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)

As high levels of Prostaglandins E2 were observed in several gastric diseases, the Authors determined the PGE2 levels in gastric cancer patients without recurrences, in pre and post-operative period. PGE levels were correlated with cancer progression and their significance as tumoral markers was also assessed.
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PMID:[Prostaglandins and gastric cancer: a preliminary study]. 251 47

Since 1984, an experimental and clinical study on the relation between PGE and gastric carcinoma has been performed by determining PGE content in the bioptic gastric mucosa and plasma. It is found the PGE content in the gastric mucosa and plasma is increased in all patients with gastric cancer, especially with signet ring cell carcinoma. It is higher in the regional lymph node metastasis than in the early cancer, extensive metastases and normal subjects. The PGE content in the plasma is reduced obviously 7-10 days after operation but is increased markedly in recurrent patients. There is no significant difference in extensive metastases, relapse free and normal subjects. The PGE content in the plasma is significantly higher in gastric carcinoma than in chronic atrophic gastritis, but no difference is present between chronic atrophic gastritis and normal subjects.
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PMID:[Prostaglandin E (PGE) and gastric carcinoma]. 303 44

Plasma prostaglandins (PGs) of normal individuals and cancer patients have been examined. With the exception of a breast carcinoma patient, all patients demonstrated significant elevations in PGE levels. Lung cancer patients showed a significant decrease in PGF, while stomach cancer patients showed a marked decrease in PGB. It is suggested that the changes in PGs may play a significant role in host-tumor metabolism.
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PMID:Distribution of prostaglandins B, E and F series in plasma of cancer patients. 694 71

Surgical treatment of gastric cancer patients is dismal because advanced tumor is often noted at diagnosis. In order to obtain better adjuvant therapy for gastric cancer patients after operation, it is important to understand the mechanism of invasion and metastasis. It is well known that binding of hepatocyte growth factor (HGF) to its receptor (c-Met) regulates gastric cancer progression and metastasis. Recently, HGF was found to up-regulate the expression of cyclooxygenase-2 (COX-2) gene and increase prostaglandin (PG)synthesis in gastric mucosa cells. Over-expression of COX-2 and increased PG secretion have also been found to be involved in the growth and metastasis of gastric cancer. These results together suggest that the signaling pathway of HGF and c-Met may be mediated through ERK2 activation, up-regulation of COX-2 and increased production of PGE(2)in gastric cancer cells. In view of the fact that c-Met is over-expressed in the majority of gastric cancer patients with poor prognosis, COX-2 specific inhibitors may provide beneficial effects in these patients.
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PMID:Nonsteroidal anti-inflammatory drugs for treatment of advanced gastric cancer: cyclooxygenase-2 is involved in hepatocyte growth factor mediated tumor development and progression. 1160 79

Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of gastrointestinal cancers. Recently, a similar protective effect has been demonstrated by the specific cyclo-oxygenase-2 (COX-2) inhibitors. However, the exact mechanism that accounts for the anti-proliferative effect of specific COX-2 inhibitors is still not fully understood, and it is still controversial whether these protective effects are predominantly mediated through the inhibition of COX-2 activity and prostaglandin synthesis. Identification of molecular targets regulated by COX-2 inhibitors could lead to a better understanding of their pro-apoptotic and anti-neoplastic activities. In the present study, we investigated the effect and the possible molecular target of a COX-2-specific inhibitor SC-236 on gastric cancer. We showed that SC-236 induced apoptosis in gastric cancer cells. However, this effect was not dependent on COX-2 inhibition. SC-236 down-regulated the protein expression and kinase activity of PKC-beta(1), increased the expression of PKCdelta and PKCeta, but did not alter the expression of other PKC isoforms in AGS cells. Moreover, exogenous prostaglandins or PGE(2) receptor antagonists could not reverse the inhibition effect on PKCbeta(1) by SC-236, which suggested that this effect occurred through a mechanism independent of cyclo-oxygenase activity and prostaglandin synthesis. Overexpression of PKCbeta(1) attenuated the apoptotic response of AGS cells to SC-236 and was associated with overexpression of p21(waf1/cip1). Inhibition of PKCbeta(1)-mediated overexpression of p21(waf1/cip1) partially reduced the anti-apoptotic effect of PKCbeta(1). The down-regulation of PKCbeta(1) provides an explanation for COX-independent apoptotic effects of specific COX-2 inhibitor in cultured gastric cancer cells. We also suggest that PKCbeta(1) act as survival mediator in gastric cancer, and its down-regulation by COX-2 inhibitor SC-236 may provide new target for future treatment of gastric cancer.
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PMID:Novel target for induction of apoptosis by cyclo-oxygenase-2 inhibitor SC-236 through a protein kinase C-beta(1)-dependent pathway. 1220 23

