@article{WobserSiedelKneitzetal.2013,
  author    = {Wobser, Marion and Siedel, Claudia and Kneitz, Hermann and Br{\"o}cker, Eva-Bettina and Goebeler, Mathias and Houben, Roland and Geissinger, Eva},
  title     = {Microvessel Density and Expression of Vascular Endothelial Growth Factor and its Receptors in Different Subtypes of Primary Cutaneous B-cell Lymphoma},
  series = {Acta Dermato-Venereologica},
  volume    = {93},
  journal   = {Acta Dermato-Venereologica},
  number    = {6},
  doi       = {10.2340/00015555-1589},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128608},
  pages     = {656-662},
  year      = {2013},
  abstract  = {A proangiogenic micromilieu is associated with a worse prognosis in systemic lymphoma. Hence, targeting the tumour microenvironment and its vasculature has evolved as a promising novel treatment strategy. The role of tumour neoangiogenesis in cutaneous B-cell lymphoma, however, has not yet been elucidated. Therefore, we examined the expression of vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and VEGFR-2, as well as microvessel density by immunohistochemistry in paraffin-embedded specimens of different subtypes of primary cutaneous B-cell lymphomas, systemic diffuse large B-cell lymphoma, and cutaneous B-cell pseudolymphoma. Primary cutaneous large B-cell lymphoma (PCLBCL) were characterized by significantly higher intratumoral expression levels of VEGF and its receptors in comparison with the indolent lymphoma subtypes. Moreover, PCLBCL exhibited significantly higher intratumoral microvessel counts. Our study provides evidence that the most aggressive subtype of cutaneous B-cell lymphoma, PCLBCL, is characterized by a proangiogenic micromilieu.},
  language  = {en}
}
@article{WobserWeberGlunzetal.2019,
  author    = {Wobser, Marion and Weber, Alexandra and Glunz, Amelie and Tauch, Saskia and Seitz, Kristina and Butelmann, Tobias and Hesbacher, Sonja and Goebeler, Matthias and Bartz, Ren{\´e} and Kohlhof, Hella and Schrama, David and Houben, Roland},
  title     = {Elucidating the mechanism of action of domatinostat (4SC-202) in cutaneous T cell lymphoma cells},
  series = {Journal of Hematology \& Oncology},
  volume    = {12},
  journal   = {Journal of Hematology \& Oncology},
  doi       = {10.1186/s13045-019-0719-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200703},
  pages     = {30},
  year      = {2019},
  abstract  = {Background Targeting epigenetic modifiers is effective in cutaneous T cell lymphoma (CTCL). However, there is a need for further improvement of this therapeutic approach. Here, we compared the mode of action of romidepsin (FK228), an established class I histone deacetylase inhibitor, and domatinostat (4SC-202), a novel inhibitor of class I HDACs, which has been reported to also target the lysine-specific histone demethylase 1A (LSD1). Methods We performed MTS assays and flow cytometric analyses of propidium iodide or annexin V-stained cells to assess drug impact on cellular proliferation, cell cycle distribution, and survival. Histone acetylation and methylation as well as caspase activation was analyzed by immunoblot. Gene expression analysis was performed using NanosString technology. Knockdown and knockout of LSD1 was achieved with shRNA and CRISPR/Cas9, respectively, while the CRISPR/Cas9 synergistic activation mediator system was used to induce expression of endogenous HDACs and LSD1. Furthermore, time-lapse fluorescence microscopy and an in vitro tubulin polymerization assay were applied. Results While FK228 as well as 4SC-202 potently induced cell death in six different CTCL cell lines, only in the case of 4SC-202 death was preceded by an accumulation of cells in the G2/M phase of the cell cycle. Surprisingly, apoptosis and accumulation of cells with double DNA content occurred already at 4SC-202 concentrations hardly affecting histone acetylation and methylation, and provoking significantly less changes in gene expression compared to biologically equivalent doses of FK228. Indeed, we provide evidence that the 4SC-202-induced G2/M arrest in CTCL cells is independent of de novo transcription. Furthermore, neither enforced expression of HDAC1 nor knockdown or knockout of LSD1 affected the 4SC-202-induced effects. Since time-lapse microscopy revealed that 4SC-202 could affect mitotic spindle formation, we performed an in vitro tubulin polymerization assay revealing that 4SC-202 can directly inhibit microtubule formation. Conclusions We demonstrate that 4SC-202, a drug currently tested in clinical trials, effectively inhibits growth of CTCL cells. The anti-cancer cell activity of 4SC-202 is however not limited to LSD1-inhibition, modulation of histone modifications, and consecutive alteration of gene expression. Indeed, the compound is also a potent microtubule-destabilizing agent.},
  language  = {en}
}