Pulmonary Cell News 6.21 June 1, 2017 | |
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TOP STORYChronic pulmonary colonization with bacterial pathogens, particularly Pseudomonas aeruginosa, is the primary cause of morbidity and mortality in patients with cystic fibrosis (CF). Investigators observed that β1-integrins accumulate on the luminal membrane of upper-airway epithelial cells from mice and humans with CF. β1-integrin accumulation was due to increased ceramide and the formation of ceramide platforms that trapped β1-integrins on the luminal pole of bronchial epithelial cells. [Cell Host Microbe] Full Article | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Researchers evaluated the therapeutic potential of rhesus θ defensin-1 (RTD-1) for cystic fibrosis (CF) airway infection and inflammation using in vitro, ex vivo, and in vivo models. RTD-1 directly reduced metalloprotease activity, as well as inflammatory cytokine secretion from CF airway leukocyte and bronchial epithelial cells. [Antimicrob Agents Chemother] Abstract Loss of epithelial barrier integrity is implicated in a number of human lung diseases. However, the molecular pathways underlying this process are poorly understood. In a phenotypic screen, investigators identified Axl kinase as a negative regulator of epithelial phenotype and function. [Lab Invest] Abstract To investigate the involvement of extracellular heat shock protein 90α (eHsp90α) in the bronchial epithelial barrier disruption induced by house dust mite (HDM), normal human bronchial epithelial cell line 16HBE14o- cells were treated by HDM, human recombinant (hr) Hsp90α and hrHsp90β respectively and pretreated by 1G6-D7, a specific anti-secreted Hsp90α monoclonal antibody. The authors found that the eHsp90α mediates HDM-induced human bronchial epithelial barrier dysfunction by activating RhoA/myosin light chain signaling. [Respir Res] Full Article Scientists examined the effect of calcitonin gene-related peptide (CGRP) on primary alveolar epithelial type II (AECII) cells and expression of Sonic hedgehog (SHH) signaling pathway components following exposure to hyperoxia. The apoptosis of AECII cells was assayed by flow cytometry, and the mRNA and protein expression levels of Shh and Ptc1 in the AECII cells were detected by reverse transcription-quantitative polymerase chain reaction, western blot analysis and immunofluorescence, respectively. [Int J Mol Med] Abstract LUNG CANCERInvestigators performed an integrative analysis of human non-small cell lung cancer (NSCLC) tumor samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas. They revealed a markedly elevated expression of the GLUT1 glucose transporter in lung squamous cell carcinoma (SqCC), which augments glucose uptake and glycolytic flux. They showed that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, while lung adenocarcinoma exhibits significant glucose independence. [Nat Commun] Full Article The authors investigated the cellular mechanisms mediating resistance of non-small cell lung cancers (NSCLCs) to vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors. Species-specific microarray analysis identified increased expression of stromal-derived hepatocyte growth factor (HGF) as a candidate mediator of TKI resistance and its receptor, c-MET, was activated in cancer cells and tumor-associated stroma. [Clin Cancer Res] Abstract FGF2/FGFR1 Regulates Autophagy in FGFR1-Amplified Non-Small Cell Lung Cancer Cells Researchers evaluated autophagic activity by immunoblotting for microtubule-associated protein 1 light chain 3 (LC3), formation of GFP-LC3 puncta, and monodansylcadaverine staining. They elucidated that fibroblast growth factor receptor 1 (FGFR1) activation suppressed autophagy. Mechanistic study revealed that the induction of autophagy by FGFR1 inhibition was mediated through inhibiting the ERK/MAPK pathway not by AKT pathway, accompanied by upregulation of beclin-1. [J Exp Clin Cancer Res] Full Article B-Myb Is Up-Regulated and Promotes Cell Growth and Motility in Non-Small Cell Lung Cancer Scientists investigated the expression profile of B-Myb and its functional impact in lung cancer. Expression analysis by quantificational real-time polymerase chain reaction and immunohistochemistry demonstrated that B-Myb expression is aberrantly overexpressed in non-small cell lung cancer (NSCLC), and positively correlated with pathologic grade and clinical stage of NSCLC. [Int J Mol Sci] Full Article Investigators found that nimbolide treatment suppressed the invasion and migration of non-small cell lung cancer cells, in a dose-dependent manner. Nimbolide treatment dose-dependently inhibited ERK1/2 activation, decreased Snail and MMP-3 expression, and increased E-cadherin expression. [Biomed Pharmacother] Abstract | |
