1,463 results match your criteria pontine glioma


Phase 1/2 Trial of Vorinostat and Radiation and Maintenance Vorinostat in Children with Diffuse Intrinsic Pontine Glioma: A Children's Oncology Group Report.

Neuro Oncol 2021 Aug 4. Epub 2021 Aug 4.

Nationwide Children's Hospital, Neuro-Oncology Program, Columbus, OH, USA.

Background: A phase 1/2 trial of vorinostat (suberoylanilide hydroxamic acid), an oral histone deacetylase (HDAC) inhibitor, was conducted in children with newly-diagnosed diffuse intrinsic pontine glioma (DIPG) through the Children's Oncology Group (COG) to: 1) determine the recommended phase 2 dose (RP2D) of vorinostat given concurrently with radiation therapy; 2) document the toxicities of continuing vorinostat as maintenance therapy after radiation; and 3) to determine the efficacy of this regimen by comparing the risk of progression or death with an historical model from past COG trials.

Methods: Vorinostat was given once daily, Monday through Friday, during radiation therapy (54 Gy in 30 fractions), and then continued at 230 mg/m 2 daily for a maximum of twelve 28-day cycles.

Results: Twelve patients enrolled on the phase 1 study; the RP2D of vorinostat given concurrently with radiation was 230 mg/m 2/day, Monday through Friday weekly. Read More

View Article and Full-Text PDF

Surgical considerations for maximal safe resection of exophytic brainstem glioma in the pediatric age group.

Surg Neurol Int 2021 28;12:310. Epub 2021 Jun 28.

Department of Neurosurgery, Kasr Alainy Faculty of Medicine, Cairo University, Giza, Egypt.

Background: Brainstem glioma is the leading cause of morbidity and mortality among all central nervous system tumors, especially in childhood as it represents about 20% of all pediatric brain tumors. Therefore, this study aimed to present our experience in a tertiary center in a developing country with limited resources for the surgical management of exophytic brainstem gliomas.

Methods: This retrospective study included pediatric patients with brainstem (midbrain, pontine, or medullary) focal or diffuse gliomas whether low or high grade that had dorsal, ventral, or lateral exophytic component who were presented to our hospitals from January 2019 to January 2021. Read More

View Article and Full-Text PDF

The spectrum of mitochondrial DNA (mtDNA) mutations in pediatric CNS tumors.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab074. Epub 2021 Jun 2.

Department of Pathology, Children's Hospital Los Angeles, Los Angeles, California, USA.

Background: We previously established the landscape of mitochondrial DNA (mtDNA) mutations in 23 subtypes of pediatric malignancies, characterized mtDNA mutation profiles among these subtypes, and provided statistically significant evidence for a contributory role of mtDNA mutations to pediatric malignancies.

Methods: To further delineate the spectrum of mtDNA mutations in pediatric central nervous system (CNS) tumors, we analyzed 545 tumor-normal paired whole-genome sequencing datasets from the Children's Brain Tumor Tissue Consortium.

Results: Germline mtDNA variants were used to determine the haplogroup, and maternal ancestry, which was not significantly different among tumor types. Read More

View Article and Full-Text PDF

Magnetic Resonance Imaging-Guided Focused Ultrasound-Based Delivery of Radiolabeled Copper Nanoclusters to Diffuse Intrinsic Pontine Glioma.

ACS Appl Nano Mater 2020 Nov 29;3(11):11129-11134. Epub 2020 Oct 29.

Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Diffuse intrinsic pontine glioma (DIPG) is an invasive pediatric brainstem malignancy exclusively in children without effective treatment due to the often-intact blood-brain tumor barrier (BBTB), an impediment to the delivery of therapeutics. Herein, we used focused ultrasound (FUS) to transiently open BBTB and delivered radiolabeled nanoclusters (Cu-CuNCs) to tumors for positron emission tomography (PET) imaging and quantification in a mouse DIPG model. First, we optimized FUS acoustic pressure to open the blood-brain barrier (BBB) for effective delivery of Cu-CuNCs to pons in wildtype mice. Read More

View Article and Full-Text PDF
November 2020

Remission of Pediatric Diffuse Intrinsic Pontine Glioma: Case Report and Review of the Literature.