Gastrointestinal carcinomas synthesize elevated levels of prostaglandin E(2) (PGE(2)), which has been mechanistically linked to carcinogenesis. Recently, microsomal prostaglandin E synthase-1 (mPGES-1) was cloned, which seems to be inducible and linked to cyclooxygenase-2 (Cox-2) in the biosynthesis of PGE(2). We examined expression of mPGES-1 in intestinal type gastric adenocarcinomas and in gastric cancer cell lines. The transcript for mPGES-1 was elevated in 57% (4/7) of gastric carcinomas as detected by Northern blot analysis. Moderate to strong mPGES-1 immunoreactivity was observed in 56% (5/9) of the carcinomas as detected by immunohistochemistry. Furthermore, mPGES-1 mRNA, protein and microsomal PGES activity were detected in gastric adenocarcinoma cell lines that originated from intestinal type tumors (MKN-7 and MKN-28). In contrast to Cox-2, however, expression of mPGES-1 mRNA or protein were not induced by phorbol 12-myristate 13-acetate (PMA) or interleukin-1beta (IL-1beta) in any of the gastric cancer cell lines tested (MKN-1, -7, -28, -45 and -74). Two gastric cancer cell lines (MKN-45 and MKN-74) did not express mPGES-1 and lacked microsomal PGES activity, but were still able to synthesize PGE(2). Because all gastric cell lines expressed cPGES as detected by immunoblotting, it is possible that Cox-2 can interact with cPGES or with some other yet unidentified PGES in gastric cancer cells. Furthermore, our data show that regulatory mechanisms that drive expression of mPGES-1 and Cox-2 dissociate in gastric cancer cell lines.
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PMID:Expression of microsomal prostaglandin E synthase-1 in intestinal type gastric adenocarcinoma and in gastric cancer cell lines. 1452 Jun 91

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

Helicobacter pylori up-regulates cyclo-oxygenase-2 (COX-2) expression, which in turn is involved in tumourigenesis. Recently, a causal link between COX-2 and multidrug resistance 1 (MDR-1) gene expression, implicated in cancer chemoresistance, has been demonstrated. Thus, the expression of COX-2 and the downstream enzyme involved in PGE2 biosynthesis, microsomal PGE-synthase1 (mPGES1), was correlated with P-gp, the product of MDR-1, and the anti-apoptotic protein, Bcl-xL, in gastric biopsies from patients with H pylori infection and in patients with gastric cancer. In a retrospective analysis of endoscopic and pathology files, 40 H pylori-negative patients (Hp-), 50 H pylori-positive patients who responded to eradication therapy (Hp+R), 84 H pylori-positive patients who did not respond to eradication therapy (Hp+NR), and 30 patients with gastric cancer (18 intestinal and 12 diffuse types) were selected. COX-2, mPGES1, P-gp, and Bcl-xL were detected by immunohistochemistry. COX-2, mPGES1, P-gp, and Bcl-xL expression was undetectable in gastric mucosa from Hp- patients. By contrast, COX-2 and mPGES1 expression was detected in 42% and 44% of Hp+R patients, respectively, and in up to 66% (range 63-66%) of Hp+NR patients (p < 0.05). The expression of COX-2 and mPGES1 correlated significantly (p < 0.0001) with that of P-gp and Bcl-xL. High levels of COX-2, mPGES1, P-gp, and Bcl-xL expression were found in intestinal-type gastric cancer samples. In conclusion, H pylori-dependent induction of COX-2 and mPGES1 is associated with enhanced production of P-gp and Bcl-xL that may contribute to gastric tumourigenesis and resistance to therapy.
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PMID:Expression of COX-2, mPGE-synthase1, MDR-1 (P-gp), and Bcl-xL: a molecular pathway of H pylori-related gastric carcinogenesis. 1499 95

