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Glioblastoma multiforme is the most common and aggressive malignant tumor that affects the central nervous system, with high mortality and low survival. Glioblastoma multiforme treatment includes resection tumor surgery, followed by radiotherapy and chemotherapy adjuvants. However, the drugs used in chemotherapy present some limitations, such as the difficulty of crossing the bloodbrain barrier and resisting the cellular mechanisms of drug efflux. The use of polymeric nanoparticles has proven to be an effective alternative to circumvent such limitations, as it allows the exploration of a range of polymeric structures that can be modified in order to control the biodistribution and cytotoxic effect of the drug delivery systems. Nanoparticles are nanometric in size and allow the incorporation of targeting ligands on their surface, favoring the transposition of the blood-brain barrier and the delivery of the drug to specific sites, increasing the selectivity and safety of chemotherapy. The present review has described the characteristics of chitosan, poly(vinyl alcohol), poly(lactic-coglycolic acid), poly(ethylene glycol), poly(ß-amino ester), and poly(ε-caprolactone), which are some of the most commonly used polymers in the manufacture of nanoparticles for the treatment of glioblastoma multiforme. In addition, some of the main targeting ligands used in these nanosystems are presented, such as transferrin, chlorotoxin, albumin, epidermal growth factor, and epidermal growth factor receptor blockers, explored for the active targeting of antiglioblastoma agents.

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Gliomas are the most common type of brain cancer, and among them, glioblastoma multiforme (GBM) is the most prevalent (about 60% of cases) and the most aggressive type of primary brain tumor. The treatment of GBM is a major challenge due to the pathophysiological characteristics of the disease, such as the presence of the blood-brain barrier (BBB), which prevents and regulates the passage of substances from the bloodstream to the brain parenchyma, making many of the chemotherapeutics currently available not able to reach the brain in therapeutic concentrations, accumulating in non-target organs, and causing considerable adverse effects for the patient. In this scenario, nanocarriers emerge as tools capable of improving the brain bioavailability of chemotherapeutics, in addition to improving their biodistribution and enhancing their uptake in GBM cells. This is possible due to its nanometric size and surface modification strategies, which can actively target nanocarriers to elements overexpressed by GBM cells (such as transmembrane receptors) related to aggressive development, drug resistance, and poor prognosis. In this review, an overview of the most frequently overexpressed receptors in GBM cells and possible approaches to chemotherapeutic delivery and active targeting using nanocarriers will be presented.

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Glioblastoma remains as the most common and aggressive malignant brain tumor, standing with a poor prognosis and treatment prospective. Despite the aggressive standard care, such as surgical resection and chemoradiation, median survival rates are low. In this regard, immunotherapeutic strategies aim to become more attractive for glioblastoma, considering its recent advances and approaches. In this review, we provide an overview of the current status and progress in immunotherapy for glioblastoma, going through the fundamental knowledge on immune targeting to promising strategies, such as Chimeric antigen receptor T-Cell therapy, immune checkpoint inhibitors, cytokine-based treatment, oncolytic virus and vaccine-based techniques. At last, it is discussed innovative methods to overcome diverse challenges, and future perspectives in this area.

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Glioblastoma multiforme is the most common and most aggressive human brain cancer. GBM treatment is still a challenge because many drugs are not able to cross the blood-brain barrier, in addition to the increasing resistance to currently available chemotherapy. New therapeutic alternatives are emerging, and, in this context, we highlight kaempferol, a flavonoid with remarkable anti-tumor activity but with limited bioavailability due to its strong lipophilic property. A promising tool to improve the biopharmaceutical properties of molecules such as kaempferol is the use of drug-delivery nanosystems, such as nanostructured lipid carriers (NLC), which can facilitate the dispersion and delivery of highly lipophilic molecules. The present work aimed at the development and characterization of kaempferol-loaded NLC (K-NLC) and the evaluation of its biological properties using in vitro models. The K-NLC showed an average size of 120 nm, zeta potential of - 21 mV, and polydispersity index of 0.099. The K-NLC presented high kaempferol encapsulation efficiency (93%), a drug loading of 3.58%, and a sustained kaempferol release profile for up to 48 h. In addition to presenting a 7-fold increase in kaempferol cytotoxicity, its encapsulation in NLC promoted a cellular uptake of 75%, which corroborates with increased cytotoxicity in U-87MG cells, as observed. Together, these data reinforce the promising antineoplastic properties of kaempferol in addition to the key role of NLC as a platform for the efficient delivery of lipophilic drugs to neoplastic cells, which improved their uptake and therapeutic efficacy in glioblastoma multiforme cells.

