Pulmonary Cell News Volume 8.19 | May 23 2019

TOP STORY

Targeting Lonidamine to Mitochondria Mitigates Lung Tumorigenesis and Brain Metastasis

Investigators modified lonidamine (LND), an antiglycolytic drug with limited efficacy, to mitochondria-targeted mito-LND which was 100-fold more potent. Mito-LND, a tumor-selective inhibitor of oxidative phosphorylation, inhibited mitochondrial bioenergetics in lung cancer cells and mitigated lung cancer cell viability, growth, progression, and metastasis of lung cancer xenografts in mice. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Inactivation of Nuclear Histone Deacetylases by EP300 Disrupts the MiCEE Complex in Idiopathic Pulmonary Fibrosis

Researchers showed that reduced levels of miRNA lethal 7d in idiopathic pulmonary fibrosis (IPF) compromised epigenetic gene silencing mediated by the ribonucleoprotein complex MiCEE. In addition, they found that hyperactive EP300 reduced nuclear HDAC activity and interfered with MiCEE function in IPF. [Nat Commun] Full Article

Organic Dust, Causing Both Oxidative Stress and Nrf2 Activation, Is Phagocytized by Bronchial Epithelial Cells

Human bronchial epithelial cells were treated with various concentrations of organic dust (OD) followed by evaluation of intracellular oxidative stress using 2′,7′ -dichlorofluorescin diacetate. Gene expression following stimulation with OD for anti-oxidant genes was performed by qPCR followed by quantification of Nrf2 nuclear using a luciferase reporter assay. [Am J Physiol Lung Cell Mol Physiol] Abstract

Cyclic Compression Increases F508 Del CFTR Expression in Ciliated Human Airway Epithelium

The authors studied 117 mature, fully ciliated airway epithelial cell filters grown at air liquid interface grown from 10 CF and 19 control subjects. These were exposed to cyclic increases in apical air pressure of 15 cm H₂O for varying times. They measured the effect on proteins relevant to lung health, with a focus on the CF transmembrane regulator. [Am J Physiol Lung Cell Mol Physiol] Abstract

LUNG CANCER

Metabolic Reprogramming and Notch Activity Distinguish between Non-Small Cell Lung Cancer Subtypes

Publicly available gene expression data from human lung cancer samples and cell lines were analyzed. Stable isotope resolved metabolomics were performed on squamous cell carcinomas and adenocarcinomas tumors in human patients and in freshly resected tumor slices. [Br J Cancer] Full Article

XPO1 Inhibitor KPT-330 Synergizes with Bcl-XL Inhibitor to Induce Cancer Cell Apoptosis by Perturbing rRNA Processing and Mcl-1 Protein Synthesis

The authors showed that the orally bioavailable XPO1 inhibitor KPT-330 reduced Mcl-1 protein level, by which it synergized with Bcl-xL inhibitor A-1331852 to induce apoptosis in cancer cells. KPT-330/A-1331852 combination disrupted bindings of Mcl-1 and Bcl-xL to Bax, Bak, and/or Bim, elicited mitochondrial outer membrane permeabilization, and triggered apoptosis. [Cell Death Dis] Full Article

Genomic Signatures Defining Responsiveness to Allopurinol and Combination Therapy for Lung Cancer Identified by Systems Therapeutics Analyses

Scientists tested allopurinol, an FDA-approved drug that inhibits xanthine dehydrogenase, on human non-small cell lung cancer (NSCLC) cell lines obtained from the Broad Institute Cancer Cell Line Encyclopedia, and identified sensitive and resistant cell lines. They utilized the transcriptomic profiles of these cell lines to identify six gene signatures for allopurinol-sensitive and -resistant cell lines. [Mol Oncol] Abstract | Full Article

In Silico Prediction of Housekeeping Long Intergenic Non-Coding RNAs Reveals HKlincR1 as an Essential Player in Lung Cancer Cell Survival

Depletion of HKlincR1 affected cell growth in multiple lung cancer cell lines, and led to disruption of genes involved in cell growth and viability. In addition, HKlincR1 expression was correlated with overall survival in lung adenocarcinoma patients. [Sci Rep] Full Article

A Gapmer Antisense Oligonucleotide Targeting SRRM4 Is a Novel Therapeutic Medicine for Lung Cancer

