Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in...Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in ovarian cancer tissues was analyzed by databases.The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry.The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay.The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens.Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells.Results The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue.The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites.The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells.M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites.M701 could mediate the binding of CD3^(+)T cells to EpCAM^(+)tumor cells and induce T cell activation in a dose-dependent manner.Conclusion M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites,which had a promising application in immunotherapy for patients with ovarian cancer ascites.展开更多
目的探讨结直肠癌细胞中EpCAM(CD326)表达的临床病理学意义及与DNA倍体改变的关系。方法应用流式细胞直接免疫荧光法检测55例结直肠癌组织及癌旁正常黏膜组织中EpCAM的表达,用阳性率(percentage of positive cells,PPC)、平均荧光强度(m...目的探讨结直肠癌细胞中EpCAM(CD326)表达的临床病理学意义及与DNA倍体改变的关系。方法应用流式细胞直接免疫荧光法检测55例结直肠癌组织及癌旁正常黏膜组织中EpCAM的表达,用阳性率(percentage of positive cells,PPC)、平均荧光强度(mean fluorescence index,MFI)表示;应用细胞周期分析仪对结直肠癌细胞进行细胞周期分析。用细胞定量术分析EpCAM表达和DNA倍体改变的相关性及其在结直肠癌早期诊断、预后中的价值。结果 55例结直肠癌组织中EpCAM蛋白的PPC为(83.48±7.07)%,明显高于癌旁正常黏膜组织(43.56±5.29)%(t=39.22,P<0.001)。55例结直肠癌组织中EpCAM蛋白MFI值为28.90(19.60~45.89),明显高于癌旁正常黏膜组织的4.89(3.79~6.28)(Z=-6.45,P<0.001)。癌组织:浸润型+溃疡型vs肿块型(包括浸润型vs溃疡型),中+低分化vs高分化(包括低分化vs中分化),Dukes分期C+D vs A+B,p TNM分期Ⅲ+ⅣvsⅠ+Ⅱ,浸润深度pT3+T4 vs pT1+T2,淋巴结转移pN1 vs pN0,差异均有统计学意义,即生物学行为越差,EpCAM蛋白表达MFI值与PPC越高,而与患者年龄、性别无关。DNA含量分析结果显示:55例结直肠癌中39例(70.90%)为多倍体,DNA指数(DNA index,DI)和DNA倍体与肿瘤分化程度、Dukes分期相关,与淋巴结转移无关。同时,在EpCAM阳性病例中,DI随着EpCAM表达增强而升高(r=0.668,P=0.000);而增殖指标S期细胞比率(S-phase fraction,SPF)和增殖指数(proliferation index,PI)也随着EpCAM表达增强而升高(r_1=0.664,P_1=0.000;r_2=0.651,P_2=0.000)。结论EpCAM在结直肠癌中的表达明显上调,与肿瘤细胞侵袭转移、增殖密切相关,同时检测EpCAM表达和DNA含量分析能为结直肠癌早期诊断和预后判断提供参考依据。展开更多
目的探讨EpCAM和Sox2在三阴性乳腺癌(triple negative breast cancer,TNBC)中的表达及临床意义。方法采用免疫组化SP法检测EpCAM和Sox2在81例TNBC、71例非三阴性乳腺癌(non-triple-negative breast cancer,non-TNBC)、20例癌旁正常乳腺...目的探讨EpCAM和Sox2在三阴性乳腺癌(triple negative breast cancer,TNBC)中的表达及临床意义。方法采用免疫组化SP法检测EpCAM和Sox2在81例TNBC、71例非三阴性乳腺癌(non-triple-negative breast cancer,non-TNBC)、20例癌旁正常乳腺组织中的表达。结果 TNBC组织中EpCAM、Sox2的阳性过表达率分别为74.1%、54.3%,均高于正常乳腺组织(15.0%和0)(P<0.05);EpCAM蛋白过表达与TNBC的组织学分级、淋巴结转移呈正相关(P<0.05);Sox2蛋白表达与TNBC淋巴结转移、pTNM分期呈正相关(P<0.05)。EpCAM和Sox2蛋白表达可能具有相关性。结论 EpCAM和Sox2蛋白在TNBC中均高表达,可能具有促癌作用及与淋巴结转移相关。展开更多
基金This work was supported by the National Key Research&Development Program of China(No.2021YFC2701402).
