Meningiomas are known to be associated with female sex hormones. Worsening neurological symptoms or newly diagnosed meningiomas have been described in the context of elevated levels of sex hormones, for example, in pregnancy. To the authors’ knowledge, tumor shrinkage after the normalization of hormones has not been described, even if it is known that neurological deficits due to meningioma compression may improve after giving birth. A 32-year-old female patient presented with severe headache and vision disturbances at the end of her second pregnancy. Magnetic resonance imaging revealed an extended mass at the lateral left-sided sphenoid wing that was suspected to be a meningioma. After delivery, the patient’s symptoms improved, and MRI obtained 2 months postpartum showed significant shrinkage of the lesion. Significant tumor shrinkage can occur after pregnancy. Thus, repeat imaging is indicated in these patients.
Sufficient gene transfer into CNS-derived cells is the most crucial step to develop strategies for gene therapy. In this study liposome-mediated gene transfer using a beta-galactosidase (beta-GAL) reporter gene was performed in vitro (C6 glioma cells, NT2 neuronal precursor cells, 3T3 fibroblasts, primary glial cells) and in vivo. Using Trypan blue exclusion staining, optimal lipid concentration was observed in the range of 10-12 microg/mL. Under optimal conditions (80,000 cells/16 mm well, incubation overnight, lipid/DNA ratio = 1:18) a high transfection rate was achieved (<9% for C6 cells; <1% for NT2 cells). In primary cultures of glial cells a fair amount of positive stained cells (glial cell) was found, but the transfection efficiency was lower (<0.1%). A "boost-lipofection" markedly increased (twice) lipofection efficiency in C6 cells. Expression of beta-GAL reached a maximum after 3-5 days. When the liposome-DNA complexes were injected/infused directly into the brains of adult rats, several weakly stained cells could be observed in the brain region adjacent to the injection site. It is concluded that liposome-mediated gene transfer is an efficient method for gene transfer into CNS cells in vitro, but the transfection efficiency into the rat brain in vivo is far too low and therefore not applicable.
Integrins have become a target for novel therapeutic strategies against malignant gliomas. Cilengitide, a synthetic Arg-Gly-Asp (RGD)-motif peptide, interferes with ligand binding to avb3 and avb5 integrins and is currently investigated in clinical trials. Integrins may also be involved in the activation of transforming growth factor (TGF)-b, a mediator of invasiveness and immune escape of glioma cells. Using flow cytometry, we demonstrate that the target integrins of cilengitide are expressed not only in glioblastoma blood vessels, but also by tumor cells. After exposure of glioma cells to cilengitide, we noticed reduced phosphorylation of Smad2 in most glioma cell lines, including stem-like glioma cells. Phophorylation of Smad2, but not cilengitide-induced detachment, is rescued by addition of recombinant TGF-b. Administration of cilengitide to glioma cells results in reduced TGF-b-mediated reporter gene activity. Furthermore, exposure to cilengitide leads to decreased TGF-b 1 and TGF-b 2 mRNA and protein expression. These effects are mimicked by blocking av, b3 or b5 antibodies or by silencing of integrins av, b3, b5 or b8 using RNA interference. Treatment of mice bearing experimental LN-308 glioma xenografts with cilengitide results in reduced pSmad2 levels. Taken together, cilengitide may exert anti-invasive and immune stimulatory activity in human glioblastoma patients by its anti-TGF-b properties.
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