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4. 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

Author

Josserand, Véronique, Pélerin, Hélène, de Bruin, Béatrice, Jego, Benoît, Kuhnast, Bertrand, Hinnen, Françoise, Ducongé, Frédéric, Boisgard, Raphaël, Beuvon, Frédéric, Chassoux, Francine, Daumas-Duport, Catherine, Ezan, Eric, Dollé, Frédéric, Mabondzo, Aloïse, and Tavitian, Bertrand

Published
2006
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16. 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

Author

Mihalescu-Maingot Maria, Berhneim Alain, Leonard Nadine, Thirant Cécile, Renault-Mihara François, Cadusseau Josette, Raponi Eric, Coulombel Laure, Varlet Pascale, Romao Luciana, Patru Cristina, Haiech Jacques, Bièche Ivan, Moura-Neto Vivaldo, Daumas-Duport Catherine, Junier Marie-Pierre, and Chneiweiss Hervé

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract 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. Results A long-term self-renewal capacity was particularly observed for cells of malignant glio-neuronal tumors (MGNTs). Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passages. Xenografts of fewer than 500 cells in Nude mouse brains induced a progressively growing tumor. CD133, CD15/LeX/Ssea-1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but was not predictive of their capacity to form secondary spheres or tumors, or to resist high doses of temozolomide. Conclusions Our results further highlight the specificity of a subset of high-grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies.

Published
2010
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21. Clinical relevance of tumor cells with stem-like properties in pediatric brain tumors

Author

Thirant, Cécile, Bessette, Barbara, Varlet, Pascale, Puget, Stéphanie, Cadusseau, Josette, Dos Reis Tavares, Silvina, Studler, Jeanne-Marie, Silvestre, David Carlos, Susini, Aurélie, Villa, Chiara, Miquel, Catherine, Bogeas, Alexandra, Surena, Anne-Laure, Dias-Morais, Amélia, Léonard, Nadine, Pflumio, Françoise, Bièche, Ivan, Boussin, François D, Sainte-Rose, Christian, Grill, Jacques, Daumas-Duport, Catherine, Chneiweiss, Hervé, Junier, Marie-Pierre, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of neuropathology, Hôpial Sainte-Anne, Service de neurochirurgie pédiatrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), INSERM U955, équipe 10, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Collège de France (CdF (institution)), Stabilité génétique, Cellules Souches et Radiations (SCSR (U_967)), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Genetique Moleculaire des Cancers d'Origine Epitheliale, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris]

Subjects
MESH: Adolescent, MESH: Neural Stem Cells, child, MESH: Humans, MESH: Immunophenotyping, MESH: Child, Preschool, MESH: Flow Cytometry, medulloblastoma, MESH: Infant, MESH: Neoplastic Stem Cells, MESH: Cell Separation, MESH: Male, MESH: Glioma, glioma, MESH: Survival Analysis, MESH: Child, MESH: Brain Neoplasms, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, TP53, pilocytic astrocytoma, MESH: Female, ganglioglioma
Abstract

International audience; 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. METHODOLOGY/PRINCIPAL FINDINGS: Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). Most high-grade glioma-derived oncospheres (10/12) sustained long-term self-renewal akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumors. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P = 0.05, chi-square test). Survival analysis of the cohort showed an association between isolation of cells with long-term self-renewal abilities and a higher patient mortality rate (P = 0.013, log-rank test). Sampling of low- and high-grade glioma cultures showed that self-renewing cells forming oncospheres shared a molecular profile comprising embryonic and neural stem cell markers. Further characterization performed on subsets of high-grade gliomas and one low-grade glioma culture showed combination of this profile with mesenchymal markers, the radio-chemoresistance of the cells and the formation of aggressive tumors after intracerebral grafting. CONCLUSIONS/SIGNIFICANCE: In brain tumors affecting adult patients, TSCs have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors.

Published
2011
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22. Proteomic analysis of oligodendrogliomas expressing a mutant isocitrate dehydrogenase‐1

Author

Thirant, Cécile, primary, Varlet, Pascale, additional, Lipecka, Joanna, additional, Le Gall, Morgane, additional, Broussard, Cédric, additional, Chafey, Philippe, additional, Studler, Jeanne‐Marie, additional, Lacombe, Joelle, additional, Lions, Séverin, additional, Guillaudeau, Angélique, additional, Camoin, Luc, additional, Daumas‐Duport, Catherine, additional, Junier, Marie‐Pierre, additional, and Chneiweiss, Hervé, additional

Published
2011
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23. Transcriptomic and Quantitative Proteomic Analysis of Transporters and Drug Metabolizing Enzymes in Freshly Isolated Human Brain Microvessels

