ERCC1与TS在非小细胞肺癌中的表达及与铂类化疗敏感性的关系

目的 通过对非小细胞肺癌(NSCLC)组织与癌旁组织中切除修复交叉互补基因1(ERCC1)、胸苷酸合成酶(TS)的检测,探讨其表达与NSCLC临床特征及预后的关系,为NSCLC个体化治疗提供实验依据.方法 采用免疫组化方法检测50例NSCLC患者术后癌组织和癌旁组织标本中ERCC1、TS蛋白的表达水平,探讨ERCC1、TS的表达与NSCLC患者总生存期(OS)、疾病进展时间(TTP)及中位OS、中位TTP之间的关系.结果 (1)ERCC1、TS在NSCLC患者癌组织与癌旁组织中的阳性表达率比较,差异具有统计学意义(64.00％ vs 20.00％,x2=19.87,P＜0.01;48.00％ vs24.00％,x2=6.25,P＜0.05).(2)接受术后铂类方案化疗并随访,ERCC1阴性表达者中位OS明显长于阳性表达者(19.10个月vs 10.00个月,x2=8.133,P=0.002),中位TTP亦明显长于阳性表达者(15.30个月vs 9.00个月,x2=7.410,P=0.003).TS阴性表达者的中位OS(17.80个月vs11.00个月,x2=7.001,P=0.008)、中位TTP(11.40个月vs 6.80个月,x2=5.884,P=0.026)均明显长于TS阳性表达者.结论 ERCC1、TS蛋白可能成为NSCLC患者对铂类药物敏感性的预测因子;二者联合检测有助于NSCLC患者个体化治疗方案的选择.     

组织δ样配体3表达和着色性干皮病基因G基因多态性与晚期肺鳞癌患者铂类化疗敏感性的关系及交互作用分析

目的探讨组织δ样配体3(DLL3)表达和着色性干皮病基因G(XPG)基因多态性对晚期肺鳞癌患者铂类化疗敏感性影响的交互作用。方法回顾性选取2019年3月至2021年12月岳池县人民医院收治的140例晚期肺鳞癌患者, 均在充分知情前提下给予卡铂+注射用紫杉醇(白蛋白结合型), 每3周为1个周期, 共治疗4个周期。根据化疗敏感性分为敏感组46例和非敏感组94例, 比较两组基线资料、组织DLL3表达评分和XPG基因多态性, 比较不同XPG基因型患者组织DLL3表达评分, 采用多因素Logistic回归分析影响化疗敏感性的危险因素, 采用交互作用系数γ分析组织DLL3表达和XPG基因多态性的交互作用是否存在及其作用类型。结果敏感组组织DLL3表达评分低于非敏感组[(3.28 ± 0.93)分比(7.59 ± 1.22)分], 差异有统计学意义(P<0.01)。敏感组CC基因型患者多于非敏感组, CT、TT基因型患者少于非敏感组(P<0.05)。CC、CT、TT基因型患者组织DLL3表达评分分别为(3.51 ± 0.93)、(6.76 ± 1.08)和(10.09 ± 1.12)分,...     

