Pulmonary Cell News Volume 6.16 | Apr 27 2017

TOP STORY

Phylogenetic ctDNA Analysis Depicts Early Stage Lung Cancer Evolution

Investigators conducted a tumor-specific phylogenetic approach to ctDNA profiling in the first 100 TRAcking non-small cell lung Cancer Evolution through therapy (Rx) study participants, including one patient co-recruited to the Posthumous Evaluation of Advanced Cancer Environment post-mortem study. They identified independent predictors of ctDNA release and performed tumor volume limit of detection analyses. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

A Three-Dimensional Model of Human Lung Development and Disease from Pluripotent Stem Cells

Researchers report the generation from human pluripotent stem cells of lung bud organoids that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel three dimensional culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation. [Nat Cell Biol] Abstract

Little Cigars are More Toxic than Cigarettes and Uniquely Change the Airway Gene and Protein Expression

The authors exposed human bronchial epithelial cultures to air or whole tobacco smoke from cigarettes vs. little cigars. Chronic smoke exposure increased the number of dead cells, lactate dehydrogenase release, and interleukin-8 secretion and decreased apical cilia, cystic fibrosis transmembrane conductance regulator protein levels, and transepithelial resistance. [Sci Rep] Full Article

MicroRNA Expression Profiling Defines the Impact of Electronic Cigarettes on Human Airway Epithelial Cells

Investigators studied the global effects of electronic cigarettes (eCig) on the microRNA transcriptome in human lung epithelial cells. Primary human bronchial epithelial (NHBE) cells differentiated at air-liquid interface were exposed to eCig liquid. Exposure of NHBE to any eCig liquid resulted in the induction of oxidative stress-response genes including GCLM, GCLC, GPX2, NQO1 and HO-1. [Sci Rep] Full Article

Transcriptomic Profiling of a Chicken Lung Epithelial Cell Line (CLEC213) Reveals a Mitochondrial Respiratory Chain Activity Boost during Influenza Virus Infection

Scientists used CLEC213 to gain a better understanding of the molecular consequences of low pathogenic avian influenza virus infection in their natural host. Using a transcriptome profiling approach based on microarrays, they identified a cluster of mitochondrial genes highly induced during the infection. [PLoS One] Full Article

Water-Pipe Smoke Condensate Increases the Internalization of Mycobacterium bovis of Type II Alveolar Epithelial Cells (A549)

Researchers studied the effects of water-pipe condense (WPC) on the internalization of M. bovis BCG by macropinocytosis in the alveolar epithelial cell line A549. WPC increased the uptake of BCG-FITC after 72 and 96 hours. No effect on BCG-FITC uptake was observed at 24 or 48 hours. WPC also significantly increased the uptake of FITC-Dextran after 24 hours. [BMC Pulm Med] Full Article

LUNG CANCER

Hypoxic Lung Cancer-Secreted Exosomal miR-23a Increased Angiogenesis and Vascular Permeability by Targeting Prolyl Hydroxylase and Tight Junction Protein ZO-1

Investigators aimed to clarify how hypoxia affects tumor angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions. [Oncogene] Abstract

Blocking Surgically Induced Lysyl Oxidase Activity Reduces the Risk of Lung Metastases

Scientists showed that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that underwent surgery or that were preconditioned with plasma from donor mice that underwent surgery succumbed to lung metastases earlier than controls. [Cell Rep] Full Article | Graphical Abstract

Dihydroberberine Exhibits Synergistic Effects with Sunitinib on NSCLC NCI-H460 Cells by Repressing MAP Kinase Pathways and Inflammatory Mediators

The authors evaluated the antitumor effects of dihydroberberine combined with sunitinib (DCS) on the human non-small cell lung cancer cell lines (NSCLC), A549, NCI-H460, and NCI-H1299 in vitro and in vivo. DCS showed synergic effects on NCI-H460 cell proliferation, colony formation and transplantable tumor growth, which suggested dihydroberberine increases the sensitivity of lung carcinoma to sunitinib. [J Cell Mol Med] Full Article

Optimized Expression-Based Microdissection of Formalin-Fixed Lung Cancer Tissue

Scientists optimized microdissection (xMD) of lung cancer tissue by enhancing staining intensity of tumor cell-specific immunostaining and processing of the stained samples. This optimized procedure did not alter DNA quality and resulted in enrichment of mutated EGFR DNA from lung adenocarcinoma specimens after xMD. [Lab Invest] Abstract

lncRNA-HIT Promotes Cell Proliferation of Non-Small Cell Lung Cancer by Association with E2F1

Researchers investigated the effects of long noncoding RNA (lncRNA)-HOXA transcript induced by TGFβ (HIT) expression on a non-small cell lung cancer (NSCLC) cell phenotype with the gain-of-function and loss-of-function assays. They found that ectopic expression or knockdown of lncRNA-HIT markedly increased or decreased NSCLC cell proliferation, respectively. [Cancer Gene Ther] Abstract

