Pulmonary Cell News Volume 7.07 | Feb 22 2018

TOP STORY

DNA Repair Deficiency Sensitizes Lung Cancer Cells to NAD⁺ Biosynthesis Blockade

Using unbiased proteomic and metabolic high-throughput profiling on a unique in-house generated isogenic model of ERCC1 deficiency, scientists found marked metabolic rewiring of ERCC1-deficient populations, including decreased levels of the metabolite NAD⁺ and reduced expression of the rate-limiting NAD⁺ biosynthetic enzyme nicotinamide phosphoribosyltransferase. [J Clin Invest] Abstract | Full Article

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Pulmonary Alveolar Type I Cell Population Consists of Two Distinct Subtypes that Differ in Cell Fate

Pulmonary alveolar type I (AT1) cells retain their cellular plasticity during injury-induced alveolar regeneration. However, very little is known about the developmental heterogeneity of the AT1 cell population. Investigators identified a robust genetic marker of postnatal AT1 cells, insulin-like growth factor-binding protein 2. [Proc Natl Acad Sci USA] Full Article | Press Release

Lack of Cystic Fibrosis Transmembrane Conductance Regulator Disrupts Fetal Airway Development in Pigs

The authors studied primary pig airway epithelial cell cultures and found that fibroblast growth factor-10 increased cellular proliferation (non-CF and CF) and CF conductance regulator (CFTR) expression/function (in non-CF only). In pseudoglandular stage lung tissue, CFTR protein was exclusively localized to the leading edges of budding airways in non-CF (but not CF) lungs. [Lab Invest] Abstract

Bronchial Extracellular Matrix from COPD Patients Induces Altered Gene Expression in Repopulated Primary Human Bronchial Epithelial Cells

To explore the impact of an aberrant extracellular matrix on epithelial cell phenotype in COPD, scientists developed a new ex vivo model, in which normal human bronchial epithelial cells repopulate and differentiate on decellularized human bronchial scaffolds derived from COPD patients and healthy individuals. [Sci Rep] Full Article

Interleukin-33 Is Activated by Allergen- and Necrosis-Associated Proteolytic Activities to Regulate Its Alarmin Activity during Epithelial Damage

Researchers report that processing of full length interleukin (IL)-33 can occur in mice deficient in these immune cell protease activities. They sought alternative mechanisms for the proteolytic activation of IL-33 and discovered that exogenous allergen proteases and endogenous calpains, from damaged airway epithelial cells, can process full length IL-33 and increase its alarmin activity up to ~60-fold. [Sci Rep] Full Article

Molecular Characterization of Gene Regulatory Networks in Primary Human Tracheal and Bronchial Epithelial Cells

These data reveal an airway cell signature that is divergent from other epithelial cell types and from common airway epithelial cell lines. The differences between tracheal and bronchial cells are clearly evident as are common regulatory features. [J Cyst Fibros] Abstract

LUNG CANCER

The E3 Ubiquitin Ligase NEDD4 Mediates Cell Migration Signaling of EGFR in Lung Cancer Cells

Scientists elucidated the mechanism by which NEDD4 mediates the EGFR lung cancer migration signaling. Knockdown of NEDD4 significantly reduced EGF-stimulated cell migration in non-small cell lung carcinoma cells. [Mol Cancer] Full Article

miR-19b Enhances Proliferation and Apoptosis Resistance via the EGFR Signaling Pathway by Targeting PP2A and BIM in Non-Small Cell Lung Cancer

Researchers showed that 17 miRNAs, including members of the miR-17~ 92 cluster, are dysregulated following PI3K/AKT inhibition of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) cells. These findings were closely mirrored by attenuation of miR-17~ 92 family member miR-19b in NSCLC cell lines, which resulted in reduced phosphorylation of ERK, AKT and STAT and effector proteins in EGFR mutant NSCLC cells. [Mol Cancer] Full Article

Long Noncoding RNA SNHG1 Promotes Non-Small Cell Lung Cancer Progression by Up-Regulating MTDH via Sponging miR-145-5p

Investigators discovered that SNHG1 was markedly up-regulated in non-small cell lung cancer tissues and cells and that SNHG1 silencing decreased tumor volumes. They explored its regulatory mechanism and found that SNHG1 directly bound to miRNA-145-5p, isolating miR-145-5p from its target gene MTDH. [FASEB J] Abstract | Full Article

IL-32 Gamma Reduces Lung Tumor Development through Upregulation of TIMP-3 Overexpression and Hypomethylation

The authors investigated whether interleukin (IL)-32γ mice inhibited lung tumor development through overexpression of tissue inhibitor of metalloproteinase 3 (TIMP-3) and its methylation. To explore the possible underlying mechanism, lung cancer cells were transfected with IL-32γ cDNA plasmid. [Cell Death Dis] Full Article

S100A4 Promotes Lung Tumor Development through β-Catenin Pathway-Mediated Autophagy Inhibition

The results revealed that extracellular S100A4 or overexpression of S100A4 inhibited starvation-induced autophagy and promoted cell proliferation in lung cancer cells in vitro; whereas small interfering RNA-mediated suppression of S100A4 increased autophagy and reduced cell viability in both A549 and LLC cells. [Cell Death Dis] Full Article

The Function and Therapeutic Targeting of Anaplastic Lymphoma Kinase (ALK) in Non-Small Cell Lung Cancer (NSCLC)

