Pulmonary Cell News Volume 8.12 | Apr 4 2019

TOP STORY

Crizotinib-Induced Immunogenic Cell Death in Non-Small Cell Lung Cancer

The combination of cisplatin and high-dose crizotinib induced immunogenic cell death in non-small cell lung carcinoma (NSCLC) cells and effectively controlled the growth of distinct orthotopic NSCLC models. These anticancer effects were linked to increased T lymphocyte infiltration and were abolished by T cell depletion or interferon-γ neutralization. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

IL-1 and TNFα Contribute to the Inflammatory Niche to Enhance Alveolar Regeneration

Using an organoid-based screening assay, investigators found that interleukin-1 (IL-1) and tumor necrosis factor α (TNFα) enhanced the proliferation of lung alveolar stem cells (AEC2s) while maintaining their differentiation capacity. [Stem Cell Reports] Full Article | Graphical Abstract

CO-Releasing Molecule-2 Induces Nrf2/ARE-Dependent Heme Oxygenase-1 Expression Suppressing TNF-α-Induced Pulmonary Inflammation

Scientists dissected the mechanisms underlying carbon monoxide-releasing molecule (CORM)-2-induced heme oxygenase-1 (HO-1) expression in human pulmonary alveolar epithelial cells (HPAEpiCs). TNF-α-induced intercellular adhesion molecule-1 expression associated with monocyte adhesion to HPAEpiCs was attenuated by infection with adenovirus-HO-1 or incubation with CORM-2. [J Clin Med] Full Article | Graphical Abstract

Tollip Inhibits ST2 Signaling in Airway Epithelial Cells Exposed to Type II Cytokines and Rhinovirus

Tollip- and IRAK1-deficient primary human tracheobronchial epithelial (HTBE) cells and Tollip knockout HTBE cells were generated using shRNA knockdown and CRISPR/Cas9 approaches, respectively. Cells were stimulated with IL-13, IL-33, and/or rhinovirus (RV) 16. Soluble ST2, activated IRAK1, and IL-8 were measured. [J Innate Immun] Full Article

Epigenetic Changes in Alveolar Type II Lung Cells of A/J Mice Following Intranasal Treatment with Lipopolysaccharide

The epigenetic effects of lipopolysaccharide (LPS) were examined in alveolar type II lung cells of A/J mice. LPS treatment was associated with epigenetic changes including decreased cytosine formylation and reduced histone H3K14 and H3K23 acetylation, as well as altered expression levels of genes involved in cell adhesion, inflammation, immune response, and epigenetic regulation. [Chem Res Toxicol] Abstract

LUNG CANCER

Wnt1 Silences Chemokine Genes in Dendritic Cells and Induces Adaptive Immune Resistance in Lung Adenocarcinoma

Researchers showed that lung adenocarcinoma (LUAD) cells used paracrine Wnt1 signaling to induce immune resistance. Altering Wnt1 expression profoundly affected growth of murine LUADs, and this was dependent on conventional dendritic cells and T cells. [Nat Commun] Full Article

Antagonism between HtrA3 and TGF-β1 Contributes to Metastasis in Non-Small-Cell Lung Cancer

The authors reported that decreased levels of high temperature requirement A3 (HtrA3 – long and short isoforms) negatively correlated with elevated TGF-β1 in lung tumor tissue with metastasis. In non-small cell lung cancer cell lines, exogenous TGF-β1 significantly downregulated the level of HtrA3, especially the long isoform, during induction of epithelial-mesenchymal transition. [Cancer Res] Full Article | Abstract

Iron-Dependent CDK1 Activity Promotes Lung Carcinogenesis via Activation of the GP130/STAT3 Signaling Pathway

Researchers found that iron-dependent CDK1 activity upregulated IL-6 receptor subunit GP130 post-transcriptionally via phosphorylation of 4E-BP1, which was critical for activation of JAK/STAT3 signaling. CDK1 knockdown and iron chelator DFO decreased tumorigenicity and GP130/STAT3 signaling in vivo. [Cell Death Dis] Full Article

CX Chemokine Receptor 7 Contributes to Survival of KRAS-Mutant Non-Small Cell Lung Cancer upon Loss of Epidermal Growth Factor Receptor

Investigators showed that ablation of epidermal growth factor receptor (EGFR) significantly suppressed tumor growth in KRAS-dependent cells and induced significantly higher expression of CX chemokine receptor 7 (CXCR7) and activation of MAPK. Dual EGFR and CXCR7 inhibition led to substantial reduction of MAPK and synergistic inhibition of cell growth. [Cancers] Full Article

Deubiquitinase DUB3 Regulates Cell Cycle Progression via Stabilizing Cyclin A for Proliferation of Non-Small Cell Lung Cancer Cells

Scientists report that DUB3 regulated cell cycle progression by deubiquitinating cyclin A that links to proliferation of non-small cell lung cancer (NSCLC) cells. They demonstrated that DUB3 regulated cell cycle progression by stabilizing cyclin A, because ablation of DUB3 arrested cell cycle from G0/G1 to S phase and the resulting effect could be rescued by introducing cyclin A into NSCLC cells. [Cells] Full Article

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Molecular Subtypes of Small Cell Lung Cancer: A Synthesis of Human and Mouse Model Data

The authors review and synthesize recent lines of evidence that appear to be converging on a new model of small cell lung cancer (SCLC) subtypes, and propose a working nomenclature for SCLC subtypes defined by relative expression of four transcription factors. [Nat Rev Cancer] Abstract

