Pulmonary Cell News Volume 8.36 | Sep 19 2019

TOP STORY

Development of Combination Therapies to Maximize the Impact of KRAS-G12C Inhibitors in Lung Cancer

Combined mammalian target of rapamycin, growth factor 1 receptor, and mitogen-activated protein kinase kinase (MEK) inhibition inhibited the principal signaling pathways required for the survival of KRAS-mutant cells and produced marked tumor regression in three different KRAS-driven lung cancer mouse models. Replacing the MEK inhibitor with the mutant-specific KRAS-G12C inhibitor ARS-1620 in these combinations was associated with greater efficacy, specificity, and tolerability. [Sci Transl Med] Abstract | Press Release

(Ranked by impact factor of the journal)

IFN-γ Restores the Impaired Function of RNase L and Induces Mitochondria-Mediated Apoptosis in Lung Cancer

Investigators showed that function of RNase L, though highly upregulated, was functionally impaired both in nuclear and cytoplasm in lung cancer cells. In normal lung epithelial cells, RNase L activation induced by 2-5A promoted nuclear condensation, DNA cleavage, and cell apoptosis, while in lung cancer cells, these processes were inhibited and RNase L-mediated downregulation of fibrillarin, Topo I and hnRNP A1 was also impaired in lung cancer cells. [Cell Death Dis] Full Article

Reversal of Surfactant Protein B Deficiency in Patient Specific Human Induced Pluripotent Stem Cell Derived Lung Organoids by Gene Therapy

Investigators showed the differentiation of patient specific induced pluripotent stem cells (iPSCs) derived from a patient with SFTPB deficiency into lung organoids with mesenchymal and epithelial cell populations from both the proximal and distal portions of the human lung. They altered the deficiency by infecting the SFTPB deficient iPSCs with a lentivirus carrying the wild type SFTPB gene. [Sci Rep] Full Article

Cucurbitacin E Ameliorates Lipopolysaccharide-Evoked Injury, Inflammation and MUC5AC Expression in Bronchial Epithelial Cells by Restraining the HMGB1-TLR4-NF-κB Signaling

Cucurbitacin E (CuE) had little cytotoxicity on cell viability of human bronchial epithelial cell line BEAS-2B. Moreover, lipopolysaccharide (LPS) exposure inhibited cell viability and induced cell apoptosis, which was reversed following CuE pretreatment. Additionally, CuE administration suppressed LPS-induced inflammatory cytokine production, including TNF-α, IL-6, and IL-8. [Mol Immunol] Abstract

LUNG CANCER

Distinct Initiating Events Underpin the Immune and Metabolic Heterogeneity of KRAS-Mutant Lung Adenocarcinoma

Researchers demonstrated that Keap1-deficient Kras^G12D lung tumors arose from a bronchiolar cell-of-origin, lacking pro-tumorigenic macrophages observed in tumors originating from alveolar cells. Keap1 loss activated the pentose phosphate pathway, inhibition of which, using 6-AN, abrogated tumor growth. [Nat Commun] Full Article

SNRPB Promotes the Tumorigenic Potential of NSCLC in Part by Regulating RAB26

The authors demonstrated that SNRPB promotes non-small cell lung cancer (NSCLC) tumorigenesis both in vitro and in vivo. Mechanistically, they revealed that RAB26 was a critical target of SNRPB. Suppression of SNRPB led to retention of intron seven in the RAB26 mRNA and reduced RAB26 mRNA through activation of nonsense-mediated RNA decay. [Cell Death Dis] Abstract

The Lytic Activity of VSV-GP Treatment Dominates the Therapeutic Effects in a Syngeneic Model of Lung Cancer

To study a tumor system with limited antiviral effects, they generated interferon receptor-deficient cells. Therapeutic efficacy of VSV-GP was assessed in vivo in syngeneic C57BL/6 and athymic nude mice bearing subcutaneous tumours. VSV-GP treatment effects were analysed using bioluminescent imaging, immunohistochemistry, ELISpot, flow cytometry, multiplex ELISA and Nanostring^® assays. [Br J Cancer] Full Article

Semaphorin 6A Attenuates the Migration Capability of Lung Cancer Cells via the NRF2/HMOX1 Axis