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Glioblastoma multiforme (GBM) is the most common malignant brain cancer, characterized by high invasiveness and poor prognosis. Docetaxel (DTX) is a chemotherapeutic drug with promising anti-tumor properties. However, conventional intravenous formulations exhibit side effects of systemic biodistribution and low brain bioavailability, limiting their clinical use. The current work aimed to evaluate the effect of DTX-loaded nanostructured lipid carriers (NLC) functionalized with bevacizumab (BVZ-NLC-DTX) against GBM using in vitro and in vivo models. The NLC was obtained by the fusion-emulsification method followed by sonication, with narrow size distribution, negative zeta potential, and low polydispersity index. NLC showed DTX entrapment efficiency above 90%. BVZ coupling efficiency was 62% and BVZ integrity after functionalization was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Calorimetry studies confirmed thermal stability and molecular dispersion of DTX in the lipid matrix. NLC showed a sustained DTX release over 84 h. In vitro anti-tumor assays shown that BVZ-NLC-DTX selectively increased the cytotoxic of DTX in cells overexpressing VEGF (U87MG and A172), but not in peripheral blood mononuclear cells (PMBCs), promoting cell death by apoptosis. BVZ functionalization did not impair cellular uptake. An in vivo orthotopic rat model demonstrated that free-DTX was not capable of reducing tumor growth whereas BVZ-NLC-DTX reduced up to 70% tumor volume after 15-days of treatment. Therefore, this study contributes to understanding new nanotechnology-based vehicles capable of reaching the brain more efficiently and repurposing the use of anti-cancer drugs in GBM treatment.

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PURPOSE: Medulloblastomas (MB) are highly malignant brain tumors that predominantly occur in young infants. Immunotherapy to boost the immune system is emerging as a novel promising approach, but is often hampered by inhibitory immune checkpoints. In the present study, we have studied immune checkpoint B7-H3 expression in a tissue cohort of human pediatric MB. METHODS: Expression of B7-H3 was detected by immunohistochemistry and classified via B7-H3 staining intensity and percentage of B7-H3 positive tumor cells. Subsequently, B7-H3 protein expression was distinguished in MB molecular subtypes and correlated to immune cell infiltrates, patient characteristics, and survival. RESULTS: B7-H3 protein expression was found in 23 out of 24 (96%) human pediatric MB cases and in 17 out of 24 (71%) MB cases > 25% of tumor cells had any level of B7-H3 expression. B7-H3 protein expression was more frequent on Group-4 MB as compared with other molecular subtypes (p = 0.02). Tumors with high B7-H3 expression showed less influx of γδT cells (p = 0.002) and CD3+ T cells (p = 0.041). CONCLUSION: Immune checkpoint B7-H3 is differentially expressed by the large majority of pediatric MB. This further warrants the development of novel B7-H3-directed (immuno)therapeutic methods for children with incurable, metastatic, or chemo-resistant MB.

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Glioblastoma multiforme (GBM) is a complicated and heterogeneous brain tumor with short-term survival outcomes. Commercial therapies are not practical due to cell infiltration capacity, high proliferative rate, and blood-brain barrier. In this context, recognition of the molecular mechanism of tumor progression might help the development of new cancer therapeutics. Recently, more evidence has supported CD73 and downstream adenosine A2A/A2B receptor signaling playing a crucial role in glioblastoma pathogenesis; therefore, targeting CD73 in murine tumor models can reduce tumor development. CD73 is an ecto-enzyme inducing tumor metastasis, angiogenesis, and immune escape via the production of extracellular adenosine in the tumor microenvironment. In this review, we provided information about clinical characteristics as well as the therapeutic management of glioblastoma. Then, we focused on newly available experimental evidence distinguishing between the essential role of CD73 on this tumor growth and a new method for the treatment of GBM patients.

