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)

We established a peritoneal-metastatic model for scirrhous gastric carcinoma. Peritoneal metastasis had developed after intraperitoneal inoculation of OCUM-2MD3 cells in nude mice. This cell line was derived from a peritoneal-metastatic nodule at the mesenterium after orthotopic implantation of OCUM-2M cells which developed no peritoneal metastasis after intraperitoneal inoculation. The histologic findings of orthotopic-implanted tumor in the stomach show scirrhous type while those of subcutaneous-implanted tumor show medullary type. There might be factors, in OCUM-2MD3 cells, which are responsible for peritoneal metastasis. We next investigated the differences in the biological behavior of the original OCUM-2M and the derived variant OCUM-2MD3. Morphology and growth activity of the two cell lines were similar to each other. The specific chromosomes, add(6)(q13), del(7)(q21.2) and inv(11)(p13q21), were found in OCUM-2MD3 cells but not in OCUM-2M cells. While the oncogenes amplification by OCUM-2M cells was found in K-sam and c-myc, that by OCUM-2MD3 cells was found only in c-myc. The expression of E-cadherin by OCUM-2MD3 cells was decreased compared with that of OCUM-2M cells. Expression level of beta 1-integrin of OCUM-2MD3 cells were higher than that of OCUM-2M cells. The binding and invasion activity of OCUM-2MD3 cells were higher than those of OCUM-2M cells, and were decreased by anti-beta 1-integrin antibody. The invasion activity of OCUM-2MD3 cells was increased in the presence of peritoneal fibroblast. In this study, it was suggested that orthotopic implantation of cancer cells might have an effect on the acquisition of metastatic ability. beta 1-integrin and peritoneal fibroblasts might be correlated with peritoneal metastasis. This peritoneal-metastatic model should be useful for analysing the mechanism of peritoneal metastasis of human scirrhous gastric cancer.
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PMID:Peritoneal metastatic model for human scirrhous gastric carcinoma in nude mice. 852 16

To evaluate the anti-cancer effects of folic acid at the molecular level, we determined plasma folic acid concentration by radioimmuno-assay and the degree of total genomic DNA methylation by incubating DNA with 3H-S-adenosylmethionine (3H-SAM) in the presence of a methylase, and analyzed the methylation status of the c-myc and c-Ha-ras oncogenes by Southern blotting in 21 patients with advanced gastric cancer. The degree of total genomic DNA methylation of cancerous tissues was significantly lower than that of paracancerous and non-cancerous tissues; c-myc and c-Ha-ras oncogenes from cancerous (10/21, 5/10) and paracancerous (13/21, 4/10) tissues were hypomethylated. The plasma folic acid concentration in patients who showed hypomethylation was lower than that patients showing normal methylation. These findings suggest that a decrease in folic acid, and the subsequent DNA hypomethylation, may be involved in human gastric carcinogenesis.
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PMID:Relationship of plasma folic acid and status of DNA methylation in human gastric cancer. 908 63

The effects of the macromolecular synthesis inhibitors 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB), actinomycin D, and cycloheximide on the human gastric cancer TMK-1 cell line were studied. These agents inhibited DNA, RNA, or protein synthesis efficiently and induced cell death rapidly in a wide range of concentrations. After 8 hr of exposure to these agents, the cells exhibited morphological features of apoptosis, including cell shrinkage, nuclear condensation, DNA fragmentation, and formation of apoptotic bodies. Western blot analysis revealed that these inhibitors altered the protein levels of apoptosis-related gene products such as c-Myc, Bcl-X(S), and the mutant p53 (mp53) in TMK-1 cells markedly. The c-myc mRNA and protein levels were decreased initially and were then induced markedly to a new level after 4 hr of exposure to DRB, a RNA polymerase II inhibitor. The Bcl-X(S) levels were increased rapidly after treatment with all of these agents, whereas the levels of Bcl-X(L) and Bax remained largely unchanged. Northern blot analysis indicated that the c-myc overexpression is concomitant to DRB-induced DNA fragmentation and that the increased mp53 protein level was mainly a posttranscriptional event. Our observations suggest that the up-regulation of Bcl-X(S) may serve as an important mechanism for the apoptosis triggered by these inhibitors. This study also provides evidence for the notion that interference with the cellular survival pathway may lead to apoptosis.
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PMID:Effects of transcription and translation inhibitors on a human gastric carcinoma cell line. Potential role of Bcl-X(S) in apoptosis triggered by these inhibitors. 917 10

