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

     

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。     

Erythema induratum of Bazin in a 10‐year‐old boy

Erythema induratum of Bazin (EIB) is a form of tuberculid resulting from hypersensitivity to tuberculosis antigen. EIB occurs most commonly in middle‐aged women and is not typically seen in children. Here, we present a rare case of EIB, presenting as a chronic nodular panniculitis, in a 10‐year‐old Korean boy.     

National level data analysis of facial lacerations in Korea using the National Health Insurance Service (NHIS) database

No national epidemiological investigations have been conducted recently regarding facial lacerations. The study was performed using the data of 3,634,229 people during the 5-year period from 2014 to 2018 archived by the National Health Information Database (NHID) of the Health Insurance Review and Assessment Service. Preschool and children under 10 years old accounted for about one-third of patients. Facial lacerations were concentrated in the “T-shaped” area, which comprised forehead, nose, lips, and the perioral area. The male to female ratio for all study subjects was 2.16:1. Age and gender are significantly related with each other (P < .001). Mean hospital stays decreased, and numbers of outpatient department visits per patient were highest for hospitals and lowest for health agencies. Over the study period, hospital costs per patient in tertiary and general hospitals increased gradually. Preschool and school-aged children are vulnerable to trauma. Male patients outnumbered female patients by a factor of more than 2. The “T-shaped’” area around forehead is vulnerable to injury. Total cost of medical care benefits per patient in tertiary hospitals was about 7 times on average than in health agencies. Regarding functional, behavioral, and aesthetic outcomes, more attention should be paid to epidemiologic data and hospital costs for facial lacerations.