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分子模拟在筛选HLA-A2.1高亲和性MART-1 CTL表位中的应用研究 被引量:2
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作者 王莉 吴玉章 +1 位作者 林治华 石统东 《第三军医大学学报》 CAS CSCD 北大核心 2002年第10期1166-1168,共3页
目的 探讨计算机分子模拟在CTL表位与HLA A2 1亲和力特性研究中的应用价值。方法 应用SiliconGraphics图像工作站及InsightⅡ软件 ,分别建立MART 16个CTL预测表位与HLA A2 1结合的三维结构 ,并进行分子动力学模拟 ,通过对各结合特... 目的 探讨计算机分子模拟在CTL表位与HLA A2 1亲和力特性研究中的应用价值。方法 应用SiliconGraphics图像工作站及InsightⅡ软件 ,分别建立MART 16个CTL预测表位与HLA A2 1结合的三维结构 ,并进行分子动力学模拟 ,通过对各结合特征性参数的计算 ,对各表位肽与HLA A2 1结合稳定性进行了比较。应用Merrifield固相多肽合成技术合成上述小肽 ,通过HLA A2 1与各肽亲和力分析试验 ,证实分子模拟结果的可靠性。结果 通过分子模拟手段计算所得 6个表位与HLA A2 1结合特性结果 ,基本与通过实验手段所得结果相符。结论 计算机分子模拟在CTL表位与MHC Ⅰ类分子的亲和力研究中 ,具有简单、直观、快速、准确等优点 ,该方法在筛选MHC Ⅰ类分子高亲和性CTL表位的研究中具有诱人的应用前景。 展开更多
关键词 mart-1 CTL表位 分子动力学模拟 结合亲和力分析 肿瘤免疫治疗 肿瘤抗原
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MART-1HLA-A2限制性CTL表位的预测
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作者 王莉 吴玉章 《第三军医大学学报》 CAS CSCD 北大核心 2000年第10期931-933,共3页
目的 预测黑色素瘤分化抗原MART 1的HLA A2限制性细胞毒性T淋巴细胞 (CTL)表位。方法 采用超基序与量化基序多项式方案相结合的办法 ,对目的抗原MART 1的HLA A2限制性CTL表位进行预测。结果 预测出了 6个九肽表位。结论 两种方法预... 目的 预测黑色素瘤分化抗原MART 1的HLA A2限制性细胞毒性T淋巴细胞 (CTL)表位。方法 采用超基序与量化基序多项式方案相结合的办法 ,对目的抗原MART 1的HLA A2限制性CTL表位进行预测。结果 预测出了 6个九肽表位。结论 两种方法预测结果的一致性较好 ,所预测出的 6个MART 1的HLA A2限制性CTL表位经后续实验筛选、鉴定后 ,可望用于新型MART 1肿瘤治疗性多肽疫苗的设计研究 。 展开更多
关键词 mart-1 HLA-A2 CTL表位 多肽疫苗 黑色素瘤
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MART-1研究进展 被引量:2
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作者 贾正才 《国外医学(免疫学分册)》 2000年第2期92-96,共5页
近年来 ,人类黑色素瘤相关抗原已被陆续鉴定。MART 1为黑色素瘤相关抗原中抗原性较强的一种 ,其基因已被克隆 ,抗原的性质及呈递MART 1的HLA分子已得到部分阐明。研究发现 ,在MART 1上有几个免疫优势表位 ,它们能在体内外诱导产生CT... 近年来 ,人类黑色素瘤相关抗原已被陆续鉴定。MART 1为黑色素瘤相关抗原中抗原性较强的一种 ,其基因已被克隆 ,抗原的性质及呈递MART 1的HLA分子已得到部分阐明。研究发现 ,在MART 1上有几个免疫优势表位 ,它们能在体内外诱导产生CTL免疫应答。其中 ,已有部分CTL表位被用于黑色素瘤的主动免疫治疗 ,是一种有着广阔应用前景的黑色素瘤治疗性疫苗的候选者。 展开更多
关键词 肿瘤抗原 mart-1
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乳腺癌组织中SHC1、CA153表达水平及其与患者病理特征、淋巴结转移的关系 被引量:3
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作者 万爽 王东和 +2 位作者 韩林荟 苗聪聪 何友新 《分子诊断与治疗杂志》 2025年第3期437-440,共4页
目的探讨乳腺癌组织中含有Src同源2结构域的衔接蛋白1(SHC1)、糖类抗原153(CA153)表达水平及其与患者病理特征、淋巴结转移的关系。方法选取2021年1月至2023年10月秦皇岛市第二医院收治的乳腺癌患者186例,切除癌组织和癌旁组织,分别设... 目的探讨乳腺癌组织中含有Src同源2结构域的衔接蛋白1(SHC1)、糖类抗原153(CA153)表达水平及其与患者病理特征、淋巴结转移的关系。方法选取2021年1月至2023年10月秦皇岛市第二医院收治的乳腺癌患者186例,切除癌组织和癌旁组织,分别设立乳腺癌组和癌旁组。比较两组SHC1、CA153表达差异,分析SHC1、CA153与患者病理特征的关系,采用多因素logistics回归分析探讨乳腺癌淋巴结转移的影响因素。结果乳腺癌组SHC1、CA153阳性率均高于癌旁组,差异有统计学意义(P<0.05)。SHC1表达阳性乳腺癌患者肿块直径>2 cm、组织学分级为Ⅲ级、分化程度为低分化、脉管有内栓塞占比高于SHC1表达阴性患者,差异有统计学意义(P<0.05),CA153表达阳性乳腺癌患者肿块直径>2 cm、组织学分级为Ⅲ级、分化程度为低分化、脉管有内栓塞的占比高于CA153表达阴性患者,差异有统计学意义(P<0.05)。淋巴结转移患者肿块直径>2 cm、组织学分型为Ⅲ级、分化程度为低分化、SHC1阳性表达及CA153阳性表达占比高于淋巴结未转移组,差异有统计学意义(P<0.05)。多因素分析显示,肿块直径、组织学分型、分化程度及SHC1、CA153表达是乳腺癌患者淋巴结转移的影响因素(P<0.05)。结论乳腺癌组织中SHC1、CA153均呈高表达,两指标与乳腺癌患者的病理特征及淋巴结的转移有一定关联,对评估乳腺癌患者淋巴结转移风险有一定临床价值。 展开更多
关键词 乳腺癌 含有Src同源2结构域的衔接蛋白1 糖类抗原153 淋巴结转移
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靶向叶酸受体α(FRα)的程序性细胞死亡受体1敲低型嵌合抗原受体T细胞杀伤肝癌细胞的效果分析
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作者 温军业 张浚琪 +2 位作者 任行 张海强 叶学帅 《临床肝胆病杂志》 北大核心 2025年第6期1128-1134,共7页
