Grading of glioma tumors using digital holographic microscopy.

Gliomas are the most common type of cerebral tumors; they occur with increasing incidence in the last decade and have a high rate of mortality. For efficient treatment, fast accurate diagnostic and grading of tumors are imperative. Presently, the grading of tumors is established by histopathological evaluation, which is a time-consuming procedure and relies on the pathologists' experience. Here we propose a supervised machine learning procedure for tumor grading which uses quantitative phase images of unstained tissue samples acquired by digital holographic microscopy. The algorithm is using an extensive set of statistical and texture parameters computed from these images. The procedure has been able to classify six classes of images (normal tissue and five glioma subtypes) and to distinguish between gliomas types from grades II to IV (with the highest sensitivity and specificity for grade II astrocytoma and grade III oligodendroglioma and very good scores in recognizing grade III anaplastic astrocytoma and grade IV glioblastoma). The procedure bolsters clinical diagnostic accuracy, offering a swift and reliable means of tumor characterization and grading, ultimately the enhancing treatment decision-making process.

Clinical outcomes of posterior fossa arteriovenous malformations: a single center experience.

BACKGROUND: Posterior fossa arterio-venous malformations (pfAVMs) are challenging lesions due to the anatomical particularities of the posterior fossa, and the high incidence of hemorrhagic presentation. The two most important goals when treating AVMs are preserving neurological function and preventing rupture, or a second hemorrhage. The aim of this study was to analyze the clinical and imaging features of pfAVMs to identify the factors that influence the prognosis of these patients. METHODS: We conducted a single-center retrospective observational study that included patients treated at our institution with pfAVMs between January 1997 and December 2021. RESULTS: A total of 48 patients were included. A good modified Rankin score (mRS) was observed in 33 cases (69%) at presentation. Thirty-four patients (71%) presented with a ruptured AVM. Out of these, 19 patients (40%) had intraventricular hemorrhage. Microsurgical resection was performed in 33 cases (69%), while in the other cases, the patients opted for conservative management (7 cases, 15%), stereotactic radiosurgery (SRS) (6 cases, 12%), or endovascular treatment (2 cases, 4%). Patients ≤ 30 years old were more prone to hemorrhagic presentation (OR: 5.23; 95% CI: 1.42-17.19; p = 0.024) and this remained an independent risk factor for rupture after multivariate analysis as well (OR: 4.81; 95% CI: 1.07-21.53; p = 0.040). Following multivariate analysis, the only factor independently associated with poor prognosis in the surgically treated subgroup was a poor clinical status (mRS 3-5) at admission (OR: 96.14; 95% CI: 5.15-1793.9; p = 0.002). CONCLUSIONS: Management of posterior fossa AVMs is challenging, and patients who present with ruptured AVMs often have a poor clinical status at admission leading to a poor prognosis. Therefore, proper and timely management of these patients is essential.

Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas.

Gliomas constitute a diverse and complex array of tumors within the central nervous system (CNS), characterized by a wide range of prognostic outcomes and responses to therapeutic interventions. This literature review endeavors to conduct a thorough investigation of gliomas, with a particular emphasis on glioblastoma (GBM), beginning with their classification and epidemiological characteristics, evaluating their relative importance within the CNS tumor spectrum. We examine the immunological context of gliomas, unveiling the intricate immune environment and its ramifications for disease progression and therapeutic strategies. Moreover, we accentuate critical developments in understanding tumor behavior, focusing on recent research breakthroughs in treatment responses and the elucidation of cellular signaling pathways. Analyzing the most novel transcriptomic studies, we investigate the variations in gene expression patterns in glioma cells, assessing the prognostic and therapeutic implications of these genetic alterations. Furthermore, the role of epigenetic modifications in the pathogenesis of gliomas is underscored, suggesting that such changes are fundamental to tumor evolution and possible therapeutic advancements. In the end, this comparative oncological analysis situates GBM within the wider context of neoplasms, delineating both distinct and shared characteristics with other types of tumors.

