Pulmonary Cell News Volume 7.28 | Jul 19 2018

TOP STORY

PP2A Inhibition Is a Druggable MEK Inhibitor Resistance Mechanism in KRAS-Mutant Lung Cancer Cells

Combination of mammalian target of rapamycin and mitogen-activated protein kinase kinase (MEK) inhibitors induced cytotoxicity in protein phosphatase 2A (PP2A)-inhibited cells, but even this drug combination could not abrogate MYC up-regulation in PP2A-inhibited cells. [Sci Transl Med] Full Article

(Ranked by impact factor of the journal)

TGF-β/SMAD4 Mediated UCP2 Downregulation Contributes to Aspergillus Protease-Induced Inflammation in Primary Bronchial Epithelial Cells

The authors investigated the role of Aspergillus proteases—which contribute to the pathogenesis of Aspergillus-induced diseases such as allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis, and atopic asthma—and their mechanisms of action in airway inflammation using primary human bronchial epithelial cells, and evaluated the inflammatory responses mediated by mitochondrial reactive oxygen species. [Redox Biol] Full Article

The Role of SerpinB2 in Human Bronchial Epithelial Cells Responses to Particulate Matter Exposure

Researchers investigated the role of SERPINB2/PAI-2 in the regulation of epithelial-to-mesenchymal transition-related effects induced by particulate matter (PM) exposure in HBEC3-KT. PM exposure increased SERPINB2 expression, reduced cell migration and induced morphological alterations in HBEC3-KT. [Arch Toxicol] Abstract

Effects of Lung and Airway Epithelial Maturation Cocktail on the Structure of Lung Bud Organoids

Scientists showed that the treatment of organoids with a lung and airway epithelial maturation cocktail containing dexamethasone drives lung bud organoids to the formation of paddle-racquet like structures. [Stem Cell Res Ther] Full Article

In Vitro Transformation of Human Bronchial Epithelial Cells by Diesel Exhaust Particles: Gene Expression Profiling and Early Toxic Responses

The potential of NIST SRM2975 diesel exhaust particles to transform human bronchial epithelial cells in vitro was investigated. [Toxicol Sci] Abstract

Poly (ADP-Ribose) Glycohydrolase Silencing-Mediated Maintenance of H2A and Downregulation of H2AK9me Protect Human Bronchial Epithelial Cells from Benzo(a)Pyrene-Induced Carcinogenesis

Histone H2A levels were abnormally decreased by benzo(a)pyrene-induced carcinogenesis, but were maintained by knockdown of poly (ADP-ribose) glycohydrolase in the 16HBE human bronchial epithelial cell line. [Toxicol Lett] Abstract

Long-Term Engraftment Promotes Differentiation of Alveolar Epithelial Cells from Human Embryonic Stem Cells Derived Lung Organoids

Researchers transplanted different stage of human embryonic stem cells derived 3D lung organoids (HLOs) into immunocompromised mice to assess whether HLOs could expand and mature in vivo. They found that short-term transplanted HLOs contained lung progenitor cells, but not SPC⁺ AT2 cells or AQP5⁺ AT1 cells. [Stem Cells Dev] Abstract

LUNG CANCER

Modification of α2,6-Sialylation Mediates the Invasiveness and Tumorigenicity of Non-Small Cell Lung Cancer Cells In Vitro and In Vivo via Notch1/Hes1/MMPs Pathway

Down-regulation of ST6Gal-I decreased protein levels of Jagged1, DLL-1, Notch1, Hes1, Hey1, matrix-metalloproteinases (MMPs) and VEGF, and suppressed proliferation, migration and invasion capabilities of A549 and H1299 cells in vitro. [Int J Cancer] Abstract

FOXO1 Inhibits Tumor Cell Migration via Regulating Cell Surface Morphology in Non-Small Cell Lung Cancer Cells

Investigators report that Forkhead box class O1 (FOXO1) was downregulated in human non-small cell lung cancer and that silencing of FOXO1 was associated with the invasive stage of tumor progression. [Cell Physiol Biochem] Full Article

Regulation of Apoptosis and Radiation Sensitization in Lung Cancer Cells via the Sirt1/NF-κB/Smac Pathway

Scientists performed colony formation, immunofluorescence microscopy, flow cytometry, RNA interference, and western blotting assays to determine whether SirT1 regulates radiation sensitization and which mechanisms and/or pathways it takes in lung cancer cell lines A549 and H460. [Cell Physiol Biochem] Full Article

ESE-1 Suppresses the Growth, Invasion and Migration of Human NSCLC Cells and Tumor Formation In Vivo

Researchers investigated whether epithelial-specific ETS-1 (ESE-1) expression affects tumorigenic activity using human non-small cell lung cancer (NSCLC) cells and a mouse xenograft model. ESE-1 expression suppressed anchorage‑independent growth in soft agar assay and led to an increase in G1 arrest and apoptosis in human NSCLC cells. [Oncol Rep] Abstract

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“Keaping” a Lid on Lung Cancer: The Keap1-Nrf2 Pathway

