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)

Whereas nitrosation of secondary amines produces nitrosamines, amino acids with primary amino groups and glycine ethyl ester were reported to react with nitrite to give unidentified agents that alkylated 4-(p-nitrobenzyl)pyridine to produce purple dyes and be direct mutagens in the Ames test. We report here that treatment of glycine ethyl ester at 37 degrees C with excess nitrite acidified with HCl, followed by ether extraction, gave 30-40% yields of a product identified as ethyl chloro(hydroximino)acetate [ClC(=NOH)COOEt, ECHA] and a 9% yield of ethyl chloroacetate. The ECHA was identical to that synthesized by a known method from ethyl acetoacetate, strongly alkylated nitrobenzylpyridine, and may have arisen by N-nitrosation of glycine ethyl ester to give ethyl diazoacetate, which was C-nitrosated and reacted with chloride to give ECHA. Nitrosation of ethyl diazoacetate also yielded ECHA. Ethyl nitroacetate was not an intermediate as its nitrosation did not produce ECHA. ECHA reacted with aniline to give ethyl (hydroxamino)(phenylimino)acetate [PhN=C(NHOH)CO2Et]. This product was different from ethyl [(phenylamino)carbonyl]carbamate [PhNHC(=O)NHCO2Et], which was synthesized by reacting ethyl isocyanatoformate (OCN.CO2Et) with aniline. ECHA reacted with guanosine to give a derivative, which may have been a guanine-C(=NOH)CO2Et derivative. ECHA showed moderate toxicity and weak but significant mutagenicity without activation in Salmonella typhimurium TA-100 (mean, 1.31 x control value for 12-18 microg/plats) and for V79 mammalian cells (1.5-1.7 x control value for 60-100 microM). In conclusion, gastric nitrosation of glycine derivatives such as peptides with a N-terminal glycine might produce ECHA analogues that alkylate bases of gastric mucosal DNA and thereby initiate gastric cancer.
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PMID:Nitrosation of glycine ethyl ester and ethyl diazoacetate to give the alkylating agent and mutagen ethyl chloro(hydroximino)acetate. 1502 13

We have previously shown that fibroblast growth factor receptor 2 (FGFR2) plays an important role in gastric carcinogenesis. In this study, we have used a differential display approach to identify basic fibroblast growth factor (bFGF)-inducible genes in gastric cancer cells. Here, we report that one of these genes is predicted to encode a RING finger protein, designated FIGC. The FIGC gene was found to encode a polypeptide of 381 amino acids with a novel RING finger module at the NH2-terminus and the COOH-terminal proline-rich region. Using an in vitro ubiquitination assay with recombinant protein, we demonstrate that FIGC has intrinsic E3 ubiquitin ligase activity and promotes ubiquitination. Our data indicate that FIGC upregulation in response to bFGF in gastric cancer might be implicated in carcinogenesis through dysregulation of growth modulator.
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PMID:FIGC, a novel FGF-induced ubiquitin-protein ligase in gastric cancers. 1558 9

Plasma thiocyanate has been reported to be high among cassava-eating populations such as that in Nigeria because of the cyanide content of cassava. Thiocyanate, which is secreted into the stomach contents of animals, has been demonstrated to catalyse the formation of nitrosamines (potent carcinogens) in the stomach from secondary amines and nitrite. The main source of the nitrite precursor in this environment is vegetables, primarily eaten as the chief supplier of proteins. The present study attempts to analyse the levels of nitrate and nitrite in vegetables commonly grown and consumed in Delta State, Nigeria. The nitrate and nitrite contents in green vegetable (Amaranthus spp.), bitter leaf (Vernonia amygdalina), pumpkin (Telfaria occidentalis) and water leaf (Talinum triangulare) grown in different localities of the state were determined by standard analytical procedures. The results show that those vegetables grown in the industrialised urban centres of the state had higher nitrate (223 (SD 71) mg/kg dry weight; P<0.05) and nitrite (12.6 (SD 1.7) mg/kg dry weight; P>0.05) levels when compared with the same species (188 (SD 77) mg nitrate/kg dry weight and 10.9 (SD 1.1) mg nitrite/kg dry weight) cultivated in less industrialised suburbs. We conclude that frequent consumption of such vegetables whose nitrate and nitrite contents are high by cassava-eating individuals might put them at risk of developing stomach cancer and other possible results of nitrate and/or nitrite toxicity. In order to avoid an outbreak in our communities, appropriate agencies should monitor and regulate the release of chemicals into the environment. In the meantime, the cultivation and consumption of vegetables grown in industrialised areas of the state should be discouraged.
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PMID:Quantitative analysis of nitrate and nitrite contents in vegetables commonly consumed in Delta State, Nigeria. 1709 80

