TY  - JOUR
A1  - Feldheim, Jonas
A1  - Kessler, Almuth F.
A1  - Feldheim, Julia J.
A1  - Schulz, Ellina
A1  - Wend, David
A1  - Lazaridis, Lazaros
A1  - Kleinschnitz, Christoph
A1  - Glas, Martin
A1  - Ernestus, Ralf-Ingo
A1  - Brandner, Sebastian
A1  - Monoranu, Camelia M.
A1  - Löhr, Mario
A1  - Hagemann, Carsten
T1  - Effects of long-term temozolomide treatment on glioblastoma and astrocytoma WHO grade 4 stem-like cells
JF  - International Journal of Molecular Sciences
N2  - Glioblastoma leads to a fatal course within two years in more than two thirds of patients. An essential cornerstone of therapy is chemotherapy with temozolomide (TMZ). The effect of TMZ is counteracted by the cellular repair enzyme O\(^6\)-methylguanine-DNA methyltransferase (MGMT). The MGMT promoter methylation, the main regulator of MGMT expression, can change from primary tumor to recurrence, and TMZ may play a significant role in this process. To identify the potential mechanisms involved, three primary stem-like cell lines (one astrocytoma with the mutation of the isocitrate dehydrogenase (IDH), CNS WHO grade 4 (HGA)), and two glioblastoma (IDH-wildtype, CNS WHO grade 4) were treated with TMZ. The MGMT promoter methylation, migration, proliferation, and TMZ-response of the tumor cells were examined at different time points. The strong effects of TMZ treatment on the MGMT methylated cells were observed. Furthermore, TMZ led to a loss of the MGMT promoter hypermethylation and induced migratory rather than proliferative behavior. Cells with the unmethylated MGMT promoter showed more aggressive behavior after treatment, while HGA cells reacted heterogenously. Our study provides further evidence to consider the potential adverse effects of TMZ chemotherapy and a rationale for investigating potential relationships between TMZ treatment and change in the MGMT promoter methylation during relapse.
KW  - glioblastoma
KW  - astrocytoma
KW  - IDH
KW  - MGMT
KW  - therapy
KW  - temozolomide
KW  - cancer stem cells
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284417
SN  - 1422-0067
VL  - 23
IS  - 9
ER  - 
TY  - JOUR
A1  - Feldheim, Jonas
A1  - Kessler, Almuth F.
A1  - Feldheim, Julia J.
A1  - Schmitt, Dominik
A1  - Oster, Christoph
A1  - Lazaridis, Lazaros
A1  - Glas, Martin
A1  - Ernestus, Ralf-Ingo
A1  - Monoranu, Camelia M.
A1  - Löhr, Mario
A1  - Hagemann, Carsten
T1  - BRMS1 in gliomas — an expression analysis
JF  - Cancers
N2  - The metastatic suppressor BRMS1 interacts with critical steps of the metastatic cascade in many cancer entities. As gliomas rarely metastasize, BRMS1 has mainly been neglected in glioma research. However, its interaction partners, such as NFκB, VEGF, or MMPs, are old acquaintances in neurooncology. The steps regulated by BRMS1, such as invasion, migration, and apoptosis, are commonly dysregulated in gliomas. Therefore, BRMS1 shows potential as a regulator of glioma behavior. By bioinformatic analysis, in addition to our cohort of 118 specimens, we determined BRMS1 mRNA and protein expression as well as its correlation with the clinical course in astrocytomas IDH mutant, CNS WHO grade 2/3, and glioblastoma IDH wild-type, CNS WHO grade 4. Interestingly, we found BRMS1 protein expression to be significantly decreased in the aforementioned gliomas, while BRMS1 mRNA appeared to be overexpressed throughout. This dysregulation was independent of patients’ characteristics or survival. The protein and mRNA expression differences cannot be finally explained at this stage. However, they suggest a post-transcriptional dysregulation that has been previously described in other cancer entities. Our analyses present the first data on BRMS1 expression in gliomas that can provide a starting point for further investigations.
KW  - glioblastoma
KW  - metastasis
KW  - suppressor
KW  - behavior
KW  - mRNA
KW  - protein
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319225
SN  - 2072-6694
VL  - 15
IS  - 11
ER  -