Immunotherapy is an important treatment method in tumor therapy. Among them, programmed death-1/programmed death ligand-1 inhibitors are the immune preparations with mature application and great survival benefit at present. Programmed death-1/programmed death ligand-1 inhibitors brought better clinical benefits to patients with esophageal cancer and provided more favorable choice for the treatment of esophageal cancer. This article introduces the mechanism of action, application in esophageal cancer, and efficacy predictors of programmed death protein-1/programmed death protein ligand-1 inhibitors, aiming to provide a theoretical basis for the more rational use of programmed death protein-1/programmed death protein ligand-1 inhibitors in patients with esophageal cancer.
【摘要】 目的 剪切修复偶联因子1（ERCC1）是核苷酸外切修复家族中的重要成员，它在核酸损伤修复过程和凋亡过程中起着重要作用；存活蛋白（Survivin）属凋亡抑制蛋白家族，是迄今发现的最强的凋亡抑制因子之一。研究中初步探索晚期非小细胞肺癌（non-small-cell lung cancer，NSCLC）中ERCC1和Survivin与铂类化学疗法敏感性的关系及其相关性。 方法 2001年1月－2002年6月对51例晚期NSCLC（ⅢB或Ⅳ期）标本经免疫组织化学检测ERCC1和Survivin的表达，患者行至少2周期含铂方案化学疗法，2周期化学疗法后评价疗效，采用SPSS 13.0软件就检测指标和化学疗法疗效评价进行相关统计分析。 结果 ERCC1和Survivin在肿瘤组织中阳性表达率分别为58.8 %（30/51）和76.5 %（39/51）。ERCC1阴性组化学疗法有效率高于阳性组（Plt;0.05），5年生存时间高于阳性组（Plt;0.05）；Survivin阴性组化学疗法有效率虽高于阳性组，但无统计学意义（Pgt;0.05），其5年生存时间与阴性组比较无差别（Pgt;0.05）。Spearman相关分析提示ERCC1与Survivin之间无相关性（rs=-0.088，P=0.537）。 结论 ERCC1和Survivin可能与NSCLC的发生相关，ERCC1可能与肿瘤的预后相关，并对化学疗法疗效具有一定预测价值。ERCC1和Survivin之间耐药机制可能各不相同。【Abstract】 Objective Excision repair cross-complementing 1 (ERCC1), an important member of the DNA repair gene family, plays a key role in nucleotide excision repair and apoptosis of tumor cells. Survivin, a member of inhibitor of apoptosis protein (IAP) family, is one of the most powerful factors in inhibiting apoptosis up to now. This study is to explore the value of ERCC1 and Survivin in predicting the sensitivity of non-small cell lung cancer (NSCLC) to platinum-based chemotherapy and the interrelationship between the two markers. Methods From January 2001 to June 2002, expressions of ERCC1 and Survivin of 51 advanced NSCLC patients (Ⅲ B or IV) were tested through immunohistochemistry. The patients were treated with at least 2 cycles of platinum-based chemotherapy. The curative effect was evaluated later, and the relationship among detected data, curative effect of chemotherapy and patients′ clinical parameters were analyzed with SPSS 13.0 software. Results The positive expression rates of ERCC1 and Survivin in NSCLC tissues were 58.8 % (30/51) and 76.5 % (39/51), respectively. The effective rate of chemotherapy and 5-year survival rate for the negative group of ERCC1 were significantly higher than those for the positive group (Plt;0.05). The results for Survivin were similar to those for ERCC1, but there was no statistical significance (Pgt;0.05). We also found there was no relationship between ERCC1 and Survivin by Spearman′s correlation analysis (rs=-0.088, P=0.537). Conclusion ERCC1 and Survivin may be correlated with the development of NSCLC, and ERCC1 may be related to curative effect and prognosis of NSCLC. There was probably no mechanism of coordination or regulation in multi-drug resistance between ERCC1 and Survivin.
目的 探讨冬凌草甲素（Ori）对白血病Molt-4细胞致凋亡作用及其可能的机制。 方法 将不同浓度的Ori（2.5、5、10、20、40 μmol/L）作用于Molt-4细胞。采用甲基噻唑基四唑（MTT）法检测细胞增殖，流式细胞术检测细胞凋亡，电子显微镜观察细胞凋亡超微结构的变化，Western blot方法分析凋亡相关蛋白及Caspase-3表达的变化。 结果 Ori可抑制Molt-4细胞的生长及诱导凋亡，并有时间-剂量依赖性；Ori可时间依赖性的下调抗凋亡蛋白Bcl-2的表达，上调促凋亡蛋白Bax和Bim表达以及活化Caspase-3。 结论 Ori可诱导Molt-4细胞凋亡，其机制可能与调节Bcl-2家族蛋白及活化Caspase-3有关。
目的 观察消化道肿瘤患者服用甲羟孕酮（medroxyprogesterone acetate, MPA）对化疗后骨髓抑制的影响。 方法 2008年11月-2009年8月，将接受化疗的消化道肿瘤患者共100例随机分为治疗组(MPA加化疗组，54例)及对照组(单纯化疗组，46例)，2周期化疗后评价骨髓抑制状况和生活质量变化。 结果 治疗组和对照组化疗后白细胞、血红蛋白和血小板Ⅰ~Ⅱ度骨髓抑制发生率没有差异（Pgt;0.05），但治疗组Ⅲ~Ⅳ度骨髓抑制发生率低于对照组，KPS评分改善率高于对照组（Plt;0.05）。未见明显不良反应。 结论 MPA可有效减轻化疗后骨髓抑制。