The authors describe the molecular mechanisms underlying Nuclear factor erythoid 2 – related factor 2 (NRF2) pathway activation in lung cancer cells, with a focus on in vivo functional studies in genetically engineered mouse models. [Cell Cycle] Abstract

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Genentech’s TECENTRIQ in Combination with Pemetrexed and Platinum-Based Chemotherapy Reduced the Risk of Disease Worsening or Death in the Initial Treatment of People with Advanced Lung Cancer

Genentech announced that the Phase III IMpower132 study met its co-primary endpoint of progression-free survival and demonstrated that the combination of TECENTRIQ^® plus chemotherapy reduced the risk of disease worsening or death compared to chemotherapy alone in the initial treatment of advanced non-squamous non-small cell lung cancer. [Genentech, Inc.] Press Release

Mersana Therapeutics Announces Partial Clinical Hold for XMT-1522 Clinical Trial

Mersana Therapeutics, Inc. announced that the FDA has placed the Phase I study of XMT-1522 on partial clinical hold. [Mersana Therapeutics, Inc.] Press Release

Online Portal of Thousands of Clinical Trials Could Aid Disease Research

Under pressure to be more transparent about the results of drug testing studies, some companies have begun to share anonymized patient data from clinical trials with approved researchers on secure websites. An online platform aims to expand such efforts by offering a one-stop clearinghouse for those seeking to mine these data for new insights. [ScienceInsider] Editorial

Dutch Publishing Giant Cuts Off Researchers in Germany and Sweden

Elsevier stopped thousands of scientists in Germany from reading its recent journal articles, as a row escalates over the cost of a nationwide open-access agreement. The move comes just two weeks after researchers in Sweden lost access to the most recent Elsevier research papers, when negotiations on its contract broke down over the same issue. [Nature News] Editorial

New Policy Aims to Free Scientists to Focus on Research, Avoid Jumping through Hoops

Chinese scientific researchers are to be evaluated on the valuable contributions they make to their field rather than their number of published papers or academic credentials, according to a new policy issued by China’s top officials. The new policy is considered by experts to be the first volley of China’s resistance to efforts by the U.S. to suppress its high-tech development. [Chinanews.com] Editorial

Hungarian Academy President Vows to Keep Fighting for Independence as Government Takes Control

Hungary’s parliament approved an amendment that makes it legally possible to transfer a large part of the budget of the Hungarian Academy of Sciences in Budapest to the country’s newly established Ministry of Innovation and Technology. [ScienceInsider] Editorial

Cancer Geneticist Quits after Harassment Allegations

Following numerous allegations that she harassed fellow employees, Nazneen Rahman, a cancer geneticist at the Institute of Cancer Research in the U.K., will leave her post. Rahman had already been on administrative leave since last November. Dozens of colleagues signed a letter last year describing bullying by Rahman. [The Scientist] Editorial

Questions Raised about “Breakthrough” Therapies’ Clinical Support

The FDAs “breakthrough therapy” designation has helped expedite the development and approval of more than 45 therapeutics in the last 5 years. But a study published in JAMA suggests that these interventions gain FDA approval on the basis of weaker clinical evidence than those that don’t have the breakthrough designation do—a finding that contrasts with public optimism about these drugs’ effectiveness. [The Scientist] Editorial

Leaky Pipeline for Women Scientists Dries Up after They Win First Big Grant

After they secure their first major research grant from the US National Institutes of Health, women are almost as successful as men at netting further awards from the agency, according to an analysis published in Proceedings of the National Academy of Sciences. [Nature News] Editorial

U.K. Votes to ‘Fully Participate’ in EMA after Brexit

British politicians have voted for the U.K. to try to remain close to the European Medicines Agency (EMA) after Brexit. The voted-for text tasks the government with seeking to secure the right for the U.K. to “fully participate” in the regional regulatory network after it leaves the European Union. [FierceBiotech] Editorial

NEW 2^nd AACR International Conference: Translational Cancer Medicine
September 27-29, 2018
Sao Paulo, Brazil

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

NEW Postdoctoral Fellow – Non-Small Cell Lung Cancer (The University of Texas MD Anderson Cancer Center)

Postdoctoral Fellow – Lung and Vascular Diseases (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Cellular Therapeutics in Chronic Lung Disease (Helmholtz Zentrum München)

Postdoctoral Associate – Chemotherapy and Radiation Therapy (Baylor College of Medicine)

Principal Investigators – Cancer (University of Alabama Birmingham)

Chief – Integrative Tumor Epidemiology Branch (National Institutes of Health – National Cancer Institute)

Postdoctoral Position – Immunology/Molecular Biology (National Heart, Lung and Blood Institute)

Postdoctoral Position – Vascular or Lung Biology (Yale University School of Medicine)

Postdoctoral Fellow – Human Lung Stem Cells and Regeneration (MedImmune)

Postdoctoral Fellow – Virology and Respiratory Biology (MedImmune)

Assistant or Associate Professor – Genetic Epidemiology (University of Kentucky)

Postdoctoral Fellow – Immunology (NYU Langone Health)

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