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The diseases affecting the Central Nervous System (CNS) can have varied etiopathology, but they have in common silent progression, global incidence, and significant impacts on the quality of life of patients and public health systems. With the advance of biomedicine and pharmaceutical technology, new and more modern diagnostic methods and treatments were developed, repurposing the use of drugs currently available for the treatment of CNS diseases. An attractive approach is the use of alternative drug delivery platforms, such as nanocarriers, and less invasive administration routes, such as the noseto- brain, extensively explored for the delivery of drugs into the CNS. Despite many promising results, the nose-to-brain route has some physiological limitations that make it difficult to deliver drugs satisfactorily to exert therapeutic activity in the CNS. To overcome these limitations, nanostructured systems with mucoadhesive properties have stood out over the last few years in pharmaceutical R&D. In this review; we discuss how the noseto- brain route limitations can influence the delivery of drugs to the CNS and highlight the benefits that mucoadhesion can bring to these nanostructured systems. The main findings in the literature are brought together and discussed critically, focusing on how mucoadhesion can improve the biopharmaceutical properties of molecules used in the clinic, as well as their biological performance. Finally, conclusions are drawn about the points of strength of mucoadhesive nanosystems and the points that still need attention to successfully use the nose-to-brain route for the treatment of diseases that affect the CNS.

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Glioblastoma is the most prevalent and malignant brain tumor identified in adults. Surgical resection followed by radiotherapy and chemotherapy, mainly with temozolomide (TMZ), is the chosen treatment for this type of tumor. However, the average survival of patients is around 15 months. Novel approaches to glioblastoma treatment are greatly needed. Here, we aimed to investigate the anti-glioblastoma effect of the combination of matteucinol (Mat) (dihydroxyflavanone derived from Miconia chamissois Naudin) with the chemotherapeutic TMZ in vitro using tumor (U-251MG) and normal astrocyte (NHA) cell lines and in vivo using the chick embryo chorioallantoic membrane (CAM) assay. The combination was cytotoxic and selective for tumor cells (28 μg/mL Mat and 9.71 μg/mL TMZ). Additionally, the combination did not alter cell adhesion but caused morphological changes characteristic of apoptosis in vitro. Notably, the combination was also able to reduce tumor growth in the chick embryo model (CAM assay). The docking results showed that Mat was the best ligand to the cell death membrane receptor TNFR1 and to TNFR1/TMZ complex, suggesting that these two molecules may be working together increasing their potential. In conclusion, Mat-TMZ can be a good candidate for pharmacokinetic studies in view of clinical use for the treatment of glioblastoma.

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Glioma is the most common and aggressive primary tumor of the central nervous system. The standard treatment for malignant gliomas is surgery followed by chemoradiotherapy. Unfortunately, this treatment has not produced an adequate patient response, resulting in a median survival time of 12-15 months and a 5-year overall survival of <5%. Although new strategies have been sought to enhance patient response, no significant increase in the global survival of glioma patients has been achieved. The option of developing new drugs implies a long and costly process, making drug repurposing a more practical alternative for improving glioma treatment. In the last few years, researchers seeking more effective cancer therapy have pursued the possibility of using anti-hormonal agents, such as mifepristone. The latter drug, an antagonist for progesterone and glucocorticoid receptors, has several attractive features: anti-tumor activity, low cytotoxicity to healthy cells, and modulation of the chemosensitivity of several cancer cell lines in vitro. Hence, the addition of mifepristone to temozolomide-based glioblastoma chemotherapy may lead to a better patient response. The mechanisms by which mifepristone enhances glioma treatment are not yet known. The current review aims to discuss the potential role of mifepristone as an adjuvant drug for the treatment of high-grade gliomas.

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Gliosarcoma is an aggressive brain tumor. Photodynamic Therapy (PDT) is a treatment that can be used for various cancers of the CNS. The aim of this study was to analyze the effects of PDT with Photodithazine (PDZ) in the treatment of gliosarcoma, using 9 L/lacZ cells and serial concentrations of 200 µg/mL to 3.1 µg/mL of PDZ. The samples were divided into two groups: dark and light (10 J/cm²). The PDZ was internalized along all the cytoplasmic extension. Viability tests demonstrated a reduction in viable cells after PDT. The production of ROS was concentration-dependent and PDZ was found in mitochondria and lysosomes, presenting a discrete connection with α-tubulin. However, this structure is likely damaged, evidenced by changes in the morphological analysis. Thus, according to the parameters of this study, PDZ proved to be an interesting PS in PDT for the treatment of gliosarcoma, with the inherent limitations of an in vitro study.

