共查询到20条相似文献,搜索用时 46 毫秒
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Chen LF 《Journal of cellular biochemistry》2012,113(5):1470-1477
Emerging evidence indicates that RUNX3 is a tumor suppressor in breast cancer. RUNX3 is frequently inactivated in human breast cancer cell lines and cancer samples by hemizygous deletion of the Runx3 gene, hypermethylation of the Runx3 promoter, or cytoplasmic sequestration of RUNX3 protein. Inactivation of RUNX3 is associated with the initiation and progression of breast cancer. Female Runx3(+/-) mice spontaneously develop ductal carcinoma, and overexpression of RUNX3 inhibits the proliferation, tumorigenic potential, and invasiveness of breast cancer cells. This review is intended to summarize these findings and discuss the tumor suppressor function of RUNX3 in breast cancer. 相似文献
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Effect of H. pylori infection on the expression of cyclooxygenase-2 in human gastric mucosa 总被引:4,自引:0,他引:4
Shah AA Byrne MF Cullen L Walsh T Fitzgerald DJ Murray FE 《Prostaglandins, leukotrienes, and essential fatty acids》2003,68(1):1-8
Cyclooxygenase-1 is the primary isoform responsible for the production of cytoprotective prostaglandins (PGE(2) and PGI(2)) in the stomach. In contrast COX-2 is induced at the sites of inflammation. Using Helicobacter pylori infection as a model of inflammation, this study was designed to evaluate the effects of H. pylori infection on prostanoid synthesis and expression of COX-2 in human gastric mucosa.Prostaglandin (PGE(2)) and prostacyclin (PGI(2)) synthesis in gastric biopsies obtained from 21 patients undergoing diagnostic endoscopy, were determined. H. pylori was detected by CLO test, histology and culture. Biopsy samples were incubated either with NS-398, selective COX-2 inhibitor or aspirin. Samples were also treated with endotoxin (LPS) in order to induce COX-2 expression. Tissue was also analysed for COX-2 expression in vivo by immunohistochemistry.In 15 out of 21 patients, H. pylori was detected by at least two of the three methods. Higher levels of PGE(2) and PGI(2) were seen in patients infected with H. pylori (191+/-30 and 245+/-88ng/mg protein, respectively) compared with non-infected patients (77+/-17 and 120+/-36ng/mg protein, respectively). There was significant inhibition of PGE(2) and PGI(2) with aspirin in both H. pylori infected (28+/-6.6 and 53+/-43ng/mg, respectively) and in non-infected patients (16+/-7 and 12.5+/-3.5ng/mg protein, respectively). However, NS-398 and LPS did not alter prostaglandin function significantly. Immunohistochemistry in all patients irrespective of Hp status demonstrated expression of COX-2.Lower concentration of constitutive expression of COX-2 was detected in human gastric mucosa by immunohistochemistry, however, H. pylori infection failed to induce COX-2 protein. In addition, increased prostaglandin synthesis in Hp-infected patients appears to be COX-1 mediated rather than COX-2. Furthermore, failure of endotoxaemia-treated sample to produce more PGE(2) in the face of enhanced COX-2 expression in gastric mucosa further suggests that increased prostanoids in human gastric stomach are COX-1 mediated. 相似文献
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Nikola Panic Elena Mastrostefano Emanuele Leoncini Roberto Persiani Dario Arzani Rosarita Amore Riccardo Ricci Federico Sicoli Stefano Sioletic Milutin Bulajic Domenico D’ Ugo Walter Ricciardi Stefania Boccia 《Molecular biology reports》2014,41(6):3637-3650
