抗原,CD44

摘要： 为探讨CD44及上下游相关细胞因子与活动性肺结核病变发展及预后的关系,笔者采用回顾性研究的方法,搜集乐山市人民医院感染科2018年1月至2019年7月治疗的86例活动性肺结核患者作为观察组,选取本院同期40名健康体检者作为对照组.应用酶联免疫吸附试验检测CD44、γ-干扰素(IFN-γ)和肿瘤坏死因子α(TNF-α)表达水平.结果 显示,观察组治疗前和治疗6个月后CD44、TNF-α和IFN-γ表达水平[治疗前分别为(54.37±8.26) μmol/L、(42.72±6.12) μmol/L、(35.83±5.14) μmol/L;治疗6个月后分别为(20.14±3.25) μmol/L、(11.38±1.52) μmol/L、(16.42±2.57) μmol/L]均明显高于对照组[分别为(12.16±1.42) μmol/L、(5.38±1.06) μmol/L、(7.52±1.22) μmol/L],差异均有统计学意义(t值分别为21.147、26.528、20.712、8.106、9.132、11.614,P值均为0.000).观察组治疗6个月后CD44、TNF-α和IFN-γ表达水平均明显低于治疗前,差异均有统计学意义(t值分别为10.713、18.552、16.124,P值均为0.000).应用受试者工作特征曲线分析CD44表达水平预测活动性肺结核的价值,曲线下面积为0.84(95％CI:0.77～0.91),截断值为26.74 μmol/L,诊断敏感度为90.3％,特异度为86.4％.由此可见,检测外周血CD44表达水平可能对活动性肺结核有诊断和评估预后的价值.

摘要： 目的 分析微小RNA-145(miR-145)与CD44在肝癌中的关系.方法 收集2015年10月至2016年6月福建医科大学附属第二医院13例肝细胞癌(HCC)患者标本,以CD44阳性表达患者为研究对象,实时荧光定量PCR检测miR-145及CD44在HCC及对应正常肝组织的表达.Western印迹检测CD44在肝癌细胞系HepG2和SNU423中的表达.生物学信息方法预测miR-145和CD44是否存在靶向作用.在CD44阳性表达的肝癌细胞系中,过表达miR-126后检测CD44表达水平.构建载体及荧光素酶报告基因验证miR-145和CD44间的靶向作用关系.四甲基偶氮唑盐(MTr)检测miR-145对CD44阳性和阴性表达肝癌细胞增殖的影响.结果 在13例患者中有8例HCC组织CD44表达阳性.与正常肝组织比较,HCC组织中miR-145相对表达更低(0.998±0.010比0.503±0.046),CD44 mRNA相对表达更高(0.996±0.005比1.878±0.108),差异有统计学意义(P＜0.05).生物信息学方法提示miR-145与CD44存在靶向作用关系.在肝癌细胞SNU423中,过表达miR-145能够显著下调CD44 mRNA的相对表达(0.941±0.010比0.515±0.021,P＜0.05),并下调CD44蛋白表达.荧光素酶报告基因实验表明CD44是miR-145直接作用的靶基因.转染miR-145模拟物后明显抑制CD44阳性表达SNU423细胞增殖.结论 miR-145可通过调控CD44的表达影响CD44阳性的肝癌细胞增殖,这可能是肝癌发病机制之一.%Objective To study the relationship of microRNA-145(miR-145) and CD44 in the hepatocellular carcinoma(HCC).Methods 13 clinical samples of HCC tissues and corresponding normal liver tissues were collected at department of General Surgery,Second Affiliated Hospital of Fujian Medical University from October 2015 to June 2016.The patients with positive expression of CD44 were studied.The expression levels of miR-145 and CD44 in HCC tissues and corresponding normal tissues were detected by real-time quantitative PCR.Western blot was performed to detect the expression of CD44 in HCC cells Hep G2 and SNU423.Biological information methods predicted whether miR-145 and CD44 have a targeted relationship.CD44 expression levels were detected after high expression of miR-145 in HCC cell line with positive expression of CD44.The vector and luciferase reporter genes were constructed to verify the interaction between miR-145 and CD44.The effects of miR-145 on proliferation in HCC cell lines with positive and negative CD44 expression were examined by tetramethylazoazole salt (MTT) assay.Results 8 of the 13 patients showed positive CD44 expression in HCC tissues.Compared with normal liver tissues,the relative expression of miR-145 in HCC tissues was significantly lower (0.998±0.010 vs.0.503±0.046,P＜0.05),and the relative expression of CD44 was higher (0.996±0.005 vs.1.878±0.108,P＜0.05).Bioinformatics suggested that miR-145 had a targeted relationship with CD44.High expression of miR-145 can significantly reduce the expression level of CD44 mRNA in HCC cell SNU423 (0.941±0.010 vs.0.515±0.021,P＜0.05) and down-regulate the expression of CD44 protein.Confirmed by luciferase reporter assay,CD44 is the target gene of miR-145.After transfection with miR-145 mimics,the proliferation of CD44 positive cell SNU423 was significantly inhibited (P＜0.05).Conclusions miR-145 can affect the proliferation of CD44 positive HCC cells by regulating the expression of CD44,which may be one of the pathogenesis of HCC.

