@article{FuchsHartmannErnestusetal.2016,
  author    = {Fuchs, Andreas and Hartmann, Stefan and Ernestus, Karen and Mutzbauer, Grit and Linz, Christian and Brands, Roman C. and K{\"u}bler, Alexander C. and M{\"u}ller-Richter, Urs D. A.},
  title     = {Mandibular intraosseous pseudocarcinomatous hyperplasia: a case report},
  series = {Journal of Medical Case Reports},
  volume    = {16},
  journal   = {Journal of Medical Case Reports},
  number    = {268},
  doi       = {10.1186/s13256-016-1052-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146873},
  year      = {2016},
  abstract  = {Background Mandibular pseudocarcinomatous hyperplasia is a rare and generally benign pathology. We report on one of these rare cases. Case presentation The case history of a 73-year-old white man stated that he had a carcinoma of the oropharynx, which was primarily treated with radiotherapy and chemotherapy 4 years prior. As a result of radiotherapy he developed an osteoradionecrosis of his mandible and a consecutive pathological fracture of his left mandibular angle. Subsequent osteosynthesis was performed with a reconstruction plate. When we first saw him, his reconstruction plate was partially exposed with intraoral and extraoral fistulation. The resected bone of his defect-bordering jaw showed the typical pathohistological findings of an intraosseous mandibular pseudocarcinomatous hyperplasia. After a first reconstruction attempt with an iliac crest graft failed, definitive reconstruction of his mandible with a microvascular anastomosed fibula graft was achieved. Conclusions Intraosseous pseudocarcinomatous hyperplasia of the mandible is a rare differential diagnosis in maxillofacial surgery. Besides other benign epithelial neoplasms, such as calcifying epithelial odontogenic tumor, squamous odontogenic tumor, or different forms of ameloblastoma, the far more frequent invasive squamous cell carcinoma needs to be excluded. A misinterpretation of pseudocarcinomatous hyperplasia as squamous cell carcinoma must be avoided because it can lead to a massive overtreatment.},
  language  = {en}
}
@article{BoschertKlenkAbtetal.2020,
  author    = {Boschert, Verena and Klenk, Nicola and Abt, Alexander and Raman, Sudha Janaki and Fischer, Markus and Brands, Roman C. and Seher, Axel and Linz, Christian and M{\"u}ller-Richter, Urs D. A. and Bischler, Thorsten and Hartmann, Stefan},
  title     = {The influence of Met receptor level on HGF-induced glycolytic reprogramming in head and neck squamous cell carcinoma},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {2},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21020471},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235995},
  year      = {2020},
  abstract  = {Head and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF receptor Met. Like other malignancies, HNSCC involves a mutual interaction between the tumor cells and surrounding tissues and cells. We hypothesized that activation of HGF/Met signaling in HNSCC influences glucose metabolism and therefore substantially changes the tumor microenvironment. To determine the effect of HGF, we submitted three established HNSCC cell lines to mRNA sequencing. Dynamic changes in glucose metabolism were measured in real time by an extracellular flux analyzer. As expected, the cell lines exhibited different levels of Met and responded differently to HGF stimulation. As confirmed by mRNA sequencing, the level of Met expression was associated with the number of upregulated HGF-dependent genes. Overall, Met stimulation by HGF leads to increased glycolysis, presumably mediated by higher expression of three key enzymes of glycolysis. These effects appear to be stronger in Met\(^{high}\)-expressing HNSCC cells. Collectively, our data support the hypothesized role of HGF/Met signaling in metabolic reprogramming of HNSCC.},
  language  = {en}
}
@article{LinzFaberSchmidetal.2022,
  author    = {Linz, Christian and Faber, Julian and Schmid, Reiner and Kunz, Felix and B{\"o}hm, Hartmut and Hartmann, Stefan and Schweitzer, Tilmann},
  title     = {Using a 3D asymmetry index as a novel form for capturing complex three-dimensionality in positional plagiocephaly},
  series = {Scientific Reports},
  volume    = {12},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-022-24555-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300427},
  year      = {2022},
  abstract  = {Positional plagiocephaly (PP) is the most common skull deformity in infants. Different classification systems exist for graduating the degree of PP, but all of these systems are based on two-dimensional (2D) parameters. This limitation leads to several problems stemming from the fact that 2D parameters are used to classify the three-dimensional (3D) shape of the head. We therefore evaluate existing measurement parameters and validate a newly developed 3D parameter for quantifying PP. Additionally, we present a new classification of PP based on a 3D parameter. 210 patients with PP and 50 patients without PP were included in this study. Existing parameters (2D and 3D) and newly developed volume parameters based on a 3D stereophotogrammetry scan were validated using ROC curves. Additionally, thresholds for the new 3D parameter of a 3D asymmetry index were assessed. The volume parameter 3D asymmetry index quantifies PP equally as well as the gold standard of 30° diagonal difference. Moreover, a 3D asymmetry index allows for a 3D-based classification of PP. The 3D asymmetry index can be used to define the degree of PP. It is easily applicable in stereophotogrammetric datasets and allows for comparability both intra- and inter-individually as well as for scientific analysis.},
