Pediatric diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), are aggressive brainstem tumors with a dire prognosis, traditionally diagnosed based on MRI characteristics. The recognition that molecular characteristics may determine prognosis and response to therapy has led to a reevaluation of biopsy necessity. This comprehensive review addresses the evolving role of brainstem biopsies in diagnosing and managing these tumors - both within the context of a clinical trial and in routine clinical care.
View Article and Find Full Text PDFPosterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues.
View Article and Find Full Text PDFGenome structural variations within species are rare. How selective constraints preserve gene order and chromosome structure is a central question in evolutionary biology that remains unsolved. Our sequencing of several genomes of the appendicularian tunicate around the globe reveals extreme genome scrambling caused by thousands of chromosomal rearrangements, although showing no obvious morphological differences between these animals.
View Article and Find Full Text PDFRemote sensing observations of Searles Lake following the 2019 moment magnitude 7.1 Ridgecrest, California, earthquake reveal an area where surface ejecta is arranged in a repeating hexagonal pattern that is collocated with a solution-mining operation. By analyzing geologic and geotechnical data, here we show that the hexagonal surface ejecta is likely not a result of liquefaction.
View Article and Find Full Text PDFObjective: Relatively little is known about the safety and accuracy of catheter placement for oncolytic viral therapy in children with malignant brain tumors. Accordingly, this study combines data from two phase I clinical trials that employed viral immunotherapy across two institutions to describe the adverse event profile, safety, and accuracy associated with the stereotactic placement and subsequent removal of intratumoral catheters.
Methods: Children with progressive/recurrent supratentorial malignant tumors were enrolled in two clinical trials (NCT03043391 and NCT02457845) and treated with either the recombinant polio:rhinovirus (lerapolturev) or the genetically modified oncolytic herpesvirus (G207).
HSV G207, a double-stranded, DNA virus, and the polio:rhinovirus chimera, PVSRIPO, a single positive-strand RNA virus, are viral immunotherapies being used to treat pediatric malignant brain tumors in clinical trials. The purpose of this work is to elucidate general response patterns and putative biomarkers of response. Multiple pediatric high-grade glioma and medulloblastoma cell lines were treated with various multiplicities of infection of G207 or PVSRIPO.
View Article and Find Full Text PDFFront Cell Dev Biol
December 2023
A single Aurora kinase found in non-vertebrate deuterostomes is assumed to represent the ancestor of vertebrate Auroras A/B/C. However, the tunicate , a member of the sister group to vertebrates, possesses two Aurora kinases (Aurora1 and Aurora2) that are expressed in proliferative cells and reproductive organs. Previously, we have shown that Aurora kinases relocate from organizing centers to meiotic nuclei and were enriched on centromeric regions as meiosis proceeds to metaphase I.
View Article and Find Full Text PDFGelatinous zooplankton are increasingly recognized to play a key role in the ocean's biological carbon pump. Appendicularians, a class of pelagic tunicates, are among the most abundant gelatinous plankton in the ocean, but it is an open question how their contribution to carbon export might change in the future. Here, we conducted an experiment with large volume in situ mesocosms (~55-60 m and 21 m depth) to investigate how ocean acidification (OA) extreme events affect food web structure and carbon export in a natural plankton community, particularly focusing on the keystone species Oikopleura dioica, a globally abundant appendicularian.
View Article and Find Full Text PDFAutologous fat grafting is hampered by unpredictable outcomes due to high tissue resorption. Hydrogels based on enzymatically pretreated tunicate nanocellulose (ETC) and alginate (ALG) are biocompatible, safe, and present physiochemical properties capable of promoting cell survival. Here, we compared in situ and ex situ crosslinking of ETC/ALG hydrogels combined with lipoaspirate human adipose tissue (LAT) to generate an injectable formulation capable of retaining dimensional stability in vivo.
View Article and Find Full Text PDFPurpose: Intraventricular hemorrhage (IVH) of prematurity can lead to hydrocephalus, sometimes necessitating permanent cerebrospinal fluid (CSF) diversion. We sought to characterize the relationship between head circumference (HC) and ventricular size in IVH over time to evaluate the clinical utility of serial HC measurements as a metric in determining the need for CSF diversion.
