Overexpression of MBD2 in glioblastoma maintains epigenetic silencing and inhibits the antiangiogenic function of the tumor suppressor gene BAI1.

Brain angiogenesis inhibitor 1 (BAI1) is a putative G protein-coupled receptor with potent antiangiogenic and antitumorigenic properties that is mutated in certain cancers. BAI1 is expressed in normal human brain, but it is frequently silenced in glioblastoma multiforme. In this study, we show that this silencing event is regulated by overexpression of methyl-CpG-binding domain protein 2 (MBD2), a key mediator of epigenetic gene regulation, which binds to the hypermethylated BAI1 gene promoter.

Controversial role of Epstein-Barr virus in multiple sclerosis.

The role of Epstein-Barr virus (EBV) in the pathogenesis of multiple sclerosis (MS) is still elusive. In 2007, Serafini et al demonstrated the direct role of EBV in brain lesions of MS patients. They found positive immunohistochemistry (IHC) staining for latency membrane protein 1 (LMP1), and EBV-encoded RNA (EBER) by in-situ hybridization (ISH) within postmortem brains of MS patients.

Multiorgan detection and characterization of protease-resistant prion protein in a case of variant CJD examined in the United States.

Background: Variant Creutzfeldt-Jakob disease (vCJD) is a prion disease thought to be acquired by the consumption of prion-contaminated beef products. To date, over 200 cases have been identified around the world, but mainly in the United Kingdom. Three cases have been identified in the United States; however, these subjects were likely exposed to prion infection elsewhere.

Apolipoprotein D expression in primary brain tumors: analysis by quantitative RT-PCR in formalin-fixed, paraffin-embedded tissue.

Apolipoprotein D (apoD) expression has been shown to correlate both with cell cycle arrest and with prognosis in several types of malignancy, including central nervous system astrocytomas and medulloblastomas. ApoD expression was investigated by real-time quantitative RT-PCR using RNA extracted from 68 formalin-fixed, paraffin-embedded brain specimens. Glyceraldehyde phosphate dehydrogenase was used as an internal control.

Microregional extracellular matrix heterogeneity in brain modulates glioma cell invasion.

The invasion of neoplastic cells into healthy brain tissue is a pathologic hallmark of gliomas and contributes to the failure of current therapeutic modalities (surgery, radiation and chemotherapy). Transformed glial cells share the common attributes of the invasion process, including cell adhesion to extracellular matrix (ECM) components, cell locomotion, and the ability to remodel extracellular space. However, glioma cells have the ability to invade as single cells through the unique environment of the normal central nervous system (CNS).

Pseudopalisades in glioblastoma are hypoxic, express extracellular matrix proteases, and are formed by an actively migrating cell population.

Necrosis and vascular proliferation are the pathologic features that distinguish the most malignant infiltrative astrocytoma, glioblastoma (GBM), from those of lower grades. In GBM, hypercellular zones called pseudopalisades typically surround necrotic foci. Although these cells are known to secrete high levels of proangiogenic factors that promote tumor growth, their origins are ill defined.

Alterations in molecular pathways of diffusely infiltrating glial neoplasms: application to tumor classification and anti-tumor therapy (Review).

Recent advances in our understanding of the molecular genetic mechanisms underlying diffusely infiltrating brain neoplasms have important implications for the classification and therapy of these tumors. Traditionally, primary brain tumors have been classified histologically; however, it is now clear that tumors within a single histologically defined category are heterogeneous from a molecular genetic perspective. Furthermore, many new experimental therapeutic strategies directed against these almost invariably fatal tumors are aimed at molecular rather than histologic abnormalities.

Genetic markers in glioblastoma: prognostic significance and future therapeutic implications.

Glioblastoma multiforme (GBM) is the highest-grade infiltrative astrocytoma and also the most common. It is generally associated with a dismal prognosis (mean survival 11 months), yet individual patient survivals vary. Histologic parameters have had limited value in predicting survival among patients with GBM.

Expression microarray analysis of brain tumors: what have we learned so far.

This review covers the emerging field of expression microarray technology as applied to human brain tumors. Dual and single color techniques are described and contrasted, and the importance of proper handling of the starting material is emphasized. Difficulties with data interpretation are described and current approaches to cluster analysis reviewed.