Regenerative Pharmacology for COPD: Breathing New Life Into Old Lungs

The authors argue, that given the widespread and irreversible nature of COPD, serious consideration of regenerative pharmacology is necessary. However, for this approach to be feasible, a better understanding of the cell-specific molecular control of regeneration, the regenerative potential of the human lung and regenerative competencies of patients with COPD are required. [Thorax] Abstract

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

Data for Merck’s KEYTRUDA^® across Different Types of Advanced Lung Cancer

Merck announced the first-time presentation of results from a post-hoc analysis of patients with liver or brain metastases from the Phase III KEYNOTE-189 trial. [Press release from Merck discussing research presented at the 2019 American Association of Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

Adding Savolitinib to Osimertinib Beneficial for Certain Pretreated Lung Cancer Patients

Adding the investigational MET inhibitor savolitinib to the EGFR inhibitor osimertinib (Tagrisso) yielded clinical responses in patients who had EGFR-mutant non-small cell lung cancer that had developed resistance to prior EGFR-targeted therapies through MET-gene amplification, according to interim results from two expansion cohorts of the Phase Ib clinical trial TATTON. [Press release from the American Association of Cancer Research (EurekAlert) discussing research presented at the 2019 American Association of Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

Combination of First-in-Class NBTXR3, Radiotherapy, and Anti-PD-1 Immunotherapy Demonstrate Efficacy in Treating Resistant Pre-Clinical In Vivo Models of Lung Cancer

NANOBIOTIX announced preclinical data from studies currently being conducted under its collaborations with the University of Texas MD Anderson Cancer Center and the Weill Cornell Medical College. [Press release from Nanobiotix discussing research presented at the 2019 American Association of Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

ArcherDX Announces Collaboration with University College London to Investigate the Novel Use of Cell-Free Tumor DNA to Detect Disease Recurrence in Lung Cancer Patients

ArcherDX, Inc. announced that it has entered into a research collaboration with the University College London (UCL) and the Francis Crick Institute to use ArcherDX’s proprietary Anchored Multiplex PCR technology to detect evidence of disease recurrence in lung cancer patients from cell-free circulating tumor DNA as part of the Cancer Research UK funded UCL-sponsored TRACERx study. [ArcherDX, Inc.] Press Release

Bristol-Myers Squibb Announces Long-Term Survival Results from Pooled Analyses of Opdivo (Nivolumab) in Previously-Treated Non-Small Cell Lung Cancer Patients

Bristol-Myers Squibb Company announced results from pooled analyses of survival data from four studies in patients with previously-treated advanced non-small cell lung cancer who were treated with Opdivo. [Bristol-Myers Squibb Company] Press Release

VolitionRx Limited Extends Clinical Trial Program in Lung Cancer

VolitionRx Limited announced that it has added to its extensive clinical trial program with the execution of a non-binding Memorandum of Understanding, through its wholly-owned subsidiary, Belgian Volition SPRL, to conduct its first large-scale lung cancer study in conjunction with the prestigious National Taiwan University. [VolitionRx Ltd] Press Release

Merck’s KEYTRUDA^® (Pembrolizumab) Approved in China for First-Line Treatment of Metastatic Nonsquamous Non-Small Cell Lung Cancer (NSCLC) in Combination with Chemotherapy

Merck announced that KEYTRUDA, Merck’s anti-PD-1 therapy, has been approved by the National Medical Products Administration in combination with pemetrexed and platinum chemotherapy for the first-line treatment of patients with metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations. [Merck & Co., Inc.] Press Release

Bioethicists Concerned over Japan’s Chimera Embryo Regulations

Japanese regulators have effectively given the green light to research involving human-animal chimera embryos. Many researchers see the move to relax the rules as a welcome change, yet some are worried the revisions don’t take public concerns enough into consideration. [The Scientist] Editorial

Risky Stem-Cell Treatments Come Under FDA Scrutiny — Again

The FDA warned rogue stem-cell clinics to stop selling unproven treatments that could harm patients. The agency’s latest effort, like most of its previous ones, consisted only of letters to companies and clinics. [The New York Times] Editorial

FTC Hits Predatory Scientific Publisher with a $50 Million Fine

The Federal Trade Commission (FTC) has won a summary judgement that just might cause some predatory publishers to step back from their business model. An India-based predatory publisher has been hit with a $50 million dollar judgement for deceptive business practices, along with permanent injunctions against most of the activities that made it money. [Ars Technica] Editorial

NEW 8^th InterAmerican Oncology Conference
October 17-18, 2019
Buenos Aires, Argentina

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

NEW Postdoctoral Position – Pulmonary/Lung Carcinogenesis Translational Research (Albert Einstein College of Medicine)

NEW Postdoctoral Position – Lung Research (Columbia University)

Scientist – Pulmonary (STEMCELL Technologies Inc.)

Postdoctoral Scholar – Acute Respiratory Distress Syndrome (University of California, San Francisco)

Molecular Biologist (Entrinsic Health Solutions, Inc.)

Research Associate – Gene Therapy for Cystic Fibrosis (Imperial College London)

Postdoctoral Position – Stem Cells, Regenerative Biology and Medicine (Helmholtz Zentrum München)

Group Leaders – Cardiopulmonary Research (Max Planck Institute for Heart and Lung Research)

Associate Professor – Primary Ciliary Dyskinesia (University of Southampton)

Postdoctoral Fellow – Lung Disease (Icahn School of Medicine at Mount Sinai)

Principal Investigator Positions – Stem Cell Research (The GDL-MP Institute for Stem Cell and Regenerative Biomedicine)

Assistant/Associate/Full Professor – Lung Cancer (University of Cincinnati College of Medicine)

Postdoctoral Position – Lung Biology & Disease (Helmholtz-Center München – German Research Center for Environmental Health)

Associate Professor – Oncology (University of California, Davis)

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