Pulmonary Cell News Volume 6.13 | Apr 6 2017

TOP STORY

O2^⋅− and H₂O₂-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate

Researchers showed that alterations in cancer cell mitochondrial oxidative metabolism resulting in increased levels of O₂^⋅− and H₂O₂ are capable of disrupting intracellular iron metabolism, thereby selectively sensitizing non-small-cell lung cancer (NSCLC) and glioblastoma (GBM) cells to ascorbate through pro-oxidant chemistry involving redox-active labile iron and H₂O₂. [Cancer Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Efficient Derivation of Functional Human Airway Epithelium from Pluripotent Stem Cells via Temporal Regulation of Wnt Signaling

Scientists showed that cyclical modulation of the canonical Wnt signaling pathway enables rapid directed differentiation of human induced pluripotent stem cells via an NKX2-1⁺ progenitor intermediate into functional proximal airway organoids. They found that human NKX2-1⁺ progenitors have high levels of Wnt activation but respond intrinsically to decreases in Wnt signaling by rapidly patterning into proximal airway lineages at the expense of distal fates. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

Pulmonary MicroRNA Profiles Identify Involvement of Creb1 and Sec14l3 in Bronchial Epithelial Changes in Allergic Asthma

Investigators aimed to use microRNAs (miRNAs), which are critical regulators of signaling cascades, to identify so far uncharacterized asthma pathogenesis pathways. Deregulation of miRNAs was assessed in whole lungs from mice with ovalbumin-induced allergic airway inflammation (AAI). In silico predicted target genes were confirmed in reporter assays and in house-dust-mite induced AAI and primary human bronchial epithelial cells cultured at the air-liquid interface. [Sci Rep] Full Article

Delivery of ENaC siRNA to Epithelial Cells Mediated by a Targeted Nanocomplex: A Therapeutic Strategy for Cystic Fibrosis

The authors have developed a self-assembling nanocomplex formulation for siRNA delivery to the airways that consists of a liposome, an epithelial targeting peptide (P) and siRNA (R). LPR formulations were assessed for their ability to silence expression of the transcript of the gene encoding the α-subunit of the sodium channel ENaC in cell lines and primary epithelial cells, in submerged cultures or grown in air-liquid interface conditions. [Sci Rep] Full Article

Modelling the Bronchial Barrier in Pulmonary Drug Delivery: A Human Bronchial Epithelial Cell Line Supplemented with Human Tracheal Mucus

Investigators aimed to more accurately model the bronchial barrier, by developing an in vitro system comprising a tight epithelial cell layer which may be optionally supplemented with a layer of human tracheal mucus. To form the epithelium in vitro, they used the cystic fibrosis cell line CFBE41o^–, which can be grown as monolayers on Transwell^® supports, expressing tight junctions as well as relevant transport proteins. [Eur J Pharm Biopharm] Abstract | Graphical Abstract

LUNG CANCER

Noncanonical GLI1 Signaling Promotes Stemness Features and In Vivo Growth in Lung Adenocarcinoma

Aberrant Hedgehog/GLI signaling has been implicated in a diverse spectrum of human cancers, but its role in lung adenocarcinoma (LAC) is still under debate. Scientists showed that the downstream effector of the Hedgehog pathway, GLI1, is expressed in 76% of LACs, but in roughly half of these tumors, the canonical pathway activator, Smoothened, was expressed at low levels, possibly owing to epigenetic silencing. [Oncogene] Full Article

Stearoyl-CoA-Desaturase 1 Regulates Lung Cancer Stemness via Stabilization and Nuclear Localization of YAP/TAZ

The authors showed, using primary cell cultures from human lung adenocarcinoma, that the effectors of the Hippo pathway, Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), are required for the generation of lung cancer three-dimensional cultures and that stearoyl-CoA-desaturase 1 knock down and pharmacological inhibition both decrease expression, nuclear localization and transcriptional activity of YAP and TAZ. [Oncogene] Abstract

G9A Promotes Tumor Cell Growth and Invasion by Silencing CASP1 in Non-Small-Cell Lung Cancer Cells

Scientists found that G9A, a histone methyltransferase responsible for mono- or di-methylation of histone 3 lysine 9, is significantly upregulated in non-small-cell lung cancer. [Cell Death Dis] Full Article

MET Amplification and Epithelial-to-Mesenchymal Transition Exist as Parallel Resistance Mechanisms in Erlotinib-Resistant, EGFR-Mutated, NSCLC HCC827 Cells

Researchers investigated parallel resistance mechanisms acquired by HCC827, an epidermal growth factor receptor (EGFR)-mutated adenocarcinoma cell line dependent on EGFR activity and sensitive to erlotinib. The cell line was treated with erlotinib by stepwise escalation of the drug-concentration and erlotinib-resistant (HCC827ER) cells created. HCC827ER cells depicted a mixed epithelial and mesenchymal phenotype. [Oncogenesis] Full Article

