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Table of contents
LIST OF TABLES
LIST OF FIGURES
ABBREVIATIONS
INTRODUCTION
1. CLASSIFICATION OF PRIMARY BRAIN TUMORS IN ADULTS
1.1 Primary brain tumors in adults
1.2 Glioblastoma IDH wildtype
1.2.1 Epidemiology
1.2.2 Clinical presentation and diagnosis of GBM
1.2.3 Standard treatment of GBM
1.2.4 Prognostic factors in GBM patients
2. GBM CELL BIOLOGY AND THEIR MICROENVIRONMENT
2.1 GBM cells and heterogeneity
2.1.1 Tumor cells origin, and intratumor cell heterogeneity
2.1.2 Four signaling pathways are disrupted in GBM
2.2 Tumor cell microenvironment
2.2.1 Niches and stem cells of GBM
2.2.2 Cellular components of TME
2.2.3 Glioma-associated neovascularization
2.2.4 The blood-brain barrier
3. THERAPEUTIC STRATEGIES TO MODULATE THE TUMOR MICROENVIRONMENT
3.2 Modulation of the immune system
3.2.1 History and concept of immune system’s modulation
3.2.2 Antitumor immune response
3.2.3 Tumor escape mechanisms
3.2.4 Immunotherapy
3.2.5 Monoclonal antibodies
3.2.6 Monoclonal antibodies against checkpoint proteins
3.3 Overcoming, disrupting, or bypassing the BBB
3.3.1 The BBB limits drug penetration into normal and tumor tissue
3.3.2 Role of ultrasound-mediated BBB opening
3.3.3 UMBO and antibodies delivery to the brain
3.3.4 Ultrasound mediated BBB opening in clinical settings
THESIS OBJECTIVES
RESULTS
Role of Multi-Drug Resistance in Glioblastoma Chemoresistance: Focus on ABC Transporters
CD80 and CD86: expression and prognostic value in newly diagnosed glioblastoma
Temporary blood-brain barrier disruption by low-intensity pulsed ultrasound increases anti-PD-L1 delivery and efficacy in glioblastoma mouse models
GENERAL DISCUSSION 152 GENERAL CONCLUSION
ALL REFERENCES
