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)

To ascertain whether the tumor cells can regulate the host immune systems through the production of the cytokines or their receptors, we examined the expressions of tumor necrosis factor alpha (TNF alpha), tumor necrosis factor beta (TNF beta), interleukin 2 (IL-2) and interleukin 2 receptor alpha chain (IL-2R alpha) on the human cancer cell lines by Northern blot analysis. We used K562 (leukemia cell line), MCF-7 (breast cancer cell line), LS180, HT29 (colon cancer cell lines), SH101 (gastric cancer cell line) and PH101 (pancreas cancer cell line). Expressions of TNF alpha, TNF beta and IL-2 mRNA were not detected in any of the tumor cell lines. However, 1.4 and 3.5 kilobases of the IL-2R alpha mRNA were expressed in the PH101 cells, but not in the other five cell lines. Furthermore, IL-2R alpha was detected on the cell surface of the PH101 cells by the flow-cytometric analysis with an anti-IL-2R alpha monoclonal antibody. Interestingly, the soluble IL-2R alpha (sIL-2R alpha) was found in the conditioned media obtained from the PH101 cell culture with a sandwich enzyme immunoassay. Moreover, the sIL-2R alpha secreted from the PH101 cells blocked the IL-2 dependent lymphocyte proliferation. These results indicate that the expression of IL-2R alpha on PH101 might suppress the IL-2 induced lymphocyte proliferation.
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PMID:The expression and biological activity of IL-2 receptor on a human pancreas cancer cell line. 850 43

Manganese superoxide dismutase (Mn-SOD), a mitochondrial enzyme, is a cytokine-regulated acute-phase protein that protects cells from free radicals. The current investigations examined the in vivo regulation of the expression of Mn-SOD mRNA and tumor necrosis factor alpha (TNFalpha) mRNA in gastric carcinoma tissue. The expression of these transcripts in breast carcinoma tissue also was examined because breast cancer is a much more TNF-sensitive tumor than gastric cancer. TNFalpha mRNA was markedly increased in gastric carcinoma tissue (p < 0.005). There were significantly higher levels of Mn-SOD mRNA in gastric carcinoma tissue than in noncancerous tissue (p < 0.0001). The level of Mn-SOD mRNA in gastric carcinoma tissue was higher than that in breast carcinoma tissue (p < 0.005). Up-regulation of Mn-SOD mRNA in gastric carcinoma tissue most likely serves as a protective mechanism against superoxide radicals and TNF cytotoxicity.
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PMID:Enhanced expression of manganese superoxide dismutase mRNA and increased TNFalpha mRNA expression by gastric mucosa in gastric cancer. 866 22

This study was performed to investigate the direct effects of recombinant human tumor necrosis factor (rH-TNF) and recombinant human interleukin-2 (rH-IL-2), either alone or in combination, on the cytotoxicity of 5-FU measured by MTT assay against human gastric adenocarcinoma cell lines (MKN-28 and MKN-45), and also to determine the optimal schedule for their combination. The antitumor activity of rH-TNF was enhanced more than 42% by 10(2) U/ml of rH-IL-2. The enhancing effects of rH-TNF and rH-IL-2 on the cytotoxicity of 5-FU were evaluated in terms of Modification Index(MI), the MI value at 10 U/ml rH-TNF was 1.6; the MI at the same concentration of rH-TNF in the presence of 10(2) U/ml of rH-IL-2 was 2.1. These results demonstrated that the antitumor effect of 5-FU was enhanced 1.6 times by 10 U/ml of rH-TNF and further enhanced by the combined use of rH-TNF and rH-IL-2. The combined effect of equal concentrations of 5-FU and rH-TNF was superior or equivalent to that of 5-FU or rH-TNF alone. The sequence of 5-FU followed by rH-TNF and rH-IL-2 showed a higher inhibitory effect than the reverse sequence. This sequence combination seems worthy of further consideration for the treatment of gastric cancer.
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PMID:Combined effect of 5-fluorouracil and recombinant tumor necrosis factor against human gastric carcinoma cell lines. 871 99

