Glioblastoma Therapy: Past, Present and Future.

Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians and researchers, no significant improvement in survival has been achieved since the Stupp protocol became the standard of care (SOC) in 2005. Despite multimodality treatments, recurrence is almost universal with survival rates under 2 years after diagnosis. Here, we discuss the recent progress in our understanding of GB pathophysiology, in particular, the importance of glioma stem cells (GSCs), the tumor microenvironment conditions, and epigenetic mechanisms involved in GB growth, aggressiveness and recurrence. The discussion on therapeutic strategies first covers the SOC treatment and targeted therapies that have been shown to interfere with different signaling pathways (pRB/CDK4/RB1/P16ink4, TP53/MDM2/P14arf, PI3k/Akt-PTEN, RAS/RAF/MEK, PARP) involved in GB tumorigenesis, pathophysiology, and treatment resistance acquisition. Below, we analyze several immunotherapeutic approaches (i.e., checkpoint inhibitors, vaccines, CAR-modified NK or T cells, oncolytic virotherapy) that have been used in an attempt to enhance the immune response against GB, and thereby avoid recidivism or increase survival of GB patients. Finally, we present treatment attempts made using nanotherapies (nanometric structures having active anti-GB agents such as antibodies, chemotherapeutic/anti-angiogenic drugs or sensitizers, radionuclides, and molecules that target GB cellular receptors or open the blood-brain barrier) and non-ionizing energies (laser interstitial thermal therapy, high/low intensity focused ultrasounds, photodynamic/sonodynamic therapies and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies and to present novel approaches that are under development or following clinical trials.

Neural Stem Cells as Potential Glioblastoma Cells of Origin.

Glioblastoma multiforme (GBM) is the most malignant brain tumor in adults and it remains incurable. These tumors are very heterogeneous, resistant to cytotoxic therapies, and they show high rates of invasiveness. Therefore, patients face poor prognosis, and the survival rates remain very low. Previous research states that GBM contains a cell population with stem cell characteristics called glioma stem cells (GSCs). These cells are able to self-renew and regenerate the tumor and, therefore, they are partly responsible for the observed resistance to therapies and tumor recurrence. Recent data indicate that neural stem cells (NSCs) in the subventricular zone (SVZ) are the cells of origin of GBM, that is, the cell type acquiring the initial tumorigenic mutation. The involvement of SVZ-NSCs is also associated with GBM progression and recurrence. Identifying the cellular origin of GBM is important for the development of early detection techniques and the discovery of early disease markers. In this review, we analyze the SVZ-NSC population as a potential GBM cell of origin, and its potential role for GBM therapies.

[Neonatal intracranial haemorrhage secondary to spontaneous rupture of an aneurysm. Illustrative case and literature review]. / Hemorragia intracraneal en el neonato secundaria a rotura aneurismatica espontanea. Caso ilustrativo y revision de la bibliografia.

INTRODUCTION: Intracranial arterial aneurysms are little frequent among the pediatric age group but the frequency is still lower in children under 1 year of age and extremely rare in neonates. We present a case, review literature and propose common characteristics and management of this pathology. CASE REPORT: A term newborn suffered reduction of the level of conscience. After brain ultrasound examination and CT scan was diagnosed with intraparenchymatous hematoma on the 7th day of life. Intraoperative, after evacuation of this hematoma, we discovered, clipped and extirpated a middle cerebral artery aneurysm without any problems. The patient's evolution was satisfactory only presenting a slight paresia of his right arm. CONCLUSION: We review the literature and find 16 cases of neonatal intracranial arterial aneurysms. Mortality rate is about 50%, but keeping in mind better survivals with surgical treatment in the last years. Thus we conclude, when it is possible, in favour of a surgical and precocious treatment of these neonatal aneurysm.