Pulmonary Cell News Volume 2.49 | Dec 12 2013

Aldehyde Dehydrogenase 3A1 Protects Airway Epithelial Cells from Cigarette Smoke-Induced DNA Damage and Cytotoxicity
Aldehyde dehydrogenase 3A1 (ALDH3A1), an ALDH superfamily member, catalyzes the oxidation of reactive aldehydes, highly toxic components of cigarette smoke (CS). Even so, the role of ALDH3A1 in CS-induced cytotoxicity and DNA damage has not been examined. Among all of the ALDH superfamily members, ALDH3A1 mRNA levels showed the greatest induction in response to CS extract (CSE) exposure of primary human bronchial epithelial cells. [Free Radic Biol Med] Abstract

Neutrophils Are Needed for an Effective Immune Response against Pulmonary Rat Coronavirus Infection, but also Contribute to Pathology
Researchers evaluated the role of polymorphonuclear neutrophils (PMN) during a non-fatal pulmonary coronavirus infection in the natural host. Combined with in vitro experiments showing that PMN express cytokines and chemokines in response to rat coronavirus (RCoV)-infected alveolar epithelial cells, findings supported a role for PMN in eliciting an inflammatory response to RCoV infection. [J Gen Virol] Abstract

Caffeine Induces Alveolar Apoptosis in the Hyperoxia-Exposed Developing Mouse Lung
Caffeine treatment increased inflammation and worsened alveolar hypoplasia in hyperoxia exposed newborn mice. These changes were associated with decreased alveolar type II cell numbers, increased cell apoptosis, and decreased expression of A_2A receptors. [Pediatr Res] Abstract

LUNG CANCER

Autophagy Facilitates TLR4- and TLR3-Triggered Migration and Invasion of Lung Cancer Cells through the Promotion of TRAF6 Ubiquitination
Researchers showed that autophagy induced by toll-like receptor (TLR)4 or TLR3 activation enhances various cytokine productions through promoting TNF receptor-associated factor 6, E3 ubiquitin protein ligase ubiquitination and thus facilitates migration and invasion of lung cancer cells. [Autophagy] Abstract

Cancer-Derived Mutations in KEAP1 Impair NRF2 Degradation But Not Ubiquitination
Researchers characterized 18 KEAP1 mutations defined in a lung squamous cell carcinoma tumor set. Cell-based and in vitro biochemical analyses demonstrated that despite its inability to suppress NRF2 activity, the R320Q ‘superbinder’ mutant maintained the ability to ubiquitinate NRF2. [Cancer Res] Abstract

Upregulation of the MicroRNA Cluster at the Dlk1-Dio3 Locus in Lung Adenocarcinoma
RNAseq transcriptome analysis of Kras^G12D tumors from F1 hybrid mice revealed features specific to tumor samples. 12qF1 RNAs were repressed in cultured Kras^G12D tumor cells but reactivated when transplanted in vivo. [Oncogene] Abstract

Stearoyl-CoA Desaturase-1 Is a Key Factor for Lung Cancer-Initiating Cells
Researchers showed both by RNA interference and through the use of a small molecule inhibitor that stearoyl-CoA desaturase is required for lung cancer spheroids propagation both in stable cell lines and in malignant pleural effusions-derived primary tumor cultures. [Cell Death Dis] Full Article

Combination MET Inhibition and Topoisomerase I Inhibition Block Cell Growth of Small Cell Lung Cancer
Scientists investigated the therapeutic potential of combinatorial targeting of MET using SU11274 and topoisomerase (Top)1 using 7-ethyl-10-hydroxycamptothecin. In vitro stimulation of H82 cells revealed HGF-induced nuclear co-localization of p-MET and Top1. [Mol Cancer Ther] Abstract

Human Neural Stem Cells Expressing Carboxyl Esterase Target and Inhibit Tumor Growth of Lung Cancer Brain Metastases
Human neural stem cells expressing rabbit carboxyl esterase, which activates CPT-11, significantly inhibit the growth of A549 human non-small cell lung adenocarcinoma cells in the presence of CPT-11 in vitro and in vivo. [Cancer Gene Ther] Abstract

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Apollo Medical Holdings and Boehringer Ingelheim to Collaborate On Care of ApolloMed Accountable Care Organization (ACO) Patients with COPD
Apollo Medical Holdings, Inc. and Boehringer Ingelheim Pharmaceuticals, Inc. announced a partnership dedicated to managing the care of ApolloMed ACO patients with chronic obstructive pulmonary disease (COPD). [PR Newswire Association LLC] Press Release

Medimmune and The Johns Hopkins University Announce Five-Year, $6.5 Million Collaboration to Drive Medical Research and Discovery
MedImmune, AstraZeneca’s global biologics research and development arm, and The Johns Hopkins University announced they have entered into a five-year, $6.5 million research collaboration. The joint research projects will focus on MedImmune’s therapeutic areas of interest, including cardiovascular and metabolic disease; oncology; respiratory, inflammation and autoimmunity; infectious disease and neuroscience. [MedImmune, LLC] Press Release

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Clinical MD – Clinical Development Program for Oncology and Autoimmune Diseases (Immunomedics, Inc.)

Chief Medical Officer – Novel Therapeutics in Oncology and Autoimmune Disease (Immunomedics, Inc.)

Assistant Professor, Associate Professor, Professor – Lung Biology or Pulmonary and Critical Care Diseases (Boston University School of Medicine & Boston Medical Center)

Associate Scientist II/Scientist I – Respiratory, Autoimmunity and Inflammation Research (MedImmune)

PhD Position – Genetics of Non-Smoker Chronic Obstructive Pulmonary Disorders (Göttingen Center for Molecular Biosciences)

Postdoctoral Researcher – Metabolomics of Pulmonary Medicine (Karolinska Institute)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

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