Pulmonary Cell News Volume 7.41 | Oct 18 2018

TOP STORY

The Lineage-Defining Transcription Factors SOX2 and NKX2-1 Determine Lung Cancer Cell Fate and Shape the Tumor Immune Microenvironment

Researchers developed a genetic model of squamous NSCLC on the basis of overexpression of the transcription factor Sox2, which specifies lung basal cell fate, and loss of the tumor suppressor Lkb1. [Immunity] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Macrophages Promote Epithelial Proliferation Following Infectious and Non-Infectious Lung Injury through a Trefoil Factor 2-Dependent Mechanism

Conditional deletion of trefoil factor 2 (TFF2) in myeloid-restricted CD11c^Cre TFF2^flox mice exacerbated lung pathology and reduced the proliferative expansion of CD45⁻ EpCAM⁺ pro-SPC⁺ alveolar type 2 cells. [Mucosal Immunol] Full Article

Efferocytosis of Apoptotic Alveolar Epithelial Cells Is Sufficient to Initiate Lung Fibrosis

Scientists treated cultured alveolar macrophages with apoptotic type II alveolar epithelial cells (AECs) and found that the uptake induced pro-fibrotic gene expression. They also found that the repetitive intrapulmonary administration of apoptotic type II AEC or MLE-12 cells induced lung fibrosis. [Cell Death Dis] Full Article

Role of Reciprocal Interaction between Autophagy and Endoplasmic Reticulum Stress in Apoptosis of Human Bronchial Epithelial Cells Induced by Cigarette Smoke Extract

Investigators showed that cigarette smoke extract treatment induced apoptosis, autophagy, and expression of endoplasmic reticulum stress-related proteins in human bronchial epithelial cells. [IUBMB Life] Abstract

Reduced Folate Carrier-Mediated Methotrexate Transport in Human Distal Lung Epithelial NCl-H441 Cells

The uptake of methotrexate (MTX) was increased remarkably after pretreatment of the cell monolayer with ethylenediaminetetraacetic acid in H441 cells but not in A549 cells, indicating the contribution of the basolaterally located transporter. Folic acid and thiamine monophosphate, reduced folate carrier inhibitors, inhibited the uptake of MTX from the basolateral side of the H441 cells. [J Pharm Pharmacol] Abstract

LUNG CANCER

KRAS G12C NSCLC Models Are Sensitive to Direct Targeting of KRAS in Combination with PI3K Inhibition.

To identify strategies to maximally leverage direct KRAS inhibition investigators defined the response of a panel of NSCLC models bearing the KRAS G12C activating mutation in vitro and in vivo. The G12Ci+PI3Ki combination was effective in vitro and in vivo on models resistant to single agent ARS1620 including patient derived xenografts models. [Clin Cancer Res] Abstract | Full Article

Deletion of ATM in Tumor but Not Endothelial Cells Improves Radiation Response in a Primary Mouse Model of Lung Adenocarcinoma

The authors used dual recombinase technology in a primary murine lung cancer model to test whether tumor cells or endothelial cells are critical high dose RT targets. Deletion of Atm in tumor cells or endothelial cells had no impact on tumor growth in the absence of radiation. [Cancer Res] Abstract

Interferon-Induced Transmembrane Protein 1-Mediated EGFR/SOX2 Signaling Axis Is Essential for Progression of Non-Small Cell Lung Cancer

Epidermal growth factor receptor/sex-determining region Y-box 2 (EGFR/SOX2) signaling axis was compromised in the absence of interferon-induced transmembrane protein 1 (IFITM1), and the ectopic expression of SOX2 partially rescued the defects caused by IFITM1 depletion. [Int J Cancer] Abstract | Full Article

CLDN18.1 Attenuates Malignancy and Related Signaling Pathways of Lung Adenocarcinoma In Vivo and In Vitro

When restored in LuAd cells that had lost expression, CLDN18.1 markedly attenuated malignant properties including xenograft tumor growth in vivo as well as cell proliferation, migration, invasion and anchorage-independent colony formation in vitro. [Int J Cancer] Abstract