文摘Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in ovarian cancer tissues was analyzed by databases.The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry.The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay.The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens.Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells.Results The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue.The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites.The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells.M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites.M701 could mediate the binding of CD3^(+)T cells to EpCAM^(+)tumor cells and induce T cell activation in a dose-dependent manner.Conclusion M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites,which had a promising application in immunotherapy for patients with ovarian cancer ascites.
文摘目的探讨结直肠癌细胞中EpCAM(CD326)表达的临床病理学意义及与DNA倍体改变的关系。方法应用流式细胞直接免疫荧光法检测55例结直肠癌组织及癌旁正常黏膜组织中EpCAM的表达,用阳性率(percentage of positive cells,PPC)、平均荧光强度(mean fluorescence index,MFI)表示;应用细胞周期分析仪对结直肠癌细胞进行细胞周期分析。用细胞定量术分析EpCAM表达和DNA倍体改变的相关性及其在结直肠癌早期诊断、预后中的价值。结果 55例结直肠癌组织中EpCAM蛋白的PPC为(83.48±7.07)%,明显高于癌旁正常黏膜组织(43.56±5.29)%(t=39.22,P<0.001)。55例结直肠癌组织中EpCAM蛋白MFI值为28.90(19.60~45.89),明显高于癌旁正常黏膜组织的4.89(3.79~6.28)(Z=-6.45,P<0.001)。癌组织:浸润型+溃疡型vs肿块型(包括浸润型vs溃疡型),中+低分化vs高分化(包括低分化vs中分化),Dukes分期C+D vs A+B,p TNM分期Ⅲ+ⅣvsⅠ+Ⅱ,浸润深度pT3+T4 vs pT1+T2,淋巴结转移pN1 vs pN0,差异均有统计学意义,即生物学行为越差,EpCAM蛋白表达MFI值与PPC越高,而与患者年龄、性别无关。DNA含量分析结果显示:55例结直肠癌中39例(70.90%)为多倍体,DNA指数(DNA index,DI)和DNA倍体与肿瘤分化程度、Dukes分期相关,与淋巴结转移无关。同时,在EpCAM阳性病例中,DI随着EpCAM表达增强而升高(r=0.668,P=0.000);而增殖指标S期细胞比率(S-phase fraction,SPF)和增殖指数(proliferation index,PI)也随着EpCAM表达增强而升高(r_1=0.664,P_1=0.000;r_2=0.651,P_2=0.000)。结论EpCAM在结直肠癌中的表达明显上调,与肿瘤细胞侵袭转移、增殖密切相关,同时检测EpCAM表达和DNA含量分析能为结直肠癌早期诊断和预后判断提供参考依据。
文摘目的探讨EpCAM和Sox2在三阴性乳腺癌(triple negative breast cancer,TNBC)中的表达及临床意义。方法采用免疫组化SP法检测EpCAM和Sox2在81例TNBC、71例非三阴性乳腺癌(non-triple-negative breast cancer,non-TNBC)、20例癌旁正常乳腺组织中的表达。结果 TNBC组织中EpCAM、Sox2的阳性过表达率分别为74.1%、54.3%,均高于正常乳腺组织(15.0%和0)(P<0.05);EpCAM蛋白过表达与TNBC的组织学分级、淋巴结转移呈正相关(P<0.05);Sox2蛋白表达与TNBC淋巴结转移、pTNM分期呈正相关(P<0.05)。EpCAM和Sox2蛋白表达可能具有相关性。结论 EpCAM和Sox2蛋白在TNBC中均高表达,可能具有促癌作用及与淋巴结转移相关。
