AIM: To examine the effects of Helicobacter pylori(Hpylori) infection on the invasiveness of gastric cancer cells,and to elucidate its mechanism. METHODS: Gastric carcinoma cells, MKN-45, were incubated with CagA-posi...AIM: To examine the effects of Helicobacter pylori(Hpylori) infection on the invasiveness of gastric cancer cells,and to elucidate its mechanism. METHODS: Gastric carcinoma cells, MKN-45, were incubated with CagA-positive H pylori, and cell invasion was determined by Matrigel analysis.The expression of matrix metallopr-oteinase-9 (MMP-9),vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) were assessed by Western-blot analysis, and transcriptional activation of the COX-2 promoter was examined by measuring luciferase and β-galactosidase activities. Lastly,the proteinDNA interaction was confirmed by an electrophoretic mobility shift assay. RESULTS: The current studies showed that: (1) incubation of CagA-positive H pylori with MKN-45 cells significantly promotes gastric cancer cells invasion, and this effect is attenuated by pre-treatment with NS-398, a COX-2 inhibitor, or PDTC,a nuclear factor κB (NF-κB) inhibitor;(2) the induction of MKN-45 cells invasion by Hpylori is associated with increases in COX-2, MMP-9, and VEGF protein expression, and co-incubation of NS-398 or PDTC significantly reduces these effects;(3) H pylori infection transactivates COX-2 promoter activity and increases the binding of NF-κB to this promoter. CONCLUSION: Our data demonstrate that H pylori infection promotes gastric epithelial cells invasion by activating MMP-9 and VEGF expression. These effects appear to be mediated through a NF-κB and COX-2 mediated pathway, as COX-2 or NF-κB inhibitor significantly attenuate the invasiveness of gastric cancer cells and the expressions of MMP-9 and VEGF protein.展开更多
AIM: To evaluate immunoexpression of cyclooxygenase-2 (COX-2) in primary gastric carcinomas and respective lymph node metastases. METHODS: Immunohistochemistry to analyze COX-2 expression was performed on tissue micro...AIM: To evaluate immunoexpression of cyclooxygenase-2 (COX-2) in primary gastric carcinomas and respective lymph node metastases. METHODS: Immunohistochemistry to analyze COX-2 expression was performed on tissue microarray slices obtained from 36 specimens of gastrectomy and satellite lymph nodes from patients with gastric carcinoma. RESULTS: Immunostaining was seen in most cases, and COX-2 expression was higher in lymph node me-tastases than in corresponding primary gastric tumors of intestinal, diffuse and mixed carcinomas, with a statistically signif icant difference in the diffuse histotype (P = 0.0108). CONCLUSION: COX-2 immunoexpression occurs frequently in primary gastric carcinomas, but higher expression of this enzyme is observed in lymph node metastases of the diffuse histotype.展开更多
Gastric cancer is one of common malignant tumors from a global perspective, and its morbidity ranks the forth and also the second largest cause of cancer-related death worldwide. Many factors can cause gastric cancer,...Gastric cancer is one of common malignant tumors from a global perspective, and its morbidity ranks the forth and also the second largest cause of cancer-related death worldwide. Many factors can cause gastric cancer, including helicobacter pylori infection, chronic inflammation, genetic factors et al. Among all of these, helicobacter pylori infection can significantly increase the production of reactive oxygen species（ROS） and reactive nitrogen species（RNS） in human stomach, which can cause the oxidative stress. Oxidative stress plays an important role in the pathogenesis of gastro-intestinal diseases such as mucosal damage, gastro-intestinal ulcers and cancer. Modern therapeutic treatments such as surgery and chemotherapy have undesired side effects, so the antioxidant therapy gains more and more attentions. Antioxidant therapy system comprises of various antioxidants（SOD, catalase, glutathione peroxidase and carnosine） and Chinese herbal medicine, which is mainly focused on the chemoprevention. Natural products and their derivatives, such as tea polyphenol, resveratrol and vitamins, have some potential benefits on their chemoprevention. Besides, much work has been done to understand the role of dietary factors playing in the prevention of gastrointestinal cancers. In this review based on some valuable studies, we aim to make some brief summaries about risk factors, pathogenic mechanism of oxidative stress and antioxidants therapy in gastric cancer.展开更多
