The authors conclude that CD44s-targeted treatment with specific mAb may represent an effective means for preventing progression of highly invasive GBMs.

The binocular depth inversion test (BDIT) measures a common illusion of visual perception whereby implausible objects are seen as normal, e.g., a hollow face is perceived as a normal, convex face. Such inversion is frequent, especially for objects with a high degree of familiarity. Under normal conditions, cognitive factors apparently override the binocular disparity cues of stereopsis. This internal mechanism of "censorship" of perception, which balances "top-down" and "bottom-up" processes of perception to come to a cognitive coherence, which is congruent to previous experience and concepts, appears to be disturbed in (pro-)psychotic states. The BDIT has been shown to be a sensitive measure of impaired higher visual processing and conceptual cognition common to conditions including schizophrenia, cannabinoid-intoxication, and sleep deprivation but not depression. In this pilot study, we tested the performance of patients with anxiety disorders (ICD-10 F40 and F41) compared to matched controls using the BDIT paradigm. Anxiety patients scored significantly higher on the BDIT than controls, in a range comparable to propsychotic conditions. The findings suggest that anxiety patients could have abnormalities in central perceptual processing, top-down processing (conceptual cognition), and reality testing similar to (pro-)psychotic conditions. Implications of these findings are discussed in relation to therapeutic interventions with anxiety disorders.

Glioma invasiveness is a complex process involving recognition and attachment of tumor cells to particular extracellular matrix (ECM) molecules prior to migrating into proteolytically modified matrix and inducing angiogenesis. CD44 is a group of transmembrane adhesion molecules found on a wide variety of cells including gliomas that has been suggested as the principal mediator of migration/invasion. The aim of the present study was to demonstrate whether antibody specific for the standard form of CD44 (CD44s, 85-90 kDa) might prevent invasion, thus blocking growth of the 9L gliosarcoma in vivo. High expression of CD44s on the surface of 9L cells and brain tumors was demonstrated by immunochemistry. Fluorescence-activated cell sorting (FACS) demonstrated binding saturation of anti-CD44s monoclonal antibody (mAb) to the receptor at 1 microg/5 x 10(5) cells. Blocking of CD44s in vitro resulted in a dose-dependent progressive, up to 95%+/-2.5% detachment of 9L cells from ECM-coated culture surfaces. Blocking of CD44s in vivo resulted in significantly reduced 9L brain tumors (2.5%+/-0.4%)--measured as the quotient: tumor surface (mm2)/brain surface (mm2) x 100--as compared to untreated (16.1%+/-2.2%) or sham-treated rats (16%+/-3.7% to 16.1%+/-3%). We conclude that CD44s-targeted treatment with specific mAb may be an effective means for preventing glioma progression.

Glioblastoma multiforme (GBM) invasiveness is a complex process that involves recognition and attachment of GBM cells to particular extracellular matrix (ECM) molecules prior to migrating into proteolytically modified matrix and inducing angiogenesis. The CD44, which is a transmembrane adhesion molecule found on a wide variety of cells including GBM, has been suggested as the principal mediator of migration and invasion. The aim of the present study was to demonstrate whether an antibody specific to the standard form of CD44 (CD44s, 85-90 kDa) might prevent invasion and thus disrupt progression of C6 GBM in vivo. Immunostaining demonstrated homogenous expression of CD44s on the surface of C6 GBM cells and tumors. Flow cytometric analysis demonstrated binding saturation of anti-CD44s mAb to the receptor at 1 μg/5 X 105 cells. Blocking of CD44s in vitro resulted in a dose-dependent progressive (up to 94 ± 2.7%; mean ± standard deviation [SD]) detachment of C6 cells from ECM-coated culture surfaces. Blocking of CD44s in vivo resulted in significantly reduced C6 brain tumors (3.6 ± 0.4% [SD])--measured as the quotient: tumor surface (mm2)/brain surface (mm2) X 100--as compared with untreated (19.9% ± 0.9%) or sham-treated rats (19.2 ± 1.1% to 19.3 ± 2.5% [SD]). Disruption of C6 GBM progression correlated with an improved food intake; treated rats were significantly less cachectic (166.6 ± 16.4 g [SD]) than those that were untreated (83.0 ± 2.7 g [SD]) or sham-treated (83.4 ± 1.1 g to 83.0 ± 2.2 g [SD]) rats. The authors conclude that CD44s-targeted treatment with specific mAb may represent an effective means for preventing progression of highly invasive GBMs.