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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substantial evidence show a higher incidence of gastric cancer in smokers than nonsmokers and that cigarette smoking is highly associated with colon cancer. The present study was designed to examine the effect of cigarette smoke extracts on gastric and colon cancer cell proliferation, which is important for tumor growth. Two different cell lines were used. One was gastric cancer cell line AGS, and the other was colon cancer cell line HT-29. It was found that cigarette smoke extracts stimulated cell proliferation and c-myc expression in AGS cells. Furthermore, this proliferative action was partially blocked by the c-myc antisense. However, the extracts significantly inhibited HT-29 cell proliferation and suppressed c-myc expression. In conclusion, cigarette smoke extracts stimulated AGS cell proliferation, while inhibiting HT-29 proliferation, which were partially mediated by a c-myc-related pathway. The former action may play a contributory role in the carcinogenic action of cigarette smoking in the stomach.
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PMID:Differential effects of cigarette smoke extracts on cell proliferation in gastric and colon cells. 1274 85

To determine the prevalence of gastric precancerous lesions and mucosal genetic alterations in relatives of a cluster of familial gastric cancer (FGC), we studied a kindred spanning two generations. The founder, daughter and niece underwent surgery for gastric cancer (GC); a son and other two daughters of the founder, presented with chronic dyspepsia. In all subjects, gastric mucosa samples were analysed for pathological features, Helicobacter pylori infection, microsatellite (MIN) and chromosomal (CIN) instability. The overexpression of mp53 and c-myc, and cytoplasmic beta-catenin delocalisation were found in the 2 younger cancer patients. All GC and gastritis patients had normal E-cadherin expression and were MIN-negative. Aneuploidy characterised all GC cases, and mixed euploid and aneuploid cell populations were present in the gastric biopsies from two of three 'at-risk' relatives. These two subjects, one of whom had severe active gastritis, and gastric mp53 and c-myc expression, were CagA-positive H. pylori-infected. DNA aneuploidy, p53 and c-myc expression disappeared after H. pylori eradication. In this FGC cluster, genetic abnormalities were found in first-degree relatives (3 patients) only in presence of H. pylori infection (2 cases H. pylori-positive versus 1 case H. pylori-negative) supporting the hypothesis that, besides the influence of a genetic profile, FGC may be, at least partly, mediated by intrafamilial clustering of H. pylori infection.
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PMID:Is there a link between environmental factors and a genetic predisposition to cancer? A lesson from a familial cluster of gastric cancers. 1285 70

Chromosomal or centromerical numerical abnormality (CNA) is a well-known characteristic of human cancer, but the extensive and specific documentation of CNA in gastric cancer is still sparse, partly because of difficulty in obtaining cytogenetic information. Taking advantage of a recently developed fluorescence in situ hybridization protocol for formalin-fixed paraffin-embedded tissues, we investigated CNA of 51 gastric cancer cases with a panel of 18 chromosome-specific alpha-satellite probes (for chromosomes 1-4, 6-12, 15-18, 20, X and Y) and region specific probes (c-myc and p53) to enumerate respective chromosome numbers in interphase nuclei. The involved chromosomes exhibiting CNA were nonrandom in gastric cancer. Aberrations of chromosomes 1, 8, 17, 20, and X were frequent regardless of histologic types, whereas aberrations chromosomes 10, 15, and 18 occurred less often (p < 0.001). From a histopathologic standpoint, the mucocellular type had stable CNA in comparison with the tubular type (mucocellular type vs tubular type carcinoma: 21.0 +/- 10.63% vs 62.8 +/- 12.79%, p < 0.001). Interestingly, there was less extensive CNA in women (men vs women: 54.3 +/- 9.49% versus 24.9 +/- 12.23%, p < 0.001). A dramatic difference in the outcome was detected according to the involvement of chromosomes 3, 10, 11, 12, 17, and Y; that is, the cases with CNA of these chromosomes had worse prognosis.
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PMID:Nonrandom chromosomal numerical abnormality predicting prognosis of gastric cancer: a retrospective study of 51 cases using pathology archives. 1367 39

