目的:探究抗AGGF1中和抗体(RDD-Ab),RDD-Ab + 抗CTLA-4抗体联合治疗对小鼠黑色素瘤的治疗作用。方法:合成AGGF1的GTFQRDDAPASVHSE肽并制备多克隆中和抗体(RDD-Ab)。为了评估RDD-Ab对血管生成活性和黑色素瘤生长的影响,我们实施了小管生...目的:探究抗AGGF1中和抗体(RDD-Ab),RDD-Ab + 抗CTLA-4抗体联合治疗对小鼠黑色素瘤的治疗作用。方法:合成AGGF1的GTFQRDDAPASVHSE肽并制备多克隆中和抗体(RDD-Ab)。为了评估RDD-Ab对血管生成活性和黑色素瘤生长的影响,我们实施了小管生成实验、迁移实验、细胞增殖实验、黑色素瘤细胞皮下移植性模型实验和免疫组化等实验。结果:实验结果显示,制备的RDD-Ab可以识别细胞中天然的AGGF1蛋白和过表达的AGGF1蛋白。RDD-Ab可显著抑制血管内皮细胞小管形成、迁移和增殖。与IgG对照组相比,RDD-Ab治疗显著减缓黑色素瘤生长,RDD-Ab + CTLA-4抗体联合治疗时肿瘤生长速度最慢。免疫组化实验也表明,RDD-Ab显著减少瘤内微血管生成与肿瘤细胞增殖,同时,联合治疗可显著增加瘤内CD4+和CD8+淋巴细胞的浸润。结论:RDD-Ab可在体外抑制血管内皮细胞的血管新生功能,具有高效的黑色素瘤生长抑制作用,RDD-Ab + CTLA-4联合治疗黑色素瘤效果更佳(显著增加瘤内CD4+和CD8+淋巴细胞的浸润),这为未来黑色素瘤的临床干预提供了一种新的潜在治疗方案。Objective: To investigate the therapeutic effect of neutralizing antibody (against AGGF1, RDD-Ab), RDD-Ab + CTLA-4 therapy on mouse melanoma. Methods: Synthesize GTFQRDAPASVHSE peptide of AGGF1 and prepare polyclonal neutralizing antibody (RDD-Ab). In order to evaluate the effects of RDD-Ab on angiogenesis and melanoma growth, we conducted tube formation, migration, cell proliferation, subcutaneous melanoma cell transplantation model and immunohistochemistry (IHC). Results: RDD-Ab can recognize both natural AGGF1 protein and overexpressed AGGF1 protein in cells. The experimental results showed that RDD-Ab significantly inhibits the formation, migration, and proliferation of endothelial cell tubules. Compared with the IgG control group, RDD-Ab significantly slowed down the growth of melanoma. IHC experiments showed that RDD-Ab significantly suppressed tumor angiogenesis and proliferation. The combination therapy of RDD-Ab + CTLA-4 antibody has the slowest tumor growth rate, and the combination therapy increases the infiltration of CD4+ and CD8+ lymphocytes robustly in solid tumors. Conclusion: RDD-Ab can inhibit the angiogenesis function of endothelial cells in vitro and has a highly effective inhibitory effect on melanoma growth has an efficient inhibitory effect on melanoma growth, and the combined treatment with CTLA-4 antibody is more effective. This provides a new potential treatment option for clinical intervention of melanoma in the future.展开更多
BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of gr...BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.展开更多
