目的探讨贝伐珠单抗联合TP(紫杉醇+顺铂)化疗方案治疗晚期非小细胞肺癌(NSCLC)的疗效及对预后的影响。方法选取晚期NSCLC患者78例,随机分为A组(39例,予以TP化疗方案)和B组(39例,予以TP化疗方案+贝伐珠单抗)。比较2组的客观缓解率(ORR)...目的探讨贝伐珠单抗联合TP(紫杉醇+顺铂)化疗方案治疗晚期非小细胞肺癌(NSCLC)的疗效及对预后的影响。方法选取晚期NSCLC患者78例,随机分为A组(39例,予以TP化疗方案)和B组(39例,予以TP化疗方案+贝伐珠单抗)。比较2组的客观缓解率(ORR)、疾病控制率(DCR)和血清肿瘤标志物[血管内皮生长因子(VEGF)、细胞角蛋白19片段(CYFRA21-1)、癌胚抗原(CEA)]水平。记录治疗期间肝肾功能损害、白细胞减少、中性粒细胞减少、血小板减少、胃肠道反应等不良反应发生情况。自实施治疗日始对患者进行随访,统计2组患者的5年生存率、无进展生存期(PFS)和总生存期(OS)。结果B组ORR、DCR分别为58.97%、89.74%,分别高于A组的35.90%、71.79%(P<0.05)。治疗后2组血清VEGF、CYFRA21-1、CEA水平均降低,且B组低于A组(P<0.05)。2组肝、肾功能损害,白细胞减少,中性粒细胞减少,血小板减少,胃肠道反应发生率均无明显差异(P>0.05)。B组5年生存率为20.51%,与A组(12.82%)相比无明显差异(P>0.05)。Kaplan-Meier生存曲线显示,B组的中位PFS长于A组(8.9 vs 7.2个月)(P<0.05);B组的中位OS长于A组(25.6 vs 17.9个月)(P<0.05)。结论相比于TP化疗方案治疗晚期NSCLC,联合贝伐珠单抗可提高ORR和DCR,延长PFS和OS,且可降低VEGF、CYFRA21-1、CEA肿瘤标志物水平。展开更多
The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatm...The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget actions.As a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(P.grandiflorum)and is used as an expectorant for pulmonary disease in Asia[2].展开更多
The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)inductio...The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.展开更多
文摘目的探讨贝伐珠单抗联合TP(紫杉醇+顺铂)化疗方案治疗晚期非小细胞肺癌(NSCLC)的疗效及对预后的影响。方法选取晚期NSCLC患者78例,随机分为A组(39例,予以TP化疗方案)和B组(39例,予以TP化疗方案+贝伐珠单抗)。比较2组的客观缓解率(ORR)、疾病控制率(DCR)和血清肿瘤标志物[血管内皮生长因子(VEGF)、细胞角蛋白19片段(CYFRA21-1)、癌胚抗原(CEA)]水平。记录治疗期间肝肾功能损害、白细胞减少、中性粒细胞减少、血小板减少、胃肠道反应等不良反应发生情况。自实施治疗日始对患者进行随访,统计2组患者的5年生存率、无进展生存期(PFS)和总生存期(OS)。结果B组ORR、DCR分别为58.97%、89.74%,分别高于A组的35.90%、71.79%(P<0.05)。治疗后2组血清VEGF、CYFRA21-1、CEA水平均降低,且B组低于A组(P<0.05)。2组肝、肾功能损害,白细胞减少,中性粒细胞减少,血小板减少,胃肠道反应发生率均无明显差异(P>0.05)。B组5年生存率为20.51%,与A组(12.82%)相比无明显差异(P>0.05)。Kaplan-Meier生存曲线显示,B组的中位PFS长于A组(8.9 vs 7.2个月)(P<0.05);B组的中位OS长于A组(25.6 vs 17.9个月)(P<0.05)。结论相比于TP化疗方案治疗晚期NSCLC,联合贝伐珠单抗可提高ORR和DCR,延长PFS和OS,且可降低VEGF、CYFRA21-1、CEA肿瘤标志物水平。
基金funded by the National Natural Science Foundation of China(Grant Nos.:82004081 and 52073145)the National Natural Science Foundation of Nanjing University of Chinese Medicine,China(Grant No.:NZY82004081).
文摘The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget actions.As a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(P.grandiflorum)and is used as an expectorant for pulmonary disease in Asia[2].
基金National Natural Science Foundation of China(Grants Numbers 81902878 and 81971468).
文摘The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.
