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)

Interleukin-18 (IL-18) is a pleiotropic cytokine that enhances Th1 or Th2 immune response. We show a novel mechanism of gastric cancer cells that allows their immune escape utilizing IL-18. All 4 gastric cancer cell lines, but not colon lines, constitutively expressed IL-18 receptors and IL-18 dose-dependently enhanced their in vitro proliferation accompanied by nuclear factor kappaB activation. When IL-18-pretreated gastric cancer cells were cultured with cytokine-activated peripheral blood killer lymphocytes, the antitumor machineries, perforin or interferon-gamma production of killer lymphocytes decreased, resulting in a decreased susceptibility of cancer cells to killer lymphocytes. Furthermore, gastric cancer cells cultured with IL-18 showed an increased expression of a granzyme B inhibitor, protease inhibitor 9. IL-18 injections into severe combined immuno-deficient mice intraperitoneally inoculated with gastric cancer cells consistently decreased the mouse survival time. Our results indicate that gastric cancers exploit IL-18 to grow/invade and evade immunosurveillance in the hosts.
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PMID:Exploitation of interleukin-18 by gastric cancers for their growth and evasion of host immunity. 1604 75

We review the current information concerning the role of cytokine polymorphisms and the risk of develop distal gastric cancer in different populations. We have included populations colonized with Helicobacter pylori as well as populations without colonization. We found that the study of polymorphisms alone seems insufficient to assess gastric cancer risk and it is necessary to examine environmental factors in different ethnic groups and geographic areas along with the study of H. pylori strains to define better the risk factors associated with distal gastric cancer.
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PMID:Role of cytokine polymorphisms in the risk of distal gastric cancer development. 1610 28

Autocrine motility factor (AMF) is a cytokine known to regulate tumor cell motility. Recent studies have extended its role to many other aspects of cancer biology. In the present study, we examined the level of AMF expression and its relationship with vascular endothelial growth factor (VEGF) expression and the angiogenic phenotype in human gastric cancer and their effect on survival. The AMF and VEGF expression level and tumor microvessel density (MVD) status in archived tissue specimens from 86 resected gastric cancer cases were determined. AMF expression was significantly higher in both primary tumors and lymph node metastases than in adjacent normal gastric mucosa and normal gastric mucosa from individuals without gastric cancer. In univariate survival analyses, strong AMF expression was associated with inferior survival (P = 0.028). In a Cox proportional hazards model, strong AMF expression (P = 0.019) was independently prognostic of poor survival. Strong AMF expression in the lymph node metastases was associated with poor survival (P = 0.011). Furthermore, AMF expression in the primary tumors was directly correlated with VEGF expression and MVD status. We found the first clinical evidence that AMF expression is directly correlated with VEGF expression and MVD status and predicts clinical outcome in patients with gastric cancer, supporting the hypothesis that the AMF/AMF receptor pathway plays an important role in multiple aspects of cancer biology.
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PMID:Expression of autocrine motility factor correlates with the angiogenic phenotype of and poor prognosis for human gastric cancer. 1611 16

Helicobacter pylori (H. pylori), a long term colonizer of human stomach is known to infect a half of mankind. Gastric and duodenal ulcer, gastric adenocarcinoma and MALT lymphoma develop in a subset of infected individuals. Pathogenesis of H. pylori infection is based on the long-term host to bacterial interaction and affected by the virulence factors of the bacterium, environmental and host factors (age, sex, blood type). Mucosal inflammation is the basic principle mechanism underlying the disease development in which tissue destruction may be initiated and maintained by both the bacterial toxins (CagA, VacA, LPS) and immune responses by the host. Immune evasion with bacterial modulation of host response affects the long-term host colonization. Colonization is also affected by urease and/or motility of the bacterium, presence of lipopolysaccharide (LPS) and various bacterial enzymes. Gastric mucosal atrophy and intestinal metaplasia can develop during the course of H. pylori infection predisposing to carcinogenesis. Host cytokine gene polymorphism would be the one explanation for host susceptibility to peptic ulcer or gastric cancer. Investigation into the pathogenesis of H. pylori related diseases could provide an answer to the impact of chronic host to microbial interaction resulting human diseases.
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PMID:[Pathogenesis of Helicobacter pylori infection]. 1617 34