目的 探究靶向叶酸受体α(FRα)嵌合抗原受体(CAR)的程序性细胞死亡受体1(PD-1)敲低型T细胞(si-PD-1-CAR-T)对肝癌细胞的清除能力。方法 应用生物信息学数据库TCGA分析FRα抗原在肝癌及正常肝组织中的表达情况,以及FRα表达与肝癌患者... 目的 探究靶向叶酸受体α(FRα)嵌合抗原受体(CAR)的程序性细胞死亡受体1(PD-1)敲低型T细胞(si-PD-1-CAR-T)对肝癌细胞的清除能力。方法 应用生物信息学数据库TCGA分析FRα抗原在肝癌及正常肝组织中的表达情况,以及FRα表达与肝癌患者生存期的关系。分别将编码靶向FRα抗原的CAR结构的mRNA及mRNA联合靶向PD-1基因的小干扰RNA(siRNA)使用电穿孔仪转导入T细胞,制备FRα-CAR-T和si-PD-1-CAR-T。流式细胞术分析FRα-CAR的表达效率和PD-1的敲低效率。体外培养肝癌细胞系JHH-1和HepG2,采用流式细胞术分析FRα在肿瘤细胞表面的表达情况,将FRα-CAR-T、si-PD-1-CAR-T及空载体转导的T细胞(Mock T)作为效应细胞,JHH-1和HepG2作为靶细胞,CCK-8法检测在不同效靶比(1∶1、2.5∶1、5∶1、10∶1、20∶1)时对靶细胞的杀伤效率;采用ELISA法分别检测效应细胞与靶细胞(10∶1)共培养上清中IFN-γ和IL-2的分泌情况。计量资料符合正态分布时,两组间比较采用成组t检验,多组间比较采用单因素方差分析,进一步两两比较采用SNK检验。采用Kaplan-Meier法分析比较患者生存差异。结果 TCGA数据库分析显示,FOLR1在肝癌组织中表达水平明显升高,FOLR1高表达肝癌患者的总生存期显著低于FOLR1低表达者(P=0.013)。将m RNA转导入T细胞后,FRα-CAR在CAR-T和si-PD-1-CAR-T中的表达率可达89.8%和84.7%,使用m RNA和si RNA共转染可将T细胞的PD-1下调并维持至少7天的PD-1低表达状态。FRα抗原在JHH-1细胞中表达率为100%,而在Hep G2细胞中呈阴性表达。CCK-8结果显示,si-PD-1-CAR-T对JHH-1细胞杀伤效率显著高于FRα-CAR-T细胞(P<0.05);ELISA结果显示,FRα-CAR-T细胞与JHH-1细胞共培养时,IL-2分泌量较Mock T细胞显著增加[(1 032.50±135.90) pg/mL vs (50.26±7.87) pg/mL,P<0.001],IFN-γ分泌量显著增加[(1 430.56±184.20) pg/mL vs (89.05±11.26) pg/mL, P<0.001];si-PD-1-CAR-T与JHH-1细胞共培养后,IFN-γ和IL-2的释放水平较FRα-CAR-T均显著提高(P值均<0.05)。结论 FRα是肝癌治疗的潜在靶点,敲低T细胞PD-1可显著提高FRα-CAR-T在体外的杀伤活性。 展开更多
关键词 肝细胞 嵌合抗原受体 叶酸盐受体1 程序性细胞死亡受体1
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PD-1/PD-L1抑制剂对晚期胃癌术后患者的临床疗效及安全性
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作者 张迪 戴领 +4 位作者 张博亚 王英杰 郭琳娜 徐福田 刘莉莎 《临床误诊误治》 2025年第22期90-95,共6页
目的探讨程序性死亡受体1(PD-1)/程序性死亡受体配体1(PD-L1)抑制剂对晚期胃癌术后患者的临床疗效及安全性。方法选取2019年1月至2023年1月就诊的80例晚期胃癌术后患者为研究对象,其中40例术后采用常规化疗纳入对照组,另外40例术后应用P... 目的探讨程序性死亡受体1(PD-1)/程序性死亡受体配体1(PD-L1)抑制剂对晚期胃癌术后患者的临床疗效及安全性。方法选取2019年1月至2023年1月就诊的80例晚期胃癌术后患者为研究对象,其中40例术后采用常规化疗纳入对照组,另外40例术后应用PD-1/PD-L1抑制剂进行免疫治疗纳入观察组。比较两组复发生存时间(RFS)及总生存时间(OS)、肿瘤标志物[癌胚抗原(CEA)与细胞角蛋白19片段抗原21-1(CYFRA21-1)]、不良反应发生情况、癌组织和癌旁组织PD-1/PD-L1表达情况、Karnofsky功能状态(KPS)评分,Cox风险比例模型分析患者预后影响因素。结果癌组织PD-1、PD-L1表达阳性率远高于癌旁组织(P<0.05)。随访截止日期2025年6月,中位随访时间为28.33个月,两组共有死亡病例40例,失访2例。观察组中位OS为34.95个月(95%CI:26.56,52.01),对照组中位OS为25.71个月(95%CI:18.89,32.79),两组OS比较有统计学差异(HR=0.453,P=0.004)。观察组中位RFS为20.01个月(95%CI:10.95,41.43),对照组中位RFS为12.63个月(95%CI:7.29,17.58),两组RFS比较有统计学差异(HR=0.588,P=0.019)。两组复发转移发生率比较无统计学差异(P>0.05)。治疗后,观察组CEA、CYFRA21-1水平较对照组降低更加显著(P<0.05)。两组不良反应分度及不良反应发生率比较无统计学差异(P>0.05);两组KPS评分比较未见统计学差异(P>0.05)。PD-1、PD-L1表达均是影响晚期胃癌术后患者预后的危险因素(P<0.05)。结论PD-1/PD-L1抑制剂在提高晚期胃癌术后患者生存获益方面具有临床优势,且安全性可控,PD-1/PD-L1表达水平可作为预后评估的关键指标。 展开更多
关键词 晚期胃癌 程序性死亡受体1 程序性死亡受体配体1 免疫治疗 癌胚抗原 细胞角蛋白19片段抗原21-1 不良反应
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Early gastric cancer frequently has high expression of KKLC-1, a cancer-testis antigen 被引量:6
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作者 Nobue Futawatari Takashi Fukuyama +7 位作者 Rui Yamamura Akiko Shida Yoshihito Takahashi Yatsushi Nishi Yoshinobu Ichiki Noritada Kobayashi Hitoshi Yamazaki Masahiko Watanabe 《World Journal of Gastroenterology》 SCIE CAS 2017年第46期8200-8206,共7页
AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this stu... AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1(KK-LC-1), melanoma antigen(MAGE)-A1, MAGE-A3 and New York esophageal cancer-1(NYESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. RESULTS The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion(MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion(MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage(36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NYESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1(MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). CONCLUSION The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer. 展开更多
