Expression of Wnt genes in human breast cancer cell lines and tumor-associated macrophages

Die Interaktion zwischen Tumorzellen und Stromazellen spielt eine wichtige Rolle für die lokale Tumorprogression, die Invasivität und Metastasierung von soliden Tumoren wie dem Mammakarzinom. Es ist bekannt, dass die Kokultivierung von MCF-7 Mammakarzinomzellen mit humanen Makrophagen zu einer Wnt5a abhängigen Invasivitätssteigerung der Mammkarzinomzellen führt, welche durch den Wnt-Antagonisten Dkk-1 verhindert werden kann. Unbekannt war, ob sich primär hoch invasive Mammakarzinomzellen wie etwa die tripe-negative (TN) Mammakarzinomzelllinie MDA-MB-231 und die schwach invasive Zelllinie MCF-7 hinsichtlich ihrer Expression von Wnt- und Wnt-abhängigen Genen unterscheiden. So zeigten sich sowohl die nicht-kanonischen Wnt-Liganden Wnt5a und Wnt5b als auch die Wnt-assoziierten Gene VEGF-A und PLAU-R in der MDA-MB-231 Zelllinie als deutlich höher exprimiert im Vergleich zu MCF-7. Insbesondere die Expressionsunterschiede von Wnt5a und Wnt5b waren zuvor unbekannt und erweitern die molekulare Charakteristik dieser Zelllinien. In Kokulturexperimten von MCF-7 Mammakarzinomzellen und humanen Makrophagen zeigte sich in dieser Arbeit eine signifkant höhere Expression von Wnt5a, VEGF-A und TNF-α in MCF-7 nach 24h. Dies ist ein weiterer Aspekt für die molekularen Mechanismen, welche zu einer Invasivitätssteigerung solider Tumore durch Tumor-assoziierte Makrophagen (TAM) führen können. Interessanterweise blieb diese Regulation unter Zugabe von rh Dkk-1 aus, was eine wichtige Rolle von Dkk-1 möglicherweise auch aus therapeutischer Sicht nahelegt

Fully Reversible Contrast-Induced Encephalopathy Mimicking Stroke after Flow Diverter Treatment of Carotid Cave Aneurysm

Contrast-induced encephalopathy (CIE) is a rare complication of coronary and neurointerventional procedures. The condition is believed to arise from endothelial damage secondary to exposure to iodinated contrast media. A wide spectrum of clinical manifestations has been reported including seizures, cortical blindness, and focal neurological deficits. This report details the case of fully reversible CIE mimicking severe anterior circulation stroke in a 55-year-old female following elective endovascular treatment with a flow diverter of a carotid cave aneurysm. The patient was managed conservatively with intravenous hydration and steroids and showed an excellent prognosis with supportive management

Inhouse Bridging Thrombolysis Is Associated With Improved Functional Outcome in Patients With Large Vessel Occlusion Stroke: Findings From the German Stroke Registry

