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  - 
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  -