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Preliminary study on the clinical significance of kinesin Kif18a in nonsmall cell lung cancer: An analysis of 100 cases.

驱动蛋白Kif18a在 100 例非小细胞肺癌中临床意义的初步研究.

  • 影响因子:1.95
  • DOI:10.1097/MD.0000000000019011
  • 作者列表:"Guo W","Zeng H","Zheng J","He Y","Zhuang X","Cai J","Huang H","Huang H","Xu M
  • 发表时间:2020-01-01
Abstract

:The aim of this study was to investigate the expression of Kif18A in cancerous and paracancerous tissues from 100 patients with nonsmall cell lung cancer (NSCLC).This was a prospective study of 100 patients with pathologically confirmed NSCLC (adenocarcinoma and squamous cell carcinoma [SCC], n = 50/group) that were operated at the Quanzhou First Hospital Affiliated to Fujian Medical University between June 2015 and December 2016. Kif18A protein expression in cancerous and paracancerous normal tissues was detected by western blot and immunohistochemistry.The expression of the Kif18A protein was higher in adenocarcinoma and SCC tissues than in the corresponding paracancerous normal tissues. The expression of the Kif18A protein was higher in highly differentiated tumors, in patients with lymph node metastasis (vs no lymph node metastasis), adenocarcinoma, and in stage III NSCLC. There were no associations between Kif18A expression and age, gender, and pathologic type.The expression of the Kif18A protein by immunohistochemistry was higher in NSCLC tissues than in normal tissues, and was associated with tumor differentiation, lymph node metastasis, and TNM staging. These results could provide a theoretical basis for novel molecular targeted therapies against NSCLC.

摘要

: 本研究的目的是研究Kif18A在 100 例非小细胞肺癌 (NSCLC) 患者癌组织和癌旁组织中的表达。这是一项前瞻性研究,纳入 100 例经病理证实的NSCLC患者 (腺癌和鳞状细胞癌 [SCC],n   = 50/组)。2015 年 6 月至 2016 年 12 月在福建医科大学附属泉州第一医院手术。采用western blot和免疫组织化学法检测Kif18A蛋白在癌及癌旁正常组织中的表达,Kif18A蛋白在腺癌和SCC组织中的表达均高于相应癌旁正常组织。Kif18A蛋白在高分化肿瘤、淋巴结转移患者 (与无淋巴结转移患者相比) 、腺癌和III期NSCLC中的表达较高。Kif18A表达与年龄、性别和病理类型无关。免疫组化结果显示Kif18A蛋白在NSCLC组织中的表达高于正常组织,并与肿瘤分化程度、淋巴结转移和TNM分期相关。本研究结果可为NSCLC分子靶向治疗提供理论依据。

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DOI:10.1016/j.athoracsur.2019.04.100
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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.

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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.

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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.

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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。

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