Expression of decitabine-targeted oncogenes in meningiomas in vivo

Neurosurgical Review - Treatment of meningiomas refractory to surgery and irradiation is challenging and effective chemotherapies are still lacking. Recently, in vitro analyses revealed decitabine...     

Mal perforant du pied nach Embolie der Arteria poplitea

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Acute morphological sequelae of photodynamic therapy with 5-aminolevulinic acid in the C6 spheroid model

Objective Aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) may represent a treatment option for malignant brain tumors. We used a three-dimensional cell culture system, the C6 glioma spheroid model, to study acute effects of PDT and how they might be influenced by treatment conditions. Methods Spheroids were incubated for 4 h in 100 μg/ml ALA in 5% CO₂ in room air or 95% O₂ with subsequent irradiation using a diode laser (λ = 635 nm, 40 mW/cm², total fluence 25 J/cm²). Control groups were “laser only”, “ALA only”, and “no drug no light”. Annexin V-FITC, a marker used for detection of apoptosis, propidium iodide (PI), a marker for necrotic cells and H 33342, a chromatin stain, were used for morphological characterization of PDT effects by confocal laser scanning and fluorescence microscopy. Hematoxylin–eosin staining and TdT-FragEL (TUNEL) assay were used on cryosections. Growth kinetics were followed for 8 days after PDT. Results PDT after incubation in 5% CO₂ provided incomplete cell death and growth delay in spheroids of >350 μm diameter. However, complete cell death and growth arrest occurred in smaller spheroids (<350 μm). Incubation in 95% O₂ with subsequent PDT resulted in complete cell death and growth arrest regardless of spheroid size. In incompletely damaged spheroids viable cells were restricted to spheroid centers. The rate of cell death in all control groups was negligible. Cell death was accompanied by annexin/PI costaining, but there was also evidence for annexin V-FITC staining without PI uptake. Conclusions PDT of experimental glioma results in rapid and significant cell death that could be verified as acute necrosis immediately after irradiation. This effect depended on O₂ concentration and spheroid size.     

18F-FET PET differentiation of ring-enhancing brain lesions.

The aim of this study was to explore the differential diagnostic value of PET using the amino acid O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) in patients with newly diagnosed solitary intracerebral lesions showing ring enhancement on contrast-enhanced MRI. METHODS: (18)F-FET PET analyses were performed on 14 consecutive patients with intracerebral ring-enhancing lesions. Eleven of the patients were additionally studied with (18)F-FDG PET. In all patients, the main differential diagnosis after MRI was a malignant lesion, in particular glioblastoma multiforme, versus a benign lesion, in particular brain abscess. A malignant tumor was suspected for lesions showing increased (18)F-FET uptake on PET images with a mean lesion-to-brain ratio of at least 1.6 ((18)F-FET PET positive). A nonneoplastic lesion was suspected in cases of minimal or absent (18)F-FET uptake, with a mean lesion-to-brain ratio of less than 1.6 ((18)F-FET PET negative). Histologic diagnosis was obtained by serial biopsies in 13 of the 14 patients. One patient refused the biopsy, but follow-up indicated an abscess because his lesion regressed under antibiotic therapy. RESULTS: Histology and clinical follow-up showed high-grade malignant gliomas in 5 patients and nonneoplastic lesions in 9 patients. The findings of (18)F-FET PET were positive in all 5 glioma patients and in 3 of 9 patients with nonneoplastic lesions, including 2 patients with brain abscesses and 1 patient with a demyelinating lesion. The findings of (18)F-FDG PET were positive (mean lesion-to-gray matter ratio > or = 0.7) in 4 of 4 glioma patients and 3 of 7 patients with nonneoplastic lesions. CONCLUSION: Although (18)F-FET PET has been shown to be valuable for the diagnostic evaluation of brain tumors, our data indicate that, like (18)F-FDG PET, (18)F-FET PET has limited specificity in distinguishing between neoplastic and nonneoplastic ring-enhancing intracerebral lesions. Thus, histologic investigation of biopsy specimens remains mandatory to make this important differential diagnosis.