The acute phase protein, alpha1-acid glycoprotein (AGP), is a normal constituent of human blood (0.2-1 mg ml(-1)) and its glycosylation and concentration in the blood change during inflammation. In this review of our recent work, we discuss the immunomodulatory properties of AGP in connection with the structure of its carbohydrate chains. AGP samples prepared from normal donor serum (nAGP), serum obtained during abortion (fAGP), serum of cancer patients (cAGP), and ascitic fluid of patients with stomach cancer (sAGP) were subjected to analysis. All the samples except for fAGP had five N-linked chains of the 'complex' type, however, the numbers of bi-, tri-, and tetra-antennary chains, as well as glycan structures terminating these chains, were different. fAGP had three N-linked chains of the lactosamine and polylactosamine type and three O-chains which were not present in AGP isolated from the other sources. The glycoforms of nAGP and sAGP that were isolated using a ConA affinity column were similar in respect to their branching, but differed in their terminal oligosaccharides. sAGP was enriched in units ending in Le(x) and asialoagalacto (GlcNAc-terminating) forms. Immunomodulatory activity of different AGP preparations was tested in vitro by measuring their effect on the proliferative response of human lymphocytes stimulated by PHA, and by determining their influence on the production of IL-1, IL-2, IL-6, and TNF in the stimulated cells. nAGP was less active compared to cancer or fetal AGP in the proliferation test, but more active in affecting cytokine production. Some AGP glycoforms had opposite immunomodulatory effects. A new approach was developed in order to clarify the role of carbohydrate chains in the biological activity of AGP. A pool of N-linked oligosaccharide chains were attached to a soluble polyacrylamide matrix. This 'pseudoglycoprotein' was similar to AGP in its molecular weight; in its relative amounts of tetra-, tri-, and bi-antennary chains; and in the content of mono-, di-, tri-, and tetra-sialylated-oligosaccharides. This pseudo-AGP displayed a similar activity to its parent AGP in the biological tests. Analytical flow cytometry of leukocyte subpopulation from human peripheral blood showed that monocytes and granulocytes but not lymphocytes were the main targets for the binding of AGP and pseudo-AGP. This binding was inhibited by synthetic glycoconjugates containing mannose or sialic acid. The binding curve data suggested that there are two monocyte and granulocyte populations. These may have different carbohydrate specificities. All the evidence provided by these studies indicate that it is the carbohydrate chains on AGP that are important in modulating the immune system and not the AGP molecule itself.
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PMID:Carbohydrate composition and immunomodulatory activity of different glycoforms of alpha1-acid glycoprotein. 929 96

We have constructed a fusion protein composed of tumor necrosis factor alpha (TNF-alpha) fused at its COOH terminus to the scFv region of monoclonal antibody (mAb) B1, an antibody that recognizes LeY antigen present on many human cancer cells. Our rationale for fusing the scFv to the COOH terminus of TNF was to diminish the binding of the fusion protein to TNF receptors because the COOH terminus of TNF is involved in binding, and thus to partially inactivate (detoxify) the molecule. The Fv region should then target and accumulate the fusion protein on cancer cells, which should compensate for the reduced binding affinity of the TNF moiety and lead to selective killing of TNF-sensitive antigen-expressing cancer cells. The fusion protein was expressed in Escherichia coli and found in insoluble inclusion bodies. After refolding and purification by anion exchange, Ni-NTA affinity, and size-exclusion chromatography, we obtained monomeric TNF-B1(Fv). This molecule binds to LeY antigen on cancer cells with the same affinity as B1(scFv) and B1(scFv) immunotoxins but with significantly lower affinity to the TNF receptor compared to the TNF trimer. TNF-B1(Fv) is very toxic to LeY antigen-expressing cancer cells that are sensitive to TNF (e.g., MCF-7 breast or CRL-1739 gastric cancer cells). This cytotoxicity is antibody targeted and TNF mediated because it can be prevented (as shown on MCF-7 cells) by an antibody competing for LeY antigen binding and by an antibody that neutralizes TNF-alpha. TNF-B1(Fv) kills TNF-alpha-sensitive cells that do not express the target antigen only at much higher doses than TNF trimer, and it does not kill LeY-bearing but TNF-alpha-resistant cells. TNF-B1(Fv) can cause significant tumor regression of MCF-7 tumor xenografts in mice at doses that are not toxic to the mice. Thus, the reduced binding of the TNF moiety to TNF receptors, combined with binding of the B1(Fv) portion to LeY antigen, makes TNF-B1(Fv) an agent for selective killing of LeY-expressing TNF-sensitive cancer cells.
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PMID:Cytotoxic and antitumor activity of a recombinant tumor necrosis factor-B1(Fv) fusion protein on LeY antigen-expressing human cancer cells. 981 29