草酸铂联合体外化疗药物敏感实验指导肝癌术后个体性化疗

目的评估草酸铂用于原发性肝癌术后化疗的疗效,同时联合体外药敏试验进行药物筛选,评估该系统是否可提高化疗疗效。方法26例原发性肝癌患者均在接受手术切除后肿瘤标本采用了体外药物敏感实验一三磷酸腺苷肿瘤化疗敏感实验（adenosine triphosphate tumor chemosensi-tivityassay,ATP-TCA）进行了药物（阿霉素、丝裂霉素、诺消灵、草酸铂、开普拓、5一Fu、健择、卡铂、顺铂、泰索帝和足叶已甙）评估,其中草酸铂敏感11例（敏感组）,15例未报敏感（对照组）。全部患者接受了以草酸铂为主的化疗方案治疗。参照RECIST标准对该方案疗效（CR、PR、SD、PD、ORRxOS和DFS）以及ATP—TCA试验系统的效力进行评估,按照抗癌药毒副反应的分度标准（WHO标准）评价疗效及毒副反应。结果26例获得可评估客观疗效。该方案总疗效分析：CR10例（38．46％）,PR5例（12．23％）,SD6例（23．08％）,PD5例（12．23％）。在敏感组患者中,6例患者获得CR,3例PR,1例SD,1例PD;对照组4例获得CR,2例PR,5例SD,4例PD。两组比较差异无统计学意义（P〉0．05）,两组在总生存期（OS,P=0．1116）和无瘤生存期（DFS,P=0．2328）方面差异无统计学意义（P〉0．05）,而敏感组在总病情缓解率（ORR,81．8％VS40．0％,P=0．040）方面表现出明显的优势。共发生Ⅰ、Ⅱ度骨髓抑制14例（53．8％）,Ⅰ、Ⅱ度胃肠道反应13例（50％）,Ⅰ、Ⅱ度肝功能损害15例（57．7％）,Ⅰ、Ⅱ度周围神经病变6例（23．1％）。以上并发症多为Ⅰ、Ⅱ度,均可耐受,经过治疗后均恢复正常,两组毒副反应差异无统计学意义（P〉0．05）。结论以草酸铂为主的联合化疗方案在原发性肝癌术后化疗的疗效较高,此化疗方案可能提高肝癌术后患者的总病情缓解率,安全性好。联合应用ATP—TCA系统进行药物评估,可能提高该方案使用效率。     

Immunogenicity and safety of the quadrivalent meningococcal vaccine MenACWY-TT co-administered with a combined diphtheria-tetanus-acellular pertussis vaccine versus their separate administration in adolescents and young adults: A phase III,randomized study

BackgroundThis study evaluated the immunogenicity and safety of quadrivalent meningococcal conjugate vaccine using tetanus (T) toxoid as carrier protein (MenACWY-TT) co-administered with combined diphtheria-tetanus-acellular pertussis vaccine (Tdap) versus their separate administration in adolescents and young adults.MethodsIn this phase III, randomized, partially-blind study (NCT01767376), healthy 11–25-year-olds (N = 660) were randomized (1:1:1) to receive MenACWY-TT and Tdap at Month 0 (Co-ad group), MenACWY-TT at Month 0 and Tdap at Month 1 (ACWY_Tdap group) or Tdap at Month 0 and MenACWY-TT at Month 1 (Tdap_ACWY group). Immune responses to MenACWY-TT were measured by serum bactericidal assay using rabbit complement (rSBA). Anti-diphtheria (D), anti-tetanus (T), anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibody concentrations were assessed using enzyme-linked immunosorbent assays. Non-inferiority of immunogenicity was assessed using pre-defined clinical criteria. Safety was also evaluated.ResultsNon-inferiority of immunogenicity of MenACWY-TT and Tdap when co-administered versus their separate administration was demonstrated in terms of rSBA geometric mean titers (GMTs) for 4 meningococcal serogroups and of the percentage of participants with antibody concentrations >1 IU/ml for D and T. Among the pertussis antigens, non-inferiority criteria for geometric mean concentrations (GMCs) were reached for PT, but not met for FHA and PRN. Across all groups, ≥93.2% of participants had vaccine responses to each meningococcal serogroup, ≥99.1% were seroprotected against T and D, and ≥85.5% had booster responses to each pertussis antigen. Robust increases in antibody GMTs/GMCs were observed for all antigens between pre-and post-vaccination. Both vaccines had clinically acceptable safety profiles.ConclusionImmune responses to MenACWY-TT and to the T and D antigens from Tdap were not impacted by their co-administration. The lower antibody concentrations observed against the pertussis components may be of limited clinical relevance since robust anti-pertussis booster responses were observed. This study supports concurrent administration of the 2 vaccines in adolescents.