TY  - JOUR
A1  - Meyer, Till Jasper
A1  - Stöth, Manuel
A1  - Moratin, Helena
A1  - Ickrath, Pascal
A1  - Herrmann, Marietta
A1  - Kleinsasser, Norbert
A1  - Hagen, Rudolf
A1  - Hackenberg, Stephan
A1  - Scherzad, Agmal
T1  - Cultivation of head and neck squamous cell carcinoma cells with wound fluid leads to cisplatin resistance via epithelial-mesenchymal transition induction
JF  - International Journal of Molecular Sciences
N2  - 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.
KW  - cell proliferation
KW  - wound fluid
KW  - epithelial-mesenchymal transition
KW  - cisplatin resistance
KW  - Interleukin
KW  - head and neck squamous cell carcinoma
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258722
SN  - 1422-0067
VL  - 22
IS  - 9
ER  - 
TY  - JOUR
A1  - Meyer, Till Jasper
A1  - Scherzad, Agmal
A1  - Moratin, Helena
A1  - Gehrke, Thomas Eckert
A1  - Killisperger, Julian
A1  - Hagen, Rudolf
A1  - Wohlleben, Gisela
A1  - Polat, Bülent
A1  - Dembski, Sofia
A1  - Kleinsasser, Norbert
A1  - Hackenberg, Stephan
T1  - The radiosensitizing effect of zinc oxide nanoparticles in sub-cytotoxic dosing is associated with oxidative stress in vitro
JF  - Materials
N2  - 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.
KW  - zinc oxide nanoparticles
KW  - irradiation
KW  - oxidative DNA damage
KW  - head and neck squamous cell carcinoma
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193897
SN  - 1996-1944
VL  - 12
IS  - 24
ER  -