关键词 Cancer-testis antigen Kitakyushu lung cancer antigen-1 Melanoma antigen-A1 Melanoma antigen-A3 Gastric cancer New York esophageal cancer-1 Clinicopathological factor early stage
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骨髓基质细胞抗原1基因多态性与新疆地区帕金森病的相关性研究
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作者 宋秋霞 张晓莺 +1 位作者 李燕云 刘燕 《脑与神经疾病杂志》 2025年第3期175-180,共6页
目的 探讨骨髓基质细胞抗原1 (BST1)基因rs11931532位点、rs4698412位点多态性与帕金森病(PD)的相关性。方法 应用竞争性等位基因特异PCR(KASP)技术对新疆地区200例散发性PD(IPD)患者和197例健康对照者进行BST1基因rs11931532位点、rs46... 目的 探讨骨髓基质细胞抗原1 (BST1)基因rs11931532位点、rs4698412位点多态性与帕金森病(PD)的相关性。方法 应用竞争性等位基因特异PCR(KASP)技术对新疆地区200例散发性PD(IPD)患者和197例健康对照者进行BST1基因rs11931532位点、rs4698412位点多态性分析。结果(1)在总体样本中,PD组和对照组间rs11931532的基因型分布频率比较差异均无统计学意义(P>0.05)。进一步按照性别、年龄进行分层,在男性PD组和男性对照组间、女性PD组和女性对照组间、年龄≤68岁的PD组和年龄≤68岁对照组间、在年龄>68岁的PD组和年龄>68岁对照组间,其基因型分布频率比较差异均无统计学意义(^(均)P> 0.05)。(2)在总体样本中,PD组和对照组间rs4698412基因型、等位基因频率比较差异无统计学意义(^(均)P> 0.05)。进一步按照性别、年龄进行分层,在男性PD组和男性对照组间、女性PD组和女性对照组间、年龄≤68岁的PD组和年龄≤68岁对照组间rs4698412基因型、等位基因频率比较差异无统计学意义(^(均)P> 0.05),在年龄> 68岁的PD组和年龄> 68岁的对照组间,PD组A/A基因型频率(20.4%)高于对照组(8.40%),差异有统计学意义(P=0.036),两组间的等位基因分布差异无统计学(P> 0.05)。结论 BST1基因rs11931532位点多态性不是新疆地区PD的潜在易感位点。BST1基因rs4698412位点多态性可能是新疆地区年龄> 68岁PD患者的潜在易感位点,rs4698412 A/A是其易感基因型。 展开更多
关键词 帕金森病 骨髓基质细胞抗原1基因 多态性
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Establishment and preliminery use of hepatitis Bvirus preS1/2 antigen assay 被引量:14
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作者 CHEN Kun, HAN Bao Guang, MA Xian Kai, ZHANG He Qiu, MENG Li, WANG Guo Hua, XIA Fang, SONG Xiao Guo and LING Shi Gan 《World Journal of Gastroenterology》 SCIE CAS CSCD 1999年第6期550-552,共3页
关键词 HEPATITIS B VIRUS PreS1/*!S2 antigen ELISA HEPATITIS B E antigen/analysis
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Cancer/testis antigen, Kita-Kyushu lung cancer antigen-1 and ABCD stratification for diagnosing gastric cancers 被引量:5
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作者 Akiko Shida Takashi Fukuyama +8 位作者 Nobue Futawatari Haruki Ohmiya Yoshinobu Ichiki Tetsuro Yamashita Yatsushi Nishi Noritada Kobayashi Hitoshi Yamazaki Masahiko Watanabe Yoshihito Takahashi 《World Journal of Gastroenterology》 SCIE CAS 2020年第4期424-432,共9页
BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk... BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk of developing gastric cancer(GC).The Kita–Kyushu lung cancer antigen-1(KK-LC-1)is a Cancer/Testis antigen frequently expressed in GC.AIM To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC.METHODS We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors.The levels of serum PG I/PG II and IgG against H.pylori were measured.According to their serological status,the patients were classified into the four groups of the ABCD stratification.RESULTS Of the 77 examined patients,63(81.8%)expressed KK-LC-1.The IgG titers of H.pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1(P=0.0289 and P=0.0041,respectively).The expression of KK-LC-1 in group C[PG method(+)/H.pylori infection(+)]was as high as 93.9%high.KK-LC-1 was also detected in group A[-/-].CONCLUSION The KK-LC-1 expression in GC was associated with H.pylori infection and atrophic status,so that,KK-LC-1 may be a useful marker for the diagnosis of GC. 展开更多
关键词 Gastric cancer Tumor antigen Cancer/testis antigen Kita–Kyushu lung cancer antigen-1 Helicobacter pylori Early detection of cancer
