Histone deacetylase inhibition sensitizes osteosarcoma to heavy ion radiotherapy

Background: Minimal improvements in treatment or survival of patients with osteosarcoma have been achieved during the last three decades. Especially in the case of incomplete tumor resection, prognosis remains poor. Heavy ion radiotherapy (HIT) and modern anticancer drugs like histone deacetylase inhibitors (HDACi) have shown promising effects in osteosarcoma in vitro. In this study, we tested the effect of HIT and the combination of HIT and the HDACi suberoylanilide hydroxamic acid (SAHA) in a xenograft mouse model. Methods: Osteosarcoma xenografts were established by subcutaneous injection of KHOS-24OS cells and treated with either vehicle (DMSO), SAHA, HIT or HIT and SAHA. Tumor growth was determined and tumor necrosis, proliferation rate, apoptotic rate as well as vessel density were evaluated. Results: Here, we show that the combination of HIT and SAHA induced a significant delay of tumor growth through increased rate of apoptosis, increased expression of p53 and p21Waf1/Cip1, inhibition of proliferation and angiogenesis compared to tumors treated with HIT only. Conclusion: HIT and in particular the combination of HIT and histone deacetylase inhibition is a promising treatment strategy in OS and may be tested in clinical trials

High SIRT1 expression is a negative prognosticator in pancreatic ductal adenocarcinoma

Background: Several lines of evidence indicate that Sirt1, a class III histone deacetylase (HDAC) is implicated in the initiation and progression of malignancies and thus gained attraction as druggable target. Since data on the role of Sirt1 in pancreatic ductal adenocarcinoma (PDAC) are sparse, we investigated the expression profile and prognostic significance of Sirt1 in vivo as well as cellular effects of Sirt1 inhibition in vitro. Methods: Sirt1 expression was analyzed by immunohistochemistry in a large cohort of PDACs and correlated with clinicopathological and survival data. Furthermore, we investigated the impact of overexpression and small molecule inhibition on Sirt1 in pancreatic cancer cell culture models including combinatorial treatment with chemotherapy and EGFR-inhibition. Cellular events were measured quantitatively in real time and corroborated by conventional readouts including FACS analysis and MTT assays. Results: We detected nuclear Sirt1 expression in 36 (27.9%) of 129 PDACs. SIRT1 expression was significantly higher in poorly differentiated carcinomas. Strong SIRT1 expression was a significant predictor of poor survival both in univariate (p = 0.002) and multivariate (HR 1.65, p = 0.045) analysis. Accordingly, overexpression of Sirt1 led to increased cell viability, while small molecule inhibition led to a growth arrest in pancreatic cancer cells and impaired cell survival. This effect was even more pronounced in combinatorial regimens with gefitinib, but not in combination with gemcitabine. Conclusions: Sirt1 is an independent prognosticator in PDACs and plays an important role in pancreatic cancer cell growth, which can be levered out by small molecule inhibition. Our data warrant further studies on SIRT1 as a novel chemotherapeutic target in PDAC

Selfies and Dronies. Zu Chancen und Gefährdungen der Dynamisierung des Selbst in virtuellen Welten

Die Phänomene Selfies und Dronies werden einer genaueren Betrachtung unterzogen und immanente Chancen und Gefährdungen aufgezeigt. Die für die Identitätsentwicklung massgebliche Spiegelungsfunktion, welche diesen egotechnischen Medien innewohnen, kann als eine wertvolle Errungenschaft für individuelle Erkenntnisprozesse gewertet werden. Als Kehrseite der Medaille können Suchtverhalten und andere psychiatrische Erkrankungen begünstigt werden. Aber auch andere Formen von virtuellen Selbstprojektionen und Neuverkörperlichungen in Form von Avataren und Cyborgs können, begleitet von sorgfältiger Handhabung in Therapie und Kunsttherapie, eingesetzt werden, um identitätsbildende Prozesse anzustossen und Selbstwahrnehmungsprozesse zu fördern

Virtual Reality Therapie. Entwicklung, Durchführung und Evaluation eines Applikationsmodells für die kunsttherapeutische Arbeit mit psychiatrischen Patienten

