Pulmonary Cell News Volume 8.13 | Apr 11 2019

TOP STORY

Lung Cancer Deficient in the Tumor Suppressor GATA4 Is Sensitive to TGFBR1 Inhibition

Through the genome-wide screening of tumor-suppressive transcription factors, researchers demonstrated that GATA4 functioned as an essential tumor suppressor in lung cancer in vitro and in vivo. Ectopic GATA4 expression resulted in lung cancer cell senescence. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Platelet Activating Factor Receptor Regulates Colitis-Induced Pulmonary Inflammation through the NLRP3 Inflammasome

Lipopolysaccharide from phosphorylcholine (ChoP)-positive bacteria induced NLRP3 and caspase-1 proteins in human alveolar epithelial cells, however antagonism of platelet activating factor receptor (PAFR) prevented NLRP3 activation by ChoP. Amoxicillin reduced bacterial populations in the lungs and reduced NLRP3 inflammasome protein levels, but did not reduce PAFR. [Mucosal Immunol] Abstract

Cationic Nanoliposomes Are Efficiently Taken Up by Alveolar Macrophages but Little Access Dendritic Cells and Interstitial Macrophages in the Normal and CpG-Stimulated Lungs

Although liposomes could permanently entrap a large fraction of actives, they could not sustain their release in vitro. Liposomes made of dioleoyltrimethylammoniumpropane were safe to respiratory cells in vitro while liposomes composed of dimethylaminoethanecarbamoyl-cholesterol were cytotoxic. [Mol Pharm] Abstract

Polarized AAVR Expression Determines Infectivity by AAV Gene Therapy Vectors

Scientists found adeno-associated virus receptor (AAV) receptor (AAVR) in human airway epithelia by western blot and RNA-Seq analyses. Using immunocytochemistry, they did not find endogenous AAVR at membranes but overexpression localized AAVR to the basolateral membrane, where it preferentially increased transduction. [Gene Ther] Abstract

LUNG CANCER

LncRNA NORAD Is Repressed by the YAP Pathway and Suppresses Lung and Breast Cancer Metastasis by Sequestering S100P

Scientists showed that long noncoding RNA (lncRNA) NORAD was downregulated in lung and breast cancers, and that NORAD low expression in these cancer types was associated with lymph node metastasis and poor prognosis. NORAD was transcriptionally repressed by the Hippo pathway transducer YAP/TAZ-TEAD complex in conjunction with the action of NuRD complex. [Oncogene] Abstract

JMJD2 Promotes Acquired Cisplatin Resistance in Non-Small Cell Lung Carcinoma Cells

Investigators screened gene expression of known histone methyltransferases and demethylases in three non-small-cell lung carcinoma (NSCLC) cell lines with or without acquired resistance to cisplatin (CP). They found expression of several JMJD2 family genes upregulated in CP-resistant cells, with JMJD2B expression being upregulated in all three CP-resistant NSCLC cell lines. [Oncogene] Full Article

Increased Expression of the Immunosuppressive Interleukin-35 in Patients with Non-Small Cell Lung Cancer

The authors found elevated levels of interleukin 35 (IL-35) in the tumoural (TU) region as well as postoperative serum from patients with lung adenocarcinoma. Consistently, they found increased expression of IL-35⁺Foxp-3⁺ cells, which associated with ARG1 mRNA expression and decreased TNFA in the TU region of the lung of patients with non-small cell lung cancer as compared to their control region. [Br J Cancer] Full Article

Unveiling the Potentials of Biocompatible Silver Nanoparticles on Human Lung Carcinoma A549 Cells and Helicobacter pylori

Toxicodendron vernicifluum (Tv)-silver nanoparticles (AgNPs) at the concentration of 320 µg.mL-1 induced 82.5% of cell death in human lung cancer, A549 cells and further 95% of cell death with annexin V FITC/PI based apoptosis. The Tv-AgNPs selectively targeted and damaged the cancer cells through ROS generation. [Sci Rep] Full Article

PCC0208027, a Novel Tyrosine Kinase Inhibitor, Inhibits Tumor Growth of NSCLC by Targeting EGFR and HER2 Aberrations

Scientists showed that PCC0208027 effectively inhibited the enzyme activity of epidermal growth factor receptor (EGFR) family members, including drug-sensitive EGFR mutations, acquired drug-resistant EGFR T790M and EGFR C797S mutations, and wild-type HER2. [Sci Rep] Full Article

miR-147b-Mediated TCA Cycle Dysfunction and Pseudohypoxia Initiate Drug Tolerance to EGFR Inhibitors in Lung Adenocarcinoma