Background: Endovascular treatment (EVT) for large vessel occlusion stroke (LVOS) is highly effective. To date, it remains controversial if intravenous thrombolysis (IVT) prior to EVT is superior compared with EVT alone. The aim of our study was to specifically address the question, whether bridging IVT directly prior to EVT has additional positive effects on reperfusion times, successful reperfusion, and functional outcomes compared with EVT alone.Methods: Patients with LVOS in the anterior circulation eligible for EVT with and without prior IVT and direct admission to endovascular centers (mothership) were included in this multicentric, retrospective study. Patient data was derived from the German Stroke Registry (an open, multicenter, and prospective observational study). Outcome parameters included groin-to-reperfusion time, successful reperfusion [defined as a Thrombolysis in Cerebral Infarction (TICI) scale 2b-3], change in National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and mortality at 90 days.Results: Of the 881 included mothership patients with anterior circulation LVOS, 486 (55.2%) received bridging therapy with i.v.-rtPA prior to EVT, and 395 (44.8%) received EVT alone. Adjusted, multivariate linear mixed effect models revealed no difference in groin-to-reperfusion time between the groups (48 ± 36 vs. 49 ± 34 min; p = 0.299). Rates of successful reperfusion (TICI ≥ 2b) were higher in patients with bridging IVT (fixed effects estimate 0.410, 95% CI, 0.070; 0.750, p = 0.018). There was a trend toward a higher improvement in the NIHSS during hospitalization [ΔNIHSS: bridging-IVT group 8 (IQR, 9.8) vs. 4 (IQR 11) points in the EVT alone group; fixed effects estimate 1.370, 95% CI, −0.490; 3.240, p = 0.149]. mRS at 90 days follow-up was lower in the bridging IVT group [3 (IQR, 4) vs. 4 (IQR, 4); fixed effects estimate −0.350, 95% CI, −0.680; −0.010, p = 0.041]. There was a non-significantly lower 90 day mortality in the bridging IVT group compared with the EVT alone group (22.4% vs. 33.6%; fixed effects estimate 0.980, 95% CI −0.610; 2.580, p = 0.351). Rates of any intracerebral hemorrhage did not differ between both groups (4.1% vs. 3.8%, p = 0.864).Conclusions: This study provides evidence that bridging IVT might improve rates of successful reperfusion and long-term functional outcome in mothership patients with anterior circulation LVOS eligible for EVT

Effect of extracranial lesion severity on outcome of endovascular thrombectomy in patients with anterior circulation tandem occlusion: analysis of the TITAN registry

Introduction Endovascular treatment (EVT) for tandem occlusion (TO) of the anterior circulation is complex but effective. The effect of extracranial internal carotid artery (EICA) lesion severity on the outcomes of EVT is unknown. In this study we investigated the effect of EICA lesion severity on the outcomes of tandem occlusion EVT. Methods A multicenter retrospective TITAN (Thrombectomy In TANdem lesions) study that included 18 international endovascular capable centers was performed. Patients who received EVT for atherosclerotic TO with or without EICA lesion intervention were included. Patients were divided into two groups based on the EICA lesion severity (high-grade stenosis (>= 90% North American Symptomatic Carotid Endarterectomy Trial) vs complete occlusion). Outcome measures included the 90-day clinical outcome (modified Rankin Scale score (mRS)), angiographic reperfusion (modified Thrombolysis In Cerebral Ischemia (mTICI) at the end of the procedure), procedural complications, and intracranial hemorrhage at 24 hours follow-up. Results A total of 305 patients were included in the study, of whom 135 had complete EICA occlusion and 170 had severe EICA stenosis. The EICA occlusion group had shorter mean onset-to-groin time (259 +/- 120 min vs 305 +/- 202 min;p=0.037), more patients with diabetes, and fewer with hyperlipidemia. With respect to the outcome, mTICI 2b-3 reperfusion was lower in the EICA occlusion group (70% vs 81%;p=0.03). The favorable outcome (90-day mRS 0-2), intracerebral hemorrhage and procedural complications were similar in both groups. Conclusion Atherosclerotic occlusion of the EICA in acute tandem strokes was associated with a lower rate of mTICI 2b-3 reperfusion but similar functional and safety outcomes when compared with high-grade EICA stenosis

Complications Associated with Cerebral Aneurysm Morphology in Balloon-Assisted Coil Embolization of Ruptured and Unruptured Aneurysms-a Single-Center Analysis of 116 Consecutive Cases

