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Cancers
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Past, Present, and Future Strategies in the Treatment and Management...
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Past, Present, and Future Strategies in the Treatment and Management of Gliomas

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 15 May 2024 | Viewed by 2186

Special Issue Editor

Prof. Dr. Alfredo Conti

E-Mail Website
Guest Editor
1. Unit of Neurosurgery, IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy
2. Department of Biomedical and Neuromotor Sciences, Alma Mater University of Bologna, Bologna, Italy
Interests: neurosurgery; neuro-oncology; brain mapping; radiosurgery; brain injury; vascular neurosurgery; neuro-imaging
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gliomas are the most common primary malignant brain tumors, approximately accounting for 25% of all central nervous system (CNS) neoplasms and 81% of the malignant counterparts. According to the World Health Organization (WHO) histological grading, gliomas are classified into two main categories, namely low-grade gliomas (LGG (WHO I-II)) and high-grade gliomas (HGG (WHO III-IV)), which are characterized by a distinct natural history, prognosis and management. HGGs are among the most aggressive neoplasms in humans, with a median survival time that rarely overcomes 2 years. Unfortunately, surgery is not curative in patients with diffuse gliomas; therefore, adjuvant therapy (chemotherapy and radiotherapy either alone or in association) represents a pivotal component of the standard therapeutical regimens, with different timings of application between LGGs and HGGs. However, it is well-known that the natural history of these neoplasms implies inevitable recurrences, in which the combination of surgery and systemic treatments provides unsatisfactory results in the achievement of effective long-term disease control. Intriguingly, the up-to-date version of the WHO classification of CNS tumors highlighted the significance of molecular biomarkers in guiding the taxonomy, diagnosis and clinical management of gliomas, opening the door for the exploration of new therapeutical strategies directed either at specific molecular targets or at the modulation of the tumoral environment and immune response through the administration of selective immunotherapies.

Undoubtedly, gliomas of all grades continue to represent an incurable life-limiting disease and an unmet clinical need to improve under several points of view. Improvement of our current knowledge of tumor biology and potential therapeutic targets, identification of biomarkers to detect patients who are at risk of earlier recurrence or more aggressive clinical course, new surgical techniques to achieve safer and more radical surgical resection, innovative radiotherapy and nuclear medicine approaches are all fields that need deeper investigation.

This Special Issue aims to gather groundbreaking research articles and updated reviews from experts in the fields of basic, translational, and clinical research of glioma. Emphasis will be placed on recent therapeutic advancements, but even cutting-edge research in tumor biology, biomarkers, and imaging will be welcome to complement this dedicated Special Issue.

Prof. Dr. Alfredo Conti
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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

  • glioma
  • surgery
  • radiosurgery
  • immunotherapy
  • tumor biology
  • tumor biomarkers

Published Papers (2 papers)

