Tobey J. MacDonald

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Medulloblastoma is the most common embryonal tumour in children. Patients with medulloblastoma are currently staged as average-risk or poor-risk on the basis of clinical findings. With current multimodality therapy, nearly 90% of children with average-risk, non-disseminated medulloblastoma have 5-year event-free survival, and those with high-risk disease(More)
The purpose is to determine the incidence of active and latent human herpesvirus-6 (HHV-6) infection in a large cohort of adult primary and recurrent CNS tumors. We screened a tissue microarray (TMA) containing more than 200 adult primary and recurrent CNS tumors with known clinical information for the presence of HHV-6 DNA by in situ hybridization (ISH)(More)
Diffuse intrinsic pontine glioma (DIPG) is a highly morbid form of pediatric brainstem glioma. Here, we present the first comprehensive protein, mRNA, and methylation profiles of fresh-frozen DIPG specimens (n = 14), normal brain tissue (n = 10), and other pediatric brain tumors (n = 17). Protein profiling identified 2,305 unique proteins indicating(More)
BACKGROUND Pilocytic Astrocytomas (PAs) are common low-grade central nervous system malignancies for which few recurrent and specific genetic alterations have been identified. In an effort to better understand the molecular biology underlying the pathogenesis of these pediatric brain tumors, we performed higher-order transcriptional network analysis of a(More)
BACKGROUND Recent publications have described an important role for cross talk between PI-3 kinase and sonic hedgehog signaling pathways in the pathogenesis of medulloblastoma. METHODOLOGY/PRINCIPAL FINDINGS We crossed mice with constitutive activation of Smoothened, SmoA1, with Pten deficient mice. Both constitutive and conditional Pten deficiency(More)
BACKGROUND The CCL2 chemokine is involved in promoting cancer angiogenesis, proliferation and metastasis by malignancies that express CCR2 receptor. Thus the CCL2/CCR2 axis is an attractive molecular target for anticancer drug development. METHODS We have generated a novel fusion protein using GMCSF and an N-terminal truncated version of MCP1/CCL2 (6-76)(More)
For the past two decades, staging studies have been used to stratify children with medulloblastoma into risk groups. Therapeutic approaches have been based on separation of patients into 'average-risk' and 'poor-risk' categories. The extent of disease at diagnosis has been most reproducibly shown to be of prognostic significance, but age at diagnosis and(More)
Medulloblastoma (MB) is the most frequent malignant brain tumor in children. Patients with MB who are classified as having high-risk disease or those with recurrent disease respond poorly to current therapies and have an increased risk of MB-related mortality. Preclinical studies and molecular profiling of MB tumors have revealed upregulation or activation(More)
High grade glioma remains the most intractable childhood tumor of the central nervous system. The molecular genetics of childhood high grade glioma remain largely unknown in comparison to that of their adult counterparts. In an era of molecularly targeted therapies, this dearth of knowledge will present particular challenges to those who must design and(More)