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  1. Article ; Online: Functional Precision Oncology: The Next Frontier to Improve Glioblastoma Outcome?

    Panovska, Dena / De Smet, Frederik

    International journal of molecular sciences

    2022  Volume 23, Issue 15

    Abstract: Glioblastoma remains the most malignant and intrinsically resistant brain tumour in adults. Despite intensive research over the past few decades, through which numerous potentially druggable targets have been identified, virtually all clinical trials of ... ...

    Abstract Glioblastoma remains the most malignant and intrinsically resistant brain tumour in adults. Despite intensive research over the past few decades, through which numerous potentially druggable targets have been identified, virtually all clinical trials of the past 20 years have failed to improve the outcome for the vast majority of GBM patients. The observation that small subgroups of patients displayed a therapeutic response across several unsuccessful clinical trials suggests that the GBM patient population probably consists of multiple subgroups that probably all require a distinct therapeutic approach. Due to extensive inter- and intratumoral heterogeneity, assigning the right therapy to each patient remains a major challenge. Classically, bulk genetic profiling would be used to identify suitable therapies, although the success of this approach remains limited due to tumor heterogeneity and the absence of direct relationships between mutations and therapy responses in GBM. An attractive novel strategy aims at implementing methods for functional precision oncology, which refers to the evaluation of treatment efficacies and vulnerabilities of (ex vivo) living tumor cells in a highly personalized way. Such approaches are currently being implemented for other cancer types by providing rapid, translatable information to guide patient-tailored therapeutic selections. In this review, we discuss the current state of the art of transforming technologies, tools and challenges for functional precision oncology and how these could improve therapy selection for GBM patients.
    MeSH term(s) Adult ; Brain Neoplasms/drug therapy ; Brain Neoplasms/therapy ; Glioblastoma/drug therapy ; Glioblastoma/therapy ; Humans ; Medical Oncology ; Mutation ; Precision Medicine/methods
    Language English
    Publishing date 2022-08-03
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23158637
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  2. Article ; Online: The tumor micro-environment in pediatric glioma: friend or foe?

    Messiaen, Julie / Jacobs, Sandra A / De Smet, Frederik

    Frontiers in immunology

    2023  Volume 14, Page(s) 1227126

    Abstract: Brain tumors are the leading cause of morbidity and mortality related to cancer in children, where high-grade glioma harbor the worst prognosis. It has become obvious that pediatric glioma differs significantly from their adult counterparts, rendering ... ...

    Abstract Brain tumors are the leading cause of morbidity and mortality related to cancer in children, where high-grade glioma harbor the worst prognosis. It has become obvious that pediatric glioma differs significantly from their adult counterparts, rendering extrapolations difficult. Curative options for several types of glioma are lacking, albeit ongoing research efforts and clinical trials. As already proven in the past, inter- and intratumoral heterogeneity plays an important role in the resistance to therapy and thus implicates morbidity and mortality for these patients. However, while less studied, the tumor micro-environment (TME) adds another level of heterogeneity. Knowledge gaps exist on how the TME interacts with the tumor cells and how the location of the various cell types in the TME influences tumor growth and the response to treatment. Some studies identified the presence of several (immune) cell types as prognostic factors, but often lack a deeper understanding of the underlying mechanisms, possibly leading to contradictory findings. Although the TME in pediatric glioma is regarded as "cold", several treatment options are emerging, with the TME being the primary target of treatment. Therefore, it is crucial to study the TME of pediatric glioma, so that the interactions between TME, tumoral cells and therapeutics can be better understood before, during and after treatment. In this review, we provide an overview of the available insights into the composition and role of the TME across different types of pediatric glioma. Moreover, where possible, we provide a framework on how a particular TME may influence responses to conventional- and/or immunotherapy.
    MeSH term(s) Adult ; Humans ; Child ; Glioma/therapy ; Brain Neoplasms/therapy ; Immunotherapy ; Tumor Microenvironment
    Language English
    Publishing date 2023-10-13
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1227126
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  3. Article ; Online: Antioxidant network-based signatures cluster glioblastoma into distinct redox-resistant phenotypes.

