Stransky, Nicolai and Ganser, Katrin and Quintanilla-Martinez, Leticia and Gonzalez-Menendez, Irene and Naumann, Ulrike and Eckert, Franziska and Koch, Pierre and Huber, Stephan M. and Ruth, Peter (2023) Efficacy of combined tumor irradiation and KCa3.1-targeting with TRAM-34 in a syngeneic glioma mouse model. SCIENTIFIC REPORTS, 13 (1): 20604. ISSN 2045-2322,
Full text not available from this repository. (Request a copy)Abstract
The intermediate-conductance calcium-activated potassium channel K(Ca)3.1 has been proposed to be a new potential target for glioblastoma treatment. This study analyzed the effect of combined irradiation and K(Ca)3.1-targeting with TRAM-34 in the syngeneic, immune-competent orthotopic SMA-560/VM/Dk glioma mouse model. Whereas neither irradiation nor TRAM-34 treatment alone meaningfully prolonged the survival of the animals, the combination significantly prolonged the survival of the mice. We found an irradiation-induced hyperinvasion of glioma cells into the brain, which was inhibited by concomitant TRAM-34 treatment. Interestingly, TRAM-34 did neither radiosensitize nor impair SMA-560's intrinsic migratory capacities in vitro. Exploratory findings hint at increased TGF-beta 1 signaling after irradiation. On top, we found a marginal upregulation of MMP9 mRNA, which was inhibited by TRAM-34. Last, infiltration of CD3(+), CD8(+) or FoxP3(+) T cells was not impacted by either irradiation or K(Ca)3.1 targeting and we found no evidence of adverse events of the combined treatment. We conclude that concomitant irradiation and TRAM-34 treatment is efficacious in this preclinical glioma model.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CA2+-ACTIVATED K+ CHANNEL; INTERMEDIATE-CONDUCTANCE; MURINE ASTROCYTOMA; IMMUNE CELLS; DOUBLE-BLIND; TGF-BETA; GLIOBLASTOMA; RADIOTHERAPY; TEMOZOLOMIDE; MIGRATION; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Apr 2024 13:31 |
| Last Modified: | 22 Apr 2024 13:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/62955 |
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