10th Anniversary of Biomedicines—Novel Targets for Cranial Tumors

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

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 11108

Special Issue Editors


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Guest Editor
Department of Neurosurgery, S. Anna University Hospital, 44124 Ferrara, Italy
Interests: neuro-oncology; neurotrauma; spine surgery

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Guest Editor
Department of Neuroscience DINOGMI, University of Genova, Genova, Italy
Interests: neuro-oncology; glioma

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Guest Editor
Department of Morphology, Surgery & Experimental Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy
Interests: translational research; gender medicine; regenerative medicine; personalized and precision medicine; focus on inflammation and biomarkers in cardiovascular and complex diseases; aging; neurodegenerative/cognitive impairment diseases
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Guest Editor
Department of Internal Medicine (DiMI), Università degli Studi di Genova, 16132 Genoa, Italy
Interests: pharmacology of antitumor drugs; drug repositioning; cancer stem cells; 3D tumor models

Special Issue Information

Dear Colleagues,

Intracranial tumors may arise from the brain or other structures, such as the meninges, cranial nerves, and pituitary gland. The peculiarity of these tumors is that histologically benign neoplasms can also be life threatening, due to the non-expandability of the intracranial system.

The treatment options for intracranial tumors have not significantly changed over the last 20 years; surgery (from biopsy to total resection) still represents the primary option for both benign and malign neoplasms, with the exception of some pituitary adenomas. Despite advances in technology and knowledge, prognosis has not dramatically changed either.

The identification of novel potential targets for therapy and diagnosis is therefore strongly needed.

This Special Issue aims to collect original papers demonstrating possible novel targets for diagnosing or treating intracranial tumors, including, but not limited to, gliomas, schwannomas, meningiomas, pituitary adenomas, and metastases.

Prof. Dr. Pasquale De Bonis
Prof. Dr. Gianluigi Zona
Dr. Veronica Tisato
Prof. Dr. Tullio Florio
Guest Editors

Manuscript Submission Information

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Keywords

  • intracranial tumor
  • pituitary adenoma
  • biomarkers
  • targeted therapy
  • novel targets

Related Special Issue

Published Papers (5 papers)

