Michaël H. Meel

PI3K signaling promotes inflammatory tumor-macrophage crosstalk associated with mesenchymal glioblastoma

Rebeca Burgos‐Panadero, María Rosado-Sanz, Víctor Montosa-i-Micó, Zoey J. Tolboom et autres

ABSTRACT Background Glioblastoma (GBM) is a highly heterogeneous and vascularized malignancy in which the mesenchymal (MES) subtype is associated with poor prognosis, extensive macrophage infiltration and resistance to therapy. However, the signaling mechanisms integrating vascular remodeling with inflammatory tumor-macrophage crosstalk remain incompletely …

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Tumor-educated macrophages promote cytokine-driven lung colonization in triple-negative breast cancer

María Rosado-Sanz, Núria Martínez-Alarcón, Michaël H. Meel, Sergio Rius‐Pérez et autres

. Our findings reveal that blocking cytokine receptor signaling disrupts the pro-metastatic crosstalk between macrophages and TNBC cells, offering a clinically actionable strategy to restrain metastasis and overcome therapy resistance in TNBC.

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Gemcitabine therapeutically disrupts essential SIRT1-mediated p53 repression in atypical teratoid/rhabdoid tumors

Dennis S. Metselaar, Michaël H. Meel, Joshua R. Goulding, Aimée du Chatinier et autres

Atypical teratoid/rhabdoid tumors (ATRTs) are highly malignant embryonal tumors of the central nervous system with a dismal prognosis. Using a newly developed and validated patient-derived ATRT culture and xenograft model, alongside a panel of primary ATRT models, we found that ATRTs are …

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DIPG-51. DIFFUSE MIDLINE GLIOMAS HIJACK MYELOID CELL POPULATIONS TO INITIATE AN ANTI-INFLAMMATORY TUMOR IMMUNE MICROENVIRONMENT

Dennis S. Metselaar, Aimée du Chatinier, Annemieke D. Verbaan, Susanne Gamas-Vis et autres

Abstract BACKGROUND Diffuse midline gliomas (DMG) are universally fatal pediatric brain tumors, for which no effective treatment exists. These tumors are known for their “cold” non-inflammatory tumor-immune microenvironment (TIME), which is thought to be a major hurdle for immunotherapy efficacy. METHODS/RESULTS To …

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DIPG-21. PRECLINICAL ASSESSMENT OF A MULTIMODAL TREATMENT APPROACH WITH GIVINOSTAT, PAXALISIB, AND RADIOTHERAPY FOR DIFFUSE MIDLINE GLIOMA (DMG)

Aimée du Chatinier, Michaël H. Meel, Piotr Waranecki, Dennis S. Metselaar et autres

Abstract BACKGROUND Despite an extensive body of clinical research conducted, the prognosis for patients with Diffuse Midline Glioma (DMG) has remained stagnant for the past five decades. Years of investigations underscore the robust resistance of DMG tumors to treatment, rendering monotherapy an …

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The heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene expression profiles

Konstantinos Vazaios, Εftychia Stavrakaki, Lisette B. Vogelezang, Jie Ju et autres

Despite decades of research, the prognosis of high-grade pediatric brain tumors (PBTs) remains dismal; however, recent cases of favorable clinical responses were documented in clinical trials using oncolytic viruses (OVs). In the current study, we employed four different species of OVs: adenovirus …

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Microglia in pediatric brain tumors: The missing link to successful immunotherapy

Aimée du Chatinier, Irene Querol Velilla, Michaël H. Meel, Eelco Wieger Hoving et autres

Brain tumors are the leading cause of cancer-related mortality in children. Despite the development of immunotherapeutic strategies for adult brain tumors, progress in pediatric neuro-oncology has been hindered by the complex and poorly understood nature of the brain's immune system during early …

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RBIO-05. MITOTIC ENRICHMENT AS AN EFFICIENT RADIOSENSITIZATION STRATEGY FOR INTRACRANIAL TUMORS

Mark de Gooijer, Hilal Çolakoğlu, Ceren H. Çitirikkaya, Daria M. Fedorushkova et autres

Abstract Radiotherapy remains one of the most effective modalities for anticancer treatment and part of standard of care for many primary and metastatic brain tumors. Boosting the efficacy of radiotherapy is therefore a logical avenue to improve patient survival. We have developed …

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Gemcitabine therapeutically disrupts essential SIRT1-mediated p53 repression in Atypical Teratoid/Rhabdoid Tumors

Dennis S. Metselaar, Michaël H. Meel, Joshua R. Goulding, Piotr Waranecki et autres

Abstract Background Atypical Teratoid/Rhabdoid Tumors (ATRT) are highly malignant embryonal tumors of the central nervous system with a dismal prognosis. Despite recent advances in understanding the molecular characteristics and subclasses of these tumors, effective therapeutic options remain scarce. Methods In this study, …

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P03.11.B MITOTIC ENRICHMENT AS AN EFFICIENT RADIOSENSITIZATION STRATEGY FOR INTRACRANIAL TUMORS

Mark C. de Gooijer, Hilal Çolakoğlu, Ceren H. Çitirikkaya, Daria M. Fedorushkova et autres

Abstract BACKGROUND Radiotherapy remains one of the most effective modalities for anticancer treatment and part of standard of care for many primary and metastatic brain tumors. Boosting the efficacy of radiotherapy is therefore a logical avenue to improve patient survival. We have …

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Table S2 from MELK Inhibition in Diffuse Intrinsic Pontine Glioma

Michaël H. Meel, Mark C. de Gooijer, Míriam Guillén Navarro, Piotr Waranecki et autres

List of off-target effects of OTSSP167 occurring at concentrations lower than 50nM, derived from the publicly available phosphoproteomics database at http://proteomicsdb.org.

Table S1 from MELK Inhibition in Diffuse Intrinsic Pontine Glioma

Michaël H. Meel, Mark C. de Gooijer, Míriam Guillén Navarro, Piotr Waranecki et autres

shRNA sequences of constructs used in this study.