BACKGROUND We present a case of an EWSR1/FUS::NFATC2 rearranged sarcoma in the left forearm and analyze its clinicopathological and molecular features.CASE SUMMARY The patient is a 23-year-old woman.Microscopically,th...BACKGROUND We present a case of an EWSR1/FUS::NFATC2 rearranged sarcoma in the left forearm and analyze its clinicopathological and molecular features.CASE SUMMARY The patient is a 23-year-old woman.Microscopically,the tumor cells were medium-sized round cells arranged in small nests.The cytoplasm was clear,nuclei were relatively uniform,chromatin was dense,nucleoli were visible,and mitotic figures were rare.Immunohistochemically,the tumor cells were positive for Vimentin,INI-1,CD99,NKX2.2,CyclinD1,friend leukaemia virus integration 1,and NKX3.1.Next-generation sequencing revealed the presence of the EWSR1-NFATC2 fusion gene.EWSR1/FUS::NFATC2 rearranged sarcomas are rare and can easily be misdiagnosed.CONCLUSION Clinical imaging,immunohistochemistry,and molecular pathology should be considered to confirm the diagnosis.展开更多
骨骼正常的新陈代谢是维持骨骼健康的重要生物过程,需要破骨细胞与成骨细胞及其他重要因子参与。实验证明,microRNAs作为一种内源性非编码RNA,在调控骨代谢方面发挥重要作用。随着研究的深入,活化T细胞核因子1(nuclear factor of activa...骨骼正常的新陈代谢是维持骨骼健康的重要生物过程,需要破骨细胞与成骨细胞及其他重要因子参与。实验证明,microRNAs作为一种内源性非编码RNA,在调控骨代谢方面发挥重要作用。随着研究的深入,活化T细胞核因子1(nuclear factor of activated T cell cytoplasmic 1,NFATc 1)在骨代谢中的作用也逐渐被发现并成为近些年的研究热点。然而,在不同miRNAs调控下,NFATc 1最终发挥的生物学功能也大不相同。本文主要综述NFATc 1与miRNAs调控骨代谢相关实验研究进展,为骨代谢疾病的诊断及治疗提供理论依据。展开更多
活化T细胞核因子(nuclear factor-activated T cell 1,NFATc1)是一种重要的转录因子。在破骨细胞中,它由上游RANKL信号通路的诱导、Ca^(2+)相关协同刺激信号通路与Ca^(2+)非依赖信号通路的扩增,Lhx2、IRF8、Mafb及Bcl6等细胞因子负反馈...活化T细胞核因子(nuclear factor-activated T cell 1,NFATc1)是一种重要的转录因子。在破骨细胞中,它由上游RANKL信号通路的诱导、Ca^(2+)相关协同刺激信号通路与Ca^(2+)非依赖信号通路的扩增,Lhx2、IRF8、Mafb及Bcl6等细胞因子负反馈诱导,在NFATc1转录过程中的启动、扩增及靶向作用三个阶段通过复杂交互的调节影响其下游各种靶基因及蛋白,最终介导破骨细胞的分化、融合及对无机和有机骨基质的降解作用。宏观上,NFATc1还受到外界机械应力的影响从而在破骨细胞生长过程中发挥作用;并且NFATc1的调节过程受其自身节律的影响。本文就NFATc1的结构、相关调节机制和对破骨细胞的作用研究进展进行综述。展开更多
目的:探讨胞浆活化T细胞核因子1(nuclear factor of activated T-cells,cytplasmic 1,NFATc1)对人卵巢癌SKOV3细胞裸鼠移植瘤生长和肿瘤脉管生成的影响及其可能机制。方法:NFATc1 si RNA转染人上皮性卵巢癌细胞株SKOV3,免疫荧光及RT-PC...目的:探讨胞浆活化T细胞核因子1(nuclear factor of activated T-cells,cytplasmic 1,NFATc1)对人卵巢癌SKOV3细胞裸鼠移植瘤生长和肿瘤脉管生成的影响及其可能机制。方法:NFATc1 si RNA转染人上皮性卵巢癌细胞株SKOV3,免疫荧光及RT-PCR测量转染效率和基因抑制率,选取效率最高的序列建立裸鼠皮下移植瘤模型,测量各组裸鼠肿瘤体积,观察NFATc1 siRNA的体内抗肿瘤作用。免疫组织化学检测各组肿瘤组织NFATc1的表达情况,并使用细胞角蛋白染色标记上皮性来源,CD34标记微血管,podoplanin标记微淋巴管。分别计算各组微血管及微淋巴管密度并进行统计学分析。应用RT-PCR及Western blot检测各组移植瘤组织NFATc1、CXC趋化因子受体2(CXCR2)、成纤维细胞生长因子2(FGF-2)及血小板源性生长因子BB(PDGF-BB)的mRNA及蛋白表达水平。结果:3条特异性序列均可显著降低NFATc1的表达水平,以siRNA-1169最佳。NFATc1在空白组及阴性对照组瘤组织高表达。干扰组抑瘤率为57.08%,且重量和体积均低于2个对照组。空白组和阴性对照组的微血管密度和微淋巴管密度明显高于干扰组。对照组比较,NFATc1 siRNA可以在mRNA水平上明显抑制NFATC1、CXCR2、FGF-2和PDGF-BB的转录。Western blot各组细胞在相应位置出现NFATc1、CXCR2、FGF-2和PDGF-BB条带,空白组与阴性对照组的吸光度最强,与干扰组比较具有显著差异。结论:NFATc1 siRNA明显抑制人卵巢癌SKOV3细胞裸鼠皮下移植瘤生长和肿瘤脉管生成,下调CXCR2、FGF-2及PDGF-BB的表达可能为其途径之一。展开更多
基金Supported by The Shenzhen Science and Technology Program,No.JCYJ20220530144407017.
文摘BACKGROUND We present a case of an EWSR1/FUS::NFATC2 rearranged sarcoma in the left forearm and analyze its clinicopathological and molecular features.CASE SUMMARY The patient is a 23-year-old woman.Microscopically,the tumor cells were medium-sized round cells arranged in small nests.The cytoplasm was clear,nuclei were relatively uniform,chromatin was dense,nucleoli were visible,and mitotic figures were rare.Immunohistochemically,the tumor cells were positive for Vimentin,INI-1,CD99,NKX2.2,CyclinD1,friend leukaemia virus integration 1,and NKX3.1.Next-generation sequencing revealed the presence of the EWSR1-NFATC2 fusion gene.EWSR1/FUS::NFATC2 rearranged sarcomas are rare and can easily be misdiagnosed.CONCLUSION Clinical imaging,immunohistochemistry,and molecular pathology should be considered to confirm the diagnosis.
文摘活化T细胞核因子(nuclear factor-activated T cell 1,NFATc1)是一种重要的转录因子。在破骨细胞中,它由上游RANKL信号通路的诱导、Ca^(2+)相关协同刺激信号通路与Ca^(2+)非依赖信号通路的扩增,Lhx2、IRF8、Mafb及Bcl6等细胞因子负反馈诱导,在NFATc1转录过程中的启动、扩增及靶向作用三个阶段通过复杂交互的调节影响其下游各种靶基因及蛋白,最终介导破骨细胞的分化、融合及对无机和有机骨基质的降解作用。宏观上,NFATc1还受到外界机械应力的影响从而在破骨细胞生长过程中发挥作用;并且NFATc1的调节过程受其自身节律的影响。本文就NFATc1的结构、相关调节机制和对破骨细胞的作用研究进展进行综述。