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Biomedicines
Special Issues
Diagnosis, Pathogenesis and Treatment of CNS Tumors
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Diagnosis, Pathogenesis and Treatment of CNS Tumors

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 30 April 2025 | Viewed by 9830

Special Issue Editor

Prof. Dr. Dimitrios Kanakis

E-Mail Website
Guest Editor
Department of Pathology, University of Nicosia Medical School, Nicosia, Cyprus
Interests: neurooncology; neurodegenerative diseases; traumatic brain injury/chronic traumatic encephalopathy; demyelinating diseases; neurodevelopmental disorders; neuromuscular disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The current Classification of the Tumors of the Central Nervous System (CNS), published in 2021, not only incorporates histopathological features but also the molecular findings of some of the most common CNS tumors. In this context, the term ‘integrated diagnosis’ has been introduced, which refers to the combined use of these individual characteristics in the description of the final diagnosis.

Furthermore, several novel changes have affected both the nomenclature and grading of tumors. In particular, the former (i.e., terminology) is based on the recommendations of the 2019 cIMPACT-NOW Utrecht meeting, thus aiming to achieve better effectiveness and consistency. It also conforms with the HUGO Gene Nomenclature Committee (HGNC) system for gene symbols and names.

On the other hand, the recently developed grading system aims to comply with the one used for non-CNS neoplasms. More specifically, Roman numerals are replaced by Arabic numerals, which is similar to the grading of other organ systems. Additionally, grading is introduced within tumor types, which corresponds to a combined histological and molecular grading. As certain molecular markers have been found to correlate with prognosis, this fact has necessitated the inclusion of these markers in the lastly amended grading system.

All the above mentioned modifications in the fifth edition of the ‘blue book’ on CNS tumors will certainly have α substantial impact, directly on the simplification and harmonization of diagnostic procedures and indirectly on the development of more accurate and targeted therapeutic modalities. In addition, extended research on the identification of new molecular markers of diagnostic, therapeutic, and prognostic significance will further contribute to our understanding of the complex pathogenetic mechanisms behind the appearance of various CNS tumors.

This Special Issue aims to publish recent research papers on three important aspects of CNS tumors, namely diagnosis, pathogenesis, and treatment. Therefore, we welcome the submission of valuable research.

Prof. Dr. Dimitrios Kanakis
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • CNS tumors
  • diagnosis
  • pathogenesis
  • treatment
  • prognosis
  • molecular markers

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Published Papers (8 papers)