The clinical success of three ALK inhibitors has led to the development of next-generation ALK inhibitors with even greater potency and selectivity. However, patients inevitably develop resistance to ALK inhibitors leading to tumor relapse that commonly manifests in the form of brain metastasis. [Mol Cancer] Full Article

KRAS Oncogene in Non-Small Cell Lung Cancer: Clinical Perspectives on the Treatment of an Old Target

The authors review the current knowledge about KRAS-mutated lung adenocarcinoma, including a historical overview, the biology of the molecular pathways involved, the clinical relevance of KRAS mutations as a prognostic and predictive marker and the potential therapeutic approaches for a personalized treatment of KRAS-mutated non-small cell lung cancer patients. [Mol Cancer] Full Article

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

Pharmamar’s Lurbinectedin Atlantis Trial Design and Data in Small-Cell Lung Cancer Will Be an Oral Presentation

Dr. Anna Farago, oncologist form the Massachusetts General Hospital, will explain in an oral presentation what kind of molecule lurbinectedin is, how it works, and what results were obtained from the Phase I/II clinical study in combination with doxorubicin for the treatment of small-cell lung cancer, that led to the of the pivotal Phase III ATLANTIS study, which is nearing completion. [Press release from PharmaMar, S.A. discussing research to be presented at the International Association for the Study of Lung Cancer (IASLC) 18^th Lung Cancer Targeted Therapies, Santa Monica] Press Release

Ascentage Pharma to Present at the IASLC 18^th Lung Cancer Targeted Therapies Meeting

Ascentage Pharma announced the presentation of preliminary data from its ongoing Phase I trials of its lead product candidate APG-1252, a novel Bcl-2/Bcl-xL dual inhibitor. [Press release from Ascentage Pharma discussing research to be presented at the International Association for the Study of Lung Cancer (IASLC) 18^th Lung Cancer Targeted Therapies, Santa Monica] Press Release

US FDA Approves Imfinzi for Unresectable Stage III Non-Small Cell Lung Cancer

AstraZeneca and MedImmune announced that the FDA has approved Imfinzi for the treatment of patients with unresectable stage III non-small cell lung cancer whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. [AstraZeneca] Press Release 1 | Press Release 2 | Blog Post

Vertex Initiates First Phase III VX-659 Triple Combination Study in Certain People with Cystic Fibrosis

Vertex announced the initiation of the first Phase III study of VX-659, tezacaftor and ivacaftor as an investigational triple combination regimen for people with CF who have one F508del mutation and one minimal function mutation. [Vertex Pharmaceuticals Incorporated] Press Release

Daiichi Sankyo Initiates Phase I Study of DS-1062 in Patients with Advanced Non-Small Cell Lung Cancer

Daiichi Sankyo Company, Limited announced the first patient has been dosed in a Phase I study assessing the safety and tolerability of DS-1062, an investigational TROP2-targeting antibody drug conjugate, in patients with unresectable advanced non-small cell lung cancer who are refractory to or have relapsed following standard treatment or for whom no standard treatment is available. [Daiichi Sankyo Company, Limited (PR Newswire Association LLC.)] Press Release

Meet the Scientists Running to Transform Congress in 2018

The first big test for the cohort of science candidates comes on 6 March, when Texas holds the nation’s first primary elections. Several candidates are running to become Democratic nominees in that Lone Star state’s House districts. [ScienceInsider] Editorial

U.K. Scientists Increasingly Anxious about Brexit Confusion

With the second phase of Brexit negotiations approaching, scientists in the United Kingdom are urging their government to clarify its position on funding agreements and migration of research talent after the country separates from the European Union in March 2019. [ScienceInsider] Editorial

Half of Canada’s Government Scientists Still Feel Muzzled

More than half of government scientists in Canada—53%—do not feel they can speak freely to the media about their work, even after Prime Minister Justin Trudeau’s government eased restrictions on what they can say publicly, according to a survey released by a union that represents more than 16,000 federal scientists. [ScienceInsider] Editorial

Croatia’s Top Judge Sues National Ethics Panel after It Finds Him Guilty of Plagiarism

One of Croatia’s top judges is hitting back at the country’s national research ethics panel after having been found guilty of plagiarism. Miroslav Šeparović, president of the Constitutional Court of the Republic of Croatia, announced that he has filed criminal complaints against all five members of the Committee on Ethics in Science and Higher Education, after it concluded that Šeparović’s 2013 doctoral thesis about children’s rights in EU and Croatian law contained repeated instances of “incomplete and opaque citations” of other people’s work. [ScienceInsider] Editorial

NEW Cold Spring Harbor (CSH): Mouse Development, Stem Cells & Cancer
June 6-25, 2018
Cold Spring Harbor, New York, United States

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

NEW Research Fellow – Ex Vivo Response to PD-1 Blockade (Dana-Farber Cancer Institute)

Assistant Professor – Pulmonary Physiology (University of California, Riverside)

Multiple Positions – Pulmonary (University of Alabama at Birmingham)

Professor – Lung Cancer (University of Cincinnati)

Director – In Vitro Pharmacology (AstraZeneca)

Postdoctoral Fellow – Respiratory Therapy Area (AstraZeneca)

Postdoctoral Scholar – Stem Cell Biology and Cancer Biology (University of Iowa)

Postdoctoral Fellow – Lung Cancer (Van Ande Research Institute)

Postdoctoral Position – Biomedical Systems Biology (University of Zurich)

Postdoctoral Position – Pulmonary Disease Pathogenesis (Columbia University)

Postdoctoral Fellow – Lung Cancer (MD Anderson Cancer Center)

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