Objective To observe if VIR576,an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin(a1-AT)which inhibits human immunodeficiency virus type 1(HIV-1)entry into the target cells by interacting with...Objective To observe if VIR576,an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin(a1-AT)which inhibits human immunodeficiency virus type 1(HIV-1)entry into the target cells by interacting with fusion peptide(FP),can also directly inhibit CD4^(+)T cell activation in vitro.Methods Splenocytes isolated from DO11.10 OVA Tg mice were stimulated with ovalbumin or concanavalin A to test the effects of VIR576 on antigen-specific or non-antigen-specific T cell activation.Both primary CD4^(+)CD25-T cells from DO11.10 mice and CD4^(+)T cell line A2b were activated with specific antigens to evaluate the effects of VIR576.Results VIR576 inhibited antigen-specific splenocyte activation but had no significant effect on non-antigen-specific T-cell activation,which bypassed the crosstalk between the CD3-signaling complex and TCR.We furthermore observed that VIR576 could also down-regulate antigen-specific CD4^(+)T-cell activation.Conclusion Given the high susceptibility of activated CD4^(+)T cells in the mucosa to HIV-1 infection,the inhibitory effects of VIR576 on both HIV entry into the target cells and CD4^(+)T-cell activation suggest the potential of VIR576 as a microbicide for prevention of sexual transmission of HIV.展开更多
目的探讨伴破骨样巨细胞的胰腺未分化癌(undifferentiated carcinoma with osteoclast-like giant cells of the pancreas,UCOGCP)的临床病理学特征。方法回顾性分析5例UCOGCP的临床病理学特征、免疫表型及分子特征。采用免疫组化、ARMS...目的探讨伴破骨样巨细胞的胰腺未分化癌(undifferentiated carcinoma with osteoclast-like giant cells of the pancreas,UCOGCP)的临床病理学特征。方法回顾性分析5例UCOGCP的临床病理学特征、免疫表型及分子特征。采用免疫组化、ARMS-PCR(amplification refractory mutation system-polymerase chain reaction)技术检测UCOGCP的免疫组化及分子特征。结果5例UCOGCP患者中男性3例,女性2例,平均年龄55.6岁,其中4例为手术切除标本,1例为EUS-FNA标本;眼观:肿瘤最大径5.5~8.0 cm,切面灰黄色,实性质硬,局部可见坏死样物,部分病例可见白色骨样物质沉积。镜检:肿瘤细胞通常在出血或坏死区域附近,细胞黏附性差。肿瘤细胞包括三类:肿瘤性单核细胞、非肿瘤性的卵圆形或梭形单核组织细胞及破骨样巨细胞,细胞混杂分布,部分病例可见骨样基质,病理性核分裂象多见,2例合并有导管腺癌成分,1例可见神经侵犯,1例门静脉内可见癌栓,3例发生肝脏转移。免疫表型:5例单核组织细胞及破骨样巨细胞vimentin、CD68均阳性;CK(AE1/AE3)、CK7、EMA为局灶阳性(4/5);HMB-45、SMA、desmin、S-100、SOX10、SS18-SSX、HMB-45、Myogenin均阴性;Ki67增殖指数为20%~50%。其中1例进行了KRAS、NRAS、BRAF基因及TERT启动子突变检测,检测到KRAS G12D位点突变,未检测到NRAS、BRAF及TERT启动子区突变。结论UCOGCP相对较少见,此类型肿瘤的临床行为尚无法准确预测,需要积累更多病例准确了解其生物学行为。展开更多
基金Supported by National Natural Science Foundation of China(30672496 and 30801413)Guangdong Medical Research Grant(A201032)Guangdong International Cooperation Grant(2011B050200006)
文摘Objective To observe if VIR576,an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin(a1-AT)which inhibits human immunodeficiency virus type 1(HIV-1)entry into the target cells by interacting with fusion peptide(FP),can also directly inhibit CD4^(+)T cell activation in vitro.Methods Splenocytes isolated from DO11.10 OVA Tg mice were stimulated with ovalbumin or concanavalin A to test the effects of VIR576 on antigen-specific or non-antigen-specific T cell activation.Both primary CD4^(+)CD25-T cells from DO11.10 mice and CD4^(+)T cell line A2b were activated with specific antigens to evaluate the effects of VIR576.Results VIR576 inhibited antigen-specific splenocyte activation but had no significant effect on non-antigen-specific T-cell activation,which bypassed the crosstalk between the CD3-signaling complex and TCR.We furthermore observed that VIR576 could also down-regulate antigen-specific CD4^(+)T-cell activation.Conclusion Given the high susceptibility of activated CD4^(+)T cells in the mucosa to HIV-1 infection,the inhibitory effects of VIR576 on both HIV entry into the target cells and CD4^(+)T-cell activation suggest the potential of VIR576 as a microbicide for prevention of sexual transmission of HIV.