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Research

Jump to: Review, Other

19 pages, 7338 KiB  
Article
Tumor-Promoted Changes in Pediatric Brain Histology Can Be Distinguished from Normal Parenchyma by Desorption Electrospray Ionization Mass Spectrometry Imaging
by Ana L. Seidinger, Felipe L. T. Silva, Mayara F. Euzébio, Anna C. Krieger, João Meidanis, Junier M. Gutierrez, Thais M. S. Bezerra, Luciano Queiroz, Alex A. Rosini. Silva, Iva L. Hoffmann, Camila M. M. Daiggi, Helder Tedeschi, Marcos N. Eberlin, Livia S. Eberlin, José A. Yunes, Andreia M. Porcari and Izilda A. Cardinalli
Biomedicines 2024, 12(11), 2593; https://doi.org/10.3390/biomedicines12112593 - 13 Nov 2024
Viewed by 487
Abstract
Background: Central nervous system (CNS) tumors are the second most frequent type of neoplasm in childhood and adolescence, after leukemia. Despite the incorporation of molecular classification and improvement of protocols combining chemotherapy, surgery, and radiotherapy, CNS tumors are still the most lethal neoplasm [...] Read more.
Background: Central nervous system (CNS) tumors are the second most frequent type of neoplasm in childhood and adolescence, after leukemia. Despite the incorporation of molecular classification and improvement of protocols combining chemotherapy, surgery, and radiotherapy, CNS tumors are still the most lethal neoplasm in this age group. Mass spectrometry imaging (MSI) is a powerful tool to map the distribution of molecular species in tissue sections. Among MSI techniques, desorption electrospray ionization (DESI-MSI) has been demonstrated to enable reliable agreement with the pathological evaluation of different adult cancer types, along with an acceptable time scale for intraoperative use. Methods: In the present work, we aimed to investigate the chemical profile obtained by DESI-MSI as an intraoperative surgical management tool by profiling 162 pediatric brain biopsies and reporting the results according to the histopathology and molecular profile of the tumors. Results: The 2D chemical images obtained by DESI-MSI allowed us to distinguish tumor-transformed tissue from non-tumor tissue with an accuracy of 96.8% in the training set and 94.3% in the validation set after statistical modeling of our data using Lasso. In addition, high-grade and low-grade tumors also displayed a distinct chemical profile when analyzed by DESI-MSI. We also provided evidence that the chemical profile of brain tumors obtained by DESI-MSI correlates with methylation-based molecular classes and specific immunophenotypes found in brain biopsies. Conclusions: The results presented herein support the incorporation of DESI-MSI analysis as an intraoperative assistive tool in prospective clinical trials for pediatric brain tumors management in the near future. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of CNS Tumors)
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11 pages, 12098 KiB  
Article
Neuronal Differentiation of Human Glioma Cells Induced by Parthenolide Under In Vitro Conditions
by Zhaoqi Tang, Chang Cao, Weiwei Tang, Yanrong Ye, Zhenhui Chen and Yun Shen
Biomedicines 2024, 12(11), 2543; https://doi.org/10.3390/biomedicines12112543 - 7 Nov 2024
Viewed by 449
Abstract
Objective: Previous drug repositioning studies have suggested that parthenolide may be a differentiation-inducing agent for glioma cells. This study aimed to experimentally verify the neuronal differentiation-inducing effects and proliferative impact of parthenolide on human glioma cells and explore its potential mechanisms. Methods: HE [...] Read more.
Objective: Previous drug repositioning studies have suggested that parthenolide may be a differentiation-inducing agent for glioma cells. This study aimed to experimentally verify the neuronal differentiation-inducing effects and proliferative impact of parthenolide on human glioma cells and explore its potential mechanisms. Methods: HE staining was used to observe the morphological changes in human glioma cell lines U87 and A172 induced by parthenolide. Immunocytochemistry was conducted to detect the expression of differentiation markers. The Ki-67 detection and CCK-8 assay were used to assess the effects of parthenolide on cell proliferation. The sphere formation assay was conducted to evaluate the self-renewal. Glioma stem cells (GSCs) derived from U87 cells were utilized to assess the ability of parthenolide to induce differentiation in GSCs. Western blot was used to detect the expression of histone deacetylase 1 (HDAC1). Bioinformatics analysis based on the CGGA database was conducted to evaluate the role of HDAC1 in glioma. Results: Parthenolide (4 μM) altered the morphology of U87 and A172 cells, as elongated cell projections were observed. Parthenolide induced glioma cells to express neuronal markers NeuN, MAP2, SYP, and NEFL, but not astrocyte or oligodendrocyte markers. Parthenolide significantly inhibited proliferation and self-renewal in glioma cells. Similar effects were observed in U87 GSCs. Furthermore, parthenolide downregulated HDAC1 expression in glioma cells, and the bioinformatics analysis revealed a potential relationship between neuronal characteristics and low expression of HDAC1 in glioma. Conclusion: Parthenolide induced neuronal differentiation and inhibited the cell proliferation in human glioma cells, which might be associated with the inhibition of HDAC1. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of CNS Tumors)
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17 pages, 1085 KiB  
Article
Enhancing Brain Tumor Diagnosis with L-Net: A Novel Deep Learning Approach for MRI Image Segmentation and Classification
by Lehel Dénes-Fazakas, Levente Kovács, György Eigner and László Szilágyi
Biomedicines 2024, 12(10), 2388; https://doi.org/10.3390/biomedicines12102388 - 18 Oct 2024
Viewed by 847
Abstract
Background: Brain tumors are highly complex, making their detection and classification a significant challenge in modern medical diagnostics. The accurate segmentation and classification of brain tumors from MRI images are crucial for effective treatment planning. This study aims to develop an advanced neural [...] Read more.
Background: Brain tumors are highly complex, making their detection and classification a significant challenge in modern medical diagnostics. The accurate segmentation and classification of brain tumors from MRI images are crucial for effective treatment planning. This study aims to develop an advanced neural network architecture that addresses these challenges. Methods: We propose L-net, a novel architecture combining U-net for tumor boundary segmentation and a convolutional neural network (CNN) for tumor classification. These two units are coupled such a way that the CNN classifies the MRI images based on the features extracted by the U-net while segmenting the tumor, instead of relying on the original input images. The model is trained on a dataset of 3064 high-resolution MRI images, encompassing gliomas, meningiomas, and pituitary tumors, ensuring robust performance across different tumor types. Results: L-net achieved a classification accuracy of up to 99.6%, surpassing existing models in both segmentation and classification tasks. The model demonstrated effectiveness even with lower image resolutions, making it suitable for diverse clinical settings. Conclusions: The proposed L-net model provides an accurate and unified approach to brain tumor segmentation and classification. Its enhanced performance contributes to more reliable and precise diagnosis, supporting early detection and treatment in clinical applications. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of CNS Tumors)
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14 pages, 12010 KiB  
Article
Clinical Utility of Optical Genome Mapping for Improved Cytogenomic Analysis of Gliomas
by Harmanpreet Singh, Nikhil S. Sahajpal, Ashis K. Mondal, Stephanie L. Burke, Jaspreet Farmaha, Ahmet Alptekin, Ashutosh Vashisht, Kimya Jones, Vishakha Vashisht and Ravindra Kolhe
Biomedicines 2024, 12(8), 1659; https://doi.org/10.3390/biomedicines12081659 - 25 Jul 2024
Viewed by 935
Abstract
A glioma is a solid brain tumor which originates in the brain or brain stem area. The diagnosis of gliomas based on standard-of-care (SOC) techniques includes karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA), for detecting the pathogenic variants and chromosomal [...] Read more.
A glioma is a solid brain tumor which originates in the brain or brain stem area. The diagnosis of gliomas based on standard-of-care (SOC) techniques includes karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA), for detecting the pathogenic variants and chromosomal abnormalities. But these techniques do not reveal the complete picture of genetic complexity, thus requiring an alternative technology for better characterization of these tumors. The present study aimed to evaluate the clinical performance and feasibility of using optical genome mapping (OGM) for chromosomal characterization of gliomas. Herein, we evaluated 10 cases of gliomas that were previously characterized by CMA. OGM analysis showed concordance with the results of CMA in identifying the characterized Structural Variants (SVs) in these cases. More notably, it also revealed additional clinically relevant aberrations, demonstrating a higher resolution and sensitivity. These clinically relevant SVs included cryptic translocation, and SVs which are beyond the detection capabilities of CMA. Our analysis highlights the unique capability of OGM to detect all classes of SVs within a single assay, thereby unveiling clinically significant data with a shorter turnaround time. Adopting this diagnostic tool as a standard of care for solid tumors like gliomas shows potential for improving therapeutic management, potentially leading to more personalized and timely interventions for patients. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of CNS Tumors)
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Review

