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Toussaint, Jérôme. "Tumeurs mammaires de grade histologique intermédiaire et ambiguïté biologique: amélioration de l'application clinique du grade tumoral :cancer du sein et grade histologique, mythe ou réalité biologique." Doctoral thesis, Universite Libre de Bruxelles, 2010. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209987.
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Les anatomopathologistes disposent d’outils permettant d’assister leurs décisions cliniques et d’évaluer les risques de récidive des patientes atteintes d’un cancer du sein. Parmi ceux-ci, le grade histologique du cancer du sein divise les patientes en trois sous-groupes pour lesquels le grade histologique 1 et 3 sont respectivement associés à de bons et mauvais pronostics. Cependant, cet outil est loin d’être parfait, dû au manque de reproductibilité de ce système et du risque de récurrence intermédiaire, peu informatif, des patients classés dans la catégorie « grade 2 ».Afin de mieux caractériser ces tumeurs de risque intermédiaire, notre laboratoire a introduit un score appelé « Gene expression Grade Index (GGI) », basé sur l’expression de 97 gènes définis par microarrays. De façon intéressante, ce GGI permet de diviser les patientes de grade histologique 2, sur base de leur profil d’expression, en 2 groupes correspondant aux tumeurs de grade 1 ou aux tumeurs de grade 3. Cependant, bien que le GGI apporte une information importante, son applicabilité clinique est limitée par son prix et la nécessité d’utiliser du matériel congelé.
Durant ce travail de thèse, nous avons transposé la signature microarrays en un test RT-PCR, appelé PCR-GGI, basé sur l’expression de 8 gènes qui permet de reproduire les performances du GGI à partir de tissus congelés ou conservés dans de la paraffine. Cette amélioration permet de faciliter son utilisation en routine clinique.
De plus, nous avons approfondi notre connaissance du grade histologique, au niveau génomique et transcriptomique, et montré que les tumeurs mammaires (ER-positives) peuvent être divisées en deux groupes :un premier groupe de faible instabilité génomique, exprimant faiblement les gènes de prolifération et présentant un faible risque de récurrence ;et un deuxième groupe de haute instabilité génomique (impliquant principalement des amplifications localisées dans les régions 8q et 20q), une expression importante de gènes de prolifération et un mauvais pronostic.
D’autre part, les carcinomes canalaires in situ (DCIS) présentant des similarités avec les tumeurs invasives, nous avons voulu mieux comprendre le comportement du grade tumoral parmi ces tumeurs pré-invasives. Nous avons donc intégré le PCR-GGI au VNPI et défini le VNPI-GGI. Comparé au VNPI classique, le VNPI-GGI identifie mieux les patientes qui vont récidiver tôt dans les groupes de risque intermédiaire et haut, et permet donc d’éviter le sur-traitement.
Cependant, le calcul du VNPI est un travail fastidieux et le PCR-GGI seul ne permet pas de prédire les risques de récidives des DCIS. Nous avons donc cherché un nouveau marqueur pronostique. Alors, qu’il existe des preuves de plus en plus nombreuses supportant l’importance du rôle anti-tumoral des cellules myoépithéliales, nous avons montré qu’une diminution de l’expression de CD10 – un marqueur des cellules myoépithéliale – était hautement corrélée au risque de récidive. Ces résultats soulignent l’importance tant de l’agressivité de la tumeur que de son environnement directe, dans la progression tumorale.
En terme d’applications, les résultats obtenus durant ce travail de thèse nous ont permis de développer des outils utilisables par les cliniciens afin d’améliorer la prise en charge des patientes.
Traditional histopathological tools routinely used to evaluate breast cancer prognosis are designed to assist physicians in their evaluation of clinical outcome. The histological grade of invasive breast cancer, that assigns patients to one of 3 groups for which histological grade 1 and 3 tumors are respectively associated with lower and higher rate of recurrence, has long provided clinically important prognostic information. However, this tool is far from perfect due to concern over reproducibility and intermediate risk of recurrence of the histological grade 2 that is not informative for clinical decision.
To better characterize tumors classified as histological grade 2, our group has introduced a score called Gene expression Grade Index (GGI) based on a cassette of 97 genes defined by Microarrays. Interestingly, the GGI was able to reclassify patients with histological grade 2 tumors into 2 groups with distinct clinical outcomes similar to those of histological grade 1 and 3, respectively. However, its clinical applicability still remains expensive and often requires frozen tissue.
During this thesis work, we have transposed the GGI onto a qRT-PCR assay, called PCR-GGI, based on a set of 8 genes that could recapitulate in an accurate and reproducible manner the prognostic performance of GGI using both frozen and paraffin-embedded (FFPE) tumor samples, to facilitate its use in clinical practice.
