Thioredoxin, Glutathione and Related Molecules in Tumors of the Nervous System

2020 ◽  
Vol 27 (12) ◽  
pp. 1878-1900 ◽  
Author(s):  
Vasco Branco ◽  
José Pimentel ◽  
Maria Alexandra Brito ◽  
Cristina Carvalho
Keyword(s):  
Nervous System ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Malignant Tumors ◽  
Tumor Biology ◽  
Antioxidant Systems ◽  
Ros Scavenging ◽  
Survival Prognosis ◽  
Primary Tumors

Background: Central Nervous System (CNS) tumors have a poor survival prognosis due to their invasive and heterogeneous nature, in addition to the resistance to multiple treatments. Objective: In this paper, the main aspects of brain tumor biology and pathogenesis are reviewed both for primary tumors of the brain, (i.e., gliomas) and for metastasis from other malignant tumors, namely lung cancer, breast cancer and malignant melanoma which account for a high percentage of overall malignant brain tumors. We review the role of antioxidant systems, namely the thioredoxin and glutathione systems, in the genesis and/or progression of brain tumors. Methods: Although overexpression of Thioredoxin Reductase (TrxR) and Thioredoxin (Trx) is often linked to increased malignancy rate of brain tumors, and higher expression of Glutathione (GSH) and Glutathione S-Transferases (GST) are associated to resistance to therapy, several knowledge gaps still exist regarding for example, the role of Peroxiredoxins (Prx), and Glutaredoxins (Grx). Conclusion: Due to their central role in redox homeostasis and ROS scavenging, redox systems are potential targets for new antitumorals and examples of innovative therapeutics aiming at improving success rates in brain tumor treatment are discussed.

scholarly journals The Association of Human Herpesviruses with Malignant Brain Tumor Pathology and Therapy: Two Sides of a Coin

2021 ◽  
Vol 22 (5) ◽  
pp. 2250
Author(s):  
Evita Athanasiou ◽  
Antonios N. Gargalionis ◽  
Fotini Boufidou ◽  
Athanassios Tsakris
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Comprehensive Evaluation ◽  
Tumor Development ◽  
Scientific Data ◽  
Malignant Brain Tumor ◽  
Direct Role ◽  
Tumor Pathology ◽  
Human Herpesviruses

The role of certain viruses in malignant brain tumor development remains controversial. Experimental data demonstrate that human herpesviruses (HHVs), particularly cytomegalovirus (CMV), Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6), are implicated in brain tumor pathology, although their direct role has not yet been proven. CMV is present in most gliomas and medulloblastomas and is known to facilitate oncomodulation and/or immunomodulation, thus promoting cancer cell proliferation, invasion, apoptosis, angiogenesis, and immunosuppression. EBV and HHV-6 have also been detected in brain tumors and high-grade gliomas, showing high rates of expression and an inflammatory potential. On the other hand, due to the neurotropic nature of HHVs, novel studies have highlighted the engagement of such viruses in the development of new immunotherapeutic approaches in the context of oncolytic viral treatment and vaccine-based strategies against brain tumors. This review provides a comprehensive evaluation of recent scientific data concerning the emerging dual role of HHVs in malignant brain pathology, either as potential causative agents or as immunotherapeutic tools in the fight against these devastating diseases.

Epigenetics in Clinical Management of Children and Adolescents with Brain Tumors

2017 ◽  
Vol 18 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Andres Morales La Madrid ◽  
Mark W. Kieran
Keyword(s):  
Nervous System ◽  
Brain Tumors ◽  
Children And Adolescents ◽  
Tumor Biology ◽  
Tumor Development ◽  
Integrated Approach ◽  
Cell Types ◽  
Pediatric Brain Tumors ◽  
Tumor Formation ◽  
Molecular Profile

