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Objective To evaluate the expression of STAT3, VEGF and Survivin in human gastric carcinoma and its clinicopathological significance. Methods The expression of STAT3, VEGF, survivin was determined by immunohistochemical staining of specimens from 53 cases undergoing radical gastrectomy and 53 cases of normal gastric mucous membranae. We evaluated the relationship between expression of these proteins and various clinicopothological factors. Results The expression rate of STAT3, VEGF and survivin in 53 gastric carcinoma tissues was 58%, 62% and 74%, respectively, which was significantly higher than those in the normal group(P <0. 01). STAT3 expression correlated with VEGF(r =0. 608 ,P <0. 01) ,survivin(r = 0. 451, P = 0. 001). Positive STAT3, VEGF staining was significantly associated with tumor size, Lauren's classification,lymph node metastasis and clinical staging(P < 0. 05). Survivin staining was significantly associated with Lauren's classification, lymph node metastasis and clinical staging(P <0. 05). Multivariate analysis revealed STAT3 expression and lymph node metastasis were independently prognostic factors of poor survival. Conclusion VEGF, survivin possibly regulated by STAT3 leads to tumor angiogenesis and anti-apoptosis. The expression of STAT3 is an independent prognostic factors in gastric carcinoma.
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Glucagon-like peptide-2 (GLP-2) is a 33-amino acid peptide derived from the tissue-specific, post-translational processing of the proglucagon gene.GLP-2 is a newly discovered,specific for the intestine growth factor that affects gastrointestinal functions including epithelial growth of normal and developing intestinal preventing damage and facilitating intestinal repair in animal models and patients of intestinal disease. GLP-2 also inhibits gastrointestinal motility and gastric acid secretion, up-regulates intestinal blood flow and reduces food intake. The actions of GLP-2 are initiated by activation of the GLP-2 receptor (GLP-2R), a specific G-protein-linked membrane receptor. This review provides an overview of the physiological, pharmacological, and therapeutic actions of GLP-2 and GLP-2R signaling mechanism, with a focus on the most recent findings on the role of this peptide hormone in the normal and diseased gastrointestinal tract.
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AIM To investigate whether Aβ deposit in Alzheimer disease(AD) impairs signal transduction pathway responsible for neuronal survival.METHODSThe rats were randomly divided into six groups:control group and Aβ25-35 group,Aβ25-35+ibuprofen groups (7.5 and 15 mg·kg-1,respectively),Aβ25-35+ibuprofen+LY294002 group,and Aβ25-35+LY294002 group.Rats were given ibuprofen (7.5 and 15 mg·kg-1 daily,ig) for 3 weeks prior to and 1 week after icv single dose of Aβ25-35 (10 μL,1 mmol·L-1).LY294002 was injected icv 1 h before the injection of Aβ25-35.Seven days after Aβ25-35 injection,the hippocampal expressions of P53,Bax,Fas ligand (FasL),Bcl-2 proteins,phospho-Akt/PKB,and phosphorylated 70 ku ribosomal protein S6 kinase (p70S6K) and caspase 3 were determined in the brain tissue preparations from CA1 area with Western blot.The activity of caspase 3 was measured using a caspase 3 colorimetric activity assay kit.RT-PCR was used to show the change of p70s6k mRNA level.RESULTS Aβ25-35 icv injection significantly down-regulated phosphorylated Akt/PKB from 1.32±0.14 to 0.69±0.08 and p70S6K from 0.769±0.028 to 0.479±0.032 in hippocampal CA1 region.These changes were accompanied by increased expressions of the proapoptotic proteins P53,Bax,and FasL and decreased expression of the anti-apoptotic protein Bcl-2 in rat hippocampus.In addition,caspase 3 activity was significantly enhanced in hippocampal CA1 region in Aβ25-35-treated rats compared with control rats.Ibuprofen can reverse these Aβ25-35-induced changes.CONCLUSION Down-regulated anti-apoptotic PI3K/Akt/p70S6K signaling pathway induced by Aβ25-35 in rat hippocampus may contribute to the neuronal damage in AD.Ibuprofen prevents Aβ25-35-induced down-regulation of PI3K/Akt/p70S6K signaling pathway.
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Objective To investigate the inhibitory effect of octreotide on transforming growth factor-alpha (TGF-?)-induced cell proliferation of human hepatocellular carcinoma cells and its possible mechanism. Methods The effect of octreotide on TGF-?-induced cell proliferation of the liver cancer cells (LCC) was evaluated by immunohistochemistry method. The effect of octreotide on TGF-? secretion and epidermal growth factor receptor(EGFR) expression in the cells was determined by reverse-transcriptase polymerase chain reaction(RT-PCR). The effect of octreotide on extracellular signal-regulated protein kinase (ERK) expression in the cells was measured by Western-blot and immunohistochemistry method. Results The TGF-?-induced expressions of proliferating cell nuclear antigen (PCNA) in nucleus were obviously increased by TGF-?. TGF-?mRNA index of hepatocellular carcinoma cells was decreased by octreotide. Octreotide inhibited significantly the expressions of EGFR mRNA induced by TGF-?. Octreotide inhibited significantly the expressions of ERK protein induced by TGF-?. There was intense staining in the nucleus of the cells by TGF-? and weak staining in the nucleus of the cells treated simultaneously by octreotide and TGF-?.Conclusions Octreotide can inhibit the secretion of TGF-?, the expression of EGFR, and the signal transduction of EGFR of LCC, and consequently exerts an inhibitory effect on TGF-?-induced hepatocellular carcinoma cells proliferation.
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AIM: To examine the role of TLR-4 signaling pathway in laminar low shear stress-induced IL-8 gene expression in ECV304 cells. METHODS: RT-PCR and PCR were used to amplify a TLR4 mutant (lacking the 155 COOH terminal amino acids of the wild type TLR4 ) and-102-+61 bp 5′-flanking region of IL-8 gene (IL8 USCS)from endothelial cells. These two DNA fragments were cloned into pcDNA3 and pEGFP1, respectively, and the recombinant plasmid pcDNA3-mTLR4 and pEGFP1-IL8USCS were obtained. ECV304 cells were transfected with the pEGFP1-IL8USCS or co-transfected with pEGFP1-IL8USCS and pcDNA3-mTLR4 by using Dosper liposomal transfectional reagent and selected by G418, and then stimulated by 4 2 dyne/cm 2 shear stress for 3 hours. The green fluorescent protein expression was analyzed by Flow Cytometry. Immunoblotting of the cell lysates and NF-?B p65 immunocytofluorescent staining were used to determine I?B phosphorylation, degradation and NF-?B activation. RESULTS: Flow Cytometric analysis showed that when exposed to 4 2 dyne/cm 2 shear stress for 3 hours, there was a marked increase in the enhanced green fluorescent protein expression in pEGFP1-IL8USCS-transfected ECV304 cells. In contrast, there was almost no change in the green fluorescent protein expression in the cells co-transfected with pEGFP1-IL8USCS and pcDNA3-mTLR4 after the stimulation. Western blot analysis showed that a markedly increased p-I?B of cell lysates occurred at 10 min of exposure and the blot density almost dropped down to the baseline after 60 min of exposure. The density of I?B blot dropped down with increasing exposure time. NF-?B p65 immunocytofluorescent staining of ECV304 cells showed that when exposed to the same flow shear stress for 0 5,1 hours, the cell nuclei became staining, and after 1 5 or 2 hours, the staining was very strong. CONCLUSION: These results suggested that the inflammatory TLR-4/NF-?B signaling pathway may be involved in flow shear stress-induced IL-8 gene expression in human vascular endothelial cells.