Dysembryoplastic neuroepithelial tumors: where are we now?

Dysembryoplastic neuroepithelial tumors (DNTs) belong to the surgically treatable long-term epilepsy-associated group of tumors. Based on cortical specimens provided through epilepsy surgery at Sainte-Anne hospital, three histologic subtypes (simple, complex, and nonspecific) have been described. Electroclinical data, imaging, intralesional recordings (stereo-electroencephalography [EEG]) and histologic correlations have been recently reviewed in order to assess the relationship between the epileptogenic zone (EZ), the tumor, and associated focal cortical dysplasia (FCD), and to determine optimal strategy for curing epilepsy.

Dysembryoplastic neuroepithelial tumors: epileptogenicity related to histologic subtypes.

Objective: To analyze the electroclinical features and the relationship between the epileptogenic zone (EZ), the tumor and focal cortical dysplasia (FCD) in the three histologic subtypes of dysembryoplastic neuroepithelial tumors (DNTs) ("simple", "complex" and "non-specific forms").

Methods: We analyzed electroclinical data from 78 patients (50 males; 3-54 years) operated for intractable epilepsy due to a DNT. We compared EZ extent, defined by stereo-electroencephalography (n = 33), with the tumor and FCD areas, in each DNT subtype.

Dysembryoplastic neuroepithelial tumors: an MRI-based scheme for epilepsy surgery.

Objective: To determine optimal resections in the 3 dysembryoplastic neuroepithelial tumor (DNT) histologic subtypes (simple, complex, and nonspecific) based on MRI features.

Methods: In 78 consecutive epilepsy patients operated for DNT, MRI features were classified as follows: type 1 (cystic/polycystic-like, well-delineated, strongly hypointense T1), type 2 (nodular-like, heterogeneous), or type 3 (dysplastic-like, iso/hyposignal T1, poor delineation, gray-white matter blurring). Correlations between histology, neurophysiologic findings, and surgical outcome were established for each MRI subtype.

Dynamic imaging response following radiation therapy predicts long-term outcomes for diffuse low-grade gliomas.

Quantitative imaging assessment of radiation therapy (RT) for diffuse low-grade gliomas (DLGG) by measuring the velocity of diametric expansion (VDE) over time has never been studied. We assessed the VDE changes following RT and determined whether this parameter can serve as a prognostic factor. We reviewed a consecutive series of 33 adults with supratentorial DLGG treated with first-line RT with available imaging follow-up (median follow-up, 103 months).

Type II focal cortical dysplasia: electroclinical phenotype and surgical outcome related to imaging.

Purpose: Type II focal cortical dysplasia (TTFCD), a highly epileptogenic lesion with severe epilepsy curable by surgery, is missed by magnetic resonance imaging (MRI) in about one third of cases. Little is known about the electroclinical presentation in these MRI-negative patients and a poor surgical outcome is frequently reported. We compared the clinical and neurophysiologic features in MRI-negative and MRI-positive cases in order to better identify candidates for surgery.

Proteomic analysis of oligodendrogliomas expressing a mutant isocitrate dehydrogenase-1.

Gliomas are primary tumors of the human central nervous system with unknown mechanisms of progression. Isocitrate dehydrogenase-1 (IDH1) mutation is frequent in diffuse gliomas such as oligodendrogliomas. To gain insights into the physiopathology of oligodendrogliomas that have a better prognosis than other diffuse gliomas, we combined microdissection, 2-D DIGE and MS/MS focusing on proteome alterations associated with IDH1 mutation.

Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels.

We have investigated the transcriptomic and/or proteomic patterns of 71 solute carrier (SLC) and organic solute (OST) transporters, 34 ATP-binding cassette (ABC) transporters, and 51 metabolizing enzymes in human brain microvessels. We used quantitative RT-PCR and LC-MS/MS to examine isolated brain microvessels and cortex biopsies from 12 patients with epilepsia or glioma. SLC2A1/GLUT1, SLC1A3/EAAT1, and SLC1A2/EAAT2 were the main SLC proteins whereas ABCG2/BCRP, ABCB1/MDR1, ABCA2 and ABCA8 were the main ABC quantified in isolated brain microvessels; ABCG2/BCRP was 1.

Clinical relevance of tumor cells with stem-like properties in pediatric brain tumors.

Background: Primitive brain tumors are the leading cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined.

Neuropathological and Reelin deficiencies in the hippocampal formation of rats exposed to MAM; differences and similarities with schizophrenia.

Background: Adult rats exposed to methylazoxymethanol (MAM) at embryonic day 17 (E17) consistently display behavioral characteristics similar to that observed in patients with schizophrenia and replicate neuropathological findings from the prefrontal cortex of psychotic individuals. However, a systematic neuropathological analysis of the hippocampal formation and the thalamus in these rats is lacking. It is also unclear if reelin, a protein consistently associated with schizophrenia and potentially involved in the mechanism of action of MAM, participates in the neuropathological effects of this compound.

CD133, CD15/SSEA-1, CD34 or side populations do not resume tumor-initiating properties of long-term cultured cancer stem cells from human malignant glio-neuronal tumors.

Background: Tumor initiating cells (TICs) provide a new paradigm for developing original therapeutic strategies.

