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)

Treatment of human stomach cancer KATO III cells with hot-water extracts from adzuki beans led to their growth inhibition as well as apoptosis induction. There are morphological changes in the cultured cells treated with the extracts, by which DNA fragmentation characteristic of apoptosis was actualized both concentration- and time-dependently. In contrast, N-acetyl-L-cysteine suppressed such DNA fragmentation, implying that the extracts from adzuki beans might exert antitumorigenicity via active oxygen-induced apoptosis. In order to verify this hypothesis in animal experiment, the 40% ethanol fraction of hot-water extracts was examined for its preventive effect against benzo(a)pyrene-induced tumorigenesis in the forestomach of A/J mice, given as drinking water containing the above fraction at 0.5-2.0% levels. Consequently, forestomach cancer has turned out to be reduced by 36-62% in tumor weight relative to the control. These results suggest that the fraction of hot-water adzuki extracts may serve as a nutrapharmaceutical or functional food available for cancer prevention.
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PMID:Hot-water extracts from adzuki beans (Vigna angularis) suppress not only the proliferation of KATO III cells in culture but also benzo(a)pyrene-induced tumorigenesis in mouse forestomatch. 1552 74

Gastric cancer is the second most common cancer in the world and the fifth leading cause of cancer-related death in Taiwan. To improve the survival of gastric cancer patients, biomarkers for early detection and effective anticancer therapy are required. An essential first step is to profile gene expression in gastric cancer and identify genes that are aberrantly expressed, and to do this cDNA microarrays were performed. The clinic-pathologic correlation and prognostic significance of the aberrantly expressed genes were evaluated to identify novel biomarkers of gastric cancer. Fresh surgical samples of tumour tissue and matching noncancerous mucosa were obtained immediately after gastric resection in 43 patients. Secreted Protein, Acidic and Rich in Cysteine (SPARC) (Osteonectins), one of the most highly expressed genes in both intestinal and diffuse gastric cancers in our microarray results, was selected for further study. The overexpression of SPARC was verified using real-time quantitative-reverse transcription-polymerase chain reaction (Q-RT-PCR), Northern blot and immunohistochemical staining. The expression of SPARC in tumour tissues was, on average, 4.27-fold increased (95% CI 2.68-5.85) compared to adjacent noncancerous mucosa (P<0.001). The expression of SPARC was higher in advanced (T2, T3 and T4) cancer compared to the early (T1) cancer (P=0.048) with regard to depth of wall invasion. Higher expression of SPARC was significantly associated with lymph node metastasis (P<0.001), lymphatic invasion (P=0.004) and perineural invasion (P=0.047). Expression of SPARC in patients in stage II and above was significantly higher than those in stage I (P=0.017). The 3-year survival of patients with lower expression of SPARC was significantly better than those with a higher expression (log rank P=0.047). These data indicate the potential of SPARC as a prognostic marker for gastric cancer.
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PMID:Overexpression of SPARC gene in human gastric carcinoma and its clinic-pathologic significance. 1555 74

The death receptors Fas and DR5 are known to be expressed not only in immune cells but also in various tumor cells. The aim of the present study was to determine whether X irradiation enhanced induction of apoptosis in Tp53 wild type and Tp53-mutated tumor cell lines treated with agonists against these death receptors. We showed that 5 Gy of X irradiation significantly up-regulated the expression of death receptors Fas and DR5 on the plasma membrane in gastric cancer cell lines MKN45 and MKN28, lung cancer cell line A549, and prostate cancer cell line DU145, and that subsequent treatments with agonistic molecules for these death receptors, Fas antibody CH11 and TRAIL, increased the formation of active fragment p20 of caspase 3 followed by the induction of apoptosis. This death-receptor-mediated apoptosis was independent of Tp53 status since MKN28 and DU145 were Tp53-mutated. The post-irradiation treatment of the cells with N-acetyl-L-cysteine (NAC) abolished the up-regulation of the expression of Fas and DR5 on the plasma membrane. NAC also attenuated the increase in the formation of p20 and the induction of apoptosis by agonistic molecules. These results suggested that the increase in the induction of apoptosis by combined treatment with X irradiation and CH11 or TRAIL occurred through a change of the intracellular redox state independent of Tp53 status in human carcinoma cell lines.
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PMID:Enhanced induction of apoptosis by combined treatment of human carcinoma cells with X rays and death receptor agonists. 1580 65

