pontine glioma

Differential diagnosis of focal brainstem lesions detected on MRI is challenging, especially in young children. Formerly, brainstem gliomas were classified mainly based on MRI features and location. However, since 2016, the World Health Organization's brainstem lesion classification requires tissue biopsy to reveal molecular characteristics. Although modern techniques of stereotactic or navigation-guided biopsy ensure accurate biopsy of the lesion with safety, biopsy of brainstem lesions is still generally not performed...

RATIONALE: Bilateral thalamic glioma is extremely rare and characterized by strictly limited involvement of bilateral thalami. To investigate its clinical and neuroimaging features, we herein reported a rare case of anaplastic astrocytoma (AA) involving both thalami and the brainstem and reviewed the literature. PATIENT CONCERNS: A-33-year-old Chinese woman was referred to our department owing to persistent headache and nausea and vomiting. Neurological examination showed mild cognitive impairment and positive Kernig sign...

Diffuse intrinsic pontine gliomas (DIPGs) are deadly pediatric brain tumors, non-resectable due to brainstem localization and diffusive growth. Over 80% of DIPGs harbor a mutation in histone 3 (H3.3 or H3.1) resulting in a lysine-to-methionine substitution (H3K27M). Patients with DIPG have a dismal prognosis with no effective therapy. We show that histone deacetylase (HDAC) inhibitors lead to a significant reduction in the H3.3K27M protein (up to 80%) in multiple glioma cell lines. We discover that the SB939-mediated H3...

Diffuse intrinsic pontine glioma (DIPG), affecting children aged 4-7 years, is a rare, aggressive tumor that originates in the pons and then spreads to nearby tissue. DIPG is the leading cause of death for pediatric brain tumors due to its infiltrative nature and inoperability. Radiotherapy has only a palliative effect on stabilizing symptoms. In silico and preclinical studies identified ONC201 as a cytotoxic agent against some human cancer cell lines, including DIPG ones. A single-crystal X-ray analysis of the complex of the human mitochondrial caseinolytic serine protease type C ( h ClpP) and ONC201 (PDB ID: 6DL7) allowed h ClpP to be identified as its main target...

BACKGROUND AND AIM: Pediatric high-grade gliomas (pedHGG) comprise a very poor prognosis. Thus, parents of affected children are increasingly resorting to complementary and alternative medicine (CAM), among those Boswellia extracts. However, nothing is known about the therapeutic effectiveness of their active substances, Boswellic acids (BA) in pedHGG. Thus, we aimed to investigate if the three main Boswellic acids (BA) present in Boswellia plants, alpha-boswellic acid (α-BA), beta-boswellic acid (β-BA) and 3-acetyl-11-keto-beta-boswellic acid (AKBA) hold any promising potential for treatment of affected pedHGG patients...

The objective of this study was to investigate IL13Ra2 expression in brainstem glioma (BSG) and its correlation with key markers, functions, and prognostic implications, evaluating its therapeutic potential. A total of 80 tumor samples from BSG patients were analyzed. Multiplex immunofluorescence was used to examine six markers-IL13Ra2, H3.3K27M, CD133, Ki67, HLA-1, and CD4-establishing relationships between IL13Ra2 and these markers. Survival analysis, employing Kaplan-Meier and Cox proportional hazard regression models, encompassed 66 patients with complete follow-up...

Diffuse intrinsic pontine glioma (DIPG) was first described by Harvey Cushing, the father of modern neurosurgery, a century ago. Since then, the classification of this tumor changed significantly, as it is now part of the broader family of diffuse midline gliomas (DMGs), a heterogeneous group of tumors of midline structures encompassing the entire rostro-caudal space, from the thalamus to the spinal cord. DMGs are characterized by various epigenetic events that lead to chromatin remodeling similarities, as two decades of studies made possible by increased tissue availability showed...

INTRODUCTION: Brainstem is a rare yet challenging site for primary brain tumors. We present the patient characteristics, treatment-related details, and survival outcomes of patients with brain stem gliomas treated over a decade, from August 2010 to July 2022, at a tertiary care center in northern India. MATERIALS AND METHODS: Twenty-seven patients of brainstem gliomas were treated in our hospital from August 2010 to July 2022. All of these patients were treated with radiation therapy based on a radiological diagnosis only...

H3 K27M-mutant diffuse glioma is a recently identified brain tumor associated with poor prognosis. As of 2016, it is classified by the World Health Organization as a distinct form of grade IV glioma. Despite recognition as an important prognostic and diagnostic feature in diffuse glioma, radiation remains the sole standard of care and no effective systemic therapies are available for H3K27M mutant tumors. This review will detail treatment interventions applied to diffuse midline glioma (DMG) and diffuse intrinsic pontine glioma (DIPG) prior to the identification of the H3 K27M mutation, the current standard-of-care for H3 K27M-mutant diffuse glioma treatment, and ongoing clinical trials listed on w w w...

Diffuse intrinsic pontine glioma (DIPG) is the most aggressive pediatric brain tumor, and the oncohistone H3.3K27M mutation is associated with significantly worse clinical outcomes. Despite extensive research efforts, effective approaches for treating DIPG are lacking. Through drug screening, we identified the combination of gemcitabine and fimepinostat as a potent therapeutic intervention for H3.3K27M DIPG. H3.3K27M facilitated gemcitabine-induced apoptosis in DIPG, and gemcitabine stabilized and activated p53, including increasing chromatin accessibility for p53 at apoptosis-related loci...

