@article{OttoKastnerSchmidtetal.2022,
  author    = {Otto, Christoph and Kastner, Carolin and Schmidt, Stefanie and Uttinger, Konstantin and Baluapuri, Apoorva and Denk, Sarah and Rosenfeldt, Mathias T. and Rosenwald, Andreas and Roehrig, Florian and Ade, Carsten P. and Schuelein-Voelk, Christina and Diefenbacher, Markus E. and Germer, Christoph-Thomas and Wolf, Elmar and Eilers, Martin and Wiegering, Armin},
  title     = {RNA polymerase I inhibition induces terminal differentiation, growth arrest, and vulnerability to senolytics in colorectal cancer cells},
  series = {Molecular Oncology},
  volume    = {16},
  journal   = {Molecular Oncology},
  number    = {15},
  doi       = {10.1002/1878-0261.13265},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312806},
  pages     = {2788-2809},
  year      = {2022},
  abstract  = {Ribosomal biogenesis and protein synthesis are deregulated in most cancers, suggesting that interfering with translation machinery may hold significant therapeutic potential. Here, we show that loss of the tumor suppressor adenomatous polyposis coli (APC), which constitutes the initiating event in the adenoma carcinoma sequence for colorectal cancer (CRC), induces the expression of RNA polymerase I (RNAPOL1) transcription machinery, and subsequently upregulates ribosomal DNA (rDNA) transcription. Targeting RNAPOL1 with a specific inhibitor, CX5461, disrupts nucleolar integrity, and induces a disbalance of ribosomal proteins. Surprisingly, CX5461-induced growth arrest is irreversible and exhibits features of senescence and terminal differentiation. Mechanistically, CX5461 promotes differentiation in an MYC-interacting zinc-finger protein 1 (MIZ1)- and retinoblastoma protein (Rb)-dependent manner. In addition, the inhibition of RNAPOL1 renders CRC cells vulnerable towards senolytic agents. We validated this therapeutic effect of CX5461 in murine- and patient-derived organoids, and in a xenograft mouse model. These results show that targeting ribosomal biogenesis together with targeting the consecutive, senescent phenotype using approved drugs is a new therapeutic approach, which can rapidly be transferred from bench to bedside.},
  language  = {en}
}
@article{UllmannBanksSchmittetal.2017,
  author    = {Ullmann, Tobias and Banks, Sarah N. and Schmitt, Andreas and Jagdhuber, Thomas},
  title     = {Scattering characteristics of X-, C- and L-Band PolSAR data examined for the tundra environment of the Tuktoyaktuk Peninsula, Canada},
  series = {Applied Sciences},
  volume    = {7},
  journal   = {Applied Sciences},
  number    = {6},
  doi       = {10.3390/app7060595},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158362},
  pages     = {595},
  year      = {2017},
  abstract  = {In this study, polarimetric Synthetic Aperture Radar (PolSAR) data at X-, C- and L-Bands, acquired by the satellites: TerraSAR-X (2011), Radarsat-2 (2011), ALOS (2010) and ALOS-2 (2016), were used to characterize the tundra land cover of a test site located close to the town of Tuktoyaktuk, NWT, Canada. Using available in situ ground data collected in 2010 and 2012, we investigate PolSAR scattering characteristics of common tundra land cover classes at X-, C- and L-Bands. Several decomposition features of quad-, co-, and cross-polarized data were compared, the correlation between them was investigated, and the class separability offered by their different feature spaces was analyzed. Certain PolSAR features at each wavelength were sensitive to the land cover and exhibited distinct scattering characteristics. Use of shorter wavelength imagery (X and C) was beneficial for the characterization of wetland and tundra vegetation, while L-Band data highlighted differences of the bare ground classes better. The Kennaugh Matrix decomposition applied in this study provided a unified framework to store, process, and analyze all data consistently, and the matrix offered a favorable feature space for class separation. Of all elements of the quad-polarized Kennaugh Matrix, the intensity based elements K0, K1, K2, K3 and K4 were found to be most valuable for class discrimination. These elements contributed to better class separation as indicated by an increase of the separability metrics squared Jefferys Matusita Distance and Transformed Divergence. The increase in separability was up to 57\% for Radarsat-2 and up to 18\% for ALOS-2 data.},
  language  = {en}
}