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Background and Purpose: Apatinib is a novel antiangiogenic agent that can target vascular endothelial cell growth factor 2. The aim of our study was to evaluate the efficacy and safety of apatinib mesylate in the treatment of advanced hepatocellular carcinoma (HCC) in the real world. Methods: We retrospectively analyzed 178 patients with advanced HCC who had been treated with apatinib mesylate from January 2017 to March 2020. The primary outcome indexes were progression-free survival (PFS) and overall survival (OS), and the secondary outcome indexes were overall response rate (ORR), disease control rate (DCR), and incidence of treatment-related adverse reactions. Results: Univariate analysis showed that patients with third-line treatment (p <0.001), alpha fetoprotein (AFP) ≥400 ng/ml (p <0.05), distant metastasis (p <0.05), portal vein tumor thrombus (PVTT) (p <0.05), and apatinib monotherapy (p <0.001) had shorter survival. Multivariate analysis confirmed that third-line drugs, PVTT, and combination therapy were independent prognostic factors for PFS in all patients. Univariate analysis showed that Eastern Cooperative Oncology Group (ECOG) scores (p <0.05), line of apatinib (p <0.001), AFP (p <0.001), tumor progression (p <0.05), PVTT (p <0.05), and combination therapy (p <0.001) may impact the OS. Multivariate analysis proved that AFP, PVTT, and combination therapy were independent prognostic factors for OS. The most common adverse reactions were secondary hypertension (29.21%), symptoms of fatigue (16.85%), hand and foot syndrome (16.29%), vomiting (14.04%), liver dysfunction (6.18%), and proteinuria (6.74%). Most of the adverse reactions were Grade 1 or 2. Conclusion: Apatinib mesylate is an effective treatment for advanced HCC, and its adverse reactions are relatively mild. Line of apatinib, PVTT, AFP level, and combination therapy were independent prognostic factors for patients with advanced HCC who were treated with apatinib.
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Triple-negative breast cancer (TNBC) remains a significant clinical challenge because of its high vascularity and metastatic and recurrent rates. Tumor angiogenesis is considered an important mediator in the regulation of tumor cell survival and metastasis in TNBC. Angiogenesis is induced by the binding of vascular endothelial growth factor to vascular endothelial growth factor receptor 2 (VEGFR2). Focal adhesion kinase (FAK) plays an important role in regulating various cell functions in normal and cancer cells. Previous studies have focused on investigating the function of endothelial FAK in tumor cell angiogenesis. However, the association between tumor FAK and VEGFR2 in tumor angiogenesis and the possible mechanisms of this remain unclear. In this study, we used a public database and human specimens to examine the association between FAK and VEGFR2. At the same time, we verified the association between FAK and VEGFR2 through several experimental methods, such as quantitative real-time polymerase chain reaction, Western blotting, and next-generation sequencing. In addition, we used the endothelial cell model, zebrafish, and xenograft animal models to investigate the role of FAK in TNBC angiogenesis. We found that FAK and VEGFR2 were positively correlated in patients with TNBC. VEGFR2 and several other angiogenesis-related genes were regulated by FAK. In addition, FAK regulated VEGFR2 and VEGF protein expression in TNBC cells. Functional assays showed that FAK knockdown inhibited endothelial tube formation and zebrafish angiogenesis. An animal model showed that FAK inhibitors could suppress tumor growth and tumor vascular formation. FAK promotes angiogenesis in TNBC cells by regulating VEGFR2 expression. Therefore, targeting FAK could be another antiangiogenic strategy for TNBC treatment.
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OBJECTIVE: We investigated the correlation between vascular endothelial growth factor 2 (VEGFR2) polymorphism and glioma risk among Chinese population. METHOD: Case-control study design was adopted, and blood samples and clinical data of 250 glioma cases and 260 control subjects were collected. Epidemiological questionnaire survey was performed, and DNA extraction, concentration normalization and packaging were carried out using Qiagen Blood Kit. TaqMan method was performed for VEGFR2 rs2071559 genotyping. RESULTS: C allele of VEGFR2 rs2071559 genotype was the susceptibility allele contributing to the risk of glioma (OR=1.813, 95% CI: 1.393-2.359, P=0.014). CC genotypes of VEGFR2 rs2071559 were associated with increased risk of glioma (OR=2.068, 95% CI: 1.164-3.674, P=0.014; Adjusted OR=1.883, 95% CI: 1.430~3.013, P=0.018). CONCLUSION: CC genotypes of VEGFR2 rs2071559 were associated with glioma risk among Chinese population. However, the role of VEGFR2 rs2071559 polymorphism in glioma susceptibility remains to be further clarified.