The tripeptide tyroservatide (tyrosyl-seryl-valine, pTyr-Ser-Val-NH2) has been shown to have antitumor effects on experimental hepatocarcinoma. This study aimed to observe the effects of tyroservatide on other five human carcinomas: A549 (nonsmall cell lung carcinoma), BGC-823 (gastric cancer), MCF-7 (breast cancer), K562 (leukemia), A375 (melanoma) and two murine cancers: Lewis lung cancer and B16 (melanoma) in vivo. In vivo nude mice bearing xenografts of five different human tumors or C57BL/6 mice bearing xenografts of two different murine tumors were given daily intraperitoneal injections of tyroservatide or saline as controls, after tumor implantation. The inhibition of xenografts was determined by calculating the tumor volume and measuring tumor weight. Tyroservatide could significantly inhibit the growth of human lung carcinoma A549, human leukemia K562 and human melanoma A375 in nude mice (P<0.05). In addition, tyroservatide significantly inhibited the subcutaneous tumor growth of Lewis lung carcinoma and B16 melanoma (P<0.05). Tyroservatide, however, could not significantly suppress xenografts of BGC-823 and MCF-7 in nude mice (P>0.05). The results obtained indicate that tyroservatide exhibits different effects on different tumors, which will provide clinical applications guidance of tyroservatide as an anticancer drug.
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PMID:Inhibition of five xenografted human cancers and two murine cancers by the tripeptide tyroservatide. 1735 99

Thimerosal is a mercury-containing preservative in some vaccines. The effect of thimerosal on human gastric cancer cells is unknown. This study shows that in cultured human gastric cancer cells (SCM1), thimerosal reduced cell viability in a concentration- and time-dependent manner. Thimerosal caused apoptosis as assessed by propidium iodide-stained cells and caspase-3 activation. Although immunoblotting data revealed that thimerosal could activate the phosphorylation of extracellular signal-regulated kinase, c-Jun NH2-terminal protein kinase, and p38 mitogen-activated protein kinase (p38 MAPK), only SB203580 (a p38 MAPK inhibitor) partially prevented cells from apoptosis. Thimerosal also induced [Ca2+](i) increases via Ca2+ influx from the extracellular space. However, pretreatment with (bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetate)/AM, a Ca2+ chelator, to prevent thimerosal-induced [Ca2+](i) increases did not protect cells from death. The results suggest that in SCM1 cells, thimerosal caused Ca2+-independent apoptosis via phosphorylating p38 MAPK resulting in caspase-3 activation.
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PMID:Thimerosal-induced apoptosis in human SCM1 gastric cancer cells: activation of p38 MAP kinase and caspase-3 pathways without involvement of [Ca2+]i elevation. 1769 13

Although tumor necrosis factor (TNF) induces apoptosis and cell death in many tumor cells, some cancer cells are still resistant to the TNF-induced death signal. In this report, we showed that Smad7, an inhibitory Smad of transforming growth factor-beta (TGF-beta) signaling, can overcome the TNF resistance in human breast and gastric cancer cells. Overexpression of Smad7 induces the degradation of poly(ADP-ribose) polymerase and the activation of caspase cascade. Although c-Jun NH2-terminal kinase (JNK) signaling is involved in TNF-induced cell death, the expression of Smad7 does not synergize the activation of JNK. However, the activation of nuclear factor-kappaB (NF-kappaB), the cell survival factor, is markedly decreased in Smad7-stable cells. Furthermore, the expression of antiapoptotic target genes of NF-kappaB is significantly reduced in accordance with the level of Smad7. In addition, Smad7 mediates the inhibitory activity of TGF-beta on TNF-induced NF-kappaB activation and the synergistic activity of TGF-beta on TNF-induced apoptosis. These findings suggest that Smad7 sensitizes the tumor cells to TNF-induced apoptosis through the inhibition of expression of antiapoptotic NF-kappaB target genes.
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PMID:Smad7 sensitizes tumor necrosis factor induced apoptosis through the inhibition of antiapoptotic gene expression by suppressing activation of the nuclear factor-kappaB pathway. 1790 69

Glibenclamide, a blocker of ATP-sensitive potassium (K(ATP)) channels, can suppress progression of many cancers, but the involved mechanism is unclear. Herein we reported that MGC-803 cells expressed the K(ATP) channels composed of Kir6.2 and SUR1 subunits. Glibenclamide induced cellular viability decline, coupled with cell apoptosis and reactive oxygen species (ROS) generation in MGC-803 cells. Meanwhile, glibenclamide increased NADPH oxidase catalytic subunit gp91(phox) expression and superoxide anion (O2-) generation, and caused mitochondrial respiration dysfunction in MGC-803 cells, suggesting that glibenclamide induced an increase of ROS derived from NADPH oxidase and mitochondria. Glibenclamide could also lead to loss of mitochondrial membrane potential, release of cytochrome c and apoptosis-inducing factor (AIF), and activation of c-jun NH2-terminal kinase (JNK) in MGC-803 cells. Pretreatment with antioxidant N-acetyl-l-cysteine (NAC) prevented glibenclamide-induced JNK activation, apoptosis and cellular viability decline. Furthermore, glibenclamide greatly decreased the cellular viability, induced apoptosis and inhibited Akt activation in wild-type mouse embryonic fibroblast (MEF) cells but not in JNK1-/- or JNK2-/- MEF cells. Taken together, our study reveals that glibenclamide exerts an antitumor activity in MGC-803 cells by activating ROS-dependent, JNK-driven cell apoptosis. These findings provide insights into the use of glibenclamide in the treatment of human gastric cancer.
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PMID:Glibenclamide exerts an antitumor activity through reactive oxygen species-c-jun NH2-terminal kinase pathway in human gastric cancer cell line MGC-803. 1884 Apr 12