Engineering Cancer Stem-Like Cells from Normal Human Lung Epithelial Cells

Investigators demonstrated that engineered lung cancer cells derived from normal human airway basal epithelial cells possessed cancer stem cells (CSCs)-like characteristics in terms of multilineage differentiation potential and strong tumor-initiating ability. They established an in vitro 3D culture system that allowed the in vivo differentiation process of the CSC-like cells to be recapitulated. [PLoS One] Full Article

Integrating Lung Physiology, Immunology, and Tuberculosis

The authors discuss emerging views on immunologic interactions occurring in the lungs for M. tuberculosis and their impact on infection and persistence. [Trends Microbiol] Abstract

Architecture in 3D Cell Culture: An Essential Feature for In Vitro Toxicology

Scientists illustrate the fundamental characteristics of polarity that is an essential architectural feature of organs for which different 3D cell culture models are available for toxicology studies in vitro. [Toxicol In Vitro] Abstract

Visit our reviews page to see a complete list of reviews in the pulmonary cell research field.

Five-Year Survival Observed with Opdivo (Nivolumab) in Patients with Previously Treated Advanced Non-Small Cell Lung Cancer (NSCLC), in Phase I Study CA209-003

Bristol-Myers Squibb Company announced the first report of five-year overall survival data from the Phase I dose-ranging study CA209-003 evaluating Opdivo in patients with previously treated advanced non-small cell lung cancer. [Press release from Bristol-Myers Squibb Company discussing research presented at the American Association for Cancer Research (AACR) Annual Meeting 2017, Washington, D.C.] Press Release

Two Phase III Studies of the Tezacaftor/Ivacaftor Combination Treatment Met Primary Endpoints with Statistically Significant Improvements in Lung Function (FEV1) in People with Cystic Fibrosis

Vertex Pharmaceuticals Incorporated announced results from two Phase III studies of the tezacaftor/ivacaftor combination treatment that showed statistically significant improvements in lung function in people with cystic fibrosis ages 12 and older, who have certain mutations in the cystic fibrosis transmembrane conductance regulator gene. [Vertex Pharmaceuticals Incorporated] Press Release

BUILD Grant Breathes Life into Lung Disease Research

A McGill researcher has been awarded a portion of a $1.2 million grant as part of the Boehringer Ingelheim Innovation in Understanding ILD (BUILD) program. BUILD supports Canadian investigators doing research interstitial lung disease (ILD) with the hope of improving the understanding, treatment and patient outcomes in ILD, a group of nearly 200 rare lung diseases – including idiopathic pulmonary fibrosis. [McGill University] Press Release

Japanese Scientists Call for Boycott of Military Research

The Science Council of Japan, an advisory body to the cabinet, representing some 850,000 Japanese scientists, released a statement calling on scientists to boycott military research and for universities and research organizations to evaluate the threats posed by such work. [Nature News] Editorial

Initiative Aims to Break Science’s Citation Paywall

The Initiative for Open Citations (I4OC) aims to allow anyone to access science papers’ reference lists and to build analytical services on top of that raw data. Started by the Wikimedia Foundation in San Francisco, California and five other partner organizations, I4OC announced at its official launch that 29 organizations, including some of the world’s largest scientific publishers, have now agreed to openly release citation data. [Nature News] Editorial

NEW Mitochondrial Biogenesis and Dynamics in Health, Disease and Aging
May 21-26, 2017
West Palm Beach, Florida, United States

NEW Cell Culture World Congress
May 23-24, 2017
San Diego, California, United States

Visit our events page to see a complete list of events in the community.

NEW Assistant, Associate or Full Professor Position(s) – Asthma Research (University of Pennsylvania)

NIH Training Grant – Pediatric Pulmonary Medicine (University of Pittsburgh)

Postdoctoral Fellowships – Respiratory Biology and Diseases (Cedars-Sinai Medical Center)

Postdoctoral Fellow – Lung Regeneration (AstraZeneca)

Postdoctoral Research Associate – Chronic Lung Disease (Washington University St. Louis)

Faculty Position – Cancer Biology (Wake Forest School of Medicine)

Laboratory Head – Infection & Immunity Division (The Walter and Eliza Hall Institute of Medical Research)

Assistant Professor/Postdoctoral Research Fellow – Lung Injury and Repair (University of Tennessee)

Postdoctoral Opportunity – RNA and Cancer Biology (Yale University)

PhD Student – Asthma Research (Karolinska Institute)

Principal Scientist – Translational Development (Celgene Corporation)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Postdoctoral Research Fellow – Cancer Genetics/Epigenetics (Fred Hutchinson Cancer Research Center)

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