J Pediatr Neurosci 2021 Jan-Mar;16(1):1-4. Epub 2021 Jun 25.

Department of Neurology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal.

Background: Diffuse midline glioma (DMG) is one of the most aggressive pediatric tumors. Approximately 60% of pediatric DMG patients die within the first year of diagnosis. Complete clinical and radiological remission of DMG is extremely rare. Read More

View Article and Full-Text PDF

Preclinical and Early Clinical Development of PTC596, a Novel Small Molecule Tubulin-Binding Agent.

Mol Cancer Ther 2021 Jul 26. Epub 2021 Jul 26.

PTC Therapeutics (United States)

PTC596 is an investigational small molecule tubulin-binding agent. Unlike other tubulin-binding agents, PTC596 is orally bioavailable and is not a P-glycoprotein substrate. So as to characterize PTC596 to position the molecule for optimal clinical development, the interactions of PTC596 with tubulin using crystallography, its spectrum of preclinical in vitro anticancer activity, and its pharmacokinetic-pharmacodynamic relationship were investigated for efficacy in multiple preclinical mouse models of leiomyosarcomas and glioblastoma. Read More

View Article and Full-Text PDF

Chemosensitization of Temozolomide-Resistant Pediatric Diffuse Midline Glioma Using Potent Nanoencapsulated Forms of a N(3)-Propargyl Analogue.

ACS Appl Mater Interfaces 2021 Jul 26. Epub 2021 Jul 26.

Translational Health Sciences, Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, BS8 1TD, United Kingdom.

The lack of clinical response to the alkylating agent temozolomide (TMZ) in pediatric diffuse midline/intrinsic pontine glioma (DIPG) has been associated with -methylguanine-DNA-methyltransferase (MGMT) expression and mismatch repair deficiency. Hence, a potent N(3)-propargyl analogue (N3P) was derived, which not only evades MGMT but also remains effective in mismatch repair deficient cells. Due to the poor pharmacokinetic profile of N3P ( < 1 h) and to bypass the blood-brain barrier, we proposed convection enhanced delivery (CED) as a method of administration to decrease dose and systemic toxicity. Read More

View Article and Full-Text PDF

Mosaic Pattern of H3 K27M-Mutant Protein Expression in a Diffuse Midline Glioma-A Diagnostic Dilemma for the Pathologist.

J Neurosci Rural Pract 2021 Jul 10;12(3):596-598. Epub 2021 May 10.

Department of Pathology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.

Diffuse midline glioma, H3 K27M-mutant, is a World Health Organization (WHO) grade IV glioma arising in pons, thalamus, and spinal cord. They show mutations resulting in replacement of lysine at position 27 by methionine (K27M) of histone genes, , and The H3 K27M mutant protein is identified in tumor tissue by immunohistochemistry. As these mutations are clonal and homogeneous, the mutant protein is normally identified in all tumor cells. Read More

View Article and Full-Text PDF

Antibody-drug conjugates for H3K27M-mutant diffuse midline gliomas: prospects and challenges.

Ther Deliv 2021 08 21;12(8):553-557. Epub 2021 Jul 21.

Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA.

View Article and Full-Text PDF

Adult brainstem glioma presenting with isolated persistent hemifacial spasm or facial nerve palsy.

Rev Neurol (Paris) 2021 Jul 13. Epub 2021 Jul 13.

Université de Caen Basse-Normandie, UFR de Médecine, 14000 Caen, France; Service de neurologie, CHU de Caen, 14000 Caen, France; Service de neurologie, CHU de Nîmes, 30029 Nîmes, France. Electronic address:

Object: Adult brainstem gliomas are a rare group of heterogeneous brain tumors. Classical clinical presentation includes progressive impairment of cranial nerves associated with long tract signs. The prognosis and response to treatment are poor; nevertheless, some patients do have a long survival. Read More

View Article and Full-Text PDF

The H3K36me2 writer-reader dependency in H3K27M-DIPG.

Sci Adv 2021 Jul 14;7(29). Epub 2021 Jul 14.

Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA.

Histone H3K27M is a driving mutation in diffuse intrinsic pontine glioma (DIPG), a deadly pediatric brain tumor. H3K27M reshapes the epigenome through a global inhibition of PRC2 catalytic activity and displacement of H3K27me2/3, promoting oncogenesis of DIPG. As a consequence, a histone modification H3K36me2, antagonistic to H3K27me2/3, is aberrantly elevated. Read More

View Article and Full-Text PDF

Central pontine myelinolysis mimicking glioma in diabetes: A case report.

World J Clin Cases 2021 Jun;9(18):4837-4843

Department of Clinical Psychology (Sleep Medical Center), Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China.

Background: Central pontine myelinolysis (CPM) usually occurs during rapid correction of serum osmolality, typically with brainstem lesions presenting uniform signals following enhancement on magnetic resonance imaging (MRI). We report a case of CPM caused by diabetes, which was characterized by glioma-like imaging features and the patient responded well to corticosteroids.

Case Summary: A 49-year-old man with type 2 diabetes was admitted due to numbness and weakness for 6 mo with progressive aggravation for 2 wk. Read More

View Article and Full-Text PDF

Epidemiology and Survival of Patients With Brainstem Gliomas: A Population-Based Study Using the SEER Database.

Front Oncol 2021 11;11:692097. Epub 2021 Jun 11.

Department of Neurosurgery, First Hospital of Jilin University, Changchun, China.

Background: Brainstem glioma is a primary glial tumor that arises from the midbrain, pons, and medulla. The objective of this study was to determine the population-based epidemiology, incidence, and outcomes of brainstem gliomas.

Methods: The data pertaining to patients with brainstem gliomas diagnosed between 2004 and 2016 were extracted from the SEER database. Read More

View Article and Full-Text PDF

Correction to: Design considerations of an IL13Rα2 antibody-drug conjugate for difuse intrinsic pontine glioma.

Acta Neuropathol Commun 2021 Jun 25;9(1):114. Epub 2021 Jun 25.

Children's Cancer Therapy Development Institute, 12655 SW Beaverdam Road-West, Beaverton, OR, 97005, USA.

View Article and Full-Text PDF

Phase 2 Study of Pomalidomide (CC-4047) Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors.

Front Oncol 2021 8;11:660892. Epub 2021 Jun 8.

National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.

Introduction: Treatment of recurrent primary pediatric brain tumors remains a major challenge, with most children succumbing to their disease. We conducted a prospective phase 2 study investigating the safety and efficacy of pomalidomide (POM) in children and young adults with recurrent and progressive primary brain tumors.

Methods: Patients with recurrent and progressive high-grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), ependymoma, or medulloblastoma received POM 2. Read More

View Article and Full-Text PDF

Nimotuzumab therapy in the treatment of pediatric central nervous system tumors: single-center experience.

Naunyn Schmiedebergs Arch Pharmacol 2021 Aug 21;394(8):1769-1777. Epub 2021 Jun 21.

Department of Pediatric Oncology, Faculty of Medicine, Hacettepe University, 06100, Ankara, Turkey.

Relapsed or refractory central nervous system (CNS) tumors still have poor prognosis, and, therefore, new treatment options are required. We retrospectively researched treatment results of patients with CNS tumors treated with nimotuzumab from 2010 to 2015. The study included nine patients with the diffuse intrinsic pontine glioma; eight with medulloblastoma; three each with anaplastic ependymoma, glioblastoma multiforme, and central nervous system primitive neuroectodermal tumor (CNS PNET); two patients with gliomatosis cerebri; and one patient each with other tumor types, including atypical teratoid rhabdoid tumor, thalamic astrocytoma, low-grade glial tumor, high-grade glial tumor, and cribriform neuroepithelial tumor. Read More

View Article and Full-Text PDF

The lateral cerebral peduncle approach to ventrally placed intra-axial midbrain tumors: A technical note.

J Clin Neurosci 2021 Jul 12;89:226-231. Epub 2021 May 12.