摘要： Objective To analyze the expression of Kruppel-like factor 4 (KLF4 ) and CD44 in esophageal squamous cell carcinoma (ESCC) tissues and adjacent non-cancerous tissues ,and to investigate their effects on the prognosis .Methods From June 2012 to September 2016 ,in The Second People′s Hospital of Nanyang ,a total of 100 patients with ESCC who receiving operation were selected .The ESCC tissues and the adjacent non-cancerous tissues (control) of the patients were collected .The expression levels of KLF4 and CD44 protein were detected by immunohistochemistry .The expressions of KLF4 and CD44 at mRNA and protein level of 50 paired fresh tissues were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting ,respectively . T-test ,chi-square ,Kaplan-Meier method and Pearson correlation analysis were performed for statistical analysis .Results The positive expression rate of KLF4 protein in ESCC tissues was 55％ (55/100) ,which was lower than that in adjacent non-cancerous tissues (77％ ,77/100) ,and the difference was statistically significant (χ2 =10 .778 ,P=0 .001) .The positive expression rate of CD44 protein in ESCC tissues was 81％ (81/100) ,which was higher than that in adjacent non-cancerous tissues (11％ ,11/100) ,and the difference was statistically significant (χ2=112 .600 ,P<0 .01) .The expression level of KLF4 mRNA in 43 cases was lower than that in adjacent non-cancerous tissues ,the expression level of CD44 mRNA in 46 cases was much higher than that of adjacent non-cancerous tissues ,and the differences were statistically significant (χ2 =51 .837 and 70 .563 ,both P< 0 .01) .There were statistically significant differences in positive expression rates of KLF4 in cancer tissues between different gender , differentiation degree , invasion depth ,TNM stage and lymph node metastasis (all P<0 .05) .Similarly there were statistically significant differences in positive expression rates of CD 44 in cancer tissues between different differentiation degree ,invasion depth ,TNM stage and lymph node metastasis (all P< 0 .05) .The expression of KLF4 was negatively correlated with CD44 expression ,either at protein level or mRNA level (r= -0 .284、-0 .518 ,both P< 0 .01) .The median survival time of patients with positive KLF4 expression in cancer tissues was 33 months ,which was longer than that of patients with negative KLF4 expression (20 months) ,and the difference was statistically significant (χ2 =4 .021 , P= 0 .019) .The median survival time of patients with positive CD44 expression in cancer tissues was 24 months ,which was shorter than that of patients with negative CD44 expression (37 months) , and the difference was statistically significant (χ2 = 4 .379 , P= 0 .016) .The results of univariate analysis showed that TNM stage ,KLF4 expression and CD44 expression were correlated with overall survival time (all P<0 .05) . The results of multivariate analysis indicated that TNM stage ,lower KLF4 expression and higher CD44 expression were the independent risk factors for survival (all P<0 .05) .Conclusion Lower expression of KLF4 and higher expression of CD44 in ESCC may be closely correlated with its occurrence ,development and prognosis .%目的 分析Kruppel样因子4(KLF4)和CD44在食管鳞状细胞癌组织和对应的癌旁组织中的表达情况,并探讨其对预后的影响.方法 选取2012年6月至2016年9月于南阳市第二人民医院外科行手术治疗的100例食管鳞状细胞癌患者,取其食管鳞状细胞癌组织及对应的癌旁正常组织(对照),采用免疫组织化学法检测其K L F4和CD44的蛋白质表达情况;选取其中50例患者的新鲜组织标本,采用实时荧光定量PCR法和蛋白质印迹法分别检测KLF4、CD44的mRNA与蛋白质表达水平.统计学分析采用t检验、卡方检验、Kaplan-Meier法和Pearson相关性分析.结果 KLF4蛋白质在食管鳞状细胞癌组织中的阳性率为55％(55/100),低于对应癌旁组织的77％(77/100),差异有统计学意义(χ2=10.778,P=0.001).CD44蛋白质在食管鳞状细胞癌组织中的阳性率为81％(81/100),高于所对应癌旁组织的11％(11/100),差异有统计学意义(χ2=112.600,P<0.01).食管鳞状细胞癌组织中K L F4的mRNA表达水平比癌旁组织降低者43例,CD44的mRNA表达水平比癌旁组织升高者46例,差异均有统计学意义(χ2=51.837、70.563,P均<0.01).癌组织中K L F4的阳性表达在不同性别、不同分化程度、不同浸润深度、不同TNM分期和有无淋巴结转移中差异均有统计学意义(P均<0.05).癌组织中CD44的阳性表达在不同分化程度、不同浸润深度、不同T N M分期和有无淋巴结转移中差异均有统计学意义(P均<0.05).不管是蛋白质水平还是mRNA水平,KLF4与CD44的表达均呈负相关(r=-0.284、-0.518,P均<0.01).食管鳞状细胞癌组织中K L F4蛋白质阳性患者的中位生存期为33个月,长于K L F4蛋白质阴性患者的20个月,差异有统计学意义(χ2=4.021,P=0.019);食管鳞状细胞癌组织中CD44蛋白质阳性患者的中位生存期为24个月,短于CD44蛋白质阴性患者的37个月,差异有统计学意义(χ2=4.379,P=0.016).单因素分析显示,T N M分期、K L F4表达和CD44表达与总生存期相关(P均<0.05);多因素分析显示,TNM分期、KLF4低表达和CD44高表达是影响患者生存的独立危险因素(P均<0.05).结论 食管鳞状细胞癌组织中的K L F4低表达和CD44高表达可能与其发生、发展和预后密切相关.

