目的:探究病理性近视脉络膜新生血管(PM-CNV)患者玻璃体内注射抗血管内皮生长因子(VEGF)药物的远期疗效及其影响因素。方法:回顾性病例对照研究。分析2020年1月至2023年2月在南阳南石医院接受玻璃体内注射抗VEGF药物治疗的145例PM-CNV...目的:探究病理性近视脉络膜新生血管(PM-CNV)患者玻璃体内注射抗血管内皮生长因子(VEGF)药物的远期疗效及其影响因素。方法:回顾性病例对照研究。分析2020年1月至2023年2月在南阳南石医院接受玻璃体内注射抗VEGF药物治疗的145例PM-CNV患者的临床资料,观察患者治疗前后不同时间点的最佳矫正视力(BCVA)及黄斑中心视网膜厚度(CMT)情况;根据随访2 a预后情况将患者分为疗效良好组和疗效不良组,比较两组患者一般资料,多因素Logistic回归分析患者疗效不良的影响因素;基于影响因素构建PM-CNV患者疗效不良的风险预测模型,采用受试者工作特征(ROC)曲线评估该模型的预测价值。结果:与治疗前相比,治疗后1、3、6、12、24 mo CMT显著降低、BCVA显著改善(均P<0.05)。与治疗后1 mo相比,治疗后3、6、12、24 mo CMT显著降低、BCVA显著改善(均P<0.05)。与治疗后3 mo相比,治疗后6、12、24 mo CMT显著降低、BCVA显著改善(均P<0.05)。与治疗后6 mo相比,治疗后24 mo BCVA显著改善(P<0.05)。相较于疗效良好组,疗效不良组患者年龄≥50岁占比更高,病程更长、注射次数更多、治疗前BCVA较差、治疗前CMT更厚(均P<0.05)。病程长、注射次数较多、治疗前BCVA较差、治疗前CMT厚是PM-CNV患者玻璃体内注射抗VEGF药物疗效不良的影响因素(均P<0.05)。基于影响因素构建联合预测模型,ROC结果显示,该联合模型预测PM-CNV患者疗效不良的曲线下面积(AUC)为0.756(95%CI:0.678-0.824),灵敏度86.27%、特异度62.77%、约登指数0.490,该联合模型预测效能良好。结论:抗VEGF药物能改善PM-CNV患者视力,降低CMT,其中病程长、注射次数较多、治疗前BCVA较差、治疗前CMT较厚是PM-CNV患者疗效不良的影响因素。展开更多
Objectives:Vascular endothelial growth factor(VEGF)regulates tumor vascularization in response to hypoxia and inflammatory signals.The polyphenol curcumin is supposed to interfere with inflammation-induced VEGF secret...Objectives:Vascular endothelial growth factor(VEGF)regulates tumor vascularization in response to hypoxia and inflammatory signals.The polyphenol curcumin is supposed to interfere with inflammation-induced VEGF secretion and might therefore support anti-VEGF-based treatments.We aimed to investigate the interaction between curcumin and the inflammatory cytokine Interleukin-1β(IL-1β)for VEGF secretion in breast cancer cell lines representing major breast cancer subtypes.Methods:VEGF in cell cultures was detected by Western blot and enzyme-linked immunosorbent assay(ELISA).Kinase phosphorylation was investigated by Western blotting.Gene expressions were analyzed by correlation tests.VEGF was evaluated in a retrospective breast cancer cohort by immunohistochemistry.Survival analysis was performed by the Kaplan-Meier algorithm.Results:VEGF secretion and kinase signaling in response to IL-1βand curcumin varied significantly for the cell lines MCF-7(Luminal A),SK-BR-3(HER2/neu+),MDA-MB-231,and UACC-3199(triple negative breast cancer).All cell lines increased VEGF secretion under hypoxia,but IL-1βincreased VEGF secretion only in MCF-7 cells.Curcumin inhibited VEGF secretion in MDA-MB-231,but increased it in MCF-7 and UACC-3199 cells.Curcumin induced phosphorylation of extracellular signal-regulated kinase(ERK)and p38-mitogen-activated protein kinase(p38-MAPK).However,inhibitor experiments demonstrated that ERK was more important for VEGF secretion.In gene expression data from the METABRIC study,no clear correlation of hypoxia-induced factor(HIF1A),IL-1β,and VEGF mRNA expression was observed;however,a suggested crosstalk of hypoxia and inflammatory pathways was observed.Conclusion:These dissimilar responses of breast cancer cell lines suggest that therapy efficiency with anti-VEGF,anti-IL-1β,or curcumin will also vary within breast cancers.展开更多