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T cells expressing a LMP1-specific chimeric antigen receptor mediate antitumor effects against LMP1-positive nasopharyngeal carcinoma cells in vitro and in vivo 被引量:16
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作者 Xiaojun Tang Yan Zhou +4 位作者 Wenjie Li Qi Tang Renjie Chen Jin Zhu Zhenqing Feng 《The Journal of Biomedical Research》 CAS 2014年第6期468-475,共8页
T cells modified with chimeric antigen receptor are an attractive strategy to treat Epstein-Barr virus(EBV) associated malignancies.The EBV latent membrane protein 1(LMP1) is a 66-KD integral membrane protein enco... T cells modified with chimeric antigen receptor are an attractive strategy to treat Epstein-Barr virus(EBV) associated malignancies.The EBV latent membrane protein 1(LMP1) is a 66-KD integral membrane protein encoded by EBV that consists of transmembrane-spanning loops.Previously,we have identified a functional signal chain variable fragment(scFv) that specifically recognizes LMP1 through phage library screening.Here,we constructed a LMP1 specific chimeric antigen receptor containing anti-LMP1 scFv,the CD28 signalling domain,and the CD3ζchain(HELA/CAR).We tested its functional ability to target LMP1 positive nasopharyngeal carcinoma cells.HELA/CAR cells were efficiently generated using lentivirus vector encoding the LMP1-specific chimeric antigen receptor to infect activated human CD3+ T cells.The HELA/CAR T cells displayed LMP1 specific cytolytic action and produced IFN-γ and IL-2 in response to nasopharyngeal carcinoma cells overexpressing LMP1.To demonstrate in vivo anti-tumor activity,we tested the HELA/CAR T cells in a xenograft model using an LMP1 overexpressing tumor.Intratumoral injection of anti-LMP1 HELA/CAR-T cells significantly reduced tumor growth in vivo.These results show that targeting LMP1 using HELA/CAR cells could represent an alternative therapeutic approach for patients with EBV-positive cancers. 展开更多
关键词 chimeric antigen receptor LMP1 nasopharyngeal carcinoma EBV adoptive T cell therapy
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NS1 antigen: A new beam of light in the early diagnosis of dengue infection 被引量:6
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作者 Muhammad Suleman Rani Faryal +10 位作者 Muhammad Masroor Alam Salmaan Sharif Shahzad Shaukat Uzma Bashir Aamir Adnan Khurshid Mehar Angez Massab Umair Mian Muhammad Sufian Yasir Arshad Ghulam Mujtaba Syed Sohail Zahoor Zaidi 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2016年第12期1187-1189,共3页
Objective: To evaluate NS1 antigen detection ELISA for the early laboratory diagnosis of dengue virus infection. Methods: The present study was conducted to evaluate the overall positivity of NS1 antigen detection ELI... Objective: To evaluate NS1 antigen detection ELISA for the early laboratory diagnosis of dengue virus infection. Methods: The present study was conducted to evaluate the overall positivity of NS1 antigen detection ELISA and its comparison with viral RNA detection via real time PCR and Ig M antibodies detection by ELISA. Results: A total of 1 270 serum samples were tested 86%(1 097/1 270) were detected positive by one or more than one diagnostic test. Out of 1 270, 64%(807/1 270) were positive by NS1 ELISA and 52%(662/1 270), 51%(646/1 270) were positive by real-time RT-PCR and Ig M ELISA respectively.Conclusions: NS1 antigen detection ELISA is highly suitable diagnostic tools and it also has great value for use in outbreak and epidemic situation. 展开更多
