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Biomedicines
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Diagnosis, Pathogenesis, Treatment and Prognosis of Glioblastoma
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Diagnosis, Pathogenesis, Treatment and Prognosis of Glioblastoma

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (28 February 2025) | Viewed by 4949

Special Issue Editor

Prof. Dr. Paulo Linhares

E-Mail Website
Guest Editor
Clinical Neurosciences and Mental Health Department, Faculty of Medicine, University of Oporto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
Interests: glioblastoma; glioma; brain metastasis

Special Issue Information

Dear Colleagues,

Are the genetic changes already adequately known to determine the biological behavior of glioblastomas? Will there be immunotherapy and effective directed treatments for glioblastomas? What is the best treatment for elderly patients and for patients with multicentric lesions? What is the role of reirradiation? What is the experience so far with LITT and TTF?

Although there have been recent advances in molecular characterization and treatments, the prognostic remains dismissive, with most patients dying within 15–18 months. In the USA, the 5-year survival rate has been reported as 6.8%.

Despite the longer genetic and molecular assessment of glioblastoma, the standard treatment is still a combination of surgery, radiotherapy and chemotherapy; thus, significant ongoing challenges remain for the treatment.

The relationship of genetic and molecular changes with image findings may allow different diagnostic approaches.

Understanding glioblastoma and its pathogenesis is critical for researching new forms of treatment as well understanding its resistance mechanisms and escape from immune surveillance.

In addition to immunotherapy and target therapies, non-pharmacological options such as TTFs and LITT have emerged as viable treatment options, although with currently uncertain results.

Here, we will try to provide answers to some of these questions, and we will certainly raise other questions that will remain unanswered.

Prof. Dr. Paulo Linhares
Guest Editor

Manuscript Submission Information

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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

  • glioblastoma
  • immunotherapy
  • molecular subtype
  • radiotherapy
  • molecular therapy
  • emerging treatment
  • drug resistance
  • MRI
  • immune surveillance

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Published Papers (4 papers)