Proteometabolomics of initial and recurrent glioblastoma highlights an increased immune cell signature with altered lipid metabolism.

BACKGROUND: There is an urgent need to better understand the mechanisms associated with the development, progression, and onset of recurrence after initial surgery in glioblastoma (GBM). The use of integrative phenotype-focused -omics technologies such as proteomics and lipidomics provides an unbiased approach to explore the molecular evolution of the tumor and its associated environment. METHODS: We assembled a cohort of patient-matched initial (iGBM) and recurrent (rGBM) specimens of resected GBM. Proteome and metabolome composition were determined by mass spectrometry-based techniques. We performed neutrophil-GBM cell coculture experiments to evaluate the behavior of rGBM-enriched proteins in the tumor microenvironment. ELISA-based quantitation of candidate proteins was performed to test the association of their plasma concentrations in iGBM with the onset of recurrence. RESULTS: Proteomic profiles reflect increased immune cell infiltration and extracellular matrix reorganization in rGBM. ASAH1, SYMN, and GPNMB were highly enriched proteins in rGBM. Lipidomics indicates the downregulation of ceramides in rGBM. Cell analyses suggest a role for ASAH1 in neutrophils and its localization in extracellular traps. Plasma concentrations of ASAH1 and SYNM show an association with time to recurrence. CONCLUSIONS: We describe the potential importance of ASAH1 in tumor progression and development of rGBM via metabolic rearrangement and showcase the feedback from the tumor microenvironment to plasma proteome profiles. We report the potential of ASAH1 and SYNM as plasma markers of rGBM progression. The published datasets can be considered as a resource for further functional and biomarker studies involving additional -omics technologies.

From Recognition to Remedy: The Significance of Biomarkers in Neurodegenerative Disease Pathology.

With the inexorable aging of the global populace, neurodegenerative diseases (NDs) like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) pose escalating challenges, which are underscored by their socioeconomic repercussions. A pivotal aspect in addressing these challenges lies in the elucidation and application of biomarkers for timely diagnosis, vigilant monitoring, and effective treatment modalities. This review delineates the quintessence of biomarkers in the realm of NDs, elucidating various classifications and their indispensable roles. Particularly, the quest for novel biomarkers in AD, transcending traditional markers in PD, and the frontier of biomarker research in ALS are scrutinized. Emergent susceptibility and trait markers herald a new era of personalized medicine, promising enhanced treatment initiation especially in cases of SOD1-ALS. The discourse extends to diagnostic and state markers, revolutionizing early detection and monitoring, alongside progression markers that unveil the trajectory of NDs, propelling forward the potential for tailored interventions. The synergy between burgeoning technologies and innovative techniques like -omics, histologic assessments, and imaging is spotlighted, underscoring their pivotal roles in biomarker discovery. Reflecting on the progress hitherto, the review underscores the exigent need for multidisciplinary collaborations to surmount the challenges ahead, accelerate biomarker discovery, and herald a new epoch of understanding and managing NDs. Through a panoramic lens, this article endeavors to provide a comprehensive insight into the burgeoning field of biomarkers in NDs, spotlighting the promise they hold in transforming the diagnostic landscape, enhancing disease management, and illuminating the pathway toward efficacious therapeutic interventions.

Cannabinoids in Medicine: A Multifaceted Exploration of Types, Therapeutic Applications, and Emerging Opportunities in Neurodegenerative Diseases and Cancer Therapy.

