目的:研究发现,前列腺特异性膜抗原(prostrate specific membrane antigen,PSMA)在除前列腺癌之外多种肿瘤的新生血管内皮细胞(Neovascular Endothelial Cells,NEC)中表达为探讨PSMA在非小细胞肺癌(Non small cell lung cancer,NSCLC)...目的:研究发现,前列腺特异性膜抗原(prostrate specific membrane antigen,PSMA)在除前列腺癌之外多种肿瘤的新生血管内皮细胞(Neovascular Endothelial Cells,NEC)中表达为探讨PSMA在非小细胞肺癌(Non small cell lung cancer,NSCLC)中的表达及其与临床病理参数之间的关系。方法:共收集手术切除的159例NSCLC病理组织和42例癌旁肺组织,采用免疫组织化学染色法检测PSMA的表达情况。以χ2分析PSMA表达与临床病理参数间的关系。结果:54.72%NSCLC标本的肿瘤细胞表达PSMA,69.81%NSCLC标本的NECs检测到PSMA,癌旁肺组织细胞及血管内皮细胞均不表达PSMA。年龄小于60岁的NSCLC患者肿瘤细胞的PSMA阳性率(66.20%)明显高于≥60岁的患者的PSMA阳性率(45.50%),差异有统计学意义(P<0.01)。早期(Ⅰ期和Ⅱ期)患者NECs中PSMA阳性表达率(77.60%)与晚期(Ⅲ期和Ⅳ期)患者的阳性率(57.40%)比较,差异有统计学意义(P<0.01)。肿瘤细胞或NECs的PSMA表达与性别、病理类型、瘤体大小以及是否存在淋巴结转移均无关(P>0.05)。结论:PSMA可能是NSCLC的一个诊断标志和肿瘤血管生成有关的治疗靶点。展开更多
Aim To study the proliferative effeet of hydroxysaftlor yellow A （HSYA） on cultured canine aortic endothelial cell （VEC） in normoxic （21% O2 ） or hypoxic （10% O2 ） culture and the underlying mechanism. Methods...Aim To study the proliferative effeet of hydroxysaftlor yellow A （HSYA） on cultured canine aortic endothelial cell （VEC） in normoxic （21% O2 ） or hypoxic （10% O2 ） culture and the underlying mechanism. Methods The endothelial cells were scratched from trypsined canine aorta endothelium. HSYA was added to the cells at final concentrations of 1 × 10^-3, 1 × 10^-4 and 1 × 10^-5 mol· L^-1, respectively. VEGF （2.6 × 10^-7 mol· L^-1 ）-treated cells were used as the positive control. The proliferative effect of HSYA on VEC was determined at 48, 72, 96, and 120 h in normoxic culture by MTI＂ assay. Similarly, the proliferation of VEC was determined at 12, 24, 48, and 72 h in hypoxic culture by MTF assay. The effects of HSYA on VEC proliferation and VEGF secretion were investigated by MTr and ELISA assays at the presence of the antibodies to VEGF and VEGF receptors. Results Pretreatment with HSYA at concentrations of 1 × 10^-3 and 1 × 10^-4 mol· L^-1 enhanced VEC proliferation in normoxic culture. The most significant enhancing effect of HSYA on VEC proliferation was achieved at 24, 48, and 72 h in hypoxic culture in concentration-dependent and time-dependent manner. HSYA at 1 × 10^-3 mol·L^-1 showed a potency similar to VEGF at 2.6 × 10^-7 mol·L^-1 . Pretreatment with the antibodies of Flt-1, KDR or VEGF blocked the proliferative effect of HSYA with similar potencies. Antibodies of Fit-1 or VEGF antagonized the promoting effect of HSYA on VEGF secretion. Conclusion HSYA promotes VEC proliferation either in normoxic or hypoxic culture, especially in the latter condition. This effect of HSYA is at least partly mediated by VEGF and VEGF receptor.展开更多
Endothelial cilia are microtubule-based hair-like protrusions in the lumen of blood vessels that function as fluid mechanosensors to regulate vascular hemodynamics. However, the functions of endothelial cilia in vascu...Endothelial cilia are microtubule-based hair-like protrusions in the lumen of blood vessels that function as fluid mechanosensors to regulate vascular hemodynamics. However, the functions of endothelial cilia in vascular development remain controversial. In this study, depletion of several key proteins responsible for ciliogenesis allows us to identify a cilium-independent role for intraflagellar transport 88(IFT88) in mammalian angiogenesis. Disruption of primary cilia by heat shock does not affect the angiogenic process. However, depletion of IFT88 significantly inhibits angiogenesis both in vitro and in vivo. IFT88 mediates angiogenesis by regulating the migration, polarization, proliferation, and oriented division of vascular endothelial cells. Further mechanistic studies demonstrate that IFT88 interacts with c-tubulin and microtubule plus-end tracking proteins and promotes microtubule stability. Our findings indicate that IFT88 regulates angiogenesis through its actions in microtubule-based cellular processes, independent of its role in ciliogenesis.展开更多