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Glioblastoma multiforme (GBM) is the most common primary malignant Central Nervous System cancer, responsible for about 4% of all deaths associated with neoplasia, characterized as one of the fatal human cancers. Tumor resection does not possess curative character, thereby radio and/or chemotherapy are often necessary for the treatment of GBM. However, drugs used in GBM chemotherapy present some limitations, such as side effects associated with non-specific drug biodistribution as well as limited bioavailability, which limits their clinical use. To attenuate the systemic toxicity and overcome the poor bioavailability, a very attractive approach is drug encapsulation in drug delivery nanosystems. The main focus of this review is to explore the actual cancer global problem, enunciate barriers to overcome in the pharmacological treatment of GBM, as well as the most updated drug delivery nanosystems for GBM treatment and how they influence biopharmaceutical properties of anti-GBM drugs. The discussion will approach lipid-based and polymeric nanosystems, as well as inorganic nanoparticles, regarding their technical aspects as well as biological effects in GBM treatment. Furthermore, the current state of the art, challenges to overcome and future perspectives in GBM treatment will be discussed.

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PURPOSE: Somatic mutations on H3 histone are currently considered a genetic hallmark for midline pediatric high-grade gliomas (HGGs). Yet, different tumor histologies have been occasionally described to carry these mutations. Since histone modifications can lead to major epigenetic changes with direct impact on prognosis and treatment, we thought to investigate the occurrence of H3F3A K27M and G34R/V mutations in a cohort of pediatric tumors which included HGGs, low-grade gliomas, ependymomas, medulloblastomas, and a series of rare brain tumor lesions of different histologies. METHODS: A total of 82 fresh-frozen pediatric brain tumor samples were evaluated. PCR or RT-PCR followed by Sanger sequencing for the exon 2 of H3F3A (containing both K27 and G34 hotspots) were obtained and aligned to human genome. Loss of trimethylation mark (H3K27me3) in H3F3A/K27M-mutant samples was confirmed by immunohistochemistry. RESULTS: We found H3F3A/K27M mutation in 2 out of 9 cases of HGGs; no H3F3A/K27M mutations were detected in low-grade gliomas (27), ependymomas (n = 10), medulloblastomas (n = 21), or a series of rare pediatric brain tumors which included meningiomas, dysembryoplastic neuroepithelial tumors (DNETs), central nervous system (CNS) germ-cell tumors, choroid plexus tumors, cortical hamartoma, subcortical tubers, and schwannomas (n = 15). H3F3A/G34R/V mutation was not observed in any of the samples. CONCLUSIONS: Our investigation reinforces the low frequency of H3F3A somatic mutations outside the HGG setting. Interestingly, an atypical focal brainstem glioma carrying H3F3A K27M mutation that showed protracted clinical course with late-onset tumor progression was identified.

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AIMS: Glioblastoma multiforme (GBM) is the most devastating malignant primary brain tumor known. Life expectance is around 15 months after diagnosis. Several events contribute to the GBM progression such as uncontrolled genetic cancer cells proliferation, angiogenesis (mostly vascular endothelial growth factor (VEGF)-mediated), tissue invasion, glioma stem cell activity, immune system failure, and a hypoxic and inflammatory tumor microenvironment. Tumor cells antiproliferative effect of 20 nm citrate-covered gold nanoparticles (cit-AuNP) has been reported, along with anti-inflammatory and anti-oxidative effects. We aimed to test whether either chronic treatment with 20 nm cit-AuNP or anti-VEGF antibody (Ig)-covered AuNP could reduce GBM progression in mice. MAIN METHODS: Effect of the gold nanoparticles on the GL261 glioblastoma cells proliferation in vitro, and on the GL261-induced glioblastoma cell growth in C57BL/6 mice in vivo were tested. Besides, fluorophore-conjugated gold nanoparticles penetration through the GL261 plasma cell membrane, gold labelling in brain parenchyma of glioblastoma-carrying mice, and VEGF expression into the tumor were evaluated. KEY FINDINGS: We observed cit-AuNP did no change the GL261 cells proliferation. Similarly, we demonstrated chronic treatment with either cit-AuNP or anti-VEGF Ig-covered AuNP did not modify the GL261 cells-induced GBM progression in mice. By the end, we showed AuNPs did not trespass in appreciable amount both the GL261 plasma cell membrane and the tumoral blood brain barrier (BBB), and did not change the VEGF expression into the tumor. SIGNIFICANCE: 20 nm cit-AuNP or anti-VEGF Ig covered-AuNP are not good tools to reduce GBM in mice, probably because they do not penetrate both tumor cells and BBB in enough amount to reduce tumor growing.