In this review article, we embark on a thorough exploration of cannabinoids, compounds that have garnered considerable attention for their potential therapeutic applications. Initially, this article delves into the fundamental background of cannabinoids, emphasizing the role of endogenous cannabinoids in the human body and outlining their significance in studying neurodegenerative diseases and cancer. Building on this foundation, this article categorizes cannabinoids into three main types: phytocannabinoids (plant-derived cannabinoids), endocannabinoids (naturally occurring in the body), and synthetic cannabinoids (laboratory-produced cannabinoids). The intricate mechanisms through which these compounds interact with cannabinoid receptors and signaling pathways are elucidated. A comprehensive overview of cannabinoid pharmacology follows, highlighting their absorption, distribution, metabolism, and excretion, as well as their pharmacokinetic and pharmacodynamic properties. Special emphasis is placed on the role of cannabinoids in neurodegenerative diseases, showcasing their potential benefits in conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. The potential antitumor properties of cannabinoids are also investigated, exploring their potential therapeutic applications in cancer treatment and the mechanisms underlying their anticancer effects. Clinical aspects are thoroughly discussed, from the viability of cannabinoids as therapeutic agents to current clinical trials, safety considerations, and the adverse effects observed. This review culminates in a discussion of promising future research avenues and the broader implications for cannabinoid-based therapies, concluding with a reflection on the immense potential of cannabinoids in modern medicine.

Neuropsychiatric and Neuropsychological Aspects of Alcohol-Related Cognitive Disorders: An In-Depth Review of Wernicke's Encephalopathy and Korsakoff's Syndrome.

Alcohol-related cognitive disorders have long been an area of study, yet they continue to pose challenges in the diagnosis, treatment, and understanding of underlying neuropsychiatric mechanisms. The present article offers a comprehensive review of Wernicke's Encephalopathy and Korsakoff's Syndrome, two conditions often seen on a continuum of alcohol-related brain damage. Drawing on current medical literature, neuroimaging studies, and clinical case reports, we explore the neuropsychiatric and neuropsychological profiles, symptomatology, and differential diagnoses of these disorders. We delve into the biochemical pathways implicated in the development of WE and KS, notably thiamine deficiency and its impact on neurotransmitter systems and neural networks. The article also addresses the challenges in early diagnosis, often complicated by non-specific symptoms and co-occurring psychiatric conditions. Furthermore, we review the current state of treatment protocols, including pharmacological and non-pharmacological interventions. Finally, the article highlights gaps in current knowledge and suggests directions for future research to improve diagnosis, treatment, and patient outcomes. Understanding the nuanced interplay between the neuropsychiatric and neuropsychological aspects of WE and KS is crucial for both clinicians and researchers alike, in order to provide effective treatment and to advance our understanding of these complex conditions.

The role of catastrophizing and basic psychological needs satisfaction on health-related quality of life and pain in patients with lumbar disc herniation.

Introduction: Lumbar disc herniation (LDH) is one of the most common conditions associated with functional disability, affecting patients' quality of life (QOL). Disability can be affected by cognitive factors, such as pain catastrophizing. Similarly, unfulfilled basic psychological needs (i.e., autonomy, competence, relatedness) are associated with biases in pain perception and QOL. Using the fear-avoidance model and the self-determination theory, this study investigates: (1) the separate contribution of pain-related variables and basic psychological needs satisfaction in predicting QOL in patients proposed for LDH surgery; (2) pre- and post-surgical differences in pain catastrophizing and basic psychological needs satisfaction. Methods: First, we used hierarchical regression on 193 patients (Mage = 46.10, SDage = 11.40) to identify predictors of QOL. Second, we performed paired t-tests on 55 patients to investigate pre- and post-surgical differences in pain catastrophizing and basic psychological needs satisfaction. Results: Hierarchical regression showed that the model predicts 27% of the variance in QOL; medium pain level, age, pain catastrophizing, and basic psychological needs satisfaction were significant predictors. Also, pain catastrophizing significantly decreased after surgery [t (54) = 6.07, p < 0.001, Cohen's d = 0.81], but basic psychological needs satisfaction did not modify significantly. Discussion: This research confirms the importance of pain perception and pain catastrophizing for LDH patients' QOL and broadens the applicability of the self-determination theory for spinal patients.

GFAPδ: A Promising Biomarker and Therapeutic Target in Glioblastoma.

GFAPδ, the delta isoform of the glial fibrillary acidic protein, is mainly expressed in the subventricular zone of the brain, together with other neural stem cell markers like nestin. The authors of this paper were among the first that described in detail the expression of GFAPδ and its correlation with malignancy and invasiveness in cerebral astrocytoma. Later, several papers confirmed these findings, showing that the alternative splice variant GFAPδ is overexpressed in glioblastoma (CNS WHO grade 4) compared with lower grade gliomas. Other studies suggested that a high GFAPδ/α ratio is associated with a more malignant and invasive behavior of glioma cells. Moreover, the changing of GFAPδ/α ratio affects the expression of high-malignant genes. It is now suggested that discriminating between predominant GFAP isoforms, GFAPδ or GFAPα, is useful for assessing the malignancy state of astrocytoma, and may even contribute to the classification of gliomas. Therefore, the purpose of this paper is to review the literature with emphasize on the role of GFAPδ as a potential biomarker, and as a possible therapeutic target in glioblastoma.

Editing and Chemical Modifications on Non-Coding RNAs in Cancer: A New Tale with Clinical Significance.

Currently, for seemingly every type of cancer, dysregulated levels of non-coding RNAs (ncRNAs) are reported and non-coding transcripts are expected to be the next class of diagnostic and therapeutic tools in oncology. Recently, alterations to the ncRNAs transcriptome have emerged as a novel hallmark of cancer. Historically, ncRNAs were characterized mainly as regulators and little attention was paid to the mechanisms that regulate them. The role of modifications, which can control the function of ncRNAs post-transcriptionally, only recently began to emerge. Typically, these modifications can be divided into reversible (i.e., chemical modifications: m5C, hm5C, m6A, m1A, and pseudouridine) and non-reversible (i.e., editing: ADAR dependent, APOBEC dependent and ADAR/APOBEC independent). The first research papers showed that levels of these modifications are altered in cancer and can be part of the tumorigenic process. Hence, the aim of this review paper is to describe the most common regulatory modifications (editing and chemical modifications) of the traditionally considered "non-functional" ncRNAs (i.e., microRNAs, long non-coding RNAs and circular RNAs) in the context of malignant disease. We consider that only by understanding this extra regulatory layer is it possible to translate the knowledge about ncRNAs and their modifications into clinical practice.

Microsurgical approach for symptomatic brain AVMs - single center experience.

Objectives: Brain arteriovenous malformations (AVMs) represent high-flow vascular lesions made up of a complex network of feeding arteries and draining veins interposed by a nidus and without a capillary bed. The management of the AVMs represents a challenge, and the optimal treatment should be considered based on the particularities of each AVM. This paper aims to provide outcome data for the cohort of patients with AVMs that underwent surgical treatment. Methods: A retrospective review of patients who presented with AVMs between 2001 and 2019 was conducted. Patients were included if they underwent surgery, preoperative and postoperative angiographic studies were available. Results: 91 patients were included. The SM grade was 1 in 16 cases (17,6%), 2 in 27 patients (29.7%), 3 in 29 patients (31,9%), 4 in 12 cases (13.2%) and grade 5 in 7 cases (7.7%). In 58 (63.7%) cases the AVMs were ruptured. Complete microsurgical resection was achieved in 82 cases (90.1%). Unruptured AVM (87.9% vs. 63.8% for ruptured AVMs; p = 0.015), low-grade AVM (86% vs. 60.4% for grade III-V AVMs; p = 0.006) and cortical location (79.5% vs. 30.8% for deep AVM; p < 0.0001) were the factors associated with a good outcome on mRS scale. Conclusions: Microsurgical resection is the curative treatment for AVMs and offers a good functional outcome if selection criteria are met.

Fighting Cancer Stem Cell Fate by Targeting LIS1 a WD40 Repeat Protein.

