小狗阅读会员会员
医学顶刊SCI精读工具

扫码登录小狗阅读

阅读SCI医学文献
Document
订阅泛读方向 订阅泛读期刊
  • 我的关注
  • 我的关注
  • {{item.title}}

    按需关注领域/方向,精准获取前沿热点

  • {{item.title}}

    {{item.follow}}人关注

  • {{item.subscribe_count}}人订阅

    IF:{{item.impact_factor}}

    {{item.title}}

Efficacy and safety of programmed cell-death-protein-1 and its ligand inhibitors in pretreated patients with epidermal growth-factor receptor-mutated or anaplastic lymphoma kinase-translocated lung adenocarcinoma.

程序性细胞死亡蛋白-1 及其配体抑制剂在表皮生长因子受体突变或间变性淋巴瘤激酶转位肺腺癌患者中的疗效和安全性。

  • 影响因子:1.95
  • DOI:10.1097/MD.0000000000018726
  • 作者列表:"Bylicki O","Guisier F","Monnet I","Doubre H","Gervais R","Janicot H","Perol M","Fournel P","Lamy R","Auliac JB","Chouaid C
  • 发表时间:2020-01-01
Abstract

:Immune-checkpoint inhibitor (ICI) efficacy in patients with non-small cell lung cancer (NSCLC) harboring molecular alterations remains poorly elucidated. This study was undertaken to determine ICI efficacy against epidermal growth-factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1)-mutated NSCLC patients in the real-world setting.In this retrospective, multicenter study on adults with ICI-treated EGFR-mutated or ALK- or ROS1-translated NSCLCs, we analyzed clinical characteristics and outcomes: ICI-treatment duration, and progression-free survival (PFS), objective response rate, duration of response, and overall survival (OS) from immunotherapy initiation.Fifty-one NSCLC patients (mean age, 58.0 years) were included from 20 French centers: 61% were never-smokers and 59% were women. Among them, 82% had EGFR-activating mutations, 16% ALK translocations, or 2% ROS1 translocations. Before ICI therapy, patients had received a median of 3 treatment lines (including tyrosine-kinase inhibitor). The median PFS was 2.1 (95% confidence interval [CI], 1.5-3.2) months for the entire cohort, 2.2 (95% CI, 1.4-3.2) for EGFR-mutated patients, and 2.4 (95% CI, 2.1-not reached) months for ALK-translocated patients. The median OS was 14.7 (95% CI, 12.1-19.2) months for the entire population and 13.9 (95% CI, 8.8-20.0) and 19.2 (95% CI, 13.1-not reached) months for EGFR-mutated and ALK-translocated patients, respectively. Seven (13.7%) patients were treated with ICI for >9 months. Toxicities were reported in 22% (11/51), including 8% (4/51) grade ≥3.In this real-world setting, analysis of ICI PFS against EGFR-mutated or ALK-translocated NSCLC patients appeared close to that observed in pretreated unselected NSCLC patients. The more promising OS probably linked to post-ICI treatments. Large prospective studies on these patient subsets are needed.

摘要

: 免疫检查点抑制剂 (ICI) 对携带分子改变的非小细胞肺癌 (NSCLC) 患者的疗效仍未阐明。本研究旨在确定ICI对表皮生长因子受体 (EGFR)/间变性淋巴瘤激酶 (ALK)/c-ros癌基因 1 (ROS1) 的疗效。-现实世界环境中的突变NSCLC患者。在这项针对接受ICI治疗的EGFR突变或ALK或ROS1-translated nsclc的成人患者的回顾性、多中心研究中,我们分析了临床特征和结果: ICI治疗持续时间,和无进展生存期 (PFS),从免疫治疗开始的客观缓解率、缓解持续时间和总生存期 (OS)。51 例NSCLC患者 (平均年龄,58.0 岁) 来自 20 个法国中心: 61% 为从不吸烟者,59% 为女性。其中,82% 有EGFR激活突变,16% ALK易位,或 2% ROS1 易位。在ICI治疗之前,患者接受了 3 个治疗线 (包括酪氨酸激酶抑制剂) 的中位数.整个队列的中位PFS为 2.1 (95% 可信区间 [CI],1.5-3.2) 个月,EGFR突变患者为 2.2 (95% CI,1.4-3.2),和 2.4 (95% CI,2.1-未达到) 个月的ALK易位患者。整个人群的中位OS为 14.7 (95% CI,12.1-19.2) 个月,13.9 (95% CI,8.8-20.0) 和 19.2 (95% CI,13.1-未达到) 分别为EGFR突变和ALK易位患者的 6 个月。7 例 (13.7%) 患者接受ICI治疗> 9 个月。在 22% (11/51) 中报告了毒性,包括 8% (4/51) 的 ≥ 3 级。针对EGFR突变或ALK易位NSCLC患者的ICI PFS分析似乎接近于在预处理的未经选择的NSCLC患者中观察到的结果。更有前景的OS可能与ICI后治疗有关。需要对这些患者亚群进行大型前瞻性研究。

关键词:
阅读人数:6人
下载该文献
小狗阅读

帮助医生、学生、科研工作者解决SCI文献找不到、看不懂、阅读效率低的问题。提供领域精准的SCI文献,通过多角度解析提高文献阅读效率,从而使用户获得有价值研究思路。

相关文献
影响因子:1.80
发表时间:2020-01-01
DOI:10.1016/j.athoracsur.2019.04.100
作者列表:["Mammana M","Zuin A","Serra E","Bellini A","Rea F"]

METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.

关键词: 暂无
翻译标题与摘要 下载文献
影响因子:6.93
发表时间:2020-01-15
DOI:10.1002/ijc.32532
作者列表:["Hata A","Nakajima T","Matsusaka K","Fukuyo M","Morimoto J","Yamamoto T","Sakairi Y","Rahmutulla B","Ota S","Wada H","Suzuki H","Matsubara H","Yoshino I","Kaneda A"]

METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.

翻译标题与摘要 下载文献
影响因子:6.93
发表时间:2020-01-01
DOI:10.1002/ijc.32530
作者列表:["Zhang L","Yang Y","Chai L","Bu H","Yang Y","Huang H","Ran J","Zhu Y","Li L","Chen F","Li W"]

METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.

翻译标题与摘要 下载文献
肺肿瘤方向

肺肿瘤,又叫支气管肺癌,是常见的恶性肿瘤之一。肺肿瘤的治疗为包括手术、中药、放疗、化疗及免疫等多学科的综合治疗。

复制标题
发送后即可在该邮箱或我的下载查看该文献
发送
该文献默认存储到我的下载

科研福利

报名咨询

建议反馈
问题标题:
联系方式:
电子邮件:
您的需求: