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)

Overexpression of the Multiple Drug Resistance gene (MDR1) has been proposed as a major mechanism related to both intrinsic and acquired resistance to chemotherapeutic agents. The gene product is a membrane protein (P-glycoprotein), that acts as an energy-dependent drug efflux pump decreasing drug accumulation in resistant tumor cells. We have characterized MDR1 and P-Glycoprotein expression in human gastric adenocarcinoma and in precursor lesions. MDR1 mRNAs, analyzed by dot-blot technique, were detected in 9 of 10 non-tumoral gastric mucosae and in 8 of 10 gastric adenocarcinomas. Immunohistochemical analysis, using the MRK16 monoclonal antibody, revealed heterogeneous expression of P-Glycoprotein in individual cells. The P-Glycoprotein was found on the surface of cells of gastric areas with intestinal metaplasia subtype III. This type of intestinal metaplasia, also called "colonic metaplasia", has been strongly associated with a high risk for the development of gastric cancer. The fact that the P-Glycoprotein was detected in this precursor lesion is consistent with the intestinal metaplasia-dysplasia and carcinoma sequence proposed in the histogenesis of this tumour. The finding that P-Glycoprotein was heterogeneously expressed in malignant cells of some gastric adenocarcinomas also suggests that this transporter system probably contributes to primary and secondary multidrug resistance in this neoplasm.
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PMID:Multidrug resistance gene and P-glycoprotein expression in gastric adenocarcinoma and precursor lesions. 167 10

Binding of the radiolabeled bombesin analog [125I-Tyr4]bombesin to crude cell membranes of MKN45 human gastric cancer grown in nude mice was investigated in vitro. Scatchard analyses of multipoint binding data, performed by complete displacement method demonstrated the presence of two classes of [Tyr4]bombesin binding sites. The high-affinity binding sites had a mean dissociation constant (Kd1) of 2.75 nM with a mean maximal binding capacity (Bmax1) of 492 fmol/mg membrane protein, while the low-affinity binding sites showed a mean dissociation constant (Kd2) of 0.41 microM with a mean maximal binding capacity (Bmax2) of 41.4 pmol/mg membrane protein. Binding of [125(1)-Tyr4]bombesin was specific, reversible and linearly related to the protein concentration of tumor membrane. In displacement studies, the binding of radiolabeled [Tyr4]bombesin was inhibited in a dose-dependent manner by gastrin releasing peptide (GRP)(14-27) and two synthetic antagonists of bombesin/GRP, RC-3095 and RC-3950-II. Both antagonists exhibited high affinity in nearly the same concentration range as GRP(14-27). The presence of receptors for bombesin/GRP on human gastric cancer membranes suggests that bombesin-like peptides may play a role in growth of gastric cancer.
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PMID:Characterization of bombesin/gastrin-releasing peptide receptors in membranes of MKN45 human gastric cancer. 792 93

Intact Helicobacter pylori cells, as well as cellular components, stimulated nitric oxide (NO) synthesis in an in vitro murine macrophage system by the L-arginine-nitric oxide pathway. Macrophage-mediated NO formation was dependent on the presence of H. pylori and exhibited a dose-dependent increase at H. pylori concentrations between 10(6) and 5 and 10(7) cells/ml. H. pylori mediated NO synthesis also required L-arginine and was inhibited by NG-monomethyl-L-arginine (NMMA), a selective inhibitor of nitric oxide synthase. NO synthesis was induced by whole H. pylori cells. H. pylori media filtrate, extracted membrane proteins, and H. pylori lipopolysaccharide (LPS). Maximal NO synthesis was induced by viable H. pylori cells with media filtrate and membrane protein extracts inducing significant NO responses. NO stimulation by media filtrate and membrane protein extracts support secreted H. pylori products as potential activators of inflammatory cell NO synthesis in vivo. NO synthesis in response to H. pylori suggests that chronic H. pylori infection may increase endogenous formation of NO. Elevated NO exposure may represent an etiologic factor explaining the epidemiologic association between long-term H. pylori infection and gastric cancer.
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PMID:Induction of nitric oxide synthesis in murine macrophages by Helicobacter pylori. 860 78

