DDRE-38. MAGMAS INHIBITION IN MEDULLOBLASTOMA CELL CULTURES AND PATIENT-DERIVED XENOGRAFT MODELS: POTENTIAL THERAPEUTIC IMPLICATIONS
| Autor: | Javier Lepe, Clay Hoerig, Naomi Lomeli, Ashley Plant-Fox, Christopher J. Douglas, Bhaskar Das, Kaijun Di, Daniela A. Bota |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Pediatric Cancer Oncology and Carcinogenesis 26th Annual Meeting & Education Day of the Society for Neuro-Oncology Rare Diseases Stem Cell Research - Nonembryonic - Human Medicine 2.1 Biological and endogenous factors Oncology & Carcinogenesis Aetiology Tumor xenograft Cancer Medulloblastoma Pediatric business.industry Neurosciences medicine.disease Stem Cell Research Brain Disorders Brain Cancer Orphan Drug Oncology Cell culture 5.1 Pharmaceuticals Cancer research Neurology (clinical) Development of treatments and therapeutic interventions business Biotechnology |
| Zdroj: | Neuro-Oncology, vol 23, iss Supplement_6 Neuro-oncology, vol 23, iss Suppl 6 Neuro Oncol |
| Popis: | BACKGROUND Brain tumors are the second most common type of pediatric cancer and are the leading cause of all cancer-related deaths in children. Medulloblastoma (MB) is the most common type of malignant pediatric brain tumor and has a five-year overall survival ranging from 40-75%, depending on the patient’s age and other prognostic features. There are current anti-cancer therapies against medulloblastoma, but the treatment of recurrent disease remains a challenge. Magmas (mitochondria-associated protein involved in granulocyte-macrophage colony-stimulating factor signal transduction) overexpression has been reported in multiple types of metabolically active tissue and cancer cells, including prostate cancer, pituitary adenoma, and glioma. Limited data suggest that specific subgroups of medulloblastoma may also overexpress Magmas. This study aims to examine whether Magmas inhibition by compound “BT#9” could be beneficial for the treatment of medulloblastoma. METHODS We studied the ability of a Magmas inhibitor (BT#9) as a therapeutic agent in stable medulloblastoma cell lines (DAOY and D283) and patient-derived primary cultures with MTT assays, migration assays, and invasion assays. RESULTS Similar to the adult GBM studies, Magmas inhibition by BT9 had significant cytotoxic effects, causing both decreased cell proliferation and blocked cell migration in medulloblastoma cell lines DAOY and D283. IC50s determined for each during different time points demonstrated an average range of less than 3μM compared to the average range seen in adult glioblastoma cell cultures (< 10 μM). These findings suggest that the inhibition of Magmas warrants further investigation as a potential therapeutic target to optimize clinical outcomes in medulloblastoma. Our future studies will include the determination of IC50s for primary cell cultures and in vitro testing with patient-derived xenograft models. |
| Databáze: | OpenAIRE |
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