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C Daumas-Duport

Publications and source records attributed to C Daumas-Duport.

At least 19 recordsLinked to original sources
PubMed2005

Functional endothelin ET B receptors are selectively expressed in human oligodendrogliomas.

Endothelin-1 (ET-1), a vasoactive and mitogenic peptide mainly produced by vascular endothelial cells, may be involved in the progression of several human tumors. Here, we present an immunohistochemical analysis of the expression pattern of ET-1 receptor subtypes (ET(A)-R and ET(B)-R) and a functional study of their potential role in human oligodendrogliomas and oligoastrocytomas. By comparison, we assessed the corresponding expression patterns of glioblastomas. Interestingly, a nuclear localization of ET-1 receptor subtypes (associated or not with a cytoplasmic labeling) was constantly observed in tumor cells from all three glioma types. Moreover, we noted a distinct receptor distribution in the different gliomas: a nuclear expression of ET(B)-R by tumor cells was found to be restricted to oligodendrogliomas and oligoastrocytomas, while a nuclear expression of ET(A)-R was only detected in tumor cells from some glioblastomas. Using primary cultures of oligodendroglial tumor cells, we confirmed the selective expression of nuclear ET(B)-R, together with a plasma membrane expression, and further demonstrated that this receptor was functionally coupled to intracellular signaling pathways known to be involved in cell survival and/or proliferation: extracellular signal-regulated kinase and focal adhesion kinase activation, actin cytoskeleton reorganization. In addition, impairment of ET(B)-R activation in these cells by in vitro treatment with an ET(B)-R-specific antagonist induced cell death. These data point to ET-1 as a possible survival factor for oligodendrogliomas via ET(B)-R activation and suggest that ET(B)-R-specific antagonists might constitute a potential therapeutic alternative for oligodendrogliomas.

Actin Cytoskeleton↗
PubMed2005

[Oligodendrogliomas: historical background of classifications].

The story of the classifications for gliomas is related to the development of the techniques used for cytological and histological examination of brain parenchyma. After a review of these techniques and the progressive discovery of the central nervous system cell types, the main classifications are presented. The first classification is due to Bailey and Cushing in 1926. It was based on histoembryogenetic theory. Then Kernohan introduced, in 1938, the concept of anaplasia. The WHO classification was published in 1979, then revised in 1993 and 2000. It took into account some data from both previous systems and introduced gradually the notion of histological criteria of malignancy. More recently; molecular genetics data and clinical evolution were retained. The Sainte-Anne classification for oligodendrogliomas is based on both histological and imaging data. It includes the notion of spatial histological structure of oligodendrogliomas. Contrast enhancement is closely related to endotheliocapillary hyperplasia. Gliomas classifications are changing and confusions can be made because of lack of reproductibility and misinterpretations of samples.

Brain Neoplasms↗
PubMed2005

[Criteria of diagnosis and grading of oligodendrogliomas or oligo-astrocytomas according to the WHO and Sainte-Anne classifications].

Two main classification systems are used in France for the histological typing and grading of oligodendrogliomas: the WHO and Sainte-Anne Hospital (SA) classifications. According to the WHO, the typing of diffuse gliomas is based on the predominant cell type, oligodendroglial versus astrocytic. In contrast, the SA classification is based on the distinction of two patterns of tumor growth, solid tumor tissue versus isolated tumor cells and also relies on imaging and clinical features. According to this approach, the SA classification includes in the category of oligodendrogliomas, the fibrillary or gemistocytic diffuse astrocytomas (WHO grade II) as well as a substantial proportion of astrocytomas WHO grade III, 2) the WHO uses multiple histological criteria for the grading of oligodendrogliomas (grade II versus grade III), including the degree of differentiation, cellular atypia, mitotic activity and necrosis. In contrast, the SA grading of these tumors (grade A versus B) only uses two criteria: the presence or absence of endothelial hyperplasia, and the presence or absence of contrast enhancement. This last criterion allows overcoming the problems related to the representativeness of surgical samples. Difficulties and discrepancies regarding the diagnosis of oligodendrogliomas are in part due to the lack of immunomarker for the identification of tumoral oligodendrocytes. The potential interest of new markers of oligodendroglial precursors for the diagnosis of these tumors will further be discussed.