Department of Neurosurgery, K.E.M. Hospital and Seth, G.S. Medical College, Parel, Mumbai, India; Lilavati Hospital and Research Centre, Bandra (E), Mumbai, India. Electronic address:

We describe the anatomical landmarks and surgical feasibility of a novel 'safe' brainstem entry zone to approach ventrally placed intra-axial midbrain tumors. The anatomy of the brainstem was specifically studied to evaluate safe surgical entry zone in the midbrain on two formalin fixed silicon injected cadaver head specimens. A novel entry point through the lateral one - fifth of the cerebral peduncle was identified to be 'safe' to approach lesions of the ventral midbrain. Read More

View Article and Full-Text PDF

Characteristics of Patients ≥ 10 Years of Age with Diffuse Intrinsic Pontine Glioma: A Report from the International DIPG Registry.

Neuro Oncol 2021 Jun 11. Epub 2021 Jun 11.

The Ohio State University College of Medicine, Columbus, OH.

Background: DIPG generally occurs in young school-age children, although can occur in adolescents and young adults. The purpose of this study was to describe clinical, radiological, pathologic, and molecular characteristics in patients ≥10 years of age with DIPG enrolled in the International DIPG Registry (IDIPGR).

Methods: Patients ≥10 years of age at diagnosis enrolled in the IDIPGR with imaging confirmed DIPG diagnosis were included. Read More

View Article and Full-Text PDF

[Pediatric Glioma].

No Shinkei Geka 2021 May;49(3):640-646

Division of Neuro-Oncology, Children's Cancer Center, National Center for Child Health and Development.

Pediatric gliomas include various types of glioma broadly categorized as low- or hi-grade based on histopathological features. Clinically significant types include cerebellar astrocytomas, optic pathway / hypothalamic pilocytic astrocytomas, and brainstem gliomas. Neurosurgical roles vary for different kinds of pediatric gliomas. Read More

View Article and Full-Text PDF

Epigenomic landscape and 3D genome structure in pediatric high-grade glioma.

Sci Adv 2021 Jun 2;7(23). Epub 2021 Jun 2.

Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

Pediatric high-grade gliomas (pHGGs), including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG), are morbid brain tumors. Even with treatment survival is poor, making pHGG the number one cause of cancer death in children. Up to 80% of DIPGs harbor a somatic missense mutation in genes encoding histone H3. Read More

View Article and Full-Text PDF

Leveraging Open Science Drug Development for PET: Preliminary Neuroimaging of C-Labeled ALK2 Inhibitors.

ACS Med Chem Lett 2021 May 23;12(5):846-850. Epub 2021 Apr 23.

Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health (CAMH), 250 College St., M5T 1R8, Toronto, Ontario Canada.

Mutations in the gene encoding activin receptor-like kinase 2 (ALK2) are implicated in the pathophysiology of a pediatric brainstem cancer, diffuse intrinsic pontine glioma (DIPG). Inhibitors of ALK2 that cross the blood-brain barrier have been proposed as a method of treatment for DIPG. As part of an open science approach to radiopharmaceutical and drug discovery, we developed C-labeled radiotracers from potent and selective lead ALK2 inhibitors to investigate their brain permeability through positron emission tomography (PET) neuroimaging. Read More

View Article and Full-Text PDF

Primary intracranial germ cell tumour originating from right brachium Pontis with hypertrophic Olivary degeneration: a case report.

BMC Neurol 2021 May 25;21(1):210. Epub 2021 May 25.

Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, 119, South 4th Ring West Road, Fengtai District, Beijing, China.

Background: Primary right brachium pontis germinoma with hypertrophic olivary degeneration (HOD) is extremely rare. A preoperative diagnosis is challenging due to the absence of characterized clinical and neuroimaging features, and biopsy should be considered.

Case Presentation: A 20-year-old male patient presented with a case of primary intracranial germinoma originating from right brachium pontis with HOD manifesting as ocular myoclonus, nystagmus in both eyes, ataxic gait and incoordination of the limbs. Read More

View Article and Full-Text PDF

Spinal Cord Diffuse Midline Gliomas With H3 K27m-Mutant: Clinicopathological Features and Prognosis.

