Pulmonary Cell News Volume 5.44 | Nov 10 2016

TOP STORY

Vasculogenic Mimicry in Small Cell Lung Cancer

Researchers showed that small cell lung cancer (SCLC) patients have rare circulating tumor cells (CTC) subpopulations co-expressing vascular endothelial-cadherin (VE-cadherin) and cytokeratins consistent with vasculogenic mimicry, a process whereby tumor cells form ‘endothelial-like’ vessels. Single-cell genomic analysis reveals characteristic SCLC genomic changes in both VE-cadherin-positive and -negative CTCs. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Human Airway Organoid Engineering as a Step Toward Lung Regeneration and Disease Modeling

Scientists combined human adult primary bronchial epithelial cells, lung fibroblasts, and lung microvascular endothelial cells in supportive 3D culture conditions to generate airway organoids. They demonstrate that randomly-seeded mixed cell populations undergo rapid condensation and self-organization into discrete epithelial and endothelial structures that are mechanically robust and stable during long term culture. [Biomaterials] Abstract

SIRT3 Blocks Myofibroblast Differentiation and Pulmonary Fibrosis by Preventing Mitochondrial DNA Damage

Researchers determined the role of mitochondrial deacetylase, SIRT3 in transforming growth factor-β1 (TGF-β1)-induced myofibroblast differentiation in vitro and lung fibrosis in vivo. Treatment of human lung fibroblasts with TGFβ1 resulted in increased expression of fibrosis markers, smooth muscle alpha-actin, collagen-1 and fibronectin. [Am J Physiol Lung Cell Mol Physiol] Abstract

Amnion Epithelial Cells Promote Lung Repair via Lipoxin A₄

Investigators aimed to assess the effects of human amnion epithelial cells-derived proresolution lipoxin-A₄ on T-cell, macrophage, and neutrophil phenotype and function during the acute phase of bleomycin-induced lung injury. [Stem Cells Transl Med] Abstract

TNF Up-Regulates ST3GAL4 and Sialyl-Lewis^X Expression in Lung Epithelial Cells through an Intronic ATF2-Responsive Element

Scientists describe a TNF-responsive element in an intronic region of ST3GAL4 gene, whose TNF-dependent activity is repressed by extracellular-signal-regulated kinase/p38 and mitogen- and stress-activated kinase 1/2 inhibitors. This TNF-responsive element contains potential binding sites for ETS1 and ATF2 transcription factors related to TNF signaling. They also show that ATF2 is involved in TNF responsiveness, as well as in TNF-induced ST3GAL4 BX transcript and sLe^x over-expression in A549 lung epithelial cells. [Biochem J] Abstract

Comparative Analysis of Toxic Responses of Organic Extracts from Diesel and Selected Alternative Fuels Engine Emissions in Human Lung BEAS-2B Cells

Investigators characterized particles from standard diesel, biodiesel in its neat form and 30% by volume blend with diesel fuel, and neat hydrotreated vegetable oil. The concentration of polycyclic aromatic hydrocarbons and their derivatives in organic extracts was the lowest for NEXBTL100 and higher for biodiesel. They analyzed global gene expression changes in BEAS-2B cells following 4 hour and 24 hour treatment with extracts. [Int J Mol Sci] Full Article | Graphical Abstract

LUNG CANCER

A Transcriptional Signature Identifies LKB1 Functional Status as a Novel Determinant of MEK Sensitivity in Lung Adenocarcinoma

LKB1 is a commonly mutated tumor suppressor in non-small cell lung cancer that exerts complex effects on signal transduction and transcriptional regulation. The authors developed a transcriptional fingerprint assay representing this phenotype. This assay was predictive of LKB1 functional loss in cell lines and clinical specimens, even those without detected sequence alterations in the gene. [Cancer Res] Abstract

PROTOCADHERIN 7 Acts through SET and PP2A to Potentiate MAPK Signaling by EGFR and KRAS during Lung Tumorigenesis

Researchers examined cell-surface receptors that may act as drivers of lung tumorigenesis. They report that the PROTOCADHERIN PCDH7 is overexpressed frequently in non-small cell lung cancer tumors where this event is associated with poor clinical outcome. [Cancer Res] Abstract

Serglycin in Tumor Microenvironment Promotes Non-Small Cell Lung Cancer Aggressiveness in a CD44-Dependent Manner

Tumor microenvironment (TME) plays an active role in promoting tumor progression. To further understand the communication between TME and tumor cells, the authors aimed at investigating the involvement of CD44, a type I cell surface receptor, in the crosstalk between tumor cells and TME. [Oncogene] Full Article