Bone morphogenetic proteins (BMPs) are implicated in cell-fate determination of embryonic stem (ES) cells and cancer cells. GREM1 (CKTSF1B1 or DAND2) and CER1 (Cerberus 1 or DAND4) are cysteine knot superfamily proteins, functioning as secreted-type BMP antagonists. BMP4 is preferentially expressed in diffuse-type gastric cancer cells. Here, vertebrate BMP4 orthologs were identified and characterized by using bioinformatics for comparative proteomics and comparative genomics analyses. Baboon BMP4 gene within AC153751.2 genome sequence encoded a 408-aa protein, showing A152V and S298P amino-acid substitutions compared with human BMP4. Cow Bmp4, bat Bmp4 and zebrafish bmp4 genes were located within AC149774.2, AC156788.2 and CR391996.2 genome sequences, respectively. Human BMP4 showed 99.5%, 98.0%, 97.8%, 97.1%, 96.3%, 83.3% and 71.1% total-amino-acid identity with baboon BMP4, cow Bmp4, bat Bmp4, mouse Bmp4, rat Bmp4, chicken bmp4 and zebrafish bmp4, respectively. Human BMP4 gene was found consisting of six exons, including novel exon 1C, and known exons 1 (1A or I), 1B (II), 2 (III), 3 (IV) and 4 (V). Forty human BMP4 ESTs started from exon 1, seven from intron 1 (5'-flanking region of exon 2), and two from exon 1C. Fourteen mouse Bmp4 ESTs started from exon 1, and one from intron 1. The 5'-flanking region of exon 1 and exon 1 itself, but not exons 1C and 1B, were well conserved between human BMP4 and rodent Bmp4 genes. The major promoter region of human BMP4 and rodent Bmp4 genes were located within the 5'-flanking region of exon 1. FOXA2, OLF1, and MYC-binding sites were conserved among the major promoter region of human, baboon, cow, bat, mouse and rat BMP4 orthologs.
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PMID:Comparative genomics on BMP4 orthologs. 1601 Apr 42

SLIT1 gene at human chromosome 10q24.1, SLIT2 gene at 4p15.31, and SLIT3 gene at 5q34-q35.1 encode large secreted proteins functioning as ligands for Roundabout (Robo) receptors. SLIT-ROBO signaling pathway is implicated in neurogenesis, angiogenesis, and immune response through the regulation of axonal guidance, endothelial cell migration, and denderitic cell migration, respectively. GREMLIN (CKTSF1B1 or GREM1) and DANTE (CKTSF1B3 or GREM3) are secreted antagonists for BMPs and SLITs. Here, comparative integromics analyses on SLIT1, SLIT2, and SLIT3 orthologs were performed by using bioinformatics. Rat Slit2 gene, consisting of 36 exons, was located within rat genome sequences AC098362.4 and AC111627.6. Mouse Slit3 complete coding sequence was determined by assembling BB634238 EST, AF144629 cDNA, and AK129223 cDNA. Leucine-rich repeats with nine conserved cysteine (LRRCC) domains and SLIT C-terminal cysteine-rich (SLITCCR) domain were identified in this study. CPxxCxCxxxxVxCxxxxLxxxPxxxPx(10~58) Nx(19,20)LxxNx(9)Fx(8)LxLxxNxxxCxxxxxFxxLxxx xxLxLxxNx(9)Fx(13)NxxxCxCxxxWLx(15)CxxPx(17)C was the consensus sequence of LRRCC domain. Mammalian SLIT1, SLIT2 and SLIT3 orthologs were large secreted proteins with four LRRCC domains, nine EGF domains, Laminin G (LamG) domain, and SLITCCR domain. SLIT1 mRNA was expressed in fetal brain, infant brain, anaplastic oligodendroglioma, and Jurkat T cells. SLIT2 and SLIT3 mRNAs were co-expressed in embryonic stem (ES) cells with embryoid body formation, and diffuse type gastric cancer with signet ring cell features. Double TCF/LEF and bHLH-binding sites were conserved among mammalian SLIT1 promoters. FOXJ2, E47, ETS1, and FOXA2-binding sites and CCAAT box were conserved among mammalian SLIT3 promoters. Mammalian SLIT1 orthologs were identified as evolutionarily conserved targets of the WNT/beta-catenin signaling pathway.
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PMID:Comparative genomics on SLIT1, SLIT2, and SLIT3 orthologs. 1621 8

