31 research outputs found

    Perspectives pour une prise en charge plus précoce du cancer de l'ovaire (influences hormonale et immunitaire)

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    70 à 75% des cancers de l ovaire ne sont découverts qu à partir d un stade tardif (III). Les efforts actuels doivent donc converger vers la réalisation d un diagnostic plus précoce. Cette maladie n est pas complètement silencieuse. Un consensus pointe aujourd hui les symptômes clés dont l intensité et la fréquence doivent alerter les cliniciens et les patientes. Le dépistage de masse du cancer de l ovaire n est pas réalisable actuellement à défaut de marqueurs spécifiques tant biologiques que d imagerie. De nouveaux marqueurs sont en développement. L indication d un dépistage, réalisé tous les six mois à un an et utilisant conjointement le dosage du CA 125 et une échographie par voie endopelvienne, est limitée aux patientes à risque. Pour ces femmes, l annexectomie bilatérale préventive a été proposée par certaines équipes. L ovaire est un organe complexe soumis à un environnement hormonal et des dérèglements immunitaires. L influence hormonale semble désormais retenue pour le cancer de l ovaire: rôle bénéfique de la grossesse, de l allaitement et surtout de la contraception orale, mais également rôle délétère du traitement hormonal substitutif. Les hypothèses majeures impliquent l ovulation incessante , l exposition aux gonadotrophines ou l effet préjudiciable des androgènes dans le processus cancéreux mais n expliquent cependant pas toutes ces données épidémiologiques. Mieux cerner l étiologie de ce cancer permettra de développer de nouvelles thérapeutiques. La théorie de la surveillance immunitaire des tumeurs, accordant aux lymphocytes un rôle de sentinelle dans la reconnaissance et l élimination constante des tumeurs, a initié la recherche en immunothérapie anti-tumorale. Les premiers essais de vaccination par injection directe d antigènes tumoraux ou de cellules dendritiques chargées offrent aujourd hui de grands espoirs pour les patientes.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

    Cancer de la prostate évolutif et hormono-résistance

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    Considéré comme véritable problème de santé publique en raison de l augmentation de son incidence au cours des vingt dernières années, le cancer de la prostate est un cancer dont l étude et la prise en charge est devenue multidisciplinaire. Le cancer de la prostate est décrit comme hormonosensible car sa prolifération est sous la dépendance d androgènes majoritairement, mais aussi dans une moindre mesure de d œstrogènes. C est un cancer dont l évolution est lente, elle peut s étaler sur des dizaines d années, voire plus. Selon le stade auquel il est diagnostiqué, le pronostic est différent. A un stade localisé dans la glande, il est curable. Si à sa découverte, la tumeur a essaimé en métastases, le cancer est incurable. On peut soulager les symptômes et maitriser la progression grâce à l hormonothérapie, dont l efficacité est de vingt-quatre mois au maximum. Les métastases deviennent hormono-résistantes : elles reprennent leur développement malgré le traitement hormonal: c est le cancer de la prostate évolutif. C est l apparition de l hormono-résistance que nous avons étudié, en décrivant tous les mécanismes qui en sont à l origineGRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

    Intérêt de l invasive trophoblaste antigène dans le diagnostic précoce des choriocarcinomes ovariens chez la femme enceinte

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    Le choriocarcinome est une tumeur rare ovarienne dont le diagnostic repose sur la clinique, la radiologie, la biologie avec le dosage des bêta HCG plasmatiques et l anatomo-pathologie. Son diagnostic pose un problème lorsqu elle survient au cours de la grossesse en raison de la sécrétion normale de bêta HCG durant cette période. Notre patiente, trente-deux ans, présentait à deux mois du post-partum un choriocarcinome ovarien droit polymétastatique traité par l association chimiothérapie (protocole bléomycine/étoposide/platine) et chirurgie. Le résultat est satisfaisant avec rémission complète à quatorze mois. Elle présentait comme seule anomalie au cours de cette grossesse un taux anormalement élevé de bêta HCG plasmatiques qui n a pas alerté les obstétriciens du fait de la normalité de la surveillance échographique rapprochée liée à une hyperplasie congénitale des surrénales chez le premier enfant de la patiente. Pour différencier un choriocarcinome des autres pathologies en cas d anomalie quantitative ou cinétique des bêta HCG au cours de la grossesse, il faut proposer le dosage de l Invasive Trophoblaste Antigène (ITA), initialement étudié comme marqueur d anomalie chromosomique ; mais dont l élévation semble s avérer un marqueur précoce et sensible d un processus tumoral débutant dont la prise en charge rapide permet une amélioration des valeurs de morbi-mortalité du choriocarcinome ovarien pergestationnelLe choriocarcinome est une tumeur rare ovarienne dont le diagnostic repose sur la clinique, la radiologie, la biologie avec le dosage des bêta HCG plasmatiques et l anatomo-pathologie. Son diagnostic pose un problème lorsqu elle survient au cours de la grossesse en raison de la sécrétion normale de bêta HCG durant cette période. Notre patiente, trente-deux ans, présentait à deux mois du post-partum un choriocarcinome ovarien droit polymétastatique traité par l association chimiothérapie (protocole bléomycine/étoposide/platine) et chirurgie. Le résultat est satisfaisant avec rémission complète à quatorze mois. Elle présentait comme seule anomalie au cours de cette grossesse un taux anormalement élevé de bêta HCG plasmatiques qui n a pas alerté les obstétriciens du fait de la normalité de la surveillance échographique rapprochée liée à une hyperplasie congénitale des surrénales chez le premier enfant de la patiente. Pour différencier un choriocarcinome des autres pathologies en cas d anomalie quantitative ou cinétique des bêta HCG au cours de la grossesse, il faut proposer le dosage de l Invasive Trophoblaste Antigène (ITA), initialement étudié comme marqueur d anomalie chromosomique ; mais dont l élévation semble s avérer un marqueur précoce et sensible d un processus tumoral débutant dont la prise en charge rapide permet une amélioration des valeurs de morbi-mortalité du choriocarcinome ovarien pergestationnelGRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

