Prognostic and predictive biomarkers in metastatic colorectal cancer anti-EGFR therapy

AIM: To reviewing genetic and epigenetic make-up of metastatic colorectal cancers(m CRCs) addicted to epidermal growth factor receptor(EGFR) signalling.METHODS: The present study summarizes the potential value of prognostic and predictive biomarkers in selecting m CRC patients treated with anti-EGFR therapy. A meta-analysis was performed using a systematic search of Pub Med, Medline and Web of Science to identify eligible papers until March 21 st, 2016 using these following terms: ‘‘colorectal cancer'', "predictive biomarkers' ', "anti-EGFR therapy", "KRAS", "NRAS'', "PIK3CA", "TP53", "PTEN", ‘‘EGFR", "MET", "HER2", "epiregulin", "amphiregulin", "prognostic biomarkers", "BRAF", "miR NA" and "antibody-dependent cell-mediated cytotoxicity(ADCC) activity". Two investigators independently evaluated and extracted data from each identified studies based on selected criteria of inclusion and exclusion. RESULTS: The introduction of agents targeting EGFR such as cetuximab and panitumumab increased overall survival of mC RCs. Nevertheless, it has firstly became evident that response rates to cetuximab regimens in unselected patient populations were typically lower than 30%. Clinical data confirmed the predictive value of RAS mutations for resistance to cetuximab and panitumumab leading to the license of these monoclonal antibodies exclusively for the management of patients with RAS-wild type colorectal cancers. So far the identification of predictive biomarkers have generated interesting, though preliminary and, at times, conflicting data on the importance of tumour mR NA levels of EGFR ligands, of activating mutations in other genes such as NRAS and PIK3 CA. The prognostic value of selected micro RNAs level and ADCC activity is under investigation, while the prognostic impact of BRAF status remains controversial.CONCLUSION: This review focuses on the personalized treatment of m CRC and discusses the potential of new prognostic and predictive biomarkers in selecting patients treated with anti-EGFR therapy.

小鼠中性粒细胞对体外培养日本血吸虫童虫杀伤作用的研究

用体外培养方法,观察了小鼠腹腔中性粒细胞、中性粒细胞与免疫血清、补体等因子对体外机械转变的日本血吸虫童虫的杀份作用。实验结果表明:单纯小鼠中性粒细胞对童虫无杀伤作用;但在抗体及补体参与下,对童虫的杀伤明显增强,提示中性粒细胞与血清免疫因子对童虫的杀伤有协同作用。此外,比较正常小鼠和感染小鼠中性粒细胞对童虫的杀伤能力,比较不同虫龄对中性粒细胞参与的免疫作用的敏感性,证实机械转变童虫孵育24h 后对中性粒细胞参与的免疫杀伤的抵抗力增强(P<0.01)。文中对中性粒细胞依赖抗体、补体对童虫的杀伤机理进行讨论。并提出评价血吸虫细胞免疫标准化问题的意见。