TY  - JOUR
A1  - Tuca, Alexandru-Cristian
A1  - Bernardelli de Mattos, Ives
A1  - Funk, Martin
A1  - Winter, Raimund
A1  - Palackic, Alen
A1  - Groeber-Becker, Florian
A1  - Kruse, Daniel
A1  - Kukla, Fabian
A1  - Lemarchand, Thomas
A1  - Kamolz, Lars-Peter
T1  - Orchestrating the dermal/epidermal tissue ratio during wound healing by controlling the moisture content
JF  - Biomedicines
N2  - A balanced and moist wound environment and surface increases the effect of various growth factors, cytokines, and chemokines, stimulating cell growth and wound healing. Considering this fact, we tested in vitro and in vivo water evaporation rates from the cellulose dressing epicite\(^{hydro}\) when combined with different secondary dressings as well as the resulting wound healing efficacy in a porcine donor site model. The aim of this study was to evaluate how the different rates of water evaporation affected wound healing efficacy. To this end, epicite\(^{hydro}\) primary dressing, in combination with different secondary dressing materials (cotton gauze, JELONET\(^◊\), AQUACEL\(^®\) Extra\(^™\), and OPSITE\(^◊\) Flexifix), was placed on 3 × 3 cm-sized dermatome wounds with a depth of 1.2 mm on the flanks of domestic pigs. The healing process was analyzed histologically and quantified by morphometry. High water evaporation rates by using the correct secondary dressing, such as cotton gauze, favored a better re-epithelialization in comparison with the low water evaporation resulting from an occlusive secondary dressing, which favored the formation of a new and intact dermal tissue that nearly fully replaced all the dermis that was removed during wounding. This newly available evidence may be of great benefit to clinical wound management.
KW  - bacterial cellulose dressing
KW  - secondary wound dressing
KW  - moisture balance
KW  - wound healing
KW  - in vivo experiments
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275115
SN  - 2227-9059
VL  - 10
IS  - 6
ER  - 
TY  - JOUR
A1  - Djuzenova, Cholpon S.
A1  - Fiedler, Vanessa
A1  - Memmel, Simon
A1  - Katzer, Astrid
A1  - Sisario, Dmitri
A1  - Brosch, Philippa K.
A1  - Göhrung, Alexander
A1  - Frister, Svenja
A1  - Zimmermann, Heiko
A1  - Flentje, Michael
A1  - Sukhorukov, Vladimir L.
T1  - Differential effects of the Akt inhibitor MK-2206 on migration and radiation sensitivity of glioblastoma cells
JF  - BMC Cancer
N2  - Background
Most tumor cells show aberrantly activated Akt which leads to increased cell survival and resistance to cancer radiotherapy. Therefore, targeting Akt can be a promising strategy for radiosensitization. Here, we explore the impact of the Akt inhibitor MK-2206 alone and in combination with the dual PI3K and mTOR inhibitor PI-103 on the radiation sensitivity of glioblastoma cells. In addition, we examine migration of drug-treated cells.

Methods
Using single-cell tracking and wound healing migration tests, colony-forming assay, Western blotting, flow cytometry and electrorotation we examined the effects of MK-2206 and PI-103 and/or irradiation on the migration, radiation sensitivity, expression of several marker proteins, DNA damage, cell cycle progression and the plasma membrane properties in two glioblastoma (DK-MG and SNB19) cell lines, previously shown to differ markedly in their migratory behavior and response to PI3K/mTOR inhibition.

Results
We found that MK-2206 strongly reduces the migration of DK-MG but only moderately reduces the migration of SNB19 cells. Surprisingly, MK-2206 did not cause radiosensitization, but even increased colony-forming ability after irradiation. Moreover, MK-2206 did not enhance the radiosensitizing effect of PI-103. The results appear to contradict the strong depletion of p-Akt in MK-2206-treated cells. Possible reasons for the radioresistance of MK-2206-treated cells could be unaltered or in case of SNB19 cells even increased levels of p-mTOR and p-S6, as compared to the reduced expression of these proteins in PI-103-treated samples. We also found that MK-2206 did not enhance IR-induced DNA damage, neither did it cause cell cycle distortion, nor apoptosis nor excessive autophagy.

Conclusions
Our study provides proof that MK-2206 can effectively inhibit the expression of Akt in two glioblastoma cell lines. However, due to an aberrant activation of mTOR in response to Akt inhibition in PTEN mutated cells, the therapeutic window needs to be carefully defined, or a combination of Akt and mTOR inhibitors should be considered.
KW  - DNA damage
KW  - glioblastoma multiforme
KW  - histone H2AX
KW  - irradiation
KW  - migration
KW  - mTOR
KW  - PTEN
KW  - p53
KW  - radiation sensitivity
KW  - wound healing
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200290
VL  - 19
ER  -