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

Chemoprevention of cancer is reviewed from the viewpoints of action mechanisms and methodology of clinical trials in order to introduce promising agents discovered by in vitro and/or in vivo studies to applications in humans. The clinical trial procedure essentially follows the phase study which has been employed for chemotherapeutic drugs. Chemoprevention of bladder cancer, prostate cancer, gastric cancer, hepatocellular carcinoma, breast cancer, head and neck cancer, colorectal cancer and lung cancer is reviewed, mainly focusing on clinical trials. Previous clinical trials have shown the effectiveness of the following: polyprenoic acid (acyclic retinoid) for hepatocellular carcinoma; tamoxifen for breast cancer; retinoic acids for head and neck tumor; and aspirin, a COX-2 inhibitor, for colorectal cancer. Despite the advantageous effects of some of these agents, their toxic effects must also be of concern at the same time. For example, in a chemoprevention trial of lung cancer, beta-carotene was unexpectedly found to increase the risk of lung cancer among high-risk groups. It is also noted that large-scale clinical trials demand large research grants, which may not be affordable in Japan. Chemoprevention is still an emerging field of oncology where researchers in both basic and clinical sciences face great challenges.
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PMID:Chemoprevention of cancer--focusing on clinical trials. 1459 36

The relationships of gastric cancer with serum trace elements, helicobacter pylori (HP) and COX-2 in gastric tissue were investigated. We took 50 blood samples from the gastric cancer patients in Hexi region (the gastric cancer group), and 50 blood samples from healthy volunteers (control group) and detected the level of trace elements, the rate of HP infection, and the expression of COX-2 in gastric tissue. The results showed the levels of Cu/Zn, Fe in the serum of the gastric cancer group were higher than those of the control group respectively(P < 0.05, 0.01), and the levels of Zn, Mn were lower than those of the control group respectively (P < 0.05, 0.01). The data on Zn were submitted to multi-variate non-conditional logistic analysis. The rate of HP infection and the positive expression of COX-2 were 88% and 78% respectively in the gastric cancer group, 42.0% and 0 in the control group (P < 0.01). These findings suggest that the decrease of Zn in serum may be a precancerous factor of gastric cancer development which induces HP infection and the higher expression of COX-2 and hence may lead to the development of gastric cancer. Detecting the trace elements could conduce to the diagnosis of gastric cancer. Regulating the level of trace element in the patient can be an effective chemoprophylaxis for gastric cancer.
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PMID:[Research on relationships of gastric cancer with serum trace elements, Helicobacter pylori and COX-2 in gastric tissue]. 1502 77

Non-steroidal anti-inflammatory drugs (NSAIDs) are powerful chemopreventive agents in various cancers. They act by inhibiting cyclooxygenase (COX) activity, or through other mechanisms. NSAID-activated gene (NAG-1) has antitumorigenic and pro-apoptotic activities, but the mechanisms of NAG-1-induced apoptosis are poorly understood. Here we examined whether NAG-1 expression is induced in gastric cancer cells treated with NSAIDs, and the effect of NAG-1 expression on cell death. NAG-1 cDNA was transfected into SNU601 cells, and the relation between the ectopic expression of NAG-1 and death receptor-4 (DR-4) and DR-5 levels was studied. We found that NAG-1 expression was strongly induced in SNU601 cells, which lack endogenous COX-2, by sulindac sulfide, and that this was closely related with increased apoptosis and decreased cell viability. Moreover, temporal expressions of DR-4 and DR-5 induced by sulindac sulfide were similar to that of NAG-1. Most SNU601 cells transfected with NAG-1 cDNA did not survive during expansion. Forced NAG-1 expression significantly induced apoptosis and DR-4 and DR-5 expression. We conclude that NAG-1 expression is closely related to DR-4 and DR-5 induction, which could provide a mechanistic basis for the apoptotic effect of COX inhibitors in gastric cancer cells.
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PMID:Non-steroidal anti-inflammatory drug activated gene (NAG-1) expression is closely related to death receptor-4 and -5 induction, which may explain sulindac sulfide induced gastric cancer cell apoptosis. 1518 Sep 42

