Pulmonary Cell News Volume 6.43 | Nov 2 2017

TOP STORY

Drexel Researchers Identify ‘Master Regulator’ Involved in Infant Lung Damage

Researchers at Drexel University have revealed that inhibiting the micro-RNA miR-34a significantly reduces bronchopulmonary dysplasia in mice. [Press release from Drexel University discussing online prepublication in Nature Communications] Press Release | Full Article

(Ranked by impact factor of the journal)

RV568, a Narrow-Spectrum Kinase Inhibitor with p38 MAPK-α and -γ Selectivity, Suppresses COPD Inflammation

Researchers evaluated RV568, a p38 mitogen-activated protein kinase-α and -γ and SRC family kinase inhibitor, in cellular and in vivo models relevant to COPD and examined its safety and efficacy in COPD patients. [Eur Respir J] Abstract

Protein Corona: Implications for Nanoparticle Interactions with Pulmonary Cells

Cerium oxide (CeO₂), silica-coated CeO₂, barium sulfate, and zinc oxide nanoparticles (NPs) were incubated in rat lung lining fluid in vitro. Then, gel electrophoresis followed by quantitative mass spectrometry was used to characterize the adsorbed proteins stripped from these NPs. [Part Fibre Toxicol] Full Article

Histone Deacetylase Inhibition Enhances the Antitumor Activity of a MEK Inhibitor in Lung Cancer Cells Harboring RAS Mutations

Combined treatment with a MEK inhibitor and a HDAC inhibitor showed synergistic effects on cell metabolic activity of RAS mutated lung cancer cells through activation of FOXOs, with a subsequent increase in BIM and cell cycle inhibitors. [Mol Cancer Ther] Abstract

Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia

The authors identified a novel signaling pathway contributing to interleukin-8 secretion in the CF bronchial epithelium with α-klotho functioning as an endocrine and local anti-inflammatory mediator that antagonizes pro-inflammatory actions of fibroblast growth factor 23 and transforming growth factor β. [Sci Rep] Full Article

Involvement of ER Stress, PI3K/AKT Activation, and Lung Fibroblast Proliferation in Bleomycin-Induced Pulmonary Fibrosis

Scientists investigated the underlying mechanisms of endoplasmic reticulum (ER) stress inhibitors in the treatment of bleomycin-induced lung fibrosis. They demonstrated that bleomycin can activate ER stress associated proteins, including GRP78, CHOP, and ATF-4, both in vitro and in vivo. [Sci Rep] Full Article

LUNG CANCER

Sortilin Limits EGFR Signaling by Promoting Its Internalization in Lung Cancer

Researchers report that sortilin was a key regulator of epidermal growth factor receptor (EGFR) internalization. Loss of sortilin in tumor cells promoted cell proliferation by sustaining EGFR signaling at the cell surface, ultimately accelerating tumor growth. [Nat Commun] Full Article

Identification of a Folate Receptor-Targeted Near-Infrared Molecular Contrast Agent to Localize Pulmonary Adenocarcinomas

Investigators describe the use of a novel folate receptor-targeted near infrared contrast agent to improve intraoperative localization of non-small cell lung cancer during pulmonary resection. [Mol Ther] Abstract | Graphical Abstract

Induced-Decay of Glycine Decarboxylase Transcripts as an Anticancer Therapeutic Strategy for Non-Small-Cell Lung Carcinoma

The authors designed and tested splicing-modulating steric hindrance antisense oligonucleotides that efficiently induce exon skipping, disrupt the open reading frame of GLDC transcript, halt cell proliferation, and prevent colony formation in both A549 cells and tumor-initiating cells-enriched non-small-cell lung carcinoma tumor sphere cells. [Mol Ther Nucleic Acids] Full Article

iASPP Facilitates Tumor Growth by Promoting mTOR-Dependent Autophagy in Human Non-Small-Cell Lung Cancer

Scientists investigated the potential function and molecular mechanism of apoptosis-stimulating protein of p53 (iASPP) in mediating autophagy in human non-small-cell lung cancer. [Cell Death Dis] Full Article

miR-99a Reveals Two Novel Oncogenic Proteins E2F2 and EMR2 and Represses Stemness in Lung Cancer

The authors identified two novel proteins, E2F transcription factor 2 (E2F2) and EGF-like module-containing, mucin-like, hormone receptor-like 2 (EMR2), downregulated by miR-99a by its direct binding to their 3′-UTR. miR-99a expression prevented cancer cell epithelial-to-mesenchymal transition and repressed the tumorigenic potential of the cancer stem cell population in both these cell lines and mice tumors originated from H1975 cells. [Cell Death Dis] Full Article

