Pulmonary Cell News 6.25 June 29, 2017 | |
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TOP STORYTo investigate the contribution of the microenvironment to lung fibrosis and adenocarcinoma progression, researchers used mouse models to characterize the extracellular matrix composition of normal lung, fibrotic lung, lung tumors, and metastases. They found that increasing the levels of tenascin-C, via CRISPR-mediated transcriptional activation of the endogenous gene, enhanced the metastatic dissemination of lung adenocarcinoma cells. [Proc Natl Acad Sci USA] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Researchers hypothesized that epithelial cells (ECs) could directly activate basophils via cell-to-cell interaction. Basophils released histamine and marked levels of IL-4/IL-13 when cocultured with A549 EC and IL-3, without exogenous allergen or IgE cross-linking stimuli. The inability to detect IL-33 or thymic stromal lymphopoietin, or to neutralize their activity, suggested a unique mode of basophil activation by A549 EC. [J Immunol] Abstract Scientists examined the response of human primary airway epithelial cells to diesel particulate chemical extracts (DE) and characterized gene expression alterations using RNA-SEQ. Using the antagonist CH223191, DE induced CYP1A1 and attenuation of CXCL10 among other genes were observed to be aryl hydrocarbon receptor dependent. [Toxicol In Vitro] Abstract Investigators hypothesized that their sulfated dehydropolymer of caffeic acid, CDSO3, would exert anti-cell death activities and therapeutic interventions in emphysema by virtue of Fe2+ chelation-based HIF-1α/VEGF stabilization and elevation. At 10 μM, CDSO3 inhibited the lung endothelial and epithelial cell death induced by histone deacetylase inhibition with trichostatin A, VEGF receptor blockade with SU5416, and cigarette smoke extract by 65–99%, which were all significantly opposed by addition of excess Fe2+ or HIF-1α inhibitors. [Pulm Pharmacol Ther] Abstract LUNG CANCERGLI1 Blockade Potentiates the Antitumor Activity of PI3K Antagonists in Lung Squamous Cell Carcinoma The authors identified the Hedgehog pathway transcription factor GLI1 as a critical driver of lung squamous cell carcinoma (SCC). Analysis of human lung cancer datasets showed that GLI1 mRNA was highly expressed in human lung SCC and portended a poor prognosis. Inhibition of GLI1 in human lung SCC cell lines suppressed tumor cell clonogenicity and proliferation in culture and in vivo. [Cancer Res] Abstract WEE1 Kinase Inhibitor AZD1775 Has Pre-Clinical Efficacy in LKB1-Deficient Non-Small Cell Lung Cancer Scientists investigated the pre-clinical effects of AZD1775 in the context of KRAS/LKB1 in non-small cell lung cancer (NSCLC). Using NSCLC cell lines, they found that AZD1775 alone and in combination with DNA-damaging agents decreased tumor cell viability in LKB1-deficient NSCLC cells. [Cancer Res] Abstract Investigators found that CBP501 inhibits the migration of non-small cell lung cancer cells in vitro, even in the presence of migration inducing factors such as WNT, IL-6, and several growth factors. CBP501 also inhibited epidermal growth factor enhanced invasion and the epithelial-to-mesenchymal transition. This inhibition was accompanied by (i) suppression of Akt and ERK1/2 phosphorylation, and (ii) suppression of expression of transcription factor Zeb1 and the mesenchymal marker Vimentin. [Oncotarget] Full Article The authors found that quercetin inhibited the migration/invasion of non-small cell lung cancer (NSCLC) cell lines and bone metastasis in an orthotopic A549 xenograft model by suppressing the Snail-mediated epithelial-to-mesenchymal transition. Mechanistic investigations found that quercetin suppressed Snail-dependent Akt activation by upregulating maspin and Snail-independent a disintegrin and metalloproteinase 9 expression pathway to modulate the invasive ability of NSCLC cells. [Biochim Biophys Acta – Mol Cell Res] Abstract Scientists investigated what mechanism was responsible for the switch from senescence to apoptosis in pseudolaric acid B (PAB)-treated human lung cancer cell lines. In p53 wild-type A549 cells, PAB caused senescence, and time-dependently increased glucose utilization; knockdown of p53 or p21 significantly decreased the uptake and metabolism of glucose but elevated PAB-induced apoptosis. [Acta Pharmacol Sin] Abstract lncRNA XIST Interacts with miR-140 to Modulate Lung Cancer Growth by Targeting iASPP Researchers investigated the role of X-inactive specific transcript (XIST) in human lung cancer cell lines and clinical tumor samples in order to determine the function of this molecule. lncRNA-XIST was specifically upregulated in lung cancer cell lines and promoted lung cancer cell growth through targeting miR-140. Knockdown of XIST inhibited the proliferation and promoted cell apoptosis of human lung cancer cells and suppressed metastasis in vitro and in vivo. [Oncol Rep] Abstract | |
