AIM:To assess the prognostic significance of nuclear factor-kB (NF-kB) and its target genes in gastric cancer. METHODS:The tumor tissues of 115 patients with gastric cancer were immunohistochemically evaluated using m...AIM:To assess the prognostic significance of nuclear factor-kB (NF-kB) and its target genes in gastric cancer. METHODS:The tumor tissues of 115 patients with gastric cancer were immunohistochemically evaluated using monoclonal antibodies against NF-kB RelA. Preoperative serum levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) were assessed via enzyme-linked immuno-sorbent assay. C-reactive protein (CRP) and serum amyloid A (SAA) were measured via immunotrubidimetry. RESULTS:Positive rate of NF-kB RelA was 42.6%. NF-kB RelA expression in tumor tissues was also related to serum levels of IL-6 (P = 0.044) and CRP (P = 0.010). IL-6, SAA, CRP were related to depth of invasion, VEGF and SAA were correlated with lymph node metastasis. IL-6, VEGF, SAA and CRP were related to the stage. Univariate analysis demonstrated that immunostaining of NF-kB RelA, levels of IL-6, VEGF, SAA were significantly related with both disease free survival and over-all survival (OS). Multivariate analysis verified that NF-kB RelA [hazard ratio (HR): 3.40, P = 0.024] and SAA (HR: 3.39, P = 0.045) were independently associated with OS. CONCLUSION: Increased expression of NF-kB RelA and high levels of serum SAA were associated with poor OS in gastric cancer patients.展开更多
Connexin 43 (Cx43) is the major structural protein of gap junctions in the ventricular myocardium and a major determinant of myocardial electrical properties. Cx43 expression is decreased in the wild type mice after...Connexin 43 (Cx43) is the major structural protein of gap junctions in the ventricular myocardium and a major determinant of myocardial electrical properties. Cx43 expression is decreased in the wild type mice after myocardial infarction and this effect is attenuated in MMP-7-/- mice. Matrix metalloproteinase expression is regulated at the transcription level by the modulation of the activation of transcription factors such as activator protein (AP)-I and nuclear factor kappa-light-chain enhancer of activated B cells (NF-KB). Methods Rat myocardial cells (H9c2) were cultured and maintained at 37 ~C and 5% CO2. H9c2 cells in 6-well plates were treated with lipopolysaccharides (LPS), NF-kB inhibitor (JSH 23, 30 μ, Santa Cruz) + LPS and c-Jun N-terminal kinase (JNK) inhibitor (SP600125, 10μM, Sigma) + LPS for 6, 12 and 24 h. Apoptosis rate of cells was determined by flow cytometry. Cx43 expression was assessed by Western blotting. Results LPS induced a time-dependent apoptosis in all cell line. We have found that the treatment with LPS induced increase of apoptosis in H9c2 cells at 6 h, 12 h and 24 h, but the effect was decreased by the addition of JSH-23 and SP600125 to LPS respectively (P 〈 0.05) . LPS resulted in decreased expression of Cx43 expression at 6 h, 12 h and 24 h. However, JSH-23 and SP600125 attenuated the loss of Cx43 respectively (P 〈 0.05). Conclusion Transcription factors NF-kB and JNK/AP-1 signaling pathway participates in the regulation of LPS-induced Cx43 expression in the H9c2 cells, and maybe play an important role in regulation of Cx43 expression.展开更多
Objective To observe the different expression of NF-kBp65 and cyclinD1 during oral carcinogenesis and to analyze the relationship between the abnormal expression of NF-kBp65 , cyclinD1, and the occurrence and developm...Objective To observe the different expression of NF-kBp65 and cyclinD1 during oral carcinogenesis and to analyze the relationship between the abnormal expression of NF-kBp65 , cyclinD1, and the occurrence and development of oral carcinogenesis. Methods The streptavidin-biotin-peroxidase (S-P) immunohistochemical method was employed to detect the expression of NF-kBp65 and cyclinD1 protein in 38 rat tongue carcinogenesis specimens induced by 4-nitroquinoline 1-oxide. Results With the progress of tongue carcinogenesis, the expression of NF-kBp65, cyclinD1 was up-regulated. In normal, mild epithelial dysplasia, moderate epithelial dysplasia, severe epithelial dysplasia, carcinoma in situ and squamous cell carcinoma (SCC), the positive rate of NF-kBp65 was 20%, 20%, 50%, 62.5%, 50% and 83.33%, respectively. There was significant differences between normal and SCC ( P 〈 0. 05 ) ; while the level of cyclinD1 was 20%, 60%, 62. 5%, 87. 5% , 100% and 83. 33%, respec- tively. There was significant differences between normal and severe epithelial dysplasia, carcinoma in situ and SCC ( P 〈0.01 or P 〈 0. 05 ). There was a significant correlation between the increased levels of NF-kBp65, cyclinD1 and histopathological grade. The positive expression of NF-kBp65 was also associated with cyclinD1 in SCC ( r = 0. 7353, P 〈 0. 05 ). Conclusion The up-expression of NF-kBp65 and cyclinD1 protein may be correlated to the occurrence and the development of oral carcinoma ; activated NF-kB plays an important role in the overexpression of cyclinD1. Furthermore, NF-kB and cyclinD1 may be the useful biomarker of oral precancerous lesion.展开更多