Small-Cell Lung Cancer: What We Know, What We Need to Know and the Path Forward

Small-cell lung cancer is a deadly tumor accounting for approximately 15% of lung cancers and is pathologically, molecularly, biologically and clinically very different from other lung cancers. While the majority of tumors express a neuroendocrine program, an important subset of tumors have low or absent expression of this program. The probable initiating molecular events are inactivation of TP53 and RB1, as well as frequent disruption of several signaling networks, including Notch signaling. [Nat Rev Cancer] Abstract

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Transgene to Present Additional Immunology Data from the TIME Trial with TG4010 in Patients with Advanced Lung Cancer

Transgene will be presenting a poster on additional immunology data generated from the randomized, placebo-controlled Phase IIb trial (TIME) that evaluated the combination regimen of TG4010 and chemotherapy in patients with advanced lung cancer. [Press release from Transgene discussing research to be presented at the Society for Immunotherapy of Cancer (SITC) Meeting 2017, National Harbor] Press Release

Merrimack Receives Orphan Drug Designation for MM-121 for the Treatment of Heregulin Positive Non-Small Cell Lung Cancer

Merrimack Pharmaceuticals, Inc. announced that the FDA has granted orphan drug designation to MM-121, its investigational drug candidate, for the treatment of heregulin positive non-small cell lung cancer. [Merrimack Pharmaceuticals, Inc.] Press Release

Eagle Pharmaceuticals Receives Tentative FDA Approval for PEMFEXY (Pemetrexed Injection) Ready-to-Dilute

Eagle Pharmaceuticals, Inc. announced that the FDA has granted tentative approval for the company’s PEMFEXY^™. [Eagle Pharmaceuticals, Inc.] Press Release

AstraZeneca Provides Update on Tralokinumab Phase III Program in Severe, Uncontrolled Asthma

AstraZeneca and its global biologics research and development arm, MedImmune, announced the top-line results of the Phase III STRATOS 2 and TROPOS trials for tralokinumab, an anti-interleukin-13 human monoclonal antibody, in severe, uncontrolled asthma. [AstraZeneca] Press Release

Pay for US Postdocs Varies Wildly by Institution

The salary data are incomplete and — in some cases — appear to be incorrect. Some researchers are listed as earning nothing, and another study underway suggests a higher overall rate of pay for US postdocs. But the latest analysis underscores the challenges of getting basic information about an under-recognized and misunderstood segment of the academic workforce. [Nature News] Editorial

Leading Western Publisher Bows to Chinese Censorship

Springer Nature, whose publications include Nature and Scientific American, acknowledged that at the government’s request, it had removed articles from its mainland site that touch on topics the ruling Communist Party considers sensitive, including Taiwan, Tibet, human rights and elite politics. [The New York Times] Editorial

Plans to Promote German Research Excellence Come under Fire

Observers questioned whether the 88 selected projects for the The Excellence Initiative represent Germany’s best science, particularly because the focus for selection has shifted away from basic science and towards applied research. [Nature News] Editorial

Spanish Government Takes Control of Catalonian Universities

The Spanish government has taken over responsibility for higher education and research in Catalonia, following the region’s unilateral declaration of independence. It will retain control of spending on research centres and universities, which the League of European Research Universities says threatens institutional autonomy. [Nature News] Editorial

NEW European CanCer Organisation (ECCO) 2018: European Cancer Summit
September 7-9, 2018
Vienna, Austria

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NEW Postdoctoral Fellow – Lung Cancer (Moffitt Cancer Center)

Postdoctoral Position – Immunology & Respiratory Diseases (Boehringer Ingelheim)

PhD Studentships – Cancer Research (Institute of Cancer Research)

Faculty Position – Cancer Experimental Therapeutics (University of New Mexico)

PhD Position – Pulmonary Research (Helmholtz Zentrum München)

Postdoctoral Position – Immunology/Molecular Biology (Helmholtz Zentrum München)

Postdoctoral Position – Lung Adenocarcinoma (University of California, San Francisco)

Faculty Positions – Cancer Research (Huntsman Cancer Institute)

PhD Position – Molecular Pharmacology (University of Groningen)

Faculty Position – Lung Injury and Repair (The University of Texas Health Science Center)

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