CD 46, membrane cofactor protein, is a membrane protein which shows different expression and phenotypes with the organ or cell in the same individual. Previously, we reported that gastric CD 46 was expressed strongly in the mucosal epithelium, mucosa and endothelial cells of vessels in the submucosal layer. Western blot analysis revealed that gastric CD 46 was expressed as one broad band with a molecular weight ranging from 60 kDa to 69 kDa, which was different from that of lymphocytes. In this study, we investigated the differences in expression and characterization of CD 46 in gastric cancer obtained by surgery as compared with non-cancerous mucosa. Expression of CD 46 was greater in gastric cancer than in non-cancerous mucosa. In some cases, the phenotypes of CD 46 in gastric cancer were different from those in the non-cancerous tissue.
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PMID:[Demonstration and characterization of CD 46, membrane cofactor protein, in gastric cancer tissue]. 881 May 46

The 30-base pair (bp) deletion of the cytoplasmic carboxy-terminal domain of the latent membrane protein 1 (LMP-1) gene was analyzed in 37 frozen tissues from patients with Epstein-Barr virus (EBV)-related gastric cancer and 18 throat washings from healthy adults in southern Japan. The 30-bp deletion was identified in 33 (91.7%) of 36 specimens of EBV-related gastric cancers and in 15 (83.3%) of 18 throat washings from healthy adults. In one case of gastric cancer, an additional 9-bp deletion was identified downstream of the 30-bp deletion. From the last transmembrane domain to the end of the carboxy terminal of LMP-1, mutations were examined in 37 cases of gastric cancers and in three cases of throat washings. Twenty-eight nonsilent mutations were identified in this region of EBV-related gastric cancer and throat washings. Five nonsilent mutations at positions 168,755, 168,746, 168,687, 168,357, and 168,355 were identified in all 30-bp-deleted cases of EBV-related gastric cancers and throat washings. However, these nonsilent mutations were not identified in three patients without the 30-bp deletion. Although the deletion and single-base mutations of the LMP-1 gene in gastric cancers and throat washings were similar to those of nasopharyngeal carcinoma in Taiwan and China, more single-base mutations were found in southern Japan. These data indicate that high prevalence of the 30-bp deletion of the LMP-1 gene in gastric cancers may reflect the prevalence of the deletion variant in the normal population in southern Japan.
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PMID:Deletions and single-base mutations within the carboxy-terminal region of the latent membrane protein 1 oncogene in Epstein-Barr virus-related gastric cancers of southern Japan. 989

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

Considering a suspected link between Helicobacter pylori infection and human stomach cancer, a new H. pylori gene for membrane protein 1 (HP-MP1) was recently cloned. Because HP-MP1 induces release of inflammatory cytokines and tumor necrosis factor-alpha acts as both initiator and tumor promoter, we studied the possible involvement of HP-MP1 in carcinogenesis of H. pylori. Two cell lines, BALB/3T3 cells as control and v-Ha-ras-transfected BALB/3T3 cells (Bhas 42 cells) as putative initiated cells, were each transfected with HP-MP1, urease B genes, or vector alone. All of the Bhas/mpl clones showed strong expression of tumor necrosis factor-alpha gene and produced tumors in 100% of nude mice. Two Bhas/ure clones showed weak tumorigenicity; the other Bhas and BALB clones showed none. Results indicate strong carcinogenic activity of HP-MP1 in cooperation with viral Ras protein and weak activity of urease B.
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PMID:Helicobacter pylori membrane protein 1: a new carcinogenic factor of Helicobacter pylori. 1152 25