    Yang, Yihan / More, Sanket / De Smet, Frederik / De Vleeschouwer, Steven / Agostinis, Patrizia

    Frontiers in immunology

    2024  Volume 15, Page(s) 1342977

    Abstract: Introduction: Aberrant reactive oxygen species (ROS) production is one of the hallmarks of cancer. During their growth and dissemination, cancer cells control redox signaling to support protumorigenic pathways. As a consequence, cancer cells become ... ...

    Abstract Introduction: Aberrant reactive oxygen species (ROS) production is one of the hallmarks of cancer. During their growth and dissemination, cancer cells control redox signaling to support protumorigenic pathways. As a consequence, cancer cells become reliant on major antioxidant systems to maintain a balanced redox tone, while avoiding excessive oxidative stress and cell death. This concept appears especially relevant in the context of glioblastoma multiforme (GBM), the most aggressive form of brain tumor characterized by significant heterogeneity, which contributes to treatment resistance and tumor recurrence. From this viewpoint, this study aims to investigate whether gene regulatory networks can effectively capture the diverse redox states associated with the primary phenotypes of GBM.
    Methods: In this study, we utilized publicly available GBM datasets along with proprietary bulk sequencing data. Employing computational analysis and bioinformatics tools, we stratified GBM based on their antioxidant capacities and evaluated the distinctive functionalities and prognostic values of distinct transcriptional networks in silico.
    Results: We established three distinct transcriptional co-expression networks and signatures (termed clusters C1, C2, and C3) with distinct antioxidant potential in GBM cancer cells. Functional analysis of each cluster revealed that C1 exhibits strong antioxidant properties, C2 is marked with a discrepant inflammatory trait and C3 was identified as the cluster with the weakest antioxidant capacity. Intriguingly, C2 exhibited a strong correlation with the highly aggressive mesenchymal subtype of GBM. Furthermore, this cluster holds substantial prognostic importance: patients with higher gene set variation analysis (GSVA) scores of the C2 signature exhibited adverse outcomes in overall and progression-free survival.
    Conclusion: In summary, we provide a set of transcriptional signatures that unveil the antioxidant potential of GBM, offering a promising prognostic application and a guide for therapeutic strategies in GBM therapy.
    MeSH term(s) Glioblastoma/genetics ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Humans ; Antioxidants/metabolism ; Oxidation-Reduction ; Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Gene Regulatory Networks ; Phenotype ; Gene Expression Regulation, Neoplastic ; Reactive Oxygen Species/metabolism ; Oxidative Stress ; Computational Biology/methods ; Prognosis ; Gene Expression Profiling ; Transcriptome
    Chemical Substances Antioxidants ; Reactive Oxygen Species
    Language English
    Publishing date 2024-04-18
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2024.1342977
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  4. Article ; Online: Functional Precision Oncology

    Dena Panovska / Frederik De Smet

    International Journal of Molecular Sciences, Vol 23, Iss 15, p

    The Next Frontier to Improve Glioblastoma Outcome?

    2022  Volume 8637

    Abstract: Glioblastoma remains the most malignant and intrinsically resistant brain tumour in adults. Despite intensive research over the past few decades, through which numerous potentially druggable targets have been identified, virtually all clinical trials of ... ...

