Angiogenesis in human brain tumors: screening of drug response through a patient-specific cell platform for personalized therapy
| Autor: | Alessandro Cherubini, Francesco Maria Crisà, Elena Trombetta, Laura Guarnaccia, Laura Riboni, Laura Fontana, Monica Miozzo, Rolando Campanella, Marco Locatelli, Chiara Cordiglieri, Paolo Rampini, Manuela Caroli, Stefania Elena Navone, Giovanni Marfia |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Bevacizumab Angiogenesis Cell lcsh:Medicine Angiogenesis Inhibitors Vascular permeability Article Flow cytometry Neovascularization 03 medical and health sciences Tumor Cells Cultured medicine Humans Precision Medicine lcsh:Science Aged Aged 80 and over Multidisciplinary Temozolomide Neovascularization Pathologic medicine.diagnostic_test Brain Neoplasms business.industry Sunitinib lcsh:R Endothelial Cells Middle Aged nervous system diseases 030104 developmental biology medicine.anatomical_structure Cancer research lcsh:Q Drug Screening Assays Antitumor medicine.symptom Glioblastoma business medicine.drug |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-13 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Gliomas are the most common brain tumors, with diverse biological behaviour. Glioblastoma (GBM), the most aggressive and with the worst prognosis, is characterized by an intense and aberrant angiogenesis, which distinguishes it from low-grade gliomas (LGGs) and benign expansive lesions, as meningiomas (MNGs). With increasing evidence for the importance of vascularization in tumor biology, we focused on the isolation and characterization of endothelial cells (ECs) from primary GBMs, LGGs and MNGs. Gene expression analysis by Real-Time PCR, immunofluorescence and flow cytometry analysis, tube-like structures formation and vascular permeability assays were performed. Our results showed a higher efficiency of ECs to form a complex vascular architecture, as well as a greater impairment of a brain blood barrier model, and an overexpression of pro-angiogenic mediators in GBM than in LGG and MNG. Furthermore, administration of temozolomide, bevacizumab, and sunitinib triggered a different proliferative, apoptotic and angiogenic response, in a dose and time-dependent manner. An increased resistance to temozolomide was observed in T98G cells co-cultured in GBM-EC conditioned media. Therefore, we developed a novel platform to reproduce tumor vascularization as “disease in a dish”, which allows us to perform screening of sensitivity/resistance to drugs, in order to optimize targeted approaches to GBM therapy. |
| Databáze: | OpenAIRE |
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