摘要： 背景:国内外研究显示CD24、CD44表达与胃癌的疾病进展、临床病理参数及预后可能存在密切关系。目的:探讨胃癌组织中干细胞标志物CD24、CD44共表达情况及对患者临床病理参数、预后的影响。方法:收集2006年4月至2012年4月在菏泽市立医院胃肠外科行手术治疗的胃癌患者的临床资料。采用免疫组织化学法检测癌组织、癌旁组织、正常胃组织中CD24、CD44蛋白表达情况,记录患者临床病理参数并随访。统计分析CD24、CD44双阳性表达与患者临床病理参数间的关系及对患者预后的影响。结果与结论:①在180例患者中,CD24阳性率为57.5%(92/180),其中低表达54例,高表达38例;CD44阳性率为49.3%(79/180),其中低表达48例,高表达31例。二者的共表达率为24.3%(39/180),双阴性率为30.0%(48/180);②与癌组织相比,正常胃组织和癌旁组织CD24、CD44的阳性率均较低,且差异有显著性意义(P0.05)。多因素分析结果发现T分期、N分期是影响CD24、CD44在胃癌组织中共表达的独立性危险因素;④Spearman等级相关分析结果显示,CD24和CD44的表达强度之间不存在相关关系(r=0.020,P=0.795);⑤180例患者,失访17例,失访率为9.4%。5年内死亡87例,CD24单阳组53例患者,死亡21例;CD44单阳组40例患者,死亡23例;双阴组48例患者,死亡13例,双阳组39例患者,死亡30例。Log-rank统计检验显示,4组患者的生存率差异有显著性意义(χ2=21.72,P<0.001),CD24(+)CD44(+)患者预后最差;⑥结果表明,CD24、CD44在胃癌中有较高的阳性率,且与患者分期密切相关。二者的共表达是患者预后不良的强烈信号。

