Exploiting Integrin-αVβ3 to Enhance Radiotherapy Efficacy in Medulloblastoma via Ferroptosis.

Medulloblastoma, a malignant pediatric brain tumor, has a poor prognosis upon relapse, highlighting a critical clinical need. Our previous research linked medulloblastoma cell radioresistance to integrin-αvβ3 expression. β3-depleted (β3_KO) medulloblastoma cells exhibit lipid hydroxyperoxide accumulation after radiotherapy, indicating ferroptosis, a regulated cell death induced by ROS and inhibited by antioxidants such as cysteine, glutathione (GSH), and glutathione peroxidase 4 (GPx4).

Transcriptional Regulation of Protein Synthesis by Mediator Kinase Represents a Therapeutic Vulnerability in MYC-driven Medulloblastoma.

MYC-driven medulloblastoma (MB) is a highly aggressive cancer type with poor prognosis and limited treatment options. Through CRISPR-Cas9 screening of MB cell lines, we identified the Mediator-associated kinase CDK8 as a critical regulator of MYC-driven MB. Loss of CDK8 substantially reduces MYC expression, induces pronounced transcriptional changes, suppresses monosome assembly, and decreases ribosome biogenesis and protein synthesis, consequently inhibiting MB growth.

Pediatric brain tumor patients display altered immune activation and reduced lymphopoiesis at the onset of disease.

Optimal immune function is crucial in preventing cancer development and growth and for the success of anti-cancer therapies. Here, we characterized the peripheral immunological status of 83 steroids-naïve pediatric patients with central nervous system neoplasia at the disease onset. Tumors were classified into low-grade gliomas (LGG), high-grade gliomas (HGG), medulloblastoma, and other tumors.

Newcastle disease virus promotes pyroptosis in medulloblastoma cells by regulating interferon-gamma-mediated guanylate-binding protein 1 expression and activating caspase-4.

Objective: The literature has reported that Newcastle disease virus (NDV) can have inhibitory effects on various tumors. This study aims to investigate the mechanism by which NDV induces pyroptosis in medulloblastoma (MB) cells.

Material And Methods: We treated MB cell lines Daoy and D283 with NDV or recombinant interferon-gamma (IFN-g) proteins.

Cost-effectiveness analysis for multi adverse events of proton beam therapy for pediatric medulloblastoma in Japan.

Medulloblastomas are one of the most common malignant cancers of the central nervous system in children. Proton beam therapy (PBT) is expected to provide equivalent tumor control to photon therapy while reducing the various adverse events caused by irradiation. Few studies have considered the cost-effectiveness of PBT for pediatric medulloblastoma, considering the multiple adverse effects and reflecting on the latest treatment advancements.

Clinico-Demographic Profile of Paediatric Patients with Primary Intracranial Tumours in South India.

The central and peripheral nervous system cancers are the second most common cancers among the paediatric population (0-14 years). The non-specific symptoms seen in its clinical presentation make the diagnosis of these tumours extremely challenging among children compared to adults. This research study was therefore done to study the socio-demographic profile, clinical features, and management practices among paediatric patients with intracranial tumours.

Case report: A case study of variant calling pipeline selection effect on the molecular diagnostics outcome.

Next-generation sequencing technologies have not only defined a breakthrough in medical genetics, but also been able to enter routine clinical practice to determine individual genetic susceptibilities. Modern technological developments are routinely introduced to genetic analysis overtaking the established approaches, potentially raising a number of challenges. To what extent is the advantage of new methodologies in synthetic metrics, such as precision and recall, more important than stability and reproducibility? Could differences in the technical protocol for calling variants be crucial to the diagnosis and, by extension, the patient's treatment strategy? A regulatory review process may delay the incorporation of potentially beneficial technologies, resulting in missed opportunities to make the right medical decisions.

Case report: A second case of cerebral cavernous malformation after high-dose chemotherapy for medulloblastoma.

The development of cerebral cavernous malformations (CCMs) is a well-recognized sequela of irradiation to the brain in pediatric tumors, particularly in medulloblastoma, glioma, and acute lymphoblastic leukaemia. So far, only one case of cerebral cavernoma after chemotherapy with autologous hematopoietic stem cell transplantation (HSCT) has been described. We describe a case of a patient with medulloblastoma aged 18 months at the time of oncological diagnosis who was treated with high-dose chemotherapy followed by HSCT and who developed CCM two years later.

Machine learning-based models for prediction of survival in medulloblastoma: a systematic review and meta-analysis.

Background: Medulloblastoma (MB) is the pediatric population's most frequent malignant intracranial lesions. Prognostication plays a crucial role in optimizing treatment strategy in the MB setting. Several studies have developed ML-based models to predict survival outcomes in individuals with MB.

Cytokine profile of cerebrospinal fluid in pediatric patients with metastatic medulloblastoma.

Background: Medulloblastoma (MB) is a malignant pediatric central nervous system tumor that is prone to leptomeningeal metastasis. Currently, apart from magnetic resonance imaging and cerebrospinal fluid (CSF) cytology, there are no reliable biomarkers for MB progression. Cytokines are key proteins in signaling pathways in the tumor microenvironment and are closely related to tumor recurrence and progression.

Clinical and Molecular Characteristics and Outcome of Adult Medulloblastoma at a Tertiary Cancer Center.

: Adult medulloblastoma is a rare entity, with management data extrapolated from pediatric medulloblastoma cases. We aim to report the clinical characteristics, prognostic factors, and treatment outcome of a cohort of adult patients with medulloblastoma. : Fifty-three patients aged ≥ 18 years with medulloblastoma treated at King Hussein Cancer Center between 2007 and 2019 were retrospectively reviewed.

Aurora kinase B is required for growth and expansion of medulloblastoma cells in the tissue context.

The impact of the tissue context on tumor growth and drug response in medulloblastoma (MB) is poorly understood. To gain insights into the growth and dissemination behavior of the MB tumor cells under treatment, we combined three-dimensional cell culture screening with ex vivo organotypic cerebellum slice co-culture (OCSC), which allowed the assessment of tumor cell behavior in the tissue context. To identify druggable kinase pathways involved in invasion, we screened a panel of 274 kinase inhibitors and identified aurora kinase B (AURKB) as a potential anti-invasion drug target in MB.

The pivotal role of autophagy in the pathogenesis and therapy of medulloblastoma.

Medulloblastoma (MB) is the most frequent malignant brain tumor in children. MB originates from neural precursor cells in distinctive regions of the rhombic lip and their maturation occurs in the cerebellum or the brain stem during embryonal development. Autophagy is also referred to as self-eating' which is a catabolic process that often triggers cellular homeostasis through the salvaging of degenerated proteins as well as organelles.