A novel synthetic small molecule YF-452 inhibits tumor growth through antiangiogenesis by suppressing VEGF receptor 2 signaling

Tumor angiogenesis is characterized by abnormal vessel morphology, endowing tumor with highly hypoxia and unresponsive toward treatment. To date, mounting angiogenic factors have been discovered as therapeutic targets in antiangiogenic drug development. Among them, vascular endothelial growth factor receptor 2 （VEGFR2） inhibitors exerts potent antiangiogenic activity in tumor therapy. Therefore, it may provide a valid strategy for cancer treatment through targeting the tumor angiogenesis via VEGFR2 pathway. In this study, we established a high-profile compounds library and certificated a novel compound named N-（N-pyrrolidylacetyl）-9-（4-bromobenzyl）-l,3,4,9-tetrahydro-^-carboline （YF-452）, which remarkably inhibited the migration, invasion and tube-like structure formation of human umbilical vein endothelial cells （HUVECs） with little toxicity invitro. Rat thoracic aorta ring assay indicated that YF-452 significantly blocked the formation ofmicrovascular exvivo. In addition, YF-452 inhibited angiogenesis in chick chorioallantoic membrane （CAM） and mouse corneal micropocket assays. Moreover, YF-452 remarkably suppressed tumor growth in xenografts mice model. Furthermore, investigation of molecular mechanism revealed that YF-452 inhibited VEGF-induced phosphorylation of VEGFR2 kinase and the downstream protein kinases including extracellular signal regulated kinase （ERK）, focal adhesion kinase （FAK） and Src. These results indicate that YF-452 inhibits angiogenesis and may be a potential antiangiogenic drug candidate for cancer therapy.

颈动脉粥样硬化疾病的处理美国血管外科学会临床实践指南

美国血管外科学会（SVS）任命了一个专家委员会制定颈动脉狭窄处理的循证临床指南。在制定临床实践推荐意见过程中，该委员会使用系统评价对当前最件的证据进行了总结，采用GRADE标准对推荐意见的强度（强烈推荐为GRADEI级，一般推荐为GRADEⅡ级）和证据的质量（高、中、低和极低）进行了分级。对于轻度颈动脉狭窄患者（有症状患者狭窄程度〈50％和无症状患者狭窄程度〈60％），推荐进行最佳的内科治疗而非血管重建术（I级推荐，高质量证据）。对于有症状中到重度狭窄患者（狭窄程度≥50％），推荐行颈动脉内膜切除术（CEA）＋最佳的内科治疗（I级推荐，高质量证据）。对于围手术期风险高的有症状巾到重度狭窄患者（狭窄程度≥50％），建议采用颈动脉支架置入术作为其替代治疗手段（Ⅱ级推荐，低质量证据）。对于中到重度狭窄的无症状患者（狭窄程度≥60％），只要围手术期风险较低，就推荐行CEA＋内科治疗（I级推荐，高质量证据）。对于中到重度狭窄的尢症状患者（狭窄稗度≥60％），不推荐行颈动脉支架置入术（I级推荐，低质量证据）。颈动脉狭窄≥80％但存在CEA高危解剖学风险的患者可能是一个例外。