Pulmonary Cell News Volume 7.38 | Sep 27 2018

TOP STORY

Exploiting MCL-1 Dependency with Combination MEK + MCL-1 Inhibitors Leads to Induction of Apoptosis and Tumor Regression in KRAS Mutant Non-Small Cell Lung Cancer

Scientists demonstrated that concurrent MEK + MCL-1 inhibition induced apoptosis and tumor regression in KRAS mutant non-small cell lung cancer models, which responded poorly to MEK inhibition alone. [Cancer Discov] Abstract

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Mitochondrial Dysfunction Contributes to the Senescent Phenotype of IPF Lung Fibroblasts

Lung fibroblasts from idiopathic pulmonary fibrosis patients (IPF-LFs) exhibited mitochondrial dysfunction, exemplified by increases in mitochondrial superoxide, DNA, stress and activation of mTORC1. The DNA damaging agent etoposide elicited a DNA damage response and augmented senescence in control-LFs, which were accompanied by disturbances in mitochondrial homoeostasis including heightened superoxide production. [J Cell Mol Med] Full Article

Differential Bronchial Epithelial Response Regulated by ΔNp63: A Functional Understanding of the Epithelial Shedding Found in Asthma

ΔNp63 regulated bronchial apoptosis in response to toll-like receptor 3 stimulation. Phenotypic analysis revealed that ΔNp63 controlled the transcriptional expression and protein release of some epithelium-derived proinflammatory cytokines and endogenous protease inhibitors. [Lab Invest] Abstract

Medium Throughput Breathing Human Primary Cell Alveolus-on-Chip Model

Investigators describe a ‘breathing’ lung-on-chip array equipped with a passive medium exchange mechanism that provided an in vivo-like environment to primary human lung alveolar cells and primary lung endothelial cells. [Sci Rep] Full Article

Anxa4 Mediated Airway Progenitor Cell Migration Promotes Distal Epithelial Cell Fate Specification

The authors identified that Anxa4 was a downstream target of ERK1/2 signaling. Anxa4^−/− airway epithelial cells exhibitd a “lag-behind” behavior and tended to stay at the stalk airways. They demonstrated that Anxa4 functioned redundantly with Anxa1 and Anxa6 in regulating the endoderm budding process. [Sci Rep] Full Article

LUNG CANCER

Estrogen Receptor β Promotes the Vasculogenic Mimicry (VM) and Cell Invasion via Altering the lncRNA-MALAT1/miR-145-5p/NEDD9 Signals in Lung Cancer

Investigators suggested that estrogen receptor β (ERβ) could increase lncRNA-MALAT1 (MALAT1) expression via directly binding to the estrogen response elements located on the promoter of MALAT1, which could then lead to suppressing miR145-5p and increasing NEDD9 protein expression as miR145-5p could directly target the 3ʹ-UTR of NEDD9-mRNA. [Oncogene] Abstract

Aptamer-miR-34c Conjugate Affects Cell Proliferation of Non-Small Cell Lung Cancer Cells

Researchers showed that re-introduction of miR-34c-3p reduced NSCLC cell survival in vitro. They demonstrated that miR-34c-3p and the GL21.T/miR-34c chimera affected NSCLC cell proliferation and were able to overcome acquired RTK-inhibitor resistance by targeting the AXL receptor. [Mol Ther Nucleic Acids] Abstract | Full Article

Oncogenic Zinc Finger Protein ZNF322A Promotes Stem Cell-Like Properties in Lung Cancer through Transcriptional Suppression of c-Myc Expression

ZNF322A bound directly to the c-Myc promoter and recruited histone deacetylase 3 to transcriptionally suppress c-Myc expression, which in turn increased mitochondrial oxidative phosphorylation and promoted cell motility, thus maintaining the stem cell-like properties of lung cancer. [Cell Death Differ] Abstract

TC2N, a Novel Oncogene, Accelerates Tumor Progression by Suppressing p53 Signaling Pathway in Lung Cancer

The blockade of p53 attenuated the function of tac2-N (TC2N) knockdown in the regulation of cell proliferation and apoptosis. Downregulated TC2N was involved in the apoptosis of lung cancer cells induced by doxorubicin, leading to p53 pathway activation. [Cell Death Differ] Abstract

Repression of Noxa by Bmi1 Contributes to Deguelin-Induced Apoptosis in Non-Small Cell Lung Cancer Cells

Knockdown of Bmi1 significantly suppressed NSCLC cell proliferation and colony formation. Deguelin treatment attenuated the binding activity of Bmi1 to the Noxa promoter, thus resulting in Noxa transcription and apoptosis activation. [J Cell Mol Med] Full Article

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The Lung Microvasculature Is a Functional Immune Niche

Data shows that lung capillaries provide a unique anatomical site for neutrophils to capture bloodstream pathogens, which contrasts the conventional monophagocytic-dominated vascular host defense of the spleen and liver. Moreover, lung capillaries provide an efficient site for direct cell-cell communication required for the induction of apoptosis in aged neutrophils. [Trends Immunol] Abstract

