Pulmonary Cell News Volume 7.02 | Jan 18 2018

TOP STORY

PHD3 Controls Lung Cancer Metastasis and Resistance to EGFR Inhibitors through TGFα

Scientists showed that the oxygen sensor prolyl-hydroxylase domain protein 3 (PHD3) links hypoxic signaling and epithelial-mesenchymal transition (EMT) regulation in the lung tumor microenvironment. PHD3 was repressed by signals that induce EMT and acted as a negative regulator of EMT, metastasis and therapeutic resistance. [Cancer Res] Abstract | Full Article

(Ranked by impact factor of the journal)

Development and Optimization of a Differentiated Airway Epithelial Cell Model of the Bovine Respiratory Tract

Researchers optimized the culture conditions in serum-free medium that allow bovine bronchial epithelial cells grown at an air-liquid interface to differentiate into a three-dimensional epithelium that is highly representative of the bovine airway. [Sci Rep] Full Article

Leukotriene B4 Receptor 2 Regulates the Proliferation, Migration and Barrier Integrity of Bronchial Epithelial Cells

Leukotriene B4 receptor 2 (BLT2) expression in 16HBE bronchial epithelial cells were manipulated by transfection with BLT2 overexpression plasmid or BLT2 small interference RNA. 16HBE cells were then exposed to BLT2 antagonist or BLT2 agonist. [J Cell Physiol] Abstract

Lung Fibroblasts May Play an Important Role in Clearing Apoptotic Bodies of Bronchial Epithelial Cells Generated by Exposure to PHMG-P-Containing Solution

Researchers studied the toxic mechanism of polyhexamethylene guanidine-phosphate (PHMG-P)-containing solution using human normal bronchial epithelial cells. When exposed for 24 hours, PHMG-P-containing solution rapidly decreased cell viability from around 6 hours after exposure and significantly increased of the phosphatidylserine exposure and the LDH release. [Toxicol Lett] Abstract

Silica Nanoparticle-Induced Cytokine Responses in BEAS-2B and HBEC3-KT Cells: Significance of Particle Size and Signaling Pathways in Different Lung Cell Cultures

The authors previously reported that silica nanoparticles (SiNPs) of nominal size 50 nm induce the pro-inflammatory cytokines CXCL8 and IL-6 in BEAS-2B cells, via mechanisms involving MAPK p38, TACE-mediated TGFα release and the NFκB pathway. In the present study, they examined whether these findings are cell-specific or might be extended to another epithelial lung cell model, HBEC3-KT, and also to SiNPs of a smaller size. [Basic Clin Pharmacol Toxicol] Abstract

Induction of High Mobility Group Box-1 In Vitro and In Vivo by Respiratory Syncytial Virus

Glycyrrhizin dose-dependently inhibited high mobility group box type 1 upregulation in both respiratory syncytial virus-infected immortalized and primary human bronchial epithelial cells, and this effect was associated with significant reduction of viral replication. [Pediatr Res] Abstract

LUNG CANCER

Long Non-Coding RNA XIST Promotes TGF-β-Induced Epithelial-Mesenchymal Transition by Regulating miR-367/141-ZEB2 Axis in Non-Small-Cell Lung Cancer

Investigators observed increased expression of long non-coding RNA (lncRNA) XIST and ZEB2 mRNA in metastatic non-small-cell lung cancer (NSCLC) tissues. Knockdown of lncRNA XIST inhibited ZEB2 expression, and repressed transforming growth factor β (TGF-β)-induced epithelial-mesenchymal transition and NSCLC cell migration and invasion. [Cancer Lett] Abstract

Regulation of Signaling Pathways Involved in the Anti-Proliferative and Apoptosis-Inducing Effects of M22 against Non-Small Cell Lung Adenocarcinoma A549 Cells

The compound 29-(4-methylpiperazine)-luepol (M22), a novel derivative of lupeol, showed anti-proliferative effects against the human non-small cell lung cancer A549 cell line. [Sci Rep] Full Article

