@phdthesis{Schaafhausen2014,
  author    = {Schaafhausen, Maximilian},
  title     = {Development of a fish melanoma angiogenesis model},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-101043},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Malignant melanoma is the most severe form of all skin cancers with a particular poor prognosis once metastases have developed. Angiogenesis, the formation of new blood vessels, is a prominent feature of human melanoma, which have angiogenic activity already early in development. This is at least partly ascribed to the action of MAPK- and PI3K pathways which are hyperactivated in most melanoma. Animal models which combine in depth in vivo examinations with the opportunity to perform small molecular screens are well suited to gain a more detailed insight into how this type of cancer modulates its angiogenic program. Here, a first transgenic melanoma angiogenesis model was established in the fish species Oryzias latipes (Japanese medaka). In this model, tumors are generated by the pigment cell-specific expression of the oncogenic receptor tyrosine kinase Xmrk. Xmrk is a mutated version of the fish Egfp. Furthermore, to get an angiogenesis model, a medaka line with endothelial cell specific GFP expression was used. By using crosses between these Xmrk- and GFP transgenic fishes, it was shown that angiogenesis occurs in a reactive oxygen species- and NF-κB-dependent manner, but was hypoxia-independent. It was observed that blood vessel sprouting and branch point formation was elevated in this model and furthermore that sprouting could even be induced by single transformed cells. The mouse melanocytes expressing the oncogenic receptor tyrosine kinase Xmrk as well human melanoma cells, which display various oncogenic alterations, produced pro-angiogenic factors, most prominently angiogenin, via NF-κB signaling. Furthermore, inhibiting NF-κB action prevented tumor angiogenesis and even led to the regression of existing tumor blood vessels. In summary, the present medaka melanoma angiogenesis model displays a high sensitivity for angiogenesis detection and is perfectly suited as in vivo model for the testing of anti-angiogenesis inhibitors, as exemplified by the NF-kappaB inhibitor. Furthermore, results indicate that it might be a promising anti-tumor strategy to target signaling pathways such as the NF-κB pathway which are able to induce angiogenesis-dependent as well as -independent pro-tumorigenic effects.},
  subject      = {Melanom},
  language  = {en}
}
@phdthesis{Ruecker2019,
  author    = {R{\"u}cker, Christoph},
  title     = {Development of a prevascularized bone implant},
  doi       = {10.25972/OPUS-17886},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178869},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {The skeletal system forms the mechanical structure of the body and consists of bone, which is hard connective tissue. The tasks the skeleton and bones take over are of mechanical, metabolic and synthetic nature. Lastly, bones enable the production of blood cells by housing the bone marrow. Bone has a scarless self-healing capacity to a certain degree. Injuries exceeding this capacity caused by trauma, surgical removal of infected or tumoral bone or as a result from treatment-related osteonecrosis, will not heal. Critical size bone defects that will not heal by themselves are still object of comprehensive clinical investigation. The conventional treatments often result in therapies including burdening methods as for example the harvesting of autologous bone material. The aim of this thesis was the creation of a prevascularized bone implant employing minimally invasive methods in order to minimize inconvenience for patients and surgical site morbidity. The basis for the implant was a decellularized, naturally derived vascular scaffold (BioVaSc-TERM®) providing functional vessel structures after reseeding with autologous endothelial cells. The bone compartment was built by the combination of the aforementioned scaffold with synthetic β-tricalcium phosphate. In vitro culture for tissue maturation was performed using bioreactor technology before the testing of the regenerative potential of the implant in large animal experiments in sheep. A tibia defect was treated without the anastomosis of the implant's innate vasculature to the host's circulatory system and in a second study, with anastomosis of the vessel system in a mandibular defect. While the non-anastomosed implant revealed a mostly osteoconductive effect, the implants that were anastomosed achieved formation of bony islands evenly distributed over the defect. In order to prepare preconditions for a rapid approval of an implant making use of this vascularization strategy, the manufacturing of the BioVaSc-TERM® as vascularizing scaffold was adjusted to GMP requirements.},
  subject      = {Tissue Engineering},
  language  = {en}
}