The expression of the c-myc oncogenes has already been reported in human gastric carcinoma. Overexpression can be the consequence of oncogene amplification and often correlates with different prognostic factors. Authors investigated the value of c-myc oncogene amplification in 23 patients (9 male, 14 female, aged 28-85 yrs) with gastric cancer and its correlation to the following clinical and histopathological parameters: grade, TNM stage, Lauren's type, localisation and severity of disease. DNA was isolated from formalin-fixed, paraffin embedded tissue for quantitative dot-blot hybridisation. Amplified c-myc was found in 6 out of 23 cases. Its values ranged from 2.12 up to 18.2 (average 9.1). Significant association was found between the presence of c-myc amplification and distant metastasis (corr. coeff.: 0.5623, p < 0.01). High scores of the other parameters also correlated with c-myc, albeit not significantly. The result of cluster analysis, based on the similarity of the parameter values for the individual patients proved that the age was the decisive factor in creating two groups. The distribution of patients into these groups did not seem to coincide with the presence of c-myc amplification or distant metastasis, inspite of the proved correlation between them.
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PMID:Is the presence of distant metastasis associated with c-myc amplification in gastric cancer? 940 11

Capsaicin (CAP) has been known to inhibit some tumor development in vivo (J.J. Jang, S.H. Kim, T.K. Yun, Inhibitory effect of capsaicin on mouse lung tumor development, in vivo, J. Korean Med. Sci. 3 (1989) 49-53; J.J. Jang, K.J. Cho, Y.S. Lee, J.H. Bae, Different modifying responses of capsaicin in a wide-spectrum initiation model of F344 rat, J. Korean Med. 6 (1991) 31-36) [1,2] even though its mechanism of action is not well understood. The objectives of this study were to examine the effect of CAP on expression of tumor forming-related genes in a Korean stomach tumor cell, SNU-1. We used slot blot hybridization to investigate its effect on a wide spectrum of proto-oncogenes. It was found that CAP enhanced the transcripts of two proto-oncogenes (c-myc and c-Ha-ras) and tumor suppressor gene p53. While a low concentration of CAP (0.01 microM) did not significantly increase the level of p53 transcript in SNU-1, it did increase it by a factor of 3.5 at a 10 microM dose of CAP. Consequently, SNU-1 cells are sensitive to CAP in the overexpression of tumor suppressor gene, p53 and proto-oncogenes, c-myc and c-Ha-ras, but not those of c-erbB-2, c-jun and bcl-2 genes. Both cell death and DNA fragmentation were shown in SNU-1 cells with treatment of CAP. Our results suggest that CAP induces apoptotic cell death in human gastric cancer cells (SNU-1) in vitro which may be possibly mediated by the overexpression of p53 and/or c-myc genes. Because cell suicide is arguably the most potent natural defense against cancer, the correlation between the induction of apoptosis and the change of tumor forming-related gene expression after CAP treatment should be further studied in detail.
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PMID:Capsaicin can alter the expression of tumor forming-related genes which might be followed by induction of apoptosis of a Korean stomach cancer cell line, SNU-1. 946 Oct 43

Tumor necrosis factor-alpha (TNF-alpha) is a macrophage-derived multifunctional cytokine that acts as a cytostatic or cytotoxic agent in many tumor cells. However, the molecular mechanisms by which tumor cells become sensitive to the cytotoxic action of TNF-alpha are not clear. In this study we demonstrated that the cytotoxicity of TNF-alpha markedly increased in c-Myc overexpressing tumor cells. The stomach cancer cell line, SNU-16, in which c-Myc expression is high due to gene amplification, showed programmed cell death detected by DNA fragmentation and morphological changes. An antisense c-myc S-oligonucleotide specifically inhibited the TNF-alpha-induced apoptosis of SNU-16 cells, provided that the oligonucleotide was added 4 h prior to TNF-alpha treatment. Western immunoblot analysis of p53 and Bax showed that in this cell line, TNF-alpha increased the level of these proteins in a time-dependent manner and that this effect lasted for 12 h. Taken together these data indicate that the deregulation of c-Myc plays an important role in sensitizing tumor cells to TNF-alpha. Furthermore, TNF-alpha-induced apoptosis in the SNU-16 cell line showed increased expression of p53 and Bax protein levels following TNF-alpha treatment. Therefore, we suggest that TNF-alpha-induced apoptosis, which is cytotoxic to tumor cells, is coupled with a p53 and Bax apoptotic pathway.
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PMID:Increased susceptibility of the c-Myc overexpressing cell line, SNU-16, to TNF-alpha. 956 90

Gastric cancer is a rather common disease worldwide. In Italy it still accounts for 15,000 deaths annually. A sharp drop in the incidence rate of Lauren's intestinal histotype has been reported, whereas the frequency of the diffuse histotype is relatively steady. If the histogenesis of the latter is still somewhat obscure, the intestinal type confirms the sequence: atrophic gastritis--intestinal metaplasia--dysplasia--neoplasia. These different stages of development can nowadays be singled out through a series of indicators, the most reliable of which are the pepsinogen I/pepsinogen II ratio, the presence of sulphomucins and Lewis antigens in the gastric juices and NOR (Nucleolar Organizer Regions), cell ploidy and oncogenes determination. The genes involved in the neoplastic transformation are mostly oncosuppressors, the most frequent alterations being those relative to the APC gene, p53 and c-myc. In addition to the by now indispensable pathological staging of the disease, the modern prognostic factors are arising great interest: the most significant are the immunohistochemical examination of the peritoneal washing, and cell ploidy. Surgery is still the only potentially curative treatment: the earlier surgery is performed in the course of disease, the greatest the curative potential. The Authors' experience, which includes 400 operated cases with complete follow-up records, is here reported. The resectability rate turned out to be 84%, overall operative mortality was 6.5% with that due to surgical causes along being 3.7%. Overall survival at 5 years was 36%, while that of the curative operations 47%. Good results were obtained with the association surgery + intraoperative radiotherapy which resulted in a significant decrease in local recurrences of the disease.
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PMID:Gastric cancer. Clinico-biological updating and analysis of 400 operated cases. 970 May 78