  language  = {en}
}
@article{StraubBrandsBorgmannetal.2022,
  author    = {Straub, Anton and Brands, Roman and Borgmann, Anna and Vollmer, Andreas and Hohm, Julian and Linz, Christian and M{\"u}ller-Richter, Urs and K{\"u}bler, Alexander C. and Hartmann, Stefan},
  title     = {Free skin grafting to reconstruct donor sites after radial forearm flap harvesting: a prospective study with platelet-rich fibrin (PRF)},
  series = {Journal of Clinical Medicine},
  volume    = {11},
  journal   = {Journal of Clinical Medicine},
  number    = {12},
  issn      = {2077-0383},
  doi       = {10.3390/jcm11123506},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-278854},
  year      = {2022},
  abstract  = {Reconstruction of the donor site after radial forearm flap harvesting is a common procedure in maxillofacial plastic surgery. It is normally carried out with split-thickness or full-thickness free skin grafts. Unfortunately, free skin graft transplantation faces wound healing impairments such as necrosis, (partial) graft loss, or tendon exposure. Several studies have investigated methods to reduce these impairments and demonstrated improvements if the wound bed is optimised, for example, through negative-pressure wound therapy or vacuum-assisted closure. However, these methods are device-dependent, expansive, and time-consuming. Therefore, the application of platelet-rich fibrin (PRF) to the wound bed could be a simple, cost-effective, and device-independent method to optimise wound-bed conditions instead. In this study, PRF membranes were applied between the wound bed and skin graft. Results of this study indicate improvements in the PRF versus non-PRF group (93.44\% versus 86.96\% graft survival, p = 0.0292). PRF applied to the wound bed increases graft survival and reduces impairments. A possible explanation for this is the release of growth factors, which stimulate angiogenesis and fibroblast migration. Furthermore, the solid PRF membranes act as a mechanical barrier ("lubrication" layer) to protect the skin graft from tendon motion. The results of this study support the application of PRF in donor-site reconstruction with free skin grafts.},
  language  = {en}
}
@article{KodererSchmitzWuenschetal.2022,
  author    = {Koderer, Corinna and Schmitz, Werner and W{\"u}nsch, Anna Chiara and Balint, Julia and El-Mesery, Mohamed and Volland, Julian Manuel and Hartmann, Stefan and Linz, Christian and K{\"u}bler, Alexander Christian and Seher, Axel},
  title     = {Low energy status under methionine restriction is essentially independent of proliferation or cell contact inhibition},
  series = {Cells},
  volume    = {11},
  journal   = {Cells},
  number    = {3},
  issn      = {2073-4409},
  doi       = {10.3390/cells11030551},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262329},
  year      = {2022},
  abstract  = {Nonlimited proliferation is one of the most striking features of neoplastic cells. The basis of cell division is the sufficient presence of mass (amino acids) and energy (ATP and NADH). A sophisticated intracellular network permanently measures the mass and energy levels. Thus, in vivo restrictions in the form of amino acid, protein, or caloric restrictions strongly affect absolute lifespan and age-associated diseases such as cancer. The induction of permanent low energy metabolism (LEM) is essential in this process. The murine cell line L929 responds to methionine restriction (MetR) for a short time period with LEM at the metabolic level defined by a characteristic fingerprint consisting of the molecules acetoacetate, creatine, spermidine, GSSG, UDP-glucose, pantothenate, and ATP. Here, we used mass spectrometry (LC/MS) to investigate the influence of proliferation and contact inhibition on the energy status of cells. Interestingly, the energy status was essentially independent of proliferation or contact inhibition. LC/MS analyses showed that in full medium, the cells maintain active and energetic metabolism for optional proliferation. In contrast, MetR induced LEM independently of proliferation or contact inhibition. These results are important for cell behaviour under MetR and for the optional application of restrictions in cancer therapy.},
  language  = {en}
}
@article{BoschertTeuschAljasemetal.2020,
  author    = {Boschert, Verena and Teusch, Jonas and Aljasem, Anwar and Schmucker, Philipp and Klenk, Nicola and Straub, Anton and Bittrich, Max and Seher, Axel and Linz, Christian and M{\"u}ller-Richter, Urs D. A. and Hartmann, Stefan},
  title     = {HGF-induced PD-L1 expression in head and neck cancer: preclinical and clinical findings},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {20},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21228770},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236220},
  year      = {2020},
