Pulmonary Cell News Volume 7.05 | Feb 8 2018

TOP STORY

Single-Cell Wnt Signaling Niches Maintain Stemness of Alveolar Type 2 Cells

The authors showed that AT2 lung stem cells display active Wnt signaling and many of them are near single, Wnt-expressing fibroblasts. Blocking Wnt secretion depleted these stem cells. [Science] Abstract

(Ranked by impact factor of the journal)

Claudin-18–Mediated YAP Activity Regulates Lung Stem and Progenitor Cell Homeostasis and Tumorigenesis

Researchers demonstrated that knockout of Cldn18, a claudin family member highly expressed in lung alveolar epithelium, leads to lung enlargement, parenchymal expansion, increased abundance and proliferation of known distal lung progenitors, the alveolar epithelial type II cells, activation of Yes-associated protein (YAP), increased organ size, and tumorigenesis in mice. [J Clin Invest] Full Article

The Strength of Mechanical Forces Determines the Differentiation of Alveolar Epithelial Cells

Scientists developed live imaging techniques to characterize the mechanisms that control alveolar epithelial cell differentiation. They discovered that mechanical forces generated from the inhalation of amniotic fluid by fetal breathing movements are essential for alveolar epithelial type I cell differentiation. [Dev Cell] Full Article | Graphical Abstract

SIRT1/FoxO3 Axis Alteration Leads to Aberrant Immune Responses in Bronchial Epithelial Cells

Investigators evaluated whether cigarette smoke, by modulating the sirtuin-1 (SIRT1)/forkhead box class O3 (FoxO3) axis, affects airway epithelial pro-inflammatory responses. Human bronchial epithelial cells and primary bronchial epithelial cells from COPD patients and controls were treated with/without cigarette smoke extract, Sirtinol or FoxO3 siRNA. [J Cell Mol Med] Full Article

Gasoline Particle Filter Reduces Oxidative DNA Damage in Bronchial Epithelial Cells after Whole Gasoline Exhaust Exposure In Vitro

The authors exposed human bronchial epithelial cells (ECs) for six hours, and compared results with and without gasoline particle filter (GPF). The particle amount was significantly reduced due to GPF application. While most biological endpoints did not differ, oxidative DNA damage was significantly reduced in EC monocultures exposed to GPF compared to reference exhaust. [Sci Rep] Full Article

LUNG CANCER

Polo-Like Kinase 4 Inhibition Produces Polyploidy and Apoptotic Death of Lung Cancers

CFI-400945 treatment produced supernumerary centrosomes and mitotic defects in lung cancer cells. In vivo antineoplastic activity of CFI-400945 was established in mice with syngeneic lung cancer xenografts. Lung tumor growth was significantly inhibited at well-tolerated dosages. [Proc Natl Acad Sci USA] Abstract

β-Trcp Ubiquitin Ligase and RSK2 Kinase-Mediated Degradation of FOXN2 Promotes Tumorigenesis and Radioresistance in Lung Cancer

Investigators found that FOXN2 binds to and is ubiquitinated by β-Trcp ubiquitin ligase and RSK2 kinase for degradation. Furthermore, they demonstrated that the Ser365 and Ser369 sites in a conserved DSGYAS motif are critical for the degradation of FOXN2 by β-Trcp and RSK2. [Cell Death Differ] Abstract

Nf-κB Inhibition by Dimethylaminoparthenolide Radiosensitizes Non-Small-Cell Lung Carcinoma by Blocking DNA Double-Strand Break Repair

Inhibition of the NF-κB pathway is a proposed mechanism of radiosensitization. Researchers demonstrated that inhibition of the canonical NF-κB pathway by dimethylaminoparthenolide radiosensitizes non-small-cell lung carcinoma by blocking DNA double-strand break repair. [Cell Death Discov] Full Article

Antitumor Activity of EGFR-Specific CAR T Cells against Non-Small-Cell Lung Cancer Cells In Vitro and in Mice

Scientists developed an adoptive T-cell treatment through expression of a chimeric antigen receptor (CAR) to target human epidermal growth factor receptor (EGFR) in non-small-cell lung cancer. The modified CAR T cells exhibited expansion capability and anticancer efficacy in a time- and antigen-dependent manner in vitro as well as regression of EGFR-positive human lung cancer xenografts in vivo. [Cell Death Dis] Full Article

Combining Chemotherapy with PD-1 Blockade in NSCLC

There remains a crucial need for better treatment strategies for the majority of patients with advanced non-small cell lung cancer (NSCLC), particularly in the frontline setting. Chemotherapy can increase antigenicity via immunogenic cell death of tumor cells as well as also reduce “off target” immunosuppression in the tumor microenvironment. [Pharmacol Ther] Abstract

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

Pivotal Phase III Checkmate -227 Study Demonstrates Superior Progression-Free Survival (PFS) with the Opdivo Plus Yervoy Combination versus Chemotherapy in First-Line Non-Small Cell Lung Cancer (NSCLC) Patients with High Tumor Mutation Burden (TMB)

Bristol-Myers Squibb Company announced that the ongoing Phase III CheckMate -227 study met its co-primary endpoint of PFS with the Opdivo plus Yervoy combination versus chemotherapy in first-line advanced NSCLC patients whose tumors have high TMB, regardless of PD-L1 expression. [Bristol-Myers Squibb Company] Press Release | Editorial

CytRx Corporation Highlights Second NantCell Inc. Clinical Trial Evaluating Immuno-Oncology Agents and Cell-Based Therapies in Combination with Aldoxorubicin in Patients with Advanced Squamous Cell Carcinoma

CytRx Corporation highlighted that aldoxorubicin licensee NantCell, Inc. has dosed the first patient in the Phase Ib portion of a Phase Ib/II clinical trial for patients with advanced squamous cell carcinoma of either the head and neck or non-small cell lung cancer. [CytRx Corporation (PR Newswire Association LLC.)] Press Release

Daiichi Sankyo Initiates Phase I Study of U3-1402 in Patients with Metastatic EGFR-Mutated Non-Small Cell Lung Cancer

Daiichi Sankyo Company, Limited announced that the first patient has been dosed in a Phase I study evaluating the safety and tolerability of U3-1402, an investigational and potential first-in-class HER3-targeting antibody drug conjugate, in patients with metastatic or unresectable epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer whose disease has progressed while taking an EGFR tyrosine kinase inhibitor. [Daiichi Sankyo Company, Limited] Press Release

Two Women Scientists Granted $400k for Promising Lung Cancer Research

Lung Cancer Foundation of America and the International Association for the Study of Lung Cancer have partnered to fund the Lori Monroe Scholarship for Lung Cancer Research. These $200,000 grants support promising new research led by two female scientists, the second year in a row that both Lori Monroe Scholarship recipients go to women. [Lung Cancer Foundation of America (PR Newswire Association LLC.)] Press Release

NSF Requires Institutions to Report Sexual Harassment Findings

The National Science Foundation (NSF) in Alexandria, Virginia, announced a new set of measures to combat sexual harassment by people working on the projects it funds. The steps may include suspending or eliminating research grants after an institution finds that a grantee committed harassment. [ScienceInsider] Editorial

Breakthrough in Budget Negotiations Could Raise Spending for Science

Top lawmakers in Congress announced a budget agreement that could produce substantial spending increases for research at key U.S. science agencies—and avoid a partial government shutdown on Friday. But the deal must still clear a few hurdles before it is finalized. [ScienceInsider] Editorial

Restore Justice in Turkey

Peace is a dangerous cause to fight for in Turkey right now. In the latest blow to academics, 11 members of the Turkish Medical Association, including its president, Raşit Tükel, were arrested in early-morning raids. [Nature News] Editorial

Japanese Researchers Say Science-Budget Hike Isn’t Enough

Japan will sharply increase funding for science and technology in 2018 after years of stagnant support for the sector. But some scientists and policy experts worry the boost is too little to make up for more than a decade of lackluster science funding. [Nature News] Editorial

Kid Co-Authors in South Korea Spur Government Probe

The South Korean government is expanding an investigation into researchers who named their children as co-authors on papers. The extended probe comes after a government report identified 82 academic papers on which authors had named their children or relatives — many of them in middle or high school — as co-authors on the publications. [Nature News] Editorial

NEW The New York Stem Cell Foundation (NYSCF) Conference 2018
October 23-24, 2018
New York, New York, United States

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

NEW Postdoctoral Fellow – Respiratory Therapy Area (AstraZeneca)

NEW Postdoctoral Scholar – Stem Cell Biology and Cancer Biology (University of Iowa)

Postdoctoral Fellow – Human Lung Stem Cells and Regeneration (MedImmune)

Postdoctoral Fellow – Lung Cancer (Van Ande Research Institute)

Postdoctoral Position – Biomedical Systems Biology (University of Zurich)

Postdoctoral Scholarship – Translational Cancer Stem Cell Biology (Lund University)

Postdoctoral Position – Pulmonary Disease Pathogenesis (Columbia University)

Postdoctoral Fellow – Lung Regeneration after Injury (University of Michigan)

Postdoctoral Fellow – Lung Cancer (MD Anderson Cancer Center)

Postdoctoral Researcher – Cancer Research (University of California, Davis)

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