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Brain cancer is one of the most malignant types of cancer in both children and adults. Brain cancer patients tend to have a poor prognosis and a high rate of mortality. Additionally, 20-40% of all other types of cancer can develop brain metastasis. Numerous pieces of evidence suggest that omega-3-polyunsaturated fatty acids (ω-PUFAs) could potentially be used in the prevention and therapy of several types of cancer. PUFAs and oxylipins are fundamental in preserving physiological events in the nervous system; it is, therefore, necessary to maintain a certain ratio of ω-3 to ω-6 for normal nervous system function. Alterations in PUFAs signaling are involved in the development of various pathologies of the nervous system, including cancer. It is well established that an omega-6-polyunsaturated fatty acid (ω-6 PUFA)-rich diet has a pro-tumoral effect, whereas the consumption of an ω-3 rich diet has an anti-tumoral effect. This review aims to offer a better understanding of brain cancer and PUFAs and to discuss the role and impact of PUFAs on the development of different types of brain cancer. Considering the difficulty of antitumor drugs in crossing the blood-brain barrier, the therapeutic role of ω-3/ω-6 PUFAs against brain cancer would be a good alternative to consider. We highlight our current understanding of the role of PUFAs and its metabolites (oxylipins) in different brain tumors, proliferation, apoptosis, invasion, angiogenesis, and immunosuppression by focusing on recent research in vitro and in vivo.

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Glioblastoma is a difficult disease to diagnose. Proteomic techniques are commonly applied in biomedical research, and can be useful for early detection, making an accurate diagnosis and reducing mortality. The relevance of mitochondria in brain development and function is well known; therefore, mitochondria may influence the development of glioblastoma. The T98G (with oxidative metabolism) and U87MG (with glycolytic metabolism) cell lines are considered to be useful glioblastoma models for studying these tumors and the role of mitochondria in key aspects of this disease, such as prognosis, metastasis and apoptosis. In the present study, principal component analysis of protein abundance data identified by liquid chromatography coupled to tandem mass spectrometry (LC­MS/MS) and matrix­assisted laser desorption/ionization­time of flight mass spectrometry (MALDI­TOF) from 2D gels indicated that representative mitochondrial proteins were associated with glioblastoma. The selected proteins were organized into T98G­ and U87MG­specific protein­protein interaction networks to demonstrate the representativeness of both proteomic techniques. Gene Ontology overrepresentation analysis based on the relevant proteins revealed that mitochondrial processes were associated with metabolic changes, invasion and metastasis in glioblastoma, along with other non­mitochondrial processes, such as DNA translation, chaperone responses and autophagy. Despite the lower resolution of 2D electrophoresis, principal component analysis yielded information of comparable quality to that of LC­MS/MS. The present analysis pipeline described a specific and more complete metabolic status for each cell line, defined a clear mitochondrial performance for distinct glioblastoma tumors, and introduced a useful strategy to understand the heterogeneity of glioblastoma.