Helicobacter pylori is recognised as the most common cause of chronic active gastritis and this bacterium is also an important pathogenic factor in peptic ulcer disease. The biological factors that influence clinical outcome in H. pylori infection have been extensively studied. In addition to immunological factors in the host, bacterial virulence determinants in H. pylori strains are likely to play a crucial role in gastric cancer development. Singlenucleotide polymorphisms at the 5' flanking region of the interleukin (IL)-6 gene promoter (G or C at -174 base) have been identified and individuals with the G allele at position -174 have been shown to produce higher levels of IL-6 than those with the C/C genotype. The mucosal levels of IL-6 were reported to be increased in H. pylori-associated gastritis. The present study was conducted to examine any relationship between inflammatory cytokine polymorphisms and the inflammatory process in mucosa infected by H. pylori. In our study we did not find any association between the C and G alleles in adult patients with chronic gastritis and inflammatory process in gastric mucosa.
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PMID:Interleukin-6 polymorphism and Helicobacter pylori infection in Brazilian adult patients with chronic gastritis. 1628 33

Several risk factors have been associated with gastric cancer, among them Helicobacter pylori infection. This bacterium yields inflammation, the degree of which depends on the bacterial strain and the severity of the host response. The inflammatory response involves a complex cytokine network. Recently, polymorphisms of the genes coding for interleukin-1beta (IL-1B), interleukin-1Ra (ILRN) and interleukin-10 have been associated with an increased risk of gastric cancer. In order to determine the association of the IL-1B, IL-1RN and IL-10 polymorphisms with gastric cancer in a high-risk Costa Rican population, we analysed purified DNA of 58 gastric cancer patients, 99 controls and 41 patients classified as group I or II, according to the Japanese classification. Genotyping was carried out by PCR, PCR-RFLP and pyrosequencing analysis. We did not find any association of the IL-1B-31, IL-1B-511 and IL-10 polymorphisms with the risk for developing gastric cancer in the studied population. Carriers of the IL-1B+3954T/- had an increased risk for developing gastric cancer (OR 3.7; 95%CI: 1.34-10.2). Also we found an increased risk for developing gastric cancer for allele 2 heterozygotes of the IL-1RN (OR 2.94; 95%CI: 1.09-7.93). This is the first time that IL-1B+3954 has been associated with gastric cancer. This is one of the first studies trying to describe the role played by IL-1B, IL-1RN and IL-10 genetic polymorphisms in gastric cancer in one of the highest risk American countries. Further investigation on American countries is needed.
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PMID:Association of interleukin-1B and interleukin-1RN polymorphisms with gastric cancer in a high-risk population of Costa Rica. 1636 96

In a previous study, we observed that cytokine-induced apoptosis inhibitor 1 (CIAPIN1), a newly identified apoptosis inhibitor, was upregulated at the mRNA level in a multidrug-resistant gastric cancer cell line SGC7901/VCR. The aim of this study was to explore the role of CIAPIN1 in the development of multidrug resistance (MDR) in gastric cancer cells. Upregulation of CIAPIN1 in MDR gastric cancer cells was confirmed by semiquantitative RT-PCR and Western blotting. Using cDNA transfection and RNA interference, we successfully established stable transfectants with upregulation (i.e., SGC7901-pCIAPIN1) or downregulation (i.e., SGC7901-pSiCIAPIN1 and SGC7901/ADR-pSiCIAPIN1) of CIAPIN1 expression, respectively. In vitro drug sensitivity assay demonstrated that overexpression of CIAPIN1 conferred MDR in SGC7901 cells whereas downregulation of CIAPIN1 sensitized SGC7901 and SGC7901/ADR cells to anticancer drugs. CIAPIN1 protected both SGC7901 and SGC7901/ADR cells from ADR-induced apoptosis and reduced intracellular accumulation and retention of adriamycin. Moreover, expression of P-glycoprotein (P-gp or MDR-1, a product of MDR-1 gene) and MDR-related protein-1 (MRP-1) was upregulated by CIAPIN1. In addition, Western blotting revealed that CIAPIN1 decreased the expression of Bcl-2, Bax and p53. Therefore, it is concluded that CIAPIN1 confers MDR in gastric cancer cells, likely by upregulating MDR-1 and MRP-1.
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PMID:CIAPIN1 confers multidrug resistance by upregulating the expression of MDR-1 and MRP-1 in gastric cancer cells. 1641 Jul 21

