Pulmonary Cell News 5.48 December 8, 2016 | |
| |
TOP STORYMEK Inhibitors Block Growth of Lung Tumors with Mutations in Ataxia–Telangiectasia Mutated Investigators reported that ATM loss-of-function is synthetic lethal with drugs inhibiting the central growth factor kinases MEK1/2, including the FDA-approved drug trametinib. Lung cancer cells resistant to MEK inhibition become highly sensitive upon loss of ATM both in vitro and in vivo. [Nat Commun] Full Article | Press Release | |
| |
PUBLICATIONS(Ranked by impact factor of the journal)Modulation of Apical Constriction by Wnt Signaling Is Required for Lung Epithelial Shape Transition The impact of cell shapes on tissue morphogenesis remains unclear. Scientists showed that expression of Wnt components were decreased in the canalicular-saccular stages, and genetically constitutive activation of Wnt signaling impaired air sac formation by inducing apical constriction in the epithelium as seen in the pseudoglandular stage. Organ culture models also demonstrated that Wnt signaling induces apical constriction through the apical actomyosin cytoskeletal organization. [Development] Abstract Rat models of bronchopulmonary dysplasia (BPD) using varying degrees of hyperoxia to produce injury either cause early mortality or spontaneously recover following removal of the inciting stimulus, thus limiting clinical relevance. Researchers sought to refine an established rat model induced by exposure to 60% O2 from birth by following hyperoxia with intermittent hypoxia (IH). [Am J Physiol Lung Cell Mol Physiol] Abstract The authors aimed to assess the effects of cigarette smoke, carbocysteine, and beclomethasone dipropionate on histone deacetylase 3 expression/activity, N-CoR expression, histone acetyltransferases expression, p-CREB and IL-1 m-RNA expression, neutrophil chemotaxis. Increased p-CREB expression was observed in the bronchial epithelium of smokers. [J Cell Physiol] Abstract Researchers showed that alveolar epithelium type 2 cells (AEC2s) are damage resistant during acute lung injury. Then they observed the relationship between the expression of HGF, c-Met following acute lung injury (ALI) in rat lung and proliferation of AEC2s. The proliferation of AEC2s was inhibited when isolated primary AEC2s were co-cultured with c-Met inhibitor SU11274. [Respir Res] Full Article Scientists used cytotoxicity assays, proteomic and gene expression analyses to examine the difference in response of A549 cells to two silica particles that differ in physical properties, namely cristobalite and α-quartz. Cytotoxicity assays such as lactate dehydrogenase release, 5-bromo-2′-deoxyuridine incorporation and cellular ATP showed that both silica particles could cause cell death, decreased cell proliferation and metabolism in the A549 human lung epithelial cells. [J Appl Toxicol] Full Article LUNG CANCERLung cancers harboring common EGFR mutations respond to EGFR tyrosine kinase inhibitors. The authors established afatinib-resistant cells by transfecting Ba/F3 cells with common or exon 18 mutations and subjecting them to chronic exposure to increasing concentrations of afatinib. Afatinib-resistant clones were separately established through N-ethyl-N-nitrosourea mutagenesis and exposure to fixed concentrations of afatinib. [Mol Cancer Ther] Abstract Dual Targeting of Glutaminase 1 and Thymidylate Synthase Elicits Death Synergistically in NSCLC Scientists showed Glutaminase 1 (GLS1) inhibition induced cell cycle arrest with ATP depletion by glutamate reduction. Dual inhibition with bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) and thymidylate synthase inhibitor, 5-fluorouracil (5-FU), elicits cell death synergistically through cell cycle arrest in non-small cell lung cancer (NSCLC). A preclinical xenograft model of NSCLC showed remarkable anti-tumor effect synergistically in the BPTES and 5-FU dual therapy group. [Cell Death Dis] Full Article The authors showed cancer associated fibroblasts treated with cisplatin conferred chemoresistance to lung cancer cells. Meanwhile, Interleukin-11 (IL-11) was significantly up-regulated in the cancer-associated fibroblasts stimulated by cisplatin. As confirmed in lung adenocarcinoma cells in vivo and in vitro, IL-11 could protect cancer cells from cisplatin-induced apoptosis and thus promote their chemoresistance. [Sci Rep] Full Article Researchers reported that rpL3 induced by 5-FU treatment in Calu-6 cells represses CBS transcription and reduces CBS protein stability leading to a decrease of CBS protein levels. rpL3 also regulates negatively the activation of NFκB by preventing NFκB nuclear translocation through IκB-α up-regulation. [Sci Rep] Full Article The authors have simulated on cycle of environmental conditions to study the reversible nature of the stemness status in terms of chemoresistance. They first generated floating tumorspheres from lung and breast cancer cells by culturing them in serum-free media without the addition of any external mitogenic stimulation, and subsequently re-incubating them back in serum-containing media to simulate routine culture conditions. [J Cell Physiol] Abstract Investigators explored the relationship between the ethaselen dose and thioredoxin reductase (TrxR) activity level and the relationship between TrxR degradation and tumor apoptosis in a human lung carcinoma A549 xenograft model. [Acta Pharmacol Sin] Abstract | |
