138 research outputs found

    Neoadjuvant bevacizumab and anthracycline-taxane-based chemotherapy in 678 triple-negative primary breast cancers; results from the geparquinto study (GBG 44)†

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    Background We evaluated the pathological complete response (pCR) rate after neoadjuvant epirubicin, (E) cyclophosphamide (C) and docetaxel containing chemotherapy with and without the addition of bevacizumab in patients with triple-negative breast cancer (TNBC). Patients and methods Patients with untreated cT1c-4d TNBC represented a stratified subset of the 1948 participants of the HER2-negative part of the GeparQuinto trial. Patients were randomized to receive four cycles EC (90/600 mg/m2; q3w) followed by four cycles docetaxel (100 mg/m2; q3w) each with or without bevacizumab (15 mg/kg; q3w) added to chemotherapy. Results TNBC patients were randomized to chemotherapy without (n = 340) or with bevacizumab (n = 323). pCR (ypT0 ypN0, primary end point) rates were 27.9% without and 39.3% with bevacizumab (P = 0.003). According to other pCR definitions, the addition of bevacizumab increased the pCR rate from 30.9% to 41.8% (ypT0 ypN0/+; P = 0.004), 36.2% to 46.4% (ypT0/is ypN0/+; P = 0.009) and 32.9% to 43.3% (ypT0/is ypN0; P = 0.007). Bevacizumab treatment [OR 1.73, 95% confidence interval (CI) 1.23-2.42; P = 0.002], lower tumor stage (OR 2.38, 95% CI 1.24-4.54; P = 0.009) and grade 3 tumors (OR 1.68, 95% CI 1.14-2.48; P = 0.009) were confirmed as independent predictors of higher pCR in multivariate logistic regression analysis. Conclusions The addition of bevacizumab to chemotherapy in TNBC significantly increases pCR rate

    Der Umzug der Menschheit: Die transformative Kraft der Städte

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    Die Wucht der derzeitigen Urbanisierungsdynamik und ihre Auswirkungen sind so groß, dass sich weltweit Städte, Stadtgesellschaften, Regierungen und Internationale Organisationen diesem Trend stellen müssen. Ein „Weiter so wie bisher“, würde ohne gestaltende Urbanisierungspolitik zu einer nicht-nachhaltigen Welt-Städte-Gesellschaft führen. Nur wenn Städte und Stadtgesellschaften ausreichend handlungsfähig werden, können sie ihre Kraft für eine nachhaltige Entwicklung entfalten: In den Städten wird sich entscheiden, ob die Große Transformation zur Nachhaltigkeit gelingt. In diesem Buch werden die Erfolgsbedingungen dafür diskutiert

    Humanity on the move: Unlocking the transformative power of cities

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    The momentum of urbanization and its impacts are so massive that we must face up to this trend. In view of the existing cognitive, technical, economic and institutional path dependencies, a policy of business as usual – i.e. an unstructured, quasi-automatic urbanization – would lead to a non-sustainable ‘world cities society’. Only if cities and urban societies are sufficiently empowered can they make use of the opportunities for sustainability and successfully follow the urban transformation pathways. The success or failure of the Great Transformation will be decided in the cities. The WBGU discusses the relevant conditions for the success of this transformation in this report

    Development and justice through transformation: The Four Big ‘I’s. Special Report

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    2015 saw a historic double success for sustainability and climate policy. The 2030 Agenda for Sustainable Development, with its Sustainable Development Goals (SDGs), and the Paris Agreement on climate ­protection establish a system of ambitious policy goals for the world. The group of twenty major ­industrialized and emerging economies (G20) now needs to resolutely advance implementation of both agreements, seizing the opportunity of this ‘Great Transformation’ to sustainability as a unique ­modernization project that could offer substantial economic development opportunities. Complete ­decarbonization of the world economy, which is necessary to avoid the gravest climate risks, can only be achieved by profoundly ­transforming energy systems and other high-emissions infrastructures. This transformation could inspire ­Innovation and channel Investment into sustainability and climate protection, and into the kinds of ­sustainable Infrastructures that need to be ­established and expanded. At the same time, the transformation could combat inequality and promote ­Inclusion within societies and globally, thus becoming an equity project

    Deguelin Attenuates Reperfusion Injury and Improves Outcome after Orthotopic Lung Transplantation in the Rat

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    The main goal of adequate organ preservation is to avoid further cellular metabolism during the phase of ischemia. However, modern preservation solutions do rarely achieve this target. In donor organs hypoxia and ischemia induce a broad spectrum of pathologic molecular mechanisms favoring primary graft dysfunction (PGD) after transplantation. Increased hypoxia-induced transcriptional activity leads to increased vascular permeability which in turn is the soil of a reperfusion edema and the enhancement of a pro-inflammatory response in the graft after reperfusion. We hypothesize that inhibition of the respiration chain in mitochondria and thus inhibition of the hypoxia induced mechanisms might reduce reperfusion edema and consecutively improve survival in vivo. In this study we demonstrate that the rotenoid Deguelin reduces the expression of hypoxia induced target genes, and especially VEGF-A, dose-dependently in hypoxic human lung derived cells. Furthermore, Deguelin significantly suppresses the mRNA expression of the HIF target genes VEGF-A, the pro-inflammatory CXCR4 and ICAM-1 in ischemic lungs vs. control lungs. After lung transplantation, the VEGF-A induced reperfusion-edema is significantly lower in Deguelin-treated animals than in controls. Deguelin-treated rats exhibit a significantly increased survival-rate after transplantation. Additionally, a downregulation of the pro-inflammatory molecules ICAM-1 and CXCR4 and an increase in the recruitment of immunomodulatory monocytes (CD163+ and CD68+) to the transplanted organ involving the IL4 pathway was observed. Therefore, we conclude that ischemic periods preceding reperfusion are mainly responsible for the increased vascular permeability via upregulation of VEGF. Together with this, the resulting endothelial dysfunction also enhances inflammation and consequently lung dysfunction. Deguelin significantly decreases a VEGF-A induced reperfusion edema, induces the recruitment of immunomodulatory monocytes and thus improves organ function and survival after lung transplantation by interfering with hypoxia induced signaling
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