Analysis of Dual Class I Histone Deacetylase and Lysine Demethylase Inhibitor Domatinostat (4SC-202) on Growth and Cellular and Genomic Landscape of Atypical Teratoid/Rhabdoid.

Central nervous system atypical teratoid/rhabdoid tumors (ATRTs) are rare and aggressive tumors with a very poor prognosis. Current treatments for ATRT include resection of the tumor, followed by systemic chemotherapy and radiation therapy, which have toxic side effects for young children. Gene expression analyses of human ATRTs and normal brain samples indicate that ATRTs have aberrant expression of epigenetic markers including class I histone deacetylases (HDAC's) and lysine demethylase (LSD1).

4SC-202 as a Potential Treatment for the Pediatric Brain Tumor Medulloblastoma.

This project involves an examination of the effect of the small molecule inhibitor 4SC-202 on the growth of the pediatric brain cancer medulloblastoma. The small molecule inhibitor 4SC-202 significantly inhibits the viability of the pediatric desmoplastic cerebellar human medulloblastoma cell line DAOY, with an IC = 58.1 nM, but does not affect the viability of noncancerous neural stem cells (NSC).

Therapeutic Targeting of PTK7 is Cytotoxic in Atypical Teratoid Rhabdoid Tumors.

Novel discoveries involving the evaluation of potential therapeutics are based on newly identified molecular targets for atypical teratoid rhabdoid tumors (ATRT), which are the most common form of infantile brain tumors. Central nervous system ATRTs are rare, aggressive, and fast growing tumors of the brain and spinal cord and carry a very poor prognosis. Currently, the standard of care for ATRT patients is based on surgical resection followed by systemic chemotherapy and radiotherapy, which result in severe side effects.

Case report of an epidural cervical Onchocerca lupi infection in a 13-year-old boy.

A 13-year-old boy presented with fever and neck pain and stiffness, which was initially misdiagnosed as culture-negative meningitis. Magnetic resonance images of the brain and cervical spine demonstrated what appeared to be an intradural extramedullary mass at the C1-3 level, resulting in moderate cord compression, and a Chiari Type I malformation. The patient underwent a suboccipital craniectomy and a C1-3 laminectomy with intradural exploration for excisional biopsy and resection.

Cerebral peduncle tumor ablated by novel 3-mm laser tip.

Background/objective: Decisions to use open surgery or radiotherapy in pediatric patients with familial neoplastic syndromes must consider not only the symptomatic benefits of treatment, but also future limitations these treatments may impose. Specifically, open surgical resection of noncurable tumors may preclude or encumber future lesion resections, while radiotherapy has detrimental effects on pediatric cognitive development and increases the risk of future malignancy development. We provide the first report of using a novel 3.

Neuropsychiatric changes following penetrating head injury in children.

Background: Penetrating head injuries demand the prompt attention of a neurosurgeon. While most neurosurgical centers are experienced in the acute management of these injuries, less is known about the long-term neuropsychiatric sequelae of penetrating head trauma. In adults, direct injury to the frontal lobe classically has been associated with mental status changes.

Concomitant achondroplasia and Chiari II malformation: A double-hit at the cervicomedullary junction.

We report the first case of a neonate with concurrent Chiari II malformation and achondroplasia. Although rare, both these conditions contribute to several deleterious anatomical changes at the cervicomedullary junction and thus predispose to acute hydrocephalus. Although our patient was initially asymptomatic, hydrocephalus ensued several weeks after birth and required cerebral spinal fluid diversion.

Wnt pathway in atypical teratoid rhabdoid tumors.

Background: Atypical teratoid rhabdoid tumor (ATRT) is an aggressive pediatric brain tumor with limited therapeutic options. The hypothesis for this study was that the Wnt pathway triggered by the Wnt5B ligand plays an important role in ATRT biology. To address this hypothesis, the role of WNT5B and other Wnt pathway genes was analyzed in ATRT tissues and ATRT primary cell lines.

Expression of the HOX genes and HOTAIR in atypical teratoid rhabdoid tumors and other pediatric brain tumors.

Pediatric brain tumors such as atypical teratoid rhabdoid tumors (ATRTs) are highly aggressive and predominantly occur in young children. A characteristic feature of ATRT is aberrations of the SMARCB1 (hSNF5/INI1) gene. Developmental gene defects may play an important role in the biology of pediatric brain tumors.

Detection of an atypical teratoid rhabdoid brain tumor gene deletion in circulating blood using next-generation sequencing.

Circulating biomarkers such as somatic chromosome mutations are novel diagnostic tools to detect cancer noninvasively. We describe focal deletions found in a patient with atypical teratoid rhabdoid tumor, a highly aggressive early childhood pediatric tumor. First, we used magnetic resonance imaging (MRI) and histopathology to study the tumor anatomy.

Clinical trials in cellular immunotherapy for brain/CNS tumors.

High-grade gliomas are the most common type of primary malignant brain/CNS tumor. There have been only modest advances in surgical techniques, radiotherapy and chemotherapy for high-grade gliomas over the past several decades. None of these have provided a major improvement in survival for patients.

Diffusion tensor tractography detection of functional pathway for the spread of epileptiform activity between temporal lobe and Rolandic region.

Purpose: The aim of the study was to assess the connectivity between magnetoencephalographic (MEG) dipoles in the temporal lobe and Rolandic region in children with temporal lobe epilepsy using diffusion tensor imaging (DTI) tractography.

Methods: Six pediatric patients with intractable focal epilepsy had MEG performed, which showed MEG dipoles over both temporal and Rolandic regions in a unilateral hemisphere. DTI tractography was performed on each patient.

Management of pediatric brainstem cavernous malformations: experience over 20 years at the hospital for sick children.

Object: Because of their location and biological behavior, brainstem cavernous malformations (CMs) pose a formidable clinical challenge to the neurosurgeon. The optimal management of these lesions requires considerable neurosurgical judgment. Accordingly, the authors reviewed their experience with the management of pediatric brainstem CMs at the Hospital for Sick Children.

Evidence for cardiomyocyte renewal in humans.

It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of carbon-14, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from 1% turning over annually at the age of 25 to 0.

Neocortical neurogenesis in humans is restricted to development.

Stem cells generate neurons in discrete regions in the postnatal mammalian brain. However, the extent of neurogenesis in the adult human brain has been difficult to establish. We have taken advantage of the integration of (14)C, generated by nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in the major areas of the human cerebral neocortex.

Retrospective birth dating of cells in humans.

The generation of cells in the human body has been difficult to study, and our understanding of cell turnover is limited. Testing of nuclear weapons resulted in a dramatic global increase in the levels of the isotope 14C in the atmosphere, followed by an exponential decrease after 1963. We show that the level of 14C in genomic DNA closely parallels atmospheric levels and can be used to establish the time point when the DNA was synthesized and cells were born.

Prospective feasibility study of outpatient stereotactic brain lesion biopsy.

Objective: To assess the safety and feasibility of performing computed tomography-guided stereotactic brain lesion biopsy as an outpatient day-surgery procedure.

Methods: In late 1996, a prospective trial of outpatient stereotactic biopsies was initiated. The protocol consists of preadmission education of the patient, computed tomography-guided biopsy with local anesthesia (using a Brown-Roberts-Wells or Cosman-Roberts-Wells frame), postoperative observation in the postanesthetic care unit for 2 hours and in the day surgery unit for 2 hours, and then discharge home 4 hours after the procedure.