With miRNA-seq analysis, the authors found that miR-147b was the most upregulated microRNA in osimertinib-tolerant and epidermal growth factor receptor (EGFR)-mutated lung cancer cells. Whole-transcriptome analysis of single-cell-derived clones revealed a link between osimertinib tolerance and pseudohypoxia responses irrespective of oxygen levels. [Nat Metab] Abstract | Press Release

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Microbes, Metabolites, and the Gut-Lung Axis

The authors review the current understanding of host-microbe cross-talk along the gut-lung axis. They highlight the importance of short-chain fatty acids in shaping and promoting bone marrow hematopoiesis to resolve airway inflammation and to support healthy homeostasis. [Mucosal Immunol] Full Article

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

Bayer Announces Results of Sub-Group Analysis for Vitrakvi^® (larotrectinib) in Patients with NTRK Gene Fusion-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)

Bayer presented subgroup analysis data of patients with non-small cell lung cancer with neurotrophic receptor tyrosine kinase (NTRK) gene fusion treated with larotrectinib. [Press release from Bayer (PR Newswire Association LLC) discussing research presented at the 2019 European Lung Cancer Congress (ELCC), Geneva] Press Release

aTyr Pharma to Present Poster

aTyr Pharma, Inc. announced that the company will present an abstract in a poster presentation. [Press release from aTyr Pharma, Inc. discussing research to be presented at the American Thoracic Society (ATS) 2019 International Conference, Dallas] Press Release

Synspira Therapeutics Receives Orphan Designation for SNSP113 for the Treatment of Cystic Fibrosis in the European Union

Synspira Therapeutics announced that the European Medicines Agency Committee for Orphan Medicinal Products has granted orphan drug designation to the company’s lead product, SNSP113, a first-in-class glycopolymer, for the treatment of people with cystic fibrosis. [Synspira Therapeutics] Press Release

Verona Pharma Granted Key EU Patent Related to Late-Stage COPD Clinical Candidate Ensifentrine

Verona Pharma plc announced that the European Patent Office has recently granted an additional key patent relating to its lead development candidate, ensifentrine. [Verona Pharma plc] Press Release

Pliant Therapeutics Reports Positive Results of Phase I Clinical Study Support Advancement of PLN-74809 for Idiopathic Pulmonary Fibrosis

Pliant Therapeutics, Inc. announced the successful completion of its first-in-human clinical study of its lead product candidate, PLN-74809. [Pliant Therapeutics, Inc.] Press Release

Neon Therapeutics Announces Completion of Enrollment in Phase Ib NT-002 Clinical Trial of NEO-PV-01 in Metastatic Non-Small Cell Lung Cancer

Neon Therapeutics, Inc. announced the completion of enrollment in NT-002, its Phase Ib clinical trial evaluating NEO-PV-01 with pembrolizumab and chemotherapy in patients with untreated advanced or metastatic non-small cell lung cancer. [Neon Therapeutics, Inc.] Press Release

ATS Foundation/Boehringer Ingelheim Pharmaceuticals Inc. Research Fellowship in Idiopathic Pulmonary Fibrosis

Paul Andrew Reyfman, MD, MS, of Northwestern University has been awarded the ATS Foundation/Boehringer Ingelheim Pharmaceuticals, Inc. Research Fellowship in idiopathic pulmonary fibrosis. The $100,000 award will help fund Dr. Reyfman’s research, “Single Cell Transcriptomic Analysis of Pulmonary Fibrosis.” [ATS Foundation (EurekAlert!)] Press Release

The Nation’s Leading Lung Cancer Organizations Join Forces to Launch “GO₂ Foundation for Lung Cancer”

Two of the most effective and influential nonprofit organizations serving the lung cancer community, the Bonnie J. Addario Lung Cancer Foundation and Lung Cancer Alliance announced they are joining forces as the GO₂ Foundation for Lung Cancer. [GO₂ Foundation for Lung Cancer (PR Newswire Association LLC)] Press Release

Impact Factors Are Still Widely Used in Academic Evaluations

About 40% of institutes with a strong focus on research mention impact factors in documents used in the review, promotion and tenure process, according to the analysis, which examined more than 800 documents across 129 institutions in the United States and Canada. [Nature News] Editorial

FDA, New York Attorney General Go After Stem Cell Clinics

On April 3, the FDA sent letters to 20 companies providing stem cell treatments, reports The New York Times, reminding them that they may require FDA approval and should take action to comply. The agency also issued a warning to a stem cell company for violating good manufacturing practices. [The Scientist] Editorial

NEW European Society for Medical Oncology (ESMO) 2019 Congress
September 27-October 1, 2019
Barcelona, Spain

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

NEW Early Stage Researcher – Lung Organoid Culture (STEMCELL Technologies Inc.)

Scientist – Pulmonary (STEMCELL Technologies Inc.)

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

Postdoctoral Position – Lung Research (Columbia University)

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)

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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