PF4 Promotes Platelet Production and Lung Cancer Growth

Scientists identified platelet factor 4 (PF4, CXCL4) as an endocrine factor whose overexpression in tumors correlates with decreased overall patient survival. Furthermore, engineered PF4 over-production in a Kras-driven lung adenocarcinoma genetic mouse model expanded megakaryopoiesis in bone marrow, augmented platelet accumulation in lungs, and accelerated de novo adenocarcinogenesis. [Cell Rep] Full Article | Graphical Abstract

IL-17 Promotes Angiogenic Factors IL-6, IL-8, and VEGF Production via Stat1 in Lung Adenocarcinoma

The authors found that tumor microvessel density was positively associated with interleukin (IL)-17, IL-6, L-8, and vascular endothelial cell growth factor (VEGF) expression in human lung adenocarcinoma tissues, and it was increased in tumor tissues of A549-IL-17 cell-bearing nude mice. [Sci Rep] Full Article

Myofibroblasts and Lung Fibrosis Induced by Carbon Nanotube Exposure

In view of the apparent fibrogenic activity of carbon nanotubes (CNT) and the emerging role of myofibroblasts in the development of organ fibrosis, the authors discuss recent findings on CNT-induced lung fibrosis with emphasis on the role of myofibroblasts in the pathologic development of lung fibrosis. [Part Fibre Toxicol] Full Article

Targeting the KRAS Pathway in Non-Small Cell Lung Cancer

The authors provide an overview of the KRAS pathway in lung cancer and related therapeutic strategies under investigation. [Oncologist] Full Article

Regeneration of the Aging Lung: A Mini-Review

In this review, the authors examine aging as a process dependent on specific changes in molecular pathways within multiple lung cell populations. [Gerontology] Full Article

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

Case-Coulter Translational Research Partnership Awards $1 Million for Promising University-Based Biomedical Engineering Technologies

The Case-Coulter Translational Research Partnership announced more than $1 million in funding and support for the 2016 cycle. Four projects were selected for full program funding. Projects range from diagnostic and screening technologies to cancer therapeutics. [Case Western Reserve University] Press Release

Bristol-Myers Squibb and Infinity Pharmaceuticals Announce Clinical Collaboration to Evaluate Opdivo (Nivolumab) in Combination with IPI-549 in Advanced Solid Tumors

Bristol-Myers Squibb Company and Infinity Pharmaceuticals, Inc. announced a clinical trial collaboration to evaluate Bristol-Myers Squibb’s Opdivo in combination with Infinity’s IPI-549 in patients with advanced solid tumors. [Bristol-Myers Squibb] Press Release

Weill Cornell Medicine and the New York Genome Center Awarded NCI Grant to Create Specialized Genomic Data Center

Weill Cornell Medicine and the New York Genome Center were recently awarded a federal grant from the National Cancer Institute (NCI) to support a joint cancer genomics data center for the research and clinical interpretation of tumors. The grant will provide funding of $490,000 per year over the next five years. [Weill Cornell Medicine] Press Release

IBM Watson Health and Broad Institute Launch Major Research Initiative to Study Why Cancers Become Drug Resistant

IBM Watson Health and the Broad Institute of MIT and Harvard today announced a research initiative aimed at discovering the basis of cancer drug resistance. The five year, $50 million project will study thousands of drug resistant tumors and draw on Watson’s computational and machine learning methods to help researchers understand how cancers become resistant to therapies. [Broad Institute] Press Release

The Quiet Rise of the NIH’s Hot New Metric

Biomedical funders worldwide are adopting the US agency’s free Relative Citation Ratio to analyze grant outcomes. [Nature News] Press Release

Donald Trump’s US Election Win Stuns Scientists

Republican businessman and reality-television star Donald Trump will be the United States’ next president. Although science played only a bit part in this year’s dramatic, hard-fought campaign, many researchers expressed fear and disbelief as Trump defeated former secretary of state Hillary Clinton. [Nature News] Press Release

NEW 2017 European Cancer Congress
January 27-30, 2017
Amsterdam, Netherlands

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

NEW Scientists/Physicians – Laboratory/Translational/Clinical Research in Lung Cancers (University of New Mexico Comprehensive Cancer Center (UNMCCC))

Postdoctoral Research Fellow – Cancer GeneticsEpigenetics (Fred Hutchinson Cancer Research Center)

Postdoctoral Researcher – Lung Cancer (Northwestern University)

Postdoctoral Fellow – Lung Biology (Boston University)

Cell Biologist – Pulmonary Vascular Signaling (University of Maryland)

Research Fellow(s) – Pulmonary Research (Imperial College London)

Postdoctoral Position – Virus-Induced Lung Repair (Max Planck Institute for Heart and Lung Research)

Associate/Full Professor – Various Projects (University of California, San Francisco)

Postdoctoral Training Fellow, Lung Cancer and Drug Resistance (Institute of Cancer Research)

Professor Position – Pulmonary Cell Research (University of Pennsylvania)

Postdoctoral Research Fellowship – Lung Disease (Johns Hopkins University)

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