The aim of this study was to identify the clinical, demographic, lifestyle factors and selected genetic polymorphisms that affect the susceptibility towards Helicobacter pylori (H. pylori) infection in gastric cancer patients. Histological confirmed gastric adenocarcinoma cases that underwent curative gastrectomy between 2002 and 2012 were included. Gastric biopsy samples were obtained to determine the H. pylori status, and further cagA status and vacA m and s genotypes by polymerase chain reaction. Patients were interviewed with structured questionnaires, and blood samples were collected for EPHX1, GSTM1, GSTT1, IL1B, IL1-RN, MTHFR and p53 genotyping. Proportions were compared in univariate analysis, while the relation between putative risk factors and H. pylori status and genotype were measured using logistic regression analysis. One hundred forty-nine gastric cancer patients were included, of which 78.5 % were H. pylori positive. Among positive patients 50 % were cagA+, 72.5 % vacA m1 and 80.7 % vacA s1. The presence of cagA was less frequent among vacA m1 (p = 0.031) and vacA s1 (p = 0.052) subtypes. The presence of father history for any cancer was a significant risk factor for H. pylori infection [adjusted odds ratio (OR) = 8.18, 95 % confidence interval (CI) 1.04–64.55]. EPHX1 exon 3 T > C (OR = 0.35, CI 95 % 0.13–0.94), IL1B-511 T > C (OR = 0.38, CI 95 % 0.15–0.97) and IL1-RN VNTR (OR = 0.19, CI 95 % 0.06–0.58) polymorphisms were protective towards H. pylori infection in the univariate analysis. Wine consumption was associated with higher risk of carrying the H. pylori vacA m1 virulent subtype (p = 0.034). Lastly, cardiovascular diseases were less common among cagA positive subjects (p = 0.023). Father history of any cancer is a risk factor for H. pylori infection. Polymorphisms in IL1B-511, IL1-RN and EPHX1 exon 3 genes might be protective towards H. pylori infection. 相似文献
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N Vakil 《The Yale journal of biology and medicine》1998,71(2):119-124
Despite the wide dissemination of information on Helicobacter pylori, there is still a great deal of variation in how general practitioners treat the infection and in which circumstances they prescribe eradication therapy for H. pylori. Specialty societies have developed consensus guidelines that recommend a strategy to test and treat dyspeptic patients for H. pylori infection although the data to support these recommendations are weak at the present time. As a result, there is still confusion about the indications for treatment and the treatment regimens that are likely to be effective in routine clinical practice. 相似文献
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Göõz M Göõz P Smolka AJ 《American journal of physiology. Gastrointestinal and liver physiology》2001,281(3):G823-G832
To test the hypothesis that Helicobacter pylori regulates gastric cell secretion of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), culture media from infected and uninfected human gastric adenocarcinoma (AGS) cells were analyzed by zymography, MMP activity assays, and immunoblotting. AGS cells secreted gelatinolytic (prominently 90 kDa) and caseinolytic (110 kDa) activity together with MMP-1, MMP-3, and TIMP-1, TIMP-2, and TIMP-3 isoforms. H. pylori secreted caseinolytic activity (60 kDa), MMP-3-like enzyme activity, and TIMP-3 immunoreactivity. H. pylori infection increased the 110-kDa caseinolytic activity and induced new gelatinolytic (~35 kDa) and caseinolytic (22 kDa) activities. Infection also increased both basal secretion and activation of MMP-1 and MMP-3, enhanced TIMP-3 secretion, and increased the formation of MMP-3/TIMP-3 complexes. TIMP-1 and TIMP-2 secretion were unchanged. Normal AGS cells showed a pancellular distribution of TIMP-3, with redistribution of immunoreactivity toward sites of bacterial attachment after H. pylori infection. The data indicate that MMP and TIMP secretion by AGS cells is modulated by H. pylori infection and that host MMP-3 and a TIMP-3 homolog expressed by H. pylori mediate at least part of the host cell response to infection. 相似文献
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Yu-Ching Tsai Wei-Hsin Hsiao Sheng-Hsiang Lin Hsiao-Bai Yang Hsiu-Chi Cheng Wei-Lun Chang Cheng-Chan Lu Bor-Shyang Sheu 《Journal of biomedical science》2015,22(1)
Background
