Pulmonary Cell News Volume 8.24 | Jun 27 2019

TOP STORY

UDP-Glucose Accelerates SNAI1 mRNA Decay and Impairs Lung Cancer Metastasis

Researchers showed that, after activation of EGFR, UDP-glucose 6-dehydrogenase (UGDH) was phosphorylated at tyrosine 473 in human lung cancer cells. Phosphorylated UGDH interacted with Hu antigen R (HuR) and converted UDP-glucose to UDP-glucuronic acid, which attenuated the UDP-glucose-mediated inhibition of the association of HuR with SNAI1 mRNA and therefore enhanced the stability of SNAI1 mRNA. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Thy-1 Depletion and Integrin β3 Upregulation-Mediated PI3K-Akt-mTOR Pathway Activation Inhibits Lung Fibroblast Autophagy in Lipopolysaccharide-Induced Pulmonary Fibrosis

Scientists demonstrated that lipopolysaccharide (LPS) activated the PI3K-Akt-mTOR pathway and inhibited lung fibroblast autophagy by depleting thymocyte differentiation antigen-1 (Thy-1) and upregulating integrin β3. Challenge of the human lung fibroblast MRC-5 cell line with LPS resulted in significant upregulation of integrin β3, activation of the PI3K-Akt-mTOR pathway and inhibition of autophagy, which could be abolished by integrin β3 silencing by specific shRNA or treatment with the integrin β3 inhibitor cilengitide. [Lab Invest] Abstract

Contributions of Charcoal, Tobacco, and Syrup to the Toxicity and Particle Distribution of Waterpipe Tobacco Smoke

Relative toxicity of whole smoke was determined via measurement of lysosomal integrity and measures of membrane integrity following acute exposure of type II alveolar cells at the air-liquid interface. All waterpipe aerosols exhibited a unimodal particle size distribution, the peak and concentration of which varied depending upon the shisha components present. [Toxicol Lett] Abstract

Cytotoxicity Screening of Emulsifiers for Pulmonary Application of Lipid Nanoparticles

Cytotoxicity of Kolliphor RH40, Poloxamer 188, and Tween 80 was studied by integration into solid lipid nanoparticles loaded with itraconazole as model drug. Cytotoxicity of the formulations was assessed in human alveolar epithelial cells and human and murine macrophages and correlated to cell uptake. [Eur J Pharm Sci] Abstract | Graphical Abstract

LUNG CANCER

Circular RNA circHIPK3 Modulates Autophagy via MIR124-3p-STAT3-PRKAA/AMPKa Signaling in STK11 Mutant Lung Cancer

Researchers uncovered that autophagy was induced upon loss of circular RNA HIPK3 (circHIPK3) via the MIR124-3p-STAT3-PRKAA/AMPKa axis in STK11 mutant lung cancer cell lines. STAT3 abrogation as well as transfection with a MIR124-3p mimic, recapitulated the induction of autophagy. [Autophagy] Abstract

Long Noncoding RNA LINC00673-v4 Promoted Aggressiveness of Lung Adenocarcinoma via Activating WNT/β-Catenin Signaling

Investigators reported that a long noncoding RNA, LINC00673, was up-regulated in lung adenocarcinoma (LAD) cells. They found that LINC00673-v4 was the most abundant transcript of LINC00673 in LAD cells and its expression was associated with the adverse clinical outcome of LAD. [Proc Natl Acad Sci USA] Full Article

Ascl1-Induced Wnt11 Regulates Neuroendocrine Differentiation, Cell Proliferation, and E-Cadherin Expression in Small-Cell Lung Cancer and Wnt11 Regulates Small-Cell Lung Cancer Biology

The expression of Wnt11 and some neuroendocrine markers increased after the transfection of Achaete-scute complex homolog 1 (ASCL1) into the A549 ADC cell line. Knockdown of Ascl1 downregulated Wnt11 expression in small-cell lung cancer cell lines. Ascl1 regulated Wnt11 expression via lysine H3K27 acetylation at the enhancer region of the WNT11 gene. [Lab Invest] Abstract

