Pulmonary Cell News Volume 5.24 | Jun 23 2016

TOP STORY

A Combinatorial Strategy for Treating KRAS-Mutant Lung Cancer

Investigators take a systematic approach towards identifying combination targets for trametinib, a MEK inhibitor approved by the US Food and Drug Administration, which acts downstream of KRAS to suppress signaling through the mitogen-activated protein kinase cascade. [Nature] Abstract

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A Retinoic Acid-Hedgehog Cascade Coordinates Mesoderm-Inducing Signals and Endoderm Competence during Lung Specification

Using Xenopus embryology, mouse genetics, and human ES cell cultures, researchers identified a conserved signaling cascade that initiates respiratory lineage specification. They showed that retinoic acid (RA) has multiple roles; first RA pre-patterns the lateral plate mesoderm and then it promotes Hedgehog ligand expression in the foregut endoderm. [Cell Rep] Full Article | Graphical Abstract

Influenza Virus Infects Epithelial Stem/Progenitor Cells of the Distal Lung: Impact on Fgfr2b-Driven Epithelial Repair

The impact of influenza virus (IV) infection on lung stem cells and their regenerative responses remains elusive. The authors demonstrated that a highly pathogenic IV infects various cell populations in the murine lung, but displays a strong tropism to an epithelial cell subset with high proliferative capacity, defined by the signature EpCam^highCD24^lowintegrin(α6)^high. [PLoS Pathog] Full Article

Type I Interferon Promotes Alveolar Epithelial Type II Cell Survival During Pulmonary S. pneumoniae Infection and Sterile Lung Injury in Mice

Using a mouse model of pneumococcal pneumonia, investigators revealed that type I interferon (IFN-I) selectively protects alveolar epithelial type II cells (AECII) from inflammation-induced cell death. Mechanistically, signaling via the IFN-I receptor on AECII is sufficient to promote AECII survival. [Eur J Immunol] Abstract

Suppression of MUC5AC Expression in Human Bronchial Epithelial Cells by Interferon-γ

Human pulmonary mucoepidermoid carcinoma cell line and normal human bronchial epithelial cells were used to assess the effects of IFN-γ on MUC5AC transcription. [Allergol Int] Full Article

LUNG CANCER

Tumor-Initiating Cell-Specific miR-1246 and miR-1290 Expression Converge to Promote Non-Small Cell Lung Cancer Progression

Researchers identified the tumor-initiating cell (TIC)-specific microRNAs (miRNAs), miR-1246 and miR-1290, as crucial drivers for tumor initiation and cancer progression in human non-small cell lung cancer. The loss of either miRNA impacted the tumor-initiating potential of TICs and their ability to metastasize. [Nat Commun] Full Article

Oncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells

The authors showed that oncogenic epidermal growth factor receptor (EGFR) induces silencing of multiple unrelated tumor suppressors in lung adenocarcinomas and glioblastomas by inhibiting the DNA demethylase TET oncogene family member 1 (TET1) via the C/EBPα transcription factor. [Cell Rep] Full Article | Graphical Abstract

Tumor Growth Affects the Metabonomic Phenotypes of Multiple Mouse Non-Involved Organs in an A549 Lung Cancer Xenograft Model

Scientists systematically analyzed the metabolic phenotypes of multiple non-involved mouse organ tissues in an A549 lung cancer xenograft model at two different tumor-growth stages using the NMR-based metabonomics approaches. [Sci Rep] Full Article

Synergy of Radiotherapy and PD-1 Blockade in Kras-Mutant Lung Cancer

Scientists report significant (up to 70% volume reduction of the target lesion) and durable (up to 12 weeks) tumor regressions in conditional Kras-driven genetically engineered mouse models of non–small-cell lung cancer treated with radiotherapy and a programmed cell death 1 antibody (αPD-1). [JCI Insight] Full Article | Press Release

Impact of Gene Editing on the Study of Cystic Fibrosis

The authors discuss the impact on the study of cystic fibrosis of gene-editing techniques as they have developed over the last 30 years, up to and including the possibility of editing as a therapeutic approach. [Hum Genet] Abstract

Resisting Resistance: Targeted Therapies in Lung Cancer

Recent studies underscore the multifaceted, genetically heterogeneous nature of tyrosine kinase inhibitors resistance, which evolves dynamically with changes in therapy. The reviewers provide a broad framework for understanding the diverse mechanisms of resistance at play in oncogene-driven lung cancers. [Trends Cancer] Abstract

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

Concordia Healthcare Announces PDT With Photofrin^® Data And Provides Corporate Update

Concordia Healthcare Corp. announced positive findings from an analysis of Photodynamic Therapy (PDT) with Photofrin^® clinical data and also provided a corporate update. PDT with Photofrin^® is Concordia’s light-based cancer treatment that combines a photosensitizing drug called Photofrin^® with a specific type of light to attack cancer cells. [Concordia Healthcare Corp.] Press Release

Savolitinib Global Phase II Trial Initiated in EGFR Mutant Non-Small Cell Lung Cancer

Hutchison China MediTech Limited announced the initiation of a Phase II expansion of the ongoing TATTON trial to evaluate the selective c-Met inhibitor savolitinib in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer patients. [Hutchison China MediTech Limited] Press Release

NEW International Conference on Stem Cell Engineering 2016
October 23-26, 2016
Toronto, Canada

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

NEW Group Leaders – Cardiovascular or Pulmonary Science (Excellence Cluster Cardiopulmonary System)

NEW PhD Studentship – Biofilm-Penetrant Delivery Systems for Lung Pathogens (University of East Anglia)

Associate Professor – Oxidative Lung Injury (Temple University)

Research Fellow – Pulmonary and Critical Care (Mayo Clinic)

Postdoctoral Fellow – Cancer Immunobiology and Immunotherapy (Roswell Park Cancer Institute)

Postdoctoral Fellow – Cancer Immunology and Immunotherapy (Oslo University Hospital)

Postdoctoral Fellow – Vascular/Lung Biology (Yale University School of Medicine)

Postdoctoral Position – Lung Alveolar Epithelial Cell Biology/Differentiation (University of Southern California)

Postdoctoral Researcher – Biochemistry/Molecular Biology (National Jewish Health)

Postdoctoral Fellow – Immunology (New York University Medical Center)

Director Clinical Research – Medical Oncology (Fred Hutchinson Cancer Research Center)

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