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 剪切修復偶聯因子1（ERCC1）是核苷酸外切修復家族中的重要成員，它在核酸損傷修復過程和凋亡過程中起著重要作用；存活蛋白（Survivin）屬凋亡抑制蛋白家族，是迄今發現的最強的凋亡抑制因子之一。研究中初步探索晚期非小細胞肺癌（non-small-cell lung cancer，NSCLC）中ERCC1和Survivin與鉑類化學療法敏感性的關系及其相關性。 方法 2001年1月－2002年6月對51例晚期NSCLC（ⅢB或Ⅳ期）標本經免疫組織化學檢測ERCC1和Survivin的表達，患者行至少2周期含鉑方案化學療法，2周期化學療法后評價療效，采用SPSS 13.0軟件就檢測指標和化學療法療效評價進行相關統計分析。 結果 ERCC1和Survivin在腫瘤組織中陽性表達率分別為58.8 %（30/51）和76.5 %（39/51）。ERCC1陰性組化學療法有效率高于陽性組（Plt;0.05），5年生存時間高于陽性組（Plt;0.05）；Survivin陰性組化學療法有效率雖高于陽性組，但無統計學意義（Pgt;0.05），其5年生存時間與陰性組比較無差別（Pgt;0.05）。Spearman相關分析提示ERCC1與Survivin之間無相關性（rs=-0.088，P=0.537）。 結論 ERCC1和Survivin可能與NSCLC的發生相關，ERCC1可能與腫瘤的預后相關，并對化學療法療效具有一定預測價值。ERCC1和Survivin之間耐藥機制可能各不相同。【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 探討冬凌草甲素（Ori）對白血病Molt-4細胞致凋亡作用及其可能的機制。 方法 將不同濃度的Ori（2.5、5、10、20、40 μmol/L）作用于Molt-4細胞。采用甲基噻唑基四唑（MTT）法檢測細胞增殖，流式細胞術檢測細胞凋亡，電子顯微鏡觀察細胞凋亡超微結構的變化，Western blot方法分析凋亡相關蛋白及Caspase-3表達的變化。 結果 Ori可抑制Molt-4細胞的生長及誘導凋亡，并有時間-劑量依賴性；Ori可時間依賴性的下調抗凋亡蛋白Bcl-2的表達，上調促凋亡蛋白Bax和Bim表達以及活化Caspase-3。 結論 Ori可誘導Molt-4細胞凋亡，其機制可能與調節Bcl-2家族蛋白及活化Caspase-3有關。
目的 觀察消化道腫瘤患者服用甲羥孕酮（medroxyprogesterone acetate, MPA）對化療后骨髓抑制的影響。 方法 2008年11月-2009年8月，將接受化療的消化道腫瘤患者共100例隨機分為治療組(MPA加化療組，54例)及對照組(單純化療組，46例)，2周期化療后評價骨髓抑制狀況和生活質量變化。 結果 治療組和對照組化療后白細胞、血紅蛋白和血小板Ⅰ~Ⅱ度骨髓抑制發生率沒有差異（Pgt;0.05），但治療組Ⅲ~Ⅳ度骨髓抑制發生率低于對照組，KPS評分改善率高于對照組（Plt;0.05）。未見明顯不良反應。 結論 MPA可有效減輕化療后骨髓抑制。