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Peer-reviewed articles, conference papers and reports by Net4Brain members — with DOIs and full-text PDFs.

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Browse the Action's publications — filter by year or publication type.

Showing 8 of 8 publications

Journal Article2026

Brain Cancer: Molecular Alterations and Emerging Trends in Neuropharmacology

Beata Leskova, Ilaria D'Agostino, Simona Mattova, Nicol Urbanska, Alzbeta Blicharova, Patrik Simko, Aylin Toplu, Muhammet Karaman, Terezia Kiskova-Simkova

International Journal of Molecular Sciences

Central nervous system (CNS) tumors represent a heterogeneous group of neoplasms associated with significant morbidity and mortality despite their relatively low incidence. Advances in the fifth edition of the World Health Organization (WHO) classification have emphasized the integration of histopathological, immunohistochemical, and molecular features, fundamentally transforming diagnostic and prognostic frameworks in neuro-oncology. This manuscript aims to provide an overview of CNS tumor biology, focusing on key diagnostic markers, genetic and epigenetic alterations, and emerging therapeutic strategies. It further describes recent advances in multi-omics approaches and artificial intelligence, which enable deeper characterization of tumor heterogeneity and support the development of precision medicine strategies. Finally, current and emerging therapeutic modalities, including combination therapies, targeted treatments, and novel molecular targets, are examined with emphasis on overcoming resistance mechanisms and improving clinical outcomes. Overall, the integration of molecular biology, advanced diagnostics, and innovative therapeutic approaches represents a critical step toward personalized management of CNS tumors and improved patient survival.

Journal Article2026

Exploring glioblastoma microenvironment using organoids: opportunities, limitations, and emerging concepts

Anuja Lipsa, Gaëlle Triballier, Anna Golebiewska

ELSEVIER

Glioblastoma (GBM) remains the most lethal primary brain tumor in adults. These aggressive tumors evolve as dynamic, spatially organized ecosystems in which tumor cells continuously interact with the surrounding brain parenchyma and systemic environment. These reciprocal interactions actively drive invasion, therapeutic resistance, and ultimately, inevitable recurrence. Modelling this level of complexity has long required significant compromise. GBM organoids have emerged as a promising intermediate platform, bridging the gap between costly, low-throughput animal models and overly simplistic two-dimensional in vitro cultures. In this review, we summarize the diverse protocols currently used for GBM organoid derivation and long-term maintenance, focusing on the recapitulation of microenvironmental traits. We further discuss how these systems enable the investigation of tumor niche architecture and dynamic crosstalk with key components of the tumor microenvironment, including neural and immune elements, vascular-associated signals, and extracellular matrix cues. Although the inherent limitations of ex vivo systems must be carefully considered, increasingly advanced and well-designed protocols will enable robust interrogation of interactions within the GBM ecosystem and provide powerful platforms for therapeutic testing.

Journal Article2026

COST action CA22103 Net4Brain: Pan-European network advancing translational research in brain cancer

Terezia Kiskova-Simkova, Patrik Simko, Milica Pešić, Annalisa Occhipinti, Barbara Breznik, Anna Golebiewska, Alkinoos Athanasiou, Theodora Gazea, Aida Hajdarpasic, Thomas Booth, Tugba Bagci Onder, Yasin Kaymaz, Claudio Angione, Uchenna Ngameduru, Radim Jancalek, Xinzhong Li

ELSEVIER

Brain and central nervous system cancers remain the deadliest forms of cancer, with limited improvement in survival following treatment. The Net4Brain COST Action (CA22103) addresses the urgent need for coordinated and multidisciplinary approaches to understand the pathogenesis, optimize early diagnosis, and personalize treatment strategies. Net4Brain unites a pan-European network of experts in basic and clinical neuroscience, oncology, molecular biology, data science and bioengineering. Through five thematic Working Groups (WGs), innovative Young Researchers Group and one dissemination WG, supported by Creative Group, the Action focuses on non-invasive biomarker discovery, preclinical modeling, tumor profiling, computational modeling, and treatment optimization. This initiative supports collaborative research, capacity building, and the development of a shared pan-European brain cancer centralized virtual database and biobank. Progress has been made in standardizing biomarker discovery, building innovative advanced preclinical models, and fostering integration of omics and imaging data for clinical applications. Net4Brain overcomes existing fragmentation in brain cancer research by providing a transdisciplinary platform for research and development, innovation, dissemination, and training, ultimately aiming to improve diagnostic accuracy, therapeutic outcomes, and patient quality of life. It also builds critical mass of knowledge/experts in the field of brain cancer and neuro-oncology.