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Research

15 pages, 2499 KiB  
Article
Probe-Based Fluorescence Spectroscopy for In Situ Brain Tumor Measurements During Resection and Needle Biopsies
by Karin Wårdell, Elisabeth Klint and Johan Richter
Biomedicines 2025, 13(3), 537; https://doi.org/10.3390/biomedicines13030537 - 20 Feb 2025
Viewed by 368
Abstract
Background/Objectives: Primary brain tumors are difficult to identify intraoperatively due to their infiltrative character in the marginal zone. Several optical methods have been suggested. Of these, 5-ALA-induced fluorescence visualized through a microscope is the most common. The aim is to present an [...] Read more.
Background/Objectives: Primary brain tumors are difficult to identify intraoperatively due to their infiltrative character in the marginal zone. Several optical methods have been suggested. Of these, 5-ALA-induced fluorescence visualized through a microscope is the most common. The aim is to present an investigational probe-based optical system and its translation for clinical use, summarize previous studies, and give examples of clinical implementations during resection and burr hole biopsies. Methods: The FluoRa system combines 5-ALA fluorescence spectroscopy with laser Doppler flowmetry (LDF). Probe designs are available for brain tumor resection (hand-held probe) or burr hole needle biopsies (frame-based or navigated). The outer cannulas of biopsy needles are modified with an opening at the tip for simultaneous use with optical probes during insertion along the trajectory. An updated version of FluoRa is introduced and experimentally investigated. Results: Probe-based fluorescence spectroscopy has been successfully translated for clinical use and applied during brain tumor resection (n = 75) and burr hole needle biopsies (n = 47). Forward-looking optical measurements through the biopsy needle reduce the number of trajectories (28/27) compared to prior to insertion (28/20), at the same time that the target for tissue sampling can be identified in situ. Additionally, increased microcirculation is identified along the trajectory with LDF. This is accomplished with FluoRa. Conclusions: Intraoperative probe-based spectroscopic measurements quantify 5-ALA fluorescence and thus identify glioblastoma and lymphoma tissue in situ during resection and burr hole needle biopsies. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis, Treatment and Prognosis of Glioblastoma)
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20 pages, 33992 KiB  
Article
In Situ Light-Source Delivery During 5-Aminulevulinic Acid-Guided High-Grade Glioma Resection: Spatial, Functional and Oncological Informed Surgery
by José Pedro Lavrador, Francesco Marchi, Ali Elhag, Nida Kalyal, Engelbert Mthunzi, Mariam Awan, Oliver Wroe-Wright, Alba Díaz-Baamonde, Ana Mirallave-Pescador, Zita Reisz, Richard Gullan, Francesco Vergani, Keyoumars Ashkan and Ranjeev Bhangoo
Biomedicines 2024, 12(12), 2748; https://doi.org/10.3390/biomedicines12122748 - 30 Nov 2024
Cited by 1 | Viewed by 972
Abstract
Background/Objectives: 5-aminulevulinic acid (5-ALA)-guided surgery for high-grade gliomas remains a challenge in neuro-oncological surgery. Inconsistent fluorescence visualisation, subjective quantification and false negatives due to blood, haemostatic agents or optical impediments from the external light source are some of the limitations of the present [...] Read more.
Background/Objectives: 5-aminulevulinic acid (5-ALA)-guided surgery for high-grade gliomas remains a challenge in neuro-oncological surgery. Inconsistent fluorescence visualisation, subjective quantification and false negatives due to blood, haemostatic agents or optical impediments from the external light source are some of the limitations of the present technology. Methods: The preliminary results from this single-centre retrospective study are presented from the first 35 patients operated upon with the novel Nico Myriad Spectra System©. The microdebrider (Myriad) with an additional in situ light system (Spectra) can alternately provide white and blue light (405 nm) to within 15 mm of the tissue surface to enhance the morphology of the anatomical structures and the fluorescence of the pathological tissues. Results: A total of 35 patients were operated upon with this new technology. Eight patients (22.85%) underwent tubular retractor-assisted minimally invasive parafascicular surgery (tr-MIPS). The majority had high-grade gliomas (68.57%). Fluorescence was identified in 30 cases (85.71%), with residual fluorescence in 11 (36.66%). The main applications were better white–blue light alternation and visualisation during tr-MIPS, increase in the extent of resection at the border of the cavity, identification of satellite lesions in multifocal pathology, the differentiation between radionecrosis and tumour recurrence in redo surgery and the demarcation between normal ependyma versus pathological ependyma in tumours infiltrating the subventricular zone. Conclusions: This proof-of-concept study confirms that the novel in situ light-source delivery technology integrated with the usual intraoperative armamentarium provides a spatially, functionally and oncologically informed framework for glioblastoma surgery. It allows for the enhancement of the morphology of anatomical structures and the fluorescence of pathological tissues, increasing the extent of resection and, possibly, the prognosis for patients with high-grade gliomas. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis, Treatment and Prognosis of Glioblastoma)
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19 pages, 9389 KiB  
