Endothelial Cell News 2.34 October 16, 2017 | |
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TOP STORYNew Insights into CAR T-Cell Therapy’s Potential Side Effects Based on their data from 133 adult participants in one clinical trial, researchers identified potential biomarkers associated with the development of the toxic effects, known as cytokine release syndrome and neurotoxicity. They also created algorithms aimed at identifying the rare patients whose symptoms were most likely to turn life-threatening. [Press release from Fred Hutchinson Cancer Research Center discussing online prepublication in Cancer Discovery] Press Release | Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Dose-Dependent Expression of Claudin-5 Is a Modifying Factor in Schizophrenia Scientists showed that a variant in the claudin–5 gene is weakly associated with schizophrenia in 22q11 deletion syndrome, leading to 75% less claudin-5 being expressed in endothelial cells. They also showed that targeted adeno-associated virus-mediated suppression of claudin-5 in the mouse brain results in localized blood-brain barrier disruption and behavioral changes. [Mol Psychiatry] Full Article The authors showed that endothelial intracellular adenosine and its key regulator adenosine kinase (ADK) play important roles in vascular inflammation. Pro-inflammatory stimuli lead to endothelial inflammation by increasing endothelial ADK expression, reducing the level of intracellular adenosine in endothelial cells, and activating the transmethylation pathway through increasing the association of ADK with S-adenosylhomocysteine hydrolase. [Nat Commun] Full Article Blood Vessel Control of Macrophage Maturation Promotes Arteriogenesis in Ischemia Scientists showed, using conditional genetic deletion strategies together with adoptive cell transfer experiments in a mouse model of hind limb ischemia, that blood vessels control macrophage differentiation and maturation from recruited monocytes via Notch signaling, which in turn promotes arteriogenesis and tissue repair. [Nat Commun] Full Article High fat diet treated ApoE-/- mice were used as an atherosclerotic animal model. Researchers found intragastric administration of melatonin for 12 weeks markedly reduced the atherosclerotic plaque in aorta. Consistent anti-pyroptotic effects were also observed in ox-LDL-treated human aortic endothelial cells. [J Pineal Res] Abstract Investigators compared their data set with mRNA differential expression data from endothelial and stromal cells derived from two in vivo models of lymphatic vessel remodeling, viral infection and contact hypersensitivity–induced inflammation, which identified genes selectively involved in regulating lymphatic endothelial cell migration and remodeling. [Sci Signal] Full Article The authors found that key pro-angiogenic pathways are repressed in endothelial colony-forming cells due to the presence of bivalent (H3K27me3/H3K4me3) epigenetic marks, which decreases the cells’ regenerative potential. Ex vivo treatment with a combination of epigenetic drugs that resolves bivalent marks toward the transcriptionally active H3K4me3 state lead to the simultaneous activation of multiple pro-angiogenic signaling pathways. [Stem Cell Reports] Full Article | Graphical Abstract Scientists investigated the potential value of amido-bridged nucleic acid-modified antisense oligonucleotides (ASOs) targeting YB-1 (YB-1 ASOA) as an antiangiogenic cancer therapy. YB-1 ASOA was superior to natural DNA-based ASO or locked nucleic acid-modified YB-1 ASO in both knockdown efficiency and safety, the latter assessed by liver function. [Mol Ther Nucleic Acids] Full Article | Graphical Abstract The authors investigated whether adiponectin contributes to the tight junction integrity and cell death of brain endothelial cells under beta amyloid (Aβ)-induced toxicity conditions. Their results showed that Acrp30 reduces the expression of proinflammatory cytokines and the expression of RAGE as Aβ transporters into brain. [Cell Death Dis] Full Article The effects of both fresh and cultured bone marrow-derived cell populations with endothelial progenitor cell (EPC) characteristics were examined following hyperoxia in neonatal mouse lungs. Intraperitoneal injection of fresh EPCs into five-day-old mice treated with 90% oxygen resulted in full recovery of hyperoxia-induced alveolar disruption by 56 days of age. [Stem Cells Transl Med] Full Article Investigators evaluated and compared ready-to-use human umbilical cord blood cells (HUCBC) and bankable, but allogeneic, endothelial progenitors (ECFC) as cell therapy candidate for neonatal hypoxic-ischemic encephalopathy. They compared benefits of HUCBC and ECFC transplantation 48 hours after injury in male rat neonatal hypoxic-ischemic encephalopathy model, based on the Rice-Vannucci approach. [Stem Cells Transl Med] Full Article Researchers delivered the pro-angiogenic chemokine Regulated upon Activation, Normal T-cell Expressed and Secreted (RANTES)/CCL5 in the mouse ischemic hindlimb, in solution or incorporated into polysaccharide-based microparticles. They demonstrated that RANTES-loaded microparticles improve the clinical score, induce the revascularization and the muscle regeneration in injured mice limb. [Sci Rep] Full Article Transient receptor potential vanilloid subtype 4 (TRPV4) is a calcium-permeable channel involved in barrier permeability, which blockade has been shown to prevent and resolve pulmonary edema. Investigators found TRPV4 expression in the endothelium and retinal pigment epithelium components of the blood-retinal barrier (BRB), and that TRPV4-selective antagonists resolve BRB breakdown in diabetic rats. [Sci Rep] Full Article | |
