The development of human endometrial carcinoma(HEC) is a complex pathologic process involves several oncogenes and tumor suppressor genes.The full-length paired-box gene 2(pax2),a recently discovered oncogene,promotes...The development of human endometrial carcinoma(HEC) is a complex pathologic process involves several oncogenes and tumor suppressor genes.The full-length paired-box gene 2(pax2),a recently discovered oncogene,promotes cell proliferation and growth and inhibits apoptosis of HEC cells.Here,we examined the effect of pax2 small interfering RNA(siRNA) on the growth of transplanted HEC cells in nude mice.The expression of Pax2 in 21 cases of normal endometrium and 38 cases of HEC was examined by immohistochemistry(IHC).HEC models were developed by subcutaneously transferring HEC cells into nude mice,followed by treatment with empty lentivirus vector,lentivirus vector-based pax2 siRNA,and phosphate buffered saline,respectively.Four weeks later,tumor size was measured,tumor inhibition rate was calculated,and histological analyses were conducted after staining with hematoxylin and eosin.The expression of Pax2 and Bcl-2 was detected by Western blot;proliferating cell nuclear antigen(PCNA) was detected by IHC.Significant differences were observed in the positive rate of Pax2 between normal endometrium and HEC(14.2% vs.60.5%,P<0.01).The expression index of Pax2 in well differentiated tumors was 1.88±1.68,much lower than that in tumors of moderate(3.07±1.96,P<0.05) or poor differentiation(5.45±2.76,P<0.01).Tumor necrosis increased,nuclear basophilia stain decreased,tumor growth was inhibited,and PCNA,Pax2,and Bcl-2 expression was reduced in HEC models treated with pax2 siRNA.These results indicate that Pax2 expression is related to HEC tumor biology with the increased expression of Pax2 correlated to malignancy.pax2 siRNA down-regulates Pax2 expression and inhibits tumorigenesis of HEC in nude mice,possibly due to cell apoptosis and the inhibition of tumor proliferation induced by down-regulation of Bcl-2.展开更多
目的探讨源于人脑胶质瘤干细胞的绿色荧光裸小鼠皮下移植瘤组织，经长期鼠间传代后演变成纤维肉瘤的可能性。方法取浓度为1×10^6个/0.5 mL PBS的SU3胶质瘤干细胞，接种于纯合子NC-C57BL6J-增强型绿色荧光蛋白（EGFP）＋小鼠皮下，...目的探讨源于人脑胶质瘤干细胞的绿色荧光裸小鼠皮下移植瘤组织，经长期鼠间传代后演变成纤维肉瘤的可能性。方法取浓度为1×10^6个/0.5 mL PBS的SU3胶质瘤干细胞，接种于纯合子NC-C57BL6J-增强型绿色荧光蛋白（EGFP）＋小鼠皮下，致瘤后将1 mm3大小的移植瘤组织经套管针行同品系鼠间传代移植，观察移植瘤的增殖特征。取初代移植瘤和各鼠间传代的肿瘤组织进行冰冻切片，荧光显微镜下观察肿瘤组织中发绿色荧光的细胞；HE染色肿瘤组织；免疫组织化学染色检测肿瘤组织乏氧诱导因子α（HIF-α）、肿瘤坏死因子α（TNF-α）、胶质纤维酸性蛋白（GFAP）和成纤维细胞活化蛋白（FAP）的表达。结果前3代移植致瘤率是100%，肿瘤大小的个体差异较大，4-8代以后差距逐渐缩小，且增殖规律符合人脑胶质瘤裸小鼠移植模型特征。随着移植瘤传代次数增加，EGFP＋细胞在肿瘤组织中所占比例逐渐增加。HE染色显示肿瘤组织坏死、出血多见，血管丰富，核大，深染、异型明显，向肌肉间隙呈广泛侵袭性生长。免疫组织化学染色显示TNF-α＋细胞、HIF-α＋细胞广泛分布于各代移植瘤组织中，无GFAP＋细胞，90%的细胞FAP呈阳性表达，诊断为纤维肉瘤。结论源于人脑胶质瘤干细胞的裸小鼠皮下移植瘤组织经长期鼠间传代后会变成鼠源性纤维肉瘤，说明肿瘤细胞在寄生的宿主组织重构过程中能诱导成纤维间质细胞的恶性转化。展开更多
The patient-derived xenografts (PDX) model is an animal model established by transplanting primary tumors or fresh tumor tissues of patient origin directly into immunodeficient mice, which preserves the heterogeneity ...The patient-derived xenografts (PDX) model is an animal model established by transplanting primary tumors or fresh tumor tissues of patient origin directly into immunodeficient mice, which preserves the heterogeneity and survival microenvironment of the primary tumor and is widely used in preclinical and precision medicine research of tumors. This article reviews the construction of the PDX model of human bladder cancer and the progress of the application of the PDX model in bladder cancer.展开更多
文摘The development of human endometrial carcinoma(HEC) is a complex pathologic process involves several oncogenes and tumor suppressor genes.The full-length paired-box gene 2(pax2),a recently discovered oncogene,promotes cell proliferation and growth and inhibits apoptosis of HEC cells.Here,we examined the effect of pax2 small interfering RNA(siRNA) on the growth of transplanted HEC cells in nude mice.The expression of Pax2 in 21 cases of normal endometrium and 38 cases of HEC was examined by immohistochemistry(IHC).HEC models were developed by subcutaneously transferring HEC cells into nude mice,followed by treatment with empty lentivirus vector,lentivirus vector-based pax2 siRNA,and phosphate buffered saline,respectively.Four weeks later,tumor size was measured,tumor inhibition rate was calculated,and histological analyses were conducted after staining with hematoxylin and eosin.The expression of Pax2 and Bcl-2 was detected by Western blot;proliferating cell nuclear antigen(PCNA) was detected by IHC.Significant differences were observed in the positive rate of Pax2 between normal endometrium and HEC(14.2% vs.60.5%,P<0.01).The expression index of Pax2 in well differentiated tumors was 1.88±1.68,much lower than that in tumors of moderate(3.07±1.96,P<0.05) or poor differentiation(5.45±2.76,P<0.01).Tumor necrosis increased,nuclear basophilia stain decreased,tumor growth was inhibited,and PCNA,Pax2,and Bcl-2 expression was reduced in HEC models treated with pax2 siRNA.These results indicate that Pax2 expression is related to HEC tumor biology with the increased expression of Pax2 correlated to malignancy.pax2 siRNA down-regulates Pax2 expression and inhibits tumorigenesis of HEC in nude mice,possibly due to cell apoptosis and the inhibition of tumor proliferation induced by down-regulation of Bcl-2.