A New Small Cell Lung Cancer Biomarker Identified by Cell-SELEX Generated Aptamers

Attenuating high density lipoprotein binding protein (HDLBP) expression with siRNA inhibited proliferation and metastasis of SCLC cells in vitro and tumor formation in vivo. Mechanism study revealed the new function of HDLBP in promoting G1/S cell cycle transition for tumor progression. [Exp Cell Res] Abstract

Air-Liquid Interface Culture Changes Surface Properties of A549 Cells

The influence of culture in two variations of transwell cultures compared to conventional culture in plastic wells on the phenotype of A549 cells was studied. Cells were characterized by morphology, proliferation and transepithelial electrical resistance, whole genome transcription analysis, Western blot and immunocytochemical detection of pro-surfactant proteins. [Toxicol In Vitro] Abstract | Graphical Abstract

SPARC Correlates with Unfavorable Outcome and Promotes Tumor Growth in Lung Squamous Cell Carcinoma

Investigators constructed a secreted protein acidic and rich in cysteine (SPARC)-overexpression model in a lung squamous cell carcinoma (LSCC) cell line to explore the characteristics of SPARC in LSCC development both in vitro and in vivo. They demonstrated a remarkably higher level of SPARC in LSCC tissues than in corresponding non-cancerous tissues and elevated SPARC expression was significantly correlated with poor outcome in LSCC patients. [Exp Mol Pathol] Abstract

TBL1XR1 Is Involved in c-Met-Mediated Tumorigenesis of Human Nonsmall Cell Lung Cancer

Researchers selected matched and cancerous lung tissues to establish the upregulation of transducin (β)-like 1 X-linked receptor 1 (TBL1XR1). Using in vitro assays, they assessed the influence of TBL1XR1 on various cancer phenotypes, namely cell proliferation, chemoresistance, invasion, and metastases in a CRISPR-Cas9-mediated knock out model, and H460 cell lines overexpressing TBL1XR1. [Cancer Gene Ther] Abstract

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MET Inhibitors for Targeted Therapy of EGFR TKI-Resistant Lung Cancer

MET gene amplification has long been known as an important resistance mechanism to first- or second-generation epidermal growth factor receptor (EGFR)-TKIs in addition to the appearance of T790 M mutation. Recent preclinical and clinical studies have suggested that MET amplification and/or protein hyperactivation is likely to be a key mechanism underlying acquired resistance to third-generation EGFR-TKIs such as osimertinib as well, particularly when used as a first-line therapy. [J Hematol Oncol] Full Article

Translatable Gene Therapy for Lung Cancer Using CRISPR CAS9- an Exploratory Review

The authors highlight important studies and findings done till now in the perspective of lung cancer with an in-depth analysis of various clinical trials associated with the use of CRISPR Cas9 technology in the field of cancer research. [Cancer Gene Ther] Abstract

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

Imfinzi Improves Overall Survival at Interim Analysis in the Phase III CASPIAN Trial in 1^st-Line Extensive-Stage Small Cell Lung Cancer

AstraZeneca announced positive overall survival results from the Phase III CASPIAN trial with Imfinzi in 1^st-line extensive-stage small cell lung cancer, a disease with significant unmet need and limited treatment options for patients. [AstraZeneca] Press Release

Continuation of “Atalante 1” Phase III Clinical Trial of Tedopi^® in NSCLC Patients Post Checkpoint Inhibitor Failure Following IDMC Recommendation

OSE Immunotherapeutics announced that, after reviewing global study data, the Independent Data Monitoring Committee (IDMC) saw no safety concerns and recommended the continuation of patient recruitment, without any modifications, of its ongoing international pivotal Phase III trial, called Atalante 1, evaluating Tedopi^® in HLA-A2 positive non-small cell lung cancer (NSCLC) patients post immune checkpoint inhibitor failure. [OSE Immunotherapeutics] Press Release