    Abstract Glioblastoma remains the most malignant and intrinsically resistant brain tumour in adults. Despite intensive research over the past few decades, through which numerous potentially druggable targets have been identified, virtually all clinical trials of the past 20 years have failed to improve the outcome for the vast majority of GBM patients. The observation that small subgroups of patients displayed a therapeutic response across several unsuccessful clinical trials suggests that the GBM patient population probably consists of multiple subgroups that probably all require a distinct therapeutic approach. Due to extensive inter- and intratumoral heterogeneity, assigning the right therapy to each patient remains a major challenge. Classically, bulk genetic profiling would be used to identify suitable therapies, although the success of this approach remains limited due to tumor heterogeneity and the absence of direct relationships between mutations and therapy responses in GBM. An attractive novel strategy aims at implementing methods for functional precision oncology, which refers to the evaluation of treatment efficacies and vulnerabilities of (ex vivo) living tumor cells in a highly personalized way. Such approaches are currently being implemented for other cancer types by providing rapid, translatable information to guide patient-tailored therapeutic selections. In this review, we discuss the current state of the art of transforming technologies, tools and challenges for functional precision oncology and how these could improve therapy selection for GBM patients.
    Keywords functional precision oncology ; glioblastoma ; drug sensitivity ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: Recent advancements in tumour microenvironment landscaping for target selection and response prediction in immune checkpoint therapies achieved through spatial protein multiplexing analysis.

    Andhari, Madhavi Dipak / Antoranz, Asier / De Smet, Frederik / Bosisio, Francesca Maria

    International review of cell and molecular biology

    2023  Volume 382, Page(s) 207–237

    Abstract: Immune checkpoint therapies have significantly advanced cancer treatment. Nevertheless, the high costs and potential adverse effects associated with these therapies highlight the need for better predictive biomarkers to identify patients who are most ... ...

    Abstract Immune checkpoint therapies have significantly advanced cancer treatment. Nevertheless, the high costs and potential adverse effects associated with these therapies highlight the need for better predictive biomarkers to identify patients who are most likely to benefit from treatment. Unfortunately, the existing biomarkers are insufficient to identify such patients. New high-dimensional spatial technologies have emerged as a valuable tool for discovering novel biomarkers by analysing multiple protein markers at a single-cell resolution in tissue samples. These technologies provide a more comprehensive map of tissue composition, cell functionality, and interactions between different cell types in the tumour microenvironment. In this review, we provide an overview of how spatial protein-based multiplexing technologies have fuelled biomarker discovery and advanced the field of immunotherapy. In particular, we will focus on how these technologies contributed to (i) characterise the tumour microenvironment, (ii) understand the role of tumour heterogeneity, (iii) study the interplay of the immune microenvironment and tumour progression, (iv) discover biomarkers for immune checkpoint therapies (v) suggest novel therapeutic strategies.
    MeSH term(s) Humans ; Tumor Microenvironment ; Neoplasms/drug therapy ; Biomarkers ; Immunotherapy/methods ; Antibodies, Monoclonal/therapeutic use ; Biomarkers, Tumor/metabolism
    Chemical Substances Biomarkers ; Antibodies, Monoclonal ; Biomarkers, Tumor
    Language English
    Publishing date 2023-06-14
    Publishing country Netherlands
    Document type Review ; Journal Article
    ZDB-ID 2427220-6
    ISSN 1937-6448 ; 0074-7696
    ISSN 1937-6448 ; 0074-7696
    DOI 10.1016/bs.ircmb.2023.05.009
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    In stock of ZB MED Cologne/Königswinter

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  6. Article: Next-Generation Pathology by Multiplexed Immunohistochemistry.

    De Smet, Frederik / Antoranz Martinez, Asier / Bosisio, Francesca Maria

    Trends in biochemical sciences

    2020  Volume 46, Issue 1, Page(s) 80–82

    MeSH term(s) Humans ; Immunohistochemistry/methods ; Pathology/methods
    Language English
    Publishing date 2020-10-20
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 194216-5
    ISSN 1362-4326 ; 0968-0004 ; 0376-5067
    ISSN (online) 1362-4326
    ISSN 0968-0004 ; 0376-5067
    DOI 10.1016/j.tibs.2020.09.009
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  7. Article ; Online: Publisher Correction: Immunogenic cell death and its therapeutic or prognostic potential in high-grade glioma.

