@article{AscheidBaumannFunkeetal.2023,
  author    = {Ascheid, David and Baumann, Magdalena and Funke, Caroline and Volz, Julia and Pinnecker, J{\"u}rgen and Friedrich, Mike and H{\"o}hn, Marie and Nandigama, Rajender and Erg{\"u}n, S{\"u}leyman and Nieswandt, Bernhard and Heinze, Katrin G. and Henke, Erik},
  title     = {Image-based modeling of vascular organization to evaluate anti-angiogenic therapy},
  series = {Biology Direct},
  volume    = {18},
  journal   = {Biology Direct},
  doi       = {10.1186/s13062-023-00365-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357242},
  year      = {2023},
  abstract  = {In tumor therapy anti-angiogenic approaches have the potential to increase the efficacy of a wide variety of subsequently or co-administered agents, possibly by improving or normalizing the defective tumor vasculature. Successful implementation of the concept of vascular normalization under anti-angiogenic therapy, however, mandates a detailed understanding of key characteristics and a respective scoring metric that defines an improved vasculature and thus a successful attempt. Here, we show that beyond commonly used parameters such as vessel patency and maturation, anti-angiogenic approaches largely benefit if the complex vascular network with its vessel interconnections is both qualitatively and quantitatively assessed. To gain such deeper insight the organization of vascular networks, we introduce a multi-parametric evaluation of high-resolution angiographic images based on light-sheet fluorescence microscopy images of tumors. We first could pinpoint key correlations between vessel length, straightness and diameter to describe the regular, functional and organized structure observed under physiological conditions. We found that vascular networks from experimental tumors diverted from those in healthy organs, demonstrating the dysfunctionality of the tumor vasculature not only on the level of the individual vessel but also in terms of inadequate organization into larger structures. These parameters proofed effective in scoring the degree of disorganization in different tumor entities, and more importantly in grading a potential reversal under treatment with therapeutic agents. The presented vascular network analysis will support vascular normalization assessment and future optimization of anti-angiogenic therapy.},
  language  = {en}
}
@article{HenkeNandigamaErguen2020,
  author    = {Henke, Erik and Nandigama, Rajender and Erg{\"u}n, S{\"u}leyman},
  title     = {Extracellular matrix in the tumor microenvironment and its impact on cancer therapy},
  series = {Frontiers in Molecular Biosciences},
  volume    = {6},
  journal   = {Frontiers in Molecular Biosciences},
  number    = {160},
  issn      = {2296-889X},
  doi       = {10.3389/fmolb.2019.00160},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199341},
  year      = {2020},
  abstract  = {Solid tumors are complex organ-like structures that consist not only of tumor cells but also of vasculature, extracellular matrix (ECM), stromal, and immune cells. Often, this tumor microenvironment (TME) comprises the larger part of the overall tumor mass. Like the other components of the TME, the ECM in solid tumors differs significantly from that in normal organs. Intratumoral signaling, transport mechanisms, metabolisms, oxygenation, and immunogenicity are strongly affected if not controlled by the ECM. Exerting this regulatory control, the ECM does not only influence malignancy and growth of the tumor but also its response toward therapy. Understanding the particularities of the ECM in solid tumor is necessary to develop approaches to interfere with its negative effect. In this review, we will also highlight the current understanding of the physical, cellular, and molecular mechanisms by which the pathological tumor ECM affects the efficiency of radio-, chemo-, and immunotherapy. Finally, we will discuss the various strategies to target and modify the tumor ECM and how they could be utilized to improve response to therapy.},
  language  = {en}
}