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Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that exhibits high expression in various tumors and is associated with a poor prognosis. FAK activation promotes tumor growth, invasion, metastasis, and angiogenesis via both kinase-dependent and kinase-independent pathways. Moreover, FAK is crucial for sustaining the tumor microenvironment. The inhibition of FAK impedes tumorigenesis, metastasis, and drug resistance in cancer. Therefore, developing targeted inhibitors against FAK presents a promising therapeutic strategy. To date, numerous FAK inhibitors, including IN10018, defactinib, GSK2256098, conteltinib, and APG-2449, have been developed, which have demonstrated positive anti-tumor effects in preclinical studies and are undergoing clinical trials for several types of tumors. Moreover, many novel FAK inhibitors are currently in preclinical studies to advance targeted therapy for tumors with aberrantly activated FAK. The benefits of FAK degraders, especially in terms of their scaffold function, are increasingly evident, holding promising potential for future clinical exploration and breakthroughs. This review aims to clarify FAK's role in cancer, offering a comprehensive overview of the current status and future prospects of FAK-targeted therapy and combination approaches. The goal is to provide valuable insights for advancing anti-cancer treatment strategies.
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BACKGROUND: Atorvastatin has a cardiovascular protective effect that significantly improves endothelial function and promotes the mobilization,migration,and differentiation of endothelial progenitor cells.However,the screening of atorvastatin concentration for in vitro cell culture is not well documented. OBJECTIVE: To investigate the effects of different concentrations of atorvastatin on rat bone marrow-derived EPCs growth characteristics. METHODS: Bone marrow mononuclear cells from Sprague-Dawley rats were induced in selective culture fluid to culture EPCs. Immunofluorescence staining was used to identify cell surface markers. Harvested EPCs were divided into control group and atorvastatin groups with four different concentrations (0.01, 0.1, 1, and 10 μmol/L) for culture. The growth and proliferation of EPCs were observed under light microscope and MTT assay. Flow cytometry was used to detect apoptosis in EPCs. Nitric oxide and endothelial nitric oxide synthase levels in the culture fluid were measured by nitrate reductase method. RESULTS AND CONCLUSION: The number of cells tended to increase in the control and atorvastatin groups, and it was highest in the 1 μmol/L atorvastatin group. The cell number in the 10 μmol/L atorvastatin group began to decrease at 7 days of culture. Among the five groups, the apoptotic rate of cells was lowest in the 1 μmol/L atorvastatin group and highest in the 10 μmol/L atorvastatin group. The levels of nitric oxide and endothelial nitric oxide synthase were significantly higher in the 0.01, 0.1 and 1.0 μmol/L atorvastatin groups compared with the control group (P < 0.01), but lower in the 10 μmol/L atorvastatin group compare with the other groups (P < 0.01). Overall, atorvastatin can promote the proliferation of endothelial progenitor cells and reduce apoptosis by increasing the production of endothelial nitric oxide synthase and nitric oxide, and 1 μmol/L atorvastatin is most suitable for the EPCs culture.
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Objective:To observe the impact of diabetes mellitus (DM)on pacing parameters and postoperative com-plications in patients With implantation of permanent artificial cardiac pacemaker.Methods:A total of 80 patients With sick sinus syndrome,Who received implantation of permanent artificial cardiac pacemaker from Jun 2008 to Jun 2011,Were enrolled.According to complicated With DM or not,they Were divided into DM group (n=40)and non-DM control group (n=40).Pacing parameters and postoperative complications Were compared betWeen tWo groups.Results:There Were no significant difference in atrial and ventricular pacing threshold,sensing and of pace-maker impedance in baseline betWeen tWo groups (P>0.05).All parameters of pacemaker increased in tWo groups after implantation 12 months;compared With non-DM control group,there Were significant increase in pacing threshold [atrial:(0.59±0.23)V vs.(0.67±0.25)V,ventricular:(0.47±0.28)V vs.(0.54±0.35)V],sens-ing [atrial:(2.33±1.16)mV vs.(2.92±1.36)mV,ventricular:(12.21±4.82)mV vs.(12.77±5.36)mV], impedance [atrial:(537.12±115.32)Ωvs.(662.48±235.26)Ω,ventricular:(602.48±222.46)Ωvs.(762.41± 235.38)Ω]of pacemaker in DM group,P<0.05 or <0.01;and incidence rate of postoperative complications (12.5%)in DM group Was significantly higher than that of non-DM control group (5%),P<0.05.Conclusion:Electrocardiographic reconstruction is more severe in SSS patients complicated DM,in these patients postoperative complication incidence significantly elevates.