Author

Shawahna, Ramzi, primary, Uchida, Yasuo, additional, Declèves, Xavier, additional, Ohtsuki, Sumio, additional, Yousif, Salah, additional, Dauchy, Sandrine, additional, Jacob, Aude, additional, Chassoux, Francine, additional, Daumas-Duport, Catherine, additional, Couraud, Pierre-Olivier, additional, Terasaki, Tetsuya, additional, and Scherrmann, Jean-Michel, additional

Published
2011
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26. 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

Author

Patru, Cristina, primary, Romao, Luciana, additional, Varlet, Pascale, additional, Coulombel, Laure, additional, Raponi, Eric, additional, Cadusseau, Josette, additional, Renault-Mihara, François, additional, Thirant, Cécile, additional, Leonard, Nadine, additional, Berhneim, Alain, additional, Mihalescu-Maingot, Maria, additional, Haiech, Jacques, additional, Bièche, Ivan, additional, Moura-Neto, Vivaldo, additional, Daumas-Duport, Catherine, additional, Junier, Marie-Pierre, additional, and Chneiweiss, Hervé, additional

Published
2010
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28. 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

Author

Josserand, Véronique, primary, Pélerin, Hélène, additional, de Bruin, Béatrice, additional, Jego, Benoît, additional, Kuhnast, Bertrand, additional, Hinnen, Françoise, additional, Ducongé, Frédéric, additional, Boisgard, Raphaël, additional, Beuvon, Frédéric, additional, Chassoux, Francine, additional, Daumas-Duport, Catherine, additional, Ezan, Eric, additional, Dollé, Frédéric, additional, Mabondzo, Aloïse, additional, and Tavitian, Bertrand, additional

Published
2005
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29. Diffusion tensor imaging of partial intractable epilepsy

Author

Dumas de la Roque, Anne, primary, Oppenheim, Catherine, additional, Chassoux, Francine, additional, Rodrigo, Sebastian, additional, Beuvon, Fr�d�ric, additional, Daumas-Duport, Catherine, additional, Devaux, Bertrand, additional, and Meder, Jean-Fran�ois, additional

Published
2004
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34. Dysembryoplastic neuroepithelial tumors.

Author

Chassoux, Francine, Rodrigo, Sebastian, Mellerio, Charles, Landré, Elisabeth, Miquel, Catherine, Turak, Baris, Laschet, Jacques, Meder, Jean-François, Roux, François-Xavier, Daumas-Duport, Catherine, and Devaux, Bertrand

Published
2012
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36. NG2+/Olig2+ Cells are the Major Cycle-Related Cell Population of the Adult Human Normal Brain.

Author

Geha, Sameh, Pallud, Johan, Junier, Marie-Pierre, Devaux, Bertrand, Leonard, Nadine, Chassoux, Francine, Chneiweiss, Hervé, Daumas-Duport, Catherine, and Varlet, Pascale

Subjects
CELL proliferation, CELL cycle, NEURAL stem cells, NEURONS, DEVELOPMENTAL neurobiology, HIPPOCAMPUS (Brain)
Abstract

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. Here, we determined the distribution and identity of these cells in the cortex, the white matter and the hippocampal formation of adult patients with and without chronic temporal lobe epilepsy using immunohistochemistry for the cell cycle markers Ki-67 (Mib-1) and minichromosome maintenance protein 2. Rare proliferative neuronal precursors expressing the neuronal antigen neuronal nuclei were restricted to the SGL. In contrast, the oligodendrocyte progenitor cell markers Olig2 and the surface antigen NG2 were expressed by the vast majority of cycling cells scattered throughout the cortex and white matter of both control and epileptic patients. Most of these cycling cells were in early G1 phase, and were significantly more numerous in epileptic than in non-epileptic patients. These results provide evidence for a persistent gliogenesis in the human cortex and white matter that is enhanced in an epileptic environment. [ABSTRACT FROM AUTHOR]

Published
2010
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37. CD133, CD15/SSEA-1, CD34 or side populationsdo not resume tumor-initiating properties oflong-term cultured cancer stem cells from humanmalignant glio-neuronal tumors.

