Pulmonary Cell News Volume 7.23 | Jun 14 2018

TOP STORY

Mutations in the SWI/SNF Complex Induce a Targetable Dependence on Oxidative Phosphorylation in Lung Cancer

SMARCA4 mutant lung cancer cell lines and xenograft tumors have marked sensitivity to inhibition of oxidative phosphorylation by a novel small molecule, IACS-010759, that is under clinical development. Mechanistically, researchers showed that SMARCA4-deficient cells have a blunted transcriptional response to energy stress creating a therapeutically exploitable synthetic lethal interaction. [Nat Med] Abstract | Press Release

(Ranked by impact factor of the journal)

Parthenolide Attenuated Bleomycin-Induced Pulmonary Fibrosis via the NF-κB/Snail Signaling Pathway

Serum-starved primary lung fibroblasts and HFL1 cells were treated with different doses of parthenolide (PTL), and cell viability and migration rate were measured. Western blot analysis and a dual-luciferase assay were used to analyze the epithelial-mesenchymal transition-related transcription factors influenced by PTL treatment in A549 cells and primary lung epithelial cells. [Respir Res] Full Article

Identification of Key Genes in Human Airway Epithelial Cells in Response to Respiratory Pathogens Using Microarray Analysis

Scientists identified responses of the human airway epithelium cells to respiratory pathogen infection. They retrieved three mRNA expression microarray datasets from the Gene Expression Omnibus database, and identified 116 differentially expressed genes common to all three datasets. [BMC Microbiol] Full Article

Allethrin and Prallethrin Stimulates MUC5AC Expression through Oxidative Stress in Human Airway Epithelial Cells

Investigators demonstrated the effect of allethrin and prallethrin, and the mechanism involved, on mucin expression in human airway epithelial cells. [Biochem Biophys Res Commun] Abstract

The Protective Effects of a Synthetic Geranyl Acetophenone in a Cellular Model of TNF-α-Induced Pulmonary Epithelial Barrier Dysfunction

The effects of tHGA on epithelial barrier dysfunction were determined in TNF-α-induced human alveolar epithelial cells. [Molecules] Full Article

LUNG CANCER

Proscillaridin A Induces Apoptosis and Suppresses Non-Small-Cell Lung Cancer Tumor Growth via Calcium-Induced DR4 Upregulation

Researchers investigated the anti-cancer effects and the mechanisms of action of proscillaridin A in non-small-cell lung cancer cells. [Cell Death Dis] Full Article

Increased Levels of the Long Noncoding RNA, HOXA-AS3, Promote Proliferation of A549 Cells

Investigators showed that HOXA-AS3 was significantly upregulated in lung adenocarcinoma tissues and A549 cells. After knockdown of HOXA-AS3, cell proliferation, migration, and invasion were inhibited. [Cell Death Dis] Full Article

A Radiosensitizing Inhibitor of HIF-1 Alters the Optical Redox State of Human Lung Cancer Cells In Vitro

The authors investigated the longitudinal metabolic changes in radiation-resistant and sensitive A549 lung cancer cells after treatment with a combination of radiation therapy and YC-1, a potent hypoxia-inducible factor (HIF)-1 inhibitor. [Sci Rep] Full Article

Ablation of the CD9 Receptor in Human Lung Cancer Cells Using CRISPR/Cas Alters Migration to Chemoattractants Including IL-16

Using A549 cells as a model of human alveolar epithelium, CD9 expression was ablated using CRISPR/Cas technology. Decreased expression of CD9 mRNA and protein levels was confirmed through RT-qPCR and flow cytometry, respectively. Individual clones were generated that expressed high levels of CD9 or significantly less CD9. [Cytokine] Abstract | Graphical Abstract

KRAS: Reasons for Optimism in Lung Cancer

Despite being the most frequent gain-of-function genetic alteration in human cancer, KRAS mutation has to date offered only limited potential as a prognostic and predictive biomarker. [Eur J Cancer] Abstract

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Merck’s KEYTRUDA^® (Pembrolizumab) Showed Promising Anti-Tumor Activity in Patients with Advanced Small Cell Lung Cancer (SCLC) in Phase II KEYNOTE-158 Study

