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)

An 83-year-old man was admitted to our hospital for abdominal pain and severe vomiting. Gastrography and gastric endoscopy revealed that the pylorus was obstructed by a giant type 2 cancer in the lower gastric body. Furthermore, computed tomography revealed multiple metastases in the para-aortic lymph nodes. The man was unable to consume any food or liquid, and could not take medicine orally. Paclitaxel was not effective in treating the lymph node metastases or vomiting; therefore a chronomodulated schedule was used, which involved the administration of low doses of 5-fluorouracil, levofolinate calcium and cis-platinum (FLP) each night. After four cycles of low-dose FLP therapy, the patient was able to consume food orally. The patient has partially responded to this regime over five months. In the current study, low-dose FLP therapy with chronomodulation was considered an effective treatment, and there were no severe adverse side effects. This case suggested that low-dose FLP therapy with chronomodulation is promising for the treatment of gastric cancer in elderly patients who can not take medicine orally, and further trials are warranted.
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PMID:[Successful treatment of an elderly patient with advanced gastric cancer using low-doses of 5-fluorouracil, levofolinate calcium, and cis-platinum with chronomodulation]. 1710 31

Calpains are calcium activated cysteine proteases found throughout the animal, plant, and fungi kingdoms; 14 isoforms have been described in the human genome. Calpains have been implicated in multiple models of human disease; for instance, calpain 1 is activated in the brains of individuals with Alzheimer's disease, and the digestive tract specific calpain 9 is down-regulated in gastric cancer cell lines. We have solved the structures of human calpain 1 and calpain 9 protease cores using crystallographic methods; both structures have clear implications for the function of non-catalytic domains of full-length calpains in the calcium-mediated activation of the enzyme. The structure of minicalpain 1 is similar to previously solved structures of the protease core. Auto-inhibition in this system is most likely through rearrangements of a central helical/loop region near the active site cysteine, which occlude the substrate binding site. However, the structure of minicalpain 9 indicates that auto-inhibition in this enzyme is mediated through large intra-domain movements that misalign the catalytic triad. This disruption is reminiscent of the full-length inactive calpain conformation. The structures of the highly conserved, ubiquitously expressed human calpain 1 and the more tissue specific human calpain 9 indicate that although there are high levels of sequence conservation throughout the calpain family, isolated structures of family members are insufficient to explain the molecular mechanism of activation for this group of proteins.
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PMID:The crystal structures of human calpains 1 and 9 imply diverse mechanisms of action and auto-inhibition. 1715 13

Developing an efficient and safe strategy to introduce a therapeutic gene into targeting cells in vivo is a key issue in cancer gene therapy nowadays. Novel non-viral gene carriers, such as nanoparticles, have been shown to be able to deliver DNA into cancer cells efficiently. Suicide gene therapy has been demonstrated to be effective in inhibiting tumor growth, however, the lack of tumor specificity limits its application in clinic. Developing a targeting system for suicide gene is an attractive strategy in cancer gene therapy. In this study, the CMV enhancer and carcinoembryonic antigen (CEA) promoter was fused to a chimeric suicide gene yCDglyTK. This construct was delivered into SGC7901 gastric cancer cells using calcium phosphate nanoparticles (CPNPs). The expression of yCDglyTK in SGC7901 cells was confirmed by RT-PCR and western blot. Immunofluorescence experiments showed that yCDglyTK is only expressed in CEA-positive cancer cells, but not in CEA-negative cells. The expression of yCDglyTK induced cancer cell death following the addition of the prodrug 5-FC, and also elicit "bystander effect" to kill the neighboring cells. Intratumoral injection of CPNP-yCDglyTK complex followed by administration of 5-FC produced marked regression in gastric cancer xenografts. Taken together, our study suggests that the combination of calcium phosphate nanoparticles and suicide gene therapy represents a novel approach for targeting gastric cancer gene therapy.
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PMID:Tissue specific expression of suicide genes delivered by nanoparticles inhibits gastric carcinoma growth. 1722 32