文摘目的:探究病理性近视脉络膜新生血管(PM-CNV)患者玻璃体内注射抗血管内皮生长因子(VEGF)药物的远期疗效及其影响因素。方法:回顾性病例对照研究。分析2020年1月至2023年2月在南阳南石医院接受玻璃体内注射抗VEGF药物治疗的145例PM-CNV患者的临床资料,观察患者治疗前后不同时间点的最佳矫正视力(BCVA)及黄斑中心视网膜厚度(CMT)情况;根据随访2 a预后情况将患者分为疗效良好组和疗效不良组,比较两组患者一般资料,多因素Logistic回归分析患者疗效不良的影响因素;基于影响因素构建PM-CNV患者疗效不良的风险预测模型,采用受试者工作特征(ROC)曲线评估该模型的预测价值。结果:与治疗前相比,治疗后1、3、6、12、24 mo CMT显著降低、BCVA显著改善(均P<0.05)。与治疗后1 mo相比,治疗后3、6、12、24 mo CMT显著降低、BCVA显著改善(均P<0.05)。与治疗后3 mo相比,治疗后6、12、24 mo CMT显著降低、BCVA显著改善(均P<0.05)。与治疗后6 mo相比,治疗后24 mo BCVA显著改善(P<0.05)。相较于疗效良好组,疗效不良组患者年龄≥50岁占比更高,病程更长、注射次数更多、治疗前BCVA较差、治疗前CMT更厚(均P<0.05)。病程长、注射次数较多、治疗前BCVA较差、治疗前CMT厚是PM-CNV患者玻璃体内注射抗VEGF药物疗效不良的影响因素(均P<0.05)。基于影响因素构建联合预测模型,ROC结果显示,该联合模型预测PM-CNV患者疗效不良的曲线下面积(AUC)为0.756(95%CI:0.678-0.824),灵敏度86.27%、特异度62.77%、约登指数0.490,该联合模型预测效能良好。结论:抗VEGF药物能改善PM-CNV患者视力,降低CMT,其中病程长、注射次数较多、治疗前BCVA较差、治疗前CMT较厚是PM-CNV患者疗效不良的影响因素。
基金funded by the Deutsche Forschungsgemeinschaft(DFG)grant number(KA2663/3-1)supported by the Ministry of Science,Research and Cultural Affairs of the State of Brandenburg.
文摘Objectives:Vascular endothelial growth factor(VEGF)regulates tumor vascularization in response to hypoxia and inflammatory signals.The polyphenol curcumin is supposed to interfere with inflammation-induced VEGF secretion and might therefore support anti-VEGF-based treatments.We aimed to investigate the interaction between curcumin and the inflammatory cytokine Interleukin-1β(IL-1β)for VEGF secretion in breast cancer cell lines representing major breast cancer subtypes.Methods:VEGF in cell cultures was detected by Western blot and enzyme-linked immunosorbent assay(ELISA).Kinase phosphorylation was investigated by Western blotting.Gene expressions were analyzed by correlation tests.VEGF was evaluated in a retrospective breast cancer cohort by immunohistochemistry.Survival analysis was performed by the Kaplan-Meier algorithm.Results:VEGF secretion and kinase signaling in response to IL-1βand curcumin varied significantly for the cell lines MCF-7(Luminal A),SK-BR-3(HER2/neu+),MDA-MB-231,and UACC-3199(triple negative breast cancer).All cell lines increased VEGF secretion under hypoxia,but IL-1βincreased VEGF secretion only in MCF-7 cells.Curcumin inhibited VEGF secretion in MDA-MB-231,but increased it in MCF-7 and UACC-3199 cells.Curcumin induced phosphorylation of extracellular signal-regulated kinase(ERK)and p38-mitogen-activated protein kinase(p38-MAPK).However,inhibitor experiments demonstrated that ERK was more important for VEGF secretion.In gene expression data from the METABRIC study,no clear correlation of hypoxia-induced factor(HIF1A),IL-1β,and VEGF mRNA expression was observed;however,a suggested crosstalk of hypoxia and inflammatory pathways was observed.Conclusion:These dissimilar responses of breast cancer cell lines suggest that therapy efficiency with anti-VEGF,anti-IL-1β,or curcumin will also vary within breast cancers.