Cigarette smoke has been shown to cause gastric cancer. Overexpression of cyclooxygenase-2 (COX-2) is a common characteristic in gastric malignancy. The present study aimed to explore the correlation between cigarette smoke and COX-2 in the promotion of tumorigenesis in human gastric cancer cells (AGS). We further studied the action of COX-2 on other proto-oncogenes on gastric tumor growth. Results showed that chloroform extract (CE) and ethanol extract (EE) from cigarette smoke dose-dependently stimulated gastric cancer cell proliferation, which was accompanied with an activation of ornithine decarboxylase (ODC) activity, COX-2, and c-myc expressions. Both antisense of c-myc and alpha-difluoromethylornithine (DFMO, specific ODC inhibitor) inhibited cell proliferation without affecting COX-2 expression in response to cigarette smoke extracts (CSE). However, selective COX-2 inhibitor (SC-236) not only blocked the proliferative activity but also the ODC activity and c-myc protein expression by CSE in gastric cancer cells. Further, supplementation of exogenous prostaglandin (PG) E(2) reversed all the inhibitory actions of SC-236. Our results underline the importance of COX-2 in the cancer-promoting effect of CSE and its modulation on its downstream growth-related genes, such as c-myc and ODC in cancer cell proliferation. These results reveal that CSE-induced gastric carcinogenesis is via the COX-2/c-myc/ODC and PGE(2)-dependent pathway. Hence, selective COX-2 inhibitor could be an effective therapeutic agent for gastric cancer in smokers.
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PMID:A mechanistic study of cigarette smoke and cyclooxygenase-2 on proliferation of gastric cancer cells. 1496 10

The truncated myc and max proteins, only containing basic regions and helix-loop-helix/zipper (b/HLH/Zip) regions were over-expressed in E. coli and used for the determination of the binding constant and of the inhibitory mechanism on myc-max (or max-max)-DNA complex formation. The association kinetic constants (k(1) and k(-1)) of truncated max-max or myc-max dimer and DNA were determined as k(1)=(1.7+/-0.6)x10(5) M(-1) s(-1), k(-1)=(3.4+/-1.2)x10(-2) s(-1) for max-max and DNA or k(1)=(2.1+/-0.7)x10(5) M(-1) s(-1), k(-1)=(3.2+/-1.4)x10(-2) s(-1) for myc-max and DNA. The equilibrium binding constant (K(1)) was determined using these kinetic parameters [K(XXD)=(7.8+/-2.6)x10(6) M(-1) for max-max and DNA or K(XYD)=(6.9+/-2.2)x10(6) M(-1) for myc-max and DNA]. The binding constants of myc-max or max-max dimer formation were K(XX)=(2.6+/-0.9)x10(5) M(-1) or K(XY)=(1.3+/-0.4)x10(4) M(-1), respectively. When truncated proteins were used, the max-max dimer formation was easier than the myc-max dimer formation, contrary to the physiologically determined case. This leads us to deduce that domains other than b/HLH/Zip are very important for the transcriptional regulatory activity in physiological conditions. The truncated myc and max proteins, which were expressed in E. coli and contained only b/HLH/Zip regions were also used for the screening of inhibitors of myc-max-DNA complex formation. A synthesized curcuminoid, 1,7-bis(4-methyl-3-nitrophenyl)-1,6-heptadiene-3,5-dione (curcuminoid 004), showed the most potent inhibition out of the synthesized curcuminoids, in competition with DNA. The dissociation constant of max-max dimer and the inhibitor was 9 microM, when investigated using in vitro expressed b/HLH/Zip dimer proteins. The curcuminoid 004 showed an inhibitory effect on the binding of myc-max protein to the E-box element in SNU16 cells, and suppressed the expression of myc target genes including ornithine decarboxylase (ODC), cdc25a and c-myc in myc over-expressed human stomach cancer cell line SNU16.
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PMID:Determination of binding constant of transcription factor myc-max/max-max and E-box DNA: the effect of inhibitors on the binding. 1498 Apr 48