Article
Comprehensive Bioinformatics Analysis Reveals the Potential Role of the hsa_circ_0001081/miR-26b-5p Axis in Regulating COL15A1 and TRIB3 within Hypoxia-Induced miRNA/mRNA Networks in Glioblastoma Cells
by Bartosz Lenda, Marta Żebrowska-Nawrocka and Ewa Balcerczak
Biomedicines 2024, 12(10), 2236; https://doi.org/10.3390/biomedicines12102236 - 1 Oct 2024
Viewed by 1295
Abstract
Background/Objectives: The intrinsic molecular heterogeneity of glioblastoma (GBM) is one of the main reasons for its resistance to conventional treatment. Mesenchymal GBM niches are associated with hypoxic signatures and a negative influence on patients’ prognosis. To date, competing endogenous RNA (ceRNA) networks have [...] Read more.
Background/Objectives: The intrinsic molecular heterogeneity of glioblastoma (GBM) is one of the main reasons for its resistance to conventional treatment. Mesenchymal GBM niches are associated with hypoxic signatures and a negative influence on patients’ prognosis. To date, competing endogenous RNA (ceRNA) networks have been shown to have a broad impact on the progression of various cancers. In this study, we decided to construct hypoxia-specific microRNA/ messengerRNA (miRNA/mRNA) networks with a putative circular RNA (circRNA) regulatory component using available bioinformatics tools. Methods: For ceRNA network construction, we combined publicly available data deposited in the Gene Expression Omnibus (GEO) and interaction pairs obtained from miRTarBase and circBank; a differential expression analysis of GBM cells was performed with limma and deseq2. For the gene ontology (GO) enrichment analysis, we utilized clusterProfiler; GBM molecular subtype analysis was performed in the Glioma Bio Discovery Portal (Glioma-BioDP). Results: We observed that miR-26b-5p, generally considered a tumor suppressor, was upregulated under hypoxic conditions in U-87 MG cells. Moreover, miR-26b-5p could potentially inhibit TRIB3, a gene associated with tumor proliferation. Protein-protein interaction (PPI) network and GO enrichment analyses identified a hypoxia-specific subcluster enriched in collagen-associated terms, with six genes highly expressed in the mesenchymal glioma group. This subcluster included hsa_circ_0001081/miR-26b-5p-affected COL15A1, a gene downregulated in hypoxic U-87 MG cells yet highly expressed in the mesenchymal GBM subtype. Conclusions: The interplay between miR-26b-5p, COL15A1, and TRIB3 suggests a complex regulatory mechanism that may influence the extracellular matrix composition and the mesenchymal transformation in GBM. However, the precise impact of the hsa_circ_0001081/miR-26b-5p axis on collagen-associated processes in hypoxia-induced GBM cells remains unclear and warrants further investigation. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis, Treatment and Prognosis of Glioblastoma)
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12 pages, 1405 KiB  
Article
Sequential Evaluation of Hematology Markers as a Prognostic Factor in Glioblastoma Patients
by João Meira Gonçalves, Bruno Carvalho, Rui Tuna, Patricia Polónia and Paulo Linhares
Biomedicines 2024, 12(5), 1067; https://doi.org/10.3390/biomedicines12051067 - 12 May 2024
Viewed by 1510
Abstract
In our study, we investigated the prognostic significance of hematological markers—NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio), and RDW-CV (Red Blood Cell Distribution Width—Coefficient of Variation)—in 117 glioblastoma patients. The data collected from January 2016 to December 2018 included demographics, clinical scores, and treatment [...] Read more.
In our study, we investigated the prognostic significance of hematological markers—NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio), and RDW-CV (Red Blood Cell Distribution Width—Coefficient of Variation)—in 117 glioblastoma patients. The data collected from January 2016 to December 2018 included demographics, clinical scores, and treatment regimens. Unlike previous research, which often examined these markers solely before surgery, our unique approach analyzed them at multiple stages: preoperative, postoperative, and before adjuvant therapies. We correlated these markers with the overall survival (OS) and progression-free survival (PFS) using statistical tools, including ANOVA, Cox regression, and Kaplan–Meier survival analyses, employing SPSS version 29.0. Our findings revealed notable variations in the NLR, PLR, and RDW-CV across different treatment stages. The NLR and PLR decreased after surgery, with some stabilization post-STUPP phase (NLR: p = 0.007, η2p = 0.06; PLR: p = 0.001, η2p = 0.23), while the RDW-CV increased post-surgery and during subsequent treatments (RDW-CV: p < 0.001, η2p = 0.67). Importantly, we observed significant differences between the preoperative phase and other treatment phases. Additionally, a higher NLR and RDW-CV at the second-line treatment and disease progression were associated with an increased risk of death (NLR at 2nd line: HR = 1.03, p = 0.029; RDW-CV at progression: HR = 1.14, p = 0.004). We proposed specific marker cut-offs that demonstrated significant associations with survival outcomes when applied to Kaplan–Meier survival curves (NLR at 2nd line < 5: p < 0.017; RDW-CV at progression < 15: p = 0.007). An elevated NLR and RDW-CV at later treatment stages correlated with poorer OS and PFS. No significant preoperative differences were detected. These biomarkers may serve as non-invasive tools for glioblastoma management. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis, Treatment and Prognosis of Glioblastoma)
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