Numerous studies initiated by Warren and Marshall in 1982 confirmed the crucial role of H. pylori infection in the pathogenesis of gastritis, peptic ulcer and possibly also gastric cancer leading to reappraisal of fundamental concept of gastric pathophysiology. These topics were covered, in part, by our previous H. pylori-related symposium I (1995), II (1997) and III (1999) organized in Cracow. H. pylori is one of the most frequent causes of gastroduodenal infection worldwide, resulting in the release of various bacterial and host dependent cytotoxic substances including ammonia, platelet activating factor (PAF), cytotoxins and lipopolysaccharides (LPS) as well as cytokines such as interleukins (IL)-1-12, tumor necrosis factor alpha (TNF(alpha), interferon gamma (INFgamma) and reactive oxygen species (ROS). Recently, several extradigestive pathologies have been linked to H. pylori infection including cardiovascular, cutaneous, autoimmune, esophageal and other diseases such as sideropenic anemia, growth retardation, extragastric MALT-lymphoma etc. The potential role of H. pylori infection in the pathogenesis of these extradigestive disorders has been based on facts that 1) local gastric inflammation may exert systemic effects, 2) chronic infection of gastric mucosa induces immune responses that are able to cause the lesions remote to primary site of infection and 3) H. pylori eradication improves the extradigestive disorders. The aim of present III International Symposium is to provide critical reviews based on personal experience and the available literature about extragastric manifestations of H. pylori infection. The ultimate goal of this symposium is to foster interdisciplinary research and exchange of opinion about the possible involvement of H. pylori in extradigestive pathologies.
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PMID:Role of Helicobacter pylori infection in extragastroduodenal disorders: introductory remarks. 1069 51

We investigated the potential association of tumor necrosis factor-alpha (TNF-alpha) promoter polymorphisms with cancers. The study included 169 patients with gastric cancer, uterine cervical cancer, colorectal cancer, or renal cell carcinoma and 92 healthy controls. The -308 and -238 polymorphisms in the TNF-alpha promoter were analyzed by PCR-restriction fragment length polymorphism (RFLP). The proportion of individuals carrying the TNF-238A allele was significantly lower in the cancer group than in the control group. The odds ratio for cancer in subjects with the TNF-238A allele was 0.25 (95% CI, 0.10-0.64). No association was found between the -308 polymorphism and cancers. These results suggest that the -238A allele has a protective function against cancers.
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PMID:The -238 tumor necrosis factor-alpha promoter polymorphism is associated with decreased susceptibility to cancers. 1129 85

