他莫昔芬(tamoxifen,TAM)作为雌激素受体阳性(estrogen receptor,ER+)乳腺癌的一线化疗药物使大多数患者受益,但原发性和继发性耐药问题严重影响临床治疗效果。深入研究ER+乳腺癌TAM耐药机制,改善治疗效果是当前亟待解决的问题。抑癌因...他莫昔芬(tamoxifen,TAM)作为雌激素受体阳性(estrogen receptor,ER+)乳腺癌的一线化疗药物使大多数患者受益,但原发性和继发性耐药问题严重影响临床治疗效果。深入研究ER+乳腺癌TAM耐药机制,改善治疗效果是当前亟待解决的问题。抑癌因子NDRG2(N-myc downstream regulated gene 2,NDRG2)在肿瘤发生发展中发挥重要作用,但是否参与ER+乳腺癌TAM耐药尚不清楚。本研究旨在探明NDRG2在ER+乳腺癌TAM耐药中发挥的作用和机制。通过RT-PCR与免疫印迹分析对比TAM敏感型和耐药型ER+乳腺癌细胞发现,NDRG 2的mRNA转录水平和蛋白质翻译水平在TAM耐药细胞中表达显著下调,且与耐药能力负相关(P<0.001);CCK-8细胞毒性实验和软琼脂克隆形成实验证实,在耐药细胞中过表达NDRG2可显著降低TAM药物半抑制浓度IC 50和软琼脂克隆形成率(P<0.001),逆转耐药表型。分子机制上,X-box结合蛋白1(X-box binding protein 1,XBP1)mRNA剪切实验与内质网相关降解(endoplasmic-reticulum associated degradation,ERAD)报告蛋白的结果显示,过表达NDRG2可增强耐药细胞中剪切型XBP1s mRNA转录与ERAD报告蛋白CD3ε-YFP表达(P<0.001),引发耐药细胞内质网强应激反应;免疫印迹检测结果显示,过表达NDRG2可显著提高耐药细胞中内质网应激感受器肌醇需要激酶1α(inositol requiring enzyme 1,IRE1α)的磷酸化水平及其下游因子,例如内质网EIP辅助因子(endoplasmic reticulum-localized DnaJ 4,ERdj4)、PKR蛋白激酶的细胞抑制剂(cellular Inhibitor of the PKR protein kinase,P58 IPK)、α甘露糖苷酶样应激蛋白(er degradation enhancingαmannosidase likeprotein,EDEM)和蛋白质二硫键异构酶家族A成员5(protein disulfide isomerase family a member 5,PDIA5)的表达水平(P<0.001)。小鼠异种移植瘤研究进一步证实,在耐药细胞中过表达NDRG2可增强TAM治疗效果,显著抑制耐药移植瘤生长(P<0.001)。以上研究结果表明,通过提高耐药细胞中NDRG2表达,增强TAM治疗引发的内质网强烈应激,可逆转ER+乳腺癌细胞耐药性,改善TAM治疗效果。研究结果为解决ER+乳腺癌TAM耐药问题提供了新的思路和有价值的潜在药物靶点。展开更多
In order to increase the processability and process window of the selective laser melting(SLM)-fabricated Al−Mn−Mg−Er−Zr alloy,a novel Si-modified Al−Mn−Mg−Er−Zr alloy was designed.The effect of Si alloying on the sur...In order to increase the processability and process window of the selective laser melting(SLM)-fabricated Al−Mn−Mg−Er−Zr alloy,a novel Si-modified Al−Mn−Mg−Er−Zr alloy was designed.The effect of Si alloying on the surface quality,processability,microstructure,and mechanical properties of the SLM-fabricated alloy was studied.The results showed that introducing Si into the Al−Mn−Mg−Er−Zr alloy prevented balling and keyhole formation,refined the grain size,and reduced the solidification temperature,which eliminated cracks and increased the processability and process window of the alloy.The maximum relative density of the SLM-fabricated Si/Al−Mn−Mg−Er−Zr alloy reached 99.6%.The yield strength and ultimate tensile strength of the alloy were(371±7)MPa and(518±6)MPa,respectively.These values were higher than those of the SLM-fabricated Al−Mn−Mg−Er−Zr and other Sc-free Al−Mg-based alloys.展开更多
Estrogen receptor(ER) is a vital biomarker in the development and development of breast cancer, and its status has great clinical value in clinical treatment strategy, endocrine therapy efficacy prediction, and breast...Estrogen receptor(ER) is a vital biomarker in the development and development of breast cancer, and its status has great clinical value in clinical treatment strategy, endocrine therapy efficacy prediction, and breast cancer prognosis. By specifically combining <sup>18</sup>F-FES with ER, <sup>18</sup>F-FES PET/CT imaging uses standard uptake value(SUV) to semi-quantitatively reflect the distribution of ER and its biological activity in patients, and assesses the expression of ER in breast cancer patients about primary and metastases before or after treatment, to provide a basis for personalized treatment of breast cancer. In this review, we will review the imaging principles of a new ER detection method <sup>18</sup>F-FES PET/CT, and the research progress in the clinical application of breast cancer, and compare its diagnostic and treatment value with non-specific tumor imaging <sup>18</sup>F-FDG PET/CT in breast cancer.展开更多