Methods: We screened for TICs in 47 human adult brain malignant tumors. Cells forming floating spheres in culture, and endowed with all of the features expected from tumor cells with stem-like properties were obtained from glioblastomas, medulloblastoma but not oligodendrogliomas.

NG2+/Olig2+ cells are the major cycle-related cell population of the adult human normal brain.

A persistent cycling cell population in the normal adult human brain is well established. Neural stem cells or neural progenitors have been identified in the subventricular zone and the dentate gyrus subgranular layer (SGL), two areas of persistent neurogenesis. Cycling cells in other human normal brain areas, however, remains to be established.

ABC transporters, cytochromes P450 and their main transcription factors: expression at the human blood-brain barrier.

We have established the expression patterns of the genes encoding ATP-binding cassette (ABC) transporters and cytochromes P450 (CYPs) at the adult human blood-brain barrier (BBB) using isolated brain microvessels and cortex biopsies from patients with epilepsia or glioma. Microves synaptophysin (neurons) and neuron-glial antigen 2 (NG2) (pericytes). ABCG2 [breast cancer resistance protein (BCRP)] and ABCB1 (MDR1) were the main ABC transporter genes expressed in microvessels, with 20 times more ABCG2 and 25 times more ABCB1 in microvessels than in the cortex.

GFAPdelta immunostaining improves visualization of normal and pathologic astrocytic heterogeneity.

Neuropathological analysis of cellular mechanisms underlying gliosis and brain tumors is slowed by the lack of markers allowing to distinguish glial subpopulations in normal or pathological human brains. We therefore evaluated GFAPdelta immunostaining in a wide panel of astrogliosis and gliomas, and compared these with GFAP and vimentin. In normal tissue, gliosis and gliomas, GFAPdelta immunostaining was observed in astrocytes with relatively high GFAP levels.

Evaluation of drug penetration into the brain: a double study by in vivo imaging with positron emission tomography and using an in vitro model of the human blood-brain barrier.

The blood-brain barrier (BBB) permeabilities of 11 compounds were measured both in vitro with a newly developed coculture-based model of human BBB and in vivo with positron emission tomography (PET). The 11 compounds were fluoropyridinyl derivatives labeled with the positron-emitter fluorine-18, [(18)F]F-A-85380 [2-[(18)F]fluoro-3-[2(S)-2 azetidinylmethoxy]pyridine], and 10 selected N-substituted-azetidinyl and pyrrolidinyl closely related [(18)F]fluoropyridinyl derivatives (including [N'-aromatic/aliphatic]-thioureas, -ureas, and -amides). The in vitro BBB model, a new coculture system of primary human brain endothelial cells and astrocytes, was used to measure the permeability coefficient for each compound.

Diffusion tensor imaging of partial intractable epilepsy.

Our aim was to assess the value of diffusion tensor imaging (DTI) in patients with partial intractable epilepsy. We used DTI (25 non-collinear directions) in 15 patients with a cortical lesion on conventional MRI. Fractional anisotropy (FA) was measured in the internal capsule, and in the normal-appearing white matter (WM), adjacent to the lesion, and away from the lesion, at a set distance of 2-3 cm.

New variants of malignant glioneuronal tumors: a clinicopathological study of 40 cases.

Objective: To demonstrate that malignant glioneuronal tumors comprise a large spectrum of neoplasms, without mature ganglion-like cells, that may histologically resemble any malignant glioma (World Health Organization Grade III or IV) but have a distinct biological behavior.

Methods: This series includes all tumors diagnosed as malignant glioneuronal tumors (MGNTs) in our routine practice during a 2-year period during which neurofilament protein (NFP) immunostaining was performed in any case of suspected malignant glioma with unusual clinical, radiographic, and/or histological features. Immunostaining using neuronal markers (NFP, NeuN, synaptophysin, and chromogranin) and glial fibrillary acidic protein was done on paraffin sections after antigen retrieval.

Synemin expression in developing normal and pathological human retina and lens.

Synemin (Syn) is an intermediate filament (IF) protein. To gain insight into a morphogenetic role of Syn, we have studied its expression patterns in the developing human retina and lens and compared it with those of other IF proteins. In addition, we have tested Syn expression in fetuses (23 and 28 weeks) affected by Walker-Warburg syndrome (WWS), Meckel syndrome, and trisomy 13.

Cortical radial glial cells in human fetuses: depth-correlated transformation into astrocytes.

In the human brain, the transformation of radial glial cells (RGC) into astrocytes has been studied only rarely. In this work, we were interested in studying the morphologic aspects underlying this transformation during the fetal/perinatal period, particularly emphasizing the region-specific glial fiber anatomy in the medial cortex. We have used carbocyanine dyes (DiI/DiA) to identify the RGC transitional forms and glial fiber morphology.

Immunohistological localization of the myelinating cell-specific receptor LP(A1).

LP(A1) (also termed Edg-2 or VZG-1) is a G-protein-coupled receptor for lysophosphatidic acid and its gene transcripts have been found selectively expressed by mature myelin-producing cells. We have raised in rabbit a polyclonal antibody against a sequence unique to LP(A1) and common to rat, mouse, and human orthologues. In Western blots, LP(A1) immunoreactivity appeared as 44-53 kDa bands in extracts from recombinant RH7777 cells expressing LP(A1), mouse purified oligodendrocytes, or human white matter, but not from wild-type RH7777 cells or purified astrocytes.