Gastric cancer is the second most frequent type of neoplasia and also the second most common cause of death in the world. TP53 codon 72, which produces variant proteins with an arginine (Arg) or proline (Pro), has been reported to be associated with cancers of the lung, oesophagus, stomach and cervix. Werner's syndrome (WS) is a premature ageing disease caused by a mutation in the WRN gene. The WRN protein acts as a DNA helicase and as an exonuclease. WRN codon 1367 produces variant proteins with an Arg or cysteine (Cys). This polymorphism has been studied, in order to understand the clinical impact of the molecular variants in WS and in age-related disorders. In the present study, the TP53 codon 72 and the WRN codon 1367 polymorphisms were investigated in 54 gastric adenocarcinoma patients (31 diffuse-type and 25 intestinal-type) and 54 controls. DNA samples were extracted, and PCR-RFLP was utilised for genotyping TP53 codon 72 and WRN codon 1367. The allele frequencies of the TP53 polymorphism were: Arg=0.74 and Pro=0.26. The allele frequencies of the WRN polymorphism were: Cys=0.73 and Arg=0.27. The crude genotypic frequencies in gastric cancer patients were similar to those of the controls, but in the WRN codon 1367 polymorphisms the mean age tended to be higher in the Arg/Arg genotypes. There also was an association, although not statistically significant, between the presence of Helicobacter pylori and the genotypes Cys/Cys and Cys/Arg and a higher percentage of cardia cancer among the Arg/Arg genotypes, and of non-cardia cancer among genotypes Cys/Cys and Cys/Arg. These findings may be a reflection of differences in the interaction between WRN codon 1367 polymorphisms and local factors in the stomach. To our knowledge, this is the first study to examine a genetic polymorphism of the WRN gene in cancer. The precise mechanisms of action of the TP53 and WRN polymorphisms involved in the aetiopathogeny of this disease need further investigation.
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PMID:Polymorphisms of the TP53 codon 72 and WRN codon 1367 in individuals from Northern Brazil with gastric adenocarcinoma. 1636 95

We have investigated the effect of glycyrrhetic acid (GR) which is metabolic substance of glycyrrhizin, on DNA of human hepatoma (HLE), promyelotic leukemia (HL-60) and stomach cancer (KATO III) cells. GR displayed apoptotic effects against HLE, HL-60 and KATO III cells. The fragmentation of DNA by GR to oligonucleosomal-sized fragments, a characteristic of apoptosis, was dose- and time-dependent in these cell lines. These findings suggest that growth inhibition of these cell lines by GR result from the induction of apoptosis by the compound. Inhibitors of caspases did not suppress the DNA fragmentation caused by GR. N-acetyl-L-cysteine, an antioxidant drug, weakly inhibited the DNA fragmentation caused by GR suggesting that active oxidants work partly as an apoptosis-inducing transfer substance.
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PMID:Glycyrrhetic acid (a metabolic substance and aglycon of glycyrrhizin) induces apoptosis in human hepatoma, promyelotic leukemia and stomach cancer cells. 1639 18