The hedgehog and mitogen-activated protein kinase (MAPK) signaling pathways regulate growth in many tumors, suggesting cooperation between these two pathways in the regulation of cell proliferation. However, interactions between these pathways have not been extensively studied. We assessed cross-talk between hedgehog and MAPK signaling in the regulation of cell proliferation in gastric cancer. We showed that PTCH expression was significantly correlated with extracellular signal-regulated kinase (ERK) 1/2 phosphorylation (P = 0.016) as well as SHH expression (P = 0.034) in the 35 gastric cancers assessed by immunohistochemistry. Indeed, MAPK signaling increased the GLI transcriptional activity and induced the expression of hedgehog target genes in gastric cancer cells. The inductive effect of activated KRAS and mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) 1 was blocked by the suppressor of fused (SUFU), indicating that MAPK signaling regulates GLI activity via a SUFU-independent process. Moreover, the deletion of the NH2-terminal domain of GLI1 gene resulted in reduced response to MEK1 stimulation. Our results suggest that the KRAS-MEK-ERK cascade has a positive regulatory role in GLI transcriptional activity in gastric cancer.
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PMID:Regulation of the hedgehog signaling by the mitogen-activated protein kinase cascade in gastric cancer. 1914 99

We have previously reported the synergistic cytotoxic effects of Docetaxel (TXT) and S-1 in gastric cancer in vitro and in vivo, and the combination regimen is now under phase III clinical trail. In this study, to elucidate whether the rapamycin, the inhibitor of the mTOR (mammalian target of rapamaycin), can enhance the potentiation of TXT and 5-fluorouracil (5-Fu) in gastric carcinoma cells. Rapamycin inhibited the growth of TMK-1, MKN-28, MKN-45 and MKN-74 cell lines by MTT assay, and it demonstrated the cytostatic effects as G1 arrest shown by flowcytometry. However, the cytotoxic effects of 5-Fu, TXT and cisplatin were enhanced by 2 to 4 times with the concomitant administration of rapamycin. To clarify the mechanism of the potentiation, the expression changes of the enzymes relating DNA metabolism and cell growth signal transduction pathways were examined by western blot analysis. Interestingly, the expression of thymidilate synthase was markedly decreased by the administration of rapamycin in TMK-1 cells in a time- and dose-dependent manner. Moreover, rapamycin decreased the phosphorylation of 4E-BP1, the phosphorylation of ERK1/2 and enhanced the phosphorylation of c-Jun NH2-terminal kinase, and the activation of caspase of apoptotic pathways in combination with TXT. These results strongly indicate that the mTOR inhibitor can enhance the potentiation of TXT and 5-Fu or S-1 and can serve as a new therapeutic tool for advanced and recurrent gastric cancer patients.
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PMID:Rapamycin enhances chemotherapy-induced cytotoxicity by inhibiting the expressions of TS and ERK in gastric cancer cells. 1985 12

Nitrite has long been considered a potential pre-carcinogen for gastric cancer. Acidification of salivary nitrite, derived from dietary nitrate, produces nitrosative species such as NOSCN, NO(+) and N(2)O(3), which can form potentially carcinogenic N-nitroso compounds. Ascorbic acid inhibits nitrosation by converting the nitrosative species into nitric oxide (NO). However, NO diffuses rapidly to adjacent lipids, where it reacts with oxygen to reform nitrosative species. Nitrosation has been studied in vitro in aqueous systems and less frequently in organic systems; however, there is a need to investigate acid-catalysed nitrosation in a system combining aqueous and lipid environments, hence providing a physiologically relevant model. Here, we describe a two-phase system, which can be used as a tool to understand acid-catalysed nitrosation. Using gas chromatography/ion trap tandem mass spectrometry, we investigated the nitrosation of secondary amines as a function of the lipid phase composition and reaction mixing. An increased interface surface area was a driver for nitrosation, while incorporation of unsaturated fatty acids affected morpholine and piperidine nitrosation differently. Linoleic acid methyl esters did not affect morpholine nitrosation and only had a limited effect on N-nitrosopiperidine formation, while incorporation of free linoleic acid to the lipid phase significantly reduced N-nitrosopiperidine formation, but increased N-nitrosomorpholine formation at low levels. The mechanisms driving these effects are thought to involve amine partitioning, polarity and unsaturated fatty acids acting as scavengers of nitrosating species, findings relevant to the nitrosative chemistry occurring in the stomach, where the gastric acid meets a range of dietary fats which are emulsified during digestion.
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PMID:Development of an in vitro system combining aqueous and lipid phases as a tool to understand gastric nitrosation. 2011 67


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