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Research

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16 pages, 3162 KiB  
Article
Nerve Growth Factor, Antimicrobial Peptides and Chemotherapy: Glioblastoma Combination Therapy to Improve Their Efficacy
by Alexandr Chernov, Igor Kudryavtsev, Aleksei Komlev, Diana Alaverdian, Anna Tsapieva, Elvira Galimova and Olga Shamova
Biomedicines 2023, 11(11), 3009; https://doi.org/10.3390/biomedicines11113009 - 9 Nov 2023
Cited by 1 | Viewed by 1095
Abstract
Glioblastoma (GBM) is an aggressive and lethal malignancy of the central nervous system with a median survival rate of 15 months. We investigated the combined anticancer effects of nerve growth factor (NGF), cathelicidin (LL-37), and protegrin-1 (PG-1) with chemotherapy (temozolomide, doxorubicin, carboplatin, cisplatin, [...] Read more.
Glioblastoma (GBM) is an aggressive and lethal malignancy of the central nervous system with a median survival rate of 15 months. We investigated the combined anticancer effects of nerve growth factor (NGF), cathelicidin (LL-37), and protegrin-1 (PG-1) with chemotherapy (temozolomide, doxorubicin, carboplatin, cisplatin, and etoposide) in the glioblastoma U251 cell line to overcome the limitations of conventional chemotherapy and to guarantee specific treatments to succeed. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to study cell viability and to determine the cytotoxic effects of NGF, LL-37, and PG-1 and their combination with chemotherapy in U251 cells. Synergism or antagonism was determined using the combination index (CI) method. Caspase-3 activity was evaluated spectrophotometrically using a caspase-3 activity assay kit. Apoptosis was analyzed with flow cytometry using propidium iodide (PI) and YO-PRO-1. NGF and the peptides showed a strong cytotoxic effect on U251 glioma cells in the MTT test (IC50 0.0214, 3.1, and 26.1 μM, respectively) compared to chemotherapy. The combination of PG-1 + etoposide had a synergistic effect on apoptosis of U251 glioma cells. It should be noted that the cells were in the early and late stages of apoptosis, respectively, compared with the control cells. The caspase-3 activation analysis revealed that the caspase-3 level was not significantly (p > 0.05) increased in U251 cells following PG-1 with etoposide treatment compared with that in the untreated cells, suggesting that the combination of PG-1 and etoposide may induce caspase-independent apoptosis in U251 cells. NGF, LL-37, and PG-1 represent promising drug candidates as the treatment regimen for GBM. Furthermore, the synergistic efficacy of the combined protocol using PG-1 and etoposide may overcome some of the typical limitations of the conventional therapeutic protocols, thus representing a promising approach for GBM therapy. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Novel Targets for Cranial Tumors)
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15 pages, 2418 KiB  
Article
Whole Exome Sequencing Identifies PHF14 Mutations in Neurocytoma and Predicts Responsivity to the PDGFR Inhibitor Sunitinib
by Dongyun Zhang, William H. Yong, Masoud Movassaghi, Fausto J. Rodriguez, Issac Yang, Paul McKeever, Jiang Qian, Jian Yi Li, Qinwen Mao, Kathy L. Newell, Richard M. Green, Cynthia T. Welsh and Anthony P. Heaney
Biomedicines 2022, 10(11), 2842; https://doi.org/10.3390/biomedicines10112842 - 8 Nov 2022
Cited by 2 | Viewed by 2504
Abstract
Neurocytomas are rare low-grade brain tumors predominantly affecting young adults, but their cellular origin and molecular pathogenesis is largely unknown. We previously reported a sellar neurocytoma that secreted excess arginine vasopressin causing syndrome of inappropriate anti-diuretic hormone (SIADH). Whole exome sequencing in 21 [...] Read more.
Neurocytomas are rare low-grade brain tumors predominantly affecting young adults, but their cellular origin and molecular pathogenesis is largely unknown. We previously reported a sellar neurocytoma that secreted excess arginine vasopressin causing syndrome of inappropriate anti-diuretic hormone (SIADH). Whole exome sequencing in 21 neurocytoma tumor tissues identified somatic mutations in the plant homeodomain finger protein 14 (PHF14) in 3/21 (14%) tumors. Of these mutations, two were missense mutations and 4 caused splicing site losses, resulting in PHF14 dysfunction. Employing shRNA-mediated knockdown and CRISPR/Cas9-based knockout approaches, we demonstrated that loss of PHF14 increased proliferation and colony formation in five different human, mouse and rat mesenchymal and differentiated cell lines. Additionally, we demonstrated that PHF14 depletion resulted in upregulation of platelet derived growth factor receptor-alpha (PDGFRα) mRNA and protein in neuroblastoma SHSY-5Y cells and led to increased sensitivity to treatment with the PDGFR inhibitor Sunitinib. Furthermore, in a neurocytoma primary culture harboring splicing loss PHF14 mutations, overexpression of wild-type PHF14 and sunitinib treatment inhibited cell proliferation. Nude mice, inoculated with PHF14 knockout SHSY-5Y cells developed earlier and larger tumors than control cell-inoculated mice and Sunitinib administration caused greater tumor suppression in mice harboring PHF-14 knockout than control SHSY-5Y cells. Altogether our studies identified mutations of PHF14 in 14% of neurocytomas, demonstrate it can serve as an alternative pathway for certain cancerous behavior, and suggest a potential role for Sunitinib treatment in some patients with residual/recurrent neurocytoma. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Novel Targets for Cranial Tumors)
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Review