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BACKGROUND: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. OBJECTIVE: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. METHODS: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). RESULTS: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. CONCLUSION: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

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PURPOSE: We performed a cross-sectional study of neurocognitive function in non-brain cancer patients treated with long-term bevacizumab. METHODS/PATIENTS: From 2015 to 2017, we included patients with different types of cancer treated with bevacizumab with or without chemotherapy (BEV; N = 20) or only chemotherapy (ChT; N = 19) for at least 34 weeks, patients who received non-brain radiotherapy (RxT; N = 19), and healthy controls (HC; N = 19) were assessed once at week 34 of treatment (BEV and ChT) or at completion of radiotherapy. Neurocognition was evaluated with the Hopkins Verbal Learning Test-Revised (HVLT-R) total and delayed recall, the Trail Making Test A and B, and the Controlled Oral Word Association Test in the four groups. Non-parametric tests were used to assess differences between groups. RESULTS: The BEV, ChT, and RxT groups scored significantly lower than the HC group on all tests and especially on the HVLT-R total recall. In no case were the mean scores of the BEV group significantly lower than those of the ChT or RxT groups. CONCLUSIONS: Neurocognitive impairment was seen even in patients treated with local non-brain radiotherapy. Treatment with bevacizumab for a long period of time does not seem to worsen neurocognitive function to a greater extent than chemotherapy.

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Introduction The improvement on the extent of resection (EOR) of gliomas with the combination of 5-aminolevulinic acid (5-ALA) and intraoperative magnetic resonance imaging (iMRI) has been demonstrated in previous studies. We present our results with the combined use of 5-ALA and (iMRI) in the surgery of glial lesions. Methods A total of 64 cases of patients with intracranial gliomas who underwent image-guided surgery using 5-ALA with and without (iMRI) were reviewed. All patients underwent an early postoperative MRI to evaluate the EOR. Other intra-operative techniques (awake surgery, electrophysiological stimulation and monitoring) were also performed according to the location of the tumor. Results A total of 18 tumors did not show intraoperative 5-ALA fluorescence (according to the World Health Organization [WHO] classification of tumors, 2 WHO-grade I, 14 WHOgrade II, 1 WHO-grade III and 1 WHO-grade IV), and 46 tumors showed intraoperative 5-ALA fluorescence (3 WHO-grade II, 3 WHO-grade III, 40 WHO-grade IV). In 28 of the 46 5-ALA positive cases, a safe 5-ALA free resection was achieved. In the 5-ALA negative cases, the (iMRI) findings guided the EOR, and complete resection was achieved in 11 cases. Complete resection was opted out in gliomas infiltrating eloquent areas. Conclusions The combined use of 5-ALA and IMRI showed improved results in glioma surgery, offering the safest maximal EOR. In the 5-ALA positive cases (mostly highgrade), fluorescence was a more useful tool. In the 5- ALA negative cases (mostly lowgrade), the (iMRI) was decisive to guide the EOR of the tumor.

Introdução Em estudos anteriores, foi demonstrado um aperfeiçoamento na extensão da resecção (EDR) de gliomas com a combinação de ácido 5-aminolevulínico (5-ALA) e a imagem de ressonância magnética intraoperatória (iRM). Nossos resultados são apresentados com o uso combinado de 5-ALA e (iRM) para a cirurgia de lesões gliais. Métodos Foram revisados 64 casos de gliomas intracranianos submetidos a cirurgia guiada por imagem por meio do uso de 5-ALA, com ou sem RMI. Todos os pacientes foram submetidos a ressonância magnética (RM) pré-operatória para a avaliação da EDR do tumor. Outras técnicas intraoperatórias (cirurgia acordado, estimulação eletrofisiológica e monitoração) também foram realizadas segundo a localização do tumor. Resultados Um total de 18 tumores não apresentaram fluorescência com o 5-ALA (segundo a classificação de tumores da Organização Mundial de Saúde [OMS], 2 com grau OMS I, 14 com grau II, 1 com grau III e 1 com grau IV) e 46 tumores foram fluorescentes (3 com grau II, 3 com grau III, 40 com grau IV). Dos 46 casos positivos para 5-ALA, em 28 foi obtida uma ressecção segura e livre. Nos casos negativos para 5-ALA, os achados da (iRM) orientaram a EDR, e alcançou-se ressecção total em 11 casos. A ressecção total foi descartada em gliomas com infiltração em áreas eloquentes. Conclusões O uso combinado de 5-ALA e (iRM) mostrou melhores resultados na cirurgia de gliomas, oferecendo uma EDR de segurança máxima. Nos casos positivos para 5-ALA (a maioria de grau alto), a fluorescência mostrou-se um instrumento mais útil. Nos casos negativos para 5-ALA (a maioria de grau baixo), a RMI foi decisiva para orientar a EDR tumoral.

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