دورية أكاديمية
Efficacy of combined tumor irradiation and KCa3.1-targeting with TRAM-34 in a syngeneic glioma mouse model
| العنوان: | Efficacy of combined tumor irradiation and KCa3.1-targeting with TRAM-34 in a syngeneic glioma mouse model |
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| المؤلفون: | Stransky, Nicolai, Ganser, Katrin, Quintanilla-Martinez, Leticia, Gonzalez-Menendez, Irene, Naumann, Ulrike, Eckert, Franziska, Koch, Pierre, Huber, Stephan M., Ruth, Peter |
| المساهمون: | Deutsche Krebshilfe, Gesellschaft für Kinderkrebsforschung, Deutsche Forschungsgemeinschaft, Universitätsklinikum Tübingen |
| المصدر: | Scientific Reports ; volume 13, issue 1 ; ISSN 2045-2322 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Multidisciplinary |
| الوصف: | 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-β1 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41598-023-47552-4 |
| الإتاحة: | https://doi.org/10.1038/s41598-023-47552-4Test https://www.nature.com/articles/s41598-023-47552-4.pdfTest https://www.nature.com/articles/s41598-023-47552-4Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.540EA364 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-023-47552-4 |
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