Regulation of Sox2 and Stemness by Nicotine and Electronic-Cigarettes in Non-Small Cell Lung Cancer

Researchers demonstrated that nicotine could induce the expression of embryonic stem cell factor Sox2, which is indispensable for self-renewal and maintenance of stem cell properties in NSCLC cells. They further demonstrated that this occurred through a nicotinic acetylcholine receptor-Yap1-E2F1 signaling axis downstream of Src and Yes kinases. [Mol Cancer] Full Article

Functional Gene Knockout of NRF2 Increases Chemosensitivity of Human Lung Cancer A549 Cells In Vitro and in a Xenograft Mouse Model

Scientists utilized CRISPR/Cas9 to disable the nuclear factor erythroid 2- related factor (NRF2) gene in lung cancer cells by disrupting the NRF2 nuclear export signal domain; phenotypically, the protein was largely blocked from transiting into the nucleus after translation. [Mol Ther Oncolytics] Abstract | Full Article

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Pulmonary Surfactant and Drug Delivery: Focusing on the Role of Surfactant Proteins

The specific biophysical mode-of-action of the four surfactant proteins (SPs) affect the drug delivery process of nanomedicines both on the extra-and intracellular level, modulating pulmonary distribution, cell targeting and intracellular delivery. This knowledge can be harnessed to exploit SPs for the design of unique and bio-inspired drug delivery strategies. [J Control Release] Abstract | Graphical Abstract

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Eloxx Pharmaceuticals Presents Positive New Data for Lead Investigational Drug, ELX-02

Eloxx Pharmaceuticals, Inc. announced positive data demonstrating that ELX-02 showed significant increases in CFTR functional assay and mRNA levels across multiple CFTR nonsense mutations in cystic fibrosis patient-derived organoids. [Press release from Eloxx Pharmaceuticals, Inc. discussing research presented at the 32^nd North American Cystic Fibrosis Conference, Denver] Press Release

Vertex Data Presented

Vertex Pharmaceuticals Incorporated announced that eight scientific abstracts from the company’s portfolio of cystic fibrosis medicines are being presented. [Press release from Vertex Pharmaceuticals Incorporated discussing research to be presented at the 32^nd North American Cystic Fibrosis Conference, Denver] Press Release

Centre Georges François Leclerc Presents the Detailed Results of the First Two Stages of its Clinical Study in Lung Cancer

ONCODESIGN and Centre Georges François Leclerc announced the presentation of the detailed results of the first two stages of their clinical study on lung cancer. [Press release from ONCODESIGN discussing research presented at the 31^st EANM Conress, Dusseldorf] Press Release

Bristol-Myers Squibb Announces Phase III CheckMate -331 Study Does Not Meet Primary Endpoint of Overall Survival with Opdivo versus Chemotherapy in Patients with Previously Treated Relapsed Small Cell Lung Cancer

Bristol-Myers Squibb Company announced topline results from the Phase III CheckMate -331 study evaluating Opdivo versus the current standard of care, topotecan or amrubicin, in patients with SCLC who relapsed following platinum-based chemotherapy. [Bristol-Myers Squibb Company] Press Release

Savara Completes Enrollment in Pivotal Molgradex Impala Clinical Study for the Treatment of aPAP

Savara Inc. announced completion of the target enrollment of 135 patients in IMPALA, its global pivotal Phase III clinical study evaluating its lead product candidate Molgradex, an inhaled formulation of recombinant human granulocyte-macrophage colony-stimulating factor, for the treatment of autoimmune pulmonary alveolar proteinosis (aPAP). [Savara Inc.] Press Release

ORYZON Receives Approval to Start CLEPSIDRA: A Phase IIa Clinical Trial in Small Cell Lung Cancer with Iadademstat (ORY-1001)

Oryzon Genomics S.A. announced that it has received approval of a Clinical Trial Application, the European IND equivalent, from the Spanish Drug Agency to conduct a Phase IIa clinical study with Iadademstat in SCLC patients in first relapse. [Oryzon Genomics] Press Release