摘要： 目的 构建CD44基因过表达慢病毒载体并建立稳定过表达CD44的雄激素依赖前列腺癌LNCaP细胞株. 方法 聚合酶链反应(PCR)法获得CD44基因序列,与经NotI和NsiI双酶切的LV5载体连接获得CD44过表达重组慢病毒载体,重组质粒经双酶切鉴定和测序验证无误后,进行高纯度抽提,共转染293 T细胞,收集富含慢病毒颗粒的细胞上清液,对其浓缩后得到高滴度的慢病毒浓缩液,倍比稀释法检测病毒滴度.用病毒颗粒感染LNCaP细胞,荧光显微镜检测CD44荧光水平,定量反转录聚合酶链反应(QRT-PCR)检测CD44基因的表达,免疫印迹检测CD44蛋白的表达. 结果 成功构建CD44基因过表达慢病毒载体,并在293 T细胞中包装获得病毒.重组病毒感染LNCaP细胞后,荧光显微镜检测CD44基因过表达细胞荧光水平增加;QRT-PCR和免疫印迹检测显示,CD44在INCaP细胞中表达显著升高(均P＜0.05). 结论 成功构建CD44基因过表达慢病毒载体,并建立CD44过表达LNCaP细胞株.%Objective To construct an overexpression lentiviral vector of CD44 and obtain an androgen-dependent prostate cancer LNCaP cell line with CD44 overexpression.Methods CD44 gene sequence was obtained by PCR amplification.The synthesized oligonucleotides were cloned in the lentiviral vector LV5 after digested with NotI and NsiI enzyme.Recombinant plasmids were verified by enzyme digestion analysis and sequencing,and were transfected into 293T package cells.Supernatant was collected and concentrated to obtain lentivirus solution at a high titer.The titer of virus was identified by multiple proportion dilution methods.Then the recombinant viruses were transfected into LNCaP cells.Results Fluorescence intensity in infected LNCaP cells was increased,detected by a fluorescence microscope.And QRT PCR and Western blot results showed that the expression of CD44 was significantly increased(P＜0.05).Conclusions The overexpression lentiviral vector of CD44 is successfully constructed,and the LNCaP cell line with CD44 overexpression is obtained.

摘要： Objective To explore the expression and significance of osteopontin(OPN) and its receptors CD44 and integrin in the ossification of the ligamentum flavum(OLF) to pave the way for further study of the pathogenesis of OLF. Methods From June 2014 to June 2016,sections of the thoracic ligamentum flavum were obtained from 8 patients with OLF who underwent posterior thoracic decompression surgery,and from 8 control patients free of OLF. Cultured ligamentum flavum cells were examined with Western blotting for OPN. The harvested sections were examined by immunohistochemistry for the OPN and its receptors. Results The elastic fibers in the OLF samples were disordered,and a large number of chondrocytes were seen in the ossification front,but not in the normal ligamentum flavum samples. OPN and its receptor CD44 were highly expressed in the OLF samples,and mostly around the chondrocytes in the ossification region,while the expression of integrin β1 was weak. The normal ligamentum flavum samples showed low expression or no expression of OPN and its receptors. The expression of the OPN in the OLF cells was higher than the control through the Western blotting. Immunocytochemistry staining showed that the expression of integrin β3 in the OLF cells was significantly higher than that in the normal ligamentum flavum cells,and the same to the Western blotting analysis. Conclusion OPN and its receptors may play a key role in the pathogenic process of OLF.%目的 探讨骨桥蛋白(OPN)及其受体CD44、整合素在人黄韧带骨化(OLF)标本中的表达及意义.方法 2014年6月—2016年6月,收集8例在本院接受胸椎后路椎板切除的OLF患者的骨化黄韧带标本以及8例非黄韧带骨化患者的正常黄韧带标本.对所得标本进行脱钙、切片、免疫组织化学染色以及细胞体外培养和蛋白质印迹检测,观察黄韧带标本中OPN及其受体CD44、整合素的表达变化.结果 OLF标本中的弹性纤维排列杂乱无章,同时在骨化层可见大量软骨细胞;正常黄韧带标本中则无上述表现.OLF标本中OPN及其受体CD44呈高表达,且多在骨化区域的软骨细胞周围,而整合素 β1的表达较弱;正常黄韧带标本中OPN及其受体呈低表达或不表达状态.通过对体外培养的细胞进行蛋白质印迹检测发现骨化黄韧带细胞OPN的表达较正常黄韧带细胞增加.免疫细胞化学染色发现骨化黄韧带细胞整合素 β3染色呈阳性,而正常黄韧带细胞整合素 β3的表达呈阴性或弱阳性;蛋白质印迹检测发现骨化黄韧带细胞整合素β3的表达明显高于正常黄韧带细胞.结论 OPN及其受体可能在OLF的发生过程中起关键作用.