背景与目的本研究旨在探索细胞毒性T淋巴细胞相关抗原(cytotoxic T lymphocyte associated antigen-4,CTLA-4)、程序坏死因子(programmed death 1,PD-1)和程序坏死因子配体(programmed death ligand 1,PD-L1)在小细胞肺癌(small cell lu...背景与目的本研究旨在探索细胞毒性T淋巴细胞相关抗原(cytotoxic T lymphocyte associated antigen-4,CTLA-4)、程序坏死因子(programmed death 1,PD-1)和程序坏死因子配体(programmed death ligand 1,PD-L1)在小细胞肺癌(small cell lung cancer,SCLC)患者外周血中的分布情况,探索其免疫作用机制并评估其作为生物标志物的临床价值。方法招募290例SCLC患者及60例健康志愿者,收集治疗前和治疗2^(nd)周期末SCLC患者EDTA抗凝血2 mL。应用流式细胞仪检测CTLA-4、PD-1和PD-L1在外周血CD3、CD4、CD8及CD25的分布,分析其与临床病理特征的相关性;采用细胞免疫化学法和流式细胞法检测PD-L1在SCLC细胞系H446中的表达。结果 SCLC患者外周血中CTLA-4^+细胞和PD-1^+细胞水平分别为(1.56±1.24)%和(8.07±3.97)%、CTLA-4在CD3细胞和CD4细胞中的表达水平无明显差异,分别为(4.87±5.18)%和(3.85±2.60)%,均低于PD-1在CD3^+或CD4^+细胞中的表达(26.63±9.04)%和(20.79±9.41)%,与健康对照组相比,SCLC中CD4^+CD25^+CTLA-4^+细胞水平明显升高(1.91±1.27)%vs(7.09±5.09)%,P<0.001;PD-1^+(CD8^+)细胞表达水平明显降低,分别为(22.56±4.21)%vs(11.47±5.85)%,P<0.001。CD4^+CD25^+CTLA-4^+细胞或CD8^+PD-1^+细胞水平与患者的年龄、性别、吸烟状况、临床分期以及是否转移等因素无关(P>0.05)。化疗两周期末CD4^+CD25^+CTLA-4^+和CD8^+PD-1^+细胞的水平对比化疗前明显下降,分别为(5.11±2.60)%vs(6.94±4.91)%;(8.74±3.39)%vs(11.48±5.91)%,P值均<0.000,1,但与无疾病进展生存和总生存无显著相关性。PD-L1高表达于SCLC细胞系H446中并定位在细胞膜和细胞浆,但在外周血中未见表达。结论本研究首次证实SCLC外周血中CTLA4高表达于调节性T细胞中,而PD-1低表达于效应性T细胞,该结果为揭示SCLC免疫监测点免疫逃逸机制提供了理论依据,可能作为一种新的无创性且可实时监测的生物标志物。展开更多
文摘目的:探究抗AGGF1中和抗体(RDD-Ab),RDD-Ab + 抗CTLA-4抗体联合治疗对小鼠黑色素瘤的治疗作用。方法:合成AGGF1的GTFQRDDAPASVHSE肽并制备多克隆中和抗体(RDD-Ab)。为了评估RDD-Ab对血管生成活性和黑色素瘤生长的影响,我们实施了小管生成实验、迁移实验、细胞增殖实验、黑色素瘤细胞皮下移植性模型实验和免疫组化等实验。结果:实验结果显示,制备的RDD-Ab可以识别细胞中天然的AGGF1蛋白和过表达的AGGF1蛋白。RDD-Ab可显著抑制血管内皮细胞小管形成、迁移和增殖。与IgG对照组相比,RDD-Ab治疗显著减缓黑色素瘤生长,RDD-Ab + CTLA-4抗体联合治疗时肿瘤生长速度最慢。免疫组化实验也表明,RDD-Ab显著减少瘤内微血管生成与肿瘤细胞增殖,同时,联合治疗可显著增加瘤内CD4+和CD8+淋巴细胞的浸润。结论:RDD-Ab可在体外抑制血管内皮细胞的血管新生功能,具有高效的黑色素瘤生长抑制作用,RDD-Ab + CTLA-4联合治疗黑色素瘤效果更佳(显著增加瘤内CD4+和CD8+淋巴细胞的浸润),这为未来黑色素瘤的临床干预提供了一种新的潜在治疗方案。Objective: To investigate the therapeutic effect of neutralizing antibody (against AGGF1, RDD-Ab), RDD-Ab + CTLA-4 therapy on mouse melanoma. Methods: Synthesize GTFQRDAPASVHSE peptide of AGGF1 and prepare polyclonal neutralizing antibody (RDD-Ab). In order to evaluate the effects of RDD-Ab on angiogenesis and melanoma growth, we conducted tube formation, migration, cell proliferation, subcutaneous