Early studies revealed that cigarette smoke promotes gastric cancer growth through the induction of cyclooxygenase-2 (COX-2). Nicotine, one of the active ingredients in cigarette smoke, has detrimental effects in the stomach. To date, there is no direct evidence to validate the effect of nicotine on gastric tumor growth and its carcinogenic mechanism(s). We therefore investigated whether nicotine could promote tumor growth and neovascularization in vivo, and the biological mechanism(s) in connection with the signaling cascade involving COX-2 and extracellular signal-regulated protein kinase (ERK). Athymic nude mice, with gastric cancer cells (AGS) orthotopically implanted into the gastric wall, treated with nicotine (50 or 200 microg/ml) in their drinking water for 3 months developed larger tumor areas than mice in the control group. Nicotine further increased proliferating cellular nuclear antigen (PCNA) staining and microvessel density by 70 and 30%, respectively, with concomitant activation of ERK phosphorylation, COX-2 and vascular endothelial growth factor (VEGF) expression in the tumors. Intraperitoneal administration of a selective COX-2 inhibitor (SC-236, 2 mg/kg) prevented the nicotine-induced tumor growth and neovascularization dose-dependently. Consistent with our animal model, an in vitro study also demonstrated that incubation with nicotine (50-200 microg/ml) for 5 h stimulated cell proliferation dose-dependently and increased COX-2 expression, prostaglandin E(2) (PGE(2)) and VEGF release, as well as activation of ERK phosphorylation. Pre-treatment with specific mitogen-activated protein kinase kinase (MEK) inhibitors (U0126 or PD98059) attenuated COX-2 expression and subsequent PGE(2) release by nicotine. Furthermore, the stimulatory action of nicotine on cancer cell growth and angiogenic factor VEGF production was suppressed by inhibitors of MEK (U0126) and COX-2 (SC-236). These findings reveal a direct promoting action of nicotine on the growth of gastric tumor and neovascularization through sequential activation of the ERK/COX-2/VEGF signaling pathway, which can be targeted for chemoprevention of gastric cancer, particularly in cigarette smokers.
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PMID:Nicotine promotes gastric tumor growth and neovascularization by activating extracellular signal-regulated kinase and cyclooxygenase-2. 1531 99

Prostaglandin E(2) (PGE(2)) plays an important role in protection of the gastric mucosa against various damaging agents and growth-inhibitory activity on tumor cells. However, the precise regulation mechanism of PGE(2) in gastric cancer cells is still unclear. In this study, we isolated a gene, which is regulated by PGE(2) in SNU-1, human gastric adenocarcinoma cells, using differential display RT-PCR (DD RT-PCR) and characterized the function of the gene induced by PGE(2). The full-length cDNA of the gene was cloned by the rapid amplification of cDNA ends method. The 1659 base pair cDNA consists of a 30-nt 5'-noncoding region, an 891-nt open reading frame and a 738-nt 3'noncoding region that includes a poly (A) signal. As a result of protein motif search, we found that it has a conserved thioredoxin-active site, Cys-Gly-Pro-Cys and a Myb-DNA binding domain repeat signature. Thus, we designated this gene product as thioredoxin-related protein-1, TRP-1. TRP-1 was expressed in a lower extent in renal, gastric and colon cancer tissues and is translated into 33 kDa protein in nuclear and cytoplasmic fractions. TRP-1 has a thioredoxin activity, which was detected using the insulin disulfide reduction assay. Another potential role of TRP-1 is repression of B-Myb activity through direct binding to B-Myb, a transcriptional factor induced at G1-S transition. Finally, TRP-1 overexpression inhibits mammalian cell proliferation and specifically predispose to G0/G1 phase arrest. In conclusion, these results imply that TRP-1 is a mammalian thioredoxin and plays as a transcriptional repressor through direct binding to the transcription factor B-Myb.
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PMID:Expression of a thioredoxin-related protein-1 is induced by prostaglandin E(2). 1692 93


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