Transforming growth factor-beta (TGF-beta), a multifunctional cytokine, exerts contradictory roles in different kinds of cells. A number of studies have revealed its involvement in the progression of many types of tumors. To investigate the effect of TGF-beta on gastric carcinoma, SGC7901, BGC823 and MKN28 (a TGF-beta-resistant cell line) adenocarcinoma clones were used. After pretreatment in serum-free medium with or without 10 ng/ml TGF-beta1, their experimental metastatic potential, chemotaxis, and invasive and adhesive ability were measured. Furthermore, zymography for gelatinase was processed. Liver colonies were also measured 4 weeks after inoculation of SGC7901, BGC823 and MKN28 in Balb/c nude mice, and an increase in the number of surface liver metastases was seen in SGC7901 (from 11.0+/-3.0 to 53.3+/-3.3) and BGC823 (from 9.3+/-2.5 to 60.0+/-2.8) groups, whereas there was no difference between MKN28 groups (from 35.2+/-3.8 to 38.5+/-2.7). In vitro experiments showed that TGF-beta1 increased the adhesion capacity of SGC7901 and BGC823 cells to immobilized reconstituted basement membrane/fibronectin matrices and promoted their penetration through reconstituted basement membrane barriers. Zymography demonstrated that enhanced invasive potential was partly due to the increased type IV collagenolytic (gelatinolytic) activity, but there was no difference in type IV collagenolytic activity and other biological behaviors between MKN28 groups. These results suggested that TGF-beta1 might modulate the metastatic potential of gastric cancer cells by promoting their ability to break down and penetrate basement membrane barriers and their adhesive and motile activities. We speculated that TGF-beta1 might act as a progression-enhancing factor in gastric cancer. Therefore blockage of TGF-beta or TGF-beta signaling might prevent gastric cancer cells from invading and metastasizing.
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PMID:Enhancement of metastatic and invasive capacity of gastric cancer cells by transforming growth factor-beta1. 1651 42

The pathogenesis of gastric cancer (GC) includes a sequence of events that begins with Helicobacter pylori-induced chronic superficial gastritis, progressing towards atrophic gastritis, intestinal metaplasia, dysplasia and eventually GC. The association between H. pylori and GC is supported by experimental data showing a capacity of H. pylori to induce GC in animals, and the results of interventional studies showing that H. pylori eradication can lower the risk of GC and prevent development of pre-cancerous lesions in humans and in experimental animals. The "driving force" of gastric carcinogenesis is a chronic gastric inflammation, whose intensity and localisation depending on bacterial, host and environmental factors, determines the risk of GC. The mechanisms by which chronic inflammation lead to epithelial and pre-cancerous lesions include induction of oxidative stress, perturbation of the epithelial cells proliferation/apoptosis ratio, and cytokine secretion. Several molecular alterations associated with gastric carcinogenesis have also been described.
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PMID:Helicobacter pylori infection and gastric cancer. 1655 96

We report a case of dermatomyositis (DM) with hemophagocytic syndrome (HPS). The patient is a 60 year old male admitted to our hospital with muscle weakness, high fever, weight loss and pancytopenia. On physical examination, proximal muscle weakness and skin rash on the back were noted. Laboratory data revealed elevated serum levels of muscle enzymes, lactate dehydrogenase and ferritin. Serum levels of M-CSF, TNF-alpha, soluble IL 2 receptor were remarkably increased. Bone marrow aspiration showed histiocytosis of 7 to 10% with prominent hemophagocytosis. Gastroendoscopic examination revealed II-a gastric cancer. He was treated with methylprednisolone (m-PSL) pulse theraphy (1 g/ day x 3 days) followed by 60 mg/day oral prednisolone. He quickly responded to the treatment and laboratory data returned to normal in 20 days despite the remaining gastric cancer which was removed successfully 3 months later. HPS is a rare complication of DM and only three cases have been documented so far in the literature. Augmented cytokine in his serum is considered to be closely related to HPS in this case.
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PMID:[Case of hemophagocytic syndrome associated with active dermatomyositis]. 1658 41


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