 mg/kg body weight in rations either 3 weeks prior to infection or 6 weeks post-infection. Treatment with the standardized ginger extract reduced H. pylori load as compared with controls and significantly (P<0.05) reduced both acute and chronic muscosal and submucosal inflammation, cryptitis, as well as epithelial cell degeneration and erosion induced by H. pylori. Importantly, the extract did not increase morbidity or mortality. Further investigations of the mechanism demonstrated that the ginger extract inhibited the activity of cyclooxygenase-2, with 50% inhibitory concentration (IC(50)) of 8.5 mug/mL in vitro, inhibited the nuclear factor-kappaB transcriptional response in kBZ Jurkat cells (human T lymphocytes) with an IC(50) of 24.6 mug/mL, and significantly inhibited the release of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor-alpha from lipopolysaccharide-stimulated human peripheral blood mononuclear cells with IC(50) values of 3.89, 7.7, 8.5, and 8.37 mug/mL, respectively. These results suggest ginger extracts may be useful for development as agents to reduce H. pylori-induced inflammation and as for gastric cancer chemoprevention.
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PMID:Standardized ginger (Zingiber officinale) extract reduces bacterial load and suppresses acute and chronic inflammation in Mongolian gerbils infected with cagAHelicobacter pylori. 2037 96

Helicobacter pylori infection can induce aberrant CpG island hypermethylation in gastric mucosal epithelial cells. Single nucleotide polymorphisms of proinflammatory cytokine genes encoding for interleukin 1B (IL1B), IL6, and IL8 have been demonstrated to be associated with an increased risk of gastric cancer. To identify the influence of host genetic factors in CpG island hypermethylation induced by H. pylori infection, we analyzed H. pylori-infected chronic gastritis (n = 111) and gastric cancer samples (n = 78) for the methylation status of eight genes previously shown to be hypermethylated in chronic gastritis and single nucleotide polymorphisms of IL1B, IL6, and IL8. The methylation levels were then compared between different genotypes. Gastric cancers from patients with the IL1B-511T/T allele showed significantly higher methylation levels in five genes as compared with gastric cancers from IL1B-511 C carriers (P < 0.05). An increased level of hypermethylation in association with the IL1B-511T/T allele was observed in chronic gastritis samples, but the association was not statistically significant. These findings suggest that the IL1B-511T/T allele is associated with enhanced hypermethylation of multiple CpG island loci, which might contribute to an increase in the risk for gastric cancer in individuals with H. pylori infection and IL1B-511T/T allele.
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PMID:Influence of IL1B polymorphism on CpG island hypermethylation in Helicobacter pylori-infected gastric cancer. 2040 97


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