Astrocytoma↗
PubMed2005

[Reappraisal of the Sainte-Anne Hospital classification of oligodendrogliomas in view of retrospective studies].

PURPOSE: Definition of homogeneous tumor groups of oligodendrogliomas or oligo-astrocytomas is a basic condition for an adequate evaluation and comparison of the results of treatments in patients from various institutions. However, increasing discordances are observed in the histological diagnosis of these tumors. The main goal of this study is to assess whether, for retrospective studies, MRI data may serve as a common basis for encompassing asymmetry in diagnosis established according to the WHO or Ste-Anne (SA) classification. PATIENTS AND METHODS: This study included 251 adult patients in whom a SA grade A or B oligodendroglioma or oligo-astrocytoma was newly diagnosed at our institution from 1984 to 2003. Routine histological preparations and post-contrast preoperative MRI/CT-scan were simultaneously reviewed in order to assess the impact on survival of the following features: presence or absence of a polymorphous or gemistocytic astrocytic component, of necrosis and of contrast enhancement (CH); endothelial hyperplasia (EH) assessed as absent, present minor (HE+) or (HE++) when conform to the threshold of HE defined in the SA grading system of oligodendrogliomas. The tumors were graded A: no CH and no EH; in B: CH and /or HE++, and A/B: EH + but no CE. RESULTS: 70.1% of the tumors were classified as "pure" oligodendroglioma, 19.5% as "polymorphous oligo-astroastrocytoma" and 10.3% as "gemistocytic oligo-astrocytoma". In grade A, or B tumors, the presence of a polymorphous or a gemistocytic component had no significant influence on survival; however respectively 53% and 65% of these tumours versus 32% of "pure" oligodendrogliomas were grade B at the time of diagnosis. In either histological subtypes, survival was not significantly different when HE was absent or minor (HE+). After regrouping of the histological subtypes and of the tumors with HE+ or absent, the series included 153 oligodendrogliomas grade A and 98 grade B. Survival in patients with grade A versus grade B tumors was respectively 142 versus 52 months (p<0.0001). In grade B tumors, necrosis had no significant influence on survival. Ring-shaped contrast enhancement surrounding large foci of necrosis was observed in only 4 cases. In tumors with or without CE, patient survival was respectively 148 versus 40 months (p<0.0001). On post contrast MRI done in 235 patients, only 7 tumors (3%) were grade A/B (EH++ but no CH). CONCLUSIONS: From these results and our previous observation that, according to the SA classification of gliomas, only oligodendrogliomas or oligo-astrocytomas may not show CE, we propose that for retrospective studies: 1) tumors diagnosed according to the Ste-Anne classification as oligodendroglioma or oligo-astrocytoma be regrouped in a unique category, 2) independent of their histological type and grade according to the WHO, gliomas that do not show CE be regrouped with SA oligodendrogliomas grade A, 3) concerning gliomas that show CE on MRI: oligodendrogliomas or oligo-astrocytomas WHO grade II or III, as well as WHO secondary glioblastomas or glioblastomas with an oligodendroglial component, be regrouped with SA oligodendrogliomas grade B; however tumors that show ring-like CE surrounding large foci of necrosis and finger-like "peritumoral" edema should be excluded or analysed separately.

Adult↗
PubMed2005

[Spatial delimitation of low grade oligodendrogliomas].

Image-guided surgery is the central element of therapeutic management of low grade gliomas and consequently, a precise preoperative definition of their spatial extension is necessary. The question of the present work is: do the imaging abnormalities delineate the real spatial development of low grade oligodendrogliomas? A review of the literature showed that MRI on T2-weighted and FLAIR sequences are used to delineate the spatial developement of these tumours and that spectroscopic magnetic resonance imaging is more sensible to appreciate it. Moreover, mathematical models and histological studies suggest that MRI does not indicate the actual spatial extension of low grade oligodendrogliomas. This study focused on histological analysis of biopsy samples performed outside MRI imaging abnormalities in patients who harboured a low grade oligodendroglioma. It showed that isolated tumour cells were identified beyond imaging abnormalities in all of the 17 patients studied. In 15 of those 17 patients, isolated tumour cells were identified in the most distant biopsy samples taken outside imaging abnormalities. Thus, conventional imaging findings, including MRI on T2-weighted and FLAIR sequences, are not able to provide the real spatial development and boundaries of low grade oligodendrogliomas.