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21 pages, 1959 KiB  
Review
From Genes to Therapy: Pituitary Adenomas in the Era of Precision Medicine
by Corneliu Toader, Nicolaie Dobrin, Catalina-Ioana Tataru, Razvan-Adrian Covache-Busuioc, Bogdan-Gabriel Bratu, Luca Andrei Glavan, Horia Petre Costin, Antonio Daniel Corlatescu, David-Ioan Dumitrascu and Alexandru Vlad Ciurea
Biomedicines 2024, 12(1), 23; https://doi.org/10.3390/biomedicines12010023 (registering DOI) - 21 Dec 2023
Cited by 1 | Viewed by 1458
Abstract
This review presents a comprehensive analysis of pituitary adenomas, a type of brain tumor with diverse behaviors and complexities. We cover various treatment approaches, including surgery, radiotherapy, chemotherapy, and their integration with newer treatments. Key to the discussion is the role of biomarkers [...] Read more.
This review presents a comprehensive analysis of pituitary adenomas, a type of brain tumor with diverse behaviors and complexities. We cover various treatment approaches, including surgery, radiotherapy, chemotherapy, and their integration with newer treatments. Key to the discussion is the role of biomarkers in oncology for risk assessment, diagnosis, prognosis, and the monitoring of pituitary adenomas. We highlight advances in genomic, epigenomic, and transcriptomic analyses and their contributions to understanding the pathogenesis and molecular pathology of these tumors. Special attention is given to the molecular mechanisms, including the impact of epigenetic factors like histone modifications, DNA methylation, and transcriptomic changes on different subtypes of pituitary adenomas. The importance of the tumor immune microenvironment in tumor behavior and treatment response is thoroughly analyzed. We highlight potential breakthroughs and innovations for a more effective management and treatment of pituitary adenomas, while shedding light on the ongoing need for research and development in this field to translate scientific knowledge into clinical advancements, aiming to improve patient outcomes. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Novel Targets for Cranial Tumors)
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21 pages, 1559 KiB  
Review
Antitumor Potential of Antiepileptic Drugs in Human Glioblastoma: Pharmacological Targets and Clinical Benefits
by Manuela Stella, Giammarco Baiardi, Stefano Pasquariello, Fabio Sacco, Irene Dellacasagrande, Alessandro Corsaro, Francesca Mattioli and Federica Barbieri
Biomedicines 2023, 11(2), 582; https://doi.org/10.3390/biomedicines11020582 - 16 Feb 2023
Cited by 5 | Viewed by 3020
Abstract
Glioblastoma (GBM) is characterized by fast-growing cells, genetic and phenotypic heterogeneity, and radio-chemo-therapy resistance, contributing to its dismal prognosis. Various medical comorbidities are associated with the natural history of GBM. The most disabling and greatly affecting patients’ quality of life are neurodegeneration, cognitive [...] Read more.
Glioblastoma (GBM) is characterized by fast-growing cells, genetic and phenotypic heterogeneity, and radio-chemo-therapy resistance, contributing to its dismal prognosis. Various medical comorbidities are associated with the natural history of GBM. The most disabling and greatly affecting patients’ quality of life are neurodegeneration, cognitive impairment, and GBM-related epilepsy (GRE). Hallmarks of GBM include molecular intrinsic mediators and pathways, but emerging evidence supports the key role of non-malignant cells within the tumor microenvironment in GBM aggressive behavior. In this context, hyper-excitability of neurons, mediated by glutamatergic and GABAergic imbalance, contributing to GBM growth strengthens the cancer-nervous system crosstalk. Pathogenic mechanisms, clinical features, and pharmacological management of GRE with antiepileptic drugs (AEDs) and their interactions are poorly explored, yet it is a potentially promising field of research in cancer neuroscience. The present review summarizes emerging cooperative mechanisms in oncogenesis and epileptogenesis, focusing on the neuron-to-glioma interface. The main effects and efficacy of selected AEDs used in the management of GRE are discussed in this paper, as well as their potential beneficial activity as antitumor treatment. Overall, although still many unclear processes overlapping in GBM growth and seizure onset need to be elucidated, this review focuses on the intriguing targeting of GBM-neuron mutual interactions to improve the outcome of the so challenging to treat GBM. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Novel Targets for Cranial Tumors)
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Other

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12 pages, 982 KiB  
Brief Report
Next-Generation Sequencing Comparative Analysis of DNA Mutations between Blood-Derived Extracellular Vesicles and Matched Cancer Tissue in Patients with Grade 4 Glioblastoma
by Paolo Rosa, Elena De Falco, Luca Pacini, Amedeo Piazza, Paolo Ciracì, Luca Ricciardi, Francesco Fiorentino, Sokol Trungu, Massimo Miscusi, Antonino Raco and Antonella Calogero
Biomedicines 2022, 10(10), 2590; https://doi.org/10.3390/biomedicines10102590 - 15 Oct 2022
Cited by 2 | Viewed by 2127
Abstract
The biological heterogeneity of glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4), the most aggressive type of brain cancer, is a critical hallmark, caused by changes in the genomic mutational asset and influencing clinical progression over time. The understanding and monitoring of the mutational [...] Read more.
The biological heterogeneity of glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4), the most aggressive type of brain cancer, is a critical hallmark, caused by changes in the genomic mutational asset and influencing clinical progression over time. The understanding and monitoring of the mutational profile is important not only to reveal novel therapeutic targets in this set of patients, but also to ameliorate the clinical stratification of subjects and the prognostic significance. As neurosurgery represents the primary technique to manage GBM, it is of utmost importance to optimize alternative and less invasive methods to monitor the dynamic mutation profile of these patients. Extracellular vesicles (EVs) are included in the liquid biopsy analysis and have emerged as the biological mirror of escaping and surviving mechanisms by many tumors, including glioblastoma. Very few studies have investigated the technical feasibility to detect and analyze the genomic profile by Next-Generation Sequencing (UMI system) in circulating EVs of patients with grade IV glioblastoma. Here, we attempted to characterize and to compare the corresponding matched tissue samples and potential variants with pathogenic significance of the DNA contained in peripheral-blood-derived EVs. The NGS analysis has revealed that patients with grade IV glioblastoma exhibited lesser DNA content in EVs than controls and that, both in EVs and matched cancer tissues, the NF1 gene was consistently mutated in all patients, with the c.2568C>G as the most common pathogenic variant expressed. This study supports the clinical utility of circulating EVs in glioblastoma as an eligible tool for personalized medicine. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Novel Targets for Cranial Tumors)
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