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REVIEWSVascular stem/progenitor cells (VSCs) can produce functional and mature vascular cells required to build blood vessels. VSCs therefore play critical roles in vascular repair and regeneration, particularly, in various retinal vasculopathies, in which vascular defects are a devastating pathology. [Mol Aspects Med] Abstract Friends Turned Foes: Angiogenic Growth Factors beyond Angiogenesis The properties and interactions of key angiogenic molecules such as vascular endothelial growth factors, fibroblast growth factors and angiopoietins have been investigated in great detail with respect to their molecular impact on angiogenesis. Since the discovery of angiogenic growth factors, much research has been focused on their biological actions and their potential use as therapeutic targets for angiogenic or anti-angiogenic strategies in a context-dependent manner depending on the pathologies. [Biomolecules] Full Article Visit our reviews page to see a complete list of reviews in the endothelial cell research field. | |
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SCIENCE NEWSNew subgroup analysis from Eli Lilly and Company’s Phase III REVEL trial of CYRAMZA® in advanced non-small cell lung cancer was presented. Specifically, these new data were an exploratory, post-hoc analysis focused on patients whose cancer rapidly progressed on first-line therapy. [Press release from Eli Lilly and Company discussing research presented at the 18th World Conference on Lung Cancer (WCLC), Yokohama] Press Release Chi-Med Reports Preliminary Phase II Data on Fruquintinib Combination in First-Line Lung Cancer Hutchison China MediTech Limited (Chi-Med) reported preliminary clinical activity, safety, and tolerability data of fruquintinib, an investigational selective inhibitor of VEGF receptor given in combination with Iressa®. These data were from an ongoing Phase II proof-of-concept trial conducted in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer. [Press release from Hutchison China MediTech Limited discussing research presented at the 18th World Conference on Lung Cancer (WCLC), Yokohama] Press Release | |
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INDUSTRY NEWSFDA Awards 15 Grants for Clinical Trials to Stimulate Product Development for Rare Diseases The FDA announced that it has awarded 15 new clinical trial research grants totaling more than $22 million over the next four years to boost the development of products for patients with rare diseases. [U.S. Food and Drug Administration] Press Release Ipsen and its partner Exelixis announced that its global Phase III CELESTIAL trial met its primary endpoint of overall survival (OS), with cabozantinib providing a statistically significant and clinically meaningful improvement in median OS compared to placebo in patients with advanced hepatocellular carcinoma. [Ipsen] Press Release Exelixis, Inc. announced that the FDA has determined the company’s supplemental New Drug Application for CABOMETYX® for patients with previously untreated advanced renal cell carcinoma to be sufficiently complete to permit a substantive review. [Exelixis, Inc.] Press Release AVEO Oncology announced the completion of a pre-planned futility analysis of the Phase III TIVO-3 trial, the company’s randomized, controlled, multi-center, open-label study to compare FOTIVDA® to sorafenib in subjects with refractory advanced renal cell carcinoma. [AVEO Pharmaceuticals, Inc.] Press Release | |
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POLICY NEWSGerman Researchers Resign from Elsevier Journals in Push for Nationwide Open Access Five leading German scientists have resigned from their editorial positions at journals published by Elsevier, the latest step in a battle over open-access and subscription policies between the Dutch publishing giant and a consortium of German libraries, universities, and research institutes. [ScienceInsider] Editorial NSF Drops Preproposals, Deadlines for Biologists Seeking Funding The National Science Foundation (NSF) will no longer require biologists applying for grants to submit preproposals and to adhere to an annual deadline for submissions. The changes pull the plug on a five-year pilot project in two NSF divisions—and mark the agency’s latest attempt to reduce the burden of the grant review system on its staff and outside researchers without lowering its standards. [ScienceInsider] Editorial South African Researchers Bemoan Slashed Funds Academics in South Africa are in uproar after a government research agency announced plans to cut the budget of a prestigious grant program that rewards the country’s best researchers. [Nature News] Editorial
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JOB OPPORTUNITIESNEW Postdoctoral Position – Basic Neuroscience (McLean Hospital/Harvard Medical School) NEW PhD Student – Cystic Fibrosis Associated Liver Disease (KU Leuven) NEW Scientist – Angiogenesis (University of East Anglia) NEW Postdoctoral Fellowship – Pulmonary Vascular Biology (Stanford University) Postgraduate Position – Mechanobiology of Cell Fate in 3D, Multicellular Environment (KU Leuven) Postdoctoral Position – Tumor Immunology and Cancer Immunotherapy (VIB) Postdoctoral Fellow – Tumor and Vascular Biology (Karolinska Institutet) Postdoctoral Fellow – Vascular Cell Signaling (Louisiana State University Health Sciences Center) Postdoctoral Position – Biology of Blood Platelets (INSERM) 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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