Pulmonary Cell News Volume 6.26 | Jul 6 2017

TOP STORY

Human Embryonic Lung Epithelial Tips Are Multipotent Progenitors that Can Be Expanded In Vitro as Long-Term Self-Renewing Organoids

The authors hypothesized that the human distal tip epithelium is an analogous progenitor population and tested this by examining the morphology, gene expression and in vitro self-renewal and the differentiation capacity of human tips. Their experiments confirmed that human and mouse tips were analogous and identified signaling pathways that were sufficient for long-term self-renewal of human tips as differentiation-competent organoids. [Elife] Abstract | Full Article (Download)

(Ranked by impact factor of the journal)

Mitochondrial Quality Control in Alveolar Epithelial Cells Damaged by S. Aureus Pneumonia in Mice

Because the cell’s processes of mitochondrial quality control regulate the elimination and replacement of damaged mitochondria to support cell survival, researchers evaluated mitochondrial biogenesis and mitophagy in the alveolar region of mice in a validated S. aureus pneumonia model. They report that apart from cell lysis by direct contact with microbes, extensive oxidative mitochondrial damage was detected along with epithelial cell death. [Am J Physiol Lung Cell Mol Physiol] Abstract

Foxc2 Influences Alveolar Epithelial Cell Differentiation during Lung Development

Scientists identified lung abnormalities in Foxc2-knockout embryos during investigation of cardiac development. They clarified morphological characteristics during lung development using ICR-Foxc2 knockout lungs. In the Foxc2 knockout lungs, the capillary beds remained distant from the alveolar epithelium until the late stages, the number of type 2 alveolar cells per alveolar progenitor cell was lower and the type1 alveolar cells were thicker in Foxc2 knockout mice. [Dev Growth Differ] Abstract

LUNG CANCER

Blocking Autophagy Improves the Anti-Tumor Activity of Afatinib in Lung Adenocarcinoma with Activating EGFR Mutations In Vitro and In Vivo

Researchers investigated the autophagy induction as well as its influence on anti-lung adenocarcinoma activity of afatinib in two activating EGFR-mutants H1975 and H1650 cells. Growth inhibition and caspase-dependent apoptosis were observed in afatinib-treated H1975 and H1650 cells. They then confirmed afatinib-induced autophagy in H1975 and H1650 cells. [Sci Rep] Full Article

Integrated High Throughput Analysis Identifies GSK3 as a Crucial Determinant of p53-Mediated Apoptosis in Lung Cancer Cells

The authors determined the transcriptional profile of human non-small cell lung carcinoma A549 cells after treatment with two p53-activating chemical compounds, nutlin and RITA, which could induce A549 cell cycle arrest and apoptosis, respectively. Bioinformatics analysis of genome-wide gene expression data showed that distinct transcription profiles were induced by nutlin and RITA and 66 pathways were differentially regulated by these two compounds. [Cell Physiol Biochem] Full Article

Bisdemethoxycurcumin Sensitizes Cisplatin-Resistant Lung Cancer Cells to Chemotherapy by Inhibition of CA916798 and PI3K/AKT Signaling

Investigators assessed the effects of curcumin on regulating chemosensitivity in cisplatin-resistant non-small cell lung cancer cells in vitro and explored the underlying molecular mechanisms. Human cisplatin-sensitive A549 and cisplatin-resistant A549/CDDP lung adenocarcinoma cells were treated with curcumin to assess cell viability and gene modulations using quantitative reverse transcription–polymerase chain reaction and western blotting. [Apoptosis] Abstract

MicroRNA-145-3p Inhibits Non-Small Cell Lung Cancer Cell Migration and Invasion by Targeting PDK1 via the mTOR Signaling Pathway

Researchers explored the underlying mechanism involving miR-145-3p in the development and progression of non-small cell lung cancer (NSCLC) by targeting PDK1 via the mammalian target of rapamycin (mTOR) signaling pathway. Results showed lower levels of miR-145-3p and higher levels of PDK1 and mTOR in NSCLC tissues compared to the adjacent normal tissues. In vitro results showed that cell growth, cell motility and chemotaxis were all inhibited in cells transfected with miR-145-3p and those transfected with siPDK. [J Cell Biochem] Abstract

24-Methyl-Cholesta-5,24(28)-Diene-3β,19-diol-7β-Monoacetate Inhibits Human Small Cell Lung Cancer Growth In Vitro and In Vivo via Apoptosis Induction