Scientists report that Ser/Arg repetitive matrix 4 (SRRM4), a splicing activator, was abnormally expressed at high levels in small cell lung cancer (SCLC) and thus was a potential therapeutic target. They screened an effective gapmer antisense oligonucleotide targeting SRRM4 in vitro which led to cell death of SCLC. [Sci Rep] Full Article

CENPE Promotes Lung Adenocarcinoma Proliferation and Is Directly Regulated by FOXM1

Following knockdown of CENPE expression, the proliferation of lung cancer cells was inhibited. In addition, it was revealed that forkhead box M1 (FOXM1) was significantly correlated with centromere protein E (CENPE) expression. Following FOXM1-knockdown, the expression level of CENPE was decreased and the proliferation of lung cancer cells was inhibited. [Int J Oncol] Abstract

Extracellular RNAs from Lung Cancer Cells Activate Epithelial Cells and Induce Neutrophil Extracellular Traps

Lewis lung carcinoma cells were cultured with deprived sera. The cell culture supernatants (CCSs) were analyzed in vitro and in vivo. The results revealed that exRNAs from lung cancer CCSs promoted the inflammatory cytokine interleukin-1β and reduced the vascular cell adhesion molecule-1 expression in lung epithelial cells. [Int J Oncol] Abstract

MicroRNA-625 Inhibits the Progression of Non-Small Cell Lung Cancer by Directly Targeting HOXB5 and Deactivating the Wnt/β-Catenin Pathway

miR-625 expression in non-small cell lung cancer tissues and cell lines was detected using reverse transcription-quantitative polymerase chain reaction. The effects of miR-625 overexpression on NSCLC cell proliferation, apoptosis, migration and invasion in vitro were assessed using an MTT assay, flow cytometry, and cell migration and invasion assays. [Int J Mol Med] Abstract

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Combining Immunotherapies to Treat Non-Small Cell Lung Cancer

The authors review multiple strategies of combining immunotherapies that exploit not only additional immune checkpoint receptors and ligands, but also other synergistic approaches such as vaccines or indoleamine 2,3-dioxygenase inhibitors with the potential to extend the number of non-small cell lung cancer patients achieving successful outcomes. [Expert Rev Respir Med] Abstract

Delivery of Natural Phenolic Compounds for the Potential Treatment of Lung Cancer

Recent in vitro scientific literature on phenolic compounds with anticancer activity towards lung cancer cell lines is reviewed and nanoparticulate delivery is mentioned as a possible solution to the problem of bioavailability. The first part of the review explores the different classes of natural phenolic compounds and discuss recent reports on their activity on lung cancer cells. [Daru] Full Article

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

Bellerophon Presents Additional Positive Data from Cohort 1 of Ongoing Phase II/III Study of INOpulse^® for Treatment of Pulmonary Hypertension Associated with Interstitial Lung Disease

Bellerophon Therapeutics, Inc. presented additional data from Cohort 1 of its ongoing Phase II/III randomized, double-blind, placebo-controlled clinical study of INOpulse^® for the treatment of pulmonary hypertension associated with interstitial lung disease. [Press release from Bellerophon Therapeutics, Inc. discussing research presented at the American Thoracic Society (ATS) 115^th International Conference, Dallas] Press Release

Athersys Presents Data from Its Acute Respiratory Distress Syndrome Clinical Trial

Athersys, Inc. announced additional favorable data from its exploratory Phase I/II acute respiratory distress syndrome (ARDS) clinical trial. Dr. Geoff Bellingan, Medical Director at University College London Hospitals, described the data from the clinical trial, referred to as the MUST-ARDS trial, during his presentation. [Press release from Athersys, Inc. discussing research presented at the American Thoracic Society (ATS) 115^th International Conference, Dallas] Press Release

OncoCyte Presents Positive Results from R&D Validation Study of DetermaVu™

OncoCyte Corporation presented results from the company’s R&D Validation study. The poster details the results from the company’s successful R&D Validation study of DetermaVu™, OncoCyte’s liquid biopsy test for the early detection of lung cancer. [Press release from OncoCyte Corporation discussing research presented at the American Thoracic Society (ATS) 115^th International Conference, Dallas] Press Release

Verona Pharma Presents Expanded Analysis of Ensifentrine Clinical Data in COPD Maintenance Treatment

Verona Pharma plc presented clinically relevant findings from its COPD clinical trial program with lead product candidate, ensifentrine. [Press release from Verona Pharma plc discussing research presented at the American Thoracic Society (ATS) 115^th International Conference, Dallas] Press Release

