[Information support for the bioresource collection: a biological information system «NeuroOnc¼]. / Informatsionnaya podderzhka bioresursnoi kollektsii: biologicheskaya informatsionnaya sistema «NeiroOnk¼.

The manuscript is devoted to development of information support system for a bioresource collection - biological information system «NeuroOnc¼. Architecture and main functions of system are presented. This system was formed in the project «Development of bioresource collection of tumors of the human nervous system with molecular genetic certification for personalized treatment of patients with neuro-oncological diseases¼. The purpose of this project was not only formation of bioresource collection, but also development of various molecular genetic methods for analysis of biospecimens in context of clinical researches. Biological information systems created to support the work of bioresource collections in hospitals should become a natural part of information infrastructure. Information support of bioresource collections cannot imply only «warehouse¼ functions. This system should have tools to support various scientific and clinical researches. Biological information systems can sometimes expand medical information systems but remain sufficiently autonomous. It is advisable to develop biological information systems in large specialized companies that can support their products for many years.

Biological Implications and Functional Significance of Transglutaminase Type 2 in Nervous System Tumors.

Transglutaminase type 2 (TG2) is the most ubiquitously expressed member of the transglutaminase family. TG2 catalyzes the transamidation reaction leading to several protein post-translational modifications and it is also implicated in signal transduction thanks to its GTP binding/hydrolyzing activity. In the nervous system, TG2 regulates multiple physiological processes, such as development, neuronal cell death and differentiation, and synaptic plasticity. Given its different enzymatic activities, aberrant expression or activity of TG2 can contribute to tumorigenesis, including in peripheral and central nervous system tumors. Indeed, TG2 dysregulation has been reported in meningiomas, medulloblastomas, neuroblastomas, glioblastomas, and other adult-type diffuse gliomas. The aim of this review is to provide an overview of the biological and functional relevance of TG2 in the pathogenesis of nervous system tumors, highlighting its involvement in survival, tumor inflammation, differentiation, and in the resistance to standard therapies.

Natural Flavonoid Apigenin, an Effective Agent Against Nervous System Cancers.

Cancer is a serious public health concern worldwide, and nervous system (NS) cancers are among the most life-threatening malignancies. Efforts have been devoted to introduce natural anticancer agents with minimal side effects. Apigenin is an edible flavonoid that is abundantly found in many vegetables and fruits. Various pharmaceutical activities, including anti-inflammatory, antioxidative, antimicrobial, and anticancer effects have been reported for apigenin. This review provides insights into the therapeutic effects of apigenin and flavonoids with similar structure on glioblastoma and neuroblastoma. Current evidence indicates that apigenin has the unique ability to cross the blood-brain barrier, and its antioxidative, anti-inflammatory, neurogenic, and neuroprotective effects have made this flavonoid a great option for the treatment of neurodegenerative disorders. Meanwhile, apigenin has low toxicity on normal neuronal cells, while induces cytotoxicity on NS cancer cells via triggering several signal pathways and molecular targets. Anticancer effects of apigenin have been contributed to various mechanisms such as induction of cell cycle arrest and apoptosis, and inhibition of migration, invasion, and angiogenesis. Although apigenin is a promising pharmaceutical agent, its low bioavailability is an important issue that must be solved before introducing to clinic. Recently, nano-delivery of apigenin by liposomes and poly lactic-co-glycolide nanoparticles has greatly improved functionality of this agent. Hence, investigating pharmaceutical effects of apigenin-loaded nanocarriers on NS cancer cell lines and animal models is recommended for future studies.

Newly Recognized Genetic Tumor Syndromes of the CNS in the 5th WHO Classification: Imaging Overview with Genetic Updates.

The nervous system is commonly involved in a wide range of genetic tumor-predisposition syndromes. The classification of genetic tumor syndromes has evolved during the past years; however, it has now become clear that these syndromes can be categorized into a relatively small number of major mechanisms, which form the basis of the new 5th edition of the World Health Organization book (beta online version) on genetic tumor syndromes. For the first time, the World Health Organization has also included a separate chapter on genetic tumor syndromes in the latest edition of all the multisystem tumor series, including the 5th edition of CNS tumors. Our understanding of these syndromes has evolved rapidly since the previous edition (4th edition, 2016) with recognition of 8 new syndromes, including the following: Elongator protein complex-medulloblastoma syndrome, BRCA1-associated protein 1 tumor-predisposition syndrome, DICER1 syndrome, familial paraganglioma syndrome, melanoma-astrocytoma syndrome, Carney complex, Fanconi anemia, and familial retinoblastoma. This review provides a description of these new CNS tumor syndromes with a focus on imaging and genetic characteristics.

