Pulmonary Cell News Volume 6.32 | Aug 17 2017

TOP STORY

Dual MET and SMO Negative Modulators Overcome Resistance to EGFR Inhibitors in Human Non-Small Cell Lung Cancer

Since the concomitant inhibition of both Hedgehog and MET pathways restores the sensitivity to anti-EGF receptor (EGFR) drugs, scientists aimed to discover the first compounds that block simultaneously MET and SMO. By using an “in silico drug repurposing” approach and by validating their predictions both in vitro and in vivo, they identified a set of compounds with the desired dual inhibitory activity and enhanced antiproliferative activity on EGFR tyrosine kinase inhibitor-resistant non-small cell lung cancer. [J Med Chem] Abstract

(Ranked by impact factor of the journal)

The Role of PGE₂ in Alveolar Epithelial and Lung Microvascular Endothelial Crosstalk

The authors revealed that primarily prostaglandin (PG) E₂ accounts for endothelial barrier-promoting activity. Conditioned media from alveolar epithelial cells collected from BALB/c mice and A549 cells increased the electrical resistance of pulmonary human microvascular endothelial cells, respectively. [Sci Rep] Full Article

Development of a Primary Human Co-Culture Model of Inflamed Airway Mucosa

Investigators present an advanced co-culture model to explore neutrophil transepithelial migration utilizing airway mucosal barriers differentiated from primary human airway basal cells and examined by advanced imaging. Human airway basal cells were differentiated and cultured at air-liquid interface on the underside of 3 µm pore-sized transwells, compatible with the study of transmigrating neutrophils. [Sci Rep] Full Article

Brg1 Inhibits E-Cadherin Expression in Lung Epithelial Cells and Disrupts Epithelial Integrity

Researchers studied the function of brahma-related gene-1 (Brg1) in an ovalbumin-induced asthma model and human bronchial epithelial 16HBE cells stably expressing Brg1 shRNA. Their results showed that high expression of Brg1 was detected in asthmatic children and in mouse models. [J Mol Med (Berl)] Abstract

Fraction of MHCII and EpCAM Expression Characterizes Distal Lung Epithelial Cells for Alveolar Type 2 Cell Isolation

Comprehensive molecular and transcriptional profiling of purified alveolar type 2 (AT2) cells would be helpful for elucidating the underlying mechanisms of their cell-specific functions. To enable the further purification of AT2 cells, the authors aimed to discriminate AT2 cells from non-AT2 lung epithelial cells based on surface antigen expression via fluorescence activated cell sorting. [Respir Res] Full Article

MicroRNA-181c Inhibits Cigarette Smoke–Induced Chronic Obstructive Pulmonary Disease by Regulating CCN1 Expression

miR-181c expression was detected in human lung tissue samples of 34 patients, an in vivo murine model of cigarette smoke exposure, and primary human bronchial epithelial cells by qRT-PCR. Investigators showed that miR-181c was significantly down-regulated in lung tissues from patients with COPD compared to individuals who had never smoked. [Respir Res] Full Article

LUNG CANCER

P53-Dependent Downregulation of hTERT Protein Expression and Telomerase Activity Induces Senescence in Lung Cancer Cells as a Result of Pterostilbene Treatment

Scientists investigated the possible mechanisms of pterostilbene (PT)-induced senescence through telomerase inhibition in human non-small cell lung cancer cells and delineated the role of p53 in senescence. The results indicated that PT-induced senescence is characterized by a flattened morphology, positive staining for senescence-associated-β galactosidase activity, and the formation of senescence-associated heterochromatic foci. [Cell Death Dis] Full Article

Antihelminthic Drug Niclosamide Inhibits CIP2A and Reactivates Tumor Suppressor Protein Phosphatase 2A in Non-Small Cell Lung Cancer Cells

Researchers demonstrated that the antihelminthic drug niclosamide inhibited the expression of cancerous inhibitor of protein phosphatase 2A (CIP2A) and reactivated the tumor suppressor PP2A in non-small cell lung cancer (NSCLC) cells. They performed a drug-repurposing screen and identified niclosamide as a CIP2A suppressor in NSCLC cells. [Biochem Pharmacol] Abstract | Graphical Abstract

Upregulation of HINT2 Inhibits Non-Small Cell Lung Cancer Cell Invasion via COX-2/PGE₂-Mediated Activation of β-Catenin Signaling

Investigators explored the effects of histidine triad nucleotide binding protein 2 (HINT2) on the invasive potential of non-small cell lung cancer (NSCLC) cells. Their results showed that the expression of HINT2 was reduced in NSCLC tissues and cell lines. Up-regulation of HINT2 inhibited NSCLC cell invasion in vitro and tumor metastasis in vivo. [Oncol Res] Full Article

Long Intergenic Noncoding RNA 319 (linc00319) Promotes Cell Proliferation and Invasion in Lung Cancer Cells by Directly Downregulating the Tumor Suppressor MiR-32

Scientists investigated the role of linc00319 in the proliferation and invasion of lung cancer cells. They found that, compared with normal lung cell line HBE, linc00319 was increased in low metastatic lung cancer cell lines PAa and AgiY-83a, and further increased in high metastatic lung cancer cell lines A549 and Anip-973. [Oncol Res] Full Article

