Pulmonary Cell News Volume 8.04 | Feb 7 2019

TOP STORY

SMARCA4 Loss Is Synthetic Lethal with CDK4/6 Inhibition in Non-Small Cell Lung Cancer

Researchers recently uncovered that SMARCA4 (BRG1) loss in an ovarian cancer subtype causes cyclin D1 deficiency leading to susceptibility to CDK4/6 inhibition. They showed that this vulnerability is conserved in non-small cell lung cancer (NSCLC), where SMARCA4 loss also results in reduced cyclin D1 expression and selective sensitivity to CDK4/6 inhibitors. [Nat Commun] Full Article

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Analyses of Alveolar Epithelial Injury via Lipid-Related Stress in Mammalian Target of Rapamycin Inhibitor-Induced Lung Disease

The authors investigated the relationship between lipid metabolism and alveolar epithelial injury, focusing on peroxisome proliferator-activated receptor-γ as a lipid stress-related factor in mammalian target of rapamycin inhibitor-induced lung injury. [Lab Invest] Abstract

Molecular Hydrogen Attenuates Gefitinib-Induced Exacerbation of Naphthalene-Evoked Acute Lung Injury through a Reduction in Oxidative Stress and Inflammation

Naphthalene decreased glutathione in the lung, increased malondialdehyde in the plasma, and increased 4-hydroxy-2-nonenal production in airway cells, all of which were mitigated by hydrogen (H₂)-rich water, indicating that the H₂-rich water reverses cellular damage to the bronchial wall caused by oxidative stress. [Lab Invest] Abstract

A Simple Protocol for Isolating Mouse Lung Endothelial Cells

Scientists describe a simple, and reproducible protocol for the isolation and culture of mouse lung endothelial cells from adult mice using collagenase I-based enzymatic digestion, followed by sequential sorting with PECAM1 and ICAM2 coated microbeads. [Sci Rep] Full Article

LUNG CANCER

Targeting Notch Activation in Small Cell Lung Cancer through LSD1 Inhibition

Investigators found that exposure to the selective lysine-specific histone demethylase 1A inhibitor iadademstat activated the NOTCH pathway, resulted in the suppression of the transcription factor ASCL1 and the repression of small cell lung cancer tumorigenesis. [Sci Signal] Full Article

CHD1L Contributes to Cisplatin Resistance by Upregulating the ABCB1-Nf-κB Axis in Human Non-Small-Cell Lung Cancer

By employing immunohistochemistry, scientists analyzed the expression of chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) in non-small-cell lung cancer (NSCLC) samples and elucidated the roles and mechanism of CHD1L in NSCLC chemoresistance. [Cell Death Dis] Full Article

Metformin Enhances the Radiosensitizing Effect of Cisplatin in Non-Small Cell Lung Cancer Cell Lines with Different Cisplatin Sensitivities

Human non-small cell lung cancer cell lines, A549 and H460, were treated with metformin, cisplatin or a combination of both drugs before ionizing radiation. Cell proliferation, clonogenic assays, western blotting, cisplatin-DNA adduct formation and immunocytochemistry were used to characterize the treatments effects. [Sci Rep] Full Article

Nickel-Induced VEGF Expression via Regulation of Akt, ERK1/2, NFκB, and Ampk Pathways in H460 Cells

This study revealed the occurrence of vascular endothelial growth factor induction in human non-small-cell lung cancer H460 cells exposed to NiCl₂. Exposing H460 cells to NiCl₂ activated extracellular signal-regulated protein kinase, nuclear factor kappa B, and protein kinase B as well as downregulated AMP activated protein kinase expression. [Environ Toxicol] Abstract

CHAF1B Promotes Proliferation and Reduces Apoptosis in 95-D Lung Cancer Cells and Predicts a Poor Prognosis in Non-Small Cell Lung Cancer

Researchers showed that CHAF1B was highly expressed in non-small cell lung cancer lung tissues and 95-D cells. CHAF1B knockdown in 95-D cells markedly inhibited tumour proliferation, reduced colony formation, induced cell cycle arrest and promoted apoptosis. [Oncol Rep] Abstract

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Comparing and Contrasting Predictive Biomarkers for Immunotherapy and Targeted Therapy of NSCLC

The authors compare and contrast the clinical development of immunotherapy and oncogene-directed therapy for non-small-cell lung cancer, focusing on the role of predictive biomarkers. [Nat Rev Clin Oncol] Abstract

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Pulmatrix Receives IND Approval for Pulmazole Phase II Clinical Study