Moreover, we have explored histological grade of invasive breast cancer at genomic and transcriptomic level and we have shown that two classes of ER-positive invasive breast cancer are observed: a first of low genomic instability, low proliferation gene expression and low risk of recurrence; and a second of high genomic instability (implying a major role for amplification of region located on chromosome arms 8q and 20q), high proliferation gene expression and worse prognosis.
In addition, since Ductal Carcinoma in situ (DCIS) and invasive breast cancer show concordant biologic behavior, we attempted to better understand the molecular basis of grade in pre-invasive breast cancer. We have then incorporated the PCR-GGI in the VNPI and defined the VNPI-GGI to improve its prognostic value. Compared to the classic VNPI, the VNPI-GGI had a better potential to identify early relapsing patients in the intermediate and high score group, and avoid under treatment in high-risk DCIS patients.
However, VNPI scoring is a tedious work and PCR-GGI alone can’t predict recurrence in pre-invasive breast cancer. We aimed then to find news prognosis marker in the field of DCIS. As there is now growing body of evidence supporting the role of myoepithelial cells (MECs) as natural tumor suppressors, we have showed that a decrease of CD10 expression- a surface biomarker of MECs – was significantly associated with an increased risk of relapse.
These results highlight the importance of assessing intrinsic DCIS properties as well as juxta-tumoral stroma, both seems to have a major role in DCIS progression.
In terms of applications, from these results obtained during this thesis work, we developed methods applicable into clinical practice to improve patients management.
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished
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Oger, Myriam. "Indexation automatique d'images numériques : application aux images histopathologiques du cancer du sein et hématologiques de leucémies lympoïdes chroniques." Caen, 2008. http://www.theses.fr/2008CAEN2066.
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Dans un contexte où les économies de santé sont de plus en plus drastiques, où les spécialistes sont de moins en moins nombreux, alors que, grâce aux campagnes de dépistage, le nombre de cas à analyser est en constante augmentation, le travail des pathologistes devient de plus en plus difficile. En outre, les lésions précoces découvertes lors du dépistage sont souvent mal connues et/ou de très petite taille ce qui rend délicat le diagnostic histopathologique. Un problème similaire est rencontré en hématologie avec la pratique de plus en plus répandue des examens sanguins systématiques et la difficulté d'identification de cellules suspectes et d'évènements rares au sein d'un frottis sanguin. Il est par conséquent très important d’apprécier dans quelle mesure la microscopie numérique et les outils d’analyse automatique des images pourront dans l’avenir aider ces spécialistes dans l’accomplissement de leur tâche quotidienne. Le présent travail de thèse, mené dans cette optique, se fonde sur l'utilisation de lames virtuelles des préparations histologiques et cytologiques, acquises à basse ou à haute résolution. Il consiste à développer et à tester une série d'outils d'aide au diagnostic basés sur l’indexation automatique des images. Cependant, l’utilisation des lames virtuelles implique la manipulation d'une masse de données très importante, qui constitue un frein pour traiter, analyser et même visualiser les images de manière classique. Nous avons donc testé tout d’abord la pertinence d'une analyse globale des images, puis d'une analyse locale de celles-ci, accompagnées d’une réduction de dimension des données par diverses méthodes, dont l'analyse spectrale. Nous avons choisi de mettre en œuvre cette approche à propos de deux localisations dont l’incidence constitue un problème de santé publique, les tumeurs mammaires et la leucémie lymphoïde chroniqueIn a context where health economies are increasingly curbed, where specialists are fewer and fewer, while, thanks to screening campaigns, the number of cases to analyze is constantly growing, the task of pathologists is more and more difficult. In addition, early lesions discovered during the screening are often poorly known and / or of very small size which makes the histopathological diagnosis difficult. A similar problem is encountered in hematology with the increasingly widespread practice of systematic blood tests and the difficulty of identifying suspicious cells and rare events in blood smears. It is therefore very important to assess how digital microscopy and automatic processing techniques will be able to help the specialists in their daily practice in the future. This present work is based on the use of virtual slides of histological and cytological preparations, acquired at low or high resolution. It aims at developing and testing several tools for computer assisted diagnosis based on automatic indexing of images. However, the use of virtual slides involves the manipulation of very large data and it is difficult to process, analyze or visualize these images in a classical way. The first objective of the study was to assess the relevance of a global analysis of images, then the contribution of their local analysis, with a dimensional reduction of data by various methods including spectral analysis. These methods have been applied to virtual slides of breast tumors and chronic lymphoid leukemia, two tumor locations whose incidence is a public health problem
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Chamming's, Foucauld. "Elastographie quantitative des tumeurs du sein et de la réponse au traitement." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCB152/document.