Both the availability of multiple treatment modalities and novel therapeutic targets make the correct prognostic stratification and the identification of truly predictive factors an issue of major debate in gastric cancer. Along with "classic" prognostic factors such as those related to the diffusion of the tumour at diagnosis (i.e., depth of gastric wall infiltration, locoregional lymph nodes or distant metastases) or those concerning the pathologic characteristics of the tumour, other, innovative, factors should be considered if a better definition of the characteristics of the tumour is to be given. These biological factors are often derived from the genetic process, which is thought to represent a crucial step to gastric cancer (DNA copy number changes, microsatellite instability, thymidilate synthase, E-cadherin, beta-catenin, mucin antigen, p53, c-erb B-2, COX-2, matrix metalloproteinases, VEGFR and EGFR). Some of those putative prognostic indicators can also be considered predictive of response to therapy as they are a molecular target either to chemotherapeutics (i.e., thymidilate synthase that is targeted by 5FU) or to a new class of antineoplastic molecules (i.e., c-erb B-2 targeted by trastuzumab, COX-2 by NSAIDs, matrix metalloproteinases, EGFR and VEGFR by specific inhibitors).
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PMID:Molecular biology of sporadic gastric cancer: prognostic indicators and novel therapeutic approaches. 1524 77

Nonsteroidal antiinflammatory drugs (NSAIDs) have been reported to have antiproliferative effects in neoplastic cells of different origin during the past few decades. We aimed to study the effects of the selective COX-2 inhibitor, nimesulide, on cell viability and telomerase and Akt/PKB activity in the human gastric cancer cell line MKN-45 and to explore the molecular mechanism for the antitumor activity of the selective COX-2 inhibitor. We tested the influence of nimesulide on the gastric cancer cell line MKN-45 in vitro. Trypan blue exclusion was used to determine the cell viability after incubation for 0, 12, 24, and 48 hr in different concentrations of nimesulide 0, 25, 50, 100, 200 microM). After treatment or no treatment with 100 microM nimesulide for 0, 12, 24, or 48 hr in the presence or absence of 300 nM okadaic acid for 2 hr, telomerase and Akt/PKB activity was measured using TRAP PCR-ELISA and nonradioactive IP kinase assays, respectively. In the gastric cancer cell line MKN-45 nimesulide caused a time- and dose-dependent reduction in cell numbers and significantly inhibited telomerase and Akt/PKB activity; the inhibition of telomerase activity was partly associated with the attenuation of Akt/PKB activity. These results demonstrate that the selective COX-2 inhibitor suppresses the telomerase activity of gastric cancer cells, in part by blocking the activation of protein kinase B, which provides a new signaling mechanism responsible for the anticancer effects of the selective COX-2 inhibitor.
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PMID:Cyclooxygenase-2 inhibitor nimesulide suppresses telomerase activity by blocking Akt/PKB activation in gastric cancer cell line. 1530 82

The increased expression of COX-2 in carcinoma tissue is found in gastric cancer, lung cancer and breast cancer as well as colon cancer. It was shown that COX-2 played an important role in carcinogenesis by an experiment using a cultured cell and an animal experiment using a knockout mouse. The inhibitory effect of COX-2 inhibitor on polyps in familial adenomatous polyposis (FAP) patients was reported from the clinical aspect, and the U. S. Food and Drug Administration (FDA) approved administration of a COX-2 inhibitor to FAP patients. COX-2 plays an important role in proliferation, invasion and metastasis of cancer. COX-2 expression was reportedly enhanced in lung cancer by an anticancer agent and radiotherapy, and clinical application of a COX-2 inhibitor is attempted. In addition, the experimental examination showed the inhibitory effect of a COX-2 inhibitor on hematogenous metastasis of colon cancer. The mechanism of the COX-2 inhibitor remains unclear. Clinical application of the COX-2 inhibitor to an effective anti-tumor agent is expected after more studies have been conducted on its molecular biologic function.
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PMID:[COX and study of cancer therapy]. 1533 34

Prostaglandin E2 (PGE2) is related to carcinogenesis. Cyclooxygenase (COX) and prostaglandin E synthase (PGES) are involved in PGE2 synthesis. However, overall situation of COX and microsomal PGES (mPGES) expression in gastric cancer has not been studied in detail. The expression of COX and mPGES was evaluated in 45 cases of gastric cancer (22 intestinal type and 23 diffuse type), 13 gastric dysplasia, 15 intestinal metaplasia, 18 Helicobacter pylori associated gastritis, and 10 normal gastric tissues by performing immunohistochemistry and Western blot analysis. COX-1 expression was higher in intestinal type cancers than diffuse ones. COX-2 and mPGES-1 were expressed more in cancers than in paired nonneoplastic adjacent tissues, and intestinal type cancers showed higher expression of COX-2 than diffuse ones. The expression of COX and mPGES was gradually increased with progression of gastric lesions and the highest in dysplasia. mPGES-1 was expressed not only in epithelial cells but also in stromal cells, whose phenotype was myofibroblast, endothelial cells and others. In conclusion, proteins related to PGE2 biosynthesis affect both histogenesis and the carcinogenesis of human gastric cancer.
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PMID:Expression of proteins related to prostaglandin E2 biosynthesis is increased in human gastric cancer and during gastric carcinogenesis. 1537 35