Cancer is one of the most frequent and devastating diseases. Previous reports have shown that radio and chemo-resistant cancer stem cell (CSC) population is primarily responsible for cancer recurrences after radiotherapy and chemotherapy. Other studies demonstrated that Lissencephaly-1 (LIS1) protein, also known as platelet activating factor acetylhydrolase 1b regulatory subunit 1 (PAFAH1B1), a dynein-binding protein involved in neural stem cell division, plays a crucial role in maintaining CSC population in hematological malignancies. Moreover, one recent report demonstrated that LIS1 gene is preferentially expressed in CD133+ glioblastoma cells and may have also an important role in regulating CD133+ CSC in glioblastoma. The hypothesis of this paper is that LIS1 plays a key role in maintaining CD133+ CSC population in various solid cancers by orientating the cell division plane through an interaction with dynein and therefore controlling the stem cell fate regulatory mechanism. As CD133+ CSC population is responsible for radio- and chemo-resistance, which finally determines the cancer recurrences and metastases, identifying the molecular mechanisms which regulate the CD133+ CSC population represents a major target for cancer research. Given the structure of LIS1, which contains WD40 repeat domain, small peptide inhibitors could be used to alter its function. Therefore, the impact of confirming this hypothesis is significant because LIS1 may become an important molecular target for future adjuvant anticancer therapies directed against radio- and chemo-resistant CSC population.

Preferential Association of Lissencephaly-1 Gene Expression with CD133+ Glioblastoma Cells.

Lissencephaly-1 (Lis1) protein is a dynein-binding protein involved in neural stem cell division, morphogenesis and motility. To determine whether Lis1 is a key factor in glioblastoma, we evaluated its expression and function in CD133+ glioblastoma cells. Global, Lis1 gene expression is similar in glioblastoma and normal samples. Interestingly, immunohistochemistry data indicate increased Lis1 expression colocalized with CD133 in a subset of glioma cells, including the tumor cells with perivascular localization. Lis1 gene expression is increased up to 60-fold in CD133 positive cells isolated from primary cultures of glioblastoma and U87 glioblastoma cell line as compared to CD133 negative cells. To investigate the potential role of Lis1 in CD133+ glioblastoma cells, we silenced Lis1 gene in U87 cell line obtaining shLis1-U87 cells. In shLis1-U87 cell culture we noticed a significant decrease of CD133+ cells fraction as compared with control cells and also, CD133+ cells isolated from shLis1-U87 were two times less adhesive, migratory and proliferative, as compared with control transfected U87 CD133+ cells. Moreover, Lis1 silencing decreased the proliferative capacity of irradiated U87 cells, an effect attributable to the lower percentage of CD133+ cells. This is the first report showing a preferential expression of Lis1 gene in CD133+ glioblastoma cells. Our data suggest a role of Lis1 in regulating CD133+ glioblastoma cells function.

Challenges in a case of ophthalmic artery aneurysm associated with abnormal internal carotid arteries.

Ophthalmic artery aneurysms account for 5% of all cerebral aneurysms and are an important cause of morbidity and mortality related to subarachnoid hemorrhage. The diagnosis is often made only when the aneurysm is large enough to become symptomatic. They remain technically challenging for both neurosurgeon and interventional radiologist. We present the case of a 62-year-old woman admitted for transient loss of consciousness, followed by generalized tonic-clonic seizures. Computed tomography (CT) showed a subarachnoid hemorrhage (SAH), clinically graded as Hunt and Hess III. Magnetic resonance imaging (angioMR) and the four-vessel digital subtraction angiography (DSA) identified a ruptured, 8 mm left ophthalmic artery aneurysm. Embolization was the first therapeutic choice. Nevertheless, the attempt had to be aborted due to a combination of a hypoplastic right internal carotid artery (ICA) and an irregular atheromatous plaque on the left ICA, rendering the procedure unduly hazardous. Therefore, microsurgical clipping of the aneurysm became the procedure of choice. Postoperatively, the patient was in good condition, with no visual and neurological deficits. At 6 months follow up, she was assigned maximum scores of 5 and 8 on the Glasgow Outcome Scale (GOS) and Extended GOS (GOS-E), respectively. Aneurysm rupture represents a neurosurgical emergency and an early intervention (less than 48 h) is recommended to maximize the chances of deficit-free survival. The peculiarities of this case consisted in the combination between the size and the location of the aneurysm, abrupt presentation, and the impossibility of embolization due to bilateral ICA abnormalities, congenital (hypoplastic right ICA) and acquired (extensively atherosclerotic left ICA).

