TGFβ promotes YAP‐dependent AXL induction in mesenchymal‐type lung cancer cells

The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial‐to‐mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. However, the underlying mechanism of AXL induction in mesenchymal cancer cells is poorly understood. Our study revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFβ signaling coordinated YAP‐dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFβ/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal‐type lung cancer.

Abbreviations

AUC

area under the curve

AXL

AXL receptor tyrosine kinase

BCL2

B‐cell lymphoma 2

CTD2

cancer target discovery and development

CTGF

connective tissue growth factor

DEG

differentially expressed genes

DOXO

doxorubicin

EMT

epithelial–mesenchymal transition

Eto

etoposide

FDA

Food and Drug Administration

ITGB3

integrin beta‐3

MAPK

mitogen‐activated protein kinase

MMP2

matrix metalloproteinase‐2

MMP9

matrix metalloproteinase‐9

mRNA

messenger RNA

NF‐κB

nuclear factor kappa‐light‐chain‐enhancer of activated B cells

SBE

SMAD binding element

SERPINE1

serpin family E member 1

siRNA

small interfering RNA

ssGSEA

single‐sample gene set enrichment analysis

TCGA

The Cancer Genome Atlas

TGFβ

transforming growth factor beta

YAP

Yes‐associated protein

YAP8SA

mutants of inhibitory phosphorylation site at eight serine to Alanine of YAP

ZEB1

zinc finger E‐box binding homeobox 1

ZEB2

zinc finger E‐box‐binding homeobox 2

     

鼻内窥镜下鼻腔泪囊造孔术治疗慢性泪囊炎的临床观察

目的：观察鼻腔内窥镜下行鼻腔泪囊造孔术治疗慢性泪囊炎的临床疗效。方法回顾性分析2013年6月至2015年6月在我院收治的慢性泪囊炎患者39例（40只眼），采用鼻腔内窥镜下鼻腔泪囊造孔术进行手术治疗，术后随访3～6个月，观察术眼流脓、溢泪等情况。结果鼻内窥镜下鼻腔泪囊造孔术治疗39例（40只眼）患者，治愈35例（36只眼），好转3例（3只眼），无效1例（1只眼）。治愈率90％，好转率7．5％，无效率2．5％。结论经鼻内窥镜下行鼻腔泪囊造孔术治疗慢性泪囊炎，疗效确切。具有手术简单、创伤小、出血少、无需面部切口、面部不留疤痕等优点。     

人格特质对二胎返岗护士产适应水平的影响

目的 了解二胎返岗护士适应水平现状,并探讨人格特质对其返岗适应水平的影响。方法 2018年1-12月,采用便利抽样法选取山东省3所三级甲等医院360名护士为研究对象,采用一般资料调查表、艾森克人格问卷、护士产后返岗适应问卷对其进行调查。结果 护士产二胎后返岗适应水平均分为(2.16±0.51)分;外向型人格特征与返岗适应水平呈正相关(r=0.540,P<0.001),精神质、神经质人格特征与返岗适应水平均呈负相关(r=-0.410,P<0.001;r=-0.350,P<0.001)。多元线性回归分析结果显示,年龄、返岗时间、工作负荷、返岗培训、内-外倾向、精神质、神经质是护士产二胎后返岗适应的独立影响因素。结论 护士产二胎后返岗适应处于中等偏下水平,人格特质、生育年龄、返岗时间、工作负荷、返岗培训为其影响因素,护理管理者可结合人格特质等特点采取管理策略,提高护士产二胎后返岗适应的水平。     

放疗在肝癌治疗中应用的研究进展

肝癌是临床上常见的恶性肿瘤，因早期症状不典型，至发现时往往已为中晚期，失去最佳手术治疗时机和机会。作为非手术治疗之一的放射治疗技术，其发展在近年来已有了较大的进步。放疗包括体外放疗和体内放疗，皆具有一定的治疗效果和相对可控的不良反应。本文就肝癌放射治疗的应用进展作一综述。     

经自然腔道取标本手术在结直肠外科手术中的应用进展

随着腔镜技术的进一步发展以及微创理念应用于结直肠外科疾病的诊治中,结直肠相关疾病的诊治发生了翻天覆地的变化。由传统的经腹手术到腹腔镜手术、经自然腔道手术,再到经自然腔道取标本手术(NOSES),结直肠疾病的外科诊治在微创领域取得了巨大成果。NOSES技术是目前结直肠外科在微创领域前沿的手术方式之一,它通过经直肠、阴道取标本来避免了腹壁的辅助取标本切口,从而将结直肠外科手术进一步微创化。NOSES技术集传统腹腔镜手术的优势与现代微创外科的理念于一体,它在确保手术效果的基础上集中体现了微创、加速康复外科、功能外科、"无疤"等理念的特点。本文主要就国内外各中心开展NOSES技术在结直肠外科诊治开展中的相关经验、心得和体会进行综述。     

Lysophosphatidylcholine‐induced cytotoxicity and protection by heparin in mouse brain bEND.3 endothelial cells

A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low‐density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium‐dependent relaxation and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC‐induced cytotoxicity in brain EC. In this work, we found that LPC caused cytosolic Ca²⁺ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND.3 EC. In contrast to reported reactive oxygen species (ROS) generation by LPC in other EC, LPC did not trigger ROS formation in bEND.3 cells. Pharmacological inhibition of p38 alleviated LPC‐inflicted cell death. We examined whether heparin could be cytoprotective: although it could not suppress LPC‐triggered Ca²⁺ signal, p38 activation and mitochondrial membrane potential drop, it did suppress LPC‐induced caspase 3 activation and alleviate LPC‐inflicted cytotoxicity. Our data suggest LPC apoptotic death mechanisms in bEND.3 might involve mitochondrial membrane potential decrease and p38 activation. Heparin is protective against LPC cytotoxicity and might intervene steps between mitochondrial membrane potential drop/p38 activation and caspase 3 activation.