Pulmonary Cell News Volume 7.49 | Dec 13 2018

TOP STORY

Targeting PKCδ as a Therapeutic Strategy against Heterogeneous Mechanisms of EGFR Inhibitor Resistance in EGFR-Mutant Lung Cancer

Researchers report a role of nuclear protein kinase Cδ (PKCδ) as a common axis across multiple known tyrosine kinase inhibitor (TKI)-resistance mechanisms. They demonstrated that TKI-inactivated epidermal growth factor receptor (EGFR) dimerized with other membrane receptors implicated in TKI resistance to promote PKCδ nuclear translocation. [Cancer Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

TGF-β Upregulated Mitochondria Mass through the SMAD2/3→C/EBPβ→PRMT1 Signal Pathway in Primary Human Lung Fibroblasts

Scientists investigated the mechanism by which protein arginine methyltransferase-1 (PRMT1) regulates mitochondrial mass in primary human airway wall fibroblasts. Fibroblasts from control or asthma patients were stimulated with TGF-β for up to 48 hours, and the signaling pathways controlling PRMT1 expression and mitochondrial mass were analyzed. [J Immunol] Abstract | Full Article

IL-37 Alleviates House Dust Mite-Induced Chronic Allergic Asthma by Targeting TSLP through the NF-κB & ERK1/2 Signaling Pathways

The authors found that interleukin (IL)-37 inhibited the induction of thymic stromal lymphopoietin (TSLP) expression by the main antigen of house dust mite, Der p1, by suppressing NF-κB and extracellular signal regulated kinase 1/2 (ERK1/2) activation in 16-HBE cells in vitro. [Immunol Cell Biol] Abstract

miR-627/HMGB1/NF-κB Regulatory Loop Modulates TGF-β1-Induced Pulmonary Fibrosis

miR-627 overexpression could partially reverse TGF-β1-induced normal human lung fibroblast proliferation, as well as α-SMA and collagen I protein expression. Moreover, miR-627/high-mobility group box protein 1 (HMGB1) affected TGF-β1 release through RAGE/NF-κB signaling; miR-627/HMGB1 and RAGE/NF-κB signaling formed a regulatory loop to modulate TGF-β1-induced pulmonary fibrosis in vitro. [J Cell Biochem] Abstract

LUNG CANCER

Identification and Characterization of Synthetic Viability with ERCC1 Deficiency in Response to Interstrand Crosslinks in Lung Cancer

The authors created a panel of ERCC1D lung cancer cell lines which they characterized. They observed that loss of ERCC1 hypersensitized cells to cisplatin when wildtype p53 was retained, while there was only modest sensitivity in cell lines that were p53^mutant/null. [Clin Cancer Res] Abstract

CNOT3 Targets Negative Cell Cycle Regulators in Non-Small Cell Lung Cancer Development

Depletion of CNOT3 suppressed proliferation of A549 human non-small cell lung cancer cells with enhanced mRNA stability and subsequent elevated expression of p21. Aberrant up-regulation of Krüppel-like factor 2 by CNOT3 depletion led to impairment in the proliferation of A549 cells. [Oncogene] Abstract

Quinazolin-2,4-Dione-Based Hydroxamic Acids as Selective Histone Deacetylase-6 Inhibitors for Treatment of Non-Small-Cell Lung Cancer

Scientists designed and synthesized quinazolin-2,4-one-based hydroxamic acids to serve as selective competitive inhibitors of histone deacetylase-6. The most potent and selective compound, 3d substantially increased acetylation of α-tubulin instead of histones in the lung cancer cell line, LL2. [J Med Chem] Abstract

Circular RNA circPVT1 Promotes Proliferation and Invasion through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer

Knockdown of circPVT1 suppressed non-small cell lung cancer (NSCLC) cell proliferation, migration and invasion, and increased apoptosis. In addition, circPVT1 mediated NSCLC progression via the regulation of the E2F2 signaling pathway. [Cell Physiol Biochem] Full Article

MicroRNA-148a-3p Inhibited the Proliferation and Epithelial-Mesenchymal Transition Progression of Non-Small-Cell Lung Cancer via Modulating Ras/MAPK/Erk Signaling

Researchers found that miR-148a-3p acts as a tumor-suppressor in the development and progression of non-small-cell lung cancer (NSCLC). miR-148a-3p inhibited NSCLC cells proliferation and epithelial-mesenchymal transition by reducing the expression of son of sevenless 2, which referred Ras activating. [J Cell Physiol] Abstract

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The Lung Microenvironment: An Important Regulator of Tumor Growth and Metastasis

The authors highlight recent advances and emerging concepts for how the tumor-reprogrammed lung microenvironment promotes both primary lung tumors and lung metastasis from extrapulmonary neoplasms by contributing to inflammation, angiogenesis, immune modulation and response to therapies. [Nat Rev Cancer] Abstract

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New Data from the AEROSURF^® Phase IIb Clinical Program Shows AEROSURF^® Appears to Reduce Incidence and Severity of Bronchopulmonary Dysplasia in Preterm Infants with RDS

