@article {SCHMOCH1489, author = {THOMAS SCHMOCH and ZOLTAN GAL and ANDREAS MOCK and JAN MOSSEMANN and BERND LAHRMANN and NIELS GRABE and PETER SCHMEZER and FELIX LASITSCHKA and PHILIPP BECKHOVE and ANDREAS UNTERBERG and CHRISTEL HEROLD-MENDE}, title = {Combined Treatment of ATRA with Epigenetic Drugs Increases Aggressiveness of Glioma Xenografts}, volume = {36}, number = {4}, pages = {1489--1496}, year = {2016}, publisher = {International Institute of Anticancer Research}, abstract = {Background/Aim: Recently, anti-tumourigenic effects of all-trans-retinoic-acid (ATRA) on glioblastoma stem cells were demonstrated. Therefore we investigated if these beneficial effects could be enhanced by co-medication with epigenetic drugs such as the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) or the DNA-methyltransferase inhibitor 5-aza-2{\textquoteright}deoxycytidine (5-AZA). Materials and Methods: Glioma stem cell xenografts were treated for 42 days with ATRA plus SAHA or ATRA plus 5-AZA or the correspondent monotherapies. Tumour sizes, histological features, proliferation and apoptosis rates were assessed. Results: Neither SAHA nor 5-AZA were able to enhance the anti-tumourigenic effect of ATRA. Instead, tumours became more aggressive. Combination of ATRA plus 5-AZA increased tumour size (p\<0.05) and induced more frequent and larger necroses (p\<0.05) and tumours were more invasive (p\<0.05) in comparison to controls. A similar trend was observed for the combination of ATRA plus SAHA. Conclusion: Combining ATRA with epigenetic drug therapies led to the unwanted opposite effect and increased aggressiveness of glioma xenografts, arguing against future clinical applications of such combinations.}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/36/4/1489}, eprint = {https://ar.iiarjournals.org/content/36/4/1489.full.pdf}, journal = {Anticancer Research} }