Insight into brain sex differences of typically developed infants and brain pathologies: A systematic review.

The continually advancing landscape of neuroscientific and imaging research has broadened our comprehension of sex differences encoded in the human brain, expanding from the hypothalamus and sexual behaviour to encompass the entire brain, including its diverse lobes, structures, and functions. However, less is known about sex differences in the brains of neonates and infants, despite their relevance to various sex-linked diseases that develop early in life. In this review, we provide a synopsis of the literature evidence on sex differences in the brains of neonates and infants at the morphological, structural and network levels. We also briefly overview the present evidence on the sex bias in some brain disorders affecting infants and neonates.

Clinical and histopathological findings of a rare sinonasal glomangiopericytoma.

Glomangiopericytoma is a rare vascular neoplasm of the nasal cavity and paranasal sinuses that occurs during the sixth or seventh decade of life. It is categorized as a borderline tumor with low malignant potential and classified as a distinct entity of sinonasal tumors with perivascular myoid phenotype by the World Health Organization (WHO). We report the case of a 50-year-old woman with nasal obstruction and severe epistaxis. The nasal sinuses computed tomography (CT), and magnetic resonance imaging (MRI) demonstrated a 3.1 cm soft tissue mass occupying the upper part of the left nasal cavity invading the left paranasal sinuses and nasal septum, and the left eye medial rectus muscle. A total mass resection was performed by nasal endoscopy. The histological and immunohistochemical examination yielded the diagnosis of glomangiopericytoma. This case report aims to contribute to the knowledge of nasal neoplasms. The need for more data on this entity is the main obstacle to developing standardized treatment guidelines.

Clinical and histopathological findings of a rare sinonasal glomangiopericytoma

ABSTRACT Glomangiopericytoma is a rare vascular neoplasm of the nasal cavity and paranasal sinuses that occurs during the sixth or seventh decade of life. It is categorized as a borderline tumor with low malignant potential and classified as a distinct entity of sinonasal tumors with perivascular myoid phenotype by the World Health Organization (WHO). We report the case of a 50-year-old woman with nasal obstruction and severe epistaxis. The nasal sinuses computed tomography (CT), and magnetic resonance imaging (MRI) demonstrated a 3.1 cm soft tissue mass occupying the upper part of the left nasal cavity invading the left paranasal sinuses and nasal septum, and the left eye medial rectus muscle. A total mass resection was performed by nasal endoscopy. The histological and immunohistochemical examination yielded the diagnosis of glomangiopericytoma. This case report aims to contribute to the knowledge of nasal neoplasms. The need for more data on this entity is the main obstacle to developing standardized treatment guidelines.

STAT3 in medulloblastoma: a key transcriptional regulator and potential therapeutic target.

Medulloblastoma is the most common malignant brain tumor of childhood accounting for about 60% of all pediatric embryonal tumors. Despite improvements in the overall survival rate, this tumor still lacks an efficient, reliable, and less toxic therapeutic approach. Characterization of the molecular mechanisms involved in medulloblastoma initiation and progression is a crucial step for the development of effective therapies. Signal transducer and activator of transcription 3 is a convergence point for several signaling cascades that are implicated in medulloblastoma tumorigenesis. Accumulated evidence has revealed the pivotal role of signal transducer and activator of transcription 3 in medulloblastoma pathogenesis such as proliferation, survival, angiogenesis, and immunosuppression as well as maintenance, drug resistance, and recurrence. In this review, we focus on the role of signal transducer and activator of transcription 3 in medulloblastoma tumorigenesis and discuss the recent advances of signal transducer and activator of transcription 3 inhibition as a promising developed strategy for medulloblastoma therapy.

Immunohistochemical assessment of cannabinoid type-1 receptor (CB1R) and its correlation with clinicopathological parameters in glioma.