    Decraene, Brecht / Yang, Yihan / De Smet, Frederik / Garg, Abhishek D / Agostinis, Patrizia / De Vleeschouwer, Steven

    Genes and immunity

    2022  Volume 23, Issue 8, Page(s) 244

    Language English
    Publishing date 2022-11-05
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2060566-3
    ISSN 1476-5470 ; 1466-4879
    ISSN (online) 1476-5470
    ISSN 1466-4879
    DOI 10.1038/s41435-022-00187-3
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  8. Article: Hold before sacrificing the testis! There may be another possibility. A case of tuberculosis epididymo-vasitis.

    Cruyt, Ludovic / Mutluoglu, Mesut / Vandenbulcke, Ruben / Rosseel, Frederik / Gryspeerdt, Stefaan / De Smet, Kristof

    Archivos espanoles de urologia

    2021  Volume 74, Issue 8, Page(s) 808–810

    Title translation ¡Espere antes de sacrificar el testículo! Puede haber otra posibilidad. Un caso de epididimovasitis tuberculosa.
    MeSH term(s) Epididymis ; Genital Diseases, Male ; Humans ; Inflammation ; Male ; Testis ; Tuberculosis/diagnosis
    Language Spanish
    Publishing date 2021-09-24
    Publishing country Spain
    Document type Case Reports ; Journal Article
    ZDB-ID 211673-x
    ISSN 0004-0614
    ISSN 0004-0614
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  9. Article ; Online: Editorial Expression of Concern: The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system.

    Lu, Xiaowei / le Noble, Ferdinand / Yuan, Li / Jiang, Quingjan / de Lafarge, Benjamin / Sugiyama, Daisuke / Bréant, Christiane / Claes, Filip / De Smet, Frederik / Thomas, Jean- Léon / Autiero, Monica / Carmeliet, Peter / Tessier-Lavigne, Marc / Eichmann, Anne

    Nature

    2023  Volume 625, Issue 7994, Page(s) E12

    Language English
    Publishing date 2023-12-18
    Publishing country England
    Document type Expression of Concern
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-023-06944-2
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  10. Article ; Online: Immunogenic cell death and its therapeutic or prognostic potential in high-grade glioma.

    Decraene, Brecht / Yang, Yihan / De Smet, Frederik / Garg, Abhishek D / Agostinis, Patrizia / De Vleeschouwer, Steven

    Genes and immunity

    2022  Volume 23, Issue 1, Page(s) 1–11

    Abstract: Immunogenic cell death (ICD) has emerged as a key component of therapy-induced anti-tumor immunity. Over the past few years, ICD was found to play a pivotal role in a wide variety of novel and existing treatment modalities. The clinical application of ... ...

    Abstract Immunogenic cell death (ICD) has emerged as a key component of therapy-induced anti-tumor immunity. Over the past few years, ICD was found to play a pivotal role in a wide variety of novel and existing treatment modalities. The clinical application of these techniques in cancer treatment is still in its infancy. Glioblastoma (GBM) is the most lethal primary brain tumor with a dismal prognosis despite maximal therapy. The development of new therapies in this aggressive type of tumors remains highly challenging partially due to the cold tumor immune environment. GBM could therefore benefit from ICD-based therapies stimulating the anti-tumor immune response. In what follows, we will describe the mechanisms behind ICD and the ICD-based (pre)clinical advances in anticancer therapies focusing on GBM.
    MeSH term(s) Brain Neoplasms/genetics ; Brain Neoplasms/therapy ; Glioblastoma/drug therapy ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Humans ; Immunogenic Cell Death ; Prognosis
    Language English
    Publishing date 2022-01-19
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2060566-3
    ISSN 1476-5470 ; 1466-4879
    ISSN (online) 1476-5470
    ISSN 1466-4879
    DOI 10.1038/s41435-021-00161-5
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