The aim of the present paper is to review and evaluate, in a comprehensive manner, the most recent published evidence on the contribution of genetic susceptibility to gastric cancer risk in humans. We have identified all studies available in MEDLINE published up to October 2001. Only studies carried out in humans and comparing gastric cancer cases with at least 1 standard control group were included in the analysis. We were able to find 31 articles based on 25 case-control studies carried out in Caucasian, Asian and African populations. Most of the studies assess the effect of genes involved in detoxifying pathways (n = 12) and inflammatory responses (n = 7). The most widely studied is the GSTM1 null polymorphism. Only a very few studies have evaluated the risk of gastric cancer associated with genes acting on mucosa protection, oxidative damage and DNA repair. The most consistent results are the increased gastric cancer risk associated with IL1B and NAT1 variants, which may account for up to 48% of attributable risk of gastric cancer. Only polymorphisms at HLA-DQ, TNF and CYP2E genes may confer some protective effect against gastric cancer. The most important limitations that preclude definitive conclusions are (i) the lack of appropriate control of potential sources of bias (only 5 population-based studies have been published so far); (ii) the low number of cases analyzed (14 studies included fewer than 99 cases); and (iii) the low number of studies (n = 3) offering concomitant analysis of genetic susceptibility and exposure to relevant cofactors (Helicobacter pylori infection, diet and smoking). We conclude that the scientific data on the role of genetic factors in gastric cancer risk are promising. The lack of association reported so far should be considered with caution due to significant limitations in study design. Cohort studies taking into account simultaneously the different genetic and environmental factors potentially involved in gastric tumorigenesis are needed to ascertain not only the relative contribution of these factors to tumor development but also the contribution of their putative interactions.
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PMID:Genetic susceptibility and gastric cancer risk. 1211 38

Clinical scientists from eight European countries and China gathered in the ancient Chinese capital of Xi'an on April 26-28, 2001 to discuss collaboration on a modern approach to gastric cancer prevention. Participants at the First Sino-European Workshop on Immunogenetics and Pathogenesis of Gastric Cancer presented their most up-to-date research results on topics ranging from epidemiology and immune mechanisms to Helicobacter pylori and vaccine development. Researchers then formed groups with their Chinese or European counterparts to plan future research endeavors which will benefit Chinese and European populations alike. After 3 years of organization between the Institute of Digestive Diseases of the Fourth Medical University in Xi'an, China and the Laboratory of Immunogenetics, VU University Medical Center in Amsterdam, the first workshop came into being under the joint sponsorship of the Commission of the European Union, National Natural Science Foundation of China and the Institute of Digestive Diseases, Xi'an, China. As gastric cancer is the most prevalent malignant tumor in China, the workshop was of special significance to the Chinese researchers and to the Chinese population in general. During the workshop, presentations on the epidemiology of gastric cancer showed that this disease is in fact common the world over: it is the second most common cancer next to lung cancer and about 1 million new cases were diagnosed in 2000. Three-quarters of the cases of gastric cancer occur in Asia, and approximately 80% of these cases are in China and Japan. Genetic factors and environmental factors such as diet and H. pylori infection play a role in gastric carcinogenesis. As a recognized cause of gastric cancer, H. pylori was the subject of various presentations ranging from immunological studies, molecular analysis of strains and pathogenesis to vaccine development. Specific areas of discussion included bacterial-epithelial interactions in H. pylori infection, epidemiology in China, global distribution of vacA and cagA genotypes, new evidence for host factors, nonsteroidal antiinflammatory drugs and H. pylori as independent risk factor for gastric cancer, new diagnostic techniques for H. pylori using serum levels of pepsinogen I, and autoimmune processes in corpus atrophy. Vaccine development using a variety of strategies against H. pylori was the subject of an entire session of talks. Oral immunization with urease with Escherichia coli heat labile enterotoxin was shown to be safe and immunogenic in humans as a mucosal adjuvant. Results of a study using attenuated Salmonella typhimurium as a vehicle for DNA-mediated immunization in mice were also presented. A final presentation discussed an ongoing trial comparing strain variability in the vacA and cagA gene sequences and disease expression between H. pylori infection in Europe and China. Researchers also discussed the role of IL1 gene family and TNF gene polymorphisms in gastric pathology and various immune mechanisms involved in gastric cancer, such as down-regulation of NF kappa B, IL-1 and IL-1RA, cyclooxygenase signalling, and identification of MGAg antibodies. An interactive discussion followed each presentation and ideas and suggestions were provided. According to specialty, the presenters were then assigned to groups of four or five to make plans for joint research projects. A number of international and Chinese observers were present, including representatives from the European Commission, the World Health Organization and the Chinese National Center for Biotechnology Development, and offered input on the financial feasibility of such projects.
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PMID:The immunogenetics and pathogenesis of gastric cancer. Highlights of the First Sino-European Workshop on the Immunogenetics and Pathogenesis of Gastric Cancer. 1253 77

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

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