TY  - JOUR
A1  - Suliman, Salwa
A1  - Mustafa, Kamal
A1  - Krueger, Anke
A1  - Steinmüller-Nethl, Doris
A1  - Finne-Wistrand, Anna
A1  - Osdal, Tereza
A1  - Hamza, Amani O.
A1  - Sun, Yang
A1  - Parajuli, Himalaya
A1  - Waag, Thilo
A1  - Nickel, Joachim
A1  - Johannessen, Anne Christine
A1  - McCormack, Emmet
A1  - Costea, Daniela Elena
T1  - Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes
JF  - Biomaterials
N2  - This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOK\(^{Luc}\)) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOK\(^{Luc}\) previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOK\(^{Luc}\) + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOK\(^{Luc}\) both in vitro in 3D-OT and in vivo in xenografts formed by DOKLuc alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOK\(^{Luc}\) + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOK\(^{Luc}\), while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities.
KW  - Bone morphogenetic protein-2
KW  - Sinus floor augmentation
KW  - Marrow stromal cells
KW  - Growth; BMP-2
KW  - Tumorigenicity
KW  - Biodegradable polymer scaffolds
KW  - Mandibular continuity defects
KW  - Squamous-cell carcinoma
KW  - In-vitro
KW  - Mesenchymal transition
KW  - BMP-2
KW  - Bone tissue engineering
KW  - Biocompatibility
KW  - Microenvironment
KW  - Oral squamous cell carcinoma
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188287
VL  - 95
ER  - 
TY  - JOUR
A1  - Plauth, Annabell
A1  - Geikowski, Anne
A1  - Cichon, Susanne
A1  - Wowro, Sylvia J.
A1  - Liedgens, Linda
A1  - Rousseau, Morten
A1  - Weidner, Christopher
A1  - Fuhr, Luise
A1  - Kliem, Magdalena
A1  - Jenkins, Gail
A1  - Lotito, Silvina
A1  - Wainwright, Linda J.
A1  - Sauer, Sascha
T1  - Hormetic shifting of redox environment by pro-oxidative resveratrol protects cells against stress
JF  - Free Radical Biology and Medicine
N2  - Resveratrol has gained tremendous interest owing to multiple reported health-beneficial effects. However, the underlying key mechanism of action of this natural product remained largely controversial. Here, we demonstrate that under physiologically relevant conditions major biological effects of resveratrol can be attributed to its generation of oxidation products such as reactive oxygen species (ROS). At low nontoxic concentrations (in general < 50 mu M), treatment with resveratrol increased viability in a set of representative cell models, whereas application of quenchers of ROS completely truncated these beneficial effects. Notably, resveratrol treatment led to mild, Nrf2-specific gene expression reprogramming. For example, in primary epidermal keratinocytes derived from human skin this coordinated process resulted in a 1.3-fold increase of endogenously generated glutathione (GSH) and subsequently in a quantitative reduction of the cellular redox environment by 2.61 mV mmol GSH per g protein. After induction of oxidative stress by using 0.78% (v/v) ethanol, endogenous generation of ROS was consequently reduced by 24% in resveratrol pre-treated cells. In contrast to the common perception that resveratrol acts mainly as a chemical antioxidant or as a target protein-specific ligand, we propose that the cellular response to resveratrol treatment is essentially based on oxidative triggering. In physiological microenvironments this molecular training can lead to hormetic shifting of cellular defense towards a more reductive state to improve physiological resilience to oxidative stress.
KW  - Trans-reservatrol
KW  - Hydrogen-peroxide
KW  - In-vitro
KW  - Hormesis
KW  - Ethanol
KW  - Oxygen
KW  - Nrf2
KW  - Glutathione
KW  - Metabolism
KW  - Polyphenols
KW  - ROS
KW  - Oxidative stress
KW  - Redox environment
KW  - Skin
KW  - Epidermis
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187186
VL  - 99
ER  -