MBridge Biotherapeutics Announces Data Presentation from First-in-Human Study of BBT-877 for Idiopathic Pulmonary Fibrosis

Bridge Biotherapeutics Inc. announced that the company presented interim data from a Phase I clinical study on BBT-877, a drug candidate for treatment of idiopathic PF. Interim pharmacokinetic and safety results from the randomized, double-blind, placebo-controlled, Phase I study were included in a poster “BBT-877, a potent Autotaxin Inhibitor in Clinical Development to Treat Idiopathic Pulmonary Fibrosis”. [Press release from Mersana Therapeutics, Inc. discussing research presented at the American Thoracic Society (ATS) 115^th International Conference, Dallas] Press Release

FASENRA^® (Benralizumab) Reduces Oral Corticosteroid Use and Maintains Long-Term Efficacy and Safety Profile in Severe Eosinophilic Asthma

A new integrated analysis of Phase III data for FASENRA^® shows that patients with severe eosinophilic asthma who were continuously treated with the medicine for up to two years reduced their use of oral corticosteroids and experienced a sustained improvement in exacerbation rates, lung function, asthma control and health-related quality of life. [Press release from AstraZeneca (BusinessWire, Inc.) discussing research presented at the American Thoracic Society (ATS) 115^th International Conference, Dallas] Press Release

$12.5 Million Grant Funds Ambitious Health Research Collaboration

A groundbreaking research collaboration at the School of Medicine that is shedding light on everything from cancer to diabetes to cardiovascular disease has received $12.5 million from the National Institutes of Health. The grant funding from the National Heart, Lung and Blood Institute will support the next five years of research for an initiative that is unusual both in its focus and its approach. [The University of Viriginia] Press Release

Pershing Square Sohn Prize Awards $4.2M to Seven “Next Generation” Innovators in Cancer Research

The Pershing Square Sohn Cancer Research Alliance announced the seven winners of the 2019 Pershing Square Sohn Prize for Young Investigators in Cancer Research, awarded annually to talented New York City-area cancer research scientists and physician-scientists. The Prize, totaling $4.2 million in funding awarded, emboldens early-career investigators to pursue research projects at a stage when traditional funding is lacking. [-The Pershing Square Sohn Cancer Research Alliance (Business Wire, Inc.)] Press Release

How European Scientists Will Spend €100 Billion

Politicians don’t win prizes for speed, but the European Union’s parliament and the leaders of its member states made record time this year when they hammered out an agreement that could supply researchers in Europe with more than €100 billion (US$113 billion) over seven years. [Nature News] Editorial

Brazilian Academics Protest against Budget Cuts

Students and faculty across Brazil took to the streets on May 15 to protest against budget freezes and the suspension of new research scholarships enacted by the federal government on May 2. This has been the largest demonstration against the government since Jair Bolsonaro took office early this year, with an estimated turnout of more than 1 million people, according to the organizers. [TheScientist] Editorial

NEW Nordic Lung Congress
June 12-14, 2019
Tallinn, Estonia

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

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

Scientist – Pulmonary (STEMCELL Technologies Inc.)

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

Postdoctoral Researcher – Stem Cell Biology of the Lung and Intestines (Standford School of Medicine)

Postdoctoral Fellow – Inflammation Suppression & Lung Disease (National University of Singapore)

Postdoctoral Professor – Basal Allergy and Immunology (Aarhus University)

Postdoctoral Fellowship – Redox Systems in Lung and Breast Cancer (The Held Laboratory)

Postdoctoral Studentship – Lung Adenocarcinoma Research (Max Delbrück Centrum for Molecular Medicine)

Postdoctoral Fellow – Machine Learning in Cancer Treatment (Institute of Cancer Research)

Postdoctoral Fellow – Vascular & Lung Biology (Ann & Robert H. Lurie Children’s Hospital of Chicago)

Postdoctoral Researcher – Regenerative Medicine for Lung Conditions (United Therapeutics)

Postdoctoral Researcher – Causes of Allergies and Asthma (Stanford University)

Postdoctoral Position – Pulmonary/Lung Carcinogenesis Translational Research (Albert Einstein College of Medicine)

Postdoctoral Position – Lung Research (Columbia University)

Associate Professor – Oncology (University of California, Davis)

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