Cribriform-morular variant of papillary thyroid carcinoma at pediatric age - case report and review of the literature.

Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare tumor, which exceptionally occurs at pediatric age. CMV-PTC may develop in patients with familial adenomatous polyposis (FAP) or may be a sporadic tumor. The authors present a case of CMV-PTC in a 10-year-old girl patient without FAP history, who presented with a left neck mass. The patient underwent total thyroidectomy with central compartment neck dissection. Histopathological diagnosis was compatible with cribriform-morular variant of papillary thyroid carcinoma and Hashimoto's thyroiditis. Immunostaining was positive for thyroglobulin, ß-catenin, CD10 and p53. Molecular test showed the absence of BRAF, K-RAS mutations, deletions or duplications of APC (adenomatosis polyposis coli) gene and showed the presence of RET÷PTC (rearranged during transfection÷papillary thyroid carcinoma) rearrangements. At 32 months follow-up, the patient was without signs of recurrence. This particular form of thyroid carcinoma should raise suspicion of a possible familial cancer syndrome, therefore early diagnosis and thoroughly evaluation, which includes colonoscopy and genetic screening are mandatory.

A retrospective, multi-center cohort study evaluating the severity- related effects of cerebrolysin treatment on clinical outcomes in traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of death and disability for which there is currently no effective drug therapy available. Because drugs targeting a single TBI pathological pathway have failed to show clinical efficacy to date, pleiotropic agents with effects on multiple mechanisms of secondary brain damage could represent an effective option to improve brain recovery and clinical outcome in TBI patients. In this multicenter retrospective study, we investigated severity-related efficacy and safety of the add-on therapy with two concentrations (20 ml/day or 30 ml/day) of Cerebrolysin (EVER Neuro Pharma, Austria) in TBI patients. Adjunctive treatment with Cerrebrolysin started within 48 hours after TBI and clinical outcomes were ranked according to the Glasgow Outcome Scale and the Modified Rankin Disability Score at 10 and 30 days post-TBI. Analyses of efficacy were performed separately for subgroups of patients with mild, moderate or severe TBI according to Glasgow Coma Scale scores at admission. Compared to standard medical care alone (control group), both doses of Cerebrolysin were associated with improved clinical outcome scores at 10 days post-TBI in mild patients and at 10 and 30 days in moderate and severe cases. A dose-dependent effect of Cerebrolysin on TBI recovery was supported by the dose-related differences and the significant correlations with treatment duration observed for outcome measures. The safety and tolerability of Cerebrolysin in TBI patients was very good. In conclusion, the results of this large retrospective study revealed that early Cerebrolysin treatment is safe and is associated to improved TBI outcome.

Immunohistochemical analysis of GFAP-δ and nestin in cerebral astrocytomas.

GFAP-δ, the delta isoform of the glial fibrillary acidic protein, is particularly expressed in the subventricular zone (SVZ) of the brain. GFAP-δ positive cells in the SVZ co-express the neural stem cells (NSCs) marker nestin. According to the theory of glioma oncogenesis, transformation of a cell population with stem features which resides in the SVZ could be the origin of astrocytomas. Moreover, it is known that cancer stem cells promote tumor invasion in cerebral astrocytomas. Therefore, we investigated the immunostaining of GFAP-δ and nestin in cerebral astrocytomas and evaluated the correlation between the positive cell ratio of these markers and the neuroimaging features associated with tumor invasion in forty-four cases of grade II, III and IV cerebral astrocytomas (World Health Organization's classification). Tissue samples were obtained by stereotactic biopsies in all cases. According to the preoperative neuroimaging criteria, tumors were categorized into highly invasive and low invasive. Most of the low-grade and high-grade astrocytomas express GFAP-δ and nestin. The positive cell ratio of GFAP-δ and the positive cell ratio of nestin were statistically significantly higher in highly invasive tumors compared with low-invasive tumors (p < 0.05). Altogether, these results suggest that GFAP-δ and nestin could be clinically relevant markers associated with tumor invasiveness in cerebral astrocytomas.

