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
T2  - 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
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/28441
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-284417
SN  - 1422-0067
VL  - 23
IS  - 9
ER  -