Sanofi and Regeneron Announce Positive Topline Phase II Results for IL-33 Antibody in Asthma

Sanofi and Regeneron Pharmaceuticals, Inc. announced that a Phase II proof-of-concept trial evaluating the investigational IL-33 antibody REGN3500 met the primary endpoint of improvement in loss of asthma control when comparing REGN3500 monotherapy to placebo. [Sanofi] Press Release

UK’s MHRA Renews EAMS Scientific Opinion for Santhera’s Idebenone in Duchenne Muscular Dystrophy

Santhera Pharmaceuticals announced that the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has renewed for a further year the Early Access to Medicines Scheme (EAMS) scientific opinion for idebenone for patients with Duchenne muscular dystrophy in respiratory function decline who are not taking glucocorticoids. [Santhera Pharmaceuticals] Press Release

FDA Expands Approval of Treatment for Cystic Fibrosis to Include Patients Ages Six and Older

The FDA expanded the indication for Symdeko tablets for treatment of pediatric patients ages six years and older with cystic fibrosis who have certain genetic mutations. Last year, the FDA approved Symdeko to treat patients ages 12 and older who had the same specific genetic mutations. [The FDA] Press Release

Discrimination Drives LGBT+ Scientists to Think About Quitting

Nearly one-third of physical scientists from sexual and gender minorities in the United Kingdom have considered leaving their jobs because of their workplace climate, suggests a survey. And 18% who are lesbian, gay, bisexual, transgender or from other sexual and gender minorities (LGBT+) said they had experienced harassment, bullying or exclusionary behavior in the workplace. [Nature News] Editorial

NIH Probe of Foreign Ties Has Led to Undisclosed Firings-And Refunds From Institutions

An aggressive effort by the National Institutes of Health (NIH) to enforce rules requiring its grantees to report foreign ties is still gathering steam. But it has already had a major impact on the US biomedical research community. A senior NIH official tells ScienceInsider that universities have fired more scientists-and refunded more grant money-as a result of the effort than has been publicly known. [ScienceInsider] Editorial

Proposal to Close UK Mouse-Research Center Is ‘Major Threat’

Leaders and senior scientists at a national mouse-genetics center in the United Kingdom have written an open letter decrying a recommendation to close the facility’s on-site academic research unit. The closure of the MRC Harwell Institute’s Mammalian Genetics Unit – where scientists study disease using animal models – would be “a major threat to mouse genetics in the UK”, says the letter, organized by 14 senior Harwell scientists. [Nature News] Editorial

Iranian Biologists Face US Trial for Trying to Take Proteins Out of the Country

Three Iranian biologists are facing trial in a US court over charges that they violated trade sanctions by attempting to export chemicals known as growth factors, which are commonly used in medical research. The scientists have asked a federal district court judge in Atlanta, Georgia, to dismiss the criminal charges against them. [Nature News] Editorial

NEW 14^th World Congress on Inflammation Sydney 2019
September 15-19, 2019
Sydney, Australia

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

NEW Postdoctoral Fellowship – Redox Biology of Lung and Breast Cancer (Washington University School of Medicine)

Scientist – Pulmonary (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Pluripotent Stem Cell-Derived Human Lung Organoids (Columbia University Irving Medical Center)

Researcher Position – Translational Cancer Research (University of Tromsø)

Postdoctoral Researcher – Cystic Fibrosis Stem Cell Models (The University of Alabama at Birmingham)

Postdoctoral Researcher – Lung Lineage Development (Hospital for Sick Children)

Assistant Professor – Lung Disease Research (University of McGill)

Senior Scientific Officer – Lung Cancer Liquid Biopsy Biomarker Research (Cancer Research UK Manchester Institute)

Postdoctoral Fellowship – RNA in Lung Sepsis and Inflammation (Boston University)

Postdoctoral Fellowship – Respiratory and Ophthalmic Diseases (Queen’s University Belfast)

Associate Professor – Oncology (University of California, Davis)

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