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Publication Jahresbericht 2022 / Universität Hohenheim(2023) Universität Hohenheim; Dabbert, StephanPublication Jahresbericht 2021 / Universität Hohenheim(2022) Universität Hohenheim; Dabbert, StephanPublication Doing research in China : ein Einblick in die Kultur und Forschungslandschaft Chinas. - China-Kompetenz in Hohenheim(2020) Klenk, Johannes; Schmidt, Alexander; Waschek, FranziskaMit dieser Broschüre soll Wissenschaftlerinnen und Wissenschaftlern, die sich für Forschung in und mit China interessieren oder eventuell bereits ein konkretes Forschungsvorhaben mit Bezug zu China haben, einen Überblick über einige Themen geben werden, die aus der Sicht der Autoren für geplante Projekte mit chinesischen Partnerinnen und Partnern oder für Aufenthalte vor Ort relevant sind.Publication Jahresbericht 2020 / Universität Hohenheim(2021) Universität Hohenheim; Dabbert, StephanPublication Identifizierung von Zielmolekülen für die innovative Therapie pleuraler Mesotheliome : Untersuchung von Tyrosinkinasen sowie Komponenten der NF2/mTOR- und p14/p16-Signalwege(2020) Mönch, Dina; Ott, GermanMalignant pleural mesothelioma is a diffuse growing, rare form of cancer affecting the outer lining of the inner chest wall (pleura). About 90% of the cases are related to a prolonged exposure to asbestos. MPM is difficult to distinguish from other respiratory diseases and is therefore often diagnosed at late stages, when curative surgery is no longer a treatment option. Moreover, radiotherapy and chemotherapy only show limited efficacy, including a less than 5% five year survival rate. Targeting single molecules involved in progression, growth and metastasis with specific inhibitors might be a promising new approach for this tumour entity. However, till date there are no recommendations for targeted therapies in MPM. Although specific inhibitors of mTOR or single kinases suppressed MPM tumor growth in pre-clinical studies, they were not effective in clinical trials. Therefore, there is an urgent need to identify new treatment approaches and targets. The aim of this PhD thesis was to identify new therapeutical targets for the treatment of malignant pleural mesothelioma with special emphasis on the simultaneous inhibition of tyrosine kinases, p14/p16 and NF2/mTOR pathway molecules. Moreover it was focused on molecules within these pathways for which specific inhibitors are already available. One key aspect of this project was to examine mTOR and ALK as potential therapeutic targets, and to determine the efficacy of ALK and mTOR inhibition on tumor cell growth with ALK inhibitor Crizotinib and mTOR inhibitor Rapamycin, in individual and combinatorial treatment. Therefore, an ALK and mTOR co-expressing patient-derived MPM xenograft model was used. Crizotinib alone did not show anti-tumor efficacy whereas combined treatment with Rapamycin enhanced anti-tumor effect of Rapamycin treatment, and lead to a reduction in tumor volume in the MPM xenograft model. Simultaneous inhibition not only suppressed mTOR and ALK pathway transduction but also Rapamycin–induced AKT activation. Combined therapy significantly suppressed cell proliferation and induced autophagy as well as caspase-independent, necrotic cell death compared to the single treatment. Although only 5% of MPM tumors coexpress ALK and mTOR, the results of this study confirm that combined treatment with Rapamycin and Crizotinib can be a therapeutic treatment option in pleural mesothelioma. Further analyses included the investigation of p14/p16 regulator BMI1 as a therapeutic target for the treatment of MPM. Increased BMI1 expression was detected in 81.3% of the MPM patient samples analyzed. Coexpression of BMI1 and mTOR, a prerequisite for combined therapy, was present in 25% of the analyzed cases, as detected by qRT-PCR and IHC. Monotherapy with mTORC1/2 inhibitor INK-128, mTOR/PI3K inhibitor BEZ235 and BMI1 inhibitor PTC-209 resulted in dose-dependent reduction of cell viability in three MPM cell lines tested. Co-treatment with mTOR inhibitors enhanced therapeutic effect of BMI1 inhibition 2-fold (BEZ235) and 10-fold (INK-128) respectively, thus representing an appealing approach for targeted therapy in MPM. The last part of the project aimed to identify new therapeutic targets by genome-wide, array-based CNV- analysis of 42 MPM. Array-based ONCOSCAN technology, especially developed for formalin-fixed and paraffin-embedded tissue, and GISTIC algorithm identified new gains on chromosome 9p22.2, 13q34 and chromosome 19 (19p13.3, 19p13.11 and 19q13.2), which were verified via qPCR and FISH. GISTIC-reanalysis of previously published data sets provided genomic data of 182 MPM tumors in total and was used to identify critical regions for further research on new target genes like oncogenic kinases AKT1, AKT2, MAP3K10 and PTK2 among others. AKT2 and MAP3K10 gene and protein expression was elevated in the tested MPM cohort. Especially AKT isoforms AKT1 and AKT2 represent attractive targets with important therapeutic potential, since pan-AKT inhibitor Ipatasertib is currently being tested in clinical trials for other tumors. In conclusion, the results of this PhD thesis demonstrate the potential for small molecule inhibitors as therapeutic strategies for the treatment of malignant pleural mesothelioma. Moreover, the results of this study suggest that the concurrent inhibition of mTOR, ALK and AKT pathways is a viable