Background: Glioma is the most frequent primary brain tumor and one of the most aggressive forms of cancer. Recently, numerous studies have focused on cannabinoids as a new therapeutic approach due to their antineoplastic effects through activation of the cannabinoid receptors. This study aimed to investigate the immunohistochemical expression level of cannabinoid type-1 receptors (CB1R) in human glioma samples and evaluate its clinicopathologic significance. Materials and methods: We analyzed the expression of CB1R in 61 paraffin-embedded glioma and 4 normal brain tissues using automated immunohistochemical assay. CB1R expression was categorized into high versus low expression levels. Statistical analyses were performed to evaluate the association between CB1R and phosphorylated extracellular signal-related kinase (p-ERK) expression levels and the clinicopathologic features of glioma. Results: Our results showed that CB1R immunopositivity was seen in 59 of 61 cases (96.7%). CB1R was down-expressed in glioma compared to normal brain tissues. However, CB1R expression was not correlated with clinicopathological parameters except for p-ERK. Conclusion: Our findings indicate the down-expression of CB1R in glioma tissues when compared to non-cancerous brain tissues. This change in CB1R expression in gliomas should be further tested regardless of the clinicopathological findings to provide a therapeutic advantage in glioma patients.

Targeting Angiogenic Factors for the Treatment of Medulloblastoma.

OPINION STATEMENT: Medulloblastoma (MB) is the most frequent pediatric brain tumor. Despite conventional therapy, MB patients have high mortality and morbidity rates mainly due to the incomplete understanding of the molecular and cellular processes involved in development of this cancer. Similar to other solid tumors, MB demonstrated high endothelial cell proliferation and angiogenic activity, wherein new blood vessels arise from the pre-existing vasculature, a process named angiogenesis. MB angiogenesis is considered a hallmark for MB development, progression, and metastasis emphasizing its potential target for antitumor therapy. However, angiogenesis is tightly regulated by a set of angiogenic factors making it a complex process to be targeted. Although agents targeting these factors and their receptors are early in development, the potential for their targeting may translate into improvement in the clinical care for MB patients. In this review, we focus on the most potent angiogenic factors and their corresponding receptors, highlighting their basic properties and expression in MB. We describe their contribution to MB tumorigenesis and angiogenesis and the potential therapeutic targeting of these factors.

New insights into the role of fibroblast growth factors in Alzheimer's disease.

Alzheimer's disease (AD), acknowledged as the most common progressive neurodegenerative disorder, is the leading cause of dementia in the elderly. The characteristic pathologic hallmarks of AD-including the deposition of extracellular senile plaques (SP) formation, intracellular neurofibrillary tangles, and synaptic loss, along with prominent vascular dysfunction and cognitive impairment-have been observed in patients. Fibroblast growth factors (FGFs), originally characterized as angiogenic factors, are a large family of signaling molecules that are implicated in a wide range of biological functions in brain development, maintenance and repair, as well as in the pathogenesis of brain-related disorders including AD. Many studies have focused on the implication of FGFs in AD pathophysiology. In this review, we will provide a summary of recent findings regarding the role of FGFs and their receptors in the pathogenesis of AD, and discuss the possible opportunities for targeting these molecules as novel treatment strategies in AD.

Biomarkers in Neuroblastoma: An Insight into Their Potential Diagnostic and Prognostic Utilities.

OPINION STATEMENT: Neuroblastoma (NB) is a heterogeneous solid tumor of the pediatric population that originates from neural crest cells and affects the developing sympathetic nervous system. It is the most common neuroblastic tumor accounting for approximately 10% of all childhood cancers and 10-15% of pediatric tumor mortalities. The outcomes range from spontaneous tumor regression in low-risk groups to metastasis and death even after multimodal therapy in high-risk groups. Hence, the detection of NB at an early stage improves outcomes and provides a better prognosis for patients. Early detection and prognosis of NB depend on specific molecules termed biomarkers which can be tissue-specific or circulating. Certain biomarkers are employed in the classification of NB into different groups to improve the treatment and prognosis, and others can be used as therapeutic targets. Therefore, novel biomarker discovery is essential for the early detection of NB, predicting the course of the disease, and developing new targeted treatment strategies. In this review, we aim to summarize the literature pertinent to some important biomarkers of NB and discuss the prognostic role of these biomarkers as well as their potential role in targeted therapy.

Immunosuppression in Medulloblastoma: Insights into Cancer Immunity and Immunotherapy.