关键词 DENGUE Pakistan EPIDEMIOLOGY ELISA NS1 antigen
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Divergent Primary Immune Responses Induced by Human Immunodeficiency Virus-1 gp120 and Hepatitis B Surface Antigen Determine Antibody Recall Responses 被引量:2
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作者 Li Yuan Wen-Jiang Chen +8 位作者 Jia-Ye Wang Yan Li Dan Tian Ming-Xia Wang Hao-Tong Yu Ying-Chu Xu Di Li Min Zhuang Hong Ling 《Virologica Sinica》 SCIE CAS CSCD 2018年第6期502-514,共13页
The development of a vaccine based on human immunodeficiency virus type 1(HIV-1) envelope glycoprotein(Env) that elicits potent protective antibodies against infection has been challenging. Recently, we compared the a... The development of a vaccine based on human immunodeficiency virus type 1(HIV-1) envelope glycoprotein(Env) that elicits potent protective antibodies against infection has been challenging. Recently, we compared the antibody production patterns of HIV-1 Env gp120 and hepatitis B virus surface antigen(HBsAg) to provide insights into how we may improve the protective efficacy of Env-based immunogens. Our previous study showed that HIV Env and HBsAg display different mechanisms of antibody elicitation and that T cells facilitate the responses to repeated immunizations. Here, to elucidate the detailed roles of primary immunization in immune memory response formation and antibody production, we immunized C57BL/6 mice with each antigen and evaluated the development of T follicular helper(Tfh) cells, germinal centers,and the memory responses involved in prime and boost immunizations. We found that after prime immunization, compared with HBsAg, gp120 induced higher frequencies of Tfh cells and programmed death(PD)-1^+T cells, greater major histocompatibility complex II expression on B cells, comparable activated B cells, but weaker germinal center(GC)reactions and memory B cell responses in the draining lymph nodes, accompanied by slower antibody recall responses and poor immune memory responses. The above results suggested that more PD-1^+T cells arising in primary immunization may serve as major contributors to the slow antibody recall response elicited by HIV-1 Env. 展开更多
关键词 Human IMMUNODEFICIENCY virus type 1 envelope Hepatitis B surface antigen(HBsAg) IMMUNE memory Primary IMMUNE response Programmed death-1(PD-1)
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结直肠癌组织lncRNA-UCA1表达与临床病理特征、化疗敏感性的关系
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作者 张亚利 高晓会 郭艳珍 《胃肠病学和肝病学杂志》 2025年第1期64-69,共6页
目的检测结直肠癌组织长链非编码核糖核酸-尿路上皮癌胚抗原1(long non-coding RNA-urothelial carcinoma associated 1,lncRNA-UCA1)表达,并分析其与临床病理特征、化疗敏感性的关系。方法选取2021年4月至2023年4月于河南科技大学第一... 目的检测结直肠癌组织长链非编码核糖核酸-尿路上皮癌胚抗原1(long non-coding RNA-urothelial carcinoma associated 1,lncRNA-UCA1)表达,并分析其与临床病理特征、化疗敏感性的关系。方法选取2021年4月至2023年4月于河南科技大学第一附属医院行手术治疗的结直肠癌患者111例,并取其癌旁组织作为对照。比较癌组织、癌旁组织中lncRNA-UCA1的表达;比较不同临床病理特征患者癌组织lncRNA-UCA1表达;术后化疗3个周期后随访3个月,根据化疗敏感性将患者分为抵抗组、敏感组;比较抵抗组、敏感组一般资料及癌组织lncRNA-UCA1表达;用Logistic回归模型分析化疗敏感性的影响因素;绘制Kaplan-Meier曲线分析癌组织lncRNA-UCA1表达与结直肠癌生存情况的关系。结果与癌旁组织比较,癌组织lncRNA-UCA1表达升高(P<0.05);与TNMⅡ期、中/高分化、浸润深度T 1/T 2的患者比较,TNMⅢ/Ⅳ期、未/低分化、浸润深度T 3/T 4患者癌组织lncRNA-UCA1表达升高(P<0.05);患者化疗抵抗率为46.85%;Logistic回归模型分析显示,男性(OR=3.237,95%CI:1.258~8.325)、TNMⅢ/Ⅳ期(OR=4.277,95%CI:1.615~11.325)、血红蛋白(hemoglobin,Hb)(OR=0.961,95%CI:0.940~0.983)、癌组织lncRNA-UCA1表达(OR=8.939,95%CI:1.926~41.497)是结直肠癌化疗敏感性的影响因素(P<0.05)。随访3~26个月,中位随访时间14个月。lncRNA-UCA1高表达组、低表达组生存率分别为62.50%、85.11%,Log-rank检验显示,lncRNA-UCA1高表达组的生存率低于lncRNA-UCA1低表达组(χ2=4.432,P=0.035)。结论结直肠癌组织lncRNA-UCA1表达高于癌旁组织,与TNM分期、分化程度、浸润深度相关,且是化疗敏感性的影响因素,并与患者生存情况有关。 展开更多