Knockdown of Long Non-Coding RNA XIST Inhibits Cell Viability and Invasion by Regulating miR-137/PXN Axis in Non-Small Cell Lung Cancer

Scientists demonstrated that X-inactive specific transcript (XIST) was substantially upregulated and miR-137 was aberrantly downregulated in non-small-cell lung cancer tissues and cells. [Int J Biol Macromol] Abstract

Comparison of Epithelial Mesenchymal Transition Mediated Tyrosine Kinase Inhibitor Resistance in Non-Small Cell Lung Cancer Cell Lines with Wild Type EGFR and Mutant Type EGFR

The authors found upregulation of cytoplasmic p120-catenin, and it was co-localized with Kaiso factor. In the nucleus, binding of p120-catenin to Kaiso factor initiated transcription by activating epithelial-mesenchymal transition–transcription factors such as Snail, Slug, Twist, and ZEB1. [Biochem Biophys Res Commun] Abstract

Emerging Role of Twist1 in Fibrotic Diseases

Twist1, a basic helix-loop-helix transcription factor, is involved in epithelial-mesenchymal transition (EMT) and plays significant roles in various fibrotic diseases. Suppression of the EMT process represents a promising approach for the treatment of fibrotic diseases. [J Cell Mol Med] Full Article

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Merck’s KEYTRUDA^® (Pembrolizumab) Significantly Improved Overall Survival and Progression-Free Survival as First-Line Treatment in Combination with Pemetrexed and Platinum Chemotherapy for Patients with Metastatic Nonsquamous Non-Small Cell Lung Cancer (KEYNOTE-189)

Merck announced that the pivotal Phase III KEYNOTE-189 trial investigating KEYTRUDA^®, Merck’s anti-PD-1 therapy, in combination with pemetrexed and cisplatin or carboplatin, for the first-line treatment of patients with metastatic non-squamous non-small cell lung cancer, met its dual primary endpoints of overall survival and progression-free survival. [Merck & Co., Inc.] Press Release

First Patient Dosed in a Phase II Trial with Transgene’s TG4010 + Nivolumab + Chemotherapy for the First-Line Treatment of Lung Cancer (NSCLC)

Transgene announced the dosing of the first patient in the Phase II trial evaluating TG4010 in combination with Opdivo^® and chemotherapy as a first-line treatment for advanced non-squamous NSCLC with low or no expression of PD-L1 by the tumor cells. [Transgene SA] Press Release

In Trump’s First Year, Science Advice Sees a Marked Decline

Since U.S. President Donald Trump took office, expert panels that provide key federal agencies with science advice have had fewer members and met less often than at any time since 1997, when the government started tracking such numbers, a new analysis concludes. [ScienceInsider] Editorial

What a US Government Shutdown Would Mean for Science

The clock is ticking for US lawmakers, who have fewer than two days to pass a new budget or face a government shutdown. Nature explains why politicians are struggling to reach a deal, what is at stake for science and whether a crisis can be avoided. [Nature News] Editorial

NEW The Stem Cell Niche Conference 2018
May 27-31, 2018
Copenhagen, Denmark

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NEW Postdoctoral Position – Biomedical Systems Biology (University of Zurich)

Postdoctoral Scholarship – Translational Cancer Stem Cell Biology (Lund University)

Postdoctoral Fellow – Airway Ciliation Imaging in Human Lung Tissue (European Molecular Biology Laboratory)

Postdoctoral Position – Pulmonary Disease Pathogenesis (Columbia University)

Postdoctoral Training Fellow – Lung Cancer (The Francis Crick Institute)

Postdoctoral Fellow – Lung Regeneration after Injury (University of Michigan)

Postdoctoral Fellow – Lung Cancer (MD Anderson Cancer Center)

Postdoctoral Position – Cell Signaling and Cell Differentiation (Stanford University)

Postdoctoral Researcher – Cancer Research (University of California, Davis)

Postdoctoral Fellow – Human Airway Stem Cell Biology (Cornell University)

PhD Studentship – Heterogeneity in Small Cell Lung Cancer (CRUK Manchester Institute)

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