Cancer development and ageing are complex sciences. From the study on the process of rodent carcinogenesis, we identified tumor necrosis factor-alpha (TNF-alpha) as an important mediator of cancer development. This paper presents three clinical examples of TNF-alpha up-regulation: by cord factors of Mycobacterium tuberculosis, such as trehalose 6-monomycolate, as an activator of protein kinase C and by a cord factor like fraction of Microsporum canis obtained in the air inside houses in Thailand, both of which are risk factors in human lung cancer development, and by Helicobacter pylori gene product, H. pylori membrane protein 1 (HP-MP1) in relation to human stomach cancer. The second part of this paper deals with down-regulation of TNF-alpha by a wide variety of cancer preventive agents. Among the various agents, (-)-epigallocatechin gallate (EGCG) and green tea polyphenols inhibited TNF-alpha gene expression in the cells induced by tumor promoter, mediated through inhibition of NF-kappaB activation. Studying growth inhibition of human cancer cell lines by morphine, we found that morphine and the new morphine derivatives KT-90 and KT-87 have anticancer activity mediated through induction of apoptosis, in addition to analgesic action. We conclude that environmental and endogenous factors induce NF-kappaB activation mediated through expression of inflammatory cytokine genes, such as TNF-alpha, and that the expression pattern of the genes operates similarly in the aging process.
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PMID:Involvement of TNF-alpha changes in human cancer development, prevention and palliative care. 1247 Sep 3

Reciprocal interactions between Helicobacter pylori and cells of the gastric epithelium to which it adheres may affect colonization. Changes in gene expression of H. pylori induced by adhesion to AGS gastric cancer cells by coculture were compared to changes in gene expression of H. pylori cultured without AGS cells by using cDNA filter macroarrays. Adhesion was quantitatively verified by confocal microscopy of green fluorescent protein-expressing bacteria. Four experiments showed that 22 and 21 H. pylori genes were consistently up- and down-regulated, respectively. The up-regulated genes included pathogenicity island, motility, outer membrane protein, and translational genes. The sigma(28) factor antagonist flgM, flgG, the stress response gene, flaA, omp11, and the superoxide dismutase gene (sodB) were down-regulated. The up-regulation of cag3, flgB, tonB, rho, and deaD was confirmed by quantitative PCR, and the up-regulation of lpxD, omp6, secG, fabH, HP1285, HP0222, and HP0836 was confirmed by reverse transcription (RT)-PCR. The down-regulation of flaA, sodB, and HP0874 was confirmed by quantitative PCR, and the down-regulation of omp11 was confirmed by RT-PCR. The alteration of gene expression in H. pylori after adhesion to gastric cells in vitro suggests that changes in motility, outer membrane composition, and stress responses, among other changes, may be involved in gastric colonization.
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PMID:Genes of Helicobacter pylori regulated by attachment to AGS cells. 1503 61

Epstein-Barr virus (EBV) is associated with several types of malignancies including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, and gastric carcinoma. Previous reports have suggested that EBV-related antigen-targeting immunotherapy is one of the promising approaches for the treatment of these malignancies other than gastric carcinoma. EBV-associated gastric carcinoma (EBVaGC) has been shown to express Epstein-Barr virus nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2). In the present study, DNA and mRNA freshly isolated from tumors of patients with gastric cancer were subjected to polymerase chain reaction (PCR) using EBV-specific primers and reverse transcription (RT)-PCR specific for LMP2 transcripts. EBV-specific region was identified in genomic DNA isolated from cancerous tissues in 22% of gastric cancer patients. LMP2 mRNA was also detected in 3 out of these 5 DNA positive samples tested. To investigate the feasibility of specific immunotherapy for EBVaGC, we induced cytotoxic T lymphocytes (CTLs) from peripheral blood lymphocytes using two kinds of antigen-presenting cells (APCs) such as autologous lymphoblastoid cell line (LCL) and LMP2-derived peptide-pulsed dendritic cells (DCs). The cytotoxicity of these CTLs against peptide-pulsed targets was examined by standard 51Cr release assay and interferon (IFN)-gamma production assay. We further assessed the recognition of tumor cells endogenously expressing LMP2 by these T cells. T cells induced by peptide-loaded DCs and autologous LCL efficiently lysed peptide-pulsed targets. Furthermore, these T cells could recognize not only tumor cells transfected with LMP2, but also LMP2-positive gastric cancer cells which were successfully isolated and cultured from specimens obtained by surgery. Collectively, sensitization of peripheral blood lymphocytes with LMP2-derived peptide was able to induce CTL response against EBVaGC cells. Thus, EBVaGC is susceptible for the LMP2-targeting immunotherapy.
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PMID:Recognition of Epstein-Barr virus-associated gastric carcinoma cells by cytotoxic T lymphocytes induced in vitro with autologous lymphoblastoid cell line and LMP2-derived, HLA-A24-restricted 9-mer peptide. 1537 91


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