    Variability among TSH measurements can be reduced by combining a glycoengineered calibrator to epitope-defined immunoassays

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    Objectives: Measuring protein markers with variable glycosylation, such as thyroid-stimulating hormone (TSH), with high accuracy is not an easy task. Despite highly sensitive third-generation tests, discrepancies among TSH assays still remain unsolved and are the focus of important standardization efforts. Earlier work from our group showed that a lack of similarity in epitope expression between standards and samples may account for discordant hormone measurements. In this study, we aimed at producing a glycoengineered TSH with serum-type glycosylation and compared its immunological behavior to that of the international standards. Study Design: Recombinant glycoengineered TSH (rgTSH) was produced in glycoengineered Chinese hamster ovary cells to express a highly sialylated TSH and tested in newly designed assays. Two groups of assays targeting defined epitopes were constructed and TSH levels were estimated in a panel of 84 clinical samples (2.1-22.4 mIU/l) based on the use of the current 3rd IS 81/565, the 1st IRP 94/674 and rgTSH calibrations. Results: Calibration based on rgTSH was found to significantly reduce the percentage difference means of assays compared to the pituitary standard. We also found that a switch from a mIU/l (3rd IS 81/565) to ng/l (rgTSH) basis can be established within the normal as well as in the mid to upper normal range of TSH levels. Of interest, TSH assays targeting the main immunogenic region displayed variable TSH values, indicating that, in this region, epitopes should be defined for assays to deliver similar values. Conclusions: A glycoengineered TSH with serum-type glycosylation proved to be a new calibrator efficient in harmonizing TSH values

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    Background. For unknown reasons, the prevalence of thyroid autoimmune disorders is higher in patients with Down's syndrome than in the general population. The present case strongly supports a recent evaluation of propagating screening for thyroid disease in this group of patients to assure early diagnosis of hypothyroidism. Methods. In a 25-year-old man diagnosed with Down's syndrome, clinical manifestations of hypothyroidism were lacking, but profound biochemical abnormalities were found with particularly high levels of thyroid stimulating hormone (TSH). Antigenic properties of TSH were characterized using a panel of anti-TSH antibodies. Results. Technical problems not infrequently associated with TSH measurements are convincingly ruled out. Antigenic characterization of the patient's circulating TSH revealed circulating forms of TSH different from pituitary TSH which closely resembled TSH recombinant human hormone. Conclusions. It appears counterintuitive that the bioactivity of TSH decreases in the hypothyroid state as higher bioactivity of TSH is anticipated in hypothyroidism promoted by an increased hypothalamic TRH drive. In contrast, diminished negative thyroid hormone feedback will enhance posttranslational glycosylation of TSH subunits and increase sialylation of the carbohydrate side chains. Both exert a negative effect on TSH bioactivity, only compensated by the very high levels of the hormone as in the present case

    Interoceptive abilities in inflammatory bowel diseases and irritable bowel syndrome