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REVIEWSThe authors highlight the functional role of EMT in lung development and injury repair, and discuss how it can contribute to pathogenesis of chronic lung disease. [Dev Dyn] Abstract | Full Article Visit our reviews page to see a complete list of reviews in the pulmonary cell research field. | |
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SCIENCE NEWSEnanta Pharmaceuticals, Inc. announced new data on EDP-938, Enanta’s lead compound being developed for the treatment of RSV. In vitro data demonstrated that EDP-938 is a potent inhibitor of both RSV-A and RSV-B activity, maintaining antiviral activity post-infection while presenting a high barrier to resistance. New in vivo data consistent with potent inhibition of the RSV virus were also presented. [Press release from Enanta Pharmaceuticals, Inc. discussing research presented at the XIX International Symposium on Respiratory Viral Infections, Berlin] Press Release | |
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INDUSTRY NEWSTP Therapeutics, Inc. announced that the U.S. FDA has granted orphan drug designation to its leading clinical compound TPX-0005 for the treatment of non-small cell lung adenocarcinomas harboring ALK, ROS1, or NTRK oncogenic rearrangements. [TP Therapeutics, Inc. (Business Wire, Inc.)] Press Release OSE Immunotherapeutics SA announced that following the recommendation by IDMC on the Phase III clinical study, Atalante 1, which is evaluating Tedopi® for the treatment of non-small cell lung cancer, the company is temporarily pausing patient accrual while continuing treatment for patients already enrolled in order to further assess the study’s current patient profile in relation to the potential benefit of Tedopi® with more mature data. [OSE Immunotherapeutics SA] Press Release Novartis announced the European Commission approved expanding the use of Zykadia® to include the first-line treatment of patients with advanced NSCLC whose tumors are anaplastic lymphoma kinase (ALK)-positive. [Novartis] Press Release | |
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POLICY NEWSPutin Tightens Control over Russian Academy of Sciences The Russian government has taken further steps to tighten its grip on the Russian Academy of Sciences (RAS) in Moscow. The State Duma—one of the two chambers of the Russian parliament—passed the first draft of a new law that would give president Vladimir Putin the final say in the elections for RAS’s presidency. [ScienceInsider] Editorial Vaccine Ruling from Europe’s Highest Court Isn’t as Crazy as Scientists Think The Court of Justice of the European Union in Luxembourg handed down a judgment in a compensation case involving a French man who claimed that a vaccination for hepatitis B caused his multiple sclerosis. The ruling specifies what type of evidence is allowed in EU member states in such cases, but it prompted a flurry of negative press coverage. [Nature News] Editorial Scientists in Limbo as US Supreme Court Allows Modified Travel Ban The US Supreme Court has reinstated a limited version of President Donald Trump’s temporary order banning travelers from six Muslim-majority countries from entering the United States. The court will hear a legal challenge to the ban in October. The court’s decision casts doubt on the fate of students and scientists from these countries who hope to study or work in the United States. [Nature News] Editorial
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EVENTSNEW 11th American Association for Cancer Research (AACR)-Japanese Cancer Association (JCA) Joint Conference Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Fellow – Lung Microengineering (University of Colorado) NEW PhD Position – Lung Disease (Helmholtz Zentrum München) Postdoctoral Associate – Lung Cancer Research (Weill Cornell Medicine) Postdoctoral Research Training – Lung Disease (Baylor College of Medicine) Postdoctoral Research Fellow – Cancer Genetics and Genomics (Fred Hutchinson Cancer Research Center) Research Fellow – Cancer Research (National University of Singapore) Staff Research Scientist – Lung Injury (St. Michael’s Hospital) Postdoctoral Researcher – Lung Cancer Biology (Memorial Sloan Kettering Cancer Center) Postdoctoral Researcher – Inhalation & Developmental Toxicology (Louisiana State University) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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Home Pulmonary Cell News Volume 6.25 | Jun 29 2017