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  - Solimando, Antonio Giovanni
A1  - Da Vià, Matteo Claudio
A1  - Bolli, Niccolò
A1  - Steinbrunn, Torsten
T1  - The route of the malignant plasma cell in its survival niche: exploring “Multiple Myelomas”
JF  - Cancers
N2  - Growing evidence points to multiple myeloma (MM) and its stromal microenvironment using several mechanisms to subvert effective immune and anti-tumor responses. Recent advances have uncovered the tumor-stromal cell influence in regulating the immune-microenvironment and have envisioned targeting these suppressive pathways to improve therapeutic outcomes. Nevertheless, some subgroups of patients include those with particularly unfavorable prognoses. Biological stratification can be used to categorize patient-, disease- or therapy-related factors, or alternatively, these biological determinants can be included in a dynamic model that customizes a given treatment to a specific patient. Genetic heterogeneity and current knowledge enforce a systematic and comprehensive bench-to-bedside approach. Given the increasing role of cancer stem cells (CSCs) in better characterizing the pathogenesis of solid and hematological malignancies, disease relapse, and drug resistance, identifying and describing CSCs is of paramount importance in the management of MM. Even though the function of CSCs is well-known in other cancer types, their role in MM remains elusive. With this review, we aim to provide an update on MM homing and resilience in the bone marrow micro milieu. These data are particularly interesting for clinicians facing unmet medical needs while designing novel treatment approaches for MM.
KW  - multiple myeloma
KW  - cell of origin
KW  - cancer stem cells
KW  - bone marrow homing
KW  - adhesion molecule
KW  - bone marrow immune-microenvironment
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281728
SN  - 2072-6694
VL  - 14
IS  - 13
ER  -