关键词 结直肠癌 长链非编码核糖核酸-尿路上皮癌胚抗原1 病理特征 敏感性
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Human leukocyte antigen class II DQB1*0301, DRB1*1101 alleles and spontaneous clearance of hepatitis C virus infection: A meta-analysis 被引量:9
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作者 Xin Hong Rong-Bin Yu +3 位作者 Nan-Xiong Sun Bin Wang Yao-Chu Xu Guan-Ling Wu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第46期7302-7307,共6页
AIM: To assess the associations of human leukocyte antigen (HI_A) class Ⅱ DQB1*0301 and/or DRB1*1101 allele with spontaneous hepatitis C virus (HCV) clearance by meta-analysis of individual dataset from all st... AIM: To assess the associations of human leukocyte antigen (HI_A) class Ⅱ DQB1*0301 and/or DRB1*1101 allele with spontaneous hepatitis C virus (HCV) clearance by meta-analysis of individual dataset from all studies published till date. METHODS: To clarify the impact of HLA class Ⅱ polymorphisms on viral clearance, we performed a metaanalysis of the published data from 11 studies comparing the frequencies of DQB1*0301 and DRB1*1101 alleles in individuals with spontaneous resolution to those with persistent infection. As we identified the heterogeneity between studies, summary statistical data were calculated based on a random-effect model. RESULTS: Meta-analyses yielded summary estimatesodds ratio (OR) of 2.36 [95%CI (1.62, 3.43), P〈0.00001] and 2.02 [95%CI (1.56, 2.62), P〈0.00001] for the effects of DQB1*0301 and DRB1*1101 alleles on spontaneous clearance of HCV, respectively. CONCLUSION: These results support the hypothesis that specific HLA class Ⅱ alleles might influence the susceptibility or resistance to persistent HCV infection. Both DQB1*0301 and DRB1*1101 are protective alleles and present HCV epitopes more effectively to CD4^+T lymphocytes than others, and subjects with these two alleles are at a lower risk of developing chronic HCV infection. Large, multi-ethnic confirmatory and welldesigned studies are needed to determine the host genetic determinants of HCV infection. 展开更多
关键词 Human leukocyte antigen Genetic polymorphism DQB1*0301 DRB11101 Hepatitis C virus Spontaneous clearance META-ANALYSIS
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肺腺癌中TROP2、TTF-1、Napsin A表达及其临床意义
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作者 贺慧 刘秋雨 张宁 《临床肿瘤学杂志》 2025年第6期588-592,共5页
目的探讨肺腺癌中滋养层细胞表面抗原2(TROP2)、甲状腺转录因子-1(TTF-1)、天冬氨酸肽酶A(Napsin A)表达及其临床意义。方法收集河南省人民医院2021年12月至2023年12月收治的134例肺腺癌手术患者,随访至2024年12月31日,随访期间失访6例... 目的探讨肺腺癌中滋养层细胞表面抗原2(TROP2)、甲状腺转录因子-1(TTF-1)、天冬氨酸肽酶A(Napsin A)表达及其临床意义。方法收集河南省人民医院2021年12月至2023年12月收治的134例肺腺癌手术患者,随访至2024年12月31日,随访期间失访6例,最终纳入128例患者。免疫组化染色法检测肺腺癌组织和癌旁组织中TROP2、TTF-1和Napsin A表达情况,Kaplan-Meier法绘制无复发生存曲线。结果肺腺癌组织中TROP2、TTF-1阳性率(57.81%、64.84%)及Napsin A阴性表达率(42.19%)均高于癌旁组织(7.81%、7.03%及2.34%),差异有统计学意义(P<0.05)。TROP2表达与TNM分期、分化程度、淋巴结转移有关(P<0.05),与其他临床病理特征无关;TTF-1表达与分化程度、淋巴结转移有关(P<0.05),与其他临床病理特征无关;Napsin A表达与肿瘤直径、TNM分期、分化程度、淋巴结转移有关(P<0.05),与其他临床病理特征无关。复发组TROP2、TTF-1阳性率(95.24%、97.62%)及Napsin A阴性表达率(78.57%)均高于未复发组(39.53%、48.84%及24.42%),差异有统计学意义(P<0.05)。128例患者随访期间42例复发,复发率为32.81%。TROP2阳性、TTF-1阳性、Napsin A阴性表达肺腺癌患者无复发生存率均低于TROP2阴性、TTF-1阴性、Napsin A阳性患者(P<0.05)。结论患者TROP2、TTF-1、Napsin A表达与肺腺癌临床病理特征及无复发生存密切相关。 展开更多