Central nervous system (CNS) tumors represent the second most prevalent group of cancers in children and adolescents, yet account for the majority of childhood cancer-related deaths and considerable morbidity among survivors, due to high-intensity non-selective standard therapies delivered to immature nervous system structures undergoing development. These tumors arise at different ages –not infrequently very early in life-, in different locations and cellular contexts, have varied cell types of origin, and have heterogeneous responses to the “classic” current therapeutic approaches. Demographic, radiologic and morphological characterization have several limitations, putting into the “classic boxes” heterogeneous tumors that are diverse in their genetic and epigenetic background and that will likely behave biologically different. Given that, epigenetic disruption (i.e. DNA methylation, histone modification and chromatin remodeling) is a common feature identified more and more frequently in pediatric cancer, it is logical to speculate that interrogating epigenetic marks may help to further define the molecular profile, and therefore tumor biology, evolution and treatment of these tumors. An integrated approach that incorporates traditional features complemented with genetic and epigenenetic specific markers offers tremendous promise to “risk-group” stratification and better prognostication. Also, it will help unveil the key driver pathways for tumor formation and for the discovery of targeted therapy for neoplasms that appear in the developing brain, facilitating early identification of therapy responders and track accurately disease progression. In this paper, we reviewed the most representative pediatric brain tumors where epigenetic alterations have been identified as initiating or driving events in tumor development, maintenance or progression.

Brain Tumors

2016 ◽  
pp. 11-24 ◽  
Author(s):  
Chikezie Eseonu ◽  
Jordina Rincon-Torroella ◽  
Alfredo Quiñones-Hinojosa
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Demyelinating Disease ◽  
Brain Lesion ◽  
Pituitary Tumors ◽  
Current Treatment ◽  
Preoperative Care ◽  
Adult Brain ◽  
Surgical Approaches

Brain tumor cases make up a significant part of the neurosurgery Oral Board Exam. A multitude of brain tumors exist and can be intraaxial or extraaxial. When considering a differential diagnosis for a brain lesion, infection, hematomas, infarctions, thrombosed aneurysms, inflammation, and demyelinating disease must be considered in addition to tumors. Common adult brain tumors consist of gliomas, meningiomas, metastases, and pituitary tumors. Management of brain tumors consists of understanding preoperative care, indications for surgery, surgical approaches, interpretation of preoperative and postoperative imaging, intraoperative and postoperative complications, and the role of adjuvant therapy, including chemotherapy and radiotherapy. Reviewing these essential points for the most common brain tumor cases and mastering the current treatment recommendations for common tumors will also be helpful for the boards.

Role of Hospital Medicine in Management of Intracranial Brain Tumors

2019 ◽  
pp. 57-73
Author(s):  
Donald Y. Ye ◽  
Thana Theofanis ◽  
Tomas Garzon-Muvdi ◽  
James J. Evans
Keyword(s):  
Risk Factors ◽  
Brain Tumor ◽  
Postoperative Complications ◽  
Brain Tumors ◽  
Management Strategies ◽  
Hospital Medicine ◽  
Intracranial Tumors ◽  
Medical Oncologists ◽  
Insight Into

Intracranial tumors reflect a broad range of benign and malignant processes that are often managed by neurosurgeons and medical oncologists. Patients presenting with new brain tumors will undergo biopsies or resection for tissue diagnosis and resolution of neurological symptoms. These patients have significant perioperative risk factors that must be addressed to ensure the best possible outcomes. Hospitalists play a pivotal role in identifying these risk factors and offering management strategies prior to the development of an operative plan. This chapter provides insight into the range of preoperative considerations and postoperative complications that a hospitalist may face when managing brain tumor patients.

scholarly journals The Role of the JC Virus in Central Nervous System Tumorigenesis

2020 ◽  
Vol 21 (17) ◽  
pp. 6236
Author(s):  
Nicholas Ahye ◽  
Anna Bellizzi ◽  
Dana May ◽  
Hassen S. Wollebo
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Tumor ◽  
Animal Models ◽  
Causative Agent ◽  
Jc Virus ◽  
Tumor Formation ◽  
Current Evidence ◽  
Merkel Cell