Scientists investigated the anti-small cell lung cancer (SCLC) effects of 24-methyl-cholesta-5,24(28)-diene-3β,19-diol-7β-monoacetate (MeCDDA) in vitro and in vivo, as well as elucidated its underlying mechanism. Their results indicated that H1688 and H146 cells showed relevant sensitivity to MeCDDA, and the exposure to MeCDDA in SCLC cells caused dose-dependent growth inhibitory responses. [Mar Drugs] Full Article

Torilis Japonica Extract Fraction Compound, EGFR-Targeted Inhibition of Cancer Abnormal Metastasis in A549 Lung Cancer Cells

Researchers investigated the inhibitory effect of Torilis japonica extract (TJE) major fraction compound in A549 lung cancer cells by inhibiting epidermal growth factor receptor (EGFR) activity. They confirmed the inhibitory effect of TJE on the abnormal metastasis using an invasion assay and 3D cell culture method, as well as the inhibition of EGFR signaling pathway, co-binding with Stat3 and dimer formation for translocation to the nucleus. [Oncol Rep] Abstract

Endoplasmic Reticulum Stress in Lung Disease

Protein misfolding in the endoplasmic reticulum affects the pathogenesis of many diseases, ranging from pulmonary fibrosis to cancer. It is therefore important to understand how cells respond to endoplasmic reticulum stress and how this affects pulmonary tissues in disease [Eur Respir Rev] Full Article

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Sunovion Announces FDA Acceptance for Review of New Drug Application Resubmission for SUN-101/eFlow^® (Glycopyrrolate) for the Treatment of Chronic Obstructive Pulmonary Disease (COPD)

Sunovion Pharmaceuticals Inc. announced that the U.S. FDA has accepted for review the resubmission of the New Drug Application for SUN-101/eFlow^® for the long-term, maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema. [Sunovion Pharmaceuticals Inc.] Press Release

Genoptix’s Immuno-Oncology Testing Now Covers Additional Tumor Types

Genoptix, Inc. announced that it offers three diagnostic tests that support immunotherapy decisions for solid tumor cancers. PD-L1 IHC 22C3 pharmDx is an immunohistochemical test that detects the PD-L1 protein in non-small cell lung cancer tissue. It was the first U.S. FDA approved companion diagnostic to assess eligibility of non-small cell lung cancer patients for Merck’s KEYTRUDA^® lung cancer drug. [Genoptix, Inc. (PR Newswire Association LLC.)] Press Release

French Scientist Fined for Failure to Disclose Industry Ties

In an unprecedented court case in Paris, an eminent French lung specialist has been fined €50,000 and given a six-month suspended jail sentence because he didn’t disclose his ties to the oil industry during a Senate air-pollution inquiry. [Nature News] Editorial

House Lawmakers Balk at Most Trump Science Cuts in Early Bills

No. That’s the first official answer from lawmakers in the U.S. House of Representatives to President Donald Trump’s request to make deep budget cuts at several key science funding agencies. [ScienceInsider] Editorial

Europe’s Next Big Science-Funding Program Urged to Double Its Budget

Midway through the European Union’s sprawling seven-year, €75-billion research-funding program known as Horizon 2020, scientists are already angling for more money and less red tape in its successor. [Nature News] Editorial

Germany and Poland Launch Research ‘Twinning’ Effort

Germany and Poland are to jointly fund top scientists to start research groups at Polish institutes, in a scheme that could provide a new blueprint for east–west research collaboration in the European Union. [Nature News] Editorial

NEW Keystone Symposia: Endoderm Development and Disease: Cross-Organ Comparison and Interplay
February 25-March 1, 2018
Taos, New Mexico, United States

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NEW Senior Scientist – Lung Repair and Regeneration (AstraZeneca)

NEW Postdoctoral Fellow – Pathogenesis of Lung Diseases (Oklahoma State University)

Postdoctoral Fellow – Lung Microengineering (University of Colorado)

PhD Position – Lung Disease (Helmholtz Zentrum München)

Postdoctoral Associate – Lung Cancer Research (Weill Cornell Medicine)

Postdoctoral Research Training – Lung Disease (Baylor College of Medicine)

Research Fellow – Cancer Research (National University of Singapore)

Staff Research Scientist – Lung Injury (St. Michael’s Hospital)

Postdoctoral Research Scientist – miRNAs in Differentiation of Lung Progenitor Cells (Columbia University)

Postdoctoral Researcher – Inhalation & Developmental Toxicology (Louisiana State University)

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