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Research

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28 pages, 6424 KiB  
Article
Transforming Growth Factor Beta 2 (TGFB2) mRNA Levels, in Conjunction with Interferon-Gamma Receptor Activation of Interferon Regulatory Factor 5 (IRF5) and Expression of CD276/B7-H3, Are Therapeutically Targetable Negative Prognostic Markers in Low-Grade Gliomas
by Vuong Trieu, Anthony E. Maida and Sanjive Qazi
Cancers 2024, 16(6), 1202; https://doi.org/10.3390/cancers16061202 - 19 Mar 2024
Viewed by 1236
Abstract
LGG tumors are characterized by a low infiltration of immune cells, requiring therapeutic interventions to boost the immune response. We conducted a study analyzing mRNA expression datasets from the UCSC Xena web platform. To screen for upregulated genes, we sought to compare normal [...] Read more.
LGG tumors are characterized by a low infiltration of immune cells, requiring therapeutic interventions to boost the immune response. We conducted a study analyzing mRNA expression datasets from the UCSC Xena web platform. To screen for upregulated genes, we sought to compare normal brain tissue with LGG tumor samples. We also used cBioportal to determine the relationship between mRNA expression levels of 513 LGG patients and their overall survival (OS) outcomes. Three tumor-associated macrophage (TAM) markers, MSR1/CD204, CD86, and CD68, exhibited a 6-fold (p < 0.0001), 8.9-fold (p < 0.0001), and 15.6-fold increase in mRNA expression levels, respectively, in LGG tumors. In addition, both TGFB1 (4.1-fold increase, p < 0.0001) and TGFB2 (2.2-fold increase, p < 0.0001) ligands were also upregulated in these tumors compared to normal brain tissue, suggesting that TGFB ligands are pivotal in establishing an immunosuppressive, angiogenic, and pro-tumorigenic TME in gliomas mediated through TAMs. In addition, mRNA upregulation of interferon-gamma receptors, IFNGR1 and IFNGR2, and the downstream signaling molecules STAT1, IRF1, and IRF5, pointed to an essential role for IFN-γ mediated remodeling of the TME. Interestingly, the mRNA expression of a tumor-associated antigen, CD276/B7-H3, showed a significant (p < 0.0001) 4.03-fold increase in tumor tissue, giving further insights into the roles of macrophages and tumor cells in supporting the immunosuppressive TME. Multivariate Cox proportional hazards models investigating the interaction of TGFB2 and activation of IFNGR2, STAT1, IRF1, or IRF5 showed that the prognostic impact of high mRNA levels (25th percentile cut-off) of TGFB2 was independent of IFNGR2, STAT1, IRF1, or IRF5 mRNA levels (TGFB2high HR (95% CI) = 4.07 (2.35–7.06), 6 (3.62–10.11), 4.38 (2.67–7.17), and 4.48 (2.82–7.12) for models with IFNGR2, STAT1, IRF1, or IRF5, respectively) and age at diagnosis. Patients with high levels of TGFB2 and IFNGR2 were over-represented by LGG patients with isocitrate dehydrogenase wild-type (IDHwt) mutation status. The prognostic impact of high levels of TGFB2 and IDH wild-type observed by the increases in hazard ratios for TGFB2 (HR (95% CI range) = 2.02 (1.05–3.89)) and IDH wild-type (HR (95% CI range) = 4.44 (1.9–10.4)) were independent predictors of survival, suggesting that risk stratification of patients identifies LGG patients with IDH wild-type and high levels of TGFB2 in the design of clinical trials. Furthermore, we have additional IRF5 and CD276/B7-H3 as prognostic markers that can also be targeted for combination therapies with TGFB2 inhibitors. In support of these findings, we demonstrated that low levels of gene methylation in TGFB2, IFNGR2, IRF1, IRF5, STAT1, and CD276 were associated with significantly worse overall survival (OS) outcomes. This suggests that potential mechanisms to increase the expression of these prognostic markers occur via the action of demethylation enzymes. Full article
(This article belongs to the Special Issue Past, Present, and Future Strategies in the Treatment and Management of Gliomas)
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Review

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14 pages, 887 KiB  
Review
Awake Craniotomy for Gliomas in the Non-Dominant Right Hemisphere: A Comprehensive Review
by Dilshod Muhammadvalievich Mamadaliev, Ryuta Saito, Kazuya Motomura, Fumiharu Ohka, Gianluca Scalia, Giuseppe Emmanuele Umana, Alfredo Conti and Bipin Chaurasia
Cancers 2024, 16(6), 1161; https://doi.org/10.3390/cancers16061161 - 15 Mar 2024
Cited by 1 | Viewed by 593
Abstract
Awake surgery has become a standard practice for managing diffuse low-grade gliomas (LGGs), particularly in eloquent brain areas, and is established as a gold standard technique for left-dominant-hemisphere tumors. However, the intraoperative monitoring of functions in the right non-dominant hemisphere (RndH) is often [...] Read more.
Awake surgery has become a standard practice for managing diffuse low-grade gliomas (LGGs), particularly in eloquent brain areas, and is established as a gold standard technique for left-dominant-hemisphere tumors. However, the intraoperative monitoring of functions in the right non-dominant hemisphere (RndH) is often neglected, highlighting the need for a better understanding of neurocognitive testing for complex functions in the right hemisphere. This article aims to comprehensively review the current literature on the benefits of awake craniotomy in gliomas of the non-dominant right hemisphere. A systematic review was conducted using the PubMed and ScienceDirect databases with keywords such as “right hemisphere”, “awake surgery”, “direct electrical brain stimulation and mapping”, and “glioma”. The search focused on anatomical and surgical aspects, including indications, tools, and techniques of awake surgery in right cerebral hemisphere gliomas. The literature search identified 74 sources, including original articles, books, monographs, and review articles. Two papers reported large series of language assessment cases in 246 patients undergoing awake surgery with detailed neurological semiology and mapping techniques, while the remaining studies were predominantly neuroradiological and neuroimaging in nature. Awake craniotomy for non-dominant-hemisphere gliomas is an essential tool. The term “non-dominant” should be revised, as this hemisphere contributes significantly to essential cognitive functions in the human brain. Full article
(This article belongs to the Special Issue Past, Present, and Future Strategies in the Treatment and Management of Gliomas)
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