Pulmonary Cell News Volume 8.20 | May 30 2019

TOP STORY

RASSF1A Controls Tissue Stiffness and Cancer Stem-Like Cells in Lung Adenocarcinoma

Researchers showed that adverse prognosis associated with epigenetic silencing of the tumor suppressor RASSF1A was due to increased deposition of extracellular matrix, tumor stiffness and metastatic dissemination in vitro and in vivo. They found that lung cancer cells with RASSF1A promoter methylation displayed constitutive nuclear YAP1 accumulation and expression of prolyl 4-hydroxylase alpha-2 which increased collagen deposition. [EMBO J] Abstract

(Ranked by impact factor of the journal)

Cigarette Smoke Extract Alters Genome-Wide Profiles of Circular RNAs and mRNAs in Primary Human Small Airway Epithelial Cells

By using a cell model of COPD in primary human small airway epithelial cells treated with or without cigarette smoke extract (CSE), the authors uncovered 4,379 previously unknown circular RNAs (circRNAs) in human cells and 903 smoke-specific circRNAs, with the help of RNA-sequencing and bioinformatic analysis. Moreover, 3,872 up- and 4,425 down-regulated mRNAs were also identified under CSE stimulation. [J Cell Mol Med] Full Article

Andrographolide Antagonizes the Cigarette Smoke-Induced Epithelial-Mesenchymal Transition and Pulmonary Dysfunction through Anti-Inflammatory Inhibiting HOTAIR

With cell culture and animal studies, investigators showed that cigarette smoke (CS) exposure caused pulmonary dysfunction and airway remodeling with inflammatory cell infiltration. Consistent with these pulmonary lesions, the inflammatory factors interleukin-6 and interleukin-8 were increased in mice exposed to CS for four days. [Toxicology] Abstract

LUNG CANCER

Targeting HDAC/OAZ1 Axis with a Novel Inhibitor Effectively Reverses Cisplatin Resistance in Non-Small Cell Lung Cancer

Investigators identified that a novel histone deacetylase (HDAC) inhibitor S11, with P-glycoprotein inhibitory activity, could obviously suppress cell growth in cisplatin-resistant non-small cell lung cancer (NSCLC) cell lines. In addition, S11 could increase the expression of Ac-H4 and p21, which confirmed its HDAC inhibitory action, suppressed colony formation, and blocked cell migration of cisplatin-resistant NSCLC cells. [Cell Death Dis] Full Article

ZCCHC10 Suppresses Lung Cancer Progression and Cisplatin Resistance by Attenuating MDM2-Mediated p53 Ubiquitination and Degradation

The authors demonstrated that ZCCHC10 expression levels were statistically lower in lung adenocarcinoma tissues than the corresponding adjacent noncancerous tissues, and decreased expression of ZCCHC10 mRNA predicted poorer survival of the patients. Ectopic expression of ZCCHC10 in lung cancer cells harboring wild-type p53 dramatically suppressed cell proliferation, colony formation, migration, invasion and cisplatin resistance in vitro, as well as tumor growth and metastasis in vivo. [Cell Death Dis] Full Article

Increased 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase-3 Activity in Response to EGFR Signaling Contributes to Non-Small Cell Lung Cancer Cell Survival

Investigators demonstrated that exposing non-small cell lung cancer cells harboring either wildtype or mutated epidermal growth factor receptor (EGFR) to EGF rapidly increased 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) phosphorylation, expression, and activity, and that PFKFB3 inhibition markedly reduced the EGF-mediated increase in glycolysis. [J Biol Chem] Abstract

TGFβ-Induced Cytoskeletal Remodeling Mediates Elevation of Cell Stiffness and Invasiveness in NSCLC

Scientists showed that elevation of rigidity and invasiveness of TGFβ-stimulated NSCLC cells correlated with upregulation of several cytoskeletal and motor proteins including vimentin, a canonical marker of epithelial-to-mesenchymal transition, and less-known unconventional myosins. [Sci Rep] Full Article

Evaluation of Aminolevulinic Acid-Derived Tumor Fluorescence Yields Disparate Results in Murine and Spontaneous Large Animal Models of Lung Cancer