Adolescent↗
PubMed2005

[Results of the Sainte-Anne - Lyons series of 318 oligodendroglioma in adults].

INTRODUCTION: Incidence of cerebral oligodendrogliomas is increasing because of better recognition made possible by improved classifications. We studied a homogeneous series using the Sainte-Anne grading scale in order to better understanding the history of these tumors with or without treatment and to assess prognosis and associated factors. PATIENTS AND METHODS: A retrospective series of 318 adult patients with oligodendroglioma (OLG) treated at Hôpital Sainte-Anne, Paris (SA) and Hôpital Neurologique, Lyons (L) between 1984 and 2003 was analyzed: 182 grade A OLG (SA + L), 136 grade B among which a homogenous series of 98 (SA) were included. For grade A: age at diagnosis ranged from 21 to 70 (mean: 41), sex ratio was 1.28. For grade B: age at diagnosis ranged from 12 to 75 (mean: 45.5), sex-ratio was 1.58. The main first symptoms were: epilepsy (A: 91.5%; B: 76%), intracranial hypertension (A: 7.9%; B: 14.6%), neurological deficit (A: 5.1%; B: 17.7%). The most frequent locations were: frontal, insular and central for both A and B. Mean size was 55 mm for grade A, 62 mm for B. Calcifications were found in 20% of A, 48.5% of B. No tumor was enhanced on imaging (CT/MRI) in grade A, all but 7 in grade B. All patients underwent surgery either for biopsy (A: 47.2%; B: 53%), or removal which was partial (A: 26.4% vs B: 19.4%) or extended (A: 36.3% vs B: 37.8%). Fifty-six patients underwent 2 procedures and 12 three procedures. Radiotherapy was performed in 76.9% of grade A, and 91% of B patients, in the immediate postoperative period for 71% A and 82.7% B. Chemotherapy was delivered for 36% of grade A (in the event of transformation to grade B or failure of radiotherapy) and 67.5% of B patients. Among grade A tumors, 38% transformed into grade B within a mean delay of 51 months with a mean follow-up of 78 months. RESULTS: Median survival was 136 months for grade A and 52 for grade B. Survival at 5, 10 and 15 was 75.5%, 51% and 22.4% for grade A vs 45.2%, 31.3% and 0% for grade B respectively. In univariate and multivariate analysis, grade A survival was associated with age at diagnosis, tumor size, large removal and response to radiotherapy. Grade B survival was associated with age at diagnosis, wide removal and sharply defined limits of the tumor on imaging. CONCLUSIONS: Analysis of both published data and this series underlines many prognostic parameters. It shows that OLG are heterogeneous tumors even in each grade (A and B). Treatment should consequently progress towards more targeted procedures for patients mainly with postoperative radiotherapy and chemotherapy.

Adolescent↗
PubMed2003

[Dysembryoplastic neuroepithelial tumors].

Dysembryoplastic neuroepithelial tumors DNTs are highly polymorphic tumors that arise during embryogenesis. They are preferentially, but not exclusively, located in the supratentorial cortex. Histologically they may mimic any categories of low-grade or even of high-grade gliomas, but from a carcinological point of view, they behave as stable lesions. Their differential diagnosis from gliomas is obviously important to spare these young patients with a normal life expectancy the long- term deleterious effect of radiation or chemotherapy. The diagnosis of DNT must be considered when all the following criteria are present: partial seizures with or without secondary generalization, no neurological deficit or a stable congenital deficit, cortical topography on MRI, absence of peri-tumoral edema and of mass effect. In other locations, the diagnosis of DNT has to be suspected in case of discordance between the neurological status of the patient and the topography of the tumor or of unusual radiological features such as contrast enhancement but no mass effect and no edema. Supratentorial cortical DNTs tend now to be detected more systematically by imaging soon after first seizures. In most instances, the epilepsy can be cured by gross total surgical removal. Surgery also allows to prevent the risks of intratumoral hematoma or infarct. DNTs should therefore be operated soon after diagnosis. However, excellent results can also be obtained by epilepsy surgery in patients with long term drug resistant partial seizures.

