Endothelial Cell News 2.06 February 27, 2017 | |
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TOP STORYEndothelial Notch1 Activity Facilitates Metastasis Investigators showed that activated Notch1 receptors (N1ICD) are frequently observed in endothelial cells (ECs) of human carcinomas and melanoma, and in ECs of the pre-metastatic niche in mice. EC N1ICD expression in melanoma correlated with shorter progression-free survival. Sustained N1ICD activity induced EC senescence, expression of chemokines and the adhesion molecule VCAM1. This promoted neutrophil infiltration, tumor cell adhesion to the endothelium, intravasation, lung colonization, and postsurgical metastasis. [Cancer Cell] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Endothelial CD99 Supports Arrest of Mouse Neutrophils in Venules and Binds to Neutrophil PILRs CD99 is a crucial regulator of the transmigration of leukocytes through the blood vessel wall. In agreement with previous antibody blocking experiments, researchers found that CD99 gene inactivation caused neutrophil accumulation between venular endothelial cells and the basement membrane in the inflamed cremaster. Unexpectedly, they additionally found that leukocyte attachment to the luminal surface of the venular endothelium was impaired in the absence of CD99. [Blood] Abstract To assess a role for multiwalled carbon nanotubes (MWCNT)-induced circulating factors in driving neuroinflammatory outcomes, mice were acutely exposed to MWCNTs via oropharyngeal aspiration. At four hours after MWCNT exposure, broad disruption of the blood-brain barrier was observed across the capillary bed with the small molecule fluorescein, concomitant with reactive astrocytosis. Serum from MWCNT-exposed mice induced expression of adhesion molecules in primary murine cerebrovascular endothelial cells and, in a wound-healing in vitro assay, impaired cell motility and cytokinesis. [Proc Natl Acad Sci USA] Full Article The role of vascular CXCR4 in regulating vascular structure in hepatocellular carcinoma (HCC) was assessed and the clinical value of CXCR4 was explored. Investigators found that CXCR4 is selectively expressed on a fraction of tumor endothelial cells in HCC tissues, but not on the hepatic endothelium in peri-tumoral area. [Clin Cancer Res] Abstract The blood-brain barrier (BBB) is composed of four cell populations, brain endothelial cells, pericytes, neurons, and astrocytes. Researchers generated an in vitro model of the BBB by differentiating human induced pluripotent stem cells into all four populations. They performed in vitro BBB permeability tests and assessed ten clinical drugs by nanoLC-MS/MS, finding a good correlation with the BBB permeability reported in previous cases.” [Stem Cell Reports] Full Article | Graphical Abstract Elderly Patient-Derived Endothelial Cells for Vascularization of Engineered Muscle Scientists showed that adult endothelial cells formed vessel networks that were more developed and complex than those formed by human umbilical vein endothelial cells seeded with various supporting cells on three dimensional biodegradable polymer scaffolds. [Mol Ther] Full Article | Graphical Abstract The authors hypothesized that inactivation of the Pparγ gene in vascular smooth muscle cells (VSMC) would exaggerate ET-1-induced vascular injury. They found that VSMC Pparγ inactivation exaggerated ET-1-induced vascular injury, supporting a protective role for PPARγ in hypertension through modulation of pro-oxidant and proinflammatory pathways. [J Hypertens] Abstract Researchers presented nanoconstructs consisting of a DNA-amplified aptamer with a biocompatible polymer backbone for capturing target biomolecules. These polymer–DNA amplified aptamer nanoconstructs were successfully applied to alleviate tumor growth and vascular endothelial growth factor (VEGF)-induced retinal vascular hyperpermeability in vivo through the highly effective capture of human VEGF as a target molecule. [Mol Pharm] Abstract | Graphical Abstract Researchers showed that nitric oxide synthase trafficking inducer affects the functional-transcriptome of endothelial cells by down-regulating several genes, important for invasion and angiogenesis. [J Biol Chem] Abstract | Full Article TRPC5 Channel Modulates Endothelial Cells Senescence The authors investigated the involvement of transient receptor potential 5 channel (TRPC5) in the senescence of mouse aortic endothelial cells. Results showed that the endothelium-dependent relaxations were significantly promoted but the endothelium-dependent contractions were markedly attenuated in aortic rings from aged mice with TRPC5 gene knocked out compared with those from aged C57BL/6J mice. [Eur J Pharmacol] Abstract | |