Using flow cytometry and fluorescent microscopy, researchers confirmed that non-small cell lung cancer models fluoresced after exposure to 5-aminiolevulinic acid (5-ALA) in vitro. High levels of fluorescence were similarly observed in murine tumors within two hours of systemic 5-ALA delivery. [Sci Rep] Full Article

Synergistic Effects of Gefitinib and Thalidomide Treatment on EGFR-TKI-Sensitive and -Resistant NSCLC

The combination of thalidomide and gefitinib induced antiproliferative and proapoptotic effects in HCC827, PC9, and PC9GR cells. The inhibition of EGFR phosphorylation and downstream signaling was more pronounced in the thalidomide and gefitinib co-treatment group was compared with the single agent treatment groups. [Eur J Pharmacol] Abstract

Identification of Dinactin, a Macrolide Antibiotic, as a Natural Product-Based Small Molecule Targeting Wnt/β-Catenin Signaling Pathway in Cancer Cells

The authors performed MTT assays to investigate cell viability and proliferation after exposure to small molecules. Protein expression analysis was carried out by western blotting. Top-Flash reporter assays were used to score for β-catenin signaling and cell cycle analysis was carried out by flow cytometry. [Cancer Chemother Pharmacol] Abstract

LncRNA MALAT1 Promotes Lung Cancer Proliferation and Gefitinib Resistance by Acting as a miR-200a Sponge

MALAT1 in A549 and HCC 1299 human lung adenocarcinoma cell lines was silenced by shRNA or overexpressed using plasmid, and the cell viability and cell proliferation were evaluated by MTT assay and soft agar colony formation assay. RNA levels were detected by RT-PCR, and the protein expression was measured by western blot. [Arch Bronconeumol] Abstract | Graphical Abstract

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Thiol-Based Drugs in Pulmonary Medicine: Much More than Mucolytics

Thiol-based drugs act as mucolytics and antioxidants. They also interfere with inflammatory pathways, modulate human bronchial tone, and should be considered in some infections because thiols reduce bacterial adhesion to the respiratory epithelial cell surface and inhibit biofilm formation, causing biofilm disruption and improving the efficacy of antibiotic therapy. [Trends Pharmacol Sci] Abstract

Microfluidics for Studying Metastatic Patterns of Lung Cancer

The authors present the first comprehensive overview of the microfluidic systems used as innovative tools in the studies of lung cancer metastasis including single cancer cell analysis, endothelial transmigration, distant niches migration and finally neoangiogenesis. [J Nanobiotechnology] Full Article

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

AIT Therapeutics Presents On-Demand Nitric Oxide Study and Poster

IT Therapeutics, Inc. presented data from its study: “On-Demand Nitric Oxide for Ventilator-Based Nitric Oxide Inhalation: A Risk-Reduction Perspective.” [Press release from IT Therapeutics, Inc. (GlobeNewswire, Inc.) discussing research presented at the International Society for Aerosols in Medicine (ISAM) 2019 Congress, Montreux] Press Release

City of Hope Doctors Present Research on First KRAS Inhibitor and CAR T Cell Therapy

A first-ever inhibitor of a cancer gene found in some lung, colorectal and other cancers and the effectiveness of chimeric antigen receptor (CAR) T cell therapy for patients with chronic lymphocytic leukemia are just some of the research topics that City of Hope physicians and scientists will present. [Press release from City of Hope (BusinessWire, Inc.) discussing research to be presented at the American Society of Clinical Oncology (ASCO) 2019, Chicago] Press Release

Novartis’ Phase III QUARTZ Study of New Investigational Inhaled Combination Treatment QMF149 Meets Primary and Key Secondary Endpoints in Patients with Inadequately Controlled Asthma

Novartis announced the first study results from the phase III PLATINUM clinical development program assessing the safety and efficacy of QMF149, an investigational, once-daily, fixed dose combination asthma treatment containing indacaterol acetate- a long acting beta agonist and mometasone furoate. [Novartis] Press Release

Spectrum Announces Poziotinib ZENITH20 Trial HER2 Cohort (Cohort 2) Has Reached Enrollment Target