Cancer is the second leading cause of mortality worldwide. The study of DNA tumor-inducing viruses and their oncoproteins as a causative agent in cancer initiation and tumor progression has greatly enhanced our understanding of cancer cell biology. The initiation of oncogenesis is a complex process. Specific gene mutations cause functional changes in the cell that ultimately result in the inability to regulate cell differentiation and proliferation effectively. The human neurotropic Polyomavirus JC (JCV) belongs to the family Polyomaviridae and it is the causative agent of progressive multifocal leukoencephalopathy (PML), which is a fatal neurodegenerative disease in an immunosuppressed state. Sero-epidemiological studies have indicated JCV infection is prevalent in the population (85%) and that initial infection usually occurs during childhood. The JC virus has small circular, double-stranded DNA that includes coding sequences for viral early and late proteins. Persistence of the virus in the brain and other tissues, as well as its potential to transform cells, has made it a subject of study for its role in brain tumor development. Earlier observation of malignant astrocytes and oligodendrocytes in PML, as well as glioblastoma formation in non-human primates inoculated with JCV, led to the hypothesis that JCV plays a role in central nervous system (CNS) tumorigenesis. Some studies have reported the presence of both JC viral DNA and its proteins in several primary brain tumor specimens. The discovery of new Polyomaviruses such as the Merkel cell Polyomavirus, which is associated with Merkel cell carcinomas in humans, ignited our interest in the role of the JC virus in CNS tumors. The current evidence known about JCV and its effects, which are sufficient to produce tumors in animal models, suggest it can be a causative factor in central nervous system tumorigenesis. However, there is no clear association between JCV presence in CNS and its ability to initiate CNS cancer and tumor formation in humans. In this review, we will discuss the correlation between JCV and tumorigenesis of CNS in animal models, and we will give an overview of the current evidence for the JC virus’s role in brain tumor formation.

scholarly journals Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1546 ◽  
Author(s):  
Alena Kopkova ◽  
Jiri Sana ◽  
Tana Machackova ◽  
Marek Vecera ◽  
Lenka Radova ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Low Grade ◽  
Tumor Type ◽  
Tumor Patients ◽  
Primary Tumors ◽  
Mirna Profiling ◽  
Tumor Types ◽  
Cns Malignancies

Central nervous system (CNS) malignancies include primary tumors that originate within the CNS as well as secondary tumors that develop as a result of metastatic spread. Circulating microRNAs (miRNAs) were found in almost all human body fluids including cerebrospinal fluid (CSF), and they seem to be highly stable and resistant to even extreme conditions. The overall aim of our study was to identify specific CSF miRNA patterns that could differentiate among brain tumors. These new biomarkers could potentially aid borderline or uncertain imaging results onto diagnosis of CNS malignancies, avoiding most invasive procedures such as stereotactic biopsy or biopsy. In total, 175 brain tumor patients (glioblastomas, low-grade gliomas, meningiomas and brain metastases), and 40 non-tumor patients with hydrocephalus as controls were included in this prospective monocentric study. Firstly, we performed high-throughput miRNA profiling (Illumina small RNA sequencing) on a discovery cohort of 70 patients and 19 controls and identified specific miRNA signatures of all brain tumor types tested. Secondly, validation of 9 candidate miRNAs was carried out on an independent cohort of 105 brain tumor patients and 21 controls using qRT-PCR. Based on the successful results of validation and various combination patterns of only 5 miRNA levels (miR-30e, miR-140, let-7b, mR-10a and miR-21-3p) we proposed CSF-diagnostic scores for each tumor type which enabled to distinguish them from healthy donors and other tumor types tested. In addition to this primary diagnostic tool, we described the prognostic potential of the combination of miR-10b and miR-196b levels in CSF of glioblastoma patients. In conclusion, we performed the largest study so far focused on CSF miRNA profiling in patients with brain tumors, and we believe that this new class of biomarkers have a strong potential as a diagnostic and prognostic tool in these patients.

scholarly journals OMIC-13. THE ROLE OF COPY NUMBER ALTERATIONS IN PREDICTING SURVIVAL AND INFLUENCING TREATMENT OF CHILDHOOD BRAIN TUMORS

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i40-i40
Author(s):  
Sharon Freshour ◽  
Bryan Fisk ◽  
Christopher Miller ◽  
Obi Griffith ◽  
Malachi Griffith ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Copy Number ◽  
Statistical Power ◽  
Pediatric Brain Tumor ◽  
Copy Number Alterations ◽  
Childhood Brain Tumors ◽  
Entire Cohort