Cancer Predisposition Syndromes in Neuro-oncology.

Although most primary central and peripheral nervous system (NS) tumors occur sporadically, there are a subset that may arise in the context of a cancer predisposition syndrome. These syndromes occur due to a pathogenic mutation in a gene that normally functions as a tumor suppressor. With increased understanding of the molecular pathogenesis of these tumors, more people have been identified with a cancer predisposition syndrome. Identification is crucial, as this informs surveillance, diagnosis, and treatment options. Moreover, relatives can also be identified through genetic testing. Although there are many cancer predisposition syndromes that increase the risk of NS tumors, in this review, we focus on three of the most common cancer predisposition syndromes, neurofibromatosis type 1, neurofibromatosis type 2, and tuberous sclerosis complex type 1 and type 2, emphasizing the clinical manifestations, surveillance guidelines, and treatment options.

Emodin-8-O-Glucoside-Isolation and the Screening of the Anticancer Potential against the Nervous System Tumors.

Emodin-8-O-glucoside (E-8-O-G) is a glycosylated derivative of emodin that exhibits numerous biological activities, including immunomodulatory, anti-inflammatory, antioxidant, hepatoprotective, or anticancer activities. However, there are no reports on the activity of E-8-O-G against cancers of the nervous system. Therefore, the aim of the study was to investigate the antiproliferative and cytotoxic effect of E-8-O-G in the SK-N-AS neuroblastoma, T98G human glioblastoma, and C6 mouse glioblastoma cancer cells. As a source of E-8-O-G the methanolic extract from the aerial parts of Reynoutria japonica Houtt. (Polygonaceae) was used. Thanks to the application of centrifugal partition chromatography (CPC) operated in the descending mode using a mixture of petroleum ether:ethyl acetate:methanol:water (4:5:4:5 v/v/v/v) and a subsequent purification with preparative HPLC, E-8-O-G was obtained in high purity in a sufficient quantity for the bioactivity tests. Assessment of the cancer cell viability and proliferation were performed with the MTT (3-(bromide 4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium), CTG (CellTiter-Glo®) and BrdU (5-bromo-2'-deoxyuridine) assays, respectively. E-8-O-G inhibits the viability and proliferation of SK-N-AS neuroblastoma, T98G human glioblastoma multiforme, and C6 mouse glioblastoma cells dose-dependently. E-8-O-G seems to be a promising natural antitumor compound in the therapy of nervous system tumors.

Exploring Lin28 proteins: Unravelling structure and functions with emphasis on nervous system malignancies.

Cancer and stem cells share many characteristics related to self-renewal and differentiation. Both cell types express the same critical proteins that govern cellular stemness, which provide cancer cells with the growth and survival benefits of stem cells. LIN28 is an example of one such protein. LIN28 includes two main isoforms, LIN28A and LIN28B, with diverse physiological functions from tissue development to control of pluripotency. In addition to their physiological roles, LIN28A and LIN28B affect the progression of several cancers by regulating multiple cancer hallmarks. Altered expression levels of LIN28A and LIN28B have been proposed as diagnostic and/or prognostic markers for various malignancies. This review discusses the structure and modes of action of the different LIN28 proteins and examines their roles in regulating cancer hallmarks with a focus on malignancies of the nervous system. This review also highlights some gaps in the field that require further exploration to assess the potential of targeting LIN28 proteins for controlling cancer.

Transcriptional immunogenomic analysis reveals distinct immunological clusters in paediatric nervous system tumours.