melanoma cell transplantation model and immunohistochemistry (IHC). Results: RDD-Ab can recognize both natural AGGF1 protein and overexpressed AGGF1 protein in cells. The experimental results showed that RDD-Ab significantly inhibits the formation, migration, and proliferation of endothelial cell tubules. Compared with the IgG control group, RDD-Ab significantly slowed down the growth of melanoma. IHC experiments showed that RDD-Ab significantly suppressed tumor angiogenesis and proliferation. The combination therapy of RDD-Ab + CTLA-4 antibody has the slowest tumor growth rate, and the combination therapy increases the infiltration of CD4+ and CD8+ lymphocytes robustly in solid tumors. Conclusion: RDD-Ab can inhibit the angiogenesis function of endothelial cells in vitro and has a highly effective inhibitory effect on melanoma growth has an efficient inhibitory effect on melanoma growth, and the combined treatment with CTLA-4 antibody is more effective. This provides a new potential treatment option for clinical intervention of melanoma in the future.
文摘BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.
文摘背景与目的本研究旨在探索细胞毒性T淋巴细胞相关抗原(cytotoxic T lymphocyte associated antigen-4,CTLA-4)、程序坏死因子(programmed death 1,PD-1)和程序坏死因子配体(programmed death ligand 1,PD-L1)在小细胞肺癌(small cell lung cancer,SCLC)患者外周血中的分布情况,探索其免疫作用机制并评估其作为生物标志物的临床价值。方法招募290例SCLC患者及60例健康志愿者,收集治疗前和治疗2^(nd)周期末SCLC患者EDTA抗凝血2 mL。应用流式细胞仪检测CTLA-4、PD-1和PD-L1在外周血CD3、CD4、CD8及CD25的分布,分析其与临床病理特征的相关性;采用细胞免疫化学法和流式细胞法检测PD-L1在SCLC细胞系H446中的表达。结果 SCLC患者外周血中CTLA-4^+细胞和PD-1^+细胞水平分别为(1.56±1.24)%和(8.07±3.97)%、CTLA-4在CD3细胞和CD4细胞中的表达水平无明显差异,分别为(4.87±5.18)%和(3.85±2.60)%,均低于PD-1在CD3^+或CD4^+细胞中的表达(26.63±9.04)%和(20.79±9.41)%,与健康对照组相比,SCLC中CD4^+CD25^+CTLA-4^+细胞水平明显升高(1.91±1.27)%vs(7.09±5.09)%,P<0.001;PD-1^+(CD8^+)细胞表达水平明显降低,分别为(22.56±4.21)%vs(11.47±5.85)%,P<0.001。CD4^+CD25^+CTLA-4^+细胞或CD8^+PD-1^+细胞水平与患者的年龄、性别、吸烟状况、临床分期以及是否转移等因素无关(P>0.05)。化疗两周期末CD4^+CD25^+CTLA-4^+和CD8^+PD-1^+细胞的水平对比化疗前明显下降,分别为(5.11±2.60)%vs(6.94±4.91)%;(8.74±3.39)%vs(11.48±5.91)%,P值均<0.000,1,但与无疾病进展生存和总生存无显著相关性。PD-L1高表达于SCLC细胞系H446中并定位在细胞膜和细胞浆,但在外周血中未见表达。结论本研究首次证实SCLC外周血中CTLA4高表达于调节性T细胞中,而PD-1低表达于效应性T细胞,该结果为揭示SCLC免疫监测点免疫逃逸机制提供了理论依据,可能作为一种新的无创性且可实时监测的生物标志物。