  abstract  = {Head and neck squamous cell carcinoma (HNSCC) is a widespread disease with a low survival rate and a high risk of recurrence. Nowadays, immune checkpoint inhibitor (ICI) treatment is approved for HNSCC as a first-line treatment in recurrent and metastatic disease. ICI treatment yields a clear survival benefit, but overall response rates are still unsatisfactory. As shown in different cancer models, hepatocyte growth factor/mesenchymal-epithelial transition (HGF/Met) signaling contributes to an immunosuppressive microenvironment. Therefore, we investigated the relationship between HGF and programmed cell death protein 1 (PD-L1) expression in HNSCC cell lines. The preclinical data show a robust PD-L1 induction upon HGF stimulation. Further analysis revealed that the HGF-mediated upregulation of PD-L1 is MAP kinase-dependent. We then hypothesized that serum levels of HGF and soluble programmed cell death protein 1 (sPD-L1) could be potential markers of ICI treatment failure. Thus, we determined serum levels of these proteins in 20 HNSCC patients before ICI treatment and correlated them with treatment outcomes. Importantly, the clinical data showed a positive correlation of both serum proteins (HGF and sPD-L1) in HNSCC patient's sera. Moreover, the serum concentration of sPD-L1 was significantly higher in ICI non-responsive patients. Our findings indicate a potential role for sPD-L1 as a prognostic marker for ICI treatment in HNSCC.},
  language  = {en}
}
@article{StraubStapfFischeretal.2022,
  author    = {Straub, Anton and Stapf, Maximilian and Fischer, Markus and Vollmer, Andreas and Linz, Christian and L{\^a}m, Thi{\^e}n-Tr{\´i} and K{\"u}bler, Alexander and Brands, Roman C. and Scherf-Clavel, Oliver and Hartmann, Stefan},
  title     = {Bone concentration of ampicillin/sulbactam: a pilot study in patients with osteonecrosis of the jaw},
  series = {International Journal of Environmental Research and Public Health},
  volume    = {19},
  journal   = {International Journal of Environmental Research and Public Health},
  number    = {22},
  issn      = {1660-4601},
  doi       = {10.3390/ijerph192214917},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297413},
  year      = {2022},
  abstract  = {Osteonecrosis of the jaw (ONJ) occurs typically after irradiation of the head and neck area or after the intake of antiresorptive agents. Both interventions can lead to compromised bone perfusion and can ultimately result in infection and necrosis. Treatment usually consists of surgical necrosectomy and prolonged antibiotic therapy, usually through beta-lactams such as ampicillin/sulbactam. The poor blood supply in particular raises the question as to whether this form of antibiosis can achieve sufficient concentrations in the bone. Therefore, we investigated the antibiotic concentration in plasma and bone samples in a prospective study. Bone samples were collected from the necrosis core and in the vital surrounding bone. The measured concentrations in plasma for ampicillin and sulbactam were 126.3 ± 77.6 and 60.2 ± 35.0 µg/mL, respectively. In vital bone and necrotic bone samples, the ampicillin/sulbactam concentrations were 6.3 ± 7.8/1.8 ± 2.0 µg/g and 4.9 ± 7.0/1.7 ± 1.7 µg/g, respectively. These concentrations are substantially lower than described in the literature. However, the concentration seems sufficient to kill most bacteria, such as Streptococci and Staphylococci, which are mostly present in the biofilm of ONJ. We, therefore, conclude that intravenous administration of ampicillin/sulbactam remains a valuable treatment in the therapy of ONJ. Nevertheless, increasing resistance of Escherichia coli towards beta-lactam antibiotics have been reported and should be considered.},
  language  = {en}
}
@article{LinzBrandsKertelsetal.2021,
  author    = {Linz, Christian and Brands, Roman C. and Kertels, Olivia and Dierks, Alexander and Brumberg, Joachim and Gerhard-Hartmann, Elena and Hartmann, Stefan and Schirbel, Andreas and Serfling, Sebastian and Zhi, Yingjun and Buck, Andreas K. and K{\"u}bler, Alexander and Hohm, Julian and Lapa, Constantin and Kircher, Malte},
  title     = {Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity - initial experience and comparison to [\(^{18}\)F]FDG PET/CT and MRI},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {48},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {12},
  issn      = {1619-7070},
  doi       = {10.1007/s00259-021-05422-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307246},
  pages     = {3951-3960},
  year      = {2021},
  abstract  = {Purpose While [\(^{18}\)F]-fluorodeoxyglucose ([\(^{18}\)F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT. Methods Ten consecutive, treatment-na{\"i}ve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [\(^{18}\)F]FDG and [\(^{68}\)Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUV\(_{max}\)) and peak (SUV\(_{peak}\) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference. Results [\(^{18}\)F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([\(^{18}\)F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3\% vs. 87.5\%; P = 0.32) and specificity (93.3\% vs. 81.3\%; P = 0.16) to [\(^{18}\)F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples. Conclusion FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.},
  language  = {en}
}