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REVIEWSUnraveling the Biology of SCLC: Implications for Therapy The authors review the progress made in uncovering aspects of the biology of small-cell lung cancer (SCLC) and its microenvironment that are defining new therapeutic strategies and offering renewed hope for patients. [Nat Rev Clin Oncol] Abstract Visit our reviews page to see a complete list of reviews in the pulmonary cell research field. | |
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INDUSTRY NEWSWindtree Therapeutics, Inc. announced completion of enrollment in its AEROSURF® Phase IIb clinical trial evaluating aerosolized KL4 surfactant for the treatment of RDS in premature infants, 28 to 32-week gestational age, receiving nasal continuous positive airway pressure for RDS. [Windtree Therapeutics, Inc.] Press Release TaiGen Biotechnology Company, Limited announced that it has submitted a New Drug Application (NDA) for the intravenous formulation of Taigexyn® to the China Food and Drug Administration. Taigexyn® is a novel non-fluorinated quinolone antibiotic. The NDA submission is supported by a pivotal Phase III trial comparing intravenous formulations of Taigexyn® to levofloxacin in 518 patients with moderate to severe community-acquired pneumonia. [TaiGen Biotechnology Company, Limited (PR Newswire Association LLC.)] Press Release Vertex Pharmaceuticals Incorporated announced that it has reached an agreement with the Health Service Executive in the Republic of Ireland to fund ORKAMBI® for people in Ireland with cystic fibrosis (CF) ages 12 and older who have two copies of the F508del mutation. [Vertex Pharmaceuticals Incorporated] Press Release Sunovion Pharmaceuticals Inc. announced that the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter for the New Drug Application for SUN-101/eFlow® for the long-term, maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema. [Sunovion Pharmaceuticals Inc.] Press Release Novartis announced the US Food and Drug Administration (FDA) approved the expanded use of Zykadia® to include the first-line treatment of patients with metastatic NSCLC whose tumors are anaplastic lymphoma kinase-positive, as detected by an FDA-approved test. [Novartis] Press Release | |
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POLICY NEWSTrials of Embryonic Stem Cells to Launch in China In the next few months, surgeons in the Chinese city of Zhengzhou will carefully drill through the skulls of people with Parkinson’s disease and inject four million immature neurons derived from human embryonic stem (ES) cells into their brains. Then they will patch the patients up, send them home and wait. This will mark the start of the first clinical trial in China using human ES cells, and the first one worldwide aimed at treating Parkinson’s disease using ES cells from fertilized embryos. [Nature News] Editorial Pay-to-View Blacklist of Predatory Journals Set to Launch Scholarly-services firm Cabell’s International says that it will launch its own list of predatory journals: those that deceive their authors or readers, for example by charging fees to publish papers without conducting peer review. [Nature News] Editorial Web of Science Owner Buys up Booming Peer-Review Platform The owner of the vast science-citation database Web of Science — Clarivate Analytics — is buying up a firm that has gathered hundreds of thousands of peer-review records, in a deal that could lead to new ways of organizing scientific peer review and preventing peer-review fraud. [Nature News] Editorial
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EVENTSNEW ASCO/AACR Methods in Clinical Cancer Research Workshop NEW Intestinal Organoid Virtual Training Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Researcher – Lung Cancer Biology (Memorial Sloan Kettering Cancer Center) NEW Clinical Research Fellow – Lung Fibrosis (University of Oxford) Research Assistant/Associate – Regulation of Human Lung Development (University of Cambridge) Postdoctoral Researcher – Inhalation & Developmental Toxicology (Louisiana State University) Postdoctoral Scientist – Macrophage and Lung Fibrosis (University of Oxford) Faculty – Immunology of Lung Diseases (National Jewish Health) Research Administrator IV – Early Detection of Lung Cancer (Fred Hutchinson Cancer Research Center) Assistant, Associate or Full Professor Position(s) – Asthma Research (University of Pennsylvania) 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 6.21 | Jun 1 2017