Pulmonary Cell News Volume 7.45 | Nov 15 2018

TOP STORY

Role of INSL4 Signaling in Sustaining the Growth and Viability of LKB1-Inactivated Lung Cancer

Sustained INSL4 expression was required for the growth and viability of LKB1-inactivated non-small cell lung carcinoma cells in vitro and in a mouse xenograft model. Expression profiling revealed INSL4 as a critical regulator of cell cycle, growth, and survival. [J Natl Cancer Inst] Abstract

(Ranked by impact factor of the journal)

Klebsiella pneumoniae Disassembles Host Microtubules in Lung Epithelial Cells

Investigators showed that during in vitro and in vivo K. pneumoniae infections of lung epithelia, microtubules were severed and then eliminated. This destruction did not require direct association of K. pneumoniae with the host cells, as microtubules were disassembled in cells that were distant from the infecting bacteria. [Cell Microbiol] Abstract

A Standardized Herbal Extract PM014 Ameliorates Pulmonary Fibrosis by Suppressing the TGF-β1 Pathway

The authors provide in vitro evidence suggesting that PM014 inhibited TGF-β1-induced epithelial-mesenchymal transition and fibroblast activation in alveolar epithelial cells and human lung fibroblasts from healthy donor and idiopathic pulmonary fibrosis patients. [Sci Rep] Full Article

Experimental Evidence for Re-Secretion of PGE₂ across Rat Alveolar Epithelium by OATP2A1/SLCO2A1-Mediated Transcellular Transport

To investigate the role of OATP2A1 in PGE₂ handling by alveolar epithelium, researchers studied PGE₂ transport across and secretion from monolayers of rat type-1 alveolar epithelial-like cells obtained by trans-differentiation of type-2 alveolar epithelial cells isolated from male Wistar rats. [J Pharmacol Exp Ther] Abstract | Full Article

Glycosaminoglycans Are Differentially Involved in Bacterial Binding to Healthy and Cystic Fibrosis Lung Cells

Various alterations in gene expression in cystic fibrosis cells were found which affected glycosaminoglycan (GAG) structures and seemed to influence bacterial adherence to lung epithelium cells. Heparan sulfate appeared to be the most important GAG species involved in bacterial binding. [J Cyst Fibros] Abstract

LUNG CANCER

PLOD3 Promotes Lung Metastasis via Regulation of STAT3

Scientists revealed that procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD3) interacted with STAT3, thereby expressing matrix metalloproteinases and with urokinase plasminogen activator to enhance tumor metastasis. PLOD3 and the STAT3 pathway were significantly correlated in the metastatic foci of lung cancer patients; PLOD3-STAT3 levels were highly correlated with a poor prognosis. [Cell Death Dis] Full Article

Sulforaphane Metabolites Reduce Resistance to Paclitaxel via Microtubule Disruption

Researchers uncovered that either sulforaphane (SFN)-cysteine or SFN-N-acetyl-cysteine induced apoptosis via phosphorylated ERK1/2-mediated upregulation of 26-S proteasome and Hsp70, and downregulation of βIII-tubulin, XIAP, Tau, Stathmin1 and α-tubulin causing microtubule disruption in human paclitaxel-resistant non-small cell lung cancer cells. [Cell Death Dis] Full Article

Zbed3 Promotes Proliferation and Invasion of Lung Cancer Partly through Regulating the Function of Axin-Gsk3β Complex

In A549 and H1299 lung cancer cells, Zbed3 overexpression promoted cancer cell proliferation and invasiveness, as well as Wnt signaling and expression of downstream mediators, including β-catenin, cyclin D1 and MMP7. In contrast, the Zbed3 mutant failed to enhance β-catenin expression, and its ability to promote cancer cell proliferation and invasiveness was much less than wild-type Zbed3. [J Cell Mol Med] Full Article

Inactivation of ADAMTS18 by Aberrant Promoter Hypermethylation Contribute to Lung Cancer Progression

Overexpression of ADAMTS18 in lung cancer cells inhibited cell proliferation, migration, and invasiveness and induced G0/G1 cell cycle arrest. Furthermore, ADAMTS18 suppressed epidermal growth factor receptor/protein kinase B signaling, which sensitized lung cancer cells to cisplatin. [J Cell Physiol] Abstract

Impaired DNA Double-Strand Breaks Repair by Kinesin Family Member 4A Inhibition Renders Human H1299 Non-Small-Cell Lung Cancer Cells Sensitive to Cisplatin

Scientists demonstrated that cisplatin treatment stimulated the expression of kinesin family member 4A (KIF4A) protein in human non-small-cell lung cancer (NSCLC) cells. Depletion of KIF4A by small interfering RNA significantly enhanced cisplatin-induced cell cycle arrest in S and G2/M phases and cytotoxicity in human NSCLC cells. [J Cell Physiol] Abstract

Inhibition of Oncogenic Cap-Dependent Translation by 4EGI-1 Reduces Growth, Enhances Chemosensitivity and Alters Genome-Wide Translation in Non-Small Cell Lung Cancer