Merck announced interim data from a cohort of the Phase II KEYNOTE-158 study evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy in patients with previously treated advanced SCLC. [Press release from Merck & Co., Inc. discussing research presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Eloxx Pharmaceuticals Presents Positive New Data for Lead Investigational Drug, ELX-02

Eloxx Pharmaceuticals, Inc. announced positive data demonstrating that ELX-02 restores transmembrane conductance in and promotes forskolin-induced swelling of cystic fibrosis patient organoids carrying homozygous and compound heterozygous CFTR nonsense mutations. [Press release from Eloxx Pharmaceuticals, Inc. discussing research presented at the 41^st European Cystic Fibrosis Conference, Belgrade] Press Release

Asterias Biotherapeutics Announces First Patient Dosed in First-in-Human Clinical Study of Immunotherapy AST-VAC2 in Non-Small Cell Lung Cancer

Asterias Biotherapeutics, Inc. announced enrollment and dosing of the first subject in the first-in-human Phase I clinical trial of AST-VAC2 in the United Kingdom. [Asterias Biotherapeutics, Inc.] Press Release

$8.1 Million Grant Funds New Center to Research Highly Aggressive Form of Lung Cancer

Vanderbilt University has been awarded a five-year, $8.1-million grant from the National Cancer Institute to serve as a research center in the institute’s prestigious Cancer Systems Biology Consortium. [Vanderbilt University] Press Release

Sexual Harassment Is Rife in the Sciences, Finds Landmark US Study

Sexual harassment is pervasive throughout academic science in the United States, driving talented researchers out of the field and harming others’ careers, finds a report from the US National Academies of Sciences, Engineering, and Medicine in Washington DC. The analysis concludes that policies to fight the problem are ineffective because they are set up to protect institutions, not victims — and that universities, funding agencies, scientific societies and other organizations must take stronger action. [Nature News] Editorial

North American Universities Increasingly Cancel Publisher Packages

Florida State University (FSU) will head into negotiations with the publisher Elsevier to see how it can resolve a pricing issue. Back in April, FSU announced that it would not renew a so-called “big deal” with Elsevier in 2019, due to its “high and ever-increasing cost,” and would instead subscribe to a subset of the most-needed journals. [The Scientist] Editorial

China Introduces Sweeping Reforms to Crack Down on Academic Misconduct

China is getting tough on scientific misconduct. The country’s most powerful bodies, the Chinese Communist Party and the State Council, introduced a raft of reforms on 30 May aimed at improving integrity across the research spectrum, from funding and job applications to peer-review and publications. [Nature News] Editorial

More Restrictive U.S. Policy on Chinese Graduate Student Visas Raises Alarm

Reversing yet another policy of the previous administration, the U.S. Department of State began applying tougher restrictions on some Chinese graduate students. The new policy shortens from five years to one year the duration of visas for those planning to study aviation, robotics, and advanced manufacturing. [ScienceInsider] Editorial

NEW Keystone Symposia: Cellular Plasticity: Reprogramming, Regeneration and Metaplasia
January 27-31, 2019
Keystone, Colorado, United States

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NEW Principal Investigators – Cancer (University of Alabama Birmingham)

Research Technologist – Pulmonary (STEMCELL Technologies Inc.)

Chief – Integrative Tumor Epidemiology Branch (National Institutes of Health – National Cancer Institute)

Postdoctoral Position – Immunology/Molecular Biology (National Heart, Lung and Blood Institute)

Postdoctoral Position – Vascular or Lung Biology (Yale University School of Medicine)

Postdoctoral Fellow – Human Lung Stem Cells and Regeneration (MedImmune)

Postdoctoral Fellow – Virology and Respiratory Biology (MedImmune)

Assistant or Associate Professor – Genetic Epidemiology (University of Kentucky)

Postdoctoral Scholarship – Cancer Metabolism (Karolinska Institutet)

Postdoctoral Fellow – Immunology (NYU Langone Health)

PhD Student – Novel Concepts for Therapy of Allergy (Helmholtz Zentrum München)

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