Methods: We included preterm infants with IVH born between January 2000 and May 2020.
Background: Medulloblastoma is the most common malignant pediatric brain tumor, and leptomeningeal dissemination (LMD) of medulloblastoma both portends a poorer prognosis at diagnosis and is incurable at recurrence. The biological mechanisms underlying LMD are unclear. The Abelson (ABL) tyrosine kinase family members, ABL1 and ABL2, have been implicated in cancer cell migration, invasion, adhesion, metastasis, and chemotherapy resistance, and are upstream mediators of the oncogene in fibroblasts and lung cancer cells.
View Article and Find Full Text PDFBackground: Outcomes of recurrent paediatric high-grade glioma are poor, with a median overall survival of less than 6 months. Viral immunotherapy, such as the polio-rhinovirus chimera lerapolturev, is a novel approach for treatment of recurrent paediatric high-grade glioma and has shown promise in adults with recurrent glioblastoma. The poliovirus receptor CD155 is ubiquitously expressed in malignant paediatric brain tumours and is a treatment target in paediatric high-grade glioma.
View Article and Find Full Text PDFGangliogliomas are brain tumors composed of neuron-like and macroglia-like components that occur in children and young adults. Gangliogliomas are often characterized by a rare population of immature astrocyte-appearing cells expressing CD34, a marker expressed in the neuroectoderm (neural precursor cells) during embryogenesis. New insights are needed to refine tumor classification and to identify therapeutic approaches.
View Article and Find Full Text PDFObjective: The authors of this study evaluated the safety and efficacy of stereotactic laser ablation (SLA) for the treatment of drug-resistant epilepsy (DRE) in children.
Methods: Seventeen North American centers were enrolled in the study. Data for pediatric patients with DRE who had been treated with SLA between 2008 and 2018 were retrospectively reviewed.
Background And Objective: The goal of this narrative review is to report and summarize the completed pediatric immunotherapy clinical trials for primary CNS tumors. Pediatric central nervous system (CNS) tumors are the most common cause of pediatric solid cancer in children aged 0 to 14 years and the leading cause of cancer mortality. Survival rates for some pediatric brain tumors have improved, however, there remains a large portion of pediatric brain tumors with poor survival outcomes despite advances in treatment.
View Article and Find Full Text PDFExtracellular matrix fibril components, such as collagen, are crucial for the structural properties of several tissues and organs. Tunicate-derived cellulose nanofibrils (TNC) combined with living cells could become the next gold standard for cartilage and soft-tissue repair, as TNC fibrils present similar dimensions to collagen, feasible industrial production, and chemically straightforward and cost-efficient extraction procedures. In this study, we characterized the physical properties of TNC derived from aquaculture production in Norwegian fjords and evaluated its biocompatibility regarding induction of an inflammatory response and foreign-body reactions in a Wistar rat model.
View Article and Find Full Text PDFIntroduction: Intraoperative neuromonitoring (IONM) is commonly used during surgery of the spine and spinal cord for early surveillance of iatrogenic injury to the central and peripheral nervous system. However, for infants and young children under 3 years of age, the use of IONM is challenging due to incomplete central and peripheral myelination.
Case Presentation: We report a case of a T4-T6 dermal sinus tract (DST) that was resected on day of life 23, with the successful use of IONM.
Brain tumors result in significant morbidity and mortality in both children and adults. Recent data indicate that immunotherapies may offer a survival benefit after standard of care has failed for malignant brain tumors. Modest results from several late phase clinical trials, however, underscore the need for more refined, comprehensive strategies that incorporate new mechanistic and pharmacologic knowledge.
View Article and Find Full Text PDFAlginate has been used for decades for cell encapsulation. Cellulose nanofibrils (CNF) from tunicates are desirable in biomedicine due to high molecular weight, purity, crystallinity, and sustainable production. We prepared microbeads of 400-600 μm of alginate and tunicate CNF.
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