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    Alexithymia is usually described by three main dimensions difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and externally oriented thinking (EOT). The most commonly used questionnaire investigating alexithymia, the Toronto Alexithymia Scale (TAS-20), supports this three-factor structure. One important assumption is that alexithymia severity is associated to vulnerability to somatic diseases, among them gastrointestinal disorders. However, the association between alexithymia and gastrointestinal disorders is not systematic, thus questioning the role of alexithymia as a vulnerability factor for those illnesses. A recent factor analysis suggested another four-factor structure for the TAS-20: difficulties in awareness of feelings (DAF), difficulties in interoceptive abilities (DIA), externally oriented thinking (EOT), and poor affective sharing (PAS). We assume that DIA and DAF might be more relevant to investigate the association between alexithymia and gastrointestinal disorders. The rationale is that DIA and DAF reflect impairments in emotion regulation that could contribute to an inappropriate autonomic and HPA axis homeostasis in irritable bowel syndrome (IBS), ulcerative colitis (UC), or Crohn’s disease (CD). The aim of this study was to investigate whether DIA and DAF are associated with the presence of IBS, UC or CD, while checking for anxiety, depression, parasympathetic (vagus nerve) activity and cortisol levels. We recruited control participants (n=26), and patients in remission who were diagnosed with IBS (n=24), UC (n=18), or CD (n=21). Participants completed questionnaires to assess anxiety, depression, and alexithymia. A blood sample and an electrocardiogram were used to measure the level of cortisol and parasympathetic activity, respectively. Logistic regressions with the four-factor structure of the TAS-20 revealed that DIA was a significant predictor of IBS (W(1)=6.27, p=.01). Conversely, DIA and DAF were not significant predictors in CD and UC patients. However, low cortisol level was a significant predictor of UC (W(1)=4.67, p=.035). Additional logistic regressions based on the original 3-factor structure of TAS-20 (DIF, DDF, and EOT) showed that only DDF was a significant predictor of CD [W(1)=6.16, p < .001]. The present study suggests that DIA is an important dimension for assessing potential risk for gastrointestinal diseases, in particular for IBS

    Dosage de la thyroglobuline dans les liquides de rinçage d’aiguille de cytoponction ganglionnaire : influence des conditions pré-analytiques [Thyroglobulin assay in fluids from lymph node fine needle-aspiration washout: influence of pre-analytical conditions]

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    International audienceThe aim of this study was to evaluate the pre-analytical factors contributing to uncertainty in thyroglobulin measurement in fluids from fine-needle aspiration (FNA) washout of cervical lymph nodes. We studied pre-analytical stability, in different conditions, of 41 samples prepared with concentrated solutions of thyroglobulin (FNA washout or certified standard) diluted in physiological saline solution or buffer containing 6% albumin. In this buffer, over time, no changes in thyroglobulin concentrations were observed in all storage conditions tested. In albumin free saline solution, thyroglobulin recovery rates depended on initial sample concentrations and on modalities of their conservation (in conventional storage tubes, recovery mean was 56% after 3 hours-storage at room temperature and 19% after 24 hours-storage for concentrations ranged from 2 to 183 μg/L; recovery was 95%, after 3 hours or 24 hours-storage at room temperature, for a concentration of 5,656 μg/L). We show here that these results are due to non-specific adsorption of thyroglobulin in storage tubes, which depends on sample protein concentrations. We also show that possible contamination of fluids from FNA washout by plasma proteins do not always adequately prevent this adsorption. In conclusion, non-specific adsorption in storage tubes strongly contributes to uncertainty in thyroglobulin measurement in physiological saline solution. It is therefore recommended, for FNA washout, to use a buffer containing proteins provided by the laboratory

    Middle Iron-Enriched Fructose Diet on Gestational Diabetes Risk and on Oxidative Stress in Offspring Rats.

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    International audienceGestational diabetes mellitus (GDM) is associated with increased insulin resistance and a heightened level of oxidative stress (OS). Additionally, high iron consumption could also increase insulin resistance and OS, which could aggravate GDM risk. The aim of this study is to evaluate a high fructose diet (F) as an alternative experimental model of GDM on rats. We also have evaluated the worst effect of a fructose iron-enriched diet (FI) on glucose tolerance and OS status during pregnancy. Anthropometric parameters, plasma glucose levels, insulin, and lipid profile were assessed after delivery in rats fed an F diet. The effects observed in mothers (hyperglycemia, and hyperlipidemia) and on pups (macrosomia and hypoglycemia) are similar to those observed in women with GDM. Therefore, the fructose diet could be proposed as an experimental model of GDM. In this way, we can compare the effect of an iron-enriched diet on the metabolic and redox status of mother rats and their pups. The mothers' glycemic was similar in the F and FI groups, whereas the glycemic was significantly different in the newborn. In rat pups born to mothers fed on an FI diet, the activities of the antioxidant enzyme glutathione peroxidase (GPx) and glutathione-S-transferase in livers and GPx in brains were altered and the gender analysis showed significant differences. Thus, alterations in the glycemic and redox status in newborns suggest that fetuses are more sensitive than their mothers to the effect of an iron-enriched diet in the case of GDM pregnancy. This study proposed a novel experimental model for GDM and provided insights on the effect of a moderate iron intake in adding to the risk of glucose disorder and oxidative damage on newborns
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