Pulmonary Cell News Volume 8.30 | Aug 8 2019

TOP STORY

MYC Paralog-Dependent Apoptotic Priming Orchestrates a Spectrum of Vulnerabilities in Small Cell Lung Cancer

Using a unique cellular CRISPR activation model, researchers uncovered that, in contrast to MYCN and MYCL, MYC repressed BCL2 transcription via interaction with MIZ1 and DNMT3a. The resulting lack of BCL2 expression promoted sensitivity to cell cycle control inhibition and dependency on MCL1. [Nat Commun] Full Article

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Allele Specific Repair of Splicing Mutations in Cystic Fibrosis through AsCas12a Genome Editing

The 3272–26A>G and 3849+10kbC>T CFTR mutations alter the correct splicing of the CFTR gene, generating new acceptor and donor splice sites respectively. Scientists developed a genome editing approach to permanently correct these genetic defects, using a single crRNA and the Acidaminococcus sp. BV3L6, AsCas12a. [Nat Commun] Full Article | Press Release

Mitochondrial Dysfunction in Human Primary Alveolar Type II Cells in Emphysema

Investigators found high DNA damage and impairment of DNA damage repair in mitochondria in alveolar type II cells isolated from emphysema patients, which contributed to abnormal mitochondrial dynamics. [EBioMedicine] Full Article

Human Airway Epithelial Extracellular Vesicle miRNA Signature Is Altered upon Asthma Development

Normal human bronchial epithelial cells cells were cultured at air-liquid interface and treated with interleukin-13 to induce an asthma-like phenotype. Extracellular vesicle (EV) isolations by precipitation from basal culture medium or apical surface wash were characterized by Nanoparticle Tracking Analysis, Transmission Electron Microscopy and Western Blot, and EV-associated miRNAs were identified by a RT-qPCR-based profiling. [Allergy] Abstract

Autophagy Inhibition-Mediated Epithelial-Mesenchymal Transition Augments Local Myofibroblast Differentiation in Pulmonary Fibrosis

Investigators report that in alveolar epithelial cells inhibition of autophagy promoted epithelial-mesenchymal transition, a process implicated in embryonic development, wound healing, cancer metastasis and fibrosis. [Cell Death Dis] Full Article

Cigarette Smoke Activates the Parthanatos Pathway of Cell Death in Human Bronchial Epithelial Cells

Exposing cells to an increasing number of cigarettes revealed that significant activation of the parthanatos pathway occured after exposure to higher levels of smoke. Use of the specific PARP-1 inhibitor, BMN673, abrogated the effect of smoke induced activation of the parthanatos pathway. [Cell Death Discov] Full Article

Characterization of Cellular Transcriptomic Signatures Induced by Different Respiratory Viruses in Human Reconstituted Airway Epithelia

Researchers used RNAseq to characterize and compare the transcriptomic signature of infection induced by different major respiratory viruses in a model of reconstituted human airway epithelia. [Sci Rep] Full Article

LUNG CANCER

Depleting PTOV1 Sensitizes Non-Small Cell Lung Cancer Cells to Chemotherapy through Attenuating Cancer Stem Cell Traits

Depleting prostate tumor over expressed gene 1 (PTOV1) increased sensitivity to chemotherapy drugs cisplatin and docetaxel by increasing cell apoptosis, inhibiting cell migration and invasion. [J Exp Clin Cancer Res] Full Article

An Extracellular Vesicle-Associated Gene Signature Correlates with Hypoxic Microenvironment and Predicts Recurrence in Lung Adenocarcinoma

Researchers investigated the expression of coding genes of proteins carried by small extracellular vesicles in primary lung adenocarcinoma. Based on protein-protein interaction network, they identified three network modules as a signature that could predict recurrence. [Mol Ther Nucleic Acids] Abstract | Full Article

Iron Accumulation in Tumor-Associated Macrophages Marks an Improved Overall Survival in Patients with Lung Adenocarcinoma