Association of Long Non-Coding RNA H19 and MicroRNA-21 Expression with the Biological Features and Prognosis of Non-Small Cell Lung Cancer

Researchers investigated the diagnostic and prognostic value of lncRNA H19 and miR-21 expression in non-small-cell lung cancer (NSCLC). Expression of both H19 and miR-21 was significantly higher in lung tissues from patients with NSCLC than in normal lung tissues. [Cancer Gene Ther] Abstract

Lung Epithelial Cells: Therapeutically Inducible Effectors of Antimicrobial Defense

The authors review inducible lung epithelial defense mechanisms that offer opportunities for therapeutic manipulation to protect vulnerable populations against pneumonia. [Mucosal Immunol] Abstract

The Biology, Function and Clinical Implications of Exosomes in Lung Cancer

Scientists describe the biogenesis and components of exosomes mainly in lung cancer, summarize their function in lung carcinogenesis, and focus on the clinical potential of exosomes as biomarkers and therapeutics in lung cancer. [Cancer Lett] Abstract

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

Lungs in Space: UTMB and Houston Methodist Research Project Could Lead to New Lung Therapeutics

Space travel can cause a lot of stress on the human body as the change in gravity, radiation and other factors creates a hostile environment. While much is known about how different parts of the body react in space, how lungs are affected by spaceflight has received little attention until now, say researchers at The University of Texas Medical Branch at Galveston and Houston Methodist Research Institute. [The University of Texas Medical Branch] Press Release | Video

The Addario Lung Cancer Medical Institute, Champions Oncology and Motivated Patients Announce a Research Collaboration and Launch of a Patient Driven Clinical Study in ROS1 Positive Cancer

The Addario Lung Cancer Medical Institute, Champions Oncology, and the ROS1ders announced a preclinical study that will develop new models of cancers expressing a ROS1 gene rearrangement. This study is part of The Global ROS1 Research Initiative, which focuses on improving outcomes for this uncommon yet clinically important oncogene-driven cancer. [The Addario Lung Cancer Medical Institute (PR Newswire Association LLC.)] Press Release

Biocept and UT Southwestern Medical Center Announce Clinical Study to Profile and Monitor Non-Small Cell Lung Cancer Patients with ALK Rearrangements

Biocept, Inc. announced that it has entered into a clinical study agreement with the University of Texas (UT) Southwestern Medical Center. Led by recognized oncologist and ALK mutation researcher Dr. Saad Khan, the study is designed to evaluate the clinical utility of Biocept’s Target Selector^™ platform for patients diagnosed with ALK-positive non-small cell lung cancer and treated with ALK-inhibitor therapy. [Biocept, Inc.] Press Release

GLPG1690 Halts Disease Progression in IPF Patients in FLORA Phase IIa Trial

Galapagos NV announced positive topline results with its autotaxin inhibitor GLPG1690 in patients with idiopathic pulmonary fibrosis (IPF) in the FLORA Phase IIa trial. [Galapagos NV] Press Release

Trump Offers His First List of Science Priorities, and It’s America First

President Donald Trump has translated his campaign promise to “make America great again” into his administration’s first blueprint for federal investment in science and technology. [ScienceInsider] Editorial

China’s Embrace of Embryo Selection Raises Thorny Questions

Fertility centers are making a massive push to increase preimplantation genetic diagnosis in a bid to eradicate certain diseases. [Nature News] Editorial

Budget Cuts Fuel Frustration among Japan’s Academics

Japan’s premier scientific research institution, RIKEN, turned 100 this year, and celebrated with a grand ceremony attended by the empress and emperor. But not everybody was in the mood to party. In the old days, RIKEN was known as a paradise for scientists because of its generous funding. No longer: as Japan cuts off funds in the face of continuing financial uncertainty, the cracks are starting to show. [Nature News] Editorial

NEW Australian Lung Cancer Conference (ALCC) 2018
April 5-7, 2018
Melbourne, Australia

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

NEW Postdoctoral Fellow – Childhood Cardiovascular and Pulmonary Diseases (University of Colorado Anschutz Medical Campus)

Physician Scientist or Senior Scientist – Pulmonary and Critical Care Medicine (Brigham and Women’s Hospital)

Postdoctoral Fellow – Pulmonary Research (University of Maryland)

Postdoctoral Position – Cardio/Pulmonary/Mitochondrial Research (University of Pittsburgh)

Faculty Position – Cancer Biology (Cold Spring Harbor Laboratory)

Postdoctoral Position – Cell Signaling/Cancer Biology (Rutgers Cancer Institute of New Jersey)

Postdoctoral Fellow – Allergy and Immunology (New York University Medical Center)

Postdoctoral Fellow – Pathogenesis of Lung Diseases (Oklahoma State University)

Postdoctoral Fellow – Lung Microengineering (University of Colorado)

PhD Position – Lung Disease (Helmholtz Zentrum München)

Postdoctoral Associate – Lung Cancer Research (Weill Cornell Medicine)

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