Target-specific glioma therapy in an immunocompetent mouse model : meeting abstract

Objective: Establishment of an immunocompetent mouse model representing the typical progressive stages observed in malignant human gliomas for the in vivo evaluation of novel target-specific regimens. Methods: Isolated clones from tumours that arose spontaneously in GFAP-v-src transgenic mice were used to develop a transplantable brain tumour model in syngeneic B6C3F1 mice. STAT3 protein was knocked down by infection of tumour cells with replication-defective lentivirus encoding STAT3-siRNA. Apoptosis is designed to be induced by soluble recombinant TRAIL + chemical Bcl-2/Bcl-xL inhibitors. Results: Striatal implantation of 105 mouse tumour cells resulted in the robust development of microscopically (2 – 3 mm) infiltrating malignant gliomas. Immunohistochemically, the gliomas displayed the astroglial marker GFAP and the oncogenic form of STAT3 (Tyr-705-phosphorylated) which is found in many malignancies including gliomas. Phosphorylated STAT3 was particularly prominent in the nucleus but was also found at the plasma membrane of peripherally infiltrating glioma cells. To evaluate the role of STAT3 in tumour progression, we stably expressed siRNA against STAT3 in several murine glioma cell lines. The effect of STAT3 depletion on proliferation, invasion and survival will be first assessed in vitro and subsequently after transplantation in vivo. Upstream and downstream components of the STAT3 signalling pathway as well as possible non-specific side effects of STAT3-siRNA expression after lentiviral infection will be examined, too. Conclusions: Its high rate of engraftment, its similarity to the malignant glioma of origin, and its rapid locally invasive growth should make this murine model useful in testing novel therapies for malignant gliomas

Forschungsbericht Nr. 2016-01, Februar 2016

Virtualization is a promising approach for consultancies to optimize their consulting processes and thereby an innovative option to gain a sustainable competitive advantage. Using state-of-the-art ICT enables consultancies to deliver customized solutions anytime and anywhere while the individual work load of every consultant can be optimized. The downside of the virtualization is the reduced direct interaction of clients and consultants and thus the risk of weaker client-consultant-relationships. Whether virtualization is the right approach for a specific client or project should be clarified within a sound decision process. We have designed a virtualization decision process based on insights from two Delphi studies with one client panel and one consultancy panel

Ermittlung des Virtualisierungspotenzials von Beratungsleistungen im Consulting

Die Beratungsbranche sieht sich, genau wie ihre Klienten, ständig neuen Herausforderungen und sich verändernden Rahmenbedingungen gegenüber. Beratungsanbieter sollten daher ihr Leistungsportfolio immer wieder kritisch infrage stellen. Obwohl sie die Wettbewerbsfähigkeit ihrer Klienten durch innovative Lösungen stärken und dort maßgeblich an der Entwicklung neuer Konzepte zur Digitalisierung beteiligt sind, wird bei der Erbringung von Beratungsleistungen oft nur auf traditionelle Face-to-Face Ansätze zurückgegriffen. Ein virtueller Prozess ist demgegenüber ein Prozess, in dem die physische Interaktion verschwindet. Der Übergang eines physischen Prozesses hin zu einem virtuellen Prozess wird als „Prozess Virtualisierung“ bezeichnet. Virtualisierung ist ein Trend, dem sich Beratungsunternehmen auch hinsichtlich ihrer eigenen Geschäftsprozesse stellen müssen. Theoriegeleitet sowie auf Basis ergänzender empirischer Forschung leiten wir in diesem Beitrag ein mögliches Vorgehen ab, um das Virtualisierungspotenzial von Beratungsprozessen (oder deren Teilschritten) im konkreten Fall ex ante beurteilen zu können

Stärkung der Führungskompentenz in Treuhand-Beteiligungsunternehmen bei der Reorganisation und Umgestaltung der ostdeutschen Wirtschaft

"Das nachfolgende Kapitel gibt einen differenzierten Einblick in die Kommunikations- und Interaktionsprobleme und -annäherungen zwischen westdeutschen und ostdeutschen Führungskräften, die in Vorständen und Geschäftsführungen ostdeutscher Unternehmen zusammenarbeiten. Die Untersuchungen, die auch Selbst- und Fremdeinschätzungen einschlossen, zeigen deutlich, daß 1989 zwei unterschiedliche (Denk- und Arbeits-)Kulturen aufeinandergestoßen sind, die zu vielfältigen Rollenkonflikten, Vorurteilen und zeitweiligen Abgrenzungen führten, gegenwärtig und insgesamt jedoch zu Tendenzen der Annäherung und gegenseitigen Akzeptanz. Es werden vielfältige Anregungen zu Inhalten und Formen für die Führungskräfte-Weiterbildung gegeben." (Autorenreferat

