Brain tumours are a serious concern among both physicians and patients. The most feared brain tumour is glioblastoma (GBM) due to its heterogeneous histology, substantial invasive capacity, and rapid postsurgical recurrence. Even in cases of early management consisting of surgery, chemo-, and radiotherapy, the prognosis is still poor, with an extremely short survival period. Consequently, researchers are trying to better understand the underlying pathways involved in GBM development in order to establish a more personalised approach. The latest focus is on molecular characterisation of the tumour, including analysis of extracellular vesicles (EVs), nanostructures derived from both normal and pathological cells that have an important role in intercellular communication due to the various molecules they carry. There are two types of EV based on their biogenesis, but exosomes are of particular interest in GBM. Recent studies have demonstrated that GBM cells release numerous exosomes whose cargo provides them the capacity to facilitate tumour cell invasion and migration, to stimulate malignant transformation of previously normal cells, to increase immune tolerance towards the tumour, to induce resistance to chemotherapy, and to enhance the GBM vascular supply. As exosomes are specific to their parental cells, their isolation would allow a deeper perspective on GBM pathogenesis. A new era of molecular manipulation has emerged, and exosomes are rapidly proving their value not only as diagnostic and prognostic markers, but also as tools in therapies specifically targeting GBM cells. Nonetheless, further research will be required before exosomes could be used in clinical practice. This review aims to describe the structural and functional characteristics of exosomes and their involvement in GBM development, diagnosis, prognosis and treatment.
The metabolism of glucose and lipids plays a crucial role in the normal homeostasis of the body. Although glucose is the main energy substrate, in its absence, lipid metabolism becomes the primary source of energy. The main means of fatty acid oxidation (FAO) takes place in the mitochondrial matrix through β-oxidation. Glioblastoma (GBM) is the most common form of primary malignant brain tumor (45.6%), with an incidence of 3.1 per 100,000. The metabolic changes found in GBM cells and in the surrounding microenvironment are associated with proliferation, migration, and resistance to treatment. Tumor cells show a remodeling of metabolism with the use of glycolysis at the expense of oxidative phosphorylation (OXPHOS), known as the Warburg effect. Specialized fatty acids (FAs) transporters such as FAT, FABP, or FATP from the tumor microenvironment are overexpressed in GBM and contribute to the absorption and storage of an increased amount of lipids that will provide sufficient energy used for tumor growth and invasion. This review provides an overview of the key enzymes, transporters, and main regulatory pathways of FAs and ketone bodies (KBs) in normal versus GBM cells, highlighting the need to develop new therapeutic strategies to improve treatment efficacy in patients with GBM.
Background: Glioblastoma multiforme (GBM) is the most aggressive brain tumor that occurs in adults. In spite of prompt diagnosis and rapidly administered treatment, the survival expectancy is tremendously poor. Extensive research has been performed in order to establish factors to predict the outcome of GBM patients; however, worldwide accepted prognostic markers are still lacking. Methods: We retrospectively assessed all adult patients who were diagnosed with primary GBM and underwent surgical treatment during a three-year period (January 2017–December 2019) in the Neurosurgery Department of the Emergency Clinical County Hospital of Târgu Mureș, Romania. Our aim was to find any statistically relevant connections between clinical, imagistic, and histopathological characteristics and patients’ survival. Results: A total of 75 patients were eventually included in our statistical analysis: 40 males and 35 females, with a median age of 61 years. The mean tumor dimension was 45.28 ± 15.52 mm, while the mean survival rate was 4 ± 6.75 months. A univariate analysis demonstrated a statistically significant impact of tumor size, pre-, and postoperative KPSI on survival rate. In addition, a Cox multivariate assessment strengthened previous findings regarding postoperative KPSI (regression coefficient −0.03, HR 0.97, 95% CI (HR) 0.96–0.99, p = 0.002) as a favorable prognostic factor and GBM size (regression coefficient 0.03, HR 1.03, 95% CI (HR) 1.01–1.05, p = 0.005) as a poor prognostic marker for patients’ survival. Conclusions: The results of our retrospective study are consistent with prior scientific results that provide evidence supporting the importance of clinical (quantified by KPSI) and imagistic (particularly tumor dimensions) features as reliable prognostic factors in GBM patients’ survival.
