转录调节因子c-Myb通过炎症因子Ccl2抑制乳腺癌肺转移的实验研究

目的:研究乳腺癌细胞中转录调节因子c-Myb的表达对肺转移的影响及其分子机制。方法:构建c-Myb高表达的4T1乳腺癌细胞株，种植小鼠构建乳腺癌动物模型，检测实验动物肺转移情况，通过荷瘤抑制试验检测肺转移抑制效果。提取组织进行荧光PCR检测相关炎症因子的表达。利用Medisapiens数据库的生物信息学资源，对c-Myb和Ccl2的表达与乳腺癌患者的预后进行分析。结果:高表达c-Myb的荷瘤小鼠肺部转移灶明显减少，其中炎症相关因子表达受限。由数据库分析得出，c-Myb高表达患者生存期得以延长。结论:乳腺癌中c-Myb的表达能够通过炎症因子Ccl2抑制肺转移从而延长患者生存期。     

Developmental validation of the ANDE™ rapid DNA system with FlexPlex™ assay for arrestee and reference buccal swab processing and database searching

A developmental validation was performed to demonstrate reliability, reproducibility and robustness of the ANDE System with the FlexPlex assay, including an integrated Expert System, across a number of laboratories and buccal sample variations. Previously, the related DNAscan™/ANDE 4C Rapid DNA System using the PowerPlex^®16 assay and integrated Expert System Software received NDIS approval in March 2016. The enhanced ANDE instrument, referred to as ANDE 6C, and the accompanying 6-dye, 27-locus STR assay, referred to as FlexPlex, have been developed to be compatible with all widely used global loci, including the expanded set of the CODIS core 20 loci.Six forensic and research laboratories participated in the FlexPlex Rapid DNA developmental validation experiments, testing a total of 2045 swabs, including those obtained from 1387 unique individuals. The goal of this extensive and comprehensive validation was to thoroughly evaluate and document the ANDE System and its internal Expert System to reliably genotype reference buccal swab samples in a manner compliant with the FBI’s Quality Assurance Standards and the NDIS Operational Procedures.The ANDE System, including automated Expert System analysis, generated reproducible and concordant results for buccal swabs when testing various instruments at different laboratories by a number of different operators. When testing a number of non-human DNAs, including oral bacteria, the ANDE System and FlexPlex assay demonstrated limited cross-reactivity. Potential PCR inhibitors were evaluated as part of the validation and no inhibition was detected. Reproducible and concordant profiles were generated from buccal swab samples collected with a limit of detection appropriate for buccal swab collections from arrestees. The precision and resolution of the System met industry standards for detection of microvariants and single base resolution.The integrated Expert System appropriately demonstrated the ability to correctly pass or fail profiles for CODIS upload without human review. During this comprehensive developmental validation, the ANDE System successfully interpreted over 2000 samples tested with over 99.99% concordant alleles. The data package described herein led to the ANDE System with the FlexPlex assay receiving NDIS approval in June 2018.     

Changes in the Management of Patients having Radical Radiotherapy for Lung Cancer during the First Wave of the COVID-19 Pandemic in the UK

AimsIn response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I–III lung cancer from April to October 2020.Materials and methodsLung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I–III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression.ResultsIn total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease.ConclusionsThe COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes.     

肺鳞癌治疗新靶点FGFR的研究进展

肺癌是目前全球发病率和死亡率均居前列的恶性肿瘤，其中肺鳞癌经手术、放化疗等综合治疗后，其疗效仍不满意。随着分子靶向治疗在肺腺癌中取得了令人瞩目的成果，而肺鳞癌患者中EGFR基因突变及ALK融合基因少见，急需探索新的靶点指导肺鳞癌患者的临床治疗。研究表明，FGFR家族（FGFR1-4）是肺鳞癌中突变频率较高的基因，FGFR基因的激活突变和扩增与肺鳞癌的发生和发展密切相关，同时许多小分子 FGFR 抑制剂在临床应用中已经取得较好的治疗效果。目前，许多FGFR抑制剂治疗肺鳞癌的临床试验也正在进行研究，针对FGFR靶点的基因治疗可为肺鳞癌的治疗提供一种新的策略。本文就FGFR在肺鳞癌的靶向治疗中的最新研究进展进行综述。     

The Relationship Between Air Pollution and Lung Cancer in Nonsmokers in Taiwan

Introduction

For never-smokers (smoked <100 lifetime cigarettes), lung cancer (LC) has emerged as an important issue. We aimed to investigate the effects of prevalence changes in tobacco smoking and particulate matter (PM) 2.5 (PM_2.5) levels on LC in Taiwan, in relation to contrasting PM_2.5 levels, between Northern Taiwan (NT) and Southern Taiwan (ST).