文摘目的:研究发现,前列腺特异性膜抗原(prostrate specific membrane antigen,PSMA)在除前列腺癌之外多种肿瘤的新生血管内皮细胞(Neovascular Endothelial Cells,NEC)中表达为探讨PSMA在非小细胞肺癌(Non small cell lung cancer,NSCLC)中的表达及其与临床病理参数之间的关系。方法:共收集手术切除的159例NSCLC病理组织和42例癌旁肺组织,采用免疫组织化学染色法检测PSMA的表达情况。以χ2分析PSMA表达与临床病理参数间的关系。结果:54.72%NSCLC标本的肿瘤细胞表达PSMA,69.81%NSCLC标本的NECs检测到PSMA,癌旁肺组织细胞及血管内皮细胞均不表达PSMA。年龄小于60岁的NSCLC患者肿瘤细胞的PSMA阳性率(66.20%)明显高于≥60岁的患者的PSMA阳性率(45.50%),差异有统计学意义(P<0.01)。早期(Ⅰ期和Ⅱ期)患者NECs中PSMA阳性表达率(77.60%)与晚期(Ⅲ期和Ⅳ期)患者的阳性率(57.40%)比较,差异有统计学意义(P<0.01)。肿瘤细胞或NECs的PSMA表达与性别、病理类型、瘤体大小以及是否存在淋巴结转移均无关(P>0.05)。结论:PSMA可能是NSCLC的一个诊断标志和肿瘤血管生成有关的治疗靶点。
文摘Aim To study the proliferative effeet of hydroxysaftlor yellow A （HSYA） on cultured canine aortic endothelial cell （VEC） in normoxic （21% O2 ） or hypoxic （10% O2 ） culture and the underlying mechanism. Methods The endothelial cells were scratched from trypsined canine aorta endothelium. HSYA was added to the cells at final concentrations of 1 × 10^-3, 1 × 10^-4 and 1 × 10^-5 mol· L^-1, respectively. VEGF （2.6 × 10^-7 mol· L^-1 ）-treated cells were used as the positive control. The proliferative effect of HSYA on VEC was determined at 48, 72, 96, and 120 h in normoxic culture by MTI＂ assay. Similarly, the proliferation of VEC was determined at 12, 24, 48, and 72 h in hypoxic culture by MTF assay. The effects of HSYA on VEC proliferation and VEGF secretion were investigated by MTr and ELISA assays at the presence of the antibodies to VEGF and VEGF receptors. Results Pretreatment with HSYA at concentrations of 1 × 10^-3 and 1 × 10^-4 mol· L^-1 enhanced VEC proliferation in normoxic culture. The most significant enhancing effect of HSYA on VEC proliferation was achieved at 24, 48, and 72 h in hypoxic culture in concentration-dependent and time-dependent manner. HSYA at 1 × 10^-3 mol·L^-1 showed a potency similar to VEGF at 2.6 × 10^-7 mol·L^-1 . Pretreatment with the antibodies of Flt-1, KDR or VEGF blocked the proliferative effect of HSYA with similar potencies. Antibodies of Fit-1 or VEGF antagonized the promoting effect of HSYA on VEGF secretion. Conclusion HSYA promotes VEC proliferation either in normoxic or hypoxic culture, especially in the latter condition. This effect of HSYA is at least partly mediated by VEGF and VEGF receptor.
基金supported by grants from the National Key R&D Program of China(2017YFA0503502)the National Natural Science Foundation of China(31730050,31871347,and 31900502)。
文摘Endothelial cilia are microtubule-based hair-like protrusions in the lumen of blood vessels that function as fluid mechanosensors to regulate vascular hemodynamics. However, the functions of endothelial cilia in vascular development remain controversial. In this study, depletion of several key proteins responsible for ciliogenesis allows us to identify a cilium-independent role for intraflagellar transport 88(IFT88) in mammalian angiogenesis. Disruption of primary cilia by heat shock does not affect the angiogenic process. However, depletion of IFT88 significantly inhibits angiogenesis both in vitro and in vivo. IFT88 mediates angiogenesis by regulating the migration, polarization, proliferation, and oriented division of vascular endothelial cells. Further mechanistic studies demonstrate that IFT88 interacts with c-tubulin and microtubule plus-end tracking proteins and promotes microtubule stability. Our findings indicate that IFT88 regulates angiogenesis through its actions in microtubule-based cellular processes, independent of its role in ciliogenesis.
