Pulmonary Cell News Volume 6.40 | Oct 12 2017

TOP STORY

Polypharmacology-Based Ceritinib Repurposing Using Integrated Functional Proteomics

Applying an integrated phenotypic screening, chemical and phosphoproteomics strategy, researchers describe the anaplastic lymphoma kinase (ALK) inhibitor ceritinib as having activity across several ALK-negative lung cancer cell lines and identified new targets and network-wide signaling effects. [Nat Chem Biol] Abstract | Press Release

(Ranked by impact factor of the journal)

β₂-Adrenoceptor Signaling in Airway Epithelial Cells Promotes Eosinophilic Inflammation, Mucous Metaplasia, and Airway Contractility

Researchers demonstrated that β₂-adrenoreceptor (β₂AR) signaling in the airway epithelium is sufficient to mediate key features of the asthmatic responses to IL-13 in murine models. They showed that inhibition of β₂AR signaling with an aerosolized antagonist attenuated airway hyperresponsiveness, eosinophilic inflammation, and mucus-production responses to IL-13, whereas treatment with an aerosolized agonist worsened these phenotypes, suggesting that β₂AR signaling on resident lung cells modulated the asthma phenotype. [Proc Natl Acad Sci USA] Abstract

Fgf10-Hippo Epithelial-Mesenchymal Crosstalk Maintains and Recruits Lung Basal Stem Cells

The authors showed that during homeostasis, basal stem/progenitor cells in cartilaginous airways maintain their stem cell state by downregulating the Hippo pathway, which generates a localized Fgf10-expressing stromal niche; in contrast, differentiated epithelial cells in non-cartilaginous airways maintain quiescence by activating the Hippo pathway and inhibiting Fgf10 expression in airway smooth muscle cells. [Dev Cell] Full Article | Graphical Abstract

Cell-Specific Expression of Runt-Related Transcription Factor 2 Contributes to Pulmonary Fibrosis

Investigators discovered an up-regulation of runt-related transcription factor 2 (RUNX2) in fibrotic alveolar epithelial type II cells as well as an increase of RUNX2-negative fibroblasts in experimental and human pulmonary fibrosis. [FASEB J] Abstract

Endoplasmic Reticulum Stress Induces HRD1 to Protect Alveolar Type II Epithelial Cells from Apoptosis Induced by Cigarette Smoke Extract

Researchers examined the effects of cigarette smoke extract (CSE) on alveolar type II epithelial cells (AECII) and investigated the underlying mechanism. Primary AECII were isolated from rat lung tissues and exposed to CSE. [Cell Physiol Biochem] Full Article

LUNG CANCER

Simultaneous Evolutionary Expansion and Constraint of Genomic Heterogeneity in Multifocal Lung Cancer

Scientists sequenced a unique cohort of multiple synchronous lung cancers to determine the relative diversity and uniformity of genetic drivers upon identical germline and environmental background. They found that each multicentric primary tumor harbored distinct oncogenic alterations, including novel mutations that are experimentally demonstrated to be functional and therapeutically targetable. [Nat Commun] Full Article

Human Organ Chip Models Recapitulate Orthotopic Lung Cancer Growth, Therapeutic Responses, and Tumor Dormancy In Vitro

The authors showed that microfluidic organ-on-a-chip cell culture technology can be used to create in vitro human orthotopic models of non-small-cell lung cancer that recapitulate organ microenvironment-specific cancer growth, tumor dormancy, and responses to tyrosine kinase inhibitor therapy observed in human patients in vivo. [Cell Rep] Full Article | Press Release | Graphical Abstract

Interleukin-10-Regulated Tumor Tolerance in Non-Small Cell Lung Cancer

Investigators discovered a positive correlation between interleukin (IL)-10 and IL-10 receptor expression in the lung with tumor diameter in patients with non-small cell lung cancer. [Br J Cancer] Abstract

α-Lipoic Acid Inhibits Human Lung Cancer Cell Proliferation through Grb2-Mediated EGFR Downregulation