Olfactory groove meningiomas: a retrospective study on 59 surgical cases.

We report here a retrospective study of 59 consecutive patients with olfactory groove meningiomas admitted and operated on between 1991 and 2008. Our goal was to characterize clinical features, treatment strategies, and outcome of these lesions. The surgical resection grade, the histological type and the presence of recurrences in the follow-up period were analyzed. Maximum tumor diameter determined by preoperative magnetic resonance imaging (MRI) examinations was between 2 and 11 cm. In 38 surgical procedures (64.4%), the tumor was removed through a bilateral subfrontal approach, in 12 (20.3%) a unilateral subfrontal approach was used, and in nine procedures (15.3%) a pterional approach was performed. The average age at presentation was 52 years (age: 20-76 years) and the sex ratio was 1.45:1 (females/males). According to Simpson's grading system, the degree of tumor removal was: grade I in 14 cases (23.8%), grade II in 38 cases (64.4%), grade III in four cases (6.8%) and grade IV in three cases (5%). Fifty-six patients had benign meningiomas (94.9%) and three patients had atypical meningiomas (5.1%). Two patients (3.4%) died from pulmonary embolism and bronchopneumonia. There were recurrences in six patients (10.1%), between 9 months and 12 years (mean 7.2 years) after surgery. The olfactory groove is a relatively frequent location for intracranial meningiomas, accounting for 9.1% of all intracranial meningiomas in our experience. Olfactory groove meningiomas tend to be clinically silent tumors until they are very large when symptoms or other abnormalities become evident. A surgical procedure adapted to the size and the extension of the tumor combined with microsurgical techniques allows total meningioma removal with good neurological outcome.

Co-localization of PCNA, VCAM-1 and caspase-3 with nestin in xenografts derived from human anaplastic astrocytoma and glioblastoma multiforme tumor spheres.

The cancer stem cell hypothesis proposes that tumors contain a small subset of cancer cells, the cancer stem cells, which constitute a reservoir of self-sustaining cells with the exclusive ability to self-renew and maintain the tumor. Markers that define cancer stem cells that are capable of recapitulating brain tumors as xenografts in mice has not been described. We investigated the relationship between expression of nestin and that of PCNA, VCAM-1 and caspase-3 in the xenografts developed from human anaplastic astrocytoma and glioblastoma tumor-derived spheres in the brain of nude mouse. Xenografts obtained from astrocytoma tumor stem cells (ATSC) and glioblastoma tumor stem cells (GTSC) have showed a large number of cells positive for both PCNA and the nestin, demonstrating that nestin expressing cells have a high rate of proliferation. Xenografts from GTSC showed heterogeneous staining pattern with cells that express both nestin and VCAM-1, whereas others cells remained complete negative. In this case it was noticed that most tumor cells with large or multinucleated nuclei coexpress nestin and VCAM-1. In xenografts from ATSC most cells positive for nestin express VCAM-1 and in this case the two proteins appear to occupy the same cytoplasmic region. Both GTSC and ATSC derived xenografts showed cells positive for both caspase-3 and for nestin detected mainly as single cells and as cell clusters located near or around a blood vessel.

Immunohistochemical localization of caspase-3, caspase-9 and Bax in U87 glioblastoma xenografts.

Development of new therapies for glioblastoma requires animal models that mimic the biological characteristics of human brain tumors. On the other hand, potential antitumoral effects of a new therapeutic strategy are often established by evaluation of tumor cells apoptosis. Caspases are key mediators in the regulation and execution of apoptosis. Caspase-9 is activated during the intrinsic pathway downstream of mitochondria while caspase-3 is an effector caspase that initiates degradation of the cell in the final stages of apoptosis. Bax is a pro-apoptotic member of the Bcl-2 family that play key roles in the regulation of intrinsic apoptotic signaling. In the present study we investigated the immunohistochemical distribution of caspase 3, 9 and Bax in intracranial U87 glioblastoma xenograft. Immunohistochemistry showed that the glioblastoma xenografts contain cells positive for caspase-3, caspase-9, and Bax.