@article{MeyerGerhardHartmannLodesetal.2021,
  author    = {Meyer, Till Jasper and Gerhard-Hartmann, Elena and Lodes, Nina and Scherzad, Agmal and Hagen, Rudolf and Steinke, Maria and Hackenberg, Stephan},
  title     = {Pilot study on the value of Raman spectroscopy in the entity assignment of salivary gland tumors},
  series = {PLoS One},
  volume    = {16},
  journal   = {PLoS One},
  number    = {9},
  doi       = {10.1371/journal.pone.0257470},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264736},
  year      = {2021},
  abstract  = {Background The entity assignment of salivary gland tumors (SGT) based on histomorphology can be challenging. Raman spectroscopy has been applied to analyze differences in the molecular composition of tissues. The aim of this study was to evaluate the suitability of RS for entity assignment in SGT. Methods Raman data were collected in deparaffinized sections of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Multivariate data and chemometric analysis were completed using the Unscrambler software. Results The Raman spectra detected in ACC samples were mostly assigned to nucleic acids, lipids, and amides. In a principal component-based linear discriminant analysis (LDA) 18 of 20 tumor samples were classified correctly. Conclusion In this proof of concept study, we show that a reliable SGT diagnosis based on LDA algorithm appears possible, despite variations in the entity-specific mean spectra. However, a standardized workflow for tissue sample preparation, measurement setup, and chemometric algorithms is essential to get reliable results.},
  language  = {en}
}
@article{ScherzadMeyerIckrathetal.2019,
  author    = {Scherzad, Agmal and Meyer, Till and Ickrath, Pascal and Gehrke, Thomas Eckhart and Bregenzer, Maximillian and Hagen, Rudolf and Dembski, Sofia and Hackenberg, Stephan},
  title     = {Cultivation of hMSCs in human plasma prevents the cytotoxic and genotoxic potential of ZnO-NP in vitro},
  series = {Applied Sciences},
  volume    = {9},
  journal   = {Applied Sciences},
  number    = {23},
  issn      = {2076-3417},
  doi       = {10.3390/app9234994},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193063},
  year      = {2019},
  abstract  = {Zinc oxide nanoparticles (ZnO-NPs) are commonly used for industrial applications. Consequently, there is increasing exposure of humans to them. The in vitro analysis of cytotoxicity and genotoxicity is commonly performed under standard cell culture conditions. Thus, the question arises of how the results of genotoxicity and cytotoxicity experiments would alter if human plasma was used instead of cell culture medium containing of fetal calf serum (FCS). Human mesenchymal stem cells (hMSCs) were cultured in human plasma and exposed to ZnO-NPs. A cultivation in expansion medium made of DMEM consisting 10\% FCS (DMEM-EM) served as control. Genotoxic and cytotoxic effects were evaluated with the comet and MTT assay, respectively. hMSC differentiation capacity and ZnO-NP disposition were evaluated by histology and transmission electron microscopy (TEM). The protein concentration and the amount of soluble Zn2+ were measured. The cultivation of hMSCs in plasma leads to an attenuation of genotoxic and cytotoxic effects of ZnO-NPs compared to control. The differentiation capacity of hMSCs was not altered. The TEM showed ZnO-NP persistence in cytoplasm in both groups. The concentrations of protein and Zn2+ were higher in plasma than in DMEM-EM. In conclusion, the cultivation of hMSCs in plasma compared to DMEM-EM leads to an attenuation of cytotoxicity and genotoxicity in vitro.},
  language  = {en}
}
@article{ScherzadMeyerKleinsasseretal.2020,
  author    = {Scherzad, Agmal and Meyer, Till and Kleinsasser, Norbert and Hackenberg, Stephan},
  title     = {Erratum: Scherzad, A., et al. Molecular mechanisms of zinc oxide nanoparticle-induced genotoxicity short running title: Genotoxicity of ZnO NPs. Materials 2017, 10, 1427},
  series = {Materials},
  volume    = {13},
  journal   = {Materials},
  number    = {23},
  issn      = {1996-1944},
  doi       = {10.3390/ma13235462},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219440},
  year      = {2020},