Diffuse intrinsic pontine glioma (DIPG) remains intractable to conventional treatments. While targeted therapy and immuno-oncology advances offer hope, few strategies show promising results. In a recent article in Cancer Cell, Ausejo-Mauleon et al. introduce TIM-3 blockade as a potential breakthrough for DIPG treatment by targeting cancer cells and regulating the immune microenvironment simultaneously.

The BMP (Bone morphogenetic protein) signaling pathway plays a central role in metazoan biology, intricately shaping embryonic development, maintaining tissue homeostasis, and influencing disease progression. In the context of cancer, BMP signaling exhibits context-dependent dynamics, spanning from tumor suppression to promotion. Cancer stem cells (CSCs), a modest subset of neoplastic cells with stem-like attributes, exert substantial influence by steering tumor growth, orchestrating therapy resistance, and contributing to relapse...

OBJECTIVE: Brainstem tumors present a significant challenge in surgical treatment, and the prognostic factors in children are lacking. This study aimed to investigate clinical characteristics and prognostic factors of surgical treatment in children with brainstem tumors. PATIENTS AND METHODS: 50 children with brainstem tumors who underwent surgical treatment, including frameless- or frame-based stereotactic biopsy and resection, were included and followed up for clinical and biological analysis...

Introduction: Pediatric brain tumours (PBT) are one of the most common malignancies during childhood, with variable severity according to the location and histological type. Certain types of gliomas, such a glioblastoma and diffuse intrinsic pontine glioma (DIPG), have a much higher mortality than ependymoma and medulloblastoma. Early detection of PBT is essential for diagnosis and therapeutic interventions. Liquid biopsies have been demonstrated using cerebrospinal fluid (CSF), mostly restricted to cell free DNA, which display limitations of quantity and integrity...

BACKGROUND: Diffuse intrinsic pontine gliomas (DIPG/DMG) are devastating pediatric brain tumors with extraordinarily limited treatment options and uniformly fatal prognosis. Histone H3K27M mutation is a common recurrent alteration in DIPG and disrupts epigenetic regulation. We hypothesize that genome-wide H3K27M-induced epigenetic dysregulation makes tumors vulnerable to epigenetic targeting. METHODS: We performed a screen of compounds targeting epigenetic enzymes to identify potential inhibitors for the growth of patient-derived DIPG cells...

Genetic histone variants have been implicated in cancer development and progression. Mutations affecting the histone 3 (H3) family, H3.1 (encoded by HIST1H3B and HIST1H3C ) and H3.3 (encoded by H3F3A ), are mainly associated with pediatric brain cancers. While considered poor prognostic brain cancer biomarkers in children, more recent studies have reported H3 alterations in adult brain cancer as well. Here, we established reliable droplet digital PCR based assays to detect three histone mutations (H3.3-K27M, H3...

Diffuse midline gliomas (DMGs), including diffuse intrinsic pontine glioma, have among the highest mortality rates of all childhood cancers, despite recent advancements in cancer therapeutics. This is partly because, unlike some CNS tumors, the blood-brain barrier (BBB) of DMG tumor vessels remains intact. The BBB prevents the permeation of many molecular therapies into the brain parenchyma, where the cancer cells reside. Focused ultrasound (FUS) with microbubbles has recently emerged as an innovative and exciting technology that non-invasively permeabilizes the BBB in a small focal region with millimeter precision...

INTRODUCTION: Diffuse midline glioma (DMG) of the pons occurs in pediatric patients and carries a dismal prognosis. Biopsy is not necessary for diagnosis but provides information, particularly H3K27M status, with prognostic implications. Additionally, biopsy information may open therapeutic options such as clinical trials that require mutation status. Therefore, we sought to assess the safety of surgical biopsy in DMG patients as well as its potential impact on clinical course. METHODS: Retrospective analysis of patients who were radiographically and clinically diagnosed with pontine DMG in the last 5 years was performed...

The objective of the article is to report the case of three patients with diffuse intrinsic pontine glioma (DIPG) treated with immunotherapy. In particular we report the data related to the treatments' efficacy and tolerance.To achieve this, we review the medical records in the Paediatric Oncology and Haematology Unit of HM Hospitales/Centro Integral Oncológico Clara Campal (CIOCC). We focused on patients diagnosed with DIPG who were administered oncolytic viruses followed by immune checkpoint inhibitors (ICI) (pembrolizumab, anti PD-1) plus a concomitant antiangiogenic agent (bevacizumab)...

INTRODUCTION: Brainstem tumors represent a challenge. Their management and prognosis vary according to anatomopathological findings and genetic and bio-molecular fingerprints. We present our experience with pediatric brainstem tumors. MATERIAL AND METHODS: All patients admitted for a brainstem tumor at the Pediatric Neurosurgical Unit at Hôpital Femme Mère Enfant hospital between January 1997 and December 2019 were considered. Patients data were obtained through a retrospective review of the medical records; follow-up was from the last outpatient consultation...