Pulmatrix, Inc. announced that the US FDA completed its review of their Investigational New Drug (IND) Application and notified the company that they are authorized to initiate a Phase II clinical investigation for Pulmazole – an inhaled iSPERSETM formulation of the anti-fungal drug itraconazole for the treatment of allergic bronchopulmonary aspergillosis in patients with asthma. [Pulmatrix, Inc.] Press Release

Antidote Therapeutics Announces Collaboration with National Cancer Institute to Develop Ati-1013, a Novel Nicotine-Binding Antibody, for Reducing Lung Cancer in High Risk Smokers

Antidote Therapeutics, Inc. announced it has entered into a collaboration with the National Cancer Institute to further develop its lead compound, ATI-1013, to a successful filing of an Investigational New Drug application. [Antidote Therapeutics] Press Release

GSK and Merck KGaA, Darmstadt, Germany Announce Global Alliance to Jointly Develop and Commercialize M7824, a Novel Immunotherapy with Potential in Multiple Difficult-to-Treat Cancers

GlaxoSmithKline plc and Merck KGaA, Darmstadt, announced that they have entered into a global strategic alliance to jointly develop and commercialize M7824. M7824 is an investigational bifunctional fusion protein immunotherapy that is currently in clinical development, including potential registration studies, for multiple difficult-to-treat cancers. This includes a Phase II trial to investigate M7824 compared with pembrolizumab as a first-line treatment in patients with PD-L1 expressing advanced non-small cell lung cancer. [GlaxoSmithKline plc] Press Release

Taiho Pharmaceutical and Cullinan Oncology Establish Collaboration to Develop TAS6417, Novel EGFR Tyrosine Kinase Inhibitor

Taiho Pharmaceutical Co., Ltd. and Cullinan Oncology, LLC announced an agreement to develop TAS6417, a novel EGFR (epidermal growth factor receptor) tyrosine kinase inhibitor discovered by Taiho Pharmaceutical. [Taiho Pharmaceutical Co., Ltd] Press Release

Kamada Announces Additional Interim Results from Phase II Proof of Concept Clinical Trial of Intravenous Alpha-1 Antitrypsin Treatment for Prevention of Lung Transplant Rejection

Kamada Ltd. announced interim results from the company’s Phase II trial of intravenous alpha-1 antitrypsin for the prevention of lung transplant rejection following one year of treatment for all patients. [Kamada] Press Release

NIH Asks Inspector General to Investigate 12 Allegations of Foreign Influence in US Research

The National Institutes of Health (NIH) has referred 12 allegations relating to foreign influence over US-funded research to a federal oversight office, Sen. Chuck Grassley said. Grassley, the chairman of the Senate Finance Committee, has repeatedly demanded information from the NIH after the agency revealed in August it was investigating a half-dozen academic institutions — specifically, researchers who may have failed to disclose financial ties to foreign governments. [STAT News] Editorial

University of California Staff Researchers Opt to Form a Union, Joining Postdocs

After five years as a postdoc—four of them at the University of California, Los Angeles—molecular biologist Christina Priest hit the university’s time limit for postdoctoral appointments and transitioned to a university staff position as a project scientist in the same lab. Now an at-will employee in a job with no set end time, she says she finds her work “continuing the project I initiated as a postdoc … not enormously different, [despite] more responsibility.” [Science Careers] Editorial

NEW Fibrosis and Tissue Repair: From Molecules and Mechanics to Therapeutic Approaches
February 19-23, 2020
Victoria, British Columbia, Canada

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NEW PhD Position – Lung Squamous Cell Carcinoma (Cancer Research UK Manchester Institute)

Research Associate – Cystic Fibrosis (Imperial College London)

Postdoctoral Position – Respiratory Research (Monell Chemical Senses Center)

Postdoctoral Scholar – Lung Repair & Regeneration (University of California San Francisco)

Postdoctoral Position – Lung Cancer (Albert Einstein College of Medicine of Yeshiva University)

Postdoctoral Fellow – Respiratory Research (Royal College of Surgeons Ireland)

Tenure Track Group Leader – Lung Epidemiology (Helmholtz-Center Munchen)

Tenure Track Investigator – Lung Cancer (Northwestern University)

Postdoctoral Research Associate – Lung Stem/Progenitor Cell Research (The University of Texas Health Science Center at Tyler)

Associate/Full Professor – Lung Biology & Medicine (University of California, Davis)

Postdoctoral Positions – Pluripotent Stem Cell-Derived Human Lung Organoids (Columbia University Irving Medical Center)

Associate Professor – Oncology (University of California, Davis)

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