摘要： 目的 探讨胃间质瘤干细胞标志物CD44、CD133蛋白的表达及其与临床病理特征、预后的关系.方法 采用免疫组织化学法检测112例胃间质瘤组织中CD44和CD133蛋白的表达情况,并对其与临床病理指标、患者生存情况及预后的相关性进行分析.结果 CD44、CD133在胃间质瘤组织中均有表达,主要表达在细胞膜,阳性表达率分别为58.04%(65/112)、42.86%(48/112),CD44、CD133双阳性表达率为27.68%(31/112).正常瘤旁组织中CD44、CD133染色呈阴性.CD44、CD133表达均与肿瘤患者的年龄、性别、淋巴管浸润无关(P>0.05),但肿瘤核分裂数高、肿瘤直径大、有血管浸润者CD44与CD133阳性表达率高(均P0.05),但肿瘤直径越大,双阳性表达率越高(χ2=5.040,P=0.025).生存分析发现,CD44、CD133双阳性表达组的3年总生存率明显低于其他组(χ2=8.758,P=0.001).CD44蛋白与CD133蛋白的表达无相关性(r=0.126,P=0.210).多因素分析显示,肿瘤直径(P=0.042)及CD44、CD133双阳性表达(P=0.003)是影响胃间质瘤患者术后生存的独立预后因素.结论 肿瘤干细胞标志CD44和CD133可作为临床评价胃间质瘤肿瘤生物学行为及预后评估的指标.%Objective To investigate the expression of CD133 and CD44 proteins in gastric stromal tumors (GST) and their clinical significances. Methods The expression of CD44 and CD133 proteins in the GST tissues of 112 patients was detected by immunohistochemical staining. The relation between the expression of CD44 and CD133 proteins and the clinicopathological characters was analyzed. The survival and prognosis of GST were also analyzed. Results Both CD44 and CD133 were expressed on the cell membranes. The expression rates of CD44 and CD133 were 58.04 % (65/112) and 42.86 % (48/112) separately; the co-expression rate of CD44 and CD133 was 27.68 % (31/112). CD44 and CD133 were negative in normal peritumoral tissues. No correlation was found between CD44 and CD133 and the clinicopathological parameters including gender, age and lymphatic vessel invasion (all P>0.05), but the expression levels of CD44 and CD133 in patients with the mitotic count ≥ 5/50 high-power field, large diameter and vascular invasion were significantly higher (all P0.05), but the co-expression level of CD44 and CD133 in patients with tumor diameter ≥5 cm was significantly higher than that in patients with tumor diameter < 5 cm (χ2=5.040, P=0.025). The overall survival rate of the patients with co-expression of CD44 and CD133 was shorter than that in other groups (χ2 = 8.758, P= 0.001). No correlation was found between CD44 and CD133 expression (r=0.126, P=0.210). Multivariate analysis with the Cox regression models showed that the tumor diameter ≥5 cm (P=0.042) and co-expression of CD44 and CD133 (P=0.003) were significantly associated with poor prognosis. Conclusion CD44 and CD133 as robust cancer stem cell markers in GST might be the prognostic factors.

