Pulmonary Cell News Volume 9.05 | Feb 13 2020

TOP STORY

Mechanical Regulation of Glycolysis via Cytoskeleton Architecture

Scientists report that the transfer of human bronchial epithelial cells from stiff to soft substrates caused a downregulation of glycolysis via proteasomal degradation of the rate-limiting metabolic enzyme phosphofructokinase. [Nature] Abstract | Press Release

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Precise Targeting of miRNA Sites Restores CFTR Activity in CF Bronchial Epithelial Cells

Researchers reversed microRNA-mediated inhibition of CFTR using CFTR-specific target site blockers and developed a drug-device combination inhalation therapy for cystic fibrosis (CF). Lead microRNA expression was quantified in a series of human CF and non-CF samples and in vitro models. [Mol Ther] Abstract

Cytotoxicity and Genotoxicity of MWCNT-7 and Crocidolite: Assessment in Alveolar Epithelial Cells versus Their Coculture with Monocyte-Derived Macrophages

The authors compared the cytotoxicity and genotoxicity of multi-walled carbon nanotubes (MWCNT)-7 and crocidolite using A549 cells grown in a conventional monoculture or in co-culture with THP-1 macrophages. [Nanotoxicology] Abstract

PI3K-Akt-mTOR/PFKFB3 Pathway Mediated Lung Fibroblast Aerobic Glycolysis and Collagen Synthesis in Lipopolysaccharide-Induced Pulmonary Fibrosis

Investigators demonstrated that lipopolysaccharides promoted collagen synthesis in the lung fibroblasts through aerobic glycolysis via the activation of the PI3K-Akt-mTOR/PFKFB3 pathway. [Lab Invest] Abstract

LUNG CANCER

Regenerative Lineages and Immune-Mediated Pruning in Lung Cancer Metastasis

The authors showed that human primary lung adenocarcinomas were characterized by the emergence of regenerative cell types, typically seen in response to lung injury, and by striking infidelity among transcription factors specifying most alveolar and bronchial epithelial lineages. [Nat Med] Abstract

miR-196b-5p-Mediated Downregulation of TSPAN12 and GATA6 Promotes Tumor Progression in Non-Small Cell Lung Cancer

Up-regulated miR-196b-5p promoted lung cancer cell migration, proliferation, and cell cycle through directly targeting the tumor suppressors, GATA6 and TSPAN12. [Proc Natl Acad Sci USA] Abstract

The ACSL3-LPIAT1 Signaling Drives Prostaglandin Synthesis in Non-Small Cell Lung Cancer

By using lung cancer cell lines and clinically relevant Kras^G12D-driven mouse models, the authors showed that the long-chain acyl-CoA synthetase (ACSL3) channels arachidonic acid into phosphatidylinositols. [Oncogene] Full Article

lncRNA HOXB-AS3 Exacerbates Proliferation, Migration, and Invasion of Lung Cancer via Activating the PI3K-AKT Pathway

Functional assays showed that inhibition of HOXB-AS3 was able to repress A549 and H1975 cell proliferation, cell colony formation ability and triggered cell apoptosis. [J Cell Physiol] Abstract

miR-212-5p Exerts Tumor Promoter Function by Regulating the Id3/PI3K/Akt Axis in Lung Adenocarcinoma Cells

Investigators identified miR-212-5p as a negative post-transcriptional modulator of Id3. Id3 was lowly expressed and miR-212-5p was highly expressed in non-small-cell lung cancer tissues and cells. [J Cell Physiol] Abstract

Association of Divergent Carcinoembryonic Antigen Patterns and Lung Cancer Progression

Cell line experiments revealed that carcinoembryonic antigen expression (CEA) and cancer dissemination can be affected by EGFR-tyrosine kinase inhibitor selection. EGFR-mutant patients, exhibiting high CEA at initial diagnosis and low CEA disease progression, showed a potential toward displaying new metastasis. [Sci Rep] Full Article

(-)-Epigallocatechin Gallate Inhibits Stemness and Tumorigenicity Stimulated by AXL Receptor Tyrosine Kinase in Human Lung Cancer Cells