  abstract  = {No abstract available},
  language  = {en}
}
@article{MeyerStoethMoratinetal.2021,
  author    = {Meyer, Till Jasper and St{\"o}th, Manuel and Moratin, Helena and Ickrath, Pascal and Herrmann, Marietta and Kleinsasser, Norbert and Hagen, Rudolf and Hackenberg, Stephan and Scherzad, Agmal},
  title     = {Cultivation of head and neck squamous cell carcinoma cells with wound fluid leads to cisplatin resistance via epithelial-mesenchymal transition induction},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {9},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22094474},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258722},
  year      = {2021},
  abstract  = {Locoregional recurrence is a major reason for therapy failure after surgical resection of head and neck squamous cell carcinoma (HNSCC). The physiological process of postoperative wound healing could potentially support the proliferation of remaining tumor cells. The aim of this study was to evaluate the influence of wound fluid (WF) on the cell cycle distribution and a potential induction of epithelial-mesenchymal transition (EMT). To verify this hypothesis, we incubated FaDu and HLaC78 cells with postoperative WF from patients after neck dissection. Cell viability in dependence of WF concentration and cisplatin was measured by flow cytometry. Cell cycle analysis was performed by flow cytometry and EMT-marker expression by rtPCR. WF showed high concentrations of interleukin (IL)-6, IL-8, IL-10, CCL2, MCP-1, EGF, angiogenin, and leptin. The cultivation of tumor cells with WF resulted in a significant increase in cell proliferation without affecting the cell cycle. In addition, there was a significant enhancement of the mesenchymal markers Snail 2 and vimentin, while the expression of the epithelial marker E-cadherin was significantly decreased. After cisplatin treatment, tumor cells incubated with WF showed a significantly higher resistance compared with the control group. The effect of cisplatin-resistance was dependent on the WF concentration. In summary, proinflammatory cytokines are predominantly found in WF. Furthermore, the results suggest that EMT can be induced by WF, which could be a possible mechanism for cisplatin resistance.},
  language  = {en}
}
@article{MoratinIckrathScherzadetal.2021,
  author    = {Moratin, Helena and Ickrath, Pascal and Scherzad, Agmal and Meyer, Till Jasper and Naczenski, Sebastian and Hagen, Rudolf and Hackenberg, Stephan},
  title     = {Investigation of the immune modulatory potential of zinc oxide nanoparticles in human lymphocytes},
  series = {Nanomaterials},
  volume    = {11},
  journal   = {Nanomaterials},
  number    = {3},
  issn      = {2079-4991},
  doi       = {10.3390/nano11030629},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234016},
  year      = {2021},
  abstract  = {Zinc oxide nanoparticles (ZnO-NP) are commonly used for a variety of applications in everyday life. In addition, due to its versatility, nanotechnology supports promising approaches in the medical sector. NP can act as drug-carriers in the context of targeted chemo- or immunotherapy, and might also exhibit autonomous immune-modulatory characteristics. Knowledge of potential immunosuppressive or stimulating effects of NP is indispensable for the safety of consumers as well as patients. In this study, primary human peripheral blood lymphocytes of 9 donors were treated with different sub-cytotoxic concentrations of ZnO-NP for the duration of 1, 2, or 3 days. Flow cytometry was performed to investigate changes in the activation profile and the proportion of T cell subpopulations. ZnO-NP applied in this study did not induce any significant alterations in the examined markers, indicating their lack of impairment in terms of immune modulation. However, physicochemical characteristics exert a major influence on NP-associated bioactivity. To allow a precise simulation of the complex molecular processes of immune modulation, a physiological model including the different components of an immune response is needed.},
  language  = {en}
}
@article{MeyerScherzadMoratinetal.2019,
