BackgroundTumor cell invasion into adjacent normal brain is a mesenchymal feature of GBM and a major factor contributing to their dismal outcomes. Therefore, better understandings of mechanisms that promote mesenchymal change in GBM are of great clinical importance to address invasion. We previously showed that the bHLH transcription factor TWIST1 which orchestrates carcinoma metastasis through an epithelial mesenchymal transition (EMT) is upregulated in GBM and promotes invasion of the SF767 GBM cell line in vitro.ResultsTo further define TWIST1 functions in GBM we tested the impact of TWIST1 over-expression on invasion in vivo and its impact on gene expression. We found that TWIST1 significantly increased SNB19 and T98G cell line invasion in orthotopic xenotransplants and increased expression of genes in functional categories associated with adhesion, extracellular matrix proteins, cell motility and locomotion, cell migration and actin cytoskeleton organization. Consistent with this TWIST1 reduced cell aggregation, promoted actin cytoskeletal re-organization and enhanced migration and adhesion to fibronectin substrates. Individual genes upregulated by TWIST1 known to promote EMT and/or GBM invasion included SNAI2, MMP2, HGF, FAP and FN1. Distinct from carcinoma EMT, TWIST1 did not generate an E- to N-cadherin "switch" in GBM cell lines. The clinical relevance of putative TWIST target genes SNAI2 and fibroblast activation protein alpha (FAP) identified in vitro was confirmed by their highly correlated expression with TWIST1 in 39 human tumors. The potential therapeutic importance of inhibiting TWIST1 was also shown through a decrease in cell invasion in vitro and growth of GBM stem cells.ConclusionsTogether these studies demonstrated that TWIST1 enhances GBM invasion in concert with mesenchymal change not involving the canonical cadherin switch of carcinoma EMT. Given the recent recognition that mesenchymal change in GBMs is associated with increased malignancy, these findings support the potential therapeutic importance of strategies to subvert TWIST1-mediated mesenchymal change.

The availability of implantable subdural electrode arrays has made systematic studies of electrocorticographic (ECoG) coherence possible. Studies of coherence patterns recorded directly from human cortex are reviewed along with the presentation of original human clinical data, which reveal reliable and characteristic patterns of coherence. A data-driven technique for discriminating between reliable and unreliable coherence and phase values is described and used to reveal the relationship between coherence and cortical anatomy, such as in the region of the central sulcus, where low phase coherence declines and high phase-shifted coherence increases. Analysis of coherence magnitude and phase makes it possible to determine which signals likely arise from the cortical surface, and which arise from the depths of a sulcus. Alterations in coherence patterns caused by tumors or epilepsy are described and may be used to identify normal and pathological functional relationships between distant cortical areas. Some electrophysiologic/pathologic correlations indicate at least two types of epileptic abnormality, implying a sequence in breakdown of epileptic tissue. The relationship between coherence patterns and behavior and cognition is introduced and compared to similar studies of single-unit binding in animals.

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