Mesenchymal glioma stem cells trigger vasectasia-distinct neovascularization process stimulated by extracellular vesicles carrying EGFR.

Targeting neovascularization in glioblastoma (GBM) is hampered by poor understanding of the underlying mechanisms and unclear linkages to tumour molecular landscapes. Here we report that different molecular subtypes of human glioma stem cells (GSC) trigger distinct endothelial responses involving either angiogenic or circumferential vascular growth (vasectasia). The latter process is selectively triggered by mesenchymal (but not proneural) GSCs and is mediated by a subset of extracellular vesicles (EVs) able to transfer EGFR/EGFRvIII transcript to endothelial cells.

Benefit of 5 years of enzyme replacement therapy in advanced late onset Pompe. A case report of misdiagnosis for three decades with acute respiratory failure at presentation.

We report on a 57 year old female patient who presented in acute respiratory failure with severe generalized weakness. She was previously misdiagnosed for over three decades as polymyositis. She was treated with enzyme replacement therapy (ERT) for over five years, after being diagnosed with late onset Pompe Disease (LOPD).

Unusual mutation and phenocopy in the family of a young patient with acromegalic gigantism.

Unlabelled: Early-onset acromegaly causing gigantism is often associated with aryl-hydrocarbon-interacting receptor protein () mutation, especially if there is a positive family history. A15y male presented with tiredness and visual problems. He was 201 cm tall with a span of 217 cm.

Radiological Growth Patterns of Prolactinomas and Nonfunctioning Adenomas.

Objectives: To compare growth patterns of nonfunctioning and prolactin-producing pituitary macroadenomas, and to find whether their specific growth patterns are associated with clinically significant effects on vision.

Materials And Methods: From our comprehensive provincial neuropituitary registry, we retrospectively identified 35 randomly selected patients each with nonfunctioning adenomas and prolactinomas >10 mm in any dimension. MRI scans were analyzed to determine the superior and inferior growth, volume, and maximum craniocaudal height of the adenomas.

TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma.

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner.

Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis.

Background: Recurrent medulloblastoma is a therapeutic challenge because it is almost always fatal. Studies have confirmed that medulloblastoma consists of at least four distinct subgroups. We sought to delineate subgroup-specific differences in medulloblastoma recurrence patterns.

The alternative lengthening of telomere phenotype is significantly associated with loss of ATRX expression in high-grade pediatric and adult astrocytomas: a multi-institutional study of 214 astrocytomas.

Loss-of-function of alpha thalassemia/mental retardation syndrome X-linked (ATRX) protein leads to a phenotype called alternative lengthening of telomeres (ALT) in some tumors. High-grade astrocytomas comprise a heterogeneous group of central nervous system tumors. We examined a large cohort of adult (91) and pediatric (n=88) high-grade astrocytomas as well as lower grade forms (n=35) for immunohistochemical loss of ATRX protein expression and the presence of ALT using telomere-specific fluorescence in situ hybridization, with further correlation to other known genetic alterations.

PDGFRA amplification is common in pediatric and adult high-grade astrocytomas and identifies a poor prognostic group in IDH1 mutant glioblastoma.

High-grade astrocytomas (HGAs), corresponding to World Health Organization grades III (anaplastic astrocytoma) and IV (glioblastoma; GBM), are biologically aggressive, and their molecular classification is increasingly relevant to clinical management. PDGFRA amplification is common in HGAs, although its prognostic significance remains unclear. Using fluorescence in situ hybridization (FISH), the most sensitive technique for detecting PDGFRA copy number gains, we determined PDGFRA amplification status in 123 pediatric and 263 adult HGAs.

The role of drebrin in glioma migration and invasion.

Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite current advances in therapy consisting of surgery followed by chemotherapy and radiation, the overall survival rate still remains poor. Therapeutic failures are partly attributable to the highly infiltrative nature of tumor adjacent to normal brain parenchyma.

Canonical TGF-β pathway activity is a predictor of SHH-driven medulloblastoma survival and delineates putative precursors in cerebellar development.

Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Very little is known about aggressive forms of this disease, such as metastatic or recurrent MBs. In order to identify pathways involved in aggressive MB pathophysiology, we performed unbiased, whole genome microarrays on MB tumors at both the human and murine levels.

Pathology and genetics of meningiomas.

This article constitutes a mini-review of the pathology and genetics of meningiomas. Meningiomas are the most common primary intracranial tumors. They are usually durally based and are often found adjacent to venous sinuses and dural infoldings.

Multiphoton ANS fluorescence microscopy as an in vivo sensor for protein misfolding stress.

The inability of cells to maintain protein folding homeostasis is implicated in the development of neurodegenerative diseases, malignant transformation, and aging. We find that multiphoton fluorescence imaging of 1-anilinonaphthalene-8-sulfonate (ANS) can be used to assess cellular responses to protein misfolding stresses. ANS is relatively nontoxic and enters live cells and cells or tissues fixed in formalin.

An epigenetic genome-wide screen identifies SPINT2 as a novel tumor suppressor gene in pediatric medulloblastoma.

Medulloblastoma (MB) is a malignant cerebellar tumor that occurs primarily in children. The hepatocyte growth factor (HGF)/MET pathway has an established role in both normal cerebellar development as well as the development and progression of human brain tumors, including MB. To identify novel tumor suppressor genes involved in MB pathogenesis, we performed an epigenome-wide screen in MB cell lines, using 5-aza-2'deoxycytidine to identify genes aberrantly silenced by promoter hypermethylation.

Integrins mediate adhesion of medulloblastoma cells to tenascin and activate pathways associated with survival and proliferation.

Medulloblastoma spreads by leptomeningeal dissemination rather than by infiltration that characterizes other CNS tumors, eg, gliomas. This study represents an initial attempt to identify both the molecules that mediate medulloblastoma adhesion to leptomeninges and the pathways that are key to survival and proliferation of tumor following adhesion. As a first step in molecule identification, we produced adhesion of D283 medulloblastoma cells to the extracellular matrix (ECM) of H4 glioma cells in vitro.

Creation of a retrospective searchable neuropathologic database from print archives at Toronto's University Health Network.

University Health Network (UHN) Pathology, in its capacity of providing neuro-oncologic care, now utilizes a laboratory information system (LIS), which was instituted in September 2001. For the 75 years preceding the LIS, more than 50 000 pathology reports exist in paper format. High-throughput automated scanning of the paper archives was employed to add the most recent 30 years of paper records (30 000 neuropathology specimens) to the LIS.

Interaction of alpha9beta1 integrin with thrombospondin-1 promotes angiogenesis.

Thrombospondin-1 is a multifunctional protein interacting with several cell surface receptors including integrins. We found that it is a ligand for alpha9beta1 integrin, and has an integrin binding site within its N-terminal domain (NoC1). Interaction of thrombospondin-1 and its recombinant NoC1 domain with alpha9beta1 integrin was confirmed in ELISA and cell adhesion assays.

Sensory CIDP presenting as cryptogenic sensory polyneuropathy.

The objective of this study was to report that patients with chronic inflammatory demyelinating polyneuropathy (CIDP) can present with a clinical picture of cryptogenic sensory neuropathy. Patients with distal sensory neuropathy and electrodiagnostic studies that are minimally abnormal or consistent with an axonal pathology are usually diagnosed as having cryptogenic sensory neuropathy if no cause for neuropathy can be found. Some of these patients, however, may have sensory CIDP.