Gastric cancer is one of the most common malignancies and is a frequent cause of cancer-related death in Korea. Cure rate of gastric cancer is quite low because of local invasion and metastasis. S100 proteins are calcium-binding proteins which exert various calcium-mediated cellular functions including cell growth, differentiation, migration and signal transduction. S100A8 and S100A9 are overexpressed in many human tumors and have been shown to be implicated in tumor development or progression. In the present study, we investigated the role of S100A8 and S100A9 in invasive phenotype of a human gastric cancer cell line, SNU484. Expression of S100A8 and S100A9 were detected in SNU484 cells. When the expression of these proteins was suppressed by small-interfering RNA (siRNA) targeting S100A8 or S100A9, the invasive and migratory phenotypes of SNU484 cells were significantly inhibited. The siRNAs for S100A8 and S100A9 inhibited matrix metalloproteinase (MMP)-2 expression in SNU484 cells as evidenced by gelatin zymogram assay, immunoblot analysis and reverse transcription (RT)-PCR. These results demonstrate that S100A8 and S100A9 are required for transcriptional activation of MMP-2 gene in SNU484 cells. Taken together, this study revealed a functional contribution of S100A8 and S100A9 proteins to processes required for malignant progression including invasion, migration and proteinase expression in SNU484 human gastric cancer cells.
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PMID:Roles of calcium-binding proteins, S100A8 and S100A9, in invasive phenotype of human gastric cancer cells. 1732 45

In this study we investigated the effects of constituents of Amomum xanthioides (AX) on gastritis in rats and on the growth of human gastric cancer cells. The ethanol extract of Amomum xanthioides significantly inhibited HCl ethanol-induced gastric lesions and the growth of Helicobacter pylori (H. pylon). The ethanol extract of AX was further fractionated with hexane, chloroform, butanol and H20. Among these fractions, oral treatment with the butanol fraction at a dose of 350 mg/kg was the most effective at preventing HCl* ethanol-induced gastric lesions. In pylorus ligated rats, the butanol fraction also decreased the volume of gastric secretion and gastric acid output. We isolated six subfractions of the butanol fraction using open column chromatography. Subfraction 4 (150 mg/kg) significantly inhibited HCl* ethanol-induced gastric lesions and gastric secretion in pylorus ligated rats. Using GC-MS we identified the constituents of subfraction 4 to be five aliphatic compounds, 1-hexadecene, 1-nonadecene, cycloeicosane, 1-octadecene and cyclotetracosane. In addition, subfraction 4 reduced cell viability in a dose-dependent manner in human gastric cancer cells (AGS, KATOIII and SNU638). It also increased intracellular Ca2+ concentration in SNU638 cells, an effect that was significantly inhibited by dantrolene, a Ca2+ release blocker. Moreover, dantrolene significantly inhibited subfraction 4-induced cytotoxicity. Taken together, these results suggest that subfraction 4 of the butanol extract of AX has an anti-gastritic effect in rats and is cytotoxic to human gastric cancer cells. The mechanism of its anti-gastritic action may be associated with the inhibition of secretion of gastric acid and anti-H. pylori action. Its cytotoxicity against human gastric cancer cells may be, at least in part, mediated by intracellular Ca2+ dyshomeostasis. From these results, we suggest that AX may be useful for the treatment of gastritis and gastric cancer.
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PMID:Effects of constituents of Amomum xanthioides on gastritis in rats and on growth of gastric cancer cells. 1748 59

The prion protein (PrPC) has a primary role in the pathogenesis of transmissible spongiform encephalopathies, which causes prion disorders partially due to Ca2+ dysregulation. In our previous work, we found that overexpressed PrPC in gastric cancer was involved in apoptosis, cell proliferation, and metastasis of gastric cancer. To better understand how PrPC acts in gastric cancer, a human microarray was performed to select differentially regulated genes that correlate with the biological function of PrPC. The microarray data were analyzed and revealed 3798 genes whose expression increased at least 2-fold in gastric cancer cells transfected with PrPC. These genes encode proteins involved in several aspects of cell biology, among which, we specially detected molecules related to calcium, especially the S100 calcium-binding proteins, and found that PrPC upregulates S100A1, S100A6, S100B, and S100P but downregulates CacyBP in gastric cancer cells. We also found that intracellular Ca2+ levels in cells transfected with PrPC increased, whereas these levels decreased in knockdowns of these cells. Taken together, PrPC might increase intracellular Ca2+, partially through calcium-binding proteins, or PrPC might upregulate the expression of S100 proteins, partially through stimulating the intracellular calcium level in gastric cancer. Though the underlying mechanisms need further exploration, this study provides a new insight into the role of PrPC in gastric cancer and enriches our knowledge of prion protein.
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PMID:Differential expression of calcium-related genes in gastric cancer cells transfected with cellular prion protein. 1761 32

