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Brain Sciences
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Innovation in Brain Tumor Treatment
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Innovation in Brain Tumor Treatment

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neuro-oncology".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 4644

Special Issue Editor

Dr. Terry Lichtor

E-Mail Website1 Website2
Guest Editor
Department of Neurosurgery, Rush University Medical Center, Chicago, IL, USA
Interests: brain tumors; immunotherapy; Alzheimer’s disease; imaging
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A dramatic increase in knowledge regarding the molecular biology of brain has been established over the past few years.  Recent new avenues regarding the role of microRNAs along with further understanding of the importance of angiogenesis, immunotherapy, and explanations for the resistance of the tumors to radiation therapy have been developed.  Some improvements in surgical management issues including improvements in imaging along with issues concerning tumor induced epilepsy have been explored. 

Antigenic differences between normal and malignant cells of the cancer patient form the rationale for clinical immunotherapeutic strategies.  While the central nervous system has traditionally been thought of as an immune-privileged site, several studies have been conducted that demonstrate the potential efficacy of immunotherapy in management of primary and secondary brain tumors.  In addition, work has been done involving regulation of Immune checkpoint inhibitors which are capable of blocking molecules involved in inhibiting immune cells that can result in a stimulation of the T-cell response against various tumors including brain tumors.

The goal of cancer therapy is the elimination of every remaining tumor cell from the patient.  It is unlikely that a single form of therapy will be capable of achieving this goal.  For this special issue a review of novel and innovative treatments for these tumors is presented.  It is hopeful that new strategies will be efficacious in the treatment of these tumors.

Dr. Terry Lichtor
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. Brain Sciences 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 2200 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

  • brain tumors
  • gliomas
  • immunotherapy
  • angiogenesis
  • check-point inhibitors

Published Papers (4 papers)