BACKGROUND: Cancer immunotherapies including immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR) T-cell therapy have shown variable response rates in paediatric patients highlighting the need to establish robust biomarkers for patient selection. While the tumour microenvironment in adults has been widely studied to delineate determinants of immune response, the immune composition of paediatric solid tumours remains relatively uncharacterized calling for investigations to identify potential immune biomarkers. METHODS: To inform immunotherapy approaches in paediatric cancers with embryonal origin, we performed an immunogenomic analysis of RNA-seq data from 925 treatment-naïve paediatric nervous system tumours (pedNST) spanning 12 cancer types from three publicly available data sets. RESULTS: Within pedNST, we uncovered four broad immune clusters: Paediatric Inflamed (10%), Myeloid Predominant (30%), Immune Neutral (43%) and Immune Desert (17%). We validated these clusters using immunohistochemistry, methylation immune inference and segmentation analysis of tissue images. We report shared biology of these immune clusters within and across cancer types, and characterization of specific immune cell frequencies as well as T- and B-cell repertoires. We found no associations between immune infiltration levels and tumour mutational burden, although molecular cancer entities were enriched within specific immune clusters. CONCLUSIONS: Given the heterogeneity of immune infiltration within pedNST, our findings suggest personalized immunogenomic profiling is needed to guide selection of immunotherapeutic strategies.

Targeting the epigenome of cancer stem cells in pediatric nervous system tumors.

Medulloblastoma, neuroblastoma, and pediatric glioma account for almost 30% of all cases of pediatric cancers. Recent evidence indicates that pediatric nervous system tumors originate from stem or progenitor cells and present a subpopulation of cells with highly tumorigenic and stem cell-like features. These cancer stem cells play a role in initiation, progression, and resistance to treatment of pediatric nervous system tumors. Histone modification, DNA methylation, chromatin remodeling, and microRNA regulation display a range of regulatory activities involved in cancer origin and progression, and cellular identity, especially those associated with stem cell features, such as self-renewal and pluripotent differentiation potential. Here, we review the contribution of different epigenetic mechanisms in pediatric nervous system tumor cancer stem cells. The choice between a differentiated and undifferentiated state can be modulated by alterations in the epigenome through the regulation of stemness genes such as CD133, SOX2, and BMI1 and the activation neuronal of differentiation markers, RBFOX3, GFAP, and S100B. Additionally, we highlighted the stage of development of epigenetic drugs and the clinical benefits and efficacy of epigenetic modulators in pediatric nervous system tumors.

Neurons as stromal drivers of nervous system cancer formation and progression.

Similar to their pivotal roles in nervous system development, neurons have emerged as critical regulators of cancer initiation, maintenance, and progression. Focusing on nervous system tumors, we describe the normal relationships between neurons and other cell types relevant to normal nerve function, and discuss how disruptions of these interactions promote tumor evolution, focusing on electrical (gap junctions) and chemical (synaptic) coupling, as well as the establishment of new paracrine relationships. We also review how neuron-tumor communication contributes to some of the complications of cancer, including neuropathy, chemobrain, seizures, and pain. Finally, we consider the implications of cancer neuroscience in establishing risk for tumor penetrance and in the design of future anti-tumoral treatments.

Role of nerves in neurofibromatosis type 1-related nervous system tumors.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that affects nearly 1 in 3000 infants. Neurofibromin inactivation and NF1 gene mutations are involved in various aspects of neuronal function regulation, including neuronal development induction, electrophysiological activity elevation, growth factor expression, and neurotransmitter release. NF1 patients often exhibit a predisposition to tumor development, especially in the nervous system, resulting in the frequent occurrence of peripheral nerve sheath tumors and gliomas. Recent evidence suggests that nerves play a role in the development of multiple tumor types, prompting researchers to investigate the nerve as a vital component in and regulator of the initiation and progression of NF1-related nervous system tumors. CONCLUSION: In this review, we summarize existing evidence about the specific effects of NF1 mutation on neurons and emerging research on the role of nerves in neurological tumor development, promising a new set of selective and targeted therapies for NF1-related tumors.

Special Issue "Tumors of the Nervous System: New Insights into Signaling, Genetics and Therapeutic Targeting".

This Special Issue focused on the current understanding of signaling pathways as well as genetic and epigenetic features involved in the pathogenesis of brain tumors and other nervous system tumors, with emphasis on the development of novel therapeutic approaches aimed at improving the current standard of care [...].

Tele-neuro-oncology: Current Practices and Future Directions.