Chromosomal numerical abnormality (CNA) is one of the distinct characteristics of human cancers, though the mechanisms and tumor specificity of this phenomenon have not been adequately analyzed. Recently, we developed a new sensitive fluorescence in situ hybridization (FISH) method that involves short-term microwave (MW) treatment for hybridization. In this study, we applied this modified FISH technique to investigate the CNA of 60 gastric cancer cases with a panel of 18 chromosome-specific alpha-satellite probes (for chromosome 1-4, 6-12, 15-18, 20, X, and Y) and region-specific probes (c-myc, p53, and Her-2/neu) to enumerate the respective chromosome numbers in interphase nuclei of formalin-fixed paraffin-embedded sections. The numerical aberrations of chromosome 1, 3, 8, 17, 20, and X were frequent regardless of histologic types, whereas aberrations of chromosomes 10, 15, and 18 occurred less frequently (p<0.001). From a histopathological standpoint, the mucocellular type of carcinoma had stable CNA in comparison with the tubular type of carcinoma (21.7+/-9.63% vs. 58.3+/-12.32%, p<0.001) and, of note, there was less extensive CNA in female cases. A dramatic difference in patient outcome was detected according to the involvement of chromosomes 3, 10, 11, 12, 17, and Y; cases with CNA of these chromosomes had a worse prognosis (p<0.001). A two-step analysis of the CNA of 6 chromosomes and locus specific gene abnormalities successfully divided gastric cancer cases into those with a good outcome and those with a poor outcome. This analysis allows one to more accurately predict prognosis than by using a simple classification based on conventional clinicopathological diagnosis.
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PMID:Nonrandom chromosomal numerical abnormality as a new molecular cytogenetic tumor marker--a retrospective study of 60 gastric cancer cases. 1629 33

Many studies examine the molecular genetics of gastric cancer, but few look at young patients in particular and there is no comparison of molecular expression between early-onset gastric cancer (< or = 45 years old) and conventional gastric cancers. Expression of cycloxygenase-2 (COX-2) is elevated in gastric adenocarcinomas compared to non-neoplastic mucosa, and in light of studies showing reduced risk of gastric cancer in nonsteroidal anti-inflammatory drug users, we have chosen to investigate the expression of COX-2 and related molecules in 113 early-onset gastric cancers and compare it with 91 conventional gastric cancers, using tissue microarrays. These markers include molecules known to be important in conventional gastric carcinogenesis, such as E-Cadherin, p53, COX-2, Trefoil Factor-1 (TFF1), beta-catenin, p16 and c-myc; as well as molecules not yet described as being important in gastric cancer, such as the transcription factor c-jun, the COX-2 mRNA stabilizer HuR, and C/EBP-beta, a transcription factor for COX-2. All markers showed a statistically significant difference between early-onset gastric cancers and conventional gastric cancers, using a chi2 test. In particular, early-onset gastric cancers displayed a COX-2 Low, TFF1-expressing phenotype, whereas COX-2 overexpression and loss of TFF1 was found in conventional cancers, and this difference between early-onset gastric cancers and conventional cancers remained statistically significant when adjusted for location and histology (P<0.0001 and P = 0.002 respectively). We found that COX-2 overexpression correlates significantly with loss of TFF1 (P = 0.001), overexpression of C/EBP-beta (P<0.001) and cytoplasmic HuR (P = 0.016). COX-2 was significantly associated with p53 positivity (P = 0.003). Abnormalities in E-Cadherin correlated significantly with diffuse phenotype, whereas high expression of COX-2, loss of TFF1 and overexpression of C/EBP-beta correlated with the intestinal phenotype. Our results provide further evidence that early-onset gastric cancer exhibits a distinctive expression profile that may have practical implications.
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PMID:Early-onset gastric cancers have a different molecular expression profile than conventional gastric cancers. 1647 75

