Pulmonary Cell News Volume 2.14 | Apr 11 2013

Sputum PAI-1 Elevation by Oxidative Stress-Dependent NF-κB Activation in Chronic Obstructive Pulmonary Disease
This in vitro study showed that both hydrogen peroxide and cigarette smoke-conditioned medium induced plasminogen activator inhibitor-1 (PAI-1) production in A549 cells, and the production was inhibited by an inhibitor of I kappa B kinase-β in a concentration-dependent manner. [Chest] Abstract

Lipopolysaccharide-Treated Macrophages Cytokines Repress Surfactant Protein B in Lung Epithelial Cells
To investigate the mechanism of SFTPB repression, the human pulmonary epithelial NCI-H441 (H441) and NCI-H820 (H820) cells and RAW264.7 macrophages were treated with lipopolysaccharide (LPS). Whereas LPS did not decrease SFTPB transcripts in H441 or H820 cells, conditioned medium of LPS-treated RAW264.7 cells decreased SFTPB transcripts in H441 and H820 cells and inhibited SFTPB promoter activity in H441 cells. [Am J Resp Cell Mol] Abstract

Rac1 and Cdc42 Differentially Modulate Cigarette Smoke-Induced Airway Cell Migration through p120-Catenin-Dependent and Independent Pathways
Using primary human bronchial epithelial cells exposed to smoke-concentrated medium, researchers observed the translocation of Rac1 and Cdc42, but not RhoA, to the leading edge of polarized and migrating human bronchial epithelial cells. [Am J Pathol] Abstract

p53 Activation by Ni(II) Is a HIF-1α Independent Response causing Caspases 9/3-Mediated Apoptosis in Human Lung Cells
Scientists examined whether Ni(II) elicits a toxicologically significant activation of the tumor suppressor p53, which is typically associated with genotoxic responses. They found that treatments of H460 human lung epithelial cells with NiCl2 caused activating phosphorylation at p53-Ser15, accumulation of p53 protein and depletion of its inhibitor MDM4. [Toxicol Appl Pharm] Abstract

Regulation of Cigarette Smoke (CS)-Induced Autophagy by Nrf2
Using cigarette smoke (CS) extract as a surrogate for CS, scientists found that it markedly increased the expressions of both LC3B-I and LC3B-II as well as autophagosomes in airway epithelial cells. This is in contrast to the common autophagy inducer (i.e., starvation) that increases LC3B-II but reduces LC3B-I. [PLoS One] Full Article

Simultaneous Inactivation of GSK-3β Suppresses Quercetin-Induced Apoptosis by Inhibiting JNK Pathway
Scientists evaluated the apoptotic effect of quercetin and its molecular mechanisms in normal bronchial epithelial cells (BEAS-2B). Quercetin decreased the viability of BEAS-2B cells via apoptosis in a dose- and time-dependent manner. [Am J Physiol-Lung C] Abstract

Mechanism of E-Cadherin Redistribution in Bronchial Airway Epithelial Cells in a TDI-Induced Asthma Model
Investigators hypothesized that toluene diisocyanate (TDI) can injure E-cadherin both in normal and allergic-induced airway epithelium. To test this, they developed a murine model of TDI-induced asthma characterized by neutrophil-dominated airway inflammation, epithelial shedding, and obvious aberrant distribution of E-cadherin. Pretreatment with dexamethasone significantly rescued the immunoreactivity of E-cadherin, accompanied by increased neutrophils in bronchoalveolar lavage fluid. [Toxicol Lett] Abstract

LUNG CANCER

Tomatidine Inhibits Invasion of Human Lung Adenocarcinoma Cell A549 by Reducing Matrix Metalloproteinases Expression
Researchers examined the effect of tomatidine on the migration and invasion of human lung adenocarcinoma A549 cell in vitro. The data demonstrated that tomatidine does not effectively inhibit the viability of A549 cells. [Chem-Biol Interact] Abstract

Internalization of Bacillus intermedius Ribonuclease (BINASE) Induces Human Alveolar Adenocarcinoma Cell Death
Scientists found that binase selectively attacked human A549 alveolar adenocarcinoma cells to trigger an apoptotic response, whereas normal lung epithelial cells LEK were not affected by the ribonuclease. The tumor transformation led to the modification of certain cellular characteristics causing cell sensitivity to binase. [Toxicon] Abstract

The EGFR Family Members Sustain the Neoplastic Phenotype of ALK+ Lung Adenocarcinoma via EGR1
Investigators report that in ALK+ cell lines, inhibition of ALK signaling was associated with coactivation of several receptor tyrosine kinases, whose pharmacological suppression reverted the partial resistance to ALK blockade. Remarkably, ERBB2 signaling synergized with ALK and contributed to the neoplastic phenotype. [Oncogenesis] Full Article

Novocure Presents Preclinical Data at the American Association for Cancer Research (AACR)
Novocure announced that new data from preclinical testing of NovoTTF Therapy in non-small cell lung carcinoma, ovarian and pancreatic cancer have been presented. The new data builds on existing published research describing the potential efficacy of NovoTTF Therapy in a wide range of solid tumors. [Press release from PR Newswire Association LLC discussing results presented at The American Association for Cancer Research Annual Meeting 2013, Washington] Press Release

ARIAD Presents New Preclinical Data Showing AP26113 Inhibits Clinically Relevant Mutants of ALK and ROS1
ARIAD Pharmaceuticals, Inc. announced the presentation of preclinical data on AP26113, an investigational inhibitor of anaplastic lymphoma kinase (ALK), epidermal growth factor receptor, and c-ros oncogene 1 (ROS1). [Press release from ARIAD Pharmaceuticals, Inc. discussing results presented at The American Association for Cancer Research Annual Meeting 2013, Washington] Press Release

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Helix Biopharma Corp. Initiates Enrollment for Third Cohort and Expansion of Centers in Polish Phase I/II Clinical Study of Its Lung Cancer Drug Candidate L-DOS47
Helix BioPharma Corp. announced the opening of patient screening for the third dose level cohort in its ongoing Phase I/II clinical safety, tolerability and preliminary efficacy study of L-DOS47 in Poland. [Helix Biopharma Corp.] Press Release

OncoGenex Announces Plans for the Initiation of the Spruce™ Clinical Trial Evaluating OGX-427 in Combination with Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer
OncoGenex Pharmaceuticals, Inc. announced plans for the initiation of the Spruce clinical trial, an investigator-sponsored, randomized, double-blind, placebo-controlled Phase II study evaluating OGX-427 in patients with previously untreated advanced non-squamous non-small cell lung cancer. [OncoGenex Pharmaceuticals, Inc.] Press Release

New Asthma Treatment for Children: Activaero Reports Therapeutic Benefit and High Acceptance from Phase II Trial
Activaero GmbH, the therapeutic area specialist for respiratory diseases, announced positive results from its phase II trial in children with mild to moderate asthma. [Activaero GmbH] Press Release

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