@article{KuehnemundtLeifeldSchergetal.2021,
  author    = {K{\"u}hnemundt, Johanna and Leifeld, Heidi and Scherg, Florian and Schmitt, Matthias and Nelke, Lena C. and Schmitt, Tina and Bauer, Florentin and G{\"o}ttlich, Claudia and Fuchs, Maximilian and Kunz, Meik and Peindl, Matthias and Br{\"a}hler, Caroline and Kronenthaler, Corinna and Wischhusen, J{\"o}rg and Prelog, Martina and Walles, Heike and Dandekar, Thomas and Dandekar, Gudrun and Nietzer, Sarah L.},
  title     = {Modular micro-physiological human tumor/tissue models based on decellularized tissue for improved preclinical testing},
  series = {ALTEX},
  volume    = {38},
  journal   = {ALTEX},
  doi       = {10.14573/altex.2008141},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231465},
  pages     = {289-306},
  year      = {2021},
  abstract  = {High attrition-rates entailed by drug testing in 2D cell culture and animal models stress the need for improved modeling of human tumor tissues. In previous studies our 3D models on a decellularized tissue matrix have shown better predictivity and higher chemoresistance. A single porcine intestine yields material for 150 3D models of breast, lung, colorectal cancer (CRC) or leukemia. The uniquely preserved structure of the basement membrane enables physiological anchorage of endothelial cells and epithelial-derived carcinoma cells. The matrix provides different niches for cell growth: on top as monolayer, in crypts as aggregates and within deeper layers. Dynamic culture in bioreactors enhances cell growth. Comparing gene expression between 2D and 3D cultures, we observed changes related to proliferation, apoptosis and stemness. For drug target predictions, we utilize tumor-specific sequencing data in our in silico model finding an additive effect of metformin and gefitinib treatment for lung cancer in silico, validated in vitro. To analyze mode-of-action, immune therapies such as trispecific T-cell engagers in leukemia, as well as toxicity on non-cancer cells, the model can be modularly enriched with human endothelial cells (hECs), immune cells and fibroblasts. Upon addition of hECs, transmigration of immune cells through the endothelial barrier can be investigated. In an allogenic CRC model we observe a lower basic apoptosis rate after applying PBMCs in 3D compared to 2D, which offers new options to mirror antigen-specific immunotherapies in vitro. In conclusion, we present modular human 3D tumor models with tissue-like features for preclinical testing to reduce animal experiments.},
  language  = {en}
}
@article{SieglPrustyKarunakaranetal.2014,
  author    = {Siegl, Christine and Prusty, Bhupesh K. and Karunakaran, Karthika and Wischhusen, J{\"o}rg and Rudel, Thomas},
  title     = {Tumor Suppressor p53 Alters Host Cell Metabolism to Limit Chlamydia trachomatis Infection},
  series = {Cell Reports},
  volume    = {9},
  journal   = {Cell Reports},
  number    = {3},
  issn      = {2211-1247},
  doi       = {10.1016/j.celrep.2014.10.004},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118200},
  pages     = {918-929},
  year      = {2014},
  abstract  = {Obligate intracellular bacteria depend entirely on nutrients from the host cell for their reproduction. Here, we show that obligate intracellular Chlamydia downregulate the central tumor suppressor p53 in human cells. This reduction of p53 levels is mediated by the PI3K-Akt signaling pathway, activation of HDM2, and subsequent proteasomal degradation of p53. The stabilization of p53 in human cells severely impaired chlamydial development and caused the loss of infectious particle formation. DNA-damage-induced p53 interfered with chlamydial development through downregulation of the pentose phosphate pathway (PPP). Increased expression of the PPP key enzyme glucose-6-phosphate dehydrogenase rescued the inhibition of chlamydial growth induced by DNA damage or stabilized p53. Thus, downregulation of p53 is a key event in the chlamydial life cycle that reprograms the host cell to create a metabolic environment supportive of chlamydial growth.},
  language  = {en}
}