Proteostasis Therapeutics Announces Positive Preliminary Results from Proprietary Doublet in Cystic Fibrosis Patients

Proteostasis Therapeutics, Inc. announced positive preliminary results from three doublet cohorts of the company’s ongoing Phase I, randomized, double-blind, placebo-controlled studies of the company’s proprietary combination therapy doublet, PTI-808 and PTI-801, and an enrollment update from the triplet, PTI-808, PTI-801, and PTI-428, in subjects with cystic fibrosis. [Proteostasis Therapeutics, Inc.] Press Release

Daiichi Sankyo Initiates Phase I Study of AXL Inhibitor DS-1205 in Patients with EGFR-Mutated Metastatic Non-Small Cell Lung Cancer

Daiichi Sankyo Company, Limited announced that the first patient has been dosed in a first-in-human Phase I study assessing the safety and tolerability of DS-1205, a highly selective investigational AXL inhibitor, in combination with gefitinib in patients with metastatic or unresectable epidermal growth factor receptor (EGFR)-mutated NSCLC who have progressed on therapy with tyrosine kinase inhibitors. [Daiichi Sankyo Company, Limited (PR Newswire Association LLC)] Press Release

Immune Pharmaceuticals Announces Positive Preclinical Results in Asthma

Immune Pharmaceuticals, Inc. announced positive results from a mouse study demonstrating that blockade of eotaxin-1 reduces lung inflammation and has a broader inhibitory effect on inflammatory cells than does blockade of interleukin-5. [Immune Pharmaceuticals, Inc.] Press Release

Wyss Institute Receives Grant from Cystic Fibrosis Foundation

Initiative will use the Institute’s Human Organ Chip technology to model lung infection and inflammation in patients with cystic fibrosis. [Hansjörg Wyss Institute for Biologically Inspired Engineering at Harvard University] Press Release

‘Vast Majority’ of NIH Chimps to Be Moved to Retirement Sanctuary, Agency Says

The National Institutes of Health (NIH) plans to move the “vast majority” of its chimpanzees formerly used for research to a sanctuary in Louisiana, Director Francis Collins told STAT. The NIH released a slate of decisions laying out its plans for the hundreds of chimps that are still living in agency-supported research facilities. [STAT News] Editorial

‘We Are Headed for a Very Dark Period.’ Brazil’s Researchers Fear Election of Far-Right Presidential Candidate

Beset by economic woes and dissatisfied with the left-wing politicians in power for most of the past 15 years, Brazil appears poised to make a hard turn and elect a far-right candidate, Jair Bolsonaro, as its next president. His rapid ascent has unnerved local researchers, who worry about the future of Brazilian science, the protection of the country’s biodiversity, and its role in the global struggle against climate change. [ScienceInsider] Editorial

NEW 15^th Annual Stem Cell Symposium: Stem Cells B2B – Bench to Bedside
February 1, 2019
Los Angeles, California, United States

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

NEW Postdoctoral Position – Lung Cancer Biology (UT Southwestern Medical Center)

NEW Postdoctoral Research Scientist – Modeling Infection in Human Lung Organoids (Columbia University)

Postdoctoral Research Fellow – Respiratory Epithelial Cell Biology (STEMCELL Technologies Inc.)

Postdoctoral Position – Human Lung Organoid Research (Columbia University Medical Center)

Research Associate – Lung Cancer (University of Cambridge)

Tenure Track or Early Career Investigator – Cell & Developmental Biology Center (National Heart, Lung & Blood Institute)

Postdoctoral Research Associate – Lung Cancer & Hypoxia Signaling (University of Illinois Cancer Center)

Postdoctoral Fellow – Vascular and/or Lung Biology (Yale University)

Postdoctoral Fellow – Sepsis and Pulmonary Injury Research (University of Maryland)

Research Fellow – Development of Occupational Diseases (CDC/National Institute for Occupational Safety and Health)

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