therapeutic strategy, as these pathways are frequently simultaneously activated in pleural mesothelioma.Publication Jahresbericht 2019 / Universität Hohenheim(2020) Universität Hohenheim; Dabbert, StephanPublication Jahresbericht 2018 / Universität Hohenheim(2019) Universität Hohenheim; Dabbert, StephanPublication Jahresbericht 2017 / Universität Hohenheim(2018) Universität Hohenheim; Dabbert, StephanPublication Jahresbericht 2016 / Universität Hohenheim(2017) Universität Hohenheim; Dabbert, StephanPublication Jahresbericht mit Zahlenspiegel 2015 / Universität Hohenheim(2016) Universität Hohenheim; Dabbert, StephanPublication Jahresbericht mit Zahlenspiegel 2014 / Universität Hohenheim(2015) Universität Hohenheim; Dabbert, StephanPublication Jahresbericht mit Zahlenspiegel 2013 / Universität Hohenheim(2014) Universität Hohenheim; Dabbert, StephanPublication Jahresbericht 2012 / Universität Hohenheim(2013) Universität Hohenheim; Dabbert, StephanPublication Charakterisierung der antimikrobiellen Aktivität von High-mobility group box 2(2013) Küchler, Robert; Wehkamp, JanThe human body is continuously exposed to an enormous amount of microbes. Especially surfaces like the skin or the gastrointestinal mucosa are in close contact with large numbers of microorganisms, including bacteria, fungi and viruses. A very effective innate immune system protects the intestinal mucosa from an overgrowth of commensal bacteria and penetration by pathogenic microbes. Besides an efficient layer of thick mucus, antimicrobial peptides and proteins (AMPs) which can inhibit the growth of microorganisms or even destroy them are an essential part of the epithelial barrier. In 2009, as a part of my diploma thesis, I could show that high-mobility group box 2 (HMGB2) exhibits antimicrobial activity against E. coli. The aim of this PhD thesis was to characterize and further clarify this new function. HMGB2 was recombinantly expressed and systematically analyzed for antimicrobial activity. Notably, several gram-negative and gram-positive bacteria of the normal gut flora were critically affected by HMGB2. In addition, bactericidal properties against the pathogenic bacterial strain Staphylococcus aureus were detected via electron microscopic analysis. Furthermore potential influences of intestinal environmental conditions on the activity of HMGB2 were investigated. Changes in the pH or the generation of a reducing environment altered the activity of the protein only to a small amount. To localize the part of HMGB2 which is essential for its antimicrobial activity, three peptides which represent three regions of the protein were recombinantly expressed. An activity screening with the three peptides showed that the two DNA-binding-domains HMG-Box A and B are crucial for the antimicrobial effects. An expression study showed that HMGB2 is present in all analyzed stomach and intestinal sections. In addition, the expression in patients with inflammatory bowel disease (IBD) was studied. No significant differences between patients with Crohn?s disease, ulcerative colitis and unaffected controls were detected. However, the examination of stool from individuals of these three groups suggests that HMGB2 might be useful as a new marker for intestinal inflammation. In summary, HMGB2 exhibits antimicrobial activity against various commensal bacteria of the normal gut flora and is expressed in all analyzed gastrointestinal tract sections. HMGB2 is part of the intestinal barrier and protects, together with other AMPs, the intestine from microorganisms.Publication Erfolgsfaktoren von Kooperationen innerhalb der Internationalisierungsstrategien von Familienunternehmen(2012) Ostertag, Martina M.; Müller, ChristophConsidering the global economy, one can observe for some years now the growing importance of internationalization. Increasingly companies are faced with growing competitive pressure. New, foreign competitors are entering the market and more and more companies are taking advantage of the opportunities that arise in the context to globalization. Often the first step for opening new markets is to develop sales partnerships with businesses in the target country. Based on the development of international distribution partnerships, family run businesses are considering co operations. The goal is to identify specific success factors for co-operations, based on the concept of the determinants of success and the special characteristics of family run businesses and based thereon, under the aspect of the effectuation model, to develop an ideal co-operation process. The focus is on the highest possible practical use for family run businesses that want to be active internationally by setting up sales co-operations. Taking into consideration uncertainty, the result is an optimized process, which primarily meets the special needs of family run businesses and allows a structured implementation of the defined international strategy.Publication Jahresbericht 2011 / Universität Hohenheim(2012) Universität Hohenheim; Liebig, Hans-PeterPublication Jahresbericht 2010 / Universität Hohenheim(2011) Universität Hohenheim; Liebig, Hans-PeterPublication Jahresbericht 2009 / Universität Hohenheim(2010) Universität Hohenheim; Liebig, Hans-PeterPublication Jahresbericht 2008 / Universität Hohenheim(2009) Universität Hohenheim; Liebig, Hans-PeterPublication Jahresbericht 2006 des Rektors / Universität Hohenheim(2007) ; Universität Hohenheim; Liebig, Hans-Peter