TY  - JOUR
A1  - Ickrath, Pascal
A1  - Wagner, Martin
A1  - Scherzad, Agmal
A1  - Gehrke, Thomas
A1  - Burghartz, Marc
A1  - Hagen, Rudolf
A1  - Radeloff, Katrin
A1  - Kleinsasser, Norbert
A1  - Hackenberg, Stephan
T1  - Time-Dependent Toxic and Genotoxic Effects of Zinc Oxide Nanoparticles after Long-Term and Repetitive Exposure to Human Mesenchymal Stem Cells
JF  - International Journal of Environmental Research and Public Health
N2  - Zinc oxide nanoparticles (ZnO-NP) are widely spread in consumer products. Data about the toxicological characteristics of ZnO-NP is still under controversial discussion. The human skin is the most important organ concerning ZnO-NP exposure. Intact skin was demonstrated to be a sufficient barrier against NPs; however, defect skin may allow NP contact to proliferating cells. Within these cells, stem cells are the most important toxicological target for NPs. The aim of this study was to evaluate the genotoxic and cytotoxic effects of ZnO-NP at low-dose concentrations after long-term and repetitive exposure to human mesenchymal stem cells (hMSC). Cytotoxic effects of ZnO-NP were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, genotoxicity was evaluated by the comet assay. For long-term observation over 6 weeks, transmission electron microscopy (TEM) was applied. The results of the study indicated cytotoxic effects of ZnO-NP beginning at high concentrations of 50 μg/mL and genotoxic effects in hMSC exposed to 1 and 10 μg/mL ZnO-NP. Repetitive exposure enhanced cyto- but not genotoxicity. Intracellular NP accumulation was observed up to 6 weeks. The results suggest cytotoxic and genotoxic potential of ZnO-NP. Even low doses of ZnO-NP may induce toxic effects as a result of repetitive exposure and long-term cellular accumulation. This data should be considered before using ZnO-NP on damaged skin.
KW  - zinc oxide
KW  - ZnO
KW  - nanoparticles
KW  - cytotoxicity
KW  - toxicity
KW  - genotoxicity
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169932
VL  - 14
IS  - 12
ER  - 
TY  - JOUR
A1  - Polat, Bülent
A1  - Kaiser, Philipp
A1  - Wohlleben, Gisela
A1  - Gehrke, Thomas
A1  - Scherzad, Agmal
A1  - Scheich, Matthias
A1  - Malzahn, Uwe
A1  - Fischer, Thomas
A1  - Vordermark, Dirk
A1  - Flentje, Michael
T1  - Perioperative changes in osteopontin and TGFβ1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer
JF  - BMC Cancer
N2  - Background:
In head and neck cancer little is known about the kinetics of osteopontin (OPN) expression after tumor resection. In this study we evaluated the time course of OPN plasma levels before and after surgery.
Methods:
Between 2011 and 2013 41 consecutive head and neck cancer patients were enrolled in a prospective study (group A). At different time points plasma samples were collected: T0) before, T1) 1 day, T2) 1 week and T3) 4 weeks after surgery. Osteopontin and TGFβ1 plasma concentrations were measured with a commercial ELISA system. Data were compared to 131 head and neck cancer patients treated with primary (n = 42) or postoperative radiotherapy (n = 89; group B1 and B2).
Results:
A significant OPN increase was seen as early as 1 day after surgery (T0 to T1, p < 0.01). OPN levels decreased to base line 3-4 weeks after surgery. OPN values were correlated with postoperative TGFβ1 expression suggesting a relation to wound healing. Survival analysis showed a significant benefit for patients with lower OPN levels both in the primary and postoperative radiotherapy group (B1: 33 vs 11.5 months, p = 0.017, B2: median not reached vs 33.4, p = 0.031). TGFβ1 was also of prognostic significance in group B1 (33.0 vs 10.7 months, p = 0.003).
Conclusions:
Patients with head and neck cancer showed an increase in osteopontin plasma levels directly after surgery. Four weeks later OPN concentration decreased to pre-surgery levels. This long lasting increase was presumably associated to wound healing. Both pretherapeutic osteopontin and TGFβ1 had prognostic impact.
KW  - perioperative changes
KW  - osteopontin
KW  - TGFβ1
KW  - head and neck cancer
KW  - survival
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157529
VL  - 17
IS  - 6
ER  -