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Introduction : L’élastographie shear wave (ESW) est une technique récente d’échographie qui évalue quantitativement la dureté des tissus et permet d’améliorer la caractérisation des lésions mammaires. Comme toute nouvelle technique d’imagerie, l’ESW nécessite une validation préclinique pour définir les conditions d’utilisations et établir les limites des champs d’applications dans lesquelles la technique pourra être considérée comme valide. Matériels et méthodes : Dans une première partie effectuée au laboratoire de recherche en Imagerie nous avons étudié les éléments histologiques sous tendant l’image d’ESW sur un modèle de cancer du sein implanté chez la souris, au cours de sa croissance puis sous traitement. Dans une deuxième partie, nous avons étudié chez des patientes le rôle de la compression manuelle en ESW pour la caractérisation des lésions mammaires. Dans une dernière partie, effectuée en collaboration avec une équipe de l’Institut Langevin Ondes et Images, nous avons étudié la faisabilité d’un nouveau paramètre, le module de cisaillement non linéaire pour l’analyse des lésions mammaires. Résultats : Au laboratoire, nous avons établi des corrélations entre la dureté mesurée en élastographie et les caractéristiques histologiques des tumeurs, y compris sous traitement. Nous avons montré que la fibrose était associée à une dureté élevée et la nécrose à une dureté moindre. Notre étude clinique a montré qu’une compression manuelle minimale était nécessaire pour obtenir de bonnes performances de l’ESW et qu’une pression trop élevée devait être évitée. Enfin nous avons montré la faisabilité en imagerie mammaire d’un nouveau paramètre quantitatif obtenu en élastographie shear wave : le module de cisaillement non linéaire. Conclusion : A partir de travail de thèse, une meilleure compréhension de la part des éléments biologiques et techniques en ESW du sein est possible et des recommandations pour l’utilisation clinique peuvent être formulées. Nos observations cliniques ont entrainé la mise au point d’un nouveau paramètre diagnostique quantitatif : le module de cisaillement non linéaireIntroduction: Shear Wave Elastography (SWE) is a recent ultrasound technique assessing quantitatively tissue stiffness and improving breast lesions characterization. As every new imaging technique, SWE requires a pre clinical validation in order to define in which conditions it should be used and precise the applications for which the technique is validated. Materials and methods: First, in a research lab we have investigated the pathological features underlying SWE image in a breast cancer model implanted in mice, during tumor growth and under therapy. Secondly, we have studied in patients the role of manual compression in SWE for the characterization of breast lesions. Finally, in collaboration with on team from Institut Langevin Ondes et Images, we have studied the feasibility of a new parameter, the non-linear modulus, for breast lesion assessment. Results: in the research lab, we have shown correlations between stiffness as measured with SWE and pathological features of tumors, even on treatment. We have shown that fibrosis was associated with high stiffness values and necrosis with lowers. Our clinical study, showed that a minimal manual compression was required for optimal performance of SWE and that strong compression should be avoided. Finally, we demonstrated feasibility of a new parameter, derived from SWE, the non-linear modulus. Conclusion: Our work provides a better understanding of biological and technical elements of SWE. On the basis of our results, new recommendations may be made for the use of SWE in clinical practice. From our clinical findings, we developed a new quantitative parameter, which may be useful for the diagnosis of breast lesions, the non-linear modulus
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Fkih, m'hamed Insaf. "Etude de l'implication des miARNs dans le cancer du sein triple négatif et la régulation de BRCA1." Thesis, Clermont-Ferrand 1, 2015. http://www.theses.fr/2015CLF1MM19/document.