Silencing of the cellular homeostasis protein Heme-oxygenase-1 (HMOX1) and/or the transcription factor Nuclear Factor, Erythroid-2-Like-2 (NRF2) reversed the migration-suppressing effect of semaphorin-6A (SEMA6A) and the SEMA6A-driven alterations in expression of urokinase insulin-like-growth-factor-binding-protein-3, matrix metalloproteinase (MMP)-1, and MMP9, the downstream effectors of HMOX1. [Sci Rep] Full Article

Novel [1,2, 4]triazolo[1,5-a]pyrimidine Derivatives as Potent Antitubulin Agents: Design, Multicomponent Synthesis and Antiproliferative Activities

Initial biological evaluation demonstrated some of the target compounds displayed potent antitumor activity in vitro against three cancer cell lines. Among them, the most highly active analogue 26 inhibited the growth of HeLa, and A549 cell lines with indicating excellent selectivity over non-tumoral cell line HEK-293 which suggested that the target compounds might possess a high safety index. [Bioorg Chem] Abstract | Graphical Abstract

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Airway and Alveolar Epithelial Cells in Culture

The authors introduce the principles of culturing airway and alveolar epithelial cells, as well as recent new and future developments. Advantages and disadvantages of using cell lines and primary cells isolated from tissue are discussed. [Eur Respir J] Abstract

Aberrant MicroRNAomics in Pulmonary Complications: Implications in Lung Health, and Diseases

Considering the relevant roles and functions of miRNAs under physiological and pathological conditions, they may lead to the invention of new diagnostic and therapeutic tools. Investigators focus on recent advances in understanding the role of miRNAs in lung development, lung health, and diseases, while also exploring the progress and prospects of their application as therapeutic leads or as biomarkers. [Mol Ther Nucleic Acids] Abstract | Full Article

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

Bellerophon Receives Orphan Drug Designation for Nitric Oxide in the Treatment of Idiopathic Pulmonary Fibrosis

Bellerophon Therapeutics, Inc. announced the FDA has granted Orphan Drug Designation to nitric oxide for the treatment of idiopathic pulmonary fibrosis. [Bellerophon Therapeutics, Inc.] Press Release

$8M Grant Funds Cincinnati Children’s as Coordinating Center for Lung Mapping Program

The National Heart, Lung, and Blood Institute has named Cincinnati Children’s Hospital Medical Center as the new data coordinating center for LungMAP, an open-access resource for human lung data. The five-year, $8 million grant will support information sharing to help researchers better understand human lung development, ultimately leading to advancements in pulmonary care. [Cincinnati Children’s Hospital Medical Center (Newswise, Inc.)] Press Release

Number of Vaping-Related Illnesses in US Has Spiked, CDC Says

The number of serious lung injuries linked to vaping has jumped sharply, the Centers for Disease Control and Prevention said Thursday, with states reporting 530 confirmed or probable cases of the illness. That’s up from 380 reported earlier this week. [STAT News] Editorial

New Journal Seeks Typically Overlooked Studies

On September 18, Cambridge University Press launched an open-access journal that will address issues in research by taking a different approach to publishing. The journal, Experimental Results, will include findings that have inconclusive or negative results and articles that reproduce or dispute existing research. [The Scientist] Editorial

US Awards $3 Million to Fill Gaps in Medical Marijuana Research

The US government will spend $3 million to find out if marijuana can relieve pain, but none of the money will be used to study the part of the plant that gets people high. Nine research grants announced are for work on CBD, the trendy ingredient showing up in cosmetics and foods, and hundreds of less familiar chemicals. THC research was excluded. [STAT News] Editorial

NEW AACR International Conference on Molecular Targets and Cancer Therapeutics
October 26-30, 2019
Boston, Massachusetts, United States

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

NEW Scientific Officer – Lung and Skin Toxiciology (Federal Institute for Risk Assessment)

Scientist – Pulmonary (STEMCELL Technologies Inc.)

Postdoctoral Positions – Sepsis and Pulmonary Injury (University of Maryland)

Postdoctoral Position – Small Cell Lung Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Lung Inflammation (The Boston University Pulmonary Center)

Postdoctoral Scientist – Small Cell Lung Cancer (Cancer Research UK Manchester Institute)

Associate Director – Pulmonary Biology (Translate Bio, Inc.)

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

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

Postdoctoral Fellowship – Lung Epithelium (Boston University)

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