OBJECTIVE:To explore the effects of Weitiao No.3(微调3号方,WD-3)on anti-programmed cell death protein-1(PD-1)immunotherapy in gastric cancer(GC).METHODS:The intestinal microbiota was analyzed by 16S rDNA sequencing of...OBJECTIVE:To explore the effects of Weitiao No.3(微调3号方,WD-3)on anti-programmed cell death protein-1(PD-1)immunotherapy in gastric cancer(GC).METHODS:The intestinal microbiota was analyzed by 16S rDNA sequencing of fecal samples from three groups:healthy people(Health),GC patients(GC),and WD-3-treated GC patients(WD-3).Next,we established an orthotopic model of GC mice,which were treated with anti-PD-1,WD-3,or an inoculation of intestinal bacteria.Immune markers CD3,CD4,CD8,and forkhead box protein P3(FOXP3),and the cell proliferation marker Ki67,were evaluated by immunohistochemistry.Cell apoptosis in GC tumors was assessed by terminaldeoxynucleotidyl-transferase-mediated deoxyuridine triphosphate nick end labeling staining.Enzyme-linked immunosorbent assays(ELISAs)were performed to analyze the serum levels of the following cytokines in GC mice:tumor necrosis factor(TNF)-α,interleukin(IL)-2,IL-6,IL-10,interferon(IFN)-γ,and transforming growth factor(TGF)-β.RESULTS:Sequencing data showed that there were significant differences in the composition of the gut microbial community among the three human groups.The gut bacteria in the three groups mainly comprised the phyla Firmicutes,Proteobacteria,Bacteroidetes,and Actinobacteria.At the genus level,the relative abundances of Bifidobacterium and Coprococcus showed significant decreases in the GC group,and an obvious increase in the WD-3 group,compared with the Health group.Interestingly,the relative abundance of Saccharopolyspora was only detected in the WD-3 group.The results of in vivo experiments in GC mice showed that WD-3 or anti-PD-1 treatment increased the levels of CD3+,CD4+,and CD8+T cells,but decreased the levels of FOXP3+regulatory T cells.Furthermore,WD-3 or PD-1 antibody treatment inhibited proliferation and promoted apoptosis of GC tumor cells.ELISA analysis showed that WD-3 or PD-1 antibody treatment facilitated TNF-α,IL-2,and IFN-γexpression,while suppressing IL-6,IL-10,and TGF-βexpression.Combination therapy with WD-3 and anti-PD-1 intensified all of these effects.CONCLUSION:WD-3 enhanced the immunotherapeutic efficacy of anti-PD-1 by modulating the intestinal microbiota in an orthotopic model of GC mice.展开更多
目的观察微调三号方联合XELOX方案(希罗达+奥沙利铂)对Ⅳ期胃癌患者生存质量的疗效。方法将51例Ⅳ期胃癌患者随机分为治疗组和对照组,治疗组26例采用微调三号方联合XELOX方案化学治疗,对照组25例单纯接受XELOX方案化学治疗。采用欧洲癌...目的观察微调三号方联合XELOX方案(希罗达+奥沙利铂)对Ⅳ期胃癌患者生存质量的疗效。方法将51例Ⅳ期胃癌患者随机分为治疗组和对照组,治疗组26例采用微调三号方联合XELOX方案化学治疗,对照组25例单纯接受XELOX方案化学治疗。采用欧洲癌症研究与治疗组织生命质量核心量表(European organization for research and treatment of cancer quality of life core questionnaire 30,EORTCQLQ-C30)及体力状况Karnofsky评分标准,进行两组生存质量的对照观察。结果治疗组在改善Ⅳ期胃癌患者EORTC QLQ-C30量表的乏力、恶心呕吐、失眠、食欲丧失、腹泻、总体健康状况及提高Karnofsky评分方面显著优于对照组(P<0.05,或P<0.01)。结论微调三号方联合XELOX方案治疗能够提高Ⅳ期胃癌患者的生存质量。展开更多