Gastric cancer exhibits familial clustering, and gastric cancer familial relatives (GCF) tend to present with corpus-predominant gastritis and precancerous lesions as SPEM or IM after H. pylori infection. The study determined whether the children of gastric cancer patients (GCA) had genomic single nucleotide polymorphisms (SNPs) predisposed to the gastric precancerous lesions as spasmolytic polypeptide-expressing metaplasia (SPEM) or intestinal metaplasia (IM).Results
There were 389 family relatives of 193 non-cardiac GCA and 173 duodenal ulcer patients (DU), received blood sampling for DNA collection. The differences of the risk alleles of SNPs in the ITGA5, ITGB1, IL-10, COX-2, RUNX3, and TFF2 genes were compared between 195 children of GCA and 143 DU. The children of GCA had higher allele frequencies of ITGA5-1160 T-carrier (P = 0.006, OR[95% CI] = 2.2[1.2-4]), ITGB1-1949 A-carrier (P = 0.047; OR[95% CI] = 2.8[1.4-5.3]), ITGB1 + 31804 C-carrier (P = 0.013; OR[95% CI] = 4.7[1.7-13.0]), IL-10-592 AA (P = 0.014; OR[95% CI] = 2.3[1.4-4.0]) and COX-2-1195 G-carrier (P = 0.019; OR[95% CI] = 1.7[0.9-3.2]) than DU. The combined genotype with ITGA5-1160/ITGB1-1949/ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA was more prevalent in the children of GCA than in DU (P < 1×10−4), and predisposed with a 5.3-fold risk of getting SPEM in the H. pylori-infected children of GCA (P = 0.016). Such risk of getting SPEM increased to 112 folds, if combined with RUNX3 + 492/TFF2-308 as A-carrier/CC in this limited study scale (P = 1×10−4).Conclusions
The SNPs of ITGA5-1160/ITGB1-1949/ ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA, or more specific to combine RUNX3 + 492/TFF2-308 as A-carrier/CC shall be host factor predisposing to gastric cancer during H. pylori infection, and serve as marker to identify high-risk subjects for H. pylori eradication.Electronic supplementary material
The online version of this article (doi:10.1186/s12929-015-0121-7) contains supplementary material, which is available to authorized users. 相似文献13.
Muhammad Junaid Masaud Shah Abbas Khan Cheng-Dong Li Muhammad Tahir Khan Aman Chandra Kaushik 《Journal of biomolecular structure & dynamics》2013,31(15):4035-4050
AbstractHelicobacter pylori (H. pylori) is one of the most extensively studied Gram-negative bacteria due to its implication in gastric cancer. The oncogenicity of H. pylori is associated with cytotoxin-associated gene A (CagA), which is injected into epithelial cells lining the stomach. Both the C- and N-termini of CagA are involved in the interaction with several host proteins, thereby disrupting vital cellular functions, such as cell adhesion, cell cycle, intracellular signal transduction, and cytoskeletal structure. The N-terminus of CagA interacts with the tumor-suppressing protein, apoptosis-stimulating protein of p53 (ASPP2), subsequently disrupting the apoptotic function of tumor suppressor gene p53. Here, we present the in-depth molecular dynamic mechanism of the CagA–ASPP2 interaction and highlight hot-spot residues through in silico mutagenesis. Our findings are in agreement with previous studies and further suggest other residues that are crucial for the CagA–ASPP2 interaction. Furthermore, the ASPP2-binding pocket possesses potential druggability and could be engaged by decoy peptides, identified through a machine-learning system and suggested in this study. The binding affinities of these peptides with CagA were monitored through extensive computational procedures and reported herein. While CagA is crucial for the oncogenicity of H. pylori, our designed peptides possess the potential to inhibit CagA and restore the tumor suppressor function of ASPP2. 相似文献
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Dual Phosphorylation of suppressor of fused (Sufu) by PKA and GSK3beta regulates its stability and localization in the primary cilium 总被引:1,自引:0,他引:1
Chen Y Yue S Xie L Pu XH Jin T Cheng SY 《The Journal of biological chemistry》2011,286(15):13502-13511