摘要： [Objective]To investigate the relationships between cell adhesion molecule CD44 variant exon‐6 (CD44‐v6) and integrin beta 1 with the prognosis of surgical patients with pancreatic cancer .[Methods]Eight‐y‐five patients with pancreatic cancer who received treatment in our hospital were chosen as the study subjects . The positive expression rates of CD44‐v6 and integrin beta‐1 in the pancreatic cancer tissues of the patients with different clinical‐pathological features were deterimined .The correlation between the positive expression rates of CD44‐v6 ,integrin beta 1 and the levels of tumor markers (CEA ,CA19‐9 and CA125) was analyzed .[Results]The positive expression rates of CD44‐v6 ,integrin beta 1 ,antigen (CEA) ,carbohydrate antigen 19‐9 (CA19‐9) ,and carbohydrate antigen 125 (CA125) in the death group were significantly higher than those in the survival group ,the difference was statistically significant ( P <0 0.5) .Pancreatic cancer patients with old age ,lower differentiation ,distant metastasis ,and invasion of vascular showed higher positive expression rates in CD44‐v6 and integrin beta‐1 ,the differences were statistical significance ( P <0 0.5) .There were no signif‐icant differences showing the expression rates of CD44‐v6 and integrin beta 1 with patient gender ,tumor size , and local lymph node invasion ( P <0 0.5) . .The positive expression rate of CD44‐v6 and integrin beta‐1 in pancreatic cancer patients were significantly positively correlated with CA19‐9 ,CA125 and CEA ,and the difference was statistically significant ( P <0 0.5) .[Conclusion]The high expression of CD44‐v6 and integrin beta‐1 contributes to the poor prognosis in patients with pancreatic cancer ,and is associated with tumor mark‐ers (CEA ,CA19‐9 and CA125) .It can be used as an important indicator of the prognosis as well .%【目的】探讨细胞黏附分子CD44变异型外显子‐6（CD44‐v6）、整合素β1与根治性胰腺癌患者预后的关系。【方法】对在本院接受治疗的85例胰腺癌患者，比较CD44‐v6、整合素β1在不同临床病理特征的胰腺癌组织中的阳性表达率及其与肿瘤标志物癌胚抗原（CEA）、糖类抗原19‐9（CA19‐9）糖类抗原125（CA125）水平的相关性。【结果】死亡组患者CD44‐v6、整合素β1阳性表达率和CEA、CA19‐9，CA125水平明显高于生存组，且差异具有显著性（ P ＜00．5）；年龄较大、分化程度低、有远处转移、侵犯血管的胰腺癌患者CD44‐v6和整合素β1阳性表达率较高（ P ＜00．5），而不同性别、肿瘤直径和是否有淋巴结侵犯的患者术后CD44‐v6，整合素β1阳性表达率无明显差异（ P ＞0．05）；胰腺癌患者 CD44‐v6、整合素β1阳性表达率与 CA19‐9、CA125、CEA呈显著正相关（ P ＜00．5）。【结论】CD44‐v6、整合素β1在预后较差的胰腺癌患者中高表达，且与肿瘤标志物水平正相关，可作为判断患者预后的重要指标。

摘要： Objectives To explore the expression of CD44v6 protein in human bladder and urothelial carcinoma,and to study their significance in dignosis of human bladder and urothelial carcinoma.Methods Real-time fluorescent quantitative PCR was used to quantify the expression of CD44v6 protein in 80 patients with bladder and urothelial carcinoma and 20 cases with normal bladder mucosa.Results CD44v6 was negative in all normal bladder and urothelial nucosa,with a copy number less than 1 × 102 copies/mL;And 35 cases were CD44v6 positive expression(43.75％);CT values were less than 35 and copy number was greater than 1 × 104 copies/mL.Positive rate was correlated with pathological grades and TNM stages.Conclusions CD44v6 is associated with the early diagnosis of bladder urothelial carcinoma,and it could be used to evaluate differentiation,clinical staging index of bladder and urothelial carcinoma.%目的 探讨CD44v6在膀胱及尿路上皮癌中的表达,研究其在膀胱及尿路上皮癌中的表达及临床意义.方法 收集实验组膀胱及尿路上皮癌患者80例,从病理分期和临床分期两个方面通过实时荧光定量PCR对CD44v6进行定量分析.对照组为20例正常膀胱黏膜组织.结果 CD44v6蛋白在正常膀胱黏膜上皮无表达,基因拷贝数＜1×102copies/mL.在80例膀胱及尿路上皮癌中阳性表达是35例(43.75％),CT值均小于35,基因拷贝数均＞1×104copies/mL.CD44v6的表达在膀胱及尿路上皮癌TNM分期和病理分级组间比较差异具有统计学意义(P＜0.05).结论 CD44v6与膀胱及尿路上皮癌的早期诊断具有相关性,可作为判断膀胱及尿路上皮癌分化程度,临床分期的参考指标.