Genetic and epigenetic alterations of the EGFR and mutually independent association with BRCA1, MGMT,and RASSF1A methylations in Vietnamese lung adenocarcinomas

Genetic and epigenetic alterations importantly contribute to the pathogenesis of lung cancer. In the study, we measured the frequency and distribution of molecular abnormalities of EGFR as well as the aberrant promoter methylations of BRCA1, MGMT, MLH1, and RASSF1A in Vietnamese lung adenocarcinomas. We investigated the association between genetic and epigenetic alteration, and between each abnormality with clinicopathologic parameters. Somatic EGFR mutation that was found in 49/139 (35.3%) lung adenocarcinomas showed a significant association with young age, female gender, and non-smokers. EGFR overexpression was identified in 82 tumors (59.0%) and statistical relationships with EGFR or BRCA1 methylation but not EGFR mutation. In addition, EGFR, BRCA1, MGMT, MLH1, and RASSF1A methylations were found in 33 (23.7%), 41 (29.5%), 46 (33.1%), 28 (20.1%), and 41 (29.5%) cases of a total of 139 lung adenocarcinomas, respectively. The RASSF1A methylation was found to be linked to the smoking habit. Methylations in MGMT and RASSF1A were also found to correlate with metastasis status. Furthermore, the distribution of EGFR mutation and that of BRCA1, MGMT or RASSF1A methylation were significantly exclusive in lung adenocarcinomas. The main finding of our study demonstrate that epigenetic abnormalities might play a critical role for the lung tumorigenesis in patients with smoking history and metastasis, and partly affect the predictive value of EGFR mutations through blocking expression due to promoter EGFR hypermethylation. Mutually exclusive distribution of genetic and epigenetic alterations reflects differently biological characteristics in the etiology of lung adenocarcinomas.     

2019年重庆市30岁及以上人群归因于被动吸烟的肺癌疾病负担研究

目的 分析重庆市肺癌发病死亡和疾病负担归因于被动吸烟的情况,为开展肺癌防治提供建议。 方法 肺癌死亡个案数据来源于2019年重庆市肿瘤登记报告系统,被动吸烟率来自2013年重庆市慢性病及危险因素监测。计算人群归因危险度百分比(population attributable risk percent, PAR%)、被动吸烟导致的肺癌发病、死亡和疾病负担。采用Excel 2010与SPSS 25.0进行统计分析,率的比较采用χ²检验。 结果 2013年30岁及以上成年人被动吸烟率为52.37%。2019年重庆市30岁及以上人群肺癌发病率与标化发病率分别为118.44/10万与80.83/10万,死亡率与标化死亡率分别为96.51/10万、63.58/10万。肺癌发病率和死亡率归因于被动吸烟的PAR%分别为19.76和19.04,归因发病率与归因标化发病率分别为23.41/10万和16.34/10万,归因死亡率与归因标化死亡率分别为18.38/10万和12.40/10万。2019年重庆市30岁及以上肺癌早死所致寿命损失年率(years of life lost,YLL)、残疾所致寿命损失年率(years lived with disability,YLD)、调整伤残寿命损失年率(disability adjusted life year,DALY)分别为21.16‰、0.31‰、21.47‰,YLL率、YLD率、DALY率归因于被动吸烟的PAR%分别为21.16、19.76和20.49,归因YLL率为4.34‰,归因YLD率为0.06‰,归因DALY率为4.40‰。 结论 2019年重庆市30岁及以上人群肺癌发病率、死亡率、YLL率、DALY率高,被动吸烟率高,肺癌归因于被动吸烟的疾病负担重,应加强落实控烟工作。     

电针复合TCI靶控输注在单肺通气食管癌开胸手术麻醉中的应用与安全性＊

目的 探讨电针复合靶控输注（Target Controlled Infusion， TCI）在单肺通气食管癌开胸手术麻醉中的应用价值。方法 选取于我院拟行单肺通气食管癌开胸切除手术患者60例作为研究对象。随机将其分为试验组与对照组，对照组30例采取气管插管全麻及TCI靶控输注维持麻醉深度，试验组30例则在对照组方案基础上辅助电针麻醉，记录两组患者手术麻醉时间、药物用量、苏醒时间、并发症；以及术前（T_Ⅰ）、插管前即刻（T_Ⅱ）、插管后1 min（T_Ⅲ）、切皮即刻（T_Ⅳ）、去骨时（T_Ⅴ）、拔管即刻（T_Ⅵ）时平均动脉压（MAP）、平均心率（HR）、BIS值；术前、术后1天、术后3天简易智能精神状态检查量表（MMSE）；并于麻醉诱导前（T₀）、手术开始2 h（T₁）、术后1天（T₂）、术后3天（T₃）时抽取患者外周静脉血检测IL-1β、IL-6、IL-10、TNF-α浓度。结果 试验组手术用时、麻醉时间略低于对照组，但差异无统计学意义（P>0.05），试验组异丙酚、舒芬太尼用量以及苏醒时间均明显低于对照组（P<0.05）；T_Ⅱ时两组平均动脉压（Mean Arterial Pressure， MAP）、心率（Heartrate， HR）较术前明显降低，且试验组MAP明显低于对照组（P<0.05），但两组T_Ⅱ时HR比较无显著差异（P>0.05）；T_Ⅲ、T_Ⅵ时对照组MAP、HR明显高于T_Ⅰ时，而试验组MAP、HR与T_Ⅰ比较无显著差异（P>0.05）。术后1天、3天试验组简易智能精神状态检查量表（Mini-Mental State Examination， MMSE）评分低于对照组，有显著性差异（P<0.05）。T₁、T₂、T₃时试验组白介素-1β（IL-1β）、白介素-6（IL-6）、肿瘤坏死因子（Tumor Necrosis Factor-α， TNF-α）水平明显低于对照组（P<0.05），白介素-10（IL-10）水平明显高于对照组（P<0.05）。结论 采用电针复合TCI靶控输注麻醉方案可有效提升单肺通气食管癌开胸手术麻醉效果，能够降低患者术后认知功能障碍发生风险。