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Dans les cancers du sein triple négatif sporadiques, BRCA1 est fréquemment inactivé au niveau transcriptionnel, et il a été rapporté que cette inactivation peut être réalisée par une méthylation du promoteur. Plus récemment, il a été constaté que BRCA1 peut également être régulée au niveau post-transcriptionnel par les microARNs. L'accumulation de preuves indique que les miARNs ont un rôle causal dans la tumorigenèse. Nos travaux se sont axés sur l'étude de l’expression et des fonctions des microARN in vitro, in silico et ex vivo.Basé sur nos résultats de profilage de l'expression, quatre miARN candidats (miR-10b, miR-26a, miR-146a et miR-153) ont été choisis comme étant potentiellement impliqués dans le développement du cancer du sein triple négatif. Des essais d'expression exogènes ont révélé que miR-10b et miR-26a, mais pas miR-146a, peuvent réguler négativement l'expression du gène BRCA1 dans les cellules cancéreuses triple négatif MDA-MB-231 et luminales MCF7, alors que miR-153 pourrait réguler négativement l'expression du gène BRCA1 uniquement dans les cellules MCF7. L'analyse in silico des données de Cancer Genome Atlas (TCGA) a confirmé que miR-146a est significativement plus exprimé dans les tumeurs du sein triple négatif par rapport à d'autres tumeurs (non triple négatif) mammaires. L’étude ex vivo a montré que le niveau élévé d’expression de miR-146a et de miR-26 est associé à l’absence des métastases ganglionnaires dans le cancer du sein triple négatif. Aussi une corrélation entre l’expression de 4 miARNs est révélée permettant l’identification de différentes voies de signalisations impliquées dans le cancer du sein triple negatif.Nos travaux fournissent des preuves de l'implication des miARNs spécifiques comme des biomarqueurs potentiels dans le développement du cancer de sein triple négatifIn sporadic triple-negative breast cancers BRCA1 is frequently inactivated at the transcriptional level, and it has been reported that this inactivation may be brought about by promoter methylation. More recently, it was found that BRCA1 may also be regulated at the post-transcriptional level by miRNAs. Accumulating evidence indicates that miRNAs have a causal role in tumorigenesis. Our work focused on the study of microRNAs expression and functions in vitro, in silico and ex vivo.Based on our expression profiling results, four candidate miRNAs (miR-10b, miR-26a, miR-146a and miR-153) were selected as being potentially involved in triple-negative breast cancer development. Exogenous expression assays revealed that miR-10b and miR-26a, but not miR-146a, can down-regulate the expression of BRCA1 in both triple-negative MDA-MB-231 and luminal epithelial MCF7 breast cancer-derived cells, whereas miR-153 could down-regulate BRCA1 expression only in MCF7 cells. In silico analysis of The Cancer Genome Atlas (TCGA) data confirmed that miR-146a is significantly higher expressed in triple-negative breast tumors compared to other (non triple-negative) breast tumors. The ex vivo study showed that the high level expression of miR-146a and miR-26 is associated with the absence of lymph node metastasis in triple negative breast cancer. Also a correlation between the expression of the 4 miRNAs was revealed, allowing the identification of different signaling pathways involved in the triple negative breast cancer.Our work provides evidence of the involvement of specific miRNAs as potential biomarkers in breast cancer triple negative development
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LE, BAIL LAURENCE. "Exploration chirurgicale des microcalcifications groupees infra-cliniques du sein : correlation radio-histologique ; a propos de 58 observations." Rennes 1, 1993. http://www.theses.fr/1993REN1M084.
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Boa, Olivier. "Analyse in vivo du remodelage à long terme de la peau reconstruite endothélialisée et de son réseau vasculaire et étude in vitro de la pseudo-vasculogénèse lors du développement tumoral au sein de la peau reconstruite endothélialisée." Thesis, Université Laval, 2007. http://www.theses.ulaval.ca/2007/24705/24705.pdf.
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Ouldamer, Lobna. "Evaluation de la spectroscopie par résonance magnétique du tissu adipeux mammaire comme marqueur non invasif de la part nutritionnelle du cancer du sein." Thesis, Tours, 2016. http://www.theses.fr/2016TOUR3304.