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39 pages, 1421 KiB  
Review
The Role of HDAC6 in Glioblastoma Multiforme: A New Avenue to Therapeutic Interventions?
by Francesco Spallotta and Barbara Illi
Biomedicines 2024, 12(11), 2631; https://doi.org/10.3390/biomedicines12112631 - 17 Nov 2024
Viewed by 552
Abstract
Despite the great advances in basic research results, glioblastoma multiforme (GBM) still remains an incurable tumour. To date, a GBM diagnosis is a death sentence within 15–18 months, due to the high recurrence rate and resistance to conventional radio- and chemotherapy approaches. The [...] Read more.
Despite the great advances in basic research results, glioblastoma multiforme (GBM) still remains an incurable tumour. To date, a GBM diagnosis is a death sentence within 15–18 months, due to the high recurrence rate and resistance to conventional radio- and chemotherapy approaches. The effort the scientific community is lavishing on the never-ending battle against GBM is reflected by the huge number of clinical trials launched, about 2003 on 10 September 2024. However, we are still far from both an in-depth comprehension of the biological and molecular processes leading to GBM onset and progression and, importantly, a cure. GBM is provided with high intratumoral heterogeneity, immunosuppressive capacity, and infiltrative ability due to neoangiogenesis. These features impact both tumour aggressiveness and therapeutic vulnerability, which is further limited by the presence in the tumour core of niches of glioblastoma stem cells (GSCs) that are responsible for the relapse of this brain neoplasm. Epigenetic alterations may both drive and develop along GBM progression and also rely on changes in the expression of the genes encoding histone-modifying enzymes, including histone deacetylases (HDACs). Among them, HDAC6—a cytoplasmic HDAC—has recently gained attention because of its role in modulating several biological aspects of GBM, including DNA repair ability, massive growth, radio- and chemoresistance, and de-differentiation through primary cilia disruption. In this review article, the available information related to HDAC6 function in GBM will be presented, with the aim of proposing its inhibition as a valuable therapeutic route for this deadly brain tumour. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of CNS Tumors)
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15 pages, 2121 KiB  
Review
Zonulin as Gatekeeper in Gut–Brain Axis: Dysregulation in Glioblastoma
by Hannah Hagemeyer, Olaf J. C. Hellwinkel and Julio Plata-Bello
Biomedicines 2024, 12(8), 1649; https://doi.org/10.3390/biomedicines12081649 - 24 Jul 2024
Viewed by 1313
Abstract
Novel biomarkers and therapeutic strategies for glioblastoma, the most common malignant brain tumor with an extremely unfavorable prognosis, are urgently needed. Recent studies revealed a significant upregulation of the protein zonulin in glioblastoma, which correlates with patient survival. Originally identified as pre-haptoglobin-2, zonulin [...] Read more.
Novel biomarkers and therapeutic strategies for glioblastoma, the most common malignant brain tumor with an extremely unfavorable prognosis, are urgently needed. Recent studies revealed a significant upregulation of the protein zonulin in glioblastoma, which correlates with patient survival. Originally identified as pre-haptoglobin-2, zonulin modulates both the intestinal barrier and the blood–brain barrier by disassembling tight junctions. An association of zonulin with various neuroinflammatory diseases has been observed. It can be suggested that zonulin links a putative impairment of the gut–brain barrier with glioblastoma carcinogenesis, leading to an interaction of the gut microbiome, the immune system, and glioblastoma. We therefore propose three interconnected hypotheses: (I) elevated levels of zonulin in glioblastoma contribute to its aggressiveness; (II) upregulated (serum-) zonulin increases the permeability of the microbiota–gut–brain barrier; and (III) this creates a carcinogenic and immunosuppressive microenvironment preventing the host from an effective antitumor response. The role of zonulin in glioblastoma highlights a promising field of research that could yield diagnostic and therapeutic options for glioblastoma patients and other diseases with a disturbed microbiota–gut–brain barrier. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of CNS Tumors)
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28 pages, 3792 KiB  
Review
The 2021 World Health Organization Central Nervous System Tumor Classification: The Spectrum of Diffuse Gliomas
by Racine Gue and Dhairya A. Lakhani
Biomedicines 2024, 12(6), 1349; https://doi.org/10.3390/biomedicines12061349 - 18 Jun 2024
Viewed by 2478
Abstract
The 2021 edition of the World Health Organization (WHO) classification of central nervous system tumors introduces significant revisions across various tumor types. These updates, encompassing changes in diagnostic techniques, genomic integration, terminology, and grading, are crucial for radiologists, who play a critical role [...] Read more.
The 2021 edition of the World Health Organization (WHO) classification of central nervous system tumors introduces significant revisions across various tumor types. These updates, encompassing changes in diagnostic techniques, genomic integration, terminology, and grading, are crucial for radiologists, who play a critical role in interpreting brain tumor imaging. Such changes impact the diagnosis and management of nearly all central nervous system tumor categories, including the reclassification, addition, and removal of specific tumor entities. Given their pivotal role in patient care, radiologists must remain conversant with these revisions to effectively contribute to multidisciplinary tumor boards and collaborate with peers in neuro-oncology, neurosurgery, radiation oncology, and neuropathology. This knowledge is essential not only for accurate diagnosis and staging, but also for understanding the molecular and genetic underpinnings of tumors, which can influence treatment decisions and prognostication. This review, therefore, focuses on the most pertinent updates concerning the classification of adult diffuse gliomas, highlighting the aspects most relevant to radiological practice. Emphasis is placed on the implications of new genetic information on tumor behavior and imaging findings, providing necessary tools to stay abreast of advancements in the field. This comprehensive overview aims to enhance the radiologist’s ability to integrate new WHO classification criteria into everyday practice, ultimately improving patient outcomes through informed and precise imaging assessments. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of CNS Tumors)
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Other