基金Supported by The Dong-A University Research Fund
文摘AIM:To assess the prognostic significance of nuclear factor-kB (NF-kB) and its target genes in gastric cancer. METHODS:The tumor tissues of 115 patients with gastric cancer were immunohistochemically evaluated using monoclonal antibodies against NF-kB RelA. Preoperative serum levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) were assessed via enzyme-linked immuno-sorbent assay. C-reactive protein (CRP) and serum amyloid A (SAA) were measured via immunotrubidimetry. RESULTS:Positive rate of NF-kB RelA was 42.6%. NF-kB RelA expression in tumor tissues was also related to serum levels of IL-6 (P = 0.044) and CRP (P = 0.010). IL-6, SAA, CRP were related to depth of invasion, VEGF and SAA were correlated with lymph node metastasis. IL-6, VEGF, SAA and CRP were related to the stage. Univariate analysis demonstrated that immunostaining of NF-kB RelA, levels of IL-6, VEGF, SAA were significantly related with both disease free survival and over-all survival (OS). Multivariate analysis verified that NF-kB RelA [hazard ratio (HR): 3.40, P = 0.024] and SAA (HR: 3.39, P = 0.045) were independently associated with OS. CONCLUSION: Increased expression of NF-kB RelA and high levels of serum SAA were associated with poor OS in gastric cancer patients.
基金supported by the National Nature Science Foundation of China (81160152)
文摘Connexin 43 (Cx43) is the major structural protein of gap junctions in the ventricular myocardium and a major determinant of myocardial electrical properties. Cx43 expression is decreased in the wild type mice after myocardial infarction and this effect is attenuated in MMP-7-/- mice. Matrix metalloproteinase expression is regulated at the transcription level by the modulation of the activation of transcription factors such as activator protein (AP)-I and nuclear factor kappa-light-chain enhancer of activated B cells (NF-KB). Methods Rat myocardial cells (H9c2) were cultured and maintained at 37 ~C and 5% CO2. H9c2 cells in 6-well plates were treated with lipopolysaccharides (LPS), NF-kB inhibitor (JSH 23, 30 μ, Santa Cruz) + LPS and c-Jun N-terminal kinase (JNK) inhibitor (SP600125, 10μM, Sigma) + LPS for 6, 12 and 24 h. Apoptosis rate of cells was determined by flow cytometry. Cx43 expression was assessed by Western blotting. Results LPS induced a time-dependent apoptosis in all cell line. We have found that the treatment with LPS induced increase of apoptosis in H9c2 cells at 6 h, 12 h and 24 h, but the effect was decreased by the addition of JSH-23 and SP600125 to LPS respectively (P 〈 0.05) . LPS resulted in decreased expression of Cx43 expression at 6 h, 12 h and 24 h. However, JSH-23 and SP600125 attenuated the loss of Cx43 respectively (P 〈 0.05). Conclusion Transcription factors NF-kB and JNK/AP-1 signaling pathway participates in the regulation of LPS-induced Cx43 expression in the H9c2 cells, and maybe play an important role in regulation of Cx43 expression.
基金Supported by Shanghai Science and Technology Commission,China (03JC14037)
文摘Objective To observe the different expression of NF-kBp65 and cyclinD1 during oral carcinogenesis and to analyze the relationship between the abnormal expression of NF-kBp65 , cyclinD1, and the occurrence and development of oral carcinogenesis. Methods The streptavidin-biotin-peroxidase (S-P) immunohistochemical method was employed to detect the expression of NF-kBp65 and cyclinD1 protein in 38 rat tongue carcinogenesis specimens induced by 4-nitroquinoline 1-oxide. Results With the progress of tongue carcinogenesis, the expression of NF-kBp65, cyclinD1 was up-regulated. In normal, mild epithelial dysplasia, moderate epithelial dysplasia, severe epithelial dysplasia, carcinoma in situ and squamous cell carcinoma (SCC), the positive rate of NF-kBp65 was 20%, 20%, 50%, 62.5%, 50% and 83.33%, respectively. There was significant differences between normal and SCC ( P 〈 0. 05 ) ; while the level of cyclinD1 was 20%, 60%, 62. 5%, 87. 5% , 100% and 83. 33%, respec- tively. There was significant differences between normal and severe epithelial dysplasia, carcinoma in situ and SCC ( P 〈0.01 or P 〈 0. 05 ). There was a significant correlation between the increased levels of NF-kBp65, cyclinD1 and histopathological grade. The positive expression of NF-kBp65 was also associated with cyclinD1 in SCC ( r = 0. 7353, P 〈 0. 05 ). Conclusion The up-expression of NF-kBp65 and cyclinD1 protein may be correlated to the occurrence and the development of oral carcinoma ; activated NF-kB plays an important role in the overexpression of cyclinD1. Furthermore, NF-kB and cyclinD1 may be the useful biomarker of oral precancerous lesion.