Cancer stem cells were obtained from tumor spheres of H1299 human lung cancer cells. Researchers studied low stiffness, a unique biophysical property of cancer cells, in cancer stem cellsand parental H1299. [Sci Rep] Full Article

Identification of Nagilactone E as a Protein Synthesis Inhibitor with Anticancer Activity

Researchers found that nagilactone E administration significantly suppressed the tumor growth without obvious adverse effects. RNA sequencing analysis was performed to study the mechanisms of nagilactone E. [Acta Pharmacol Sin] Abstract

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Immunotherapeutic Approaches for Small-Cell Lung Cancer

The authors describe the available data on clinical efficacy, the emerging evidence regarding biomarkers and ongoing clinical trials using immune-checkpoint inhibitors and other immunotherapies in patients with small-cell lung cancer. [Nat Rev Clin Oncol] Abstract

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Aduro Biotech Announces Milestone Achieved under Merck Collaboration for Initiation of Phase II Trial of Anti-CD27 Agonist MK-5890 in Non-Small Cell Lung Cancer

Aduro Biotech, Inc. announced that the company earned a $10.0 million development milestone payment under its worldwide licensing agreement with Merck for the initiation of a Phase II clinical trial of MK-5890, an anti-CD27 agonist, in non-small cell lung cancer. [Aduro Biotech, Inc.] Press Release

Novartis Announces MET Inhibitor Capmatinib (INC280), the First Potential Treatment for METex14 Mutated Advanced Non-Small Cell Lung Cancer, Granted Priority FDA Review

Novartis, Inc. announced that the FDA accepted and granted Priority Review to capmatinib’s New Drug Application. Capmatinib is a MET inhibitor being evaluated as a treatment for first-line and previously treated patients with locally advanced or metastatic MET exon 14 skipping mutated non-small cell lung cancer. [Novartis, Inc.] Press Release

vTv Therapeutics Announces Positive Results from Part Two of the Phase II Simplici-T1 Study of TTP399, Potential First-in-Class Oral Adjunctive Therapy for Patients with Type 1 Diabetes

vTv Therapeutics Inc. announced positive results from part two of the Phase II Simplici-T1 trial assessing TTP399 as an oral adjunctive therapy to insulin in adults with type 1 diabetes. [vTv Therapeutics Inc.] Press Release

Popular Preprint Servers Face Closure Because of Money Troubles

The rise of preprint repositories has helped scientists worldwide to share results and get feedback quickly. But several platforms that serve researchers in emerging economies are struggling to raise money to stay afloat. Repositories like INA-Rxiv and IndiaRxiv boost regional science, but finding cash to run them is proving difficult. [Nature News] Editorial

FDA Now Allows Certain Lab Animals to Be Retired and Adopted

The US Food and Drug Administration will now permit certain animals used in experiments to retire and be adopted rather than face euthanasia, according to internal documents reviewed by The Hill. Although the policy changed in November, there have not been any public statements from the agency. [The Scientist] Editorial

NEW Asthma: Making New Discoveries into Better Therapies
April 2-6, 2020
Snowbird, Utah, United States

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NEW Postdoctoral Scholar – Cancer Metabolism (The Ohio State University)

Postdoctoral Training Fellow – Stem Cells in Tuberculosis (The Francis Crick Institute)

Postdoctoral Position – Lung Stem Cell Research (Columbia University Medical Center)

Postdoctoral Fellowship – Stem Cell Niche in Lung Fibrosis (University of California)

Postdoctoral Scholarship – Cancer Drug Discovery (Karolinska Institutet)

Postdoctoral Position – Bronchial Epithelial Cell Analysis (University Medical Center Groningen)

Postdoctoral Fellowship – Airway Disease Immunology (La Jolla Institute for Immunology)

Multiple Investigator Positions – Cancer Research (Winthrop P. Rockefeller Cancer Institute)

Postdoctoral Positions – Cancer and Infection (Boston Children’s Hospital)

Postdoctoral Research Scientist – Cancer Research (The Beatson Institute for Cancer Research)

Postdoctoral Fellow – Lung Cancer (Weill Cornell Medicine)

Postdoctoral Fellowship – Lung Epithelium (Boston University)

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