Patients with lung adenocarcinoma accumulating iron in the tumor microenvironment (TME) showed higher numbers of M1-like pro-inflammatory tumor-associated macrophages (TAMs) and a survival advantage compared to iron-negative patients. By contrast, in patients with lung squamous cell carcinoma iron in the TME did not affect survival, suggesting a unique influence of iron on different histological subtypes of non-small cell lung cancer. [Sci Rep] Full Article

The miR-195 Axis Regulates Chemoresistance through TUBB and Lung Cancer Progression through BIRC5

The authors assessed the correlation between tumor levels of TUBB and patient survival, the effect of TUBB on drug response, and the effect of miR-195 on migration, invasion and metastasis in vitro and in vivo. [Mol Ther Oncolytics] Abstract | Full Article

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Immunotherapy in Small-Cell Lung Cancer: From Molecular Promises to Clinical Challenges

Scientists summarize the current clinical evidence on immunotherapy in small cell lung cancer, describe the molecular bases underlying treatment resistance and discuss the potentialities and the rationale of different therapeutic combinations. [J Immunother Cancer] Full Article

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

Verona Pharma Reports Positive Phase II Results with Dry Powder Inhaler Formulation of Ensifentrine in COPD

Verona Pharma plc announced positive Phase II data with a dry powder inhaler formulation of its lead development product, ensifentrine, for the maintenance treatment of COPD. All of the primary and secondary lung function endpoints were met in the Phase II trial. [Verona Pharma plc (GlobeNewswire, Inc.)] Press Release

I-Mab Biopharma and TRACON Pharmaceuticals Announce Dosing of the First Patient in a Phase I Trial of the CD73 Antibody TJD5 in the U.S. in Patients with Advanced Solid Tumors

I-Mab Biopharma (I-Mab) and TRACON Pharmaceuticals announced that TRACON has dosed the first patient in a U.S. Phase I first-in-human clinical trial of I-Mab’s proprietary CD73 antibody TJD5, also known as TJ004309, in patients with advanced solid tumors. TJD5 will be dosed in the Phase I trial both as a single agent and in combination with TECENTRIQ^®, a PD-L1 antibody marketed by Roche. [I-Mab Biopharma] Press Release

Mexican Science Suffers under Debilitating Budget Cuts

Austerity measures recently enacted by Mexico’s president are pushing the country’s scientific efforts — chronically underfunded for years — to a breaking point, according to researchers. [Nature News] Editorial

China Approves Ethics Advisory Group after CRISPR-Babies Scandal

China will establish a national committee to advise the government on research-ethics regulations. The decision comes less than a year after a Chinese scientist sparked an international outcry over claims that he had created the world’s first genome-edited babies. [Nature News] Editorial

NEW GOLD COPD 2019 International Conference
November 5, 2019
Philadelphia, Pennsylvania, United States

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NEW Postdoctoral Research Fellow – Lung Cancer (University Hospital of Cologne)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Scientist – Pulmonary (STEMCELL Technologies Inc.)

Postdoctoral Research Fellow – Lung Cancer Immunology (Memorial Sloan Kettering Cancer Center)

Assistant/Associate Professor – Respiratory Tract Infections (Hannover Medical School)

Postdoctoral Fellowship – Lung Epithelium (Boston University)

Postdoctoral Positions – Pulmonary Injury (University of Maryland)

PhD Studentship – Extracellular Vesicles in Pulmonary Fibrosis (Université de Franche-Comté)

Postdoctoral Position – Lung Injury (University of Connecticut)

Postdoctoral Fellowship – Redox Biology of Lung and Breast Cancer (Washington University School of Medicine)

Postdoctoral Fellow – Pluripotent Stem Cell-Derived Human Lung Organoids (Columbia University Irving Medical Center)

Postdoctoral Researcher – Lung Lineage Development (Hospital for Sick Children)

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