Scientists found that alpha lipoic acid (α -LA) dramatically decreased non-small cell lung cancer cell proliferation by downregulating growth factor receptor-bound protein 2 (Grb2); in contrast, Grb2 overexpression significantly prevented α-LA-induced decrease in cell growth in vitro. [Biochem Biophys Res Commun] Abstract

Emerging Therapies for Idiopathic Pulmonary Fibrosis, a Progressive Age-Related Disease

Scientists discuss current and emerging therapies for idiopathic pulmonary fibrosis, particularly those targeting age-related mechanisms, and discuss future therapeutic approaches. [Nat Rev Drug Discov] Abstract

MicroRNAs: A Novel Potential Biomarker for Diagnosis and Therapy in Patients with Non-Small Cell Lung Cancer

The authors emphasized a variety of tissue-specific miRNAs, circulating miRNAs and miRNA-derived exosomes that could be used as potential diagnostic and therapeutic biomarkers in non-small cell lung cancer patients. [Cell Prolif] Abstract

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

Lilly Reports Topline Results from Phase III JUNIPER Trial Evaluating Verzenio^™ (Abemaciclib) in KRAS-Mutated, Advanced Non-Small Cell Lung Cancer

Eli Lilly and Company announced that its Phase III JUNIPER study evaluating Verzenio^™, a cyclin-dependent kinase (CDK)4 and CDK6 inhibitor, as monotherapy in KRAS-mutated, advanced non-small lung cancer did not meet its primary endpoint of overall survival. [Eli Lilly and Company] Press Release

MabVax Therapeutics Initiates Patient Enrollment in a Phase I Trial for MVT-1075, a New Radioimmunotherapy Treatment for Advanced Pancreatic, Colon and Lung Cancers

MabVax Therapeutics Holdings, Inc. announced the initiation of patient enrollment in a Phase I clinical trial evaluating a new radioimmunotherapy product for patients with locally advanced or metastatic adenocarcinoma of the pancreas or other CA19-9 positive malignancies including colon and lung cancers. [MabVax Therapeutics Holdings, Inc.] Press Release

FDA Grants Priority Review to Gilotrif^® for Uncommon EGFR Mutations in Advanced NSCLC

Boehringer Ingelheim announced that the supplemental New Drug Application for Gilotrif^® has been accepted for filing and granted Priority Review by the FDA. [Boehringer Ingelheim (PR Newswire Association LLC.)] Press Release

Publishers Threaten to Remove Millions of Papers from ResearchGate

Millions of articles might soon disappear from ResearchGate, the world’s largest scholarly social network. Five publishers said they had formed a coalition that would start ordering ResearchGate to remove research articles from its site because they breach publishers’ copyright. [Nature News] Editorial

Navajo Nation Reconsiders Ban on Genetic Research

When the Navajo Nation opens its first oncology center next year in Tuba City, Arizona, clinicians there may be able to offer a service that has been banned on tribal lands for 15 years: analyzing the DNA of Navajo tribe members to guide treatments and study the genetic roots of disease. [Nature News] Editorial

NEW 14^th Annual Stem Cell Symposium: Technology Innovation for Stem Cell Research and Therapy
February 2, 2018
Los Angeles, California, United States

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

NEW Postdoctoral Position – Lung Adenocarcinoma (University of California, San Francisco)

Non-Clinical Lecturer – Respiratory Gene Therapy (Imperial College London)

Postdoctoral Researcher – Lung and Breast Cancer (University of Cologne)

Faculty Positions – Cancer Research (Huntsman Cancer Institute)

Postdoctoral Research Fellow – Lung Disease (University College Dublin)

Assistant Professor – Lung Immunology (Tulane Medical School)

PhD Position – Molecular Pharmacology (University of Groningen)

Faculty Position – Lung Injury and Repair (The University of Texas Health Science Center)

Research Scientist – Lung Cancer Models (The Francis Crick Institute)

Faculty Position(s) – Basic and Translational Cancer Research (Texas Tech University Health Science Center)

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