Pulmonary Cell News Volume 5.47 | Nov 1 2016

TOP STORY

The Induction of MIG6 under Hypoxic Conditions Is Critical for Dormancy in Primary Cultured Lung Cancer Cells with Activating EGFR Mutations

Researchers revealed that primary lung cancer cells harboring activating epidermal growth factor receptor (EGFR) mutations generally entered a dormant state when hypoxic. They found that heterodimer formation of the ERBB family receptor tyrosine kinases, and their subsequent downstream signaling, was diminished under hypoxic conditions, although phosphorylation of the EGFR was retained. Dormant lung cancer cells were found to be resistant to EGFR tyrosine kinase inhibitor treatment. [Oncogene] Abstract

(Ranked by impact factor of the journal)

Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis

Using a mouse model of tuberculosis, investigators compared protection and lung cellular infiltrates of parenteral and mucosal Bacille Calmette-Guérin (BCG) vaccination. Adoptive transfer and gene expression analyses of lung airway cells were performed to determine the protective capacities and phenotypes of different memory T cell subsets. [mBio] Full Article

Host-Derived Extracellular RNA Promotes Adhesion of Streptococcus pneumoniae to Endothelial and Epithelial Cells

Scientists investigated the role of host-derived extracellular RNA in the process of pneumococcal alveolar epithelial cell infection. their study demonstrated that eRNA dose-dependently increased S. pneumoniae invasion of alveolar epithelial cells. [Sci Rep] Full Article

Hyperglycemia and Pseudomonas aeruginosa Acidify Cystic Fibrosis Airway Surface Liquid by Elevating Epithelial Monocarboxylate Transporter 2 Dependent Lactate-H⁺ Secretion

Researchers showed that primary human bronchial epithelial cells secrete lactate into airway surface liquid (ASL), which is elevated in hyperglycemia. They found that hyperglycemia and P. aeruginosa induce a metabolic shift which increases lactate generation and efflux into ASL via epithelial monocarboxylate lactate-H⁺ co-transporters transporters. [Sci Rep] Full Article

LUNG CANCER

Aldehyde Dehydrogenase Is Used by Cancer Cells for Energy Metabolism

Scientists hypothesized that the NADH produced by aldehyde dehydrogenase (ALDH) may be a reliable energy source for ATP production in non-small-cell lung cancer (NSCLC). They revealed that NADH production by ALDH contributes significantly to ATP production in NSCLC. [Exp Mol Med] Full Article

TFAP2C-Mediated Upregulation of TGFBR1 Promotes Lung Tumorigenesis and Epithelial–Mesenchymal Transition

Investigators showed that transcription factor-activating enhancer-binding protein 2C (TFAP2C) promoted tumor progression by upregulation of transforming growth factor-β receptor type 1 (TGFBR1) and consequent activation of PAK1 signaling. [Exp Mol Med] Full Article

Activation of Endoplasmic Reticulum Stress and the Extrinsic Apoptotic Pathway in Human Lung Cancer Cells by the New Synthetic Flavonoid, LZ-205

It has been shown that flavonoids have anti-tumor activity. Investigators found LZ-205, a newly synthesized flavonoid, to be effective in inducing apoptosis in human lung cancer cells in vivo and in vitro. [Oncotarget] Full Article

Sestrin-3 Modulation Is Essential for Therapeutic Efficacy of Cucurbitacin B in Lung Cancer Cells

The authors observed that cucurbitacin B, a tetracyclic triterpenoid present in pumpkins, gourds and squashes, exhibits antiproliferative effects on human non-small cell lung cancer cells at nanomolar concentrations. Treatment with cucurbitacin B was found to result in decrease in the viability of EGFR-wild type and EGFR-mutant lung cancer cells and reduction in cell-colonies but had only minimal effect on normal human bronchial epithelial cells. [Carcinogenesis] Abstract

Cigarette Smoke Alters the Secretome of Lung Epithelial Cells

Scientists used subcellular fractionation coupled to label-free quantitative mass spectrometry to globally assess alterations in the proteome of different compartments of lung epithelial cells upon exposure to cigarette smoke extract. Proteomic profiling of the human alveolar-derived cell line A549 revealed the most pronounced changes within the cellular secretome with preferential downregulation of proteins involved in wound healing and extracellular matrix organization. [Proteomics] Abstract

Sulforaphane Suppresses EMT and Metastasis in Human Lung Cancer through miR-616-5p-Mediated GSK3β/β-Catenin Signaling Pathways

In this study the authors assessed the involvement of sulforaphane and miR-616-5p in epithelial-mesenchymal transition (EMT) and non-small cell lung cancer metastasis. [Acta Pharmacol Sin] Full Article

A Global View of Regulatory Networks in Lung Cancer: An Approach to Understand Homogeneity and Heterogeneity

The authors review the homogeneity or heterogeneity of gene expression profiles among subtypes of lung cancer. [Semin Cancer Biol] Abstract

Lung Bioengineering: Physical Stimuli and Stem/Progenitor Cell Biology Interplay towards Biofabricating a Functional Organ

The authors focus on describing how the cell mechanical microenvironment can modulate stem cell differentiation and how these stimuli could be incorporated into lung bioreactors for optimizing organ bioengineering. [Respir Res] Full Article

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

New KEYTRUDA^® (Pembrolizumab) Data to Be Presented at 17^th World Conference on Lung Cancer Highlight Research across the Spectrum of Thoracic Malignancies