The Next Generation of Immunotherapy: Keeping Lung Cancer in Check

The authors summarize the latest efficacy and safety data for early and advanced non-small cell lung cancer in both the treatment-naïve and pretreated settings. The emerging role of immunotherapy for the treatment of small cell lung cancer and malignant mesothelioma are also discussed. [J Hematol Oncol] Full Article

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Transgene and Bristol-Myers Squibb Announce Clinical Research Collaboration to Evaluate TG4010 in Combination with Opdivo and Standard Chemotherapy in First Line Non-Small Cell Lung Cancer

Bristol-Myers Squibb Company and Transgene announced a new clinical research collaboration to evaluate the safety, tolerability and efficacy of Transgene’s investigational therapeutic vaccine TG4010 in combination with Bristol-Myers Squibb’s Opdivo + standard chemotherapy as a first-line treatment for advanced non-squamous non-small cell lung cancer in patients whose tumors have low or undetectable levels of PD-L1. [Bristol-Myers Squibb Company] Press Release

Hemovent Receives Government Grant to Fast-Forward Development of Its Next-Gen Artificial Lung Technologies

Hemovent GmbH announced that it has been awarded participation in a grant totaling $810,000 from the German government to fast-forward development of its novel and portable artificial lung technologies, designed for a wide range of applications from Extracorporeal CO₂ Removal to ExtraCorporeal Life Support. [Hemovent GmbH] Press Release

ALung Submits IDE Application to FDA Seeking Approval to Conduct Pivotal Study of the Hemolung RAS

ALung Technologies, Inc. announced the submission of its Investigational Device Exemption (IDE) application to the U.S. Food and Drug Administration (FDA) seeking approval to conduct a pivotal clinical study of the Hemolung Respiratory Assist System for the treatment of adults with severe acute exacerbations of chronic obstructive pulmonary disease. [ALung Technologies, Inc. (Business Wire, Inc.)] Press Release

BioRxiv Preprint Server Gets Cash Boost from Chan Zuckerberg Initiative

BioRxiv, the hub for preliminary versions of biology research papers, has announced that it will begin receiving “significant” financial support from the Chan Zuckerberg Initiative, a philanthropic effort started by Facebook co-founder Mark Zuckerberg and his physician wife Priscilla Chan. [Nature News] Editorial

California’s $3-Billion Bet on Stem Cells Faces Final Test

When California voters approved US$3 billion in funding for stem-cell research in 2004, biologists flocked to the state, and citizens dreamed of cures for Parkinson’s disease and spinal-cord injuries. Now, the pot of money — one of the biggest state investments in science — is running dry before treatments have emerged, raising questions about whether Californians will pour billions more into stem-cell research. [Nature News] Editorial

NSF’s Uphill Road to Making Prestigious Early Career Award More Diverse

Only five women have won the National Science Foundation’s (NSF) annual Alan T. Waterman Award in its 41-year history, and no woman of color has ever been selected. The 2017 winners announced this month mark the 13^th year in a row that the $1 million research prize has gone to a man (two, actually, including the second black scientist ever chosen.) [ScienceInsider] Editorial

The Broad Institute Is Testing the Limits of What ‘Nonprofit’ Means

When a federal patent court ruled that the nonprofit Broad Institute of MIT and Harvard could legally license its version of the CRISPR-Cas9 genome-editing system, it opened the door to millions of dollars of revenue for the institute. It also contributed to the seismic shift occurring in science whereby tax-exempt research institutes established under an emerging model of “free market philanthropy” can amass money to further their research and protect their commercial interests. [STAT News] Editorial

NEW GRKs and Arrestins: From Structure to Disease
June 11-16, 2017
Saxtons River, United States

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NEW Research Administrator IV – Early Detection of Lung Cancer (Fred Hutchinson Cancer Research Center)

NEW Postdoctoral Research Fellow – Lung Cancer Genetics and Genomics (Fred Hutchinson Cancer Research Center)

Tenure Track Positions – Translational Asthma Research Program (Perelman School of Medicine)

Postdoctoral Researcher – Oncology (University of Oxford)

Assistant, Associate or Full Professor Position(s) – Asthma Research (University of Pennsylvania)

NIH Training Grant – Pediatric Pulmonary Medicine (University of Pittsburgh)

Postdoctoral Research Associate – Chronic Lung Disease (Washington University St. Louis)

Faculty Position – Cancer Biology (Wake Forest School of Medicine)

Laboratory Head – Infection & Immunity Division (The Walter and Eliza Hall Institute of Medical Research)

PhD Student – Asthma Research (Karolinska Institute)

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