Brain metastases represent more than 50% of all cerebral tumors encountered in clinical practice. Recently, there has been increased interest in the study of extracellular vesicles, and the knowledge about exosomes is constantly expanding. Exosomes are drivers for organotropic metastatic spread, playing important roles in the brain metastatic process by increasing the permeability of the blood–brain barrier and preparing the premetastatic niche. The promising results of the latest experimental studies raise the possibility of one day using exosomes for liquid biopsies or as drug carriers, contributing to early diagnosis and improving the efficacy of chemotherapy in patients with brain metastases. In this review, we attempted to summarize the latest knowledge about the role of exosomes in the brain metastatic process and future research directions for the use of exosomes in patients suffering from brain metastatic disease.
Background: Glioblastoma multiforme (GBM) is the most aggressive brain tumor affecting adult patients, with an extremely reduced overall survival despite rapid diagnosis and treatment. Therefore, it is crucial to establish accurate and affordable markers that allow an individualized approach to GBM patients. Serum biomarkers could be the most accessible, as complete blood counts should be performed on all GBM patients before undergoing any surgical and/or pharmacological treatment. However, their prognostic role is still unclear. Our study aims to assess the influence of various hematological markers of inflammation in predicting the outcome of GBM patients. Material and methods: We retrospectively analyzed all adult patients diagnosed with primary glioblastoma in the Neurosurgery Department of the Emergency Clinical County Hospital of Târgu Mureș, Romania, from January 2017 until December 2019. We aimed to discover whether the immune/inflammatory status of the patients before receiving any kind of pharmacological or surgical treatment influenced their overall survival. Results: Our study showed that pre-therapeutic elevated white blood count could predict reduced overall survival in not otherwise specified subtype (NOS) of GBMs (HR 0.4153, 95% CI 0.1825-0.9449, p 0.0362). Furthermore, patients with increased systemic immune response index (SIRI) had much larger tumors at the time of diagnosis (p 0.0359). In wild type, isocitrate dehydrogenase subpopulation (IDHwt), the higher values of neutrophil-to-lymphocyte ratio (NLR, p 0.0412), platelet-to-lymphocyte ratio (PLR, p 0.0376) and monocyte-to-lymphocyte ratio (MLR, p 0.0412) were related to more advanced age at the moment of diagnosis. Moreover, our results revealed a weakly positive association between tumor size and NLR values in the NOS group (Spearman r 0.3212, p 0.0493). Conclusions: Our study does not provide enough evidence for the immune/inflammatory status of GBM patients to be used as an efficient prognostic marker to guide the therapeutic approach.
Large to giant sphenoid wing meningiomas (SWMs) remain surgically challenging due to frequent vascular encasement and a tendency for tumoral invasion of the cavernous sinus and optic canal. We aimed to study the quality of resection, postoperative clinical evolution, and recurrence rate of large SWMs. This retrospective study enrolled 21 patients who underwent surgery between January 2014 and December 2019 for SWMs > 5 cm in diameter (average 6.3 cm). Tumor association with cerebral edema, extension into the cavernous sinus or optic canal, degree of encasement of the major intracranial arteries, and tumor resection grade were recorded. Cognitive decline was the most common symptom (65% of patients), followed by visual decline (52%). Infiltration of the cavernous sinus and optical canal were identified in five and six patients, respectively. Varying degrees of arterial encasement were seen. Gross total resection was achieved in 67% of patients. Long-term follow-up revealed improvement in 17 patients (81%), deterioration in two patients (9.5%), and one death (4.7%) directly related to the surgical procedure. Seven patients displayed postoperative tumor progression and two required reintervention 3 years post initial surgery. Tumor size, vascular encasement, and skull base invasion mean that, despite technological advancements, surgical results are dependent on surgical strategy and skill. Appropriate microsurgical techniques can adequately solve arterial encasement but tumor progression remains an issue.