OPINION STATEMENT: Medulloblastoma (MB) is the most common pediatric brain malignancy, with a 5-year overall survival (OS) rate of around 65%. The conventional MB treatment, comprising surgical resection followed by irradiation and adjuvant chemotherapy, often leads to impairment in normal body functions and poor quality of life, especially with the increased risk of recurrence and subsequent development of secondary malignancies. The development and progression of MB are facilitated by a variety of immune-evading mechanisms such as the secretion of immunosuppressive molecules, activation of immunosuppressive cells, inhibition of immune checkpoint molecules, impairment of adhesive molecules, downregulation of the major histocompatibility complex (MHC) molecules, protection against apoptosis, and activation of immunosuppressive pathways. Understanding the tumor-immune relationship in MB is crucial for effective development of immune-based therapeutic strategies. In this comprehensive review, we discuss the immunological aspect of the brain, focusing on the current knowledge tackling the mechanisms of MB immune suppression and evasion. We also highlight several key immunotherapeutic approaches developed to date for the treatment of MB.

Deciphering the roles of glycogen synthase kinase 3 (GSK3) in the treatment of autism spectrum disorder and related syndromes.

Autism spectrum disorder (ASD) is a complex and multifactorial neurodevelopmental disorder characterized by the presence of restricted interests and repetitive behaviors besides deficits in social communication. Syndromic ASD is a subset of ASD caused by underlying genetic disorders, most commonly Fragile X Syndrome (FXS) and Rett Syndrome (RTT). Various mutations and consequent malfunctions in core signaling pathways have been identified in ASD, including glycogen synthase kinase 3 (GSK3). A growing body of evidence suggests a key role of GSK3 dysregulation in the pathogenesis of ASD and its related disorders. Here, we provide a synopsis of the implication of GSK3 in ASD, FXS, and RTT as a promising therapeutic target for the treatment of ASD.

Drug Repurposing in Medulloblastoma: Challenges and Recommendations.

OPINION STATEMENT: Medulloblastoma is the most frequently diagnosed primary malignant brain tumor among children. Currently available therapeutic strategies are based on surgical resection, chemotherapy, and/or radiotherapy. However, majority of patients quickly develop therapeutic resistance and are often left with long-term therapy-related side effects and sequelae. Therefore, there remains a dire need to develop more effective therapeutics to overcome the acquired resistance to currently available therapies. Unfortunately, the process of developing novel anti-neoplastic drugs from bench to bedside is highly time-consuming and very expensive. A wide range of drugs that are already in clinical use for treating non-cancerous diseases might commonly target tumor-associated signaling pathways as well and hence be of interest in treating different cancers. This is referred to as drug repurposing or repositioning. In medulloblastoma, drug repurposing has recently gained a remarkable interest as an alternative therapy to overcome therapy resistance, wherein existing non-tumor drugs are being tested for their potential anti-neoplastic effects outside the scope of their original use.

Prognostic impact of adenylyl cyclase-associated protein 2 (CAP2) in glioma: A clinicopathological study.

BACKGROUND: Gliomas are a group of diseases arising from intracranial neoplastic tissues that produce a wide spectrum of clinicopathological features and morphological changes. Key questions that intrigue neuro-oncology researchers include defining novel oncophenotypic signatures relevant to diagnosing such tumors and predicting prognoses among patients. One of the key regulators of the cellular actin dynamics is adenylyl cyclase-associated protein 2 (CAP2), a protein that has been studied before in the milieu of cancer and shown to be associated with tumor progression; yet, its expression levels in the context of gliomas have not been assessed. Hence, we were interested in investigating CAP2 expression in gliomas and evaluating its clinicopathological and prognostic significance. MATERIALS AND METHODS: CAP2 expression at the protein level was analyzed in 47 human paraffin-embedded gliomas and normal brain tissues by automated immunohistochemical analysis. Statistical analysis was also performed to assess CAP2 expression level in normal and tumor tissues, and to evaluate its clinicopathological and prognostic significance. RESULTS: Our results revealed high expression of CAP2 protein in tumors of gliomas compared to normal tissues and normal areas adjacent to tumors. High expression of CAP2 was also associated with advanced tumor grades among gliomas. Kaplan-Meier analysis revealed that high CAP2 expression was associated with poor prognosis of patients with glioma (P < 0.05). In Cox regression analysis, CAP2 expression was indicated as an independent prognostic factor for overall survival (hazard ratio (HR) = 1.843, 95% confidence interval (CI), 1.252-2.714; P < 0.005). CONCLUSION: CAP2 is overexpressed in glioma and it is proposed as a potential prognostic biomarker for patients with gliomas. CAP2 expression level may serve as a promising target for diagnosis and treatment of glioma.