Treatment of cells with 4EGI-1 reduced cell proliferation, decreased cap-dependent complex formation, induced apoptosis, enhanced sensitivity to gemcitabine, and altered global cellular translation. Suppression of cap-dependent translation by 4EGI-1 resulted in diminished expression of oncogenic proteins c-Myc, Bcl-2, cyclin D1, and survivin, whereas β-actin expression was left unchanged. [Cancer Gene Ther] Abstract

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Bronchiectasis

Bronchiectasis can be the result of several different underlying disorders, and identifying the etiology is crucial to guide management. Although no therapy is licensed for bronchiectasis by regulatory agencies, evidence supports the effectiveness of airway clearance techniques, antibiotics and mucolytic agents, such as inhaled isotonic or hypertonic saline, in some patients. [Nat Rev Dis Primers] Abstract

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

Pulmatrix to Present Results from the Pulmazole (PUR1900) Phase I/Ib Study

Pulmatrix, Inc. will present the results of the recently completed Phase I/Ib clinical trial of Pulmazole, an inhaled dry-powder iSPERSE^™ formulation of itraconazole. [Press release from Pulmatrix, Inc. discussing research to be presented at the 2018 Annual Scientific Meeting of the American College of Allergy, Asthma, and Immunology, Seattle] Press Release

Ascentage Pharma Presenting New Clinical Data of Novel Dual Bcl-2/Bcl-XL Inhibitor APG-1252

Ascentage Pharma Group Corporation, Ltd. announced that the company presented new clinical data of the dual Bcl-2/Bcl-xL inhibitor APG-1252, a new oncology drug under development. [Press release from Ascentage Pharma Group Corporation, Ltd. (PR Newswire Association LLC.) discussing research presented at the Asia Conference on Lung Cancer 2018 (ACLC), Guangzhou] Press Release

Mersana Therapeutics Presents Pre-Clinical Data

Mersana Therapeutics, Inc. announced it will present data on two new, novel antibody-drug conjugate platforms. Additionally, the company will present pre-clinical data on the efficacy of XMT-1522 in non-small cell lung cancer patient-derived xenograft models. [Press release from Mersana Therapeutics discussing research to be presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Dublin] Press Release

U.S. FDA Approves LORBRENA^® (Lorlatinib) for Previously-Treated ALK-Positive Metastatic NSCLC

Pfizer Inc. announced that the FDA has approved LORBRENA^®, a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor for patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease; or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease. [Pfizer Inc.] Press Release

Once-Daily Trelegy Ellipta Gains Expanded COPD Indication in Europe

GlaxoSmithKline plc and Innoviva, Inc. announced that the European Commission has authorized an expanded label for once-daily Trelegy Ellipta, recognizing its effect on exacerbations and making it the first single inhaler triple therapy indicated for patients with moderate to severe COPD not adequately treated with dual bronchodilation or with an inhaled corticosteroid and a long-acting β2-agonist. [GlaxoSmithKline plc.] Press Release

Patients Launch New Study to Shed Light on EGFR-Positive Lung Cancers

The Addario Lung Cancer Medical Institute, Champions Oncology and EGFR Resisters announced the launch of a new study to create a novel bank of patient derived xenograft models to help researchers better understand why patients living with epidermal growth factor receptor (EGFR) positive lung cancer develop resistance to treatment over time, or do not respond at all. [The Addario Lung Cancer Medical Institute] Press Release

Dartmouth Faces Lawsuit Over Sexual Misconduct by Professors

Seven women filed a $70 million lawsuit against Dartmouth College over its alleged role in allowing a toxic culture to form, which led to harassment, discrimination, and assault. The lawsuit argues that the university failed to protect its students from misconduct, which in two cases included rape, The Chronicle of Higher Education reports. [The Scientist] Editorial

Brexit: What the Draft Deal Means for Science

After two years of negotiations, the first real glimmers of what Brexit might involve have emerged. On 14 November, the Cabinet, the UK government’s senior decision-making body, backed a draft agreement on the terms of the country’s withdrawal from the European Union. For science, many of the details that will be most relevant are still to be thrashed out. [Nature News] Editorial

NEW 2^nd Annual Meeting of the French Society for Stem Cell Research (FSSCR)
December 11, 2018
Nantes, France

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

NEW Staff Scientist/ Tier 2 Canada Research Chair – Lung Research (University of Toronto)

NEW Faculty Positions – Cancer-Focused Target & Drug Discovery (University of New Mexico)

Postdoctoral Research Fellow – Sepsis & Lung Inflammation Pathogenesis Research (Boston University)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Scholar – Cancer Metabolism (The Moffitt Cancer Center)

Chair – Cancer Metabolomics Non-Clinical (Imperial College of London)

Postdoctoral Position – Lung Cancer Biology (UT Southwestern Medical Center)

Postdoctoral Research Scientist – Modeling Infection in Human Lung Organoids (Columbia University)

Postdoctoral Position – Human Lung Organoid Research (Columbia University Medical Center)

Postdoctoral Research Associate – Lung Cancer & Hypoxia Signaling (University of Illinois Cancer Center)

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