Pulmonary Cell News Volume 7.21 | May 31 2018

TOP STORY

SHP2 Is Required for Growth of KRAS-Mutant Non-Small-Cell Lung Cancer In Vivo

Inhibition of SHP2, which links receptor tyrosine kinase signaling to the RAS-RAF-MEK-ERK pathway, was shown to be ineffective in KRAS-mutant or BRAF-mutant cancer cell lines. Scientists also indicated that SHP2 inhibition in KRAS-mutant non-small-cell lung cancer cells under normal cell culture conditions has little effect. [Nat Med] Abstract

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Acute Effects of Multi-Walled Carbon Nanotubes on Primary Bronchial Epithelial Cells from COPD Patients

Researchers simulated acute inhalation of multi-walled carbon nanotubes (MWCNTs) employing an air-liquid interface cell exposure system: primary human bronchial epithelial cells from chronic obstructive pulmonary disease (COPD) patients and healthy donors, cultured at the air-liquid interface were exposed to MWCNTs. [Nanotoxicology] Abstract

Epigenetic Reactivation of LINE-1 Retrotransposon Disrupts NuRD Co-Repressor Functions and Induces Oncogenic Transformation in Human Bronchial Epithelial Cells

Investigators showed that challenge of human bronchial epithelial cells with the lung carcinogen, benzo(a)pyrene, shifted the L1 promoter from a heterochromatic to euchromatic state through disassembly of the nucleosomal and remodeling deacetylase (NuRD) complex. [Mol Oncol] Abstract | Full Article

Topotecan Alleviates Ventilator-Induced Lung Injury via NF-κB Pathway Inhibition

Compared to PBS treatment, topotecan significantly decreased the acute lung injury score, myeloperoxidase content, total protein concentration, and presence of inflammatory cells and inflammatory cytokines in bronchoalveolar lavage fluid. Topotecan also reduced caspase-3 activation and type II alveolar epithelial cell apoptosis. [Cytokine] Abstract

Cross-Talk between Human Airway Epithelial Cells and 3T3-J2 Feeder Cells Involves Partial Activation of Human MET by Murine HGF

The authors investigated secreted growth factors that are produced by 3T3-J2 cells and act upon primary human airway basal cells. They found robust production of hepatocyte growth factor from fibroblast feeder cells following mitotic inactivation. [PLoS One] Full Article

Host-Directed Combinatorial RNAi Improves Inhibition of Diverse Strains of Influenza A Virus in Human Respiratory Epithelial Cells

The effect of single and combinatorial RNA interference (RNAi) on the replication of 12 diverse influenza A viruses, including three strains isolated from birds and one strain isolated from seals, was then evaluated in primary normal human bronchial epithelial cells. [PLoS One] Full Article

Stability of Gene Expression by Primary Bronchial Epithelial Cells over Increasing Passage Number

Expression of TGFβ1, TGFβ2, activin A, FSTL3, MUC5AC, CXCL10, IFIH1, p63, KT5, TUBB4A, TJP1, OCLN, and FOXJ1 by primary bronchial epithelial cells (BECs) from asthmatic and healthy children was stable with no significant differences between passages 1, 2 and 3; however, gene expression at cell passages 4 and 5 was significantly greater and more variable compared to passage 1 BECs for many of these genes. [BMC Pulm Med] Full Article

LUNG CANCER

Cancer Cells Co-Opt the Neuronal Redox-Sensing Channel TRPA1 to Promote Oxidative-Stress Tolerance

Scientists showed a non-canonical oxidative-stress defense mechanism through TRPA1, a neuronal redox-sensing Ca²⁺-influx channel. In TRPA1-enriched breast and lung cancer spheroids, TRPA1 is critical for survival of inner cells that exhibit reactive oxygen species accumulation. [Cancer Cell] Abstract | Press Release | Graphical Abstract

xCT (SLC7A11)-Mediated Metabolic Reprogramming Promotes Non-Small Cell Lung Cancer Progression

Investigators hypothesized that overexpression of xCT occurs in lung cancer cells to satisfy the metabolic requirements for growth and survival. [Oncogene] Full Article

Proliferating Cell Nuclear Antigen Promotes Cell Proliferation and Tumorigenesis by Up-Regulating STAT3 in Non-Small Cell Lung Cancer

Overexpression of proliferating cell nuclear antigen promoted cell proliferation, clonal formation, and tumorigenesis in lung cancer cells and inhibited cell apoptosis. In contrast, these effects were inhibited when knockdown of signal transducer and activator of transcription-3 (STAT3). [Biomed Pharmacother] Abstract

The Importance of Tyrosine Phosphorylation Control of Cellular Signaling Pathways in Respiratory Disease: pY and pY Not

The roles of various protein tyrosine kinases and protein tyrosine phosphatases in acute lung injury and repair, pulmonary fibrosis, pulmonary vascular disease and inflammatory airways disease will be discussed in this review. [Am J Respir Cell Mol Biol] Abstract

Visit our reviews page to see a complete list of reviews in the pulmonary cell research field.