Auf dem Hintergrund von medientheoretischen und gesellschaftspolitischen Positionen von Autoren wie Rittmann, Nusselder, Rötzer, Volkart, Flusser, McLuhan und Turkle sowie kunsttherapeutischen Perspektiven von Schütz, Neumann, Parker-Bell, Orr und Wichelhaus zur Funktion von virtuellen Welten und digitalen Bildern für Wahrnehmung und Erfahrung heute lebender Menschen rückte zunehmend auch die Frage nach der Bedeutung für die Gesundheit in den Blick. Können diese Medien Krankheiten auslösen oder sinnvoll für Therapien genutzt werden? Zur Beantwortung dieser Frage wurde mit der vorliegenden Untersuchung eine kunsttherapeutische Behandlungsmethode in der Virtual Reality „Second Life“ für psychiatrische Patienten entwickelt, durchgeführt und evaluiert. An der randomisierten Pilotstudie nahmen 24 Probanden mit Persönlichkeitsstörungen und Depressionen teil. Ausgehend von der These, dass sich das für die Studie/Untersuchung konzipierte kunsttherapeutische Virtual Therapie Modell positiv auf Körperselbstbild, Befindlichkeit und Identität auswirkt wurden diese Faktoren mit qualitativen und quantitativen diagnostischen Methoden nachgewiesen. Die Resultate sind positiv, zeigen jedoch auch Unterschiede in der Reagibilität auf die Therapieinhalte zwischen Patienten mit Depressionen und Persönlichkeitsstörungen. Anhand einer exemplarischen Fallanalyse werden die Behandlungsmethode und die therapeutischen Ergebnisse abschließend differenziert aufgezeigt

The convergency of print and online-media, showed on the example of the company BACKSPIN.Media

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A statistical analysis of Navy bachelor housing user requirements.

An analysis of previously collected data pertaining to critical areas of user satisfaction with government bachelor quarters was conducted to pin point critical areas for consideration in future housing design and construction. The data, collected from enlisted men and officers "living both on and off base, was analyzed using both non-parametric comparative statistics (including correlation measures) and the parametric analyses of the variance. The survey which served as the data source was designed and administered as a previous thesis requirement.http://archive.org/details/statisticalanaly00ehemLieutenant, United States NavyApproved for public release; distribution is unlimited

Detection of hydrogen using graphene

Irradiation dynamics of a single graphene sheet bombarded by hydrogen atoms is studied in the incident energy range of 0.1 to 200 eV. Results for reflection, transmission, and adsorption probabilities, as well as effects of a single adsorbed atom to the electronic properties of graphene, are obtained by the quantum-classical Monte Carlo molecular dynamics within a self-consistent-charge-density functional tight binding formalism We compare these results with those, distinctly different, obtained by the classical molecular dynamics

Role of PP2Cα in cell growth, in radio- and chemosensitivity, and in tumorigenicity

<p>Abstract</p> <p>Background</p> <p>PP2Cα is the representative member of the type 2C family of protein phosphatases, and it has recently been implicated in the regulation of p53-, TGFβ-, cyclin-dependent kinase- and apoptosis-signaling. To investigate the role of PP2Cα in cell growth and in radio- and chemosensitivity, wild type and PP2Cα siRNA-expressing MCF7 cells were subjected to several different viability and cell cycle analyses, both under basal conditions and upon treatment with radio- and chemotherapy. By comparing the growth of tumors established from both types of cells, we also evaluated the involvement of PP2Cα in tumorigenesis.</p> <p>Results</p> <p>It was found that knockdown of PP2Cα did not affect the proliferation, the clonogenic survival and the membrane integrity of MCF7 cells. In addition, it did not alter their radio- and chemosensitivity. For PP2Cα siRNA-expressing MCF7 cells, the number of cells in the G0/G1 phase of the cell cycle was reduced, the induction of the G1 block was attenuated, the number of cells in G2/M was increased, and the induction of the G2 block was enhanced. The tumorigenic potential of PP2Cα siRNA-expressing MCF7 cells was found to be higher than that of wild type MCF7 cells, and the in vivo proliferation of these cells was found to be increased.</p> <p>Conclusion</p> <p>Based on these findings, we conclude that PP2Cα is not involved in controlling cell growth and radio- and chemosensitivity in vitro. It does, however, play a role in the regulation of the cell cycle, in the induction of cell cycle checkpoints and in tumorigenesis. The latter notion implies that PP2Cα may possess tumor-suppressing properties, and it thereby sets the stage for more elaborate analyses on its involvement in the development and progression of cancer.</p