Telomerase activity is detected in more than 90% of examined tumors but not in most normal somatic cells. Among three subunits of human telomerase, human telomerase reverse transcriptase (hTERT) is the rate-limiting component for telomerase activity. Therefore, targeting hTERT represents a promising approach for diminishing telomerase function that will probably not cause substantial side effects on telomerase negative somatic cells. To explore the effects of antisense hTERT (ahTERT) on the malignant phenotypes of human SGC-7901 gastric cancer cell line in vitro, an antisense eukaryotic expression vector of hTERT was constructed by gene recombinant technology. Telomerase activity by telomeric repeat amplification protocol-ELISA, mRNA of telomerase subunits, c-myc and bcl-2 by reverse transcript-PCR, terminal restriction fragment (TRF) by Southern blot, cell cycle distribution by flow cytometry and protein expression of hTERT, c-myc and bcl-2 by Western blot were analyzed in SGC-7901 cells before and after transfection. Cloning efficiency assay in soft agar and tumorigenesis in nude mice were also examined and evaluated in the above cells. The results demonstrated that after ahTERT transfection, the proliferation of SGC-7901 cells was significantly inhibited. Further study showed that telomerase activity, telomere length, the mRNA and protein expression of hTERT, bcl-2 and c-myc were decreased in ahTERT-transfected cells. There were, however, no obvious effects on transcription of human telomerase RNA (hTR) and human telomerase associated protein1 (TP1) in both transfected and untransfected cells. Flow cytometric analysis displayed an accumulation of G0/G1 phase and a decreasing proliferation index (PI) in ahTERT-transfected cells. Moreover, no tumorigenicity was found after subcutaneous injection of ahTERT-transfected cells in nude mice, whereas palpable tumors were observed in mice injected with control cells. Our study indicates that exogenous ahTERT can inhibit proliferation and partially reverse malignant phenotypes of SGC-7901 cells via the suppression of telomerase activity, hTERT, c-myc and bcl-2 expression. Antisense technology targeted hTERT strategy might be a potential approach for gastric cancer therapy.
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PMID:Antisense human telomerase reverse transcriptase could partially reverse malignant phenotypes of gastric carcinoma cell line in vitro. 1841 91

Aloe-emodin is a hydroxyanthraquinone found in Aloe vera, as well as in leaves and roots of other plants. The mechanisms of its anticancer effect are largely unknown. The present study investigated its molecular mechanisms. Crystal violet assay showed that aloe-emodin had a long-term anti-proliferation effect on human gastric cancer MGC-803 and SGC-7901 cells. Scratch wound-healing motility assays indicated its anti-migration effect. Aloe-emodin arrested SGC-7901 cells at G2/M phase. More importantly, aloe-emodin inhibited the expressions of protein kinase C and c-myc. In conclusion, the anticancer effect of aloe-emodin on gastric cancer cells involves suppression of c-myc expression.
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PMID:Suppression of C-myc expression associates with anti-proliferation of aloe-emodin on gastric cancer cells. 1844 57

The present study aimed to investigate the effect of knocking-down methylenetetrahydrofolate reductase (MTHFR) on the survival of the human gastric cancer cell line MKN45. Antisense and small interfering RNA (siRNA) plasmids were used to target MTHFR in MKN45. Meanwhile, we also constructed a wild-type MTHFR plasmid to assess the effect of over-expression of this protein on cell viability. The knock-down of MTHFR decreased cell survival by approximately 30% compared to the control and resulted in cell cycle arrest at the G2 phase. These cells also had lower levels of c-myc compared to control cells, while over-expression of MTHFR increased cell proliferation and induced the down-regulation of p21WAF1 and hMLH1. Inhibiting MTHFR with either antisense or siRNA decreases the viability of methionine-dependent transformed gastric cancer cells and suggests that MTHFR inhibition may be a novel anticancer approach.
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PMID:Knock-down of methylenetetrahydrofolate reductase reduces gastric cancer cell survival: an in vitro study. 1848 1


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