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Research

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11 pages, 1170 KiB  
Communication
Gene Expression of GABAA Receptor Subunits and Association with Patient Survival in Glioma
by Rafael Badalotti, Matheus Dalmolin, Osvaldo Malafaia, Jurandir M. Ribas Filho, Rafael Roesler, Marcelo A. C. Fernandes and Gustavo R. Isolan
Brain Sci. 2024, 14(3), 275; https://doi.org/10.3390/brainsci14030275 - 14 Mar 2024
Viewed by 909
Abstract
Rapid neuronal inhibition in the brain is mediated by γ-aminobutyric acid (GABA) activation of GABAA receptors. The GABRA5 gene, which encodes the α5 subunit of the GABAA receptor, has been implicated in an aggressive subgroup of medulloblastoma (MB), a type of [...] Read more.
Rapid neuronal inhibition in the brain is mediated by γ-aminobutyric acid (GABA) activation of GABAA receptors. The GABRA5 gene, which encodes the α5 subunit of the GABAA receptor, has been implicated in an aggressive subgroup of medulloblastoma (MB), a type of pediatric brain tumor. However, the possible role of GABAA receptor subunits in glioma remains poorly understood. Here, we examined the expression of genes encoding GABAA receptor subunits in different types of glioma, and its possible association with patient prognosis assessed by overall survival (OS). Data were obtained from the French and The Cancer Genome Atlas Brain Lower Grade Glioma (TCGA-LGG) datasets and analyzed for expression of GABAA receptor subunit genes. OS was calculated using the Kaplan–Meier estimate. We found that genes GABRA2, GABRA3, GABRB3, GABRG1, and GABRG2 showed a significant association with OS, with higher gene expression indicating better prognosis. In patients with GBM, high expression of GABRA2 was associated with shorter OS, whereas, in contrast, higher levels of GABRB3 were associated with better prognosis indicated by longer OS. In patients with lower grade gliomas, GABRA3, GABRB3, GABRG1, and GABRG2, were associated with longer OS. High GABRB3 expression was related to longer survival when low grade glioma types were analyzed separately. Our results suggest an overall association between higher expression of most genes encoding GABAA receptor subunits and better prognosis in different types of glioma. Our findings support the possibility that down-regulation of GABAA receptors in glioma contributes to promoting tumor progression by reducing negative inhibition. These findings might contribute to further evaluation of GABAA receptors as a therapeutic target in glioma. Full article
(This article belongs to the Special Issue Innovation in Brain Tumor Treatment)
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16 pages, 11379 KiB  
Article
A Prediction Model for Deciphering Intratumoral Heterogeneity Derived from the Microglia/Macrophages of Glioma Using Non-Invasive Radiogenomics
by Yunyang Zhu, Zhaoming Song and Zhong Wang
Brain Sci. 2023, 13(12), 1667; https://doi.org/10.3390/brainsci13121667 - 01 Dec 2023
Viewed by 1001
Abstract
Microglia and macrophages play a major role in glioma immune responses within the glioma microenvironment. We aimed to construct a prognostic prediction model for glioma based on microglia/macrophage-correlated genes. Additionally, we sought to develop a non-invasive radiogenomics approach for risk stratification evaluation. Microglia/macrophage-correlated [...] Read more.
Microglia and macrophages play a major role in glioma immune responses within the glioma microenvironment. We aimed to construct a prognostic prediction model for glioma based on microglia/macrophage-correlated genes. Additionally, we sought to develop a non-invasive radiogenomics approach for risk stratification evaluation. Microglia/macrophage-correlated genes were identified from four single-cell datasets. Hub genes were selected via lasso–Cox regression, and risk scores were calculated. The immunological characteristics of different risk stratifications were assessed, and radiomics models were constructed using corresponding MRI imaging to predict risk stratification. We identified eight hub genes and developed a relevant risk score formula. The risk score emerged as a significant prognostic predictor correlated with immune checkpoints, and a relevant nomogram was drawn. High-risk groups displayed an active microenvironment associated with microglia/macrophages. Furthermore, differences in somatic mutation rates, such as IDH1 missense variant and TP53 missense variant, were observed between high- and low-risk groups. Lastly, a radiogenomics model utilizing five features from magnetic resonance imaging (MRI) T2 fluid-attenuated inversion recovery (Flair) effectively predicted the risk groups under a random forest model. Our findings demonstrate that risk stratification based on microglia/macrophages can effectively predict prognosis and immune functions in glioma. Moreover, we have shown that risk stratification can be non-invasively predicted using an MRI-T2 Flair-based radiogenomics model. Full article
(This article belongs to the Special Issue Innovation in Brain Tumor Treatment)
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13 pages, 2590 KiB  
Article
Effect of Different Timing of Local Brain Radiotherapy on Survival of EGFR-Mutated NSCLC Patients with Limited Brain Metastases
by Yu Wang, Shenghong Wu, Jing Li, Xiaohua Liang and Xinli Zhou
Brain Sci. 2023, 13(9), 1280; https://doi.org/10.3390/brainsci13091280 - 03 Sep 2023
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Abstract
(1) Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been the first line therapy for EGFR-mutant lung adenocarcinoma (LAC) patients with brain metastases (BMs). However, the role and the optimal time of brain radiotherapy remains controversial. We aimed to investigate [...] Read more.
(1) Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been the first line therapy for EGFR-mutant lung adenocarcinoma (LAC) patients with brain metastases (BMs). However, the role and the optimal time of brain radiotherapy remains controversial. We aimed to investigate the role of upfront brain stereotactic radiotherapy (SRS) and the impact of deferral radiotherapy on patients’ clinical outcomes. (2) Methods: We retrospectively studied 53 EGFR-mutant LAC patients with limited synchronous BMs between 2014 and 2020 at our institute. The limited BMs was defined with one to four BM lesions, with a maximal size of ≤4 cm. Patients were categorized into two groups: upfront brain SRS (upfront RT) and upfront TKIs. The intracranial progression-free survival (iPFS), progression-free survival (PFS), and overall survival (OS) between groups were analyzed. (3) Results: The median iPFS (21.0 vs. 12.0 months, p = 0.002) and PFS (20.0 vs. 11.0 months, p = 0.004) of the upfront RT group was longer than that of the upfront TKI group. There were no significant differences in median OS (30.0 vs. 26.0 months, p = 0.552) between the two groups. The upfront RT group is less likely to suffer from intracranial progression of the original sites than that of upfront TKIs during the disease course (36.1% vs. 0.0%, p = 0.025). Multivariate analysis showed that the Karnofsky Performance Scale and the presence of synchronous meningeal metastases were associated with overall survival. (4) Conclusions: Compared with upfront TKI, the combination of upfront SRS with TKIs can improve the iPFS and PFS in EGFR-mutant LAC with synchronous BMs. The addition of upfront brain SRS was useful for the original intracranial metastatic lesions. Full article
(This article belongs to the Special Issue Innovation in Brain Tumor Treatment)
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Review

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13 pages, 939 KiB  
Review
Cytokine Gene Vaccine Therapy for Treatment of a Brain Tumor
by Terry Lichtor, Bingtao Tang and Edward J. Roy
Brain Sci. 2023, 13(11), 1505; https://doi.org/10.3390/brainsci13111505 - 25 Oct 2023
Viewed by 1255
Abstract
A glioma is a malignant brain tumor with a poor prognosis. Attempts at the surgical removal of the tumor are the first approach, but additional treatment strategies, including radiation therapy and systemic or local chemotherapy, are necessary. Furthermore, the treatments are often associated [...] Read more.
A glioma is a malignant brain tumor with a poor prognosis. Attempts at the surgical removal of the tumor are the first approach, but additional treatment strategies, including radiation therapy and systemic or local chemotherapy, are necessary. Furthermore, the treatments are often associated with significant adverse side effects. Normal and malignant cells generally have antigenic differences, and this is the rationale for clinical immunotherapeutic strategies. Cytokines such as IL-15 or IL-2, which stimulate an anti-tumor immune response, have been shown to have a particularly high potential for use in immunotherapy against various tumors. In this review, treatments with either a poxvirus, genetically engineered to secrete IL-15, or allogeneic fibroblasts, transfected with tumor DNA and engineered to secrete IL-2, are shown to be effective strategies in extending the survival of mice with malignant brain tumors upon intracerebral injection of the treatment cells. Future studies with these treatment strategies in patients with intracerebral tumors are urgently needed. Full article
(This article belongs to the Special Issue Innovation in Brain Tumor Treatment)
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