基金the National Natural Science Foundation of China:to Explore the Role and Mechanism of Weitiao No.3 in Promoting Immunotherapy of Gastric Cancer by Activating Peroxisome Proliferator-activated Receptor-γ/AMP-activated Protein Kinase Signaling Pathway through Short Chain Fatty Acid based on Intestinal Flora(No.82274269)the Nature Foundation of Nanjing University of Chinese Medicine:to Investigate the Effect and Mechanism of Weitiao No.3 on Immunotherapy of Gastric Cancer based on Peroxisome Proliferator-activated Receptor-γ/AMP-activated Protein Kinase Signaling Pathway(No.XZR2020079)the Wuxi Administration of Traditional Chinese Medicine Scientific Research Project:Clinical and Basic Study on the Effect of Weitiao No.3 Mixture on Immunotherapy of Gastric Cancer by Regulating Intestinal Microecology(No.ZYKJ201906)。
文摘OBJECTIVE:To explore the effects of Weitiao No.3(微调3号方,WD-3)on anti-programmed cell death protein-1(PD-1)immunotherapy in gastric cancer(GC).METHODS:The intestinal microbiota was analyzed by 16S rDNA sequencing of fecal samples from three groups:healthy people(Health),GC patients(GC),and WD-3-treated GC patients(WD-3).Next,we established an orthotopic model of GC mice,which were treated with anti-PD-1,WD-3,or an inoculation of intestinal bacteria.Immune markers CD3,CD4,CD8,and forkhead box protein P3(FOXP3),and the cell proliferation marker Ki67,were evaluated by immunohistochemistry.Cell apoptosis in GC tumors was assessed by terminaldeoxynucleotidyl-transferase-mediated deoxyuridine triphosphate nick end labeling staining.Enzyme-linked immunosorbent assays(ELISAs)were performed to analyze the serum levels of the following cytokines in GC mice:tumor necrosis factor(TNF)-α,interleukin(IL)-2,IL-6,IL-10,interferon(IFN)-γ,and transforming growth factor(TGF)-β.RESULTS:Sequencing data showed that there were significant differences in the composition of the gut microbial community among the three human groups.The gut bacteria in the three groups mainly comprised the phyla Firmicutes,Proteobacteria,Bacteroidetes,and Actinobacteria.At the genus level,the relative abundances of Bifidobacterium and Coprococcus showed significant decreases in the GC group,and an obvious increase in the WD-3 group,compared with the Health group.Interestingly,the relative abundance of Saccharopolyspora was only detected in the WD-3 group.The results of in vivo experiments in GC mice showed that WD-3 or anti-PD-1 treatment increased the levels of CD3+,CD4+,and CD8+T cells,but decreased the levels of FOXP3+regulatory T cells.Furthermore,WD-3 or PD-1 antibody treatment inhibited proliferation and promoted apoptosis of GC tumor cells.ELISA analysis showed that WD-3 or PD-1 antibody treatment facilitated TNF-α,IL-2,and IFN-γexpression,while suppressing IL-6,IL-10,and TGF-βexpression.Combination therapy with WD-3 and anti-PD-1 intensified all of these effects.CONCLUSION:WD-3 enhanced the immunotherapeutic efficacy of anti-PD-1 by modulating the intestinal microbiota in an orthotopic model of GC mice.
文摘目的观察微调三号方联合XELOX方案(希罗达+奥沙利铂)对Ⅳ期胃癌患者生存质量的疗效。方法将51例Ⅳ期胃癌患者随机分为治疗组和对照组,治疗组26例采用微调三号方联合XELOX方案化学治疗,对照组25例单纯接受XELOX方案化学治疗。采用欧洲癌症研究与治疗组织生命质量核心量表(European organization for research and treatment of cancer quality of life core questionnaire 30,EORTCQLQ-C30)及体力状况Karnofsky评分标准,进行两组生存质量的对照观察。结果治疗组在改善Ⅳ期胃癌患者EORTC QLQ-C30量表的乏力、恶心呕吐、失眠、食欲丧失、腹泻、总体健康状况及提高Karnofsky评分方面显著优于对照组(P<0.05,或P<0.01)。结论微调三号方联合XELOX方案治疗能够提高Ⅳ期胃癌患者的生存质量。