The nontoxic natural compound Curcumin exerts anti-proliferative, anti-migratory, and anti-invasive properties against malignant gliomas

Background: New drugs are constantly sought after to improve the survival of patients with malignant gliomas. The ideal substance would selectively target tumor cells without eliciting toxic side effects. Here, we report on the anti-proliferative, anti-migratory, and anti-invasive properties of the natural, nontoxic compound Curcumin observed in five human glioblastoma (GBM) cell lines in vitro. Methods: We used monolayer wound healing assays, modified Boyden chamber trans-well assays, and cell growth assays to quantify cell migration, invasion, and proliferation in the absence or presence of Curcumin at various concentrations. Levels of the transcription factor phospho-STAT3, a potential target of Curcumin, were determined by sandwich-ELISA. Subsequent effects on transcription of genes regulating the cell cycle were analyzed by quantitative real-time PCR. Effects on apoptosis were determined by caspase assays. Results: Curcumin potently inhibited GBM cell proliferation as well as migration and invasion in all cell lines contingent on dose. Simultaneously, levels of the biologically active phospho-STAT3 were decreased and correlated with reduced transcription of the cell cycle regulating gene c-Myc and proliferation marking Ki-67, pointing to a potential mechanism by which Curcumin slows tumor growth. Conclusions: Curcumin is part of the diet of millions of people every day and is without known toxic side effects. Our data show that Curcumin bears anti-proliferative, anti-migratory, and anti-invasive properties against GBM cells in vitro. These results warrant further in vivo analyses and indicate a potential role of Curcumin in the treatment of malignant gliomas

Unsecured Intracranial Aneurysms and Induced Hypertension in Cerebral Vasospasm: Is Induced Hypertension Safe?

Background: Induced hypertension is an established therapy to treat cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH) to prevent delayed ischemic deficits. Currently, there is minimal evidence available assessing the risk of induced hypertension in the presence of unsecured aneurysms. The aim of this study was to investigate the impact of induced hypertension on the rupturing of unsecured aneurysms in treating CVS. Methods: We conducted a retrospective analysis between 1999 and 2009. Patients with unsecured aneurysms treated with induced hypertension were identified and stratified as having (1) additional unruptured unsecured aneurysms or (2) ruptured unsecured aneurysms. Hemodynamic parameters were analyzed and any bleeding recorded. Results: Forty-five patients were included. Of those, 41 had 71 additional unruptured unsecured aneurysms and four patients had four ruptured unsecured aneurysms. The mean size of unsecured aneurysms was: 4.0±1.9mm (additional unruptured) and 5.3±2.2mm (ruptured), respectively. No aneurysm ruptured during therapy. Combining our data with previously published studies, there appears to be no increase of risk for aneurysm rupture by induced hypertension when compared to the natural history (0.5% for group 1, 2.9% for group 2). Conclusion: These data corroborate that induced hypertension may be a safe treatment option to prevent cerebral infarction in CVS, even in the presence of unsecured aneurysms. Our findings suggest that induced hypertension does not increase rupture of unsecured aneurysms. Given the high risk for cerebral infarction in severe CVS, we conclude that induced hypertension should not be omitted due to the presence of unsecured aneurysm

Micromagnetic investigation of domain and domain wall evolution through the spin-reorientation transition of an epitaxial NdCo5 film

The domain pattern and the domain wall microstructure throughout the spin-reorientation transition of an epitaxial NdCo5 thin film are investigated by micromagnetic simulations. The temperature-dependent anisotropy constants K1 and K2, which define the anisotropy energy term in the model, are chosen to reflect the easy axis—easy cone—easy plane spin-reorientation transition observed in epitaxial NdCo5 thin films. Starting at the high-temperature easy c-axis regime, the anisotropy constants are changed systematically corresponding to a lowering of the temperature of the system. The character of the domain walls and their profiles are analysed. The calculated domain configurations are compared to the experimentally observed temperature-dependent domain structure of an in-plane textured NdCo5 thin film