TY - JOUR A1 - Linke, Christian A1 - Wösle, Markus A1 - Harder, Anja T1 - Anti-cancer agent 3-bromopyruvate reduces growth of MPNST and inhibits metabolic pathways in a representative in-vitro model JF - BMC cancer N2 - Background Anticancer compound 3-bromopyruvate (3-BrPA) suppresses cancer cell growth via targeting glycolytic and mitochondrial metabolism. The malignant peripheral nerve sheath tumor (MPNST), a very aggressive, therapy resistant, and Neurofibromatosis type 1 associated neoplasia, shows a high metabolic activity and affected patients may therefore benefit from 3-BrPA treatment. To elucidate the specific mode of action, we used a controlled cell model overexpressing proteasome activator (PA) 28, subsequently leading to p53 inactivation and oncogenic transformation and therefore reproducing an important pathway in MPNST and overall tumor pathogenesis. Methods Viability of MPNST cell lines S462, NSF1, and T265 in response to increasing doses (0-120 mu M) of 3-BrPA was analyzed by CellTiter-Blue (R) assay. Additionally, we investigated viability, reactive oxygen species (ROS) production (dihydroethidium assay), nicotinamide adenine dinucleotide dehydrogenase activity (NADH-TR assay) and lactate production (lactate assay) in mouse B8 fibroblasts overexpressing PA28 in response to 3-BrPA application. For all experiments normal and nutrient deficient conditions were tested. MPNST cell lines were furthermore characterized immunohistochemically for Ki67, p53, bcl2, bcl6, cyclin D1, and p21. Results MPNST significantly responded dose dependent to 3-BrPA application, whereby S462 cells were most responsive. Human control cells showed a reduced sensitivity. In PA28 overexpressing cancer cell model 3-BrPA application harmed mitochondrial NADH dehydrogenase activity mildly and significantly failed to inhibit lactate production. PA28 overexpression was associated with a functional glycolysis as well as a partial resistance to stress provoked by nutrient deprivation. 3-BrPA treatment was not associated with an increase of ROS. Starvation sensitized MPNST to treatment. Conclusions Aggressive MPNST cells are sensitive to 3-BrPA therapy in-vitro with and without starvation. In a PA28 overexpression cancer cell model leading to p53 inactivation, thereby reflecting a key molecular feature in human NF1 associated MPNST, known functions of 3-BrPA to block mitochondrial activity and glycolysis were reproduced, however oncogenic cells displayed a partial resistance. To conclude, 3-BrPA was sufficient to reduce NF1 associated MPNST viability potentially due inhibition of glycolysis which should lead to the initiation of further studies and promises a potential benefit for NF1 patients. KW - MPNST KW - NF1 KW - 3-BrPA KW - glycolysis KW - mitochondrial respiration KW - p53 KW - starvation KW - cell cycle KW - PA28 KW - B8 fibroblasts Y1 - 2020 U6 - https://doi.org/10.1186/s12885-020-07397-w SN - 1471-2407 VL - 20 IS - 1 PB - BioMed Central CY - London ER - TY - JOUR A1 - Kruckenberg, Helmut A1 - Müller, Thomas A1 - Freuling, Conrad A1 - Mühle, Ralf-Udo A1 - Globig, Anja A1 - Schirrmeier, Horst A1 - Buss, Melanie A1 - Harder, Timm A1 - Kramer, Matthias A1 - Teske, Kathrin A1 - Polderdijk, Kees A1 - Wallschläger, Hans-Dieter A1 - Hlinak, Andreas T1 - Serological and virological survey and resighting of marked wild geese in Germany JF - European journal of wildlife research N2 - In order to investigate the potential role of arctic geese in the epidemiology, the spatial and temporal spread of selected avian diseases, in autumn 2002, a virological and serological survey designed as capture-mark-resighting study was conducted in one of the most important coastal resting sites for migratory waterfowl in Germany. Orophatyngeal, cloacal swabs and blood samples were collected from a total of 147 birds comprising of three different arctic geese species including White-fronted Goose (Anser albifrons), Tundra Bean Goose (Anser fabalis rossicus), Pink-footed Goose (Anser brachyrhynchus) as well as from 29 non-migratory Canada Geese (Branta canadensis). Altogether, six adeno-like viruses (ALV; 95% CI, 1.74-9.92%) and two avian paramyxoviruses (APMV-4; 95% Cl, 0.19-5.53%) were isolated mainly from juvenile White-fronted Geese. In addition, four Canada Geese were infected with lentogenic APMV-1 (95% CI, 3.89-31.66%) at the date of sampling. No avian influenza viruses, reo-like viruses could be isolated despite serological evidence. Likewise, no evidence of current or previous infection by West Nile virus was found. Of the 147 birds tagged in the following years, 137 birds were resighted between 2002 and 2008 accumulating to 1925 sightings. About 90% of all sightings were reported from the main wintering and resting sites in Germany and The Netherlands. Eight of the resighted geese were virus positive (ALV and APMV-4) at the time point of sampling in 2002. KW - Wild geese KW - Anser albifrons KW - White-fronted goose KW - Disease KW - Spatial distribution KW - Winter KW - Distribution KW - Branta canadensis KW - Canada goose KW - Virus KW - Infection KW - Neckbanding Y1 - 2011 U6 - https://doi.org/10.1007/s10344-011-0514-1 SN - 1612-4642 VL - 57 IS - 5 SP - 1025 EP - 1032 PB - Springer CY - New York ER -