文摘目的探讨源于人脑胶质瘤干细胞的绿色荧光裸小鼠皮下移植瘤组织，经长期鼠间传代后演变成纤维肉瘤的可能性。方法取浓度为1×10^6个/0.5 mL PBS的SU3胶质瘤干细胞，接种于纯合子NC-C57BL6J-增强型绿色荧光蛋白（EGFP）＋小鼠皮下，致瘤后将1 mm3大小的移植瘤组织经套管针行同品系鼠间传代移植，观察移植瘤的增殖特征。取初代移植瘤和各鼠间传代的肿瘤组织进行冰冻切片，荧光显微镜下观察肿瘤组织中发绿色荧光的细胞；HE染色肿瘤组织；免疫组织化学染色检测肿瘤组织乏氧诱导因子α（HIF-α）、肿瘤坏死因子α（TNF-α）、胶质纤维酸性蛋白（GFAP）和成纤维细胞活化蛋白（FAP）的表达。结果前3代移植致瘤率是100%，肿瘤大小的个体差异较大，4-8代以后差距逐渐缩小，且增殖规律符合人脑胶质瘤裸小鼠移植模型特征。随着移植瘤传代次数增加，EGFP＋细胞在肿瘤组织中所占比例逐渐增加。HE染色显示肿瘤组织坏死、出血多见，血管丰富，核大，深染、异型明显，向肌肉间隙呈广泛侵袭性生长。免疫组织化学染色显示TNF-α＋细胞、HIF-α＋细胞广泛分布于各代移植瘤组织中，无GFAP＋细胞，90%的细胞FAP呈阳性表达，诊断为纤维肉瘤。结论源于人脑胶质瘤干细胞的裸小鼠皮下移植瘤组织经长期鼠间传代后会变成鼠源性纤维肉瘤，说明肿瘤细胞在寄生的宿主组织重构过程中能诱导成纤维间质细胞的恶性转化。
文摘目的探讨125I标记的Flt4多抗(125I-Flt4PcAb)对荷瘤小鼠前哨淋巴结(sentinel lymph node,SLN)的检测,为应用Flt4PcAb进行SLN特异性定位提供实验依据。方法建立BALB/c裸小鼠后肢荷瘤模型,7周后应用125I-Flt4PcAb检测肿瘤的SLN,健侧作为对照,切取窝淋巴结探测γ射线的每分钟计数率(count per minute,Cpm),并进行HE及角蛋白免疫组化染色;分析不同状态淋巴结摄取125I-Flt4PcAb的特点。结果BALB/c裸小鼠后肢皮下注射Tca-8113细胞悬液,移植瘤成功率达100%;患侧70枚窝淋巴结中,HE染色3枚(4.3%)出现肿瘤转移;角蛋白免疫组化染色为5枚(7.1%);125I-Flt4PcAb摄取方面,肿瘤转移淋巴结、反应性增生淋巴结和正常淋巴结之间均有显著差异(P<0.05)。结论BALB/c裸小鼠后肢皮下注射Tca-8113细胞悬液可成功致瘤,但淋巴结转移率低;免疫组化染色较HE染色检测肿瘤转移更敏感;125I-Flt4PcAb能够检测到荷瘤鼠的SLN,肿瘤转移淋巴结对125I-Flt4PcAb的摄取下降。
文摘The patient-derived xenografts (PDX) model is an animal model established by transplanting primary tumors or fresh tumor tissues of patient origin directly into immunodeficient mice, which preserves the heterogeneity and survival microenvironment of the primary tumor and is widely used in preclinical and precision medicine research of tumors. This article reviews the construction of the PDX model of human bladder cancer and the progress of the application of the PDX model in bladder cancer.