BACKGROUND: We investigated the complication rates of balloon-assisted coil embolization of ruptured and unruptured cerebral aneurysms dependent on their morphologic characteristics in angiography. METHODS: The study was a single-center retrospective analysis of all consecutive endovascular balloon-assisted coiling interventions performed between April 2008 and December 2013. Data were extracted from a prospective database on an intention-to-treat basis. We described the clinical (Hunt & Hess score, modified Rankin scale) and technical results (Raymond Roy aneurysm occlusion scale) and analyzed the rate of periprocedural complications with regard to aneurysm subgroups of bifurcation aneurysms versus sidewall aneurysms. RESULTS: There were 116 interventions performed on 108 patients (mean age: 51.7 +/- 11.1 years), with 70/116 emergency procedures (60%), 36/116 elective procedures (31%), and 10/116 elective procedures on recurrent aneurysms (9%). The balloon was used in 108/116 cases (93%). Among the cases, 76/116 were bifurcation aneurysms and 40/116 were sidewall aneurysms. Periprocedural complications, such as rerupture, thrombus formation, distal embolism, coil-loop protrusion, and coil migration, occurred in 26/116 cases (22%). Complications occurred significantly more often in ruptured than unruptured bifurcation aneurysms (23 vs. 3 events, P < 0.05). There was a significantly higher rate of complications in bifurcation aneurysms compared with sidewall aneurysms (17% vs. 3%, P = 0.03). Six periprocedural complications were associated with a permanent neurologic deficit (6% of cases), all of which occurred in the subgroup of acutely ruptured aneurysms. CONCLUSION: The risk of periprocedural complications in balloon-assisted coil embolization of ruptured and unruptured cerebral aneurysms is linked to the morphologic presentation of the aneurysm; the complication rate was significantly higher in bifurcation aneurysms

Evaluation of flushing parameters for clear view vascular endoscopy

Vascular diseases like aneurysms or atherosclerosis belong to the leading causes of death. For diagnosis and treatment, medical imaging is essential. Standard imaging methods are Ultrasound, X-ray-based Angiography, Computed tomography or Magnet Resonant Imaging. Additionally, Intravascular Ultrasound or Optical Coherence Tomography are available for intravascular imaging. One imaging technique for direct investigation of the inner vessel is vascular endoscopy, also called angioscopy. It is based on the insertion of an optical endoscope into the blood vessel for direct imaging. Dependent on the vessel diameter, these endoscopes have to be very small. Angioscopy can provide valuable information about the condition of the vessel wall and serve for procedure observation or implant assessment. But angioscopy requires the absence of blood for a clear field of view. In prior research, we have already developed methods for the placement of a tiny optical fiber inside a catheter combination. As an essential step toward a clinical study, we now want to evaluate the flushing parameters needed to achieve a clear field of view for the endoscope. The parameters are affected by the blood flow and vessel diameter. We designed a test setup that allows angioscopic examination and the simulation of realistic conditions, such as blood flow and different vessel diameters and that includes a test pattern for image quality assessment

Direct aspiration first pass technique for the treatment of acute ischemic stroke: initial experience at a European stroke center

Introduction Over the past decade, endovascular techniques for the treatment of acute ischemic stroke have emerged significantly. However, revascularization rates are limited at approximately 80%, and mechanical thrombectomy procedures still last about 1h. Therefore, we investigated the novel direct aspiration first pass technique for its efficacy and safety. Methods Our neurointerventional database was screened for patients who received mechanical thrombectomy for acute ischemic stroke using the Penumbra 5MAX ACE aspiration catheter on an intention to treat basis between November 2013 and June 2014. Procedural data, including modified Thrombolysis in Cerebral Infarction (mTICI) score, procedural timings, and complications, as well as clinical data at admission and discharge, were analyzed. Results 54 patients received mechanical thrombectomy using the 5MAX ACE. Median age was 69 (39-94) years (54% were men). Baseline National Institutes of Health Stroke Scale (NIHSS) score was 15 (2-27) and 44/54 (81%) patients received intravenous thrombolysis. Vessel occlusion sites were 91% anterior circulation and 9% posterior circulation. A successful revascularization result (mTICI 2b) was achieved in 93% of cases whereas direct aspiration alone was successful in 30/54 (56%) cases; among these, median time from groin puncture to revascularization was 30min (9-113). Symptomatic intracranial hemorrhage occurred in 2/54 (4%) patients, and embolization to new territories in 3/54 (6%). Median NIHSS at discharge was 6 (0-24); 46% of patients were independent at discharge. Conclusions The direct aspiration first pass technique proofed to be fast, effective, and safe. Promising revascularization results can be achieved quickly in more than 50% of patients using this technique as the firstline option. Nevertheless, stent retrievers are still warranted in approximately 40% of cases to achieve a favorable revascularization result