Expression and significance of phosphorylated protein kinase B and spleen tyrosine protein kinase in different TNM stages of gastric cancer patients / 中国医师杂志

Objective To investigate the expression of phosphorylated protein kinase B (PKB/AKT) and spleen tyrosine protein kinase (Syk) in different tumor node metastasis (TNM) stages of gastric cancer patients.Methods From January 2015 to April 2018,82 patients with gastric cancer confirmed by gastroscopy and surgical pathology were enrolled in this study.All patients were selected for cancer tissue,and 30 patients were randomly selected from normal gastric mucosa at 5 cm adjacent to the tumor.Immunohistochemistry was used to detect the expression of PKB/AKT and Syk protein.To compare the expression of PKB/AKT and Syk in gastric cancer and adjacent normal tissues,and to analyze the relationship between PKB/AKT and Syk expression and clinicopathological features in gastric cancer tissues,and the correlation between PKB/AKT and Syk and TNM staging of gastric cancer patients.Results The positive expression rate of PKB/AKT in gastric cancer tissues was higher than that in adjacent tissues (P ＜ 0.05).The positive expression rate of Syk was lower than that in adjacent tissues (P ＜ 0.05).PKB/Akt and Syk gene expression in gastric cancer were related to histological grade,tumor infiltration,TNM staging,lymph node metastasis and distant metastasis (P ＜ 0.05),and the expression of PKB/AKT was significantly increased with the increase of TNM staging in gastric cancer patients,and the positive expression of Syk was significantly decreased (P ＜ 0.05).Conclusions PKB/AKT is positively correlated with TNM staging of gastric cancer patients.Syk is negatively correlated with TNM staging of gastric cancer patients.The clinical expression of PKB/AKT and Syk can be used to determine the TNM staging of gastric cancer,which provides a strong basis for tumor treatment.It is of great significance in treatment.

Expression and significance of phosphorylated protein kinase B and spleen tyrosine protein kinase in different TNM stages of gastric cancer patients / 中国医师杂志

Objective@#To investigate the expression of phosphorylated protein kinase B (PKB/AKT) and spleen tyrosine protein kinase (Syk) in different tumor node metastasis (TNM) stages of gastric cancer patients.@*Methods@#From January 2015 to April 2018, 82 patients with gastric cancer confirmed by gastroscopy and surgical pathology were enrolled in this study. All patients were selected for cancer tissue, and 30 patients were randomly selected from normal gastric mucosa at 5 cm adjacent to the tumor. Immunohistochemistry was used to detect the expression of PKB/AKT and Syk protein. To compare the expression of PKB/AKT and Syk in gastric cancer and adjacent normal tissues, and to analyze the relationship between PKB/AKT and Syk expression and clinicopathological features in gastric cancer tissues, and the correlation between PKB/AKT and Syk and TNM staging of gastric cancer patients.@*Results@#The positive expression rate of PKB/AKT in gastric cancer tissues was higher than that in adjacent tissues (P<0.05). The positive expression rate of Syk was lower than that in adjacent tissues (P<0.05). PKB/Akt and Syk gene expression in gastric cancer were related to histological grade, tumor infiltration, TNM staging, lymph node metastasis and distant metastasis (P<0.05), and the expression of PKB/AKT was significantly increased with the increase of TNM staging in gastric cancer patients, and the positive expression of Syk was significantly decreased (P<0.05).@*Conclusions@#PKB/AKT is positively correlated with TNM staging of gastric cancer patients. Syk is negatively correlated with TNM staging of gastric cancer patients. The clinical expression of PKB/AKT and Syk can be used to determine the TNM staging of gastric cancer, which provides a strong basis for tumor treatment. It is of great significance in treatment.

A spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cells

BACKGROUND: Pathologic vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury promotes the development of occlusive vascular disease. Therefore, an effective chemical agent to suppress aberrant proliferation and migration of VSMCs can be a potential therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. To find an anti-proliferative chemical agent for VSMCs, we screened an in-house small molecule library, and the selected small molecule was further validated for its anti-proliferative effect on VSMCs using multiple approaches, such as cell proliferation assays, wound healing assays, transwell migration assays, and ex vivo aortic ring assay. RESULTS: Among 43 initially screened small molecule inhibitors of kinases that have no known anti-proliferative effect on VSMCs, a spleen tyrosine kinase (Syk) inhibitor (BAY61-3606) showed significant anti-proliferative effect on VSMCs. Further experiments indicated that BAY61 attenuated the VSMC proliferation in both concentration- and time-dependent manner, and it also significantly suppressed the migration of VSMCs as assessed by both wound healing assays and transwell assays. Additionally, BAY61 suppressed the sprouting of VSMCs from endothelium-removed aortic rings. CONCLUSION: The present study identified a Syk kinase inhibitor as a potent VSMC proliferation and migration inhibitor and warrants further studies to elucidate its underlying molecular mechanisms, such as its primary target, and to validate its in vivo efficacy as a therapeutic agent for restenosis and atherosclerosis.

Britanin Suppresses IgE/Ag-Induced Mast Cell Activation by Inhibiting the Syk Pathway

The aim of this study was to determine whether britanin, isolated from the flowers of Inula japonica (Inulae Flos), modulates the generation of allergic inflammatory mediators in activated mast cells. To understand the biological activity of britanin, the authors investigated its effects on the generation of prostaglandin D2 (PGD2), leukotriene C4 (LTC4), and degranulation in IgE/Ag-induced bone marrow-derived mast cells (BMMCs). Britanin dose dependently inhibited degranulation and the generations of PGD2 and LTC4 in BMMCs. Biochemical analyses of IgE/Ag-mediated signaling pathways demonstrated that britanin suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes, including phospholipase Cgamma1 (PLCgamma1)-mediated calcium influx, the activation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase and p38), and the nuclear factor-kappaB (NF-kappaB) pathway. Taken together, the findings of this study suggest britanin suppresses degranulation and eicosanoid generation by inhibiting the Syk-dependent pathway and britanin might be useful for the treatment of allergic inflammatory diseases.