Deficiency of the mannose-binding lectin (MBL) protein, an antigen-recognition molecule involved in systemic and mucosal innate immunity, is determined by variant alleles in MBL2 gene promoter and exon-1 regions. We conducted a population-based study on 305 stomach cancer cases and 427 controls in Warsaw, Poland to determine whether MBL2 gene variants predispose to stomach cancer. Single nucleotide polymorphisms (SNPs) in MBL2 were determined by TaqMan. The 5 tested MBL2 variants are in complete linkage disequilibrium and comprise 6 different haplotypes. The risk of stomach cancer was increased in subjects carrying the H/H promoter genotype (OR = 1.8, 95%CI 1.1-2.9; p = 0.020) relative to L/L carriers, after adjustment for age, gender, education and smoking. Carrying at least one D exon-1 allele was associated with nonsignificant excess risk (OR = 1.5, 95% CI 0.9-2.4; p = 0.081). In haplotype analysis, the HYD haplotype was associated with increased risk of stomach cancer when compared with HYA, the most common haplotype (OR = 1.9, 95% CI 1.1-3.2; p = 0.021). In diplotype analysis, subjects carrying the YA/D haplotype combination showed the highest risk (OR = 3.0, 95% CI 1.2-7.1; p = 0.015), compared with YA/YA. Further analyses to examine the joint effect of MBL2 and IL-1B polymorphisms, previously shown to predispose to stomach cancer, indicated that the combination of at-risk IL-1B genotypes (CT or TT at location -511) and HYD MBL2 haplotype was associated with a 3.5-fold risk (OR = 3.5, 95% CI 1.6-7.6; p = 0.001). Our findings suggest that the codon 52 D MBL2 variant causing a cysteine > arginine replacement, but not B and C variants producing glycine substitutions, is specifically associated with gastric cancer risk.
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PMID:Mannose-binding lectin-2 genetic variation and stomach cancer risk. 1735 1

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

The gastric pathogen, helicobacter pylori (H. pylori), has been associated with the progression of gastric cancer. It was previously reported that H. pylori induced urokinase plasminogen activator receptor (uPAR) expression and stimulated cell invasiveness in human gastric cancer AGS cells. However, the precise mechanisms for how H. pylori upregulates uPAR are unclear. This study investigated the underlying signal pathways in H. pylori-induced uPAR in human gastric cancer AGS cells. The intracellular H2O2 content, as determined using H2O2-sensitive probe 2',7'-dichlorodihydrofluorescein, increased after the H. pylori treatment. N-acetyl cysteine (NAC), an antioxidant, prevented the H. pylori-induced production of H2O2 and uPAR expression. In addition, exogenous H2O2 was found to increase uPAR mRNA expression and its promoter activity. Site-directed mutagenesis of the potential NF-kappaB element in the uPAR promoter showed that the redox-sensitive transcription factor NF-kappaB was essential for H. pylori-induced uPAR expression. The expression of vectors encoding a mutated-type NF-kappaB-inducing kinase and I-kappaB, and a specific inhibitor of NF-kappaB (BAY11-7082) decreased the H. pylori-induced uPAR promoter activity. Chromatin immunoprecipitation and the electrophoretic mobility shift assay confirmed that H. pylori increased the DNA binding activity of NF-kappaB. With the aid of NAC and H2O2, it was determined that reactive oxygen species (ROS) is an upstream signaling molecule for activating the NF-kappaB induced by H. pylori. The enhanced AGS cell invasiveness by H. pylori was partially abrogated by an NAC and BAY11-7082 treatment. These results suggest that the ROS and NF-kappaB signaling pathway is important in H. pylori-induced uPAR expression and the increased cell invasiveness of human gastric cancer AGS cells.
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PMID:Helicobacter pylori stimulates urokinase plasminogen activator receptor expression and cell invasiveness through reactive oxygen species and NF-kappaB signaling in human gastric carcinoma cells. 1733 46


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