  author    = {Meyer, Till Jasper and Scherzad, Agmal and Moratin, Helena and Gehrke, Thomas Eckert and Killisperger, Julian and Hagen, Rudolf and Wohlleben, Gisela and Polat, B{\"u}lent and Dembski, Sofia and Kleinsasser, Norbert and Hackenberg, Stephan},
  title     = {The radiosensitizing effect of zinc oxide nanoparticles in sub-cytotoxic dosing is associated with oxidative stress in vitro},
  series = {Materials},
  volume    = {12},
  journal   = {Materials},
  number    = {24},
  issn      = {1996-1944},
  doi       = {10.3390/ma12244062},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193897},
  pages     = {4062},
  year      = {2019},
  abstract  = {Radioresistance is an important cause of head and neck cancer therapy failure. Zinc oxide nanoparticles (ZnO-NP) mediate tumor-selective toxic effects. The aim of this study was to evaluate the potential for radiosensitization of ZnO-NP. The dose-dependent cytotoxicity of ZnO-NP\(_{20 nm}\) and ZnO-NP\(_{100 nm}\) was investigated in FaDu and primary fibroblasts (FB) by an MTT assay. The clonogenic survival assay was used to evaluate the effects of ZnO-NP alone and in combination with irradiation on FB and FaDu. A formamidopyrimidine-DNA glycosylase (FPG)-modified single-cell microgel electrophoresis (comet) assay was applied to detect oxidative DNA damage in FB as a function of ZnO-NP and irradiation exposure. A significantly increased cytotoxicity after FaDu exposure to ZnO-NP\(_{20 nm}\) or ZnO-NP\(_{100 nm}\) was observed in a concentration of 10 µg/mL or 1 µg/mL respectively in 30 µg/mL of ZnO-NP\(_{20 nm}\) or 20 µg/mL of ZnO-NP\(_{100 nm}\) in FB. The addition of 1, 5, or 10 µg/mL ZnO-NP\(_{20 nm}\) or ZnO-NP\(_{100 nm}\) significantly reduced the clonogenic survival of FaDu after irradiation. The sub-cytotoxic dosage of ZnO-NP\(_{100 nm}\) increased the oxidative DNA damage compared to the irradiated control. This effect was not significant for ZnO-NP\(_{20 nm}\). ZnO-NP showed radiosensitizing properties in the sub-cytotoxic dosage. At least for the ZnO-NP\(_{100 nm}\), an increased level of oxidative stress is a possible mechanism of the radiosensitizing effect.},
  language  = {en}
}
@article{ScherzadMeyerKleinsasseretal.2017,
  author    = {Scherzad, Agmal and Meyer, Till and Kleinsasser, Norbert and Hackenberg, Stephan},
  title     = {Molecular Mechanisms of Zinc Oxide Nanoparticle-Induced Genotoxicity Short Running Title: Genotoxicity of ZnO NPs},
  series = {Materials},
  volume    = {10},
  journal   = {Materials},
  number    = {12},
  doi       = {10.3390/ma10121427},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169948},
  pages     = {1427},
  year      = {2017},
  abstract  = {Background: Zinc oxide nanoparticles (ZnO NPs) are among the most frequently applied nanomaterials in consumer products. Evidence exists regarding the cytotoxic effects of ZnO NPs in mammalian cells; however, knowledge about the potential genotoxicity of ZnO NPs is rare, and results presented in the current literature are inconsistent. Objectives: The aim of this review is to summarize the existing data regarding the DNA damage that ZnO NPs induce, and focus on the possible molecular mechanisms underlying genotoxic events. Methods: Electronic literature databases were systematically searched for studies that report on the genotoxicity of ZnO NPs. Results: Several methods and different endpoints demonstrate the genotoxic potential of ZnO NPs. Most publications describe in vitro assessments of the oxidative DNA damage triggered by dissoluted Zn2+ ions. Most genotoxicological investigations of ZnO NPs address acute exposure situations. Conclusion: Existing evidence indicates that ZnO NPs possibly have the potential to damage DNA. However, there is a lack of long-term exposure experiments that clarify the intracellular bioaccumulation of ZnO NPs and the possible mechanisms of DNA repair and cell survival.},
  language  = {en}
}
@article{HackenbergMeyerHaefneretal.2022,
  author    = {Hackenberg, Stephan and Meyer, Till Jasper and H{\"a}fner, Johannes and Scheich, Matthias and St{\"o}th, Manuel and Al-Tinawi, Fadi and Neun, Tilmann and Mlynski, Robert and Hagen, Rudolf and Scherzad, Agmal},
  title     = {Surgical management of tympanojugular paragangliomas using the flexible CO\(_2\) laser},