Author

Patru, Cristina, Romao, Luciana, Varlet, Pascale, Coulombel, Laure, Raponi, Eric, Cadusseau, Josette, Renault-Mihara, François, Thirant, Cécile, Leonard, Nadine, Berhneim, Alain, Mihalescu-Maingot, Maria, Haiech, Jacques, Bièche, Ivan, Moura-Neto, Vivaldo, Daumas-Duport, Catherine, Junier, Marie-Pierre, and Chneiweiss, Hervé

Subjects
CEREBELLAR tumors, STEM cells, CANCER cells, LABORATORY animals, GLIOMAS
Abstract

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. Results: A long-term self-renewal capacity was particularly observed for cells of malignant glio-neuronal tumors (MGNTs). Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passages. Xenografts of fewer than 500 cells in Nude mouse brains induced a progressively growing tumor. CD133, CD15/LeX/Ssea-1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but was not predictive of their capacity to form secondary spheres or tumors, or to resist high doses of temozolomide. Conclusions: Our results further highlight the specificity of a subset of high-grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies. [ABSTRACT FROM AUTHOR]

Published
2010
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39. Diffusion tensor imaging of partial intractable epilepsy.

Author

de la Roque, Anne Dumas, Oppenheim, Catherine, Chassoux, Francine, Rodrigo, Sebastian, Beuvon, Frédéric, Daumas-Duport, Catherine, Devaux, Bertrand, and Meder, Jean-François

Subjects
EPILEPSY, BRAIN, MEDICAL imaging systems, DIAGNOSTIC imaging, RADIOLOGY, MEDICAL research
Abstract

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 tothe lesion, andaway fromthe lesion, at a set distance of 2-3 cm. In each patient, increased or decreased FA measurements were those that varied from mirror values using an arbitrary 10% threshold. Over the whole population, ipsi- and contralateral FA measurements were also compared using a Wilcoxon test (p<0.05). Over the whole population, FA was significantly reduced in the WMadjacent toandaway fromthe lesion, whilst being normal in the internal capsule. FA was reduced by more than 10% in the WMadjacent toanddistant fromthe lesion in 13 and 12 patients respectively. For nine of the ten patients for whom the surgical resection encompassed the limits of the lesion on conventional MRI, histological data showed WM alterations (gliosis, axonal loss, abnormal cells). DTI often reveals WM abnormalities that are undetected on conventional MRI in patients with partial intractable epilepsy. [ABSTRACT FROM AUTHOR]

Published
2005
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42. Stereoelectroencephalography in focal cortical dysplasia

Author

Chassoux, Francine, Devaux, Bertrand, Landré, Elisabeth, Turak, Baris, Nataf, François, Varlet, Pascale, Chodkiewicz, Jean-Paul, and Daumas-Duport, Catherine

Abstract

Focal cortical dysplasia (FCD) is an increasingly recognized cause of intractable epilepsy. Surgical data suggest that the dysplastic cortex should be removed to obtain freedom from seizures, but the prognosis remains poor as FCD is difficult to delineate by imaging. We retrospectively analysed a series of 28 patients (aged 5-41 years, median 16.5 years) with FCD who had been investigated by stereoelectroencephalography (SEEG) between 1964 and 1995. Neurophysiological data were correlated with histological findings and surgical outcome. MRI was available for only seven patients. Severe partial epilepsy of early onset, pre-existing neurological deficit (68%) and cognitive impairment were the main clinical features. FCD was distributed equally between all lobes except for the temporal lobe, and was found predominantly on the mesial aspect of the cerebral hemispheres. SEEG findings provided evidence of dysplastic tissue epileptogenicity, as demonstrated by intralesional rhythmic spike discharges, the onset of ictal discharges and a low epileptogenic threshold. The epileptogenic zone corresponded to histologically defined FCD in 82% of the cases. Despite the lack of adequate neuroimaging in most cases, 64% of the patients became seizure-free after surgery. The main predictors of a favourable outcome were complete removal of the epileptogenic zone (P< 0.01) and complete removal of the dysplastic cortex (P< 0.01). These results emphasize the usefulness of neurophysiological data in accurately assessing the extent of the FCD.

Published
2000

43. Histological grading of gliomas

Author

Daumas-Duport, Catherine

Abstract

Usefulness of grading systems based on non-specific features (e.g. mitosis, necrosis) is unequivocal in only certain types of astrocytomas, and their efficiency remains to be seen in oligodendrogliomas and in mixed oligo-astrocytomas. The possibility of grading ependymomas is still uncertain. Accordingly, only a small proportion of gliomas which occur in children can be reliably graded. Lack of reproducibility is a severe impediment of both current conventional and kinetic methods in the prognosis of gliomas.

Published
1992

48. Postoperative radiotherapy of supratentorial low-grade gliomas

Author

Shaw, Edward G., primary, Scheithauer, Bernd W., additional, Gilbertson, David T., additional, Nichols, Douglas A., additional, Laws, Edward R., additional, Earle, John D., additional, Daumas-Duport, Catherine, additional, O'Fallon, Judith R., additional, and Dinapoli, Robert P., additional

Published
1989
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