基金Supported by the Taichung Veterans General Hospital Research Grant: TCVGH-933308C
文摘AIM: To examine the effects of Helicobacter pylori(Hpylori) infection on the invasiveness of gastric cancer cells,and to elucidate its mechanism. METHODS: Gastric carcinoma cells, MKN-45, were incubated with CagA-positive H pylori, and cell invasion was determined by Matrigel analysis.The expression of matrix metallopr-oteinase-9 (MMP-9),vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) were assessed by Western-blot analysis, and transcriptional activation of the COX-2 promoter was examined by measuring luciferase and β-galactosidase activities. Lastly,the proteinDNA interaction was confirmed by an electrophoretic mobility shift assay. RESULTS: The current studies showed that: (1) incubation of CagA-positive H pylori with MKN-45 cells significantly promotes gastric cancer cells invasion, and this effect is attenuated by pre-treatment with NS-398, a COX-2 inhibitor, or PDTC,a nuclear factor κB (NF-κB) inhibitor;(2) the induction of MKN-45 cells invasion by Hpylori is associated with increases in COX-2, MMP-9, and VEGF protein expression, and co-incubation of NS-398 or PDTC significantly reduces these effects;(3) H pylori infection transactivates COX-2 promoter activity and increases the binding of NF-κB to this promoter. CONCLUSION: Our data demonstrate that H pylori infection promotes gastric epithelial cells invasion by activating MMP-9 and VEGF expression. These effects appear to be mediated through a NF-κB and COX-2 mediated pathway, as COX-2 or NF-κB inhibitor significantly attenuate the invasiveness of gastric cancer cells and the expressions of MMP-9 and VEGF protein.
基金Supported by Institute of Molecular Pathology and Immunology of the University of PortoCoordination for the Development of Post-Graduation ProgramsNational Council for Scientific and Technological Development
文摘AIM: To evaluate immunoexpression of cyclooxygenase-2 (COX-2) in primary gastric carcinomas and respective lymph node metastases. METHODS: Immunohistochemistry to analyze COX-2 expression was performed on tissue microarray slices obtained from 36 specimens of gastrectomy and satellite lymph nodes from patients with gastric carcinoma. RESULTS: Immunostaining was seen in most cases, and COX-2 expression was higher in lymph node me-tastases than in corresponding primary gastric tumors of intestinal, diffuse and mixed carcinomas, with a statistically signif icant difference in the diffuse histotype (P = 0.0108). CONCLUSION: COX-2 immunoexpression occurs frequently in primary gastric carcinomas, but higher expression of this enzyme is observed in lymph node metastases of the diffuse histotype.
基金National Natural Science Foundation of China(Grant Nos.31471338,81260338)
文摘Gastric cancer is one of common malignant tumors from a global perspective, and its morbidity ranks the forth and also the second largest cause of cancer-related death worldwide. Many factors can cause gastric cancer, including helicobacter pylori infection, chronic inflammation, genetic factors et al. Among all of these, helicobacter pylori infection can significantly increase the production of reactive oxygen species（ROS） and reactive nitrogen species（RNS） in human stomach, which can cause the oxidative stress. Oxidative stress plays an important role in the pathogenesis of gastro-intestinal diseases such as mucosal damage, gastro-intestinal ulcers and cancer. Modern therapeutic treatments such as surgery and chemotherapy have undesired side effects, so the antioxidant therapy gains more and more attentions. Antioxidant therapy system comprises of various antioxidants（SOD, catalase, glutathione peroxidase and carnosine） and Chinese herbal medicine, which is mainly focused on the chemoprevention. Natural products and their derivatives, such as tea polyphenol, resveratrol and vitamins, have some potential benefits on their chemoprevention. Besides, much work has been done to understand the role of dietary factors playing in the prevention of gastrointestinal cancers. In this review based on some valuable studies, we aim to make some brief summaries about risk factors, pathogenic mechanism of oxidative stress and antioxidants therapy in gastric cancer.