  series = {European Archives of Oto-Rhino-Laryngology},
  volume    = {279},
  journal   = {European Archives of Oto-Rhino-Laryngology},
  number    = {12},
  doi       = {10.1007/s00405-022-07416-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324164},
  pages     = {5623-5630},
  year      = {2022},
  abstract  = {Purpose Surgery is a standard therapy for tympanojugular paragangliomas (TJP). Maintaining the quality of life (QoL) requires functional preservation. The flexible CO\(_2\) laser allows contact-free tumor removal. This retrospective study compares the postoperative functional outcomes of TJP surgery with and without the flexible CO\(_2\) laser. Methods Between 2005 and 2019, 51 patients with TJP were surgically treated at a tertiary hospital. Until 2012, 17 patients received conventional surgery. Thereafter, the flexible laser was used in 34 patients. Tumor extend, pre- and postoperative cranial nerve function, and complications were compared between the groups. Results The cohort consisted of 33 class A and B tumors and 18 class C and D tumors. Preoperative embolization was performed in 17 cases. Class C/D TJP were usually removed via an infratemporal fossa type A approach. Gross total tumor removal was achieved in 14/18 class C/D tumors. 3/51 patients suffered from long-term partial or complete facial palsy. No differences in post-therapeutic cranial nerve function or complications were noted between the conventional and laser group. One recurrence was observed after complete tumor resection. Conclusion The flexible CO\(_2\) laser was shown to be a safe and effective alternative to conventional bipolar cauterization, which is appreciated by the surgeon in these highly vascularized tumors. Both techniques allowed a high tumor control rate and good long-term results also from a functional point of view.},
  language  = {en}
}
@article{StefanakisBasslerWalczuchetal.2023,
  author    = {Stefanakis, Mona and Bassler, Miriam C. and Walczuch, Tobias R. and Gerhard-Hartmann, Elena and Youssef, Almoatazbellah and Scherzad, Agmal and St{\"o}th, Manuel Bernd and Ostertag, Edwin and Hagen, Rudolf and Steinke, Maria R. and Hackenberg, Stephan and Brecht, Marc and Meyer, Till Jasper},
  title     = {The impact of tissue preparation on salivary gland tumors investigated by Fourier-transform infrared microspectroscopy},
  series = {Journal of Clinical Medicine},
  volume    = {12},
  journal   = {Journal of Clinical Medicine},
  number    = {2},
  issn      = {2077-0383},
  doi       = {10.3390/jcm12020569},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304887},
  year      = {2023},
  abstract  = {Due to the wide variety of benign and malignant salivary gland tumors, classification and malignant behavior determination based on histomorphological criteria can be difficult and sometimes impossible. Spectroscopical procedures can acquire molecular biological information without destroying the tissue within the measurement processes. Since several tissue preparation procedures exist, our study investigated the impact of these preparations on the chemical composition of healthy and tumorous salivary gland tissue by Fourier-transform infrared (FTIR) microspectroscopy. Sequential tissue cross-sections were prepared from native, formalin-fixed and formalin-fixed paraffin-embedded (FFPE) tissue and analyzed. The FFPE cross-sections were dewaxed and remeasured. By using principal component analysis (PCA) combined with a discriminant analysis (DA), robust models for the distinction of sample preparations were built individually for each parotid tissue type. As a result, the PCA-DA model evaluation showed a high similarity between native and formalin-fixed tissues based on their chemical composition. Thus, formalin-fixed tissues are highly representative of the native samples and facilitate a transfer from scientific laboratory analysis into the clinical routine due to their robust nature. Furthermore, the dewaxing of the cross-sections entails the loss of molecular information. Our study successfully demonstrated how FTIR microspectroscopy can be used as a powerful tool within existing clinical workflows.},
  language  = {en}
}