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Brigatinib Becomes Potential New First-Line Option for ALK-Positive Non-Small Lung Cancer

Results of a 275-patient, multi-national Phase III clinical trial known as ALTA-1L were published in the New England Journal of Medicine and presented concurrently. [Press release from University of Colorado Cancer Center discussing research presented at the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer 2018, Toronto] Press Release

Promising Phase I/II Results for Entrectinib against ROS1+ Non-Small Cell Lung Cancer

Results of Phase I and Phase II clinical trials of the drug entrectinib in ROS1-positive non-small cell lung cancer were presented. [Press release from University of Colorado Cancer Center discussing research presented at the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer 2018, Toronto] Press Release

Genentech’s TECENTRIQ in Combination with Chemotherapy Helped People Live Significantly Longer as an Initial Treatment for People with Extensive-Stage Small Cell Lung Cancer

Genentech announced positive results from the Phase III IMpower133 study of TECENTRIQ^® plus carboplatin and etoposide for the initial treatment of people with previously-untreated extensive-stage small cell lung cancer. [Press release from Genentech, Inc. discussing research presented at the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer 2018, Toronto] Press Release

Spectrum Pharmaceuticals Announces Release of Updated Poziotinib Data from MD Anderson Phase II Study in Non-Small Cell Lung Cancer Patients

Spectrum Pharmaceuticals, Inc. announced preliminary poziotinib data from the University of Texas, MD Anderson Cancer Center Phase II non-small cell lung cancer study. [Press release from Spectrum Pharmaceuticals, Inc. discussing research presented at the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer 2018, Toronto] Press Release

Genentech’s Investigational Medicine Entrectinib Showed a Durable Response of More than Two Years in People with a Specific Type of Lung Cancer

Genentech announced results for its investigational medicine entrectinib, from an integrated analysis of the pivotal Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA trials, which showed that entrectinib shrank tumors in 77.4 percent of people with locally advanced or metastatic ROS1-positive non-small cell lung cancer. [Genentech, Inc.] Press Release

Anaptysbio Reports Positive Topline Data from Phase IIa Proof-of-Concept Clinical Trial of Etokimab in Severe Eosinophilic Asthma

AnaptysBio, Inc. announced positive topline proof-of-concept data for etokimab, its investigational anti-IL-33 therapeutic antibody, in an ongoing single dose Phase IIa clinical trial in adult patients with severe eosinophilic asthma. [AnaptysBio, Inc.] Press Release

Takeda Receives Positive CHMP Opinion Recommending ALUNBRIG^® (Brigatinib) for the Treatment of ALK+ Non-Small Cell Lung Cancer in Patients Previously Treated with Crizotinib

Takeda Pharmaceutical Company Limited announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending the full approval of ALUNBRIG^® as a monotherapy for the treatment of adult patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer previously treated with crizotinib. [Takeda Pharmaceutical Company Limited (Business Wire, Inc.)] Press Release

Trelegy Ellipta Receives Positive CHMP Opinion Supporting Expanded COPD Indication in Europe

GlaxoSmithKline plc and Innoviva, Inc. announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion today supporting the use of Trelegy Ellipta in a broader group of patients with moderate to severe COPD and that labelling, if approved, will be updated to further reflect its effect on exacerbations of COPD. [GlaxoSmithKline plc.] Press Release

France Seeks Slim Rise to Research Budget Amid Spending Cuts

The French government has called for a modest increase to its higher education and research budget for 2019 as it strives to rein in public spending amid a sluggish economic growth forecast. [Nature News] Editorial

Science Learns from Its Mistakes Too

Scientific studies should always be published irrespective of their result. That is one of the conclusions of a research project conducted by the German Centre for the Protection of Laboratory Animals at the German Federal Institute for Risk Assessment, the results of which have now been published in the journal PLOS ONE. [EurekAlert!] Editorial

Why Chinese Medicine Is Heading for Clinics around the World

For the first time, the World Health Organization will recognize traditional medicine in its influential global medical compendium. [Nature News] Editorial

NEW Gordon Research Conference: Lung Development, Injury and Repair 2019
August 4-9, 2019
Lewiston, Maine, United States

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NEW Postdoctoral Research Associate – Lung Cancer & Hypoxia Signaling (University of Illinois Cancer Center)

Postdoctoral Fellow – Vascular and/or Lung Biology (Yale University)

Postdoctoral Research Fellow – Respiratory Epithelial Cell Biology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Sepsis and Pulmonary Injury Research (University of Maryland)

Research Fellow – Development of Occupational Diseases (CDC/National Institute for Occupational Safety and Health)

Postdoctoral Scientist – Cancer Biology and Immunology (Technical University of Munich)

Faculty Investigators – Cancer Research (The University of Alabama at Birmingham)

Postdoctoral Position – Lung Diseases (German Research Center for Environmental Health)

Postdoctoral Position – Acute Lung Injury (University of Kentucky)

Principal Investigators – Cancer (University of Alabama Birmingham)

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