Brain Neoplasms↗
PubMed2002

Comparison of somatostatin receptor expression in human gliomas and medulloblastomas.

The expression of the five somatostatin receptor subtypes, sst1-5 was compared on tissue containing glial tumours (glioblastomas or oligodendrogliomas), medulloblastomas, and on normal human cortex. By semiquantitative reverse transcription coupled to polymerase chain reaction, the receptor expression profiles were high in cortex and in tissue containing oligodendrogliomas. It was moderate in medulloblastomas. Tissue containing glioblastomas displayed lower expression of somatostatin receptor subtypes, sst1 and sst3 being mostly expressed. By 125I-Tyr0DTrp8 somatostatin-14 or 125I-Leu8DTrp22 Tyr25 somatostatin-28 autoradiography combined with synaptophysin immunohistochemistry, it was possible to differentiate between isolated tumoral cell component infiltrating the cerebral parenchyma (cortex or white matter) and tumoral tissue (without residual parenchyma) in glioblastomas or oligodendrogliomas. Glial tumoral tissue per se presented few somatostatin receptors. By contrast, medulloblastoma tumoral cells exhibited numerous octreotide sensitive somatostatin receptors. sst2 immunocytochemistry demonstrated immunostaining of neuronal cells and neuropile; sst2 and sst3 immunostaining was identified on glioblastoma proliferating vessels endothelial cells and on medulloblastomas tumoral cells. Faint sst2 immunostaining among glial tumoral cells was due to microglia, while glioma cells did not significantly stain. In summary, medulloblastoma tumoral cells express sst2/sst3 receptors at a high level while glioma cells do not. In gliomas, sst expression is restricted to endothelial cells on proliferating vessels (displaying both sst2 and sst3 receptors), including parenchyma and reactive microglia (only sst2). The differential expression of sst2/sst3 receptors on gliomas and medulloblastomas has implications for the therapy of these tumours.

Adolescent↗
PubMed2000

Apoptosis in the central nervous system of cerebral adrenoleukodystrophy patients.

The childhood cerebral form of adrenoleukodystrophy (ALD) is a fatal demyelinating disease, yet mice deficient in the ALD gene do not show such clinicopathological phenotype. We have therefore investigated in human autopsy tissues whether the ALD gene mutation results in apoptosis of CNS cells. Specimens from telencephalic and brainstem regions of four patients, and three controls were examined for internucleosomal DNA fragmentation, in situ detection of DNA breaks by the TUNEL method, and caspase-3 immunostaining. None of the controls showed significant apoptosis in white matter, while apoptotic nuclei with chromatin alterations were detected in areas of active demyelination in three ALD patients. A large proportion of apoptotic cells were oligodendrocytes and some express activated caspase-3. TUNEL-positive nuclei and/or caspase-3 staining were also detected in perivascular infiltrates and, occasionally, in neurons. We conclude that apoptosis of oligodendrocytes may account, at least in part, for the demyelinating process in the ALD brain.

Adolescent↗
PubMed2000

Vascular endothelial growth factor expression in oligodendrogliomas: a correlative study with Sainte-Anne malignancy grade, growth fraction and patient survival.

Microangiogenesis is a delayed but crucial event in the malignant progression of oligodendrogliomas. Accord-ingly, in the new Sainte-Anne grading system of oligodendrogliomas, endothelial hyperplasia and contrast enhancement, both being indicators of microangiogenesis, are key criteria for the distinction of grade A from grade B tumours. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor: a strong correlation between VEGF expression, Sainte-Anne malignancy grade and patient outcome might thus be expected. In order to assess this hypothesis, VEGF immunostaining was performed in a series of 34 oligodendrogliomas that included 11 grade B and 23 grade A, of which nine became grade B during the study period (mean clinical and imaging follow-up: 41 months). VEGF expression correlated strongly with Sainte-Anne tumour grade (P < 0.001), and inversely with patient survival (P < 0.001) and recurrence-free survival (P = 0.002). One hundred per cent of grade B but only 17% of grade A were VEGF-positive. By contrast, the MIB-1 labelling index did not correlate with VEGF expression, total survival or recurrence-free survival. In accordance with the grading system, this study showed that, in oligodendrogliomas, VEGF expression and microangiogenesis are progression-related phenomena that confer on these tumours a growth advantage by presumably reducing hypoxia-induced apoptotic cell death. These findings might have important implications in the future for the indication and timing of anti-angiogenic therapies.

