肺癌(lung cancer, LC)作为全世界疾病中负担最重的恶性肿瘤之一,在全球恶性肿瘤死亡顺位中占头位,也是全世界男性癌症发病和死亡的重要原因,女性LC的发病率仅次于乳腺癌和结直肠癌,死亡率仅次于乳腺癌。我国是LC大国,全球将近一半的LC发病和死亡发生在我国。非小细胞肺癌(NSCLC)是肺癌的重要病理类型,大约占所有LC的85%,由于早期症状的非特异性及缺乏早期有效的筛查方法,多数发现时已是晚期。含铂双药化疗是以往晚期非小细胞肺癌患者的标准诊疗方案,但其治疗效果不佳,同时伴有严重不良反应降低患者的生活质量等缺点。如何延长晚期非小细胞肺癌患者的生存期是目前亟待解决的难题。免疫检测点抑制剂(ICIs)作为一种新兴免疫疗法,极大地改变了肺癌的诊疗模式,有效地提高了晚期肺癌患者的总生存率,从而在世界范围肺癌治疗领域掀起了免疫研究热点。本综述梳理了免疫检查点抑制剂(ICIs)在晚期NSCLC中的研究进展、安全性及其疗效预测标记物。Lung cancer (LC), one of the most burdensome malignant tumors in the world, ranks first in the global mortality rate of malignant tumors and is a significant cause of cancer morbidity and mortality among men worldwide. The incidence of LC in women is only second to breast cancer and colorectal cancer, and the mortality rate is only second to breast cancer. China is a major country with LC, with nearly half of the global LC cases and deaths occurring in China. Non-small cell lung cancer (NSCLC) is an important pathological type of LC, accounting for approximately 85% of all LC cases. Due to the non-specificity of early symptoms and the lack of effective early screening methods, most cases are discovered at an advanced stage. Platinum-based doublet chemotherapy was the standard treatment for advanced NSCLC patients in the past, but its therapeutic effect was poor and it was accompanied by severe adverse reactions that reduced the quality of life of patients. How to prolong the survival period of advanced NSCLC patients is currently an urgent problem to be solved. Immune checkpoint inhibitors (ICIs), as a new type of immunotherapy, have greatly changed the treatment model of lung cancer, effectively improving the overall survival rate of advanced lung cancer patients, thus triggering a research hotspot in the field of lung cancer treatment worldwide. This review briefly summarizes the research progress, safety, and efficacy prediction markers of immune checkpoint inhibitors (ICIs) in advanced NSCLC.
目的研究髓样细胞触发受体-1(TREM-1)在人肝细胞癌(HCC)发生发展过程中的表达及意义。方法应用免疫组化法检测HCC 76例、肝硬化33例、肝炎30例、正常肝组织20例中TREM-1蛋白的表达及定位,并对该蛋白与HCC临床病理特征之间的关系进行分析。进一步在体外使用人正常肝细胞LO2和肝癌细胞SMMC-7721,采用RT-PCR和Western blotting法检测TREM-1 m RNA及蛋白表达,以证实组织学结果。结果正常肝组织中TREM-1为阴性表达;肝炎、肝硬化和HCC组织中该蛋白表达显著上调,阳性表达率分别为20.00%(6/30)、24.24%(8/33)和21.05%(16/76),但该3组间差异无统计学意义(χ2=0.195,P=0.907)。与非癌肝组织(肝炎、肝硬化组织)相比,HCC组织中阳性表达的TREM-1蛋白定位发生明显改变:非癌肝组织中TREM-1主要定位于肝细胞胞核中,偶见定位于细胞质;HCC组织中阳性表达的蛋白颗粒均位于癌细胞胞质,未见细胞核定位。TREM-1蛋白与癌病理分级呈负相关(r=-0.261,P=0.023),而与年龄、性别、肿瘤大小、临床分期、肝病背景、淋巴结转移及脉管癌栓无明显相关(均P>0.05)。细胞学实验显示LO2细胞有部分TREM-1 m RNA及蛋白表达,而SMMC-7721肝癌细胞该指标明显上调。结论 TREM-1蛋白的表达上调及在胞质中的异常定位可能与HCC发生发展相关。
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