Most gastric adenocarcinomas arise as a longterm complication of Helicobacter pylori infection of the stomach, but the high prevalence of this infection limits the cost-effectiveness of antibiotic eradication as a cancer prevention strategy. Here we have used phosphorylation-specific antibodies against the Akt kinase consensus sequence to detect downstream substrates of this oncogenic signaling pathway in normal and malignant gastric tissues. In vitro studies confirm that phosphorylation of Akt and its substrates is inducible by epithelial mitogens such as epidermal growth factor (EGF), which is implicated in the pathogenesis of H. pylori gastritis. Control clinical studies confirm far stronger Akt substrate phosphorylation in primary human breast cancers than in matched adjacent normal breast tissues; unexpectedly, however, increased Akt signaling is apparent in both primary stomach cancers and adjacent normal gastric tissues. These findings raise the possibility of a preneoplastic field defect induced in morphologically normal tissues, and suggest that immunoassays of mucosal Akt activity could guide preventive surveillance and/or intervention in patients at risk of gastric cancer. Moreover, since recent reports confirm Akt inhibition by COX-2 inhibitors, these data support the chemopreventive efficacy of such drugs for at-risk individuals.
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PMID:Upregulated Akt signaling adjacent to gastric cancers: implications for screening and chemoprevention. 1592 57

The effect of the selective COX-2 inhibitor, etodolac, on Helicobacter pylori (Hp)-associated stomach carcinogenesis was investigated in Mongolian gerbils (MGs). Hp-infected MGs were fed for 23 weeks with drinking water containing 10 ppm N-methyl-N-nitrosourea. They were then switched to distilled water and placed on a diet containing 5-30 mg/kg/day etodolac for 30 weeks. We found that etodolac dose-dependently inhibited the development of gastric cancer, and no cancer was detected at a dose of 30 mg/kg/day. Etodolac did not affect the extent of inflammatory cell infiltration or oxidative DNA damage, but it significantly inhibited mucosal cell proliferation and dose-dependently repressed the development of intestinal metaplasia in the stomachs of Hp-infected MGs. These results suggest that COX-2 is a key molecule in inflammation-mediated stomach carcinogenesis and that chemoprevention of stomach cancer should be possible by controlling COX-2 expression or activity.
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PMID:Inhibitory effect of etodolac, a selective cyclooxygenase-2 inhibitor, on stomach carcinogenesis in Helicobacter pylori-infected Mongolian gerbils. 1600 42

The cyclooxygenase (COX)-2 inhibitor has been reported to impede the progression of gastric cancer, but underlying mechanisms remain unclear. We therefore investigated the effect of a COX-2 inhibitor, JTE-522, on the ability of orthotopic fibroblasts to stimulate invasion of scirrhous gastric carcinoma cells. The human scirrhous gastric cancer cell lines OCUM-2D or OCUM-2M, and human gastric fibroblasts (NF-21) were cultured in the absence or presence of JTE-522 at various concentrations. Cancer cells were then assayed for invasiveness in vitro by invasion assay. The effect of prostaglandins (PG) on growth factor production in NF-21 cells was examined by ELISA. Finally, the effects of orally administrated JTE-522 on orthotopically transplanted tumors were examined in nude mice. NF-21 cells stimulated invasion by OCUM-2D cells, an effect suppressed by JTE-522 at 5 x 10(-6) M. Hepatocyte growth factor (HGF) and PGE2 production by NF-21 cells were suppressed by JTE-522 (P < 0.01). PGE2 stimulated HGF production by NF-21 cells in a dose-dependent manner. JTE-522 significantly suppressed orthotopic tumor growth and lymph node metastasis, and also decreased HGF expression by fibroblasts within the gastric tumor. In conclusion, we found that gastric fibroblasts stimulated invasiveness in scirrhous gastric cancer cells, whereas a selective COX-2 inhibitor inhibited this paracrine effect by decreasing fibroblast PGE2 production, resulting in downregulation of HGF production.
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PMID:Inhibitory effect of a selective cyclooxygenase inhibitor on the invasion-stimulating activity of orthotopic fibroblasts for scirrhous gastric cancer cells. 1605 17


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