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REVIEWSMind the Gap: Mechanisms Regulating the Endothelial Barrier Both types of barrier-forming junctions, i.e. the adherens junction serving mechanical anchorage and mechanotransduction and the tight junction sealing the intercellular space to limit paracelullar permeability, are tethered to the actin cytoskeleton. In the situation of an inflammatory response such as in anaphylaxis or sepsis intercellular contacts disintegrate in postcapillary venules leading to intercellular gap formation. The resulting edema can cause shock and multi-organ failure. Therefore, maintenance as well as coordinated opening and closure of interendothelial junctions is tightly regulated. [Acta Physiol (Oxf)] Abstract Interaction of Endothelial Cells with Macrophages—Linking Molecular and Metabolic Signaling The authors highlight the complexity of the interrelationship between the inflammatory response and angiogenesis. More in particular, the interaction between macrophages and endothelial cells will be discussed with a special focus on how their metabolism can contribute to (patho-)physiological conditions. [Pflugers Arch] Abstract Visit our reviews page to see a complete list of reviews in the endothelial cell research field. | |
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SCIENCE NEWSExelixis, Inc. announced results from a Phase I trial of cabozantinib in combination with either nivolumab or nivolumab plus ipilimumab in patients with refractory genitourinary tumors. The primary endpoint of the trial was to determine the dose limiting toxicity and recommended Phase II doses of the doublet and triplet combinations. [Press release from Exelixis, Inc. discussing research presented at the American Society of Clinical Oncology (ASCO) 2017 Genitourinary Cancers Symposium, Orlando] Press Release Genentech announced encouraging results from the Phase II IMmotion150 study that compared TECENTRIQ® plus Avastin® and TECENTRIQ monotherapy to sunitinib alone in people with previously untreated, locally advanced or metastatic renal cell carcinoma. [Press release from Genentech, Inc. discussing research presented at the American Society of Clinical Oncology (ASCO) 2017 Genitourinary Cancers Symposium, Orlando] Press Release | |
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INDUSTRY NEWSAVEO Announces TIVO-3 Passes the First Safety Monitoring Committee Safety Review AVEO Oncology announced that its pivotal, Phase III TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma, has successfully completed the first safety review by the study’s Safety Monitoring Committee. [AVEO Oncology] Press Release Exelixis, Inc. and Bristol-Myers Squibb Company announced the companies have entered into a clinical development collaboration to evaluate CABOMETYX™, Exelixis’ small molecule inhibitor of receptor tyrosine kinases, with Opdivo, Bristol-Myers Squibb’s PD-1 immune checkpoint inhibitor, either alone or in combination with Yervoy. [Exelixis, Inc.] Press Release Exelixis, Inc. announced a new collaboration with Roche on a Phase Ib dose escalation study that will evaluate the safety and tolerability of cabozantinib, Exelixis’ tyrosine kinase inhibitor, in combination with atezolizumab, Roche’s anti-PD-L1 immunotherapy, in patients with locally advanced or metastatic solid tumors. Enrollment is scheduled to begin mid-year 2017; Exelixis will be the sponsor of the trial, and Roche will provide atezolizumab. [Exelixis, Inc.] Press Release | |
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POLICY NEWSTwo Top Chinese-American Scientists Have Dropped Their U.S. Citizenship Two top Chinese scientists, one a Nobel laureate and the other a winner of a top computer science prize, have renounced their U.S. citizenship to become citizens of China. [ScienceInsider] Editorial U.S. Researchers Guilty of Misconduct Later Won More than $100 Million in NIH Grants, Study Finds Many believe that once a scientist is found guilty of research misconduct, his or her scientific career is over. But a new study suggests that, for many U.S. researchers judged to have misbehaved, there is such a thing as a second chance. [ScienceInsider] Editorial Biologists Propose to Sequence the DNA of All Life on Earth At a meeting organized by the Smithsonian Initiative on Biodiversity Genomics and the Shenzhen, China–based sequencing powerhouse BGI, a small group of researchers upped the ante even more, announcing their intent to, eventually, sequence “all life on Earth.” [ScienceInsider] Editorial
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EVENTSNEW American Thoracic Society (ATS) Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Research Positions – Tissue Microenvironment in Chronic Kidney Disease (Inserm) Postdoctoral Fellow – Stem Cell Biology (Northwestern University) PhD Position – Blood-Brain Barrier Biology (Technical University of Denmark) PhD Position – Molecular Biology (Institut of Molecular Biology) Postdoctoral Fellow – Cardiopulmonary Molecular Biology (Hannover Medical School) Postdoctoral Fellowship – RNA Biology (Goethe University Frankfurt) Assistant/Associate Professor – Angiogenesis in Urology (Northwestern University) PhD Position – Genome Engineering (KU Leuven, Stem Cell Institute) Postdoctoral Fellow – Cardiovascular Research (Thomas Jefferson University) Postdoctoral Fellow – Tumor Angiogenesis (Thomas Jefferson University) Postdoctoral Associate – Molecular Biology (Virginia Commonwealth University) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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Home Endothelial Cell News Volume 2.06 | Feb 27 2017