Stefan Holzhauser1, Monika Lukoseviciute1, Teodora Andonova2, Ramona G Ursu3, Tina Dalianis1, Malin Wickström4, Ourania N Kostopoulou5. 1. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. 2. Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. 3. Department of Microbiology, University of Medicine and Pharmacy, Grigore T. Popa, Iasi, Romania. 4. Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden ourania.kostopoulou@ki.se malin.wickstrom@ki.se. 5. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden ourania.kostopoulou@ki.se malin.wickstrom@ki.se.
Abstract
BACKGROUND/AIM: Medulloblastoma (MB) accounts for ~20% of pediatric malignant central nervous system tumors. Treatment strategies, including surgery, radiation therapy and/or chemotherapy, are effective, but recurrence and metastasis frequently occur. Therefore, novel therapies are required. Herein, the effects of fibroblast growth factor receptor (FGFR) and phosphoinositide 3-kinase (PI3K) inhibitors on MB cells lines were evaluated. MATERIALS AND METHODS: MB cell lines (UW228-3, DAOY, Med8a, D425, D283) were tested for sensitivity to FGFR (AZD4547) and PI3K (BEZ235 and BYL719) inhibitors by viability, cytotoxicity, apoptosis, and proliferation assays. RESULTS: Single treatments with FGFR and PI3K inhibitors decreased viability and proliferation in a dose-dependent pattern in most cell lines. Combinination of the two type of drugs, increased sensitivity, especially of the most resistant cell line UW228-3. CONCLUSION: Combination treatments with FGFR and PI3K inhibitors were superior to single treatments with FGFR and PI3K inhibitors, especially with BEZ235, for MB cell lines. Copyright
BACKGROUND/AIM: Medulloblastoma (MB) accounts for ~20% of pediatric malignant central nervous system tumors. Treatment strategies, including surgery, radiation therapy and/or chemotherapy, are effective, but recurrence and metastasis frequently occur. Therefore, novel therapies are required. Herein, the effects of fibroblast growth factor receptor (FGFR) and phosphoinositide 3-kinase (PI3K) inhibitors on MB cells lines were evaluated. MATERIALS AND METHODS:MB cell lines (UW228-3, DAOY, Med8a, D425, D283) were tested for sensitivity to FGFR (AZD4547) and PI3K (BEZ235 and BYL719) inhibitors by viability, cytotoxicity, apoptosis, and proliferation assays. RESULTS: Single treatments with FGFR and PI3K inhibitors decreased viability and proliferation in a dose-dependent pattern in most cell lines. Combinination of the two type of drugs, increased sensitivity, especially of the most resistant cell line UW228-3. CONCLUSION: Combination treatments with FGFR and PI3K inhibitors were superior to single treatments with FGFR and PI3K inhibitors, especially with BEZ235, for MB cell lines. Copyright
Authors: Stefan Holzhauser; Monika Lukoseviciute; Christina Papachristofi; Christina Vasilopoulou; Nikolas Herold; Malin Wickström; Ourania N Kostopoulou; Tina Dalianis Journal: Int J Oncol Date: 2021-01-05 Impact factor: 5.650
Authors: Stefan Holzhauser; Nicole Wild; Mark Zupancic; Ramona G Ursu; Cinzia Bersani; Anders Näsman; Ourania N Kostopoulou; Tina Dalianis Journal: Front Oncol Date: 2021-05-11 Impact factor: 6.244