Adult↗
PubMed2000

Stereoelectroencephalography in focal cortical dysplasia: a 3D approach to delineating the dysplastic cortex.

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.

Adolescent↗
PubMed2000

[The "smears" technique for the extemporaneous examination: diagnostic contribution to neurosurgical pathology].

Smear preparation is a fairly accurate, simple and reliable tool for rapid intraoperative diagnosis of central nervous system tumors. Compared with frozen sections this technique has the advantage of being both more accurate for cytological details and of requiring less tissue. In addition final histological analysis after direct formalin fixation is of better quality than post freezing fixation. This technique is most helpful in the field of neuro-oncological pathology specially in glial tumors and in stereotactic biopsy procedures. The cytological aspects and smear patterns disclose important complementary diagnostic information for the histopathological examination.

Brain Neoplasms↗
PubMed1999

Modulated release of IdUrd from poly (D,L-lactide-co-glycolide) microspheres by addition of poly (D,L-lactide) oligomers.

This paper reports the release characteristics of a radiosensitizer, 5-iodo-2'-deoxyuridine (IdUrd), from poly (D,L-lactide-co-glycolide) 50: 50 (PLGA) microparticles obtained by a phase separation technique. Poly (D,L-lactide) oligomers (D,L-PLA) were incorporated into the PLGA matrix in order to accelerate the overall drug release rate and regulate the triphasic release profile exhibited by the standard PLGA microparticles. For D,L-PLA (800), the burst effect was large and the IdUrd release was complete between 28 and 35 days. These results were attributed to rapid pore formation on the periphery of the microsphere in the early stages of incubation, due to hydrosolubility of the smallest oligomers (D,L-PLA (800)). In the case of D,L-PLA (1,100), drug release occurred over a six week period, the standard time course of conventional radiation therapy. The period during which the radiosensitizer was incorporated in human brain tumor cell nuclei after its entrapment in biodegradable microspheres was determined by using an organotypical tissue culture. The presence of radiosensitizer in the DNA of tumor cell nuclei was detected by immunohistochemical labelling of tumor fragments. IdUrd release from standard microspheres (7+/-0.5 weeks) was longer than from oligomer-containing batches. For D,L-PLA (800)-containing microspheres, the radiosensitizer was entirely released within 4. 5+/-0.5 weeks. The microspheres containing D,L-PLA (1,100) allowed an IdUrd release over a 5 to 6 week period. The ex vivo data were consistent with the in vitro findings in terms of release duration.

Biodegradation, Environmental↗
PubMed1999

Edg-2 in myelin-forming cells: isoforms, genomic mapping, and exclusion in Charcot-Marie-Tooth disease.

Edg-2 is an heptahelical receptor whose spatio-temporal distribution during rat brain development is consistent with a role in the control of myelination. We have now identified two splice variants of Edg-2 mRNA in rat brain that encode two receptor isoforms differing by a stretch of 18 amino acids in the NH2-terminal extracellular tail of the receptor. Prenatally (i.e., before oligodendrocyte myelination), the two variants detected by selective in situ hybridization are equally abundant, vary in parallel, and remain restricted to proliferative zones in the brain. Postnatally, the long isoform becomes predominant in myelinating structures, where its abundance increases sharply during the period of myelination. In the adult human brain, only the long variant was detected, while in situ hybridization showed it selectively expressed in the white matter and in clusters of cells showing features of oligodendrocytes of the temporal cerebral cortex. Consequently, the human Edg-2 gene was studied to assess its possible contribution in inherited neuropathies. The coding sequence was found to be contained in three exons and to map to chromosome 9q31.3-32 by using radiation hybrid panel and Yeast-Artificial Chromosomes. Two intragenic bi-allelic polymorphisms and a rare mutation were identified. As a first application to molecular genetic studies, they were used to exclude the Edg-2 gene in six families with phenotype of demyelinating Charcot-Marie-Tooth disease of unknown origin.

Adult↗