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Glioblastoma multiforme (GBM) is a lethal and highly vascular type of brain tumor. We previously reported that isolinderalactone enhances GBM apoptosis in vitro and in vivo, but its role in tumor angiogenesis is unknown. Here, we investigated the anti-angiogenic activity of isolinderalactone and its mechanisms. In a human GBM xenograft mouse model, isolinderalactone significantly reduced tumor growth and vessels. Isolinderalactone decreased the expression of vascular endothelial growth factor (VEGF) mRNA, protein, and VEGF secretion in hypoxic U-87 GBM cells and also in xenograft GMB tissue. In addition, we demonstrated that isolinderalactone significantly inhibited the proliferation, migration, and capillary-like tube formation of human brain microvascular endothelial cells (HBMECs) in the presence of VEGF. We also found that isolinderalactone decreased sprout diameter and length in a 3D microfluidic chip, and strongly reduced VEGF-triggered angiogenesis in vivo Matrigel plug assay. Isolinderalactone downregulated hypoxia-inducible factor-1α (HIF-1α) and HIF-2α proteins, decreased luciferase activity driven by the VEGF promoter in U-87 cells under hypoxic conditions, and suppressed VEGF-driven phosphorylation of VEGFR2 in HBMECs. Taken together, our results suggest that isolinderalactone is a promising candidate for GBM treatment through tumor angiogenesis inhibition. BACKGROUND & AIMS There is debate over the type of electrosurgical setting that should be used for polyp resection. Some endoscopists use a type of blended current (yellow) whereas others prefer coagulation (blue). this website We performed a single-blind, randomized trial to determine whether type of electrosurgical setting affects risk of adverse events or recurrence. METHODS Patients undergoing endoscopic mucosal resection of non-pedunculated colorectal polyps 20 mm or larger (n=928) were randomly assigned, in a 2x2 design, to groups that received clip closure or no clip closure of the resection defect (primary intervention) and then to either a blended current (Endocut Q) or coagulation current (forced coagulation; Erbe Inc.) (secondary intervention and focus of the study). The study was performed at multiple centers, from April 2013 through October 2017. Patients were evaluated 30 days after the procedure (n=919), and 675 patients underwent a surveillance colonoscopy at a median 6 months after the procedure. The primgulation), we found no difference in risk of serious adverse events, complete resection rate, or polyp recurrence. Electrosurgical settings can therefore be selected based on endoscopist expertise and preference. Clinicaltrials.gov no NCT01936948. BACKGROUND Chronic iliocaval obstruction is a challenging clinical entity to treat. Endovenous iliocaval stenting is becoming the treatment of choice for central vein stenosis and occlusion. However, outcomes in thrombotic disease have not been as robust as non-thrombotic disease. In this article we describe our experience utilizing covered stents as a novel tool for chronic total occlusions of the iliocaval veins. METHODS We performed a retrospective review of a prospectively maintained database of all patients undergoing endovenous stenting with a covered stent for chronic occlusive iliocaval disease over a 3 year period at our institution. Patients were followed clinically and with venous duplexes to assess the feasibility, safety, and outcomes of iliocaval endovenous stenting with covered stents. RESULTS A total of 10 patients (8 men and 2 women) underwent iliocaval stenting with covered stents from July 2015 - May 2018. A total of 20 self-expanding covered stents (SECS) and 13 balloon expandable covered promising procedure. Their use may improve the short and long term outcomes in this challenging patient population. Further studies are required to evaluate the long term efficacy and cost of their use. INTRODUCTION Abdominal aortic aneurysm (AAA) is a progressive dilation of the aortic wall, determined by the unbalanced activity of matrix metalloproteinase (MMPs). In vitro and in vivo studies support the pivotal role of MMP-9 to AAA pathogenesis. In our experience, we elucidated the expression of MMP-9 in an ex-vivo model of human Mesenchymal Stem Cells isolated from AAA specimen (AAA-MSCs). Thus, MMP-9 inhibition could be an attractive therapeutic strategy for inhibiting AAA degeneration and rupture. Our study was aimed at testing the effect of three different drugs (pioglitazone, doxycycline, simvastatin) on MMP-9 and PPAR-γ expression in AAA-MSCs. METHODS Aneurysmal aortic wall segments were taken from AAA patients after the open surgical treatment. MSCs were isolated from AAA (n=20) tissues through enzymatic digestion. AAA-MSCs were exposed to different doses of pioglitazone (5-10-25 μM), doxycycline (10-25 μM) and simvastatin (10 μM) for 24 h. The effect of each drug was evaluated in terms of cell survival, by crystal violet stain. MMP-9 and PPAR- γ mRNA were analysed by Real Time PCR. RESULTS AAA-MSCs were not affected by the exposure to the selected drugs, as shown by the analysis of cell viability. Interestingly, MMP-9 mRNA resulted significantly decreased after each treatment, recording a down-regulation of 50% in presence of pioglitazone, 90% with doxycycline and 40% with exposed to simvastatin, in comparison to untreated cells. We further analysed the expression of PPAR-γ, target of pioglitazone, observing an up-regulation in exposed AAA-MSCs to controls. CONCLUSIONS Our data support the potential therapeutic effect of pioglitazone, doxycycline and simvastatin on AAA by reducing the MMP-9 expression in a patient-specific model (AAA-MSCs). In addition, pioglitazone drives the increase of PPAR-G, another promising target for AAA therapy. Further studies are necessary to elucidate the mechanism driving this inhibitory pathway, which can reduces the mortality risk associated with AAA rupture. BACKGROUND Considering the longevity of the worldwide population, the cardiovascular diseases deserve particular attention, specially the carotid artery disease in the ≥ 80 years old population. The stiffness of the common carotid artery, for example, has been showed in numerous clinical studies as a marker of increased risk of stroke, dementia and depression. Besides, with the emergence of new surgical techniques like the transcarotid artery revascularization that uses the common carotid artery as a workstation, the biomechanical and histological features of this vessel, more than ever, must be detailed. METHODS Left common carotid artery fragments from 9 cadaver donors (≥ 80 years old) were evaluated. Biomechanical (failure stress, tension and strain) and histological (percentage of collagen and elastic fibers) features of these samples were analyzed with special focus on gender differences. RESULTS Statistically significant differences in biomechanical and histological features between the genders were observed.
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