Spectrum Pharmaceuticals, Inc. announced the full enrollment of cohort 2 for previously treated non-small cell lung cancer (NSCLC) patients with HER2 exon 20 insertion mutations. Topline results from this cohort are expected by mid 2020. This is the second cohort that has met enrollment target in Spectrum’s ZENITH20 trial – an open-label, multi-center, global Phase II trial evaluating NSCLC patients with EGFR or HER2 exon 20 insertion mutations. [Spectrum Pharmaceuticals, Inc] Press Release

Last Patient Enrolled in the Phase II Trial with Transgene’s TG4010 + Nivolumab + Chemotherapy for the First-Line Treatment of Advanced Lung Cancer (NSCLC)

Transgene announced that the last patient has been included in the Phase II trial evaluating TG4010 in combination with Opdivo^® and chemotherapy as a first-line treatment for advanced non-squamous NSCLC with low or no expression of PD-L1 by the tumor cells. [Transgene SA] Press Release

Vertex Selects Triple Combination Regimen of VX-445, Tezacaftor and Ivacaftor to Submit for Global Regulatory Approvals in Cystic Fibrosis

Vertex Pharmaceuticals Incorporated announced that it has selected the triple combination of the next-generation corrector VX-445, tezacaftor and ivacaftor to submit for potential global regulatory approvals for people ages 12 and older with cystic fibrosis. Final data announced today from a 24-week Phase III study in people with one F508del mutation and one minimal function mutation and from a four-week Phase III study in people with two F508del mutations will form the basis of these submissions. [Vertex Pharmaceuticals Incorporated] Press Release

Here’s Why the Outcomes of This Week’s European Elections Are Good News for Science

Although populist and euroskeptic parties grew in last week’s elections for the European Parliament, the tsunami that EU supporters feared didn’t happen. That comes as a relief to many scientists, because several of the populist movements now on the rise in Europe appear to have little interest in science, flirt with antiscientific ideas, or have tried to curtail academic freedom. [ScienceInsider] Editorial

White House Sends Mixed Messages on 2020 Research Spending Bills

President Donald Trump doesn’t want Congress to boost the budgets of the National Institutes of Health or the National Science Foundation. But he has no objection to giving more research dollars to parts of the Department of Energy and NASA. [ScienceInsider] Editorial

Labor Agency Revisits Whether Graduate Students Can Unionize

Since 2016, graduate teaching and research assistants at private institutions have had legal protection to form unions thanks to a ruling by the National Labor Relations Board determining that the students qualify as employees. But that may soon change: The NLRB, which now has a Republican majority, announced last week that it will make a new rule regarding students’ employee status. [The Scientist] Editorial

NEW 20^th Annual International Lung Cancer Congress^®
July 25-27, 2019
Huntington Beach, California, United States

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

NEW Postdoctoral Fellow – Pulmonary and Cardiovascular Diseases (Oslo University Hospital)

NEW Senior Scientific Officer – Lung Cancer Liquid Biopsy Biomarker Research (Cancer Research UK Manchester Institute)

Scientist – Pulmonary (STEMCELL Technologies Inc.)

Postdoctoral Fellowship – RNA in Lung Sepsis and Inflammation (Boston University)

Postdoctoral Fellowship – Respiratory and Ophthalmic Diseases (Queen’s University Belfast)

Postdoctoral Researcher – Stem Cell Biology of the Lung and Intestines (Stanford School of Medicine)

Postdoctoral Fellow – Inflammation Suppression & Lung Disease (National University of Singapore)

Postdoctoral Fellowship – Redox Systems in Lung and Breast Cancer (The Held Laboratory)

Postdoctoral Studentship – Lung Adenocarcinoma Research (Max Delbrück Centrum for Molecular Medicine)

Postdoctoral Fellow – Vascular & Lung Biology (Ann & Robert H. Lurie Children’s Hospital of Chicago)

Postdoctoral Researcher – Regenerative Medicine for Lung Conditions (United Therapeutics)

Postdoctoral Researcher – Causes of Allergies and Asthma (Stanford University)

Postdoctoral Position – Pulmonary/Lung Carcinogenesis Translational Research (Albert Einstein College of Medicine)

Postdoctoral Position – Lung Research (Columbia University)

Associate Professor – Oncology (University of California, Davis)

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