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1Expression of p-STAT3 and vascular endothelial growth factor in MNNG-induced precancerous lesions and gastric tumors in rats显示文摘AIM: To investigate the dynamic expression of p-signal transducer and activator of transcription 3(STAT3) and vascular endothelial growth factor(VEGF) in the formation of gastric tumors induced by drinking water containing N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) in Wistar rats.METHODS: One hundred and twenty Wistar rats were randomly divided into two groups(60 in each group): Control group and Model group. The rats in each group were then randomly divided into three groups(20 in each group): C/M15, C/M25 and C/M40(15, 25 and 40 represent the number of feeding weeks from termination). Rats in the control group received normal drinking water and rats in the model group received drinking water containing 100 μg/m L MNNG. Stomach tissues were collected at the end of the 15 th, 25 th and 40 th week, respectively, for microscopic measurement using hematoxylin and eosin staining. The expression of p-STAT3 and VEGF in different pathological types of gastric tissue, including normal, inflammation, atrophy, hyperplasia and gastric stromal tumor, was observed by immunohistochemistry and Western blot, and the corelation between p-STAT3 and VEGF was analyzed. RESULTS:(1) The expression of p-STAT3 in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor were significantly increased in the model group compared with the control group(2.5 ± 1.0, 2.75 ±0.36, 6.2 ± 0.45, 5.67 ± 0.55 vs 0.75 ± 0.36, P = 0.026, 0.035, 0.001, 0.002, respectively); the expression of p-STAT3 in tissue with dysplasia was higher than that in samples with gastritis or atrophy(6.2 ± 0.45 vs 2.5 ± 1.0, P = 0.006; 6.2 ± 0.45 vs 2.75 ± 0.36, P = 0.005, respectively); however, the expression of p-STAT3 in gastritis and atrophy was not significantly different(P > 0.05);(2) the expression of VEGF in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor was significantly increased in the model group compared with normal gastric mucosa; and the expression of VEGF in tissue with dysplasia was higher than that in tissue with inflammation and atrophy(10.8 ± 1.96 vs 7.62 ± 0.25, P = 0.029; 10.8 ± 1.96 vs 6.26 ± 0.76, P = 0.033, respectively); similarly, the expression of VEGF in tissue with gastritis and atrophy was not significantly different(P > 0.05); and(3) the expression of VEGF was positively correlated with p-STAT3. CONCLUSION: p-STAT3 plays an important role in gastric cancer formation by regulating the expression of VEGF to promote the progression of gastric tumor from gastritis.Xiao-Yan Wang Lou-Lei Wang Xuan Zheng Li-Na Meng Bin Lyu Hai-Feng Jin 2016World Journal of Gastrointestinal Oncology2016,8,3:14
2Signal transducer and activator of transcription 3 regulation by novel binding partners显示文摘Signal transducers and activators of transcription(STATs) mediate essential signals for various biological processes,including immune responses,hematopoiesis,and neurogenesis. STAT3,for example,is involved in the pathogenesis of various human diseases,including cancers,autoimmune and inflammatory disorders. STAT3 activation is therefore tightly regulated at multiple levels to prevent these pathological conditions. A number of proteins have been reported to associate with STAT3 and regulate its activity. These STAT3-interacting proteins function to modulate STAT3-mediated signaling at various steps and mediate the crosstalk of STAT3 with other cellular signaling pathways. This article reviews the roles of novel STAT3 binding partners such as DAXX,zipperinteracting protein kinase,Krüppel-associated box-associated protein 1,Y14,PDZ and LIM domain 2 and signal transducing adaptor protein-2,in the regulation of STAT3-mediated signaling.Tadashi Matsuda Ryuta Muromoto Yuichi Sekine Sumihito Togi Yuichi Kitai Shigeyuki Kon Kenji Oritani 2015World Journal of Biological Chemistry2015,6,4:2
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