Abstract Brain and central nervous system tumors are the most common form of solid tumor cancers and the second most common cancer overall among children. While many advances have been made in understanding the genomics of childhood brain tumors in recent years, the role of copy number alterations (CNAs) has not been fully characterized. Although the genomes of childhood brain tumor patients are generally considered to be relatively stable diploid genomes, analysis of a subset of pretreatment diagnostic samples from a cohort of 84 deceased patients from Washington University revealed widespread alterations, suggesting CNAs may play a larger role in the progression and prognosis of childhood brain tumors than originally thought. Follow up analysis of the entire cohort, containing a variety of tumor types that had low-pass whole genome sequencing performed, similarly showed evidence of CNAs across samples. 75 out 84 patients showed the presence of CNAs with an average of 16% of the genome being altered per sample and a median of 7%. Preliminary results examining correlations between the percentage of the genome that was copy number altered and event free survival or overall survival indicated that CNA percentage may have some prognostic value. For example, ependymoma samples showed positive correlation between alteration percentage and overall survival, while glioblastoma samples showed negative correlation. To explore copy number alteration in a larger cohort and increase statistical power, similar analyses are being performed using an additional 950 samples from the Pediatric Brain Tumor Atlas curated by The Children’s Brain Tumor Network (CBTN) to determine if CNVs and CNV percentage or specific alterations can serve as prognostic markers and whether the biology of this genomic instability could inform therapeutic strategy.

scholarly journals The Role of Neurodevelopmental Pathways in Brain Tumors

2021 ◽  
Vol 9 ◽  
Author(s):  
Rachel N. Curry ◽  
Stacey M. Glasgow
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Disease Progression ◽  
Adult Brain ◽  
Signaling Cascades ◽  
Tumor Initiation ◽  
Developmental Factors ◽  
Developmental Signaling ◽  
Cell Signaling Pathways

Disruptions to developmental cell signaling pathways and transcriptional cascades have been implicated in tumor initiation, maintenance and progression. Resurgence of aberrant neurodevelopmental programs in the context of brain tumors highlights the numerous parallels that exist between developmental and oncologic mechanisms. A deeper understanding of how dysregulated developmental factors contribute to brain tumor oncogenesis and disease progression will help to identify potential therapeutic targets for these malignancies. In this review, we summarize the current literature concerning developmental signaling cascades and neurodevelopmentally-regulated transcriptional programs. We also examine their respective contributions towards tumor initiation, maintenance, and progression in both pediatric and adult brain tumors and highlight relevant differentiation therapies and putative candidates for prospective treatments.

scholarly journals SL1 GENETICS OF PEDIATRIC BRAIN TUMORS: RECENT ADVANCES AND FUTURE PERSPECTIVES

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii1-ii1
Author(s):  
David T W Jones
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Somatic Hypermutation ◽  
Tumor Biology ◽  
Pediatric Brain Tumor ◽  
Pediatric Brain Tumors ◽  
Braf V600e ◽  
Enhancer Element ◽  
Frequent Mutations ◽  
Pediatric Brain

Abstract The last decade has seen a true revolution in our understanding of the oncogenic mechanisms underlying human tumors, brought about by transformative advances in the technologies available to interrogate the (epi)genetic composition of cancer cells. The dynamic pediatric neuro-oncology community has proven to be very agile in adapting to these changes, and has arguably been at the forefront of some of the most exciting new discoveries in tumor biology in recent years. For example, high-throughput genomic sequencing has revealed highly frequent mutations in histone genes in pediatric glioblastoma; highlighted an ever-expanding role for oncogenic gene fusions in multiple pediatric brain tumor types, and also shed light on novel phenotypic patterns such as chromothripsis (dramatic chromosomal shattering) and somatic hypermutation - the latter being a possible marker for response to novel immunotherapeutic approaches. Epigenetic profiling has also identified a role for ‘enhancer hijacking’ (whereby genomic rearrangement brings an active enhancer element in close proximity to a proto-oncogene) in multiple pediatric brain tumors, and is even pointing towards a fundamentally new way in which tumors may be molecularly classified. In coming years, the major challenge will be to harness the power of these discoveries to more accurately diagnose patients and to identify potential therapeutic targets in a more personalized way, so that these major biological advances can also be translated into substantial clinical benefit. Examples such as the dramatic responses observed in childhood brain tumor sufferers to BRAF V600E and NTRK inhibitors demonstrate the promise that such an approach can hold, but it will require a fundamental shift in the way that clinical trials are planned and conducted in order to optimize patient care. This talk will highlight some of the most striking developments in the field, and look at the challenges that remain before these can lead to improved patient outcomes.

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