Our Work
- Cancer
- Inflammation
Cancer
Wnt-signalling in melanoma-induced angiogenesis
Wnt proteins play important roles during embryonic vascular development. The role of wnt in angiogenesis in the adult is less defined. In human melanoma, lymphatic vessels play a critical role in tumor spread to lymph nodes. We are therefore investigating the role of wnt for lymph vessel neoformation employing in vitro and in vivo models for human metastatic melanomas. Our aim is to find new tools to prevent lymph node metatstasis.
The molecular basis of melanoma metastasis to Sentinel nodes
Cutaneous melanoma first metastasizes into sentinel lymph nodes that control the lymphatic drain from the area of the primary tumor. Successful colonization of tumor cells into sentinel lymph nodes is thought to require priming of this environment, but these priming factors are as yet undefined. We aim to identify and analyze a gene expression signature reflecting priming events by using a mouse xenotransplantation model, in which human M24met melanoma cells grafted into the skin of SCID mice metastasize to sentinel lymph nodes. Results will be correlated with specimens of sentinel nodes from human patients. This approach offers two long term perspectives: 1. Identification of new prognostic factors; and 2. Establishment of a novel therapeutic approach preventing melanoma cells from colonizing sentinel lymph node
Angiogenesis as a predictive parameter for the development of invasive squamous cell carcinoma
Actinic keratosis (AK) is an in situ carcinoma of the skin affecting up to 50% of persons over 40. Some instances evolve into invasive cancer, but it is difficult to predict which lesions are at risk. We are performing a prospective study to test the hypothesis that the amount of angiogenesis within lesions is an independent parameter that can help predict lesions at risk.
Inflammation
The action of fibrin fragments in the context of vascular leak and inflammation
The loss of vascular barrier function leads to inflammation and causes leak of fluid and proteins into tissues, extensive leak leads to shock and death. We have defined a novel function of a small peptide Bbeta15-42 (also called FX06). This peptide is a natural fibrin degradation product following plasmin digestion. It preserves endothelial barrier function and reduces leak and inflammation in situations of stress. We characterize functions of this peptide by means of protein and molecular biology techniques, in cell culture and in in vivo models. Our aim is to outline signalling pathways and relevant binding structures in the cause-and-effect chain between the peptide, the endothelial junction zone and the cytoskeleton.
The power of fumaric acid esters in psoriasis treatment
Fumaric acid esters are derivatives of fumaric acid and have been used empirically in the treatment of psoriasis fore decades. We have identified Dimethylfumarate (DMF) as the most effective of all fumarates tested so far 1 and we were able to reveal that DMF inhibits the expression of NF-κB dependent proteins, by impairing nuclear import of active NF-κB dimers 2. The NF-κB inhibitory effect together with the known antiproliferative, antiinflammatory and immunomodulatory effects of DMF, encouraged us to address the question of whether DMF might be a new therapeutic option for the treatment of human malignancies. In animal models for human melanoma, we were able to demonstrate that DMF reduces tumor growth and metastasis 3. To evaluate the therapeutic capability of DMF in human patients with malignant melanoma, a first clinical trial is currently being planned.