Windtree Therapeutics, Inc. announced that data from the AEROSURF^® Phase II clinical program in premature infants with respiratory distress syndrome (RDS) was presented. [Press release from Windtree Therapeutics, Inc. discussing research presented at the 2018 Hot Topics in Neonatology Annual Meeting, Washington D.C] Press Release

CBT Pharmaceuticals and Strata Oncology Announce Collaboration to Accelerate Development of CBT-101, a C-Met Inhibitor, for Patients with Non-Small Cell Lung Cancer and Other Solid Tumors

CBT Pharmaceuticals (CBT), Inc. and Strata Oncology, Inc. announced that the companies have entered into an agreement to drive patient enrollment in CBT’s ongoing Phase I/II trial of CBT-101 in cancer patients with c-Met dysregulated malignancies including non-small cell lung cancer. [CBT Pharmaceuticals, Inc.] Press Release

Health Canada Grants Market Authorization for ORKAMBI^® (Lumacaftor/Ivacaftor) for Children with Cystic Fibrosis Aged 2 to 5 Years Old with Most Common Form of the Disease

Vertex Pharmaceuticals Incorporated announced that Health Canada has granted Market Authorization for ORKAMBI^® to include use in children ages two through five years with CF who have two copies of the F508del CFTR mutation. [Vertex Pharmaceuticals Inc.] Press Release

Innovent Announces Two Clinical Studies with the Anti-VEGF Monoclonal Antibody IBI305, a Biosimilar Candidate to Avastin (Bevacizumab), Met Primary Endpoints

Innovent Biologics, Inc. announced that IBI305, a recombinant humanized anti-VEGF monoclonal antibody being developed as potential biosimilar to Avastin, has met pre-defined primary endpoints in two randomized, head to head, clinical trials comparing IBI305 versus branded bevacizumab: a Phase III clinical trial in patients with advanced non-squamous non-small cell lung cancer and a pharmacokinetic study in healthy subjects. [Innovent Biologics, Inc.] Press Release

AR-501 (Cystic Fibrosis) Enrolls First Subject in Phase I/IIa Clinical Trial for Treatment of Chronic Lung Infections in Cystic Fibrosis Patients

Aridis Pharmaceuticals announced that the first subject has been enrolled in a Phase I/IIa clinical study evaluating the investigational candidate AR-501 for treatment of chronic bacterial lung infections in patients with CF. [Aridis Pharmaceuticals, Inc.] Press Release

Vast Therapeutics Announces Funding from Cystic Fibrosis Foundation for Further Development of BIOC51

Vast Therapeutics, Inc., announced that the company has received an award from Cystic Fibrosis Foundation, to support the continued development of its lead NO-release drug candidate, BIOC51 for the treatment of Pseudomonas aeruginosa in patients with CF. [Vast Therapeutics, Inc. (PR Newswire Association LLC.)] Press Release

NCFB, FDA Grants “Fast Track” and QIDP

Zambon announced that colistimethate sodium powder for nebulizer solution, delivered by the I-neb AAD system obtained QIDP and Fast Track designation by the FDA for the indication “prevention of pulmonary exacerbations in adult patients with non-cystic fibrosis bronchiectasis (NCFB) colonized with Pseudomonas aeruginosa”. [Zambon Company S.P.A] Press Release

New 2-in-1 Powder Aerosol to Upgrade Fight against Deadly Superbugs in Lungs

Purdue researchers have invented a drug formulation that uses two synergistic antibiotics – colistin and ciprofloxacin – in one single particle that is shown to reach infection sites in the deep lung area with the capability to kill multi-drug-resistant superbugs. [Purdue University] Press Release

NIH Report Scrutinizes Role of China in Theft of U.S. Scientific Research

Institutions across the U.S. may have fallen victim to a tiny fraction of foreign researchers who worked to feed American intellectual property to their home countries, an advisory committee to the National Institutes of Health (NIH) found in a report. [STAT News] Editorial

The End of DACA Would Be a Blow to Science

With the end of Deferred Action for Childhood Arrivals (DACA), undocumented scientists will lose what few protections they currently have under immigrant law, lose their access to their scientific research, and once again live in fear, as they are caught in legal limbo. [Scientific America] Editorial

NEW 2019 ASCO Annual Meeting
May 31-June 4, 2019
Chicago, Illinois, United States

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NEW Assistant Professor – Cancer Biology (Cold Spring Harbor Laboratory)

Postdoctoral Position – Asthma Epigenetics & Genomics (La Jolla Institute for Allergy & Immunology)

Postdoctoral Researcher – Lung Cancer Research (University of Cologne)

Research Associate – Gene Therapy Lung Research (Imperial College of London)

Postdoctoral Position – Pulmonary Fibrosis Research (University of California San Francisco)

Staff Scientist/ Tier 2 Canada Research Chair – Lung Research (University of Toronto)

Faculty Positions – Cancer-Focused Target & Drug Discovery (University of New Mexico)

Postdoctoral Research Fellow – Sepsis & Lung Inflammation Pathogenesis Research (Boston University)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Scholar – Cancer Metabolism (The Moffitt Cancer Center)

Postdoctoral Position – Lung Cancer Biology (UT Southwestern Medical Center)

Postdoctoral Research Scientist – Modeling Infection in Human Lung Organoids (Columbia University)

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