关键词 肺腺癌 滋养层细胞表面抗原2 甲状腺转录因子-1 天冬氨酸肽酶A 临床病理特征 预后
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Antigenicity of tissues and organs from GGTA1/CMAH/β4GalNT2 triple gene knockout pigs 被引量:5
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作者 Ronggen Wang Miaomiao Ruan +14 位作者 Runjie Zhang Lei Chen Xiaoxue Li Bin Fang Chu Li Xueyang Ren Jiying Liu Qiang Xiong Lining Zhang Yong Jin Lin Li Rongfeng Li Ying Wang Haiyuan Yang Yifan Dai 《The Journal of Biomedical Research》 CAS CSCD 2019年第4期235-243,共9页
Clinical xenotransplantations have been hampered by human preformed antibody-mediated damage of the xenografts.To overcome biological incompatibility between pigs and humans,one strategy is to remove the major antigen... Clinical xenotransplantations have been hampered by human preformed antibody-mediated damage of the xenografts.To overcome biological incompatibility between pigs and humans,one strategy is to remove the major antigens[Gal,Neu5 Gc,and Sd(a)]present on pig cells and tissues.Triple gene(GGTAI,CMAH,and β4 GalNT2)knockout(TKO)pigs were produced in our laboratory by CRISPR-Cas9 targeting.To investigate the antigenicity reduction in the TKO pigs,the expression levels of these three xenoantigens in the cornea,heart,liver,spleen,lung,kidney,and pancreas tissues were examined.The level of human IgG/IgM binding to those tissues was also investigated,with wildtype pig tissues as control.The results showed that aGal,Neu5 Gc,and Sd(a)were markedly positive in all the examined tissues in wildtype pigs but barely detected in TKO pigs.Compared to wildtype pigs,the liver,spleen,and pancreas of TKO pigs showed comparable levels of human IgG and IgM binding,whereas corneas,heart,lung,and kidney of TKO pigs exhibited significantly reduced human IgG and IgM binding.These results indicate that the antigenicity of TKO pig is significantly reduced and the remaining xenoantigens on porcine tissues can be eliminated via a gene targeting approach. 展开更多
关键词 PIG XENOTRANSPLANTATION GGTA1 CMAH β4GaINT2 antigenICITY
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信迪利单抗联合恩度注射液治疗PD-L1阳性老年肺鳞癌患者的有效性和安全性观察
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作者 李小雪 姚舒洋 +1 位作者 农靖颖 张毅 《免疫学杂志》 2025年第6期409-416,共8页
目的探讨信迪利单抗联合恩度注射液治疗程序性细胞死亡配体-1(PD-L1)阳性老年肺鳞癌患者的有效性及安全性。方法选取2019年11月至2021年11月诊治的94例PD-L1阳性老年肺鳞癌患者为研究对象,采用随机数字表法分为观察组和对照组各47例。... 目的探讨信迪利单抗联合恩度注射液治疗程序性细胞死亡配体-1(PD-L1)阳性老年肺鳞癌患者的有效性及安全性。方法选取2019年11月至2021年11月诊治的94例PD-L1阳性老年肺鳞癌患者为研究对象,采用随机数字表法分为观察组和对照组各47例。观察组予信迪利单抗联合恩度注射液治疗,对照组予信迪利单抗治疗,21 d为1个治疗周期,连续治疗3个周期。统计分析两组临床疗效、卡氏功能状态评分量表(KPS)评分改善率,以及治疗前后肿瘤标志物[癌胚抗原(CEA)、癌抗原125(CA125)、细胞角蛋白19片段(CYFRA21-1)]、血管生成因子[内皮抑素、胰岛素样生长因子-1(IGF-1)、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)、血小板源性生长因子(PDGF)]、凋亡因子[B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)、Livin蛋白、程序性细胞死亡分子5(PDCD5)],并比较两组治疗期间毒副反应及随访2年无进展生存率和中位生存时间。结果治疗后观察组客观缓解率、疾病控制率高于对照组(P<0.01);治疗后观察组KPS评分改善率高于对照组(P<0.01);治疗后两组血清CEA、CA125、CYFRA21-1水平均降低,且观察组低于对照组(P<0.05,P<0.01);治疗后两组内皮抑素升高,IGF-1、VEGF、bFGF、PDGF降低,且观察组内皮抑素水平高于对照组,IGF-1、VEGF、bFGF、PDGF水平低于对照组(P<0.05,P<0.01);治疗后两组Bcl-2、Livin降低,Bax、PDCD5升高,且观察组Bcl-2、Livin水平低于对照组,Bax、PDCD5水平高于对照组(P<0.05,P<0.01);两组治疗期间毒副反应比较差异无统计学意义(P>0.05);观察组随访2年无进展生存率高于对照组、中位生存时间长于对照组(P<0.05,P<0.01)。结论PD-L1阳性老年肺鳞癌患者予信迪利单抗联合恩度注射液治疗,可提高治疗效果,改善患者生存状况,抑制肿瘤新生血管形成,诱导肿瘤凋亡,延长患者生存期,且安全性良好。 展开更多
