Pulmonary Cell News Volume 7.35 | Sep 6 2018

TOP STORY

Path to a Targeted Treatment for Small-Cell Lung Cancer?

Scientists at Fred Hutchinson Cancer Research Center revealed how losing a specific gene – which happens in about 15 percent of small-cell lung cancer patients – accelerated tumor formation in mice. And, most exciting to the researchers, these tumors seemed to be uniquely sensitive to a specific drug, which dramatically shrunk some tumors in mice with the mutation. [Press release from the Fred Hutchinson Cancer Research Center discussing online prepublication in Cancer Discov] Press Release | Abstract

(Ranked by impact factor of the journal)

Regulation of Human Airway Epithelial Tissue Stem Cell Differentiation by β-Catenin, P300, and CBP

Researchers reported that human bronchiolar tissue stem cell differentiation to mucus and ciliated cells could be divided into two stages, specification and commitment. A β-catenin/E1A-binding protein (P300) complex promoted mucus cell specification and β-catenin interacted with either P300 or cAMP response element binding protein (CBP) to inhibit ciliated cell commitment. [Stem Cells] Abstract

Characterization of a Lung Epithelium Specific E-Cadherin Knock-Out Model: Implications for Obstructive Lung Pathology

Investigators observed normal lung development at the time of birth in mice lacking E-cadherin in the lung epithelium. E-cadherin deficiency led to progressive epithelial damage in mice growing into adulthood, as evidenced by airway epithelial denudation, decreased zonula occludens-1 expression, loss of ciliated cells, and enlarged alveolar spaces. [Sci Rep] Full Article

Malignant Transformation of Human Bronchial Epithelial Cells Induced by Arsenic through STAT3/miR-301a/SMAD4 Loop

miR-301a was found to be upregulated during arsenic-induced BEAS-2B transformation and the overexpression of miR-301a was dependent on IL-6/STAT3 signaling. SMAD4 was confirmed to be a direct target of miR-301a in BEAS-2B cells and upregulation of SMAD4 was involved the restraining cell growth and migration. [Sci Rep] Full Article

Interrupted Reprogramming of Alveolar Type II Cells Induces Progenitor-Like Cells that Ameliorate Pulmonary Fibrosis

Scientists demonstrated that interrupted reprogramming resulted in controlled expansion of cell numbers yet preservation of the differentiation pathway to the alveolar epithelial lineage. When transplanted to the injured lungs, alveolar epithelial type II-induced progenitor-like cells were retained in the lung and ameliorated bleomycin-induced pulmonary fibrosis. [NPJ Regen Med] Full Article

LUNG CANCER

Gjb4 Serves as a Novel Biomarker for Lung Cancer and Promotes Metastasis and Chemoresistance via Src Activation

Gap junction beta-4 protein (Gjb4) activated Src signaling via MET, and overexpression of Gjb4 enhanced sphere-forming ability and anchorage-independent growth, which were reversed by inhibition of Src. Investigators demonstrated that Gjb4-mediated Src activation enhanced chemoresistance of cancer cells toward gemcitabine and etoposide. [Oncogene] Abstract

Targeting the EMT Transcription Factor TWIST1 Overcomes Resistance to EGFR Inhibitors in EGFR-Mutant Non-Small-Cell Lung Cancer

Scientists demonstrated that genetic silencing of TWIST1 or treatment with the TWIST1 inhibitor, harmine, resulted in growth inhibition and apoptosis in EGFR-mutant non-small-cell lung cancer. Genetic and pharmacological inhibition of TWIST1 in EGFR tyrosine kinase inhibitor (TKI)-resistant EGFR-mutant cells increased sensitivity to EGFR TKIs. [Oncogene] Abstract

miR-409 Inhibits Human Non-Small Cell Lung Cancer Progression by Directly Targeting SPIN1

The authors revealed that miR-409 inhibited the expression of Spindlin 1 (SPIN1) through binding directly to the 3′-untranslated region of SPIN1. Overexpression of miR-409 significantly suppressed cell migration, growth and proliferation by inhibiting SPIN1 in vitro and in vivo. [Mol Ther Nucleic Acids] Full Article

YXQ-EQ Induces Apoptosis and Inhibits Signaling Pathways Important for Metastasis in Non-Small Cell Lung Carcinoma Cells

External qi of Yan Xin Qigong (YXQ-EQ) induced apoptosis in A549 cells, resulting in a pronounced reduction in viability and clonogenic formation. This was associated with inhibition of phosphorylation of AKT and ERK1/2 and reduced expression of anti-apoptotic proteins BCL-xL, XIAP and survivin. [Cell Physiol Biochem] Full Article

Alectinib Resistance in ALK-rearranged Lung Cancer by Dual Salvage Signaling in a Clinically Paired Resistance Model

