Stotz M.,Auenbruggerplatz |
Gerger A.,Auenbruggerplatz |
Haybaeck J.,Medical University of Graz |
Kiesslich T.,Paracelsus Medical University |
And 3 more authors.
Anticancer Research | Year: 2015
Hepatocellular carcinoma (HCC) is an aggressive tumor and the sixth most common form of cancer worldwide. Surgery is the gold-standard treatment for local disease and often complemented by radiofrequency ablation or transarterial chemoembolization. In advanced disease, therapy options are limited and relapse and metastasis are common. Systemic therapy with cytotoxic drugs such as doxorubicin and cisplatin achieves low objective response rates (typically <10%) and even sorafenib, an orally administered tyrosine kinase inhibitor considered a breakthrough when introduced, prolongs median survival by little more than a year. Sorafenib blocks platelet-derived growth factor, vascular endothelial growth factor, c-KIT and rapidly accelerated fibrosarcoma signaling, and belongs to a new class of targeted drugs. It has become standard treatment for advanced-stage HCC in recent years. To date, no other agent has been shown to be more effective than sorafenib in the clinical setting, which highlights the need for ongoing research to address this important clinical challenge. The current review focuses on recent advances in molecular targeted therapy for HCC. We explore the current status of evidence, identify areas of pressing experimental need, and provide an outline of promising future therapeutic options.
Papp Z.,Debrecen University |
Edes I.,Debrecen University |
Fruhwald S.,Auenbruggerplatz |
De Hert S.G.,Ghent University |
And 21 more authors.
International Journal of Cardiology | Year: 2012
The molecular background of the Ca2+-sensitizing effect of levosimendan relates to its specific interaction with the Ca2+-sensor troponin C molecule in the cardiac myofilaments. Over the years, significant preclinical and clinical evidence has accumulated and revealed a variety of beneficial pleiotropic effects of levosimendan and of its long-lived metabolite, OR-1896. First of all, activation of ATP-sensitive sarcolemmal K+ channels of smooth muscle cells appears as a powerful vasodilator mechanism. Additionally, activation of ATP-sensitive K+ channels in the mitochondria potentially extends the range of cellular actions towards the modulation of mitochondrial ATP production and implicates a pharmacological mechanism for cardioprotection. Finally, it has become evident, that levosimendan possesses an isoform-selective phosphodiesterase-inhibitory effect. Interpretation of the complex mechanism of levosimendan action requires that all potential pharmacological interactions are analyzed carefully in the framework of the currently available evidence. These data indicate that the cardiovascular effects of levosimendan are exerted via more than an isolated drug-receptor interaction, and involve favorable energetic and neurohormonal changes that are unique in comparison to other types of inodilators. © 2011 Elsevier Ireland Ltd.
Berger L.,Vienna University of Technology |
Eichler J.,Medical University of Graz |
Ryll E.J.S.,Westphalian Wilhelms University |
Fischerauer S.,Auenbruggerplatz |
And 4 more authors.
Materials Science and Engineering C | Year: 2016
Flexible intramedullary nailing (FIN) is a minimally invasive and widespread standard method for osteosynthesis of pediatric long bone fractures. In the case of unstable fractures of the lower extremity, interlocking systems need to be used to prevent axial shortening and subsequent perforation of the nail at its insertion site. In the present study, four different screw-fixed interlocking systems for FINs (Hofer TwinPlug with two 3-mm titanium interlocking screws, Hofer FixPlug with 3-mm titanium interlocking screw, Hofer Plug with 3.5-mm titanium interlocking screw, and Hofer Plug with 3-mm titanium interlocking screw) in comparison with the commonly used Ender stainless steel nails (locked with 3.5-mm screw) were experimentally investigated in cadaveric lamb tibiae, regarding their load characteristics and failure modes in the case of heavy loading. The specimens were subjected to sequential axial cyclic loading of 5000cycles with stepwise increase of the load amplitude until failure. Migration of locking screws and internal damage of bone tissue was quantified by micro-computed tomography (CT) imaging. Ender nails failed on average at a peak load of 800 N, TwinPlugs at 1367 N, FixPlugs at 1222 N, Plugs 3.5mm at 1225 N and Plugs 3.0mm at 971 N. TwinPlugs, FixPlugs, and Plugs 3.5mm failed in a slow manner over several hundred loading cycles, whereas Ender nails and Plugs 3.0mm exhibited abrupt failure without any prior indication. Our results confirm that axial stability of FIN can be further improved by screw-fixed plugs by simultaneously avoiding shortcomings of an eye-locked system, which the Ender nails are. Considering biomechanical results, plug interlocking systems with 3.5-mm screws should be favored over conventional Ender nails and plugs with 3-mm screws. © 2016 Elsevier B.V. All rights reserved.
Mrak K.,Auenbruggerplatz |
Liegl-Atzwanger B.,Institute of Pathology |
Haybaeck J.,Institute of Pathology |
Petritsch W.,Medical University of Graz |
And 2 more authors.
Anticancer Research | Year: 2015
Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal tumor entity of the gastrointestinal tract. In fewer than 5% of cases, primary GISTs are located in the duodenum. Surgery represents the treatment of choice for localized tumor disease and remains challenging in GISTs located at the duodenum. The optimal surgical approach is currently discussed controversially in the literature due to the fact that extended resections in terms of pancreaticoduodenectomy may cause significant postoperative morbidity and mortality compared to limited resection. We report on a rare case of GIST located in the upper part of the duodenum treated by limited surgical resection. Avoidance of postoperative complications may lead to optimal oncological outcome in selected patients.