Although temporal trends and regional-racial variations in gastric cancer incidence have led to the formulation of different hypotheses, no definite association has been seen between this disease and any behavioural or genetic determinant. In fact, several aetiological factors have been associated with risk of gastric cancer, but not without controversy. Various studies have suggested that genetic factors might be of importance in the pathogenesis of gastric tumours. In fact, stomach carcinoma occurs more frequently among close relatives of affected individuals than in the general population and some of the most common pre-cancerous lesions seem to be genetically determined. In the light of this circumstantial evidence, we decided to investigate the role of various genetic alterations in gastric cancer in order to study their relationship with aetiopathogenesis and disease progression and their value as indicators of risk and prognosis. Our main areas of interest were: i. c-Ha-ras locus polymorphism; ii, truncated c-myc gene variant; iii. loss of heterozygosity, iv. p53 gene mutations; v. oncogene amplification; vi. oncogene amplification proliferative activity and their relation to prognosis in gastric cancer.
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PMID:Gastric cancer: epidemiologic and biological aspects. 992 23

Apoptosis plays a major role in gastrointestinal epithelial cell turnover, ulcerogenesis and tumorigenesis. We have examined apoptosis induction by non-steroidal anti-inflammatory drugs (NSAIDs) in human gastric (AGS) cancer cells and the role of protein kinase C (PKC) and apoptosis-related oncogenes. After treatment with aspirin or indomethacin, cell growth was quantified by MTT assay, and apoptosis was determined by acridine orange staining, DNA fragmentation and flow cytometry. The mRNA and protein of p53, p21waf1/cip1 and c-myc was detected by Northern and Western blotting respectively. The influence of PKC on indomethacin-induced apoptosis was determined by co-incubation of 12-O-tetradecanoylphorbol 13-acetate (TPA). The role of c-myc was determined using its antisense oligonucleotides. The results showed that both aspirin and indomethacin inhibited cell growth and induced apoptosis of AGS cells in a dose- and time-dependent manner, without altering the cell cycle. Indomethacin increased c-myc mRNA and protein, whereas p53 and p21wafl/cip1 were unchanged. Down-regulation of c-myc by its antisense oligonucleotides reduced apoptosis induction by indomethacin. TPA could inhibit indomethacin-induced apoptosis and accumulate cells in G2/M. Overexpression of c-myc was inhibited by TPA and p21waf1/cip1 mRNA increased. In conclusion, NSAIDs induce apoptosis in gastric cancer cells which may be mediated by up-regulation of c-myc proto-oncogene. PKC activation can abrogate the effects of NSAIDs by decreasing c-myc expression.
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PMID:Non-steroidal anti-inflammatory drug-induced apoptosis in gastric cancer cells is blocked by protein kinase C activation through inhibition of c-myc. 1002 4

Nonsteroidal anti-inflammatory drug (NSAID)-induced apoptosis is considered to be an important mechanism in the antineoplastic effects and damage produced by the drugs in the gastrointestinal tract. In this study, two different gastric cancer cell lines, MKN28 (mutant-type p53) and AGS (wild-type p53), were compared as to growth inhibition, apoptosis, and cell cycle and apoptosis-related gene expression in response to indomethacin treatment. Cell growth was measured by MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Apoptosis was characterized by acridine orange staining and DNA fragmentation, and cell cycle kinetics by flow cytometry. The mRNA and protein levels of p53, p21waf1/cip1, and c-myc were determined by Northern and Western blotting. The results showed that indomethacin initiated growth inhibition and apoptosis in both cell lines without cell cycle shifting. AGS cells were more sensitive to growth inhibitory activity and apoptosis of indomethacin than MKN28 cells. In MKN28 cells, the levels of p53, p21waf1/cip1, and c-myc mRNA remained unchanged over the 24-hr treatment with indomethacin, but the p53 protein level was elevated after 4 hr. There was no change in the p21waf1/cip1 and c-myc protein levels in the MKN28 cells. In AGS cells, a progressive increase in c-myc mRNA and protein levels was noted, while p53 and p21waf1/cip1 remained unchanged. It can be concluded that wild-type p53 and/or up-regulation of c-myc is associated with indomethacin-mediated differential apoptosis in gastric epithelial cells.
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PMID:Differential apoptosis by indomethacin in gastric epithelial cells through the constitutive expression of wild-type p53 and/or up-regulation of c-myc. 1040 34


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