Increased apoptosis, reduction of tumor volume, and inhibition of MAPK and PI3K/AKT signaling molecules for proliferation and survival were observed when three kinases (Src, MET, and ALK) were inhibited. A patient-derived xenograft from alectinib-resistant cells indicated that combination therapy with saracatinib and crizotinib significantly decreased tumor size in vivo. [Mol Cancer Res] Abstract

CircRNA hsa_circ_100395 Regulates miR-1228/TCF21 Pathway to Inhibit Lung Cancer Progression

Researchers showed that hsa_circ_100395 served as a sponge for miR-1228 targeting TCF21 in lung cancer. Rescue assays indicated that hsa_circ_100395 regulated lung cancer cell proliferation, migration and invasion through modulating miR-1228/TCF21 pathway. [Cell Cycle] Abstract

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Oxidative, Inflammatory, Genetic, and Epigenetic Biomarkers Associated with Chronic Obstructive Pulmonary Disorder

The authors summarize findings that highlight the role of dimensions of chronic obstructive pulmonary disorder in the investigation of oxidative stress, inflammatory responses, genetic and epigenetic studies, and pharmacological and dietary antioxidant intervention. [J Cell Physiol] Abstract

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

Vium and 3Scan Collaborate to Transform Scientific Discovery with Breakthrough Disease Models to Improve Preclinical Research

Vium, Inc. announced it will collaborate with 3Scan, Inc. to quantify lung and liver disease to improve preclinical research. [Vium, Inc.] Press Release

Vertex Completes Enrollment of Two Phase III Studies of VX-659 in Triple Combination with Tezacaftor and Ivacaftor for the Treatment of Cystic Fibrosis

Vertex Pharmaceuticals Incorporated announced that enrollment is complete for the two Phase III studies of the next-generation corrector VX-659 in triple combination with tezacaftor and ivacaftor in people with cystic fibrosis with one F508del mutation and one minimal function mutation and in people with two F508del mutations. [Vertex Pharmaceuticals Incorporated] Press Release

Merrimack Completes Enrollment in Randomized Phase II SHERLOC Study of MM-121 (Seribantumab) in Non-Small Cell Lung Cancer (NSCLC)

Merrimack Pharmaceuticals, Inc. announced that it has completed enrollment in its ongoing SHERLOC study, a Phase 2 clinical trial evaluating its lead investigational drug candidate, MM-121, in patients with heregulin positive NSCLC. [Merrimack Pharmaceuticals, Inc.] Press Release

TESARO Announces Expansion to Second Stage of JASPER Trial of ZEJULA^® in Combination with TSR-042 in Non-Small Cell Lung Cancer

TESARO, Inc. announced that it has initiated the second stage of the JASPER study that is designed to assess clinical benefit of ZEJULA^® in combination with an anti-PD-1 antibody in first-line non-small cell lung cancer patients. [TESARO, Inc.] Press Release

South Africa Pushes Science to Improve Daily Life

South Africa’s science system is set for its biggest shake-up in 20 years, amid proposed legislation changes that aim to make research efforts better serve citizens and address problems such as poverty and unemployment. It also reaffirms a key government goal to boost total research and development spending from 0.8% to 1.5% of gross domestic product in the next decade. [Nature News] Editorial

AACR Apologizes for Delays in Retracting Papers

The American Association for Cancer Research (AACR) has issued retractions, corrections, or editor’s notes for a handful papers across five of its journals and is sorry for the time it’s taken to do so, according to a statement published in Cancer Research. [The Scientist] Editorial

Google Unveils Search Engine for Open Data

Google has unveiled a search engine to help researchers locate online data that is freely available for use. The company launched the service, saying that it is aimed at “scientists, data journalists, data geeks, or anyone else”. [Nature News] Editorial

UK ‘Missing Out’ on Overseas Students

University leaders are calling for changes to the UK visa system to allow international students to stay and work for two years after they graduate. Universities UK says otherwise overseas students, worth £26bn to the UK economy, will opt for countries such as the US, Canada and Australia. [The BBC] Editorial

NEW Cell Symposia: Engineering Organoids and Organs
August 25-27, 2019
San Diego, California, United States

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

NEW Postdoctoral Scientist – Cancer Biology and Immunology (Technical University of Munich)

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

PhD Students – Lung Disease Research (Justus-Liebig-Universität Gießen)

Faculty Investigators – Cancer Research (The University of Alabama at Birmingham)

Postdoctoral Position – Lung Diseases (German Research Center for Environmental Health)

Postdoctoral Position – Acute Lung Injury (University of Kentucky)

Cancer Research Scholar – Lung Cancer (University of California)

Postdoctoral Fellow – BCL-2 & Pathogenesis & Targeted Therapy of Lung Cancer (Memorial Sloan Kettering Cancer Center)

Principal Investigators – Cancer (University of Alabama Birmingham)

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