摘要： 目的探讨肿瘤干细胞标志物CD44^+/CD24^(-/low)和乙醛脱氢酶1(ALDH1)在浸润性乳癌组织中的表达及其与乳癌分子亚型和预后的关系。方法制备组织芯片,使用罗氏Ventana Benchmark XT autostainer仪器,采用免疫组化法检测259例乳癌手术切除标本中CD44、CD24和ALDH1的表达。结果乳癌病例中CD44^+/CD24^(-/low)的阳性表达率为37.1%,其在乳癌各分子亚型中的表达差异具有统计学意义(χ~2=17.84,P0.05)。CD44^+/CD24^(-/low)阳性表达的乳癌病人5年无病生存率(DFS)为55.2%,较阴性表达病人显著降低(χ~2=10.34,P<0.01);ALDH1阳性表达的乳癌病人5年DFS为61.0%,较阴性表达病人显著降低(χ~2=12.28,P<0.01)。结论乳癌干细胞标志物CD44^+/CD24^(-/low)和ALDH1在乳癌组织中的表达不高,在乳癌各分子亚型中的表达有差异,联合检测这些标志物有可能预测病人预后。

摘要： 本发明公开了编码靶向CD123的嵌合抗原受体的核酸分子，所述嵌合抗原受体包含胞外区、跨膜区和胞内信号转导区，其编码的所述胞外区包含CD123结合结构域，所述CD123结合结构域为抗CD123的单链抗体可变区片段；所述抗CD123的单链抗体可变区片段为SEQ ID NO.13所示的氨基酸序列或与其具有90％～99％同一性的序列、SEQ ID NO.14所示的氨基酸序列或与其具有90％～99％同一性的序列，或SEQ ID NO.15所示的氨基酸序列或与其具有90％～99％同一性的序列。本发明嵌合抗原受体可用于CD123+和/或CD33+血液肿瘤的治疗，有效防止脱靶效应，使治疗效果更好，不易发生逃逸。

摘要： 本发明提供一种特异性地与人CD19结合的单克隆抗体和杂交瘤细胞。本发明还提供一种包含CD19单链抗体区(scFv)的嵌合抗原受体(CAR)。本发明还涉及包括CD19单链抗体区(scFv)或CD19单链抗体区(scFv)的嵌合抗原受体(CAR)的药物组合物。

摘要： 本发明公开了一种靶向CD19和CD20双抗原的嵌合性抗原受体T细胞治疗肿瘤的方法。本发明提供了本发明提供的嵌合性抗原受体，包括细胞外识别域和细胞内信号转导结构域，其中细胞外识别域依次包括信号肽、双抗原识别区、铰链区和跨膜区；所述双抗原识别区包括CD20单链抗体(scfv)和CD19单链抗体，其中，所述CD19单链抗体靠近所述跨膜区。本发明的优点是DCAR‑013‑T细胞可以识别CD19和CD20任意一个抗原，杀伤肿瘤细胞；在B细胞来源的血液肿瘤和淋巴瘤患者中CD19和CD20均为阴性的肿瘤细胞极少，针对CD19和CD20的双靶点CAR显示了良好的体外杀伤和临床治疗效果，体现了这种双靶点设计的优越性。