关键词 肺肿瘤 老年人 信迪利单抗 恩度注射液 程序性细胞死亡配体-1 癌胚抗原 内皮抑素 程序化细胞死亡分子5 无进展生存期
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Anti-tumor Angiogenesis with a Recombinant Ag43/FGFR1 Chimeric Protein As a Model Antigen 被引量:1
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作者 郑少萍 翁志宏 +3 位作者 郑少江 郭峻莉 黄风迎 谢明星 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2010年第1期25-28,共4页
In order to investigate the anti-tumor angiogenesis activity with a recombinant Ag43/FGFR1 chimeric protein(AF)vaccine in a mouse H22 hepatoma model,tumor volume and survival rate of the mice were studied at a 3-day i... In order to investigate the anti-tumor angiogenesis activity with a recombinant Ag43/FGFR1 chimeric protein(AF)vaccine in a mouse H22 hepatoma model,tumor volume and survival rate of the mice were studied at a 3-day interval.Microvessel density(MVD)was detected by immunohistochemistry.The endothelial deposition of autoantibodies within tumor tissues was examined by immunofluorescent staining,and anti-FGFR1 antibody-producing B cells(APBCs)were tested by enzyme-linked immunospot(ELISPOT)assay.Compared with t... 展开更多
关键词 fibroblast growth factor receptor-1 antigen 43 ANGIOGENESIS IMMUNOTHERAPY
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An Inactivated Vaccine from a Field Strain of Bovine Herpesvirus-1(BoHV-1) has High Antigenic Mass and Induces Strong Efficacy in a Rabbit Model 被引量:2
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作者 Julian Ruiz-Sáenz Jairo Jaime Victor Vera 《Virologica Sinica》 SCIE CAS CSCD 2013年第1期36-42,共7页
Bovine Herpesvirus-1 (BoHV-1) is a DNA virus belonging to the family Herpesviridae, subfamily Alfaherpesvirinae; it is a worldwide pathogen, causing serious economic losses in livestock. In Colombia there have been ... Bovine Herpesvirus-1 (BoHV-1) is a DNA virus belonging to the family Herpesviridae, subfamily Alfaherpesvirinae; it is a worldwide pathogen, causing serious economic losses in livestock. In Colombia there have been multiple isolates of BoHV-1 that have been subjected to molecular characterization, classifying most of the country isolates as BoHV-I.1. In the present study we developed and evaluated an ethyleneimine binary inactivated isolate from the native BoHV-1 strain (C6rdoba-2) in a rabbit model of vaccination and infection. The vaccine was evaluated in two phases, one of immunogenicity with vaccination and a booster after 21 days, and an evaluation phase of protection against challenge with a highly virulent reference strain. The results demonstrate optimum serum-conversion, with protective neutralizing antibody titers 28 days post vaccination and optimal protection against challenge with the reference strain with decreased clinical signs of infection, protection against the onset of fever and decrease of virus excretion post challenge. In conclusion, our results show the enormous potential that an immunogenic inactivated vaccine has produced from the native BoHV-I.1 strain, which produces a high antigen mass to the vaccine to induce optimal immunity and protection, and it is a strong candidate for evaluation and possible future use in different cattle populations. 展开更多
关键词 antigenic Mass ADJUVANT Binary Ethyleneimine Bovine Herpesvirus-1 VACCINE
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