Merck announced that new data investigating the use of KEYTRUDA^® (pembrolizumab), the company’s anti-PD-1 therapy, across multiple thoracic malignancies, including non-small cell lung cancer, small cell lung cancer and malignant pleural mesothelioma, will be presented. [Press release from Merck discussing research presented at 17^th World Conference on Lung Cancer, Vienna] Press Release

Parker Institute for Cancer Immunotherapy and Cancer Research Institute Launch Collaboration on Cancer Neoantigens

The Parker Institute for Cancer Immunotherapy and the Cancer Research Institute announced a major collaboration focused on neoantigens. The search for these unique cancer markers has become a robust area of research as scientists believe they may hold the key to developing a new generation of personalized, targeted cancer immunotherapies. [The Parker Institute for Cancer Immunotherapy] Press Release

Pitt Researchers Awarded $1.7 Million NIH Grant to ‘Sniff out’ Treatment for Lung Disease

The National Institutes of Health (NIH) awarded a research team at the University of Pittsburgh’s schools of engineering and medicine a highly competitive $1.7 million U01 grant to develop new mathematical models of liquid and ion transport in the human lung. [University of Pittsburgh] Press Release

Nivalis Therapeutics Announces Results from Phase II Clinical Trial of Cavosonstat for Treatment of Cystic Fibrosis

Nivalis Therapeutics, Inc. announced topline results from the company’s Phase II trial evaluating the efficacy and safety of two doses of cavosonstat, 200 mg and 400 mg, in adult patients with cystic fibrosis who had two copies of the F508del-CFTR mutation and were being treated with Orkambi^™. The trial failed to demonstrate benefit in absolute change in percent predicted FEV, the trial’s primary endpoint, or in sweat chloride reduction at 12 weeks. [Nivalis Therapeutics, Inc.] Press Release

Aradigm Announces Top-Line Results from Two Phase III Studies Evaluating Pulmaquin for the Chronic Treatment of Non-Cystic Fibrosis Bronchiectasis Patients with Lung Infections with Pseudomonas aeruginosa

Aradigm Corporation announced top-line results from its two Phase III clinical trials evaluating the safety and efficacy of Pulmaquin^®, the company’s investigational proprietary formulation of once daily ciprofloxacin for inhalation, in patients with non-cystic fibrosis bronchiectasis with chronic lung infections with Pseudomonas aeruginosa. [Aradigm Corporation] Press Release

DEPArray^™ Single-Cell Isolation Technology Enables Researchers to Develop a Model for Predicting Response to Treatment in Patients with Lung Cancer

Menarini-Silicon Biosystems announced the company’s DEPArray^™ single-cell isolation technology played a key role in a study conducted by researchers from The University of Manchester to develop a model for predicting whether small-cell lung cancer patients will be sensitive or resistant to initial chemo­therapy treatment. [Menarini-Silicon Biosystems] Press Release

FDA Chief Pushes Back against Criticism of Stem Cell Treatment Regulations

The country’s top drug regulators pushed back on claims they move too slowly in approving new stem cell treatments and sought to temper expectations for the field’s potential to benefit patients, emphasizing the hazards and the unknowns that persist with developing such therapies. [STAT News] Editorial

Battle over US Overtime Pay Rules Leaves Many Postdocs in Limbo

Institutions struggle to respond after court blocks regulations that would have increased wages for junior researchers. Some universities are proceeding with planned salary increases for postdocs, but others have cancelled — or at least, temporarily halted — changes to researchers’ pay. The uncertainty over how the legal battle will play out is already affecting some postdocs’ career and family plans. [Nature News] Editorial

Big Biology Projects Warm up to Preprints

The 4D Nucleome, a major research consortium funded by the US National Institutes of Health, is now requiring that all manuscripts related to its US$120-million, five-year program are posted to an online preprint server ahead of peer review. And a privately funded, US$600-million biomedical research initiative in California is considering whether to demand its investigators do the same. [Nature News] Editorial

NIH Says It Will Raise Postdoc Salaries, Despite Threats to Overtime Rule

Republicans in Congress have vowed to roll back a controversial new rule expanding the number of workers eligible for overtime pay when President-elect Donald Trump takes office. And a federal judge has already blocked implementation of the rule, which covers postdoctoral researchers. But the National Institutes of Health says that, regardless of those developments, it will move ahead with its plan to raise the stipends of certain biomedical postdocs so they aren’t affected by the rule. [Science Insider] Editorial

NEW 19^th International Conference on Clinical Application of Adult Stem Cells
February 14-15, 2017
Havana, Cuba

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

NEW Post-Doctoral Research Fellow – Neurobiology (Institut of Molecular Biology (IMB))

NEW Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

NEW Postdoctoral Research Assistant/Associate(s) (University of Cambridge)

NEW Postdoctoral Position – Heart, Lung and Blood Vascular Medicine (University of Pittsburgh)

Postdoctoral Fellow – System Genetics and Genomics of Lung Diseases (Brigham & Women’s Hospital – Harvard Medical School)

Research Associate – Modeling Tumor Development and Therapy (University of Cambridge)

Scientists/Physicians – Laboratory/Translational/Clinical Research in Lung Cancers (University of New Mexico Comprehensive Cancer Center)

Postdoctoral Research Fellow – Cancer GeneticsEpigenetics (Fred Hutchinson Cancer Research Center)

Postdoctoral Researcher – Lung Cancer (Northwestern University)

Postdoctoral Fellow – Lung Biology (Boston University)

Cell Biologist – Pulmonary Vascular Signaling (University of Maryland)

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