Journal Article2026

Bridging modalities with AI: a review of AI advances in multimodal biomedical imaging

Le Minh Thao Doan, Kaveh Shahhosseini, Suraj Verma, Abdolreza Marefat, Giorgio Locicero, Sneha Verma, Claudio Angione, Annalisa Occhipinti

communications engineering

The rapid evolution of AI has facilitated innovative solutions in analysing different biomedical imaging modalities. By leveraging the complementary information from each modality, multimodal AI solutions have shown a huge potential to go beyond human capabilities and offer advances in bioimaging. At the same time, new foundation models and transformer-based architectures are now poised to address unsolved challenges in this field. This review aims to explore and discuss the state-of-the-art AI techniques applied in multimodal biomedical imaging, presenting the key challenges and future directions. We discuss several integration strategies to combine multiple biomedical imaging data types. We also focus on methods to overcome the open challenges related to data quality, model interpretability, and ethical implications.

Journal Article2026

Case Report: Rare presentation of spinal meningioma in Kosovo

Flamur Hasimi, Fjolla Ymeri

Open Research Europe

This case report outlines the diagnosis and management of a spinal meningioma in an 18-year-old female presenting with progressive weakness in both lower limbs. Magnetic resonance imaging revealed an intradural extramedullary tumour compressing the spinal cord, subsequently confirmed as a meningioma. Urgent neurosurgical intervention was performed, involving total laminectomy at the TH6/7 vertebral level and meticulous tumour resection. Postoperatively, the patient demonstrated significant neurological improvement, with muscle strength increasing from 2/5 to 4/5. This case highlights the importance of prompt diagnosis, multidisciplinary management, and close postoperative monitoring in achieving favourable outcomes for spinal meningiomas.

Journal Article2026

Integrating computational fluid dynamics into organ-on-chip systems: a glioblastoma-centred design and validation framework

Hooman Taleban, Xinzhong Li, Zulfiqur Ali, Karunakaran Kalesh, Jai Prakash, Tugba Bagci-Onder, Barbara Breznik

Frontiers in Bioengineering and Biotechnology

Glioblastoma (GBM) remains one of the most lethal and treatment-resistant brain cancers, driven in part by the complexity of its tumour microenvironment (TME). While organ-on-chip (OoC) platforms offer more physiologically relevant models than traditional 2D or static 3D systems, their design remains largely empirical, lacking predictive control over flow conditions, biochemical gradients, and mechanical cues. Computational Fluid Dynamics (CFD) has emerged as a powerful tool to enhance the design, precision, and biological fidelity of OoC platforms. This comprehensive review highlights current limitations in replicating GBM's biological complexity and technical constraints in device fabrication and maintenance, mapping them to specific CFD strategies. It synthesises current strategies into a structured workflow for integrating CFD into the design, optimisation, and validation of microfluidic tumour models. Finally, this review positions CFD as a core component of GBM-on-chip development and explores how its integration with AI-based optimisation can advance the creation of more predictive, scalable, and biologically relevant in vitro tumour models.

Journal Article2025

Novel Adamantane–Sclareol Hybrids Exploit ROS Vulnerability to Overcome Multidrug-Resistance in Glioblastoma Cells

Ema Lupšić, Pavle Stojković, Marija Grozdanić, Nataša Terzić-Jovanović, Milica Pajović, Fani Koutsougianni, Dimitra Alexopoulou, Igor M. Opsenica, Milica Pešić, Ana Podolski-Renić

Molecules

Multidrug resistance (MDR) presents a significant challenge in the treatment of glioblastoma. We evaluated six novel adamantane–sclareol hybrids that integrate a natural labdane diterpene scaffold with an adamantane moiety to address this issue. Compounds 2, 5, and 6 demonstrated the ability to bypass P-glycoprotein (P-gp)-mediated resistance in resistant U87-TxR cells and induced collateral sensitivity, with compound 2 exhibiting the highest selectivity for glioblastoma compared to normal glial cells. Mechanistic studies revealed that compounds 2 and 5 selectively triggered early apoptosis in MDR cells, significantly elevated levels of H2O2 and peroxynitrite, and disrupted mitochondrial membrane potential. Additionally, these compounds altered the expression of key genes involved in glutathione (GSH) and thioredoxin (Trx) antioxidant defense systems and increased ASK1 protein levels, indicating the activation of ROS-driven apoptotic signaling. A preliminary Rag1 xenograft study demonstrated that compound 5 effectively suppressed tumor growth without causing significant weight loss.

Report2024

Sabbatical Report: Hands-On Experience in 3D Cell Culture and Glioma-on-Chip Research

Hooman Taleban

Twente University Sabbatical Report

This sabbatical report details Hooman Taleban's one-month research visit to Twente University, Netherlands, from 19 August to 23 September 2024. The goal was to gain hands-on experience in 3D cell culture, organoids, and spheroids to support ongoing PhD research on glioma-on-chip. Hosted in Prof. Jai Prakash's laboratory, the sabbatical focused on learning fundamental biological techniques such as cell handling, scaffolding, and spheroid formation. Despite the absence of active glioma-on-chip projects, work on breast cancer cell lines provided critical transferable skills. Collaborations with researchers including Prof. Andries van der Meer, Dr. Liliana Moreira Teixeira, and Prof. Marcel Karperien enriched the experience, fostering interdisciplinary perspectives on organ-on-chip systems. The sabbatical strengthened both technical proficiency and conceptual understanding, bridging the gap between engineering and biological experimentation.

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