Integrins have been suggested as possible targets in anticancer therapy. Here we show that knockdown of integrins αVβ3, αVβ5, α3β1 and α4β1 and pharmacological inhibition using a cyclo-RGD integrin αVβ3/αVβ5 antagonist sensitized multiple high-grade glioma cell lines to temozolomide (TMZ)-induced cytotoxicity. The greatest effect was observed in LN229 cells upon integrin β3 silencing, which led to inhibition of the FAK/Src/Akt/NFκB signaling pathway and increased formation of γH2AX foci. The integrin β3 knockdown led to the proteasomal degradation of Rad51, reduction of Rad51 foci and reduced repair of TMZ-induced DNA double-strand breaks by impairing homologous recombination efficiency. The down-regulation of β3 in Rad51 knockdown (LN229-Rad51kd) cells neither further sensitized them to TMZ nor increased the number of γH2AX foci, confirming causality between β3 silencing and Rad51 reduction. RIP1 was found cleaved and IκBα significantly less degraded in β3-silenced/TMZ-exposed cells, indicating inactivation of NFκB signaling. The anti-apoptotic proteins Bcl-xL, survivin and XIAP were proteasomally degraded and caspase-3/−2 cleaved. Increased H2AX phosphorylation, caspase-3 cleavage, reduced Rad51 and RIP1 expression, as well as sustained IκBα expression were also observed in mouse glioma xenografts treated with the cyclo-RGD inhibitor and TMZ, confirming the molecular mechanism in vivo. Our data indicates that β3 silencing in glioma cells represents a promising strategy to sensitize high-grade gliomas to TMZ therapy.

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The objective was to investigate the applicability of UV-C technology to inactivate yeasts and bacteria in must and wine. Experiments were carried out in vintage 2016 with Riesling musts of different quality containing their natural microflora. Yeasts were tested more resistant to UV-C energy than bacteria. Saccharomyces cerevisiae showed higher tolerance against UV-C irradiation than Hanseniaspora uvarum facilitating new opportunities to control spontaneous fermentations. However, inactivation efficacy was strongly dependent on turbidity of musts and the initial degree of contamination suggesting a shadowing effect of individual germs. Compared with thermal pasteurization, UV-C treatment of must with 1 kJ/L showed similar effects in germ-reduction. While thermal pasteurization significantly decreased aroma precursors in musts, UV-C treatment did not change concentrations of glycosidically-bound C6-alcohols, monoterpenes and C13-norisoprenoids as shown by GC-MS analysis. Applying UV-C technology in wines, it was possible to irreversibly stop ongoing alcoholic fermentation indicating that UV-C treatment is capable to replace SO 2 addition to produce wines with residual sugar. Besides inactivation power, UV-C is known for its ability to form powerful off-flavours such as methional or methanethiol. Sensory analysis revealed that the application of UV-C at doses < 2 kJ/L in must is uncritical. However, applying UV-C after alcoholic fermentation can result in rising concentrations of mercaptans already at doses < 1 kJ/L. In this context, compounds such as caftaric acid, riboflavin and dissolved oxygen are thought to positively contribute to the UV-induced formation of off-flavours in wine.