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La composition en acides gras du tissu adipeux mammaire est reconnue comme marqueur qualitatif de la consommation lipidique antérieure mais aussi de la part nutritionnelle du risque / pronostic du cancer du sein. Ceci ouvre la perspective d’individualiser dans la population générale, un groupe de personnes à risque, susceptibles de bénéficier d’une intervention nutritionnelle ciblée. L’approche du dépistage d’une population à risque par l’utilisation de la composition du tissu adipeux comme biomarqueur se heurte i) à l’aspect invasif que représente le prélèvement d’un fragment de tissu adipeux mammaire, et ii) à la lourdeur contraignante du conditionnement et de l’analyse systématique des acides gras du tissu adipeux. Les méthodes analytiques actuellement disponibles sont incompatibles avec la perspective d’un dépistage de masse. Cependant, les descriptions récentes de l’utilisation de la spectroscopie par résonance magnétique (SRM) pour décrire la composition lipidique des triglycérides du tissu adipeux permettent d’envisager de l’utiliser dans cet objectif. Ce travail de thèse présente: 1) l’évaluation de la SRM pour caractériser la composition en acides gras du tissu adipeux chez l’animal (le rat) suite à une intervention nutritionnelle, 2) l’évaluation du profil lipidique du tissu adipeux par SRM chez la femme sur une plateforme clinique 3T, 3) l’étude des liens entre la composition en acides gras du tissu adipeux et la présentation du cancer du sein, et 4) la comparaison des données de la SRM in vitro (11.7T) et in vivo (3T) du tissu adipeux chez des patientes prises en charge pour un cancer du sein avec les données de la chromatographie gazeuseFatty acid composition of the white adipose tissue remains the most reliable qualitative biomarker of previous dietary intake of fatty acids and may provide information on the nutritional part of the risk or evolution of breast cancer. This opens the prospect of individualization of women at high nutritional risk of breast cancer that may benefit from a targeted nutritional intervention but 1) the need for biopsy and 2) subsequent time-consuming biochemical analyses hamper any application of this approach. Proton magnetic resonance spectroscopy (1H-MRS) of adipose tissue lipids represents an appealing, non-invasive approach, which could circumvent these limitations. This manuscript reports: 1) an assessment of feasibility of (1H-MRS) to evaluate the consequences of a nutritional intervention in a rat mammary tumor model on the adipose tissue fatty acid composition, 2) an assessment of the feasibility of in vivo measurement of the fatty acid composition of breast adipose tissue by (1H-MRS) on a clinical platform, 3) an assessment of the relation of specific patterns of composition of adipose tissue fatty acids with the presentation of breast cancer, and 4) a comparison with gas chromatography of (1H-MRS) data acquired on breast adipose tissue in vitro (11.7T) and in vivo (3T) on patients managed for breast cancer
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Raibaut, Xavier. "Le diagnostic du carcinome canalaire in situ du sein en 1990 : données de l'imagerie et corrélations radio-histologiqes : à propos d'un cas." Montpellier 1, 1990. http://www.theses.fr/1990MON11210.
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Feudjio, Kougoum Cyrille Désiré. "Segmentation of mammographic images for computer aided diagnosis." Thesis, Lille 1, 2016. http://www.theses.fr/2016LIL10152/document.
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Les outils d’aide au diagnostic sont de nos jours au cœur de plusieurs protocoles cliniques car ils améliorent la qualité du diagnostic posé et des soins médicaux. Ce travail de recherche met en avant une architecture hiérarchique pour la conception d'un outil d'aide à la détection du cancer du sein robuste et performant. Il s’intéresse à la réduction des fausses alarmes en identifiant les régions potentiellement cancérogènes. La gamme dynamique des niveaux de gris des zones sombres est étirée pour améliorer le contraste entre la région du sein et l'arrière plan et permettre une meilleure extraction de celle-ci. Toutefois, le muscle pectoral demeure incrusté dans la région du sein et interfère avec l'analyse des tissus. Son extraction est à la fois difficile et complexe à mettre en œuvre à cause de son chevauchement avec les tissus denses du sein. Dans ces conditions, même en exploitant l'information spatiale pendant la clusterisation par un algorithme de fuzzy C-means ne produit pas toujours des résultats de segmentation pertinents. Pour s'affranchir de cette difficulté, une étape de validation suivie d'un ajustement de contour est mise sur pied pour détecter et corriger les imperfections de segmentation. La seconde étape est consacrée à la caractérisation de la densité des tissus. Pour faire face au problème de variabilité des distributions de niveaux de gris dans les classes de densités, nous introduisons une modification de contraste basée sur un transport optimisé de niveaux de gris. Grâce à cette technique, la surface relative de tissus denses estimée par simple segmentation est très fortement corrélée aux classes de densités issues d’un jeu de données étiquetéesComputer-aided diagnosis systems are currently at the heart of many clinical protocols since they significantly improve diagnosis making and therefore medical care. This research work therefore puts forward a hierarchical architecture for the design of a robust and efficient CAD tool for breast cancer detection. More precisely, it focuses on the reduction of false alarms rate through the identification of image regions of foremost interest i.e potential cancerous areas. The dynamic range of gray level intensities in dark regions is, first of all stretched to enhance the contrast between tissues and background and thus favors accurate breast region extraction. A second segmentation follows since pectoral muscle which regularly tampers breast tissue analysis remains inlaid in the foreground region. Extracting pectoral muscle tissues is both hard and challenging due to its overlap with dense tissues. In such conditions, even exploiting spatial information during the clustering process of the fuzzy C-means algorithm does not always produce a relevant segmentation. To overcome this difficulty, a new validation process followed by a refinement strategy is proposed to detect and correct the segmentation imperfections. The second macro-step is devoted to breast tissue density analysis. To address the variability in gray levels distributions with of mammographic density classes, we introduce an optimized gray level transport map for mammographic image contrast standardization. Thanks to this technique, dense region areas computed using simple thresholding are highly correlