Pulmonary Cell News Volume 6.10 | Mar 16 2017

TOP STORY

A Combined PD-1/C5a Blockade Synergistically Protects against Lung Cancer Growth and Metastasis

The authors hypothesized that a combined inhibition of C5a/C5aR1 and programmed cell death protein 1 (PD-1) signaling may have an antitumor synergistic effect. RMP1-14 antibody was used to block PD-1 and an L-aptamer to inhibit signaling of complement C5a with its receptors. Using syngeneic models of lung cancer they demonstrated that the combination of C5a and PD-1 blockade markedly reduces tumor growth and metastasis, and leads to prolonged survival. [Cancer Discov] Abstract

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Lung Epithelial Cell Focal Adhesion Kinase Signaling Inhibits Lung Injury and Fibrosis

Scientists utilized mice with alveolar epithelial cell (AEC)-specific focal adhesion kinase (FAK) deletion to isolate the epithelial aspect of integrin signaling in the bleomycin model of lung injury and fibrosis. Within primary AECs, activated FAK directly associates with caspase8 and inhibit activation of the caspase cascade resulting in less apoptosis in response to TGFβ. [Am J Physiol Lung Cell Mol Physiol] Abstract

Foxp3⁺ Regulatory T Cell Expression of Keratinocyte Growth Factor Enhances Lung Epithelial Proliferation

Investigators sought to determine the contribution of Treg-specific expression of a growth factor, keratinocyte growth factor (Kgf), known to be important in lung repair. In vitro experiments demonstrate that type II alveolar epithelial cells co-cultured with Tregs lacking Kgf have decreased rates of proliferation compared to AT2 cells co-cultured with wild-type Tregs. [Am J Respir Cell Mol Biol] Abstract

Transcriptome Profiling of Influenza a Virus-Infected Lung Epithelial (A549) Cells with Lariciresinol-4-β-D-Glucopyranoside Treatment

The authors employed high-throughput RNA sequencing to investigate the transcriptomic responses of influenza A virus-infected lung epithelial cells with lariciresinol-4-β-D-glucopyranoside treatment. [PLoS One] Full Article

LUNG CANCER

Antagonism of EGFR and Notch Limits Resistance to EGFR Inhibitors and Radiation by Decreasing Tumor-Initiating Cell Frequency

Scientists showed that dual targeting of epidermal growth factor receptor (EGFR) and Notch2/3 receptors with antibody CT16 not only inhibited signaling mediated by these receptors but also showed a strong anti–stem cell effect both in vitro and in vivo. Treatment with CT16 prevented acquired resistance to EGFR inhibitors and radiation in non–small cell lung cancer cell line models and patient-derived xenograft tumors. [Sci Transl Med] Abstract | Press Release

Brigatinib Combined with Anti-EGFR Antibody Overcomes Osimertinib Resistance in EGFR-Mutated Non-Small-Cell Lung Cancer

There are no effective therapeutic strategies to overcome the C797S/T790M/activating-mutation (triple-mutation)-mediated EGFR–TKI resistance. Researchers identified brigatinib to be effective against triple-mutation-harboring cells in vitro and in vivo. [Nat Commun] Full Article

MUC1-C Integrates PD-L1 Induction with Repression of Immune Effectors in Non-Small-Cell Lung Cancer

Scientists demonstrated that mucin 1 (MUC1-C) activates programmed death ligand 1 (PD-L1) expression in non-small-cell lung cancer cells. They showed that MUC1-C increases nuclear factor-κB (NF-κB) p65 occupancy on the CD274/PD-L1 promoter and thereby drives CD274 transcription. They demonstrated that MUC1-C-induced activation of NF-κB→ZEB1 signaling represses the TLR9, IFNG, MCP-1 and GM-CSF genes, and that this signature is associated with decreases in overall survival. [Oncogene] Abstract

Induction of Reactive Oxygen Species-Stimulated Distinctive Autophagy by Chelerythrine in Non-Small Cell Lung Cancer Cells

The effect and mechanism of the chelerythrine (CHE)-induced autophagy, a type II programmed cell death, in non-small cell lung cancer (NSCLC) cells were studied for the first time. The authors showed that CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a concentration-dependent manner in NSCLC A549 and NCI-H1299 cells. [Redox Biol] Full Article

Phosphoproteomics Reveals HMGA1, a CK2 Substrate, as a Drug-Resistant Target in Non-Small Cell Lung Cancer

Investigators quantitatively profiled the phosphoproteome and proteome of drug-sensitive and drug-resistant non-small-cell lung cancer cells under gefitinib treatment. [Sci Rep] Full Article

Evidence, Mechanism, and Clinical Relevance of the Transdifferentiation from Lung Adenocarcinoma to Squamous Cell Carcinoma

The authors summarize the current understanding of the transdifferentiation from lung adenocarcinoma (ADC) to squamous cell carcinoma (SCC). ADC and SCC are two distinct subtypes of non–small-cell lung carcinoma. Approximately 4% to 9% of human non–small-cell lung carcinoma tumors contain mixed adenomatous and squamous pathologies in a single lesion, clinically termed adenosquamous cell carcinoma. [Am J Pathol] Abstract

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SenzaGen and AstraZeneca Initiate Technology Development Collaboration

SenzaGen has signed a collaboration agreement with the global biopharmaceutical company AstraZeneca. The collaboration focuses on testing and development of SenzaGen’s sensitization test GARDair, in order to distinguish between allergens and irritants in the respiratory tract. [SenzaGen] Press Release

First Patient Dosed in Phase II Trial Evaluating Transgene’s TG4010 in Combination with Opdivo^® (Nivolumab) for Second Line Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC)

Transgene announced the dosing of the first patient of the Phase II trial evaluating TG4010 in combination with Opdivo^® (nivolumab) for the treatment of metastatic non-small cell lung cancer (NSCLC) after failure of one line of platinum-based chemotherapy. [Transgene] Press Release

US Science Agencies Face Deep Cuts in Trump Budget

When it comes to science, there are few winners in US President Donald Trump’s first budget proposal. The plan outlines double-digit cuts for the Environmental Protection Agency and the National Institutes of Health. The Trump budget would cut funding for the entire NIH by 18%, to $25.9 billion, making it one of the hardest-hit research agencies. [Nature News] Editorial

‘Zombie’ Patent Fights over Mutant Mice Return

Like a zombie that keeps on kicking, legal battles over mutant mice used for Alzheimer’s research are haunting the field once again — four years after the last round of lawsuits. In the latest case, the University of South Florida in Tampa has sued the US National Institutes of Health for authorizing the distribution of a particular type of mouse used in the field. [Nature News] Editorial

U.K. Scientists Prepare for Impending Break with European Union

For months after the United Kingdom (U.K.) voted last June to leave the European Union (EU), many British scientists clung to hopes of a “soft Brexit,” which would not cut them off from EU funding and collaborators. But Prime Minister Theresa May, who is expected to trigger the two-year process of exiting the European Union, has signaled the break will be sharp. U.K. researchers are now facing up to the prospect that they won’t be able to apply for EU funding or easily recruit students and colleagues from the rest of Europe. [ScienceInsider] Editorial

Canada’s New Genetic Privacy Law Is Causing Huge Headaches for Justin Trudeau

A vote in Canada’s Parliament to approve a genetic privacy bill is creating a self-inflicted political headache for Prime Minister Justin Trudeau’s Liberal government—and could result in a relatively rare and unusual court case. [ScienceInsider] Editorial

NEW ELCC 2017 European Lung Cancer Conference
May 5-8, 2017
Geneva, Switzerland

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NEW Postdoctoral Research Associate – Chronic Lung Disease (Washington University St. Louis)

NEW Faculty Position – Cancer Biology (Wake Forest School of Medicine)

Laboratory Head – Infection & Immunity Division (The Walter and Eliza Hall Institute of Medical Research)

Assistant Professor/Postdoctoral Research Fellow – Lung Injury and Repair (University of Tennessee)

Postdoctoral Opportunity – RNA and Cancer Biology (Yale University)

PhD Student – Asthma Research (Karolinska Institute)

Postdoctoral Fellow – Airway Biology (Harvard T.H. Chan School of Public Health)

Principal Scientist – Translational Development (Celgene Corporation)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Postdoctoral Research Fellow – Cancer Genetics/Epigenetics (Fred Hutchinson Cancer Research Center)

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