摘要： 本发明公开了编码靶向CD123的嵌合抗原受体的核酸分子，所述嵌合抗原受体包含胞外区、跨膜区和胞内信号转导区，其编码的所述胞外区包含CD123结合结构域，所述CD123结合结构域为抗CD123的单链抗体可变区片段；所述抗CD123的单链抗体可变区片段为SEQ ID NO.13所示的氨基酸序列或与其具有90％～99％同一性的序列、SEQ ID NO.14所示的氨基酸序列或与其具有90％～99％同一性的序列，或SEQ ID NO.15所示的氨基酸序列或与其具有90％～99％同一性的序列。本发明嵌合抗原受体可用于CD123+和/或CD33+血液肿瘤的治疗，有效防止脱靶效应，使治疗效果更好，不易发生逃逸。

摘要： 本发明涉及特异性结合人白细胞介素3(IL3)受体α链的单克隆抗CD123抗体或其片段。进一步地，本发明涉及编码嵌合抗原受体(CAR)的分离的核酸分子，其中CAR包含包括抗CD123结合结构域的抗体或抗体片段、跨膜结构域和至少包含刺激结构域的胞内信号传导结构域，由所述核酸分子编码的多肽以及包含这种抗体或抗体片段的分离的嵌合抗原受体(CAR)分子。本发明还涉及包含编码CAR的核酸分子的载体，以及包含所述载体的T细胞，并涉及表达CAR分子的T细胞用于治疗哺乳动物中增殖性疾病(例如癌症)的用途。

摘要： 本发明涉及靶向CD276抗原也称B7‑H3的抗体或其他抗原结合蛋白。本发明提供了改善的抗体集合，所述抗体在CD276抗原内的新位置结合并在CD276阳性癌症的治疗中特别用作治疗剂。此外，本发明提供了基于本发明的新型抗CD276抗体开发的抗体偶联物和双特异性抗体。此外，本发明公开了抗体和其他调节剂在CD276阳性癌症的治疗中的治疗用途。最后，提供了编码本发明的分子的核酸构建体、表达它们的重组细胞以及特定的用途和方法。

摘要： 本发明提供一种特异性地与人CD19结合的单克隆抗体和杂交瘤细胞。本发明还提供一种包含CD19单链抗体区(scFv)的嵌合抗原受体(CAR)。本发明还涉及包括CD19单链抗体区(scFv)或CD19单链抗体区(scFv)的嵌合抗原受体(CAR)的药物组合物。

摘要： 本发明公开了一种靶向CD19和CD20双抗原的嵌合性抗原受体T细胞治疗肿瘤的方法。本发明提供了本发明提供的嵌合性抗原受体，包括细胞外识别域和细胞内信号转导结构域，其中细胞外识别域依次包括信号肽、双抗原识别区、铰链区和跨膜区；所述双抗原识别区包括CD20单链抗体(scfv)和CD19单链抗体，其中，所述CD19单链抗体靠近所述跨膜区。本发明的优点是DCAR‑013‑T细胞可以识别CD19和CD20任意一个抗原，杀伤肿瘤细胞；在B细胞来源的血液肿瘤和淋巴瘤患者中CD19和CD20均为阴性的肿瘤细胞极少，针对CD19和CD20的双靶点CAR显示了良好的体外杀伤和临床治疗效果，体现了这种双靶点设计的优越性。

摘要： 本发明涉及结合CD3和CD137(4‑1BB)的抗原结合分子，包含所述抗原结合分子的组合物及其使用方法。本发明提供了抗原结合分子，其包含能够结合CD3和CD137(4‑1BB)但不同时结合CD3和CD137的抗体可变区，以及与不同于CD3和CD137的第三抗原结合的可变区。这些抗原结合分子通过与三种不同抗原的结合而表现出由这些抗原结合分子诱导的增强的T细胞依赖性细胞毒活性。

摘要： 本发明属于生物与新医药技术领域。公开了一种嵌合抗原受体（Chimeric Antigen Receptor,CAR）iRGD-scFv(G250)-CD8-CD28-CD137-CD3ζ及其应用。该嵌合抗原受体由肿瘤穿透肽iRGD、人源化抗人肾癌抗原G250的单链抗体、CD8的hinge区和跨膜区及CD28、CD137、CD3ζ的胞内信号结构域串联构成。该嵌合抗原受体可用于修饰T淋巴细胞。修饰后的T淋巴细胞可用于肾癌治疗。