A multiple-unit-type oral floating dosage form (FDF) of 5-fluorouracil (5-FU) was developed to prolong gastric residence time, target stomach cancer, and increase drug bioavailability. The floating bead formulations were prepared by dispersing 5-FU together with calcium carbonate into a mixture of sodium alginate and hydroxypropyl methylcellulose solution and then dripping the dispersion into an acidified solution of calcium chloride. Calcium alginate beads were formed, as alginate undergoes ionotropic gelation by calcium ions and carbon dioxide develops from the reaction of carbonate salts with acid. The evolving gas permeated through the alginate matrix, leaving gas bubbles or pores, which provided the beads buoyancy. The prepared beads were evaluated for percent drug loading, drug entrapment efficiency, image, surface topography, buoyancy, and in vitro release. The formulations were optimized for different weight ratios of gas-forming agent and sodium alginate. The beads containing higher amounts of calcium carbonate demonstrated instantaneous, complete, and excellent floating ability over a period of 24 hours. The optimized formulation was subjected to in vivo antitumor studies to check the therapeutic efficacy of the floating dosage forms containing 5-FU against benzo(a)pyrene-induced stomach tumors in albino female mice (Balb/C strain). The multiple-bead FDF was found to reduce the tumor incidence in mice by 74%, while the conventional tablet dosage form reduced this incidence by only 25%. Results indicate that FDF performed significantly better than the simple tablet dosage form.
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PMID:Stomach-specific drug delivery of 5-fluorouracil using floating alginate beads. 1762 5

Thimerosal is a mercury-containing preservative in some vaccines. The effect of thimerosal on human gastric cancer cells is unknown. This study shows that in cultured human gastric cancer cells (SCM1), thimerosal reduced cell viability in a concentration- and time-dependent manner. Thimerosal caused apoptosis as assessed by propidium iodide-stained cells and caspase-3 activation. Although immunoblotting data revealed that thimerosal could activate the phosphorylation of extracellular signal-regulated kinase, c-Jun NH2-terminal protein kinase, and p38 mitogen-activated protein kinase (p38 MAPK), only SB203580 (a p38 MAPK inhibitor) partially prevented cells from apoptosis. Thimerosal also induced [Ca2+](i) increases via Ca2+ influx from the extracellular space. However, pretreatment with (bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetate)/AM, a Ca2+ chelator, to prevent thimerosal-induced [Ca2+](i) increases did not protect cells from death. The results suggest that in SCM1 cells, thimerosal caused Ca2+-independent apoptosis via phosphorylating p38 MAPK resulting in caspase-3 activation.
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PMID:Thimerosal-induced apoptosis in human SCM1 gastric cancer cells: activation of p38 MAP kinase and caspase-3 pathways without involvement of [Ca2+]i elevation. 1769 13

Multidrug resistance (MDR) is a major obstacle to successful cancer treatment. To understand the mechanism of MDR better, a subcelluar proteomics approach was used to compare the protein profile between vincristine-resistant human gastric cancer cell line SGC7901/VCR and its parental cell line SGC7901. After differential solubilization, the subfractionation proteins were separate by two-dimensional gel electrophoresis (2-DE), and the differential protein spots were identified by both MALDI-TOF-MS and ESI-Q-TOF-MS. Then the differential expressional levels of partial identified proteins were determined by Western blot analysis. Furthermore, one of the highly expressed proteins in SGC7901/VCR, Sorcin, associated with MDR was analyzed. In this study, the well-resolved, reproducible 2-DE patterns of subfractionation proteins from SGC7901/VCR and SGC7901 were established, and 30 differential proteins between the two cell lines were identified. The functional validation showed that the elevated sorcin expression could contribute considerably to the vincristine resistance in SGC7901/VCR. The 30 differentially expressed proteins could be divided into six groups based on their functions: calcium binding proteins, chaperones, metabolic enzymes, proteins relative to signal transduction, proteins involved in transcription and translation, and transportation proteins, and most of them might be new MDR associated proteins, which have not been detected previously. These data will be valuable for further to study the mechanisms of MDR in human gastric cancer.
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PMID:A subcelluar proteomic investigation into vincristine-resistant gastric cancer cell line. 1825 33

Our previous study demonstrated that PPARgamma ligand rosiglitazone prevents gastric carcinogenesis in rats induced by chemical carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In this study, we attempted to identify novel anti-cancer mechanisms of rosiglitazone. By examining the gene expression profiles of MNNG-induced and rosiglitazone-treated gastric cancer with Uniset Rat I Bioarray microarray, we identified a gene that showed prominent responses in the rosiglitazone-treated group. The hypertension-related, calcium-regulated gene (HCaRG) was significantly up-regulated in rat gastric carcinoma of the rosiglitazone-treated group when compared with the MNNG group. We further examined HCaRG expression in human gastric cancer and found that the expression of HCaRG was down-regulated in human gastric cancerous tissue. Rosiglitazone markedly induced the expression of HCaRG in the AGS cell line. The up-regulation of HCaRG may be one of the mechanisms underlying the chemopreventive effect of rosiglitazone in gastric cancer.
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PMID:Rosiglitazone suppresses gastric carcinogenesis by up-regulating HCaRG expression. 1894 6


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