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12 pages, 7093 KiB  
Case Report
A High-Grade Glioma, Not Elsewhere Classified in an Older Adult with Discordant Genetic and Epigenetic Analyses
by Carlen A. Yuen, Silin Bao, Xiao-Tang Kong, Merryl Terry, Alexander Himstead, Michelle Zheng and Melike Pekmezci
Biomedicines 2024, 12(9), 2042; https://doi.org/10.3390/biomedicines12092042 - 8 Sep 2024
Viewed by 946
Abstract
The World Health Organization’s (WHO) classification of central nervous system (CNS) tumors is continually being refined to improve the existing diagnostic criteria for high-grade gliomas (HGGs), including glioblastoma. In 2021, advances in molecular analyses and DNA methylation profiling were incorporated to expand upon [...] Read more.
The World Health Organization’s (WHO) classification of central nervous system (CNS) tumors is continually being refined to improve the existing diagnostic criteria for high-grade gliomas (HGGs), including glioblastoma. In 2021, advances in molecular analyses and DNA methylation profiling were incorporated to expand upon the diagnostic criteria for HGG, including the introduction of high-grade astrocytoma with piloid features (HGAP), a new tumor entity for which a match to the HGAP class in DNA methylation profiling is an essential criterion. We present an equivocal case of a 72-year-old male with an HGG exhibiting features of both HGAP and glioblastoma, but which did not conform to any existing 2021 WHO classification of CNS tumor entities. This “no match” in DNA methylation profiling resulted in a final diagnosis of HGG not elsewhere classified (NEC), for which standard treatment options do not exist. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of CNS Tumors)
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