Update on TERRANOVA Phase III Trial for Fasenra in Chronic Obstructive Pulmonary Disease

AstraZeneca and MedImmune announced top-line results from TERRANOVA, the second of two pivotal Phase III trials for Fasenra in patients with moderate to very severe chronic obstructive pulmonary disease. [AstraZeneca] Press Release

Imfinzi Significantly Improves Overall Survival in the Phase III PACIFIC Trial for Unresectable Stage III Non-Small Cell Lung Cancer

AstraZeneca and MedImmune announced positive overall survival results for the Phase III PACIFIC trial, a randomized, double-blinded, placebo-controlled, multi-center trial of Imfinzi in patients with unresectable Stage III non-small cell lung cancer whose disease had not progressed following platinum-based chemotherapy concurrent with radiation therapy. [AstraZeneca] Press Release

Positive Recommendation of IDMC to Zepsyre^® to Continue the Phase III Trial within Small-cell Lung Cancer (ATLANTIS)

PharmaMar announced that the Independent Data Monitoring Committee (IDMC) has notified the company of its recommendation that the Phase III (ATLANTIS) trial currently under way with Zepsyre^® in combination with doxorubicin in small-cell lung cancer patients should continue without any changes. [PharmaMar, S.A.] Press Release

CIRM Invests in Stem Cell Clinical Trial Targeting Lung Cancer and Promising Research into Osteoporosis and Incontinence

The five-year survival rate for people diagnosed with the most advanced stage of non-small cell lung cancer (NSCLC) is pretty grim, only between one and ten percent. To address this devastating condition, the Board of the California Institute for Regenerative Medicine (CIRM) voted to invest almost $12 million in a team from UCLA that is pioneering a combination therapy for NSCLC. [California Institute for Regenerative Medicine] Press Release

Pfizer’s Xalkori^® (Crizotinib) Receives FDA Breakthrough Therapy Designation in Two New Indications

Pfizer Inc. announced that the FDA granted Breakthrough Therapy designation for XALKORI^® for the treatment of patients with metastatic non-small cell lung cancer with MET exon 14 alterations with disease progression on or after platinum-based chemotherapy. [Pfizer Inc.] Press Release

After Brexit, Can British Science Have Its Cake and Eat It, Too?

Nearly two years after Britons voted to leave the European Union, Brexit’s impact on European science is finally coming into focus. Prime Minister Theresa May announced that the United Kingdom wants to take part in the next EU research-funding program, set to be worth almost €100 billion (US$116 billion). [Nature News] Editorial

Max Planck Scientists Criticize Handling of Animal-Rights Charges against Leading Neuroscientist

Scientists at one of Germany’s leading neuroscience institutes say that their employer, the Max Planck Society, is failing in its responsibility to defend the institute’s scientists against efforts by animal-rights activists to disrupt research. [Nature News] Editorial

Brexit: UK May Get Poorer Access than Israel to EU Science Scheme

Theresa May’s appeal for a special Brexit deal on science and research collaboration, worth billions to the British economy, is being stonewalled by Brussels as it prepares to offer an arrangement less privileged and more expensive than that given to non-EU states such as Israel. [The Guardian] Editorial

Will U.S. Academies Expel Sexual Harassers?

As high-profile sexual harassment cases fuel public criticism, the presidents of the U.S. National Academies of Sciences, Engineering, and Medicine announced they may adopt new policies allowing the prestigious bodies to eject members who have committed harassment and other forms of misconduct. [ScienceInsider] Editorial

NEW Cell Symposia: Translation of Stem Cells to the Clinic: Challenges and Opportunities
December 2-4, 2018
Los Angeles, California, United States

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

NEW Postdoctoral Fellow – Immunology (NYU Langone Health)

NEW Postdoctoral Fellow – Interface between Single-Cell Biology and Disease (European Molecular Biology Laboratory)

Research Technologist – Pulmonary (STEMCELL Technologies Inc.)

Call for Research Fellow Applications – Heart and Lung (Imperial College London)

PhD Student – Novel Concepts for Therapy of Allergy (Helmholtz Zentrum München)

Research Associate – Acute Lung Injury, Trauma, and Sepsis (University of Maryland School of Medicine)

Postdoctoral Fellowship – Genetic Epidemiology of Lung Disease (Brigham & Women’s Hospital – Harvard Medical School)

Postdoctoral Research Scientist – Gene Therapy (University of Oxford)

Postdoctoral Fellow Position – Lung Injury and Repair (University of Kentucky)

Senior Research Associate – Lung Biology and Alveolar Epithelial Cells (University of Southern California)

Postdoctoral Positions – Long Noncoding RNA in Tumor Development and Cellular Differentiation (University of Gothenburg)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

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