PURPOSE OF REVIEW: The purpose of this review is to describe the current state of telemedicine within neuro-oncology. This article will address the development of tele-neuro-oncology over time with a focus on current use and applications of telemedicine within the field. Current modalities and practical considerations for tele-neuro-oncology visits and opportunities for growth will be highlighted. RECENT FINDINGS: The use of telemedicine has expanded significantly during the COVID-19 pandemic, particularly within neuro-oncology. The use of telemedicine is widely accepted by neuro-oncologic patients and providers and continues to expand in utilization and scope. The use of tele-neuro-oncology is expected to develop further with opportunities for multidisciplinary and integrated care, clinical trials, research, and education. Telemedicine provides a unique, patient-centered approach to neuro-oncologic care. Telehealth will remain a valuable tool, and its use and role are expected to expand within neuro-oncology.

Comprehensive analysis of the ErbB receptor family in pediatric nervous system tumors and rhabdomyosarcoma.

BACKGROUND: There is a paucity of knowledge regarding pediatric biomarkers, including the relevance of ErbB pathway aberrations in pediatric tumors. We investigated the occurrence of ErbB receptor aberrations across different pediatric malignancies, to identify patterns of ErbB dysregulation and define biomarkers suitable for patient enrichment in clinical studies. PROCEDURE: Tissue samples from 297 patients with nervous system tumors and rhabdomyosarcoma were analyzed for immunohistochemical expression or gene amplification of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Exploratory analyses of HER3/HER4 expression, and mRNA expression of ErbB receptors/ligands (NanoString) were performed. Assay validation followed general procedures, with additional validation to address Clinical Laboratory Improvement Amendments (CLIA) requirements. RESULTS: In most tumor types, samples with high ErbB receptor expression were found with heterogeneous distribution. We considered increased/aberrant ErbB pathway activation when greater than or equal to two EGFR/HER2 markers were simultaneously upregulated. ErbB pathway dysregulation was identified in ∼20%-30% of samples for most tumor types (medulloblastoma/primitive neuroectodermal tumors 31.1%, high-grade glioma 27.1%, neuroblastoma 22.7%, rhabdomyosarcoma 23.1%, ependymoma 18.8%), 4.2% of diffuse intrinsic pontine gliomas, and no recurrent or refractory low-grade astrocytomas. In medulloblastoma/primitive neuroectodermal tumors and neuroblastoma, this was attributed mainly to high EGFR polysomy/HER2 amplification, whereas EGFR gene amplification was observed in some high-grade glioma samples. EGFR/HER2 overexpression was most prevalent in ependymoma. CONCLUSIONS: Overexpression and/or amplification of EGFR/HER2 were identified as potential enrichment biomarkers for clinical trials of ErbB-targeted drugs.

Current state of therapeutic focused ultrasound applications in neuro-oncology.

INTRODUCTION: Despite manifold advances in oncology, cancers of the central nervous system remain among the most lethal. Unique features of the brain, including distinct cellular composition, immunological privilege, and physical barriers to therapeutic delivery, likely contribute to the poor prognosis of patients with neuro-oncological disease. Focused ultrasound is an emerging technology that allows transcranial delivery of ultrasound energy to focal brain targets with great precision. METHODS: A review of the clinical and preclinical focused ultrasound literature was performed to obtain data regarding the current state of the focused ultrasound in context of neuro-oncology. A narrative review was then constructed to provide an overview of current and future applications of this technology. RESULTS: Focused ultrasound can facilitate direct control of tumors by thermal or mechanical ablation, as well as enhance delivery of diverse therapeutics by disruption of the blood-brain barrier without local tissue damage. Indeed, ultrasound-sensitive drug formulations or sonosensitizers may be combined with ultrasound blood-brain barrier disruption to achieve high local drug concentration while limiting systemic exposure to therapeutics. Furthermore, focused ultrasound can induce radiosensitization, immunomodulation, and neuromodulation. Here we review applications of focused ultrasound with a focus on approaches currently under clinical investigation for the treatment of neuro-oncological disease, such as blood-brain barrier disruption for drug delivery and thermal ablation. We also discuss design of clinical trials, selection of patient cohorts, and emerging approaches to improve the efficacy of transcranial ultrasound, such as histotripsy, as well as combinatorial strategies to exploit synergistic biological effects of existing cancer therapies and ultrasound. CONCLUSIONS: Focused ultrasound is a promising and actively expanding therapeutic modality for diverse neuro-oncological diseases.