| |
REVIEWSNew Horizons for Cystic Fibrosis Treatment The authors discuss how CFTR mutations translate to disturbed synthesis or function of the CFTR protein and how its understanding has opened the way to ‘personalized’ treatments to correct the basic defect. The first two drugs have reached the clinic: a CFTR potentiator to augment CFTR channel function, and the combination of this potentiator with a corrector to increase CFTR expression at the cell membrane. [Pharmacol Ther] Abstract Visit our reviews page to see a complete list of reviews in the pulmonary cell research field. | |
| |
SCIENCE NEWSUpdated KEYTRUDA® (Pembrolizumab) Data in Small Cell Lung Cancer and Mesothelioma Presented Merck announced that updated findings from the Phase Ib KEYNOTE-028 study investigating the use of KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, in previously treated patients with advanced small cell lung cancer and malignant pleural mesothelioma, showed clinical activity and durable responses in some patients. [Press release from Merck discussing research presented at 17th World Conference on Lung Cancer, Vienna] Press Release | |
| |
INDUSTRY NEWSBristol-Myers Squibb Company announced updated results for Opdivo monotherapy and in combination with Yervoy in previously treated small cell lung cancer patients, a cohort of the Phase I/II open-label CheckMate -032 trial. [Bristol-Myers Squibb Company] Press Release Novartis announced results from its Phase III open-label, randomized, active-controlled, multi-center ASCEND-4 study, which found that patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC) treated with first-line Zykadia® (ceritinib) had a median progression-free survival of 16.6 months, compared to 8.1 months in patients treated with standard first-line chemotherapy with maintenance. [Novartis] Press Release The Breakthrough Prize and founders Sergey Brin and Anne Wojcicki, Yuri and Julia Milner, and Mark Zuckerberg and Priscilla Chan, announced the recipients of the 2017 Breakthrough Prizes, marking the organization’s fifth anniversary recognizing top achievements in Life Sciences, Fundamental Physics and Mathematics. A combined total of $25 million was awarded at the gala ceremony in Silicon Valley, hosted by Morgan Freeman. Each of the Breakthrough Prizes is worth $3 million, the largest individual monetary prize in science. [Breakthrough Prize] Press Release | |
| |
POLICY NEWSSenate Sends Massive Biomedical Innovation Bill to Obama for Signing By a 94-to-five vote, the Senate approved the 21st Century Cures Act, clearing the way for President Barack Obama to sign the measure into law. The massive bill dedicates $4.8 billion over the next decade to research initiatives at the National Institutes of Health and makes an array of changes at the Food and Drug Administration designed to speed the approval of new drugs and medical devices. [ScienceInsider] Editorial Controversial Impact Factor Gets a Heavyweight Rival One of science’s most contentious metrics has a flashy new rival. Publishing giant Elsevier launched the CiteScore index to assess the quality of academic journals. Although the index ranks journals with a formula that largely mimics the influential Journal Impact Factor (JIF), it covers twice as many journals and its formula includes tweaks that produce some notably different results, including lower scores for some high-JIF journals. [Nature News] Editorial Mexico Proposal to Ban Human-Embryo Research Would Stifle Science Researchers are waiting to see whether Mexico’s legislature will approve an amendment to the national health law that would ban experiments with human embryos. The amendment is intended to regulate assisted reproduction, including the payment of surrogate mothers, donations to egg and sperm banks and the fertilization of more than three eggs at a time. But it would also ban the creation of human embryos for any purpose except reproduction and any research with existing human embryos. [Nature News] Editorial CRISPR Heavyweights Battle in US Patent Court Berkeley and its rival, the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, are each vying for the intellectual property underlying CRISPR–Cas9, which is adapted from a system that bacteria use to fend off viruses. During the hearing the US Patent and Trademark Office judges challenged Berkeley’s central claim: that once its researchers demonstrated that CRISPR–Cas9 could be used to edit DNA in bacteria, any reasonably skilled person could have adapted the technique for use in more complex cells. [Nature News] Editorial
| |
EVENTSNEW 19th International Conference on Clinical Application of Adult Stem Cells Visit our events page to see a complete list of events in the community.
| |
JOB OPPORTUNITIESPost-Doctoral Research Fellow – Neurobiology (Institut of Molecular Biology) Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College) Postdoctoral Research Assistant/Associate(s) (University of Cambridge) Postdoctoral Position – Heart, Lung and Blood Vascular Medicine (University of Pittsburgh) 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) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
| |
Have we missed an important article or publication in Pulmonary Cell News? Click here to submit! Comments or suggestions? Submit your feedback here. | |
|
Home Pulmonary Cell News Volume 5.48 | Dec 8 2016