Neurosurgery 2021 Jul;89(2):300-307

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, No. 119 South 4th Ring West Road, Fengtai District, People's Republic of China.

Background: "Diffuse midline glioma, H3 K27M-mutant" (DMG) mainly arises within the pontine, thalamic, and spinal cord regions. Because of the rarity of spinal cord gliomas, the general knowledge surrounding DMGs is mainly based on pontine and thalamic gliomas, whereas tumor location tends to influence the clinicopathological features and prognosis.

Objective: To determine the clinicopathological characteristics and molecular profiles of DMGs located in the spinal cord. Read More

View Article and Full-Text PDF

Receptor-driven invasion profiles in diffuse intrinsic pontine glioma.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab039. Epub 2021 Feb 28.

Children's Cancer Therapy Development Institute, Beaverton, Oregon, USA.

Background: Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric cancer with unmet clinical need. DIPG is invasive in nature, where tumor cells interweave into the fiber nerve tracts of the pons making the tumor unresectable. Accordingly, novel approaches in combating the disease are of utmost importance and receptor-driven cell invasion in the context of DIPG is under-researched area. Read More

View Article and Full-Text PDF
February 2021

Pathogenic ACVR1 activation by Activin A-induced receptor clustering and autophosphorylation.

EMBO J 2021 Jul 18;40(14):e106317. Epub 2021 May 18.

Developmental Signalling Laboratory, The Francis Crick Institute, London, UK.

Fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG) are debilitating diseases that share causal mutations in ACVR1, a TGF-β family type I receptor. ACVR1 is a frequent mutation in both diseases. Pathogenic signaling via the SMAD1/5 pathway is mediated by Activin A, but how the mutation triggers aberrant signaling is not known. Read More

View Article and Full-Text PDF

Radiogenomics of diffuse intrinsic pontine gliomas (DIPGs): correlation of histological and biological characteristics with multimodal MRI features.

Eur Radiol 2021 May 18. Epub 2021 May 18.

Pediatric Radiology Department, AP-HP, Hôpital Universitaire Necker-Enfants Malades, 149 rue de Sèvres, F-75015, Paris, France.

Objectives: The diffuse intrinsic pontine gliomas (DIPGs) are now defined by the type of histone H3 mutated at lysine 27. We aimed to correlate the multimodal MRI features of DIPGs, H3K27M mutant, with their histological and molecular characteristics.

Methods: Twenty-seven treatment-naïve children with histopathologically confirmed DIPG H3K27M mutant were prospectively included. Read More

View Article and Full-Text PDF

Design considerations of an IL13Rα2 antibody-drug conjugate for diffuse intrinsic pontine glioma.

Acta Neuropathol Commun 2021 05 17;9(1):88. Epub 2021 May 17.

Children's Cancer Therapy Development Institute, 12655 SW Beaverdam Road-West, Beaverton, OR, 97005, USA.

Diffuse intrinsic pontine glioma (DIPG), a rare pediatric brain tumor, afflicts approximately 350 new patients each year in the United States. DIPG is noted for its lethality, as fewer than 1% of patients survive to five years. Multiple clinical trials involving chemotherapy, radiotherapy, and/or targeted therapy have all failed to improve clinical outcomes. Read More

View Article and Full-Text PDF

Evaluation of a patient-specific algorithm for predicting distribution for convection-enhanced drug delivery into the brainstem of patients with diffuse intrinsic pontine glioma.

J Neurosurg Pediatr 2021 May 14:1-9. Epub 2021 May 14.

2Department of Neurological Surgery, Weill Medical College of Cornell University, New York, New York.

Objective: With increasing use of convection-enhanced delivery (CED) of drugs, the need for software that can predict infusion distribution has grown. In the context of a phase I clinical trial for pediatric diffuse intrinsic pontine glioma (DIPG), CED was used to administer an anti-B7H3 radiolabeled monoclonal antibody, iodine-124-labeled omburtamab. In this study, the authors retrospectively evaluated a software algorithm (iPlan Flow) for the estimation of infusate distribution based on the planned catheter trajectory, infusion parameters, and patient-specific MRI. Read More

View Article and Full-Text PDF