Suppressor of fused (Sufu) is an essential negative regulator of the sonic hedgehog (Shh) pathway, but little is known about how Sufu itself is normally regulated. Here, we report that Sufu is phosphorylated at Ser-342 and Ser-346 by GSK3β and cAMP-dependent protein kinase A (PKA), respectively, and phosphorylation at this dual site stabilizes Sufu against Shh signaling-induced degradation. We further show that localization of Sufu in the primary cilium is induced by Shh signaling and is required for the turnover of both phosphorylated and total Sufu. Perturbing Sufu phosphorylation with PKA inhibitors or replacing Ser-346 with alanine reduced the stay and replacing Ser-342 and Ser-346 with aspartic acid prolonged the stay of Sufu in the cilia. Finally, ciliary localization of Gli2/3 also required Smo and was similarly influenced by perturbations of PKA activity or mutations at the dual Sufu phosphorylation site. Thus, Shh likely induced trafficking of phospho-Sufu into the primary cilium in a complex with Gli2/3, and dephosphorylation triggered a retrograde export, allowing Sufu to be degraded by the ubiquitin-proteasome system. 相似文献
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Takenaka R Yokota K Mizuno M Okada H Toyokawa T Yamasaki R Yoshino T Sugiyama T Asaka M Shiratori Y Oguma K 《Helicobacter》2004,9(3):194-200
Background and aims. Eradication of Helicobacter pylori leads to regression of mucosa‐associated lymphoid tissue (MALT) lymphomas. In this study, we measured serum antibodies to H. pylori and H. pylori‐recombinant heat‐shock protein 60 (rHSP60) in patients with gastric MALT lymphoma to determine whether humoral immune responses to the bacterial antigens correlate with the efficacy of eradication therapy. Methods. Serum samples were obtained from 33 patients with H. pylori‐positive gastric MALT lymphoma before undergoing therapy to eradicate the bacteria. Anti‐H. pylori antibodies were measured in a commercial assay and in immunoassays to lysates and rHSP60 which were prepared from ATCC 43504 strain. Results. Helicobacter pylori were eradicated in all 33 patients, and the lymphoma completely regressed histologically in 26 patients (79%). Pre‐treatment titers of serum antibody to H. pylori and to rHSP60 in the patients whose tumor regressed were significantly higher than titers in patients whose tumors did not regress (p = .0011 and .035, respectively). By logistic regression analysis, age (odds ratio = 0.88, 95% confidence interval = 0.80–0.99), endoscopic appearance (0.053, 0.004–0.65), titers of anti‐H. pylori antibodies (67.6, 2.5–1800), and titers of anti‐rHSP60 antibody (6.4, 1.2–36) were identified as significantly associated factors with the outcome of MALT lymphoma. Conclusions. Measurement of serum antibodies to H. pylori and HSP60 might be useful for predicting the response of gastric MALT lymphoma to eradication of H. pylori. 相似文献
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H.Q. Huynh M.A.F. Campbell R.T.L. Couper C.D. Tran A. Lawrence R.N. Butler 《Letters in applied microbiology》2009,48(5):517-522
Aims: To evaluate the efficacy of bovine lactoferrin (BLf), recombinant human lactoferrin (rHLf) and desferrioxamine against Helicobacter pylori in vitro and in mice and also to determine whether BLf or rHLf alter gastric inflammation.
Methods and Results: In vitro: Broth dilution susceptibility tests were performed using different concentrations of desferrioxamine, BLf and rHLf. Murine trials: In the prevention trial, C57BL/6 female mice were treated with BLf or rHLF, and then infected with the SS1 strain of H. pylori . In the treatment trial, mice were gavaged with either BLf, rHLf or desferrioxamine. In addition, gastric myeloperoxidase activity (MPO) was measured to assess gastric inflammation. Desferoxamine was found to have a direct bactericidal effect, while BLf and rHLf only partially suppressed H. pylori growth in vitro . However, in both prevention and treatment trials all three forms of treatment failed to reduce H. pylori load in mice. Gastric MPO activity and H. pylori load were noted to be higher with lactoferrin treatments.
