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Discovering Glioblastoma: From Diagnosis to Treatment

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 10404

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Special Issue Editors

Prof. Dr. Giuseppe Lombardi

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Guest Editor

Department of Oncology, Oncology 1, Veneto Institute of Oncology-IRCCS, 35128 Padua, Italy
Interests: neuro-oncology; glioblastoma; gliomas; targeted therapy; brain tumors; immunotherapy; quality of life
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Marta Scorsetti

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Guest Editor

1. Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, Milan, Italy
2. Department of Biomedical Sciences, Humanitas University, Milan, Italy
Interests: radiotherapy; radiosurgery; glioblastoma; neuro-oncology; glioma; targeted therapy; clinical and translational research in neuro-oncology

Prof. Dr. Francois Ducray

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Guest Editor

1. Lyon's Cancer Research Center (CRCL), UMR Inserm 1052 – CNRS 5286, Lyon, France
2. Hospices Civils de Lyon, Hôpital Neurologique, Service de Neuro-oncologie, Lyon, France
Interests: glioblastoma; neuro-oncology; glioma; clinical and translational research in neuro-oncology

Dr. Evangelia D. Razis

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Guest Editor

Medical Oncology 3, Hygeia Hospital, Athens, Greece
Interests: glioblastoma; neuro-oncology; targeted therapy; translational research; breast cancer brain metastases

Special Issue Information

Dear Colleagues,

Glioblastoma represents the most frequent and aggressive malignant primary brain tumor in adults. Despite growing knowledge of the molecular changes responsible for tumor development, glioblastoma remains a neoplasm with unmet medical needs and its prognosis still remains poor. Median overall survival of glioblastoma patients is about 15 months; only 3–5% of patients are alive after five years from diagnosis and, theoretically, all patients relapse. Therefore, it appears to be very important to characterize the tumor both at diagnosis and at recurrence with advanced imaging, such as MR spectroscopy and positron emission tomography, and analyze molecular alterations.

It is noteworthy that molecular alterations could represent important prognostic factors and specific targets for precision medicine trials in primary and recurrent glioblastoma. In the last few years, many translational and clinical studies have been performed, and new treatments with targeted therapy such as precision medicine, immunotherapy and their combination are ongoing.

This Special Issue will cover all aspects of glioblastoma, including original research on advanced imaging, molecular characteristics, current and experimental treatment options, supportive care, neurocognitive functions, and quality of life. Expert opinions, systematic reviews, and meta-analyses are also welcome.

Prof. Dr. Giuseppe Lombardi
Prof. Dr. Marta Scorsetti
Prof. Dr. Francois Ducray
Dr. Evangelia D. Razis
Guest Editors

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

glioblastoma
immunotherapy
targeted therapy
immunotherapy
personalized medicine
glioma

Published Papers (5 papers)

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Research

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15 pages, 3461 KiB

Open AccessArticle

Reticulocalbin 3 Is a Novel Mediator of Glioblastoma Progression

by Yi He, Salvador Alejo, Jessica D. Johnson, Sridharan Jayamohan and Gangadhara R. Sareddy

Cancers 2023, 15(7), 2008; https://doi.org/10.3390/cancers15072008 - 28 Mar 2023

Viewed by 1696

Abstract

Glioblastoma is the most common malignant primary brain tumor. Molecular mechanisms underlying the pathobiology of glioblastoma are incompletely understood, emphasizing an unmet need for the identification of new therapeutic candidates. Reticulocalbin 3 (RCN3), an ER lumen-residing Ca²⁺ binding protein, plays an essential role in protein biosynthesis processes via the secretory pathway. Emerging studies demonstrated that RCN3 is a target for therapeutic intervention in various diseases. However, a knowledge gap exists about whether RCN3 plays a role in glioblastoma. Publicly available datasets suggest RCN3 is overexpressed in glioblastoma and portends poor survival rates. The knockdown or knockout of RCN3 using shRNA or CRISPR/Cas9 gRNA, respectively, significantly reduced proliferation, neurosphere formation, and self-renewal of GSCs. The RNA-seq studies showed downregulation of genes related to translation, ribosome, and cytokine signaling and upregulation of genes related to immune response, stem cell differentiation, and extracellular matrix (ECM) in RCN3 knockdown cells. Mechanistic studies using qRT-PCR showed decreased expression of ribosomal and increased expression of ER stress genes. Further, in silico analysis of glioblastoma patient datasets showed RCN3 expression correlated with the ribosome, ECM, and immune response pathway genes. Importantly, the knockdown of RCN3 using shRNA significantly enhanced the survival of tumor-bearing mice in orthotopic glioblastoma models. Our study suggests that RCN3 could be a potential target for the development of a therapeutic intervention in glioblastoma. Full article