文摘他莫昔芬(tamoxifen,TAM)作为雌激素受体阳性(estrogen receptor,ER+)乳腺癌的一线化疗药物使大多数患者受益,但原发性和继发性耐药问题严重影响临床治疗效果。深入研究ER+乳腺癌TAM耐药机制,改善治疗效果是当前亟待解决的问题。抑癌因子NDRG2(N-myc downstream regulated gene 2,NDRG2)在肿瘤发生发展中发挥重要作用,但是否参与ER+乳腺癌TAM耐药尚不清楚。本研究旨在探明NDRG2在ER+乳腺癌TAM耐药中发挥的作用和机制。通过RT-PCR与免疫印迹分析对比TAM敏感型和耐药型ER+乳腺癌细胞发现,NDRG 2的mRNA转录水平和蛋白质翻译水平在TAM耐药细胞中表达显著下调,且与耐药能力负相关(P<0.001);CCK-8细胞毒性实验和软琼脂克隆形成实验证实,在耐药细胞中过表达NDRG2可显著降低TAM药物半抑制浓度IC 50和软琼脂克隆形成率(P<0.001),逆转耐药表型。分子机制上,X-box结合蛋白1(X-box binding protein 1,XBP1)mRNA剪切实验与内质网相关降解(endoplasmic-reticulum associated degradation,ERAD)报告蛋白的结果显示,过表达NDRG2可增强耐药细胞中剪切型XBP1s mRNA转录与ERAD报告蛋白CD3ε-YFP表达(P<0.001),引发耐药细胞内质网强应激反应;免疫印迹检测结果显示,过表达NDRG2可显著提高耐药细胞中内质网应激感受器肌醇需要激酶1α(inositol requiring enzyme 1,IRE1α)的磷酸化水平及其下游因子,例如内质网EIP辅助因子(endoplasmic reticulum-localized DnaJ 4,ERdj4)、PKR蛋白激酶的细胞抑制剂(cellular Inhibitor of the PKR protein kinase,P58 IPK)、α甘露糖苷酶样应激蛋白(er degradation enhancingαmannosidase likeprotein,EDEM)和蛋白质二硫键异构酶家族A成员5(protein disulfide isomerase family a member 5,PDIA5)的表达水平(P<0.001)。小鼠异种移植瘤研究进一步证实,在耐药细胞中过表达NDRG2可增强TAM治疗效果,显著抑制耐药移植瘤生长(P<0.001)。以上研究结果表明,通过提高耐药细胞中NDRG2表达,增强TAM治疗引发的内质网强烈应激,可逆转ER+乳腺癌细胞耐药性,改善TAM治疗效果。研究结果为解决ER+乳腺癌TAM耐药问题提供了新的思路和有价值的潜在药物靶点。
基金the National Natural Science Foundation of China(Nos.51801079,52001140)the Portugal National Funds through FCT Project(No.2021.04115).
文摘In order to increase the processability and process window of the selective laser melting(SLM)-fabricated Al−Mn−Mg−Er−Zr alloy,a novel Si-modified Al−Mn−Mg−Er−Zr alloy was designed.The effect of Si alloying on the surface quality,processability,microstructure,and mechanical properties of the SLM-fabricated alloy was studied.The results showed that introducing Si into the Al−Mn−Mg−Er−Zr alloy prevented balling and keyhole formation,refined the grain size,and reduced the solidification temperature,which eliminated cracks and increased the processability and process window of the alloy.The maximum relative density of the SLM-fabricated Si/Al−Mn−Mg−Er−Zr alloy reached 99.6%.The yield strength and ultimate tensile strength of the alloy were(371±7)MPa and(518±6)MPa,respectively.These values were higher than those of the SLM-fabricated Al−Mn−Mg−Er−Zr and other Sc-free Al−Mg-based alloys.
文摘Estrogen receptor(ER) is a vital biomarker in the development and development of breast cancer, and its status has great clinical value in clinical treatment strategy, endocrine therapy efficacy prediction, and breast cancer prognosis. By specifically combining <sup>18</sup>F-FES with ER, <sup>18</sup>F-FES PET/CT imaging uses standard uptake value(SUV) to semi-quantitatively reflect the distribution of ER and its biological activity in patients, and assesses the expression of ER in breast cancer patients about primary and metastases before or after treatment, to provide a basis for personalized treatment of breast cancer. In this review, we will review the imaging principles of a new ER detection method <sup>18</sup>F-FES PET/CT, and the research progress in the clinical application of breast cancer, and compare its diagnostic and treatment value with non-specific tumor imaging <sup>18</sup>F-FDG PET/CT in breast cancer.