Conclusions: Our study does not support the use of BLf or rHLF in the treatment of human H. pylori infection. Interestingly, H. pylori growth and gastric inflammation appear to be enhanced by lactoferrin treatment.
Significance and Impact of the Study: The mouse model is ideal for testing novel H. pylori eradicating agents. 相似文献
Methods and Results: In vitro: Broth dilution susceptibility tests were performed using different concentrations of desferrioxamine, BLf and rHLf. Murine trials: In the prevention trial, C57BL/6 female mice were treated with BLf or rHLF, and then infected with the SS1 strain of H. pylori . In the treatment trial, mice were gavaged with either BLf, rHLf or desferrioxamine. In addition, gastric myeloperoxidase activity (MPO) was measured to assess gastric inflammation. Desferoxamine was found to have a direct bactericidal effect, while BLf and rHLf only partially suppressed H. pylori growth in vitro . However, in both prevention and treatment trials all three forms of treatment failed to reduce H. pylori load in mice. Gastric MPO activity and H. pylori load were noted to be higher with lactoferrin treatments.
Conclusions: Our study does not support the use of BLf or rHLF in the treatment of human H. pylori infection. Interestingly, H. pylori growth and gastric inflammation appear to be enhanced by lactoferrin treatment.
Significance and Impact of the Study: The mouse model is ideal for testing novel H. pylori eradicating agents. 相似文献
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Bian Y Wang L Lu H Yang G Zhang Z Fu H Lu X Wei M Sun J Zhao Q Dong G Lu Z 《Biochemical and biophysical research communications》2012,422(1):187-193
Gastric cancer (GC) is the fourth most common cancer and second leading cause of cancer-related death worldwide. RNA-binding protein Quaking (QKI) is a newly identified tumor suppressor in multiple cancers, while its role in GC is largely unknown. Our study here aimed to clarify the relationship between QKI expression with the clinicopathologic characteristics and the prognosis of GC. In the 222 GC patients' specimens, QKI expression was found to be significantly decreased in most of the GC tissues, which was largely due to promoter hypermethylation. QKI overexpression reduced the proliferation ability of GC cell line in vitro study. In addition, the reduced QKI expression correlated well with poor differentiation status, depth of invasion, gastric lymph node metastasis, distant metastasis, advanced TNM stage, and poor survival. Multivariate analysis showed QKI expression was an independent prognostic factor for patient survival. 相似文献
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Helicobacter pylori causes gastritis and some infections result in peptic ulceration, gastric adenocarcinoma or gastric lymphoma. A critical step in the pathogenesis of these diseases is the ability of H. pylori to adhere to gastric epithelial cells. A role for the lipopolysaccharide O-antigen side-chain in this process has previously been identified. In this study, evidence is presented that the receptor recognized by the O-antigen side-chain is galectin-3, a beta-galactoside-binding lectin. A variety of functions have been ascribed to galectin-3 including modulation of extracellular adhesion and chemotaxis of monocytes and neutrophils. Expression of galectin-3 is upregulated by gastric epithelial cells following adhesion of H. pylori, suggesting that in addition to colonization this protein also plays a role in the host response to infection. Upregulation of galectin-3 is inhibited by treating gastric epithelial cells with the mitogen-activated protein kinase (MAPK) inhibitors U0126 or PD098059 and does not occur in cells infected with either H. pylori cagE or cagA isogenic mutants. This implies that H. pylori-mediated expression of galectin-3 is dependent on delivery of CagA into the host cell cytosol and the subsequent stimulation of MAPK signalling. A further consequence of H. pylori adhesion is that it elicits a rapid release of galectin-3 from infected cells. A role for this phenomenon in initiating the trafficking of phagocytic cells to the site of infection is discussed. 相似文献