(This article belongs to the Special Issue Discovering Glioblastoma: From Diagnosis to Treatment)

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15 pages, 2003 KiB

Open AccessArticle

Far-Red Fluorescent Murine Glioma Model for Accurate Assessment of Brain Tumor Progression

by Tatiana A. Mishchenko, Irina V. Balalaeva, Maria O. Klimenko, Anna A. Brilkina, Nina N. Peskova, Evgenii L. Guryev, Dmitri V. Krysko and Maria V. Vedunova

Cancers 2022, 14(15), 3822; https://doi.org/10.3390/cancers14153822 - 6 Aug 2022

Cited by 1 | Viewed by 1969

Abstract

Glioma is the most common brain tumor, for which no significant improvement in life expectancy and quality of life is yet possible. The creation of stable fluorescent glioma cell lines is a promising tool for in-depth studies of the molecular mechanisms of glioma initialization and pathogenesis, as well as for the development of new anti-cancer strategies. Herein, a new fluorescent glioma GL261-kat cell line stably expressing a far-red fluorescent protein (TurboFP635; Katushka) was generated and characterized, and then validated in a mouse orthotopic glioma model. By using epi-fluorescence imaging, we detect the fluorescent glioma GL261-kat cells in mice starting from day 14 after the inoculation of glioma cells, and the fluorescence signal intensity increases as the glioma progresses. Tumor growth is confirmed by magnetic resonance imaging and histology. A gradual development of neurological deficit and behavioral alterations in mice is observed during glioma progression. In conclusion, our results demonstrate the significance and feasibility of using the novel glioma GL261-kat cell line as a model of glioma biology, which can be used to study the initialization of glioma and monitor its growth by lifetime non-invasive tracking of glioma cells, with the prospect of monitoring the response to anti-cancer therapy. Full article

(This article belongs to the Special Issue Discovering Glioblastoma: From Diagnosis to Treatment)

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13 pages, 995 KiB

Open AccessArticle

Definition of the Prognostic Role of MGMT Promoter Methylation Value by Pyrosequencing in Newly Diagnosed IDH Wild-Type Glioblastoma Patients Treated with Radiochemotherapy: A Large Multicenter Study

by Mario Caccese, Matteo Simonelli, Veronica Villani, Simona Rizzato, Tamara Ius, Francesco Pasqualetti, Marco Russo, Roberta Rudà, Rosina Amoroso, Luisa Bellu, Roberta Bertorelle, Francesco Cavallin, Angelo Dipasquale, Mariantonia Carosi, Stefano Pizzolitto, Daniela Cesselli, Pasquale Persico, Beatrice Casini, Matteo Fassan, Vittorina Zagonel and Giuseppe Lombardi Show full author list Hide full author list

Cancers 2022, 14(10), 2425; https://doi.org/10.3390/cancers14102425 - 13 May 2022

Cited by 7 | Viewed by 2249

Abstract

Background. O⁶-methylguanine (O⁶-MeG)-DNA methyltransferase (MGMT) methylation status is a predictive factor for alkylating treatment efficacy in glioblastoma patients, but its prognostic role is still unclear. We performed a large, multicenter study to evaluate the association between MGMT methylation value and survival. Methods. We evaluated glioblastoma patients with an assessment of MGMT methylation status by pyrosequencing from nine Italian centers. The inclusion criteria were histological diagnosis of IDH wild-type glioblastoma, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≤2, and radio-chemotherapy treatment with temozolomide. The relationship between OS and MGMT was investigated with a time-dependent Receiver Operating Characteristics (ROC) curve and Cox regression models. Results. In total, 591 newly diagnosed glioblastoma patients were analyzed. The median OS was 16.2 months. The ROC analysis suggested a cut-off of 15% for MGMT methylation. The 2-year Overall Survival (OS) was 18.3% and 51.8% for MGMT methylation <15% and ≥15% (p < 0.0001). In the multivariable analysis, MGMT methylation <15% was associated with impaired survival (p < 0.00001). However, we also found a non-linear association between MGMT methylation and OS (p = 0.002): median OS was 14.8 months for MGMT in 0–4%, 18.9 months for MGMT in 4–40%, and 29.9 months for MGMT in 40–100%. Conclusions. Our findings suggested a non-linear relationship between OS and MGMT promoter methylation, which implies a varying magnitude of prognostic effect across values of MGMT promoter methylation by pyrosequencing in newly diagnosed IDH wild-type glioblastoma patients treated with chemoradiotherapy. Full article

(This article belongs to the Special Issue Discovering Glioblastoma: From Diagnosis to Treatment)

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15 pages, 1847 KiB

Open AccessArticle

Impact of Levetiracetam Treatment on 5-Aminolevulinic Acid Fluorescence Expression in IDH1 Wild-Type Glioblastoma

by Johannes Wach, Ági Güresir, Motaz Hamed, Hartmut Vatter, Ulrich Herrlinger and Erdem Güresir

Cancers 2022, 14(9), 2134; https://doi.org/10.3390/cancers14092134 - 25 Apr 2022

Cited by 2 | Viewed by 1623

Abstract

The amino acid 5-aminolevulinic acid (5-ALA) is the most established neurosurgical fluorescent dye and facilitates the achievement of gross total resection. In vitro studies raised concerns that antiepileptic drugs (AED) reduce the quality of fluorescence. Between 2013 and 2018, 175 IDH1 wild-type glioblastoma (GB) patients underwent 5-ALA guided surgery. Patients’ data were retrospectively reviewed regarding demographics, comorbidities, medications, tumor morphology, neuropathological characteristics, and their association with intraoperative 5-ALA fluorescence. The fluorescence of 5-ALA was graded in a three point scaling system (grade 0 = no; grade 1 = weak; grade 2 = strong). Univariable analysis shows that the intake of dexamethasone or levetiracetam, and larger preoperative tumor area significantly reduce the intraoperative fluorescence activity (fluorescence grade: 0 + 1). Multivariable binary logistic regression analysis demonstrates the preoperative intake of levetiracetam (adjusted odds ratio: 12.05, 95% confidence interval: 3.91–37.16, p = 0.001) as the only independent and significant risk factor for reduced fluorescence quality. Preoperative levetiracetam intake significantly reduced intraoperative fluorescence. The indication for levetiracetam in suspected GB should be carefully reviewed and prophylactic treatment avoided for this tumor entity. Future comparative trials of neurosurgical fluorescent dyes need a special focus on the influence of levetiracetam on fluorescence intensity. Further trials must validate our findings. Full article

(This article belongs to the Special Issue Discovering Glioblastoma: From Diagnosis to Treatment)

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Review

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26 pages, 2407 KiB

Open AccessReview

Metabolomic and Lipidomic Profiling of Gliomas—A New Direction in Personalized Therapies

by Magdalena Gaca-Tabaszewska, Joanna Bogusiewicz and Barbara Bojko

Cancers 2022, 14(20), 5041; https://doi.org/10.3390/cancers14205041 - 14 Oct 2022

Cited by 5 | Viewed by 1677

Abstract

In addition to being the most common primary brain tumor, gliomas are also among the most difficult to diagnose and treat. At present, the “gold standard” in glioma treatment entails the surgical resection of the largest possible portion of the tumor, followed by temozolomide therapy and radiation. However, this approach does not always yield the desired results. Additionally, the ability to cross the blood-brain barrier remains a major challenge for new potential drugs. Thus, researchers continue to search for targeted therapies that can be individualized based on the specific characteristics of each case. Metabolic and lipidomic research may represent two of the best ways to achieve this goal, as they enable detailed insights into the changes in the profile of small molecules in a biological system/specimen. This article reviews the new approaches to glioma therapy based on the analysis of alterations to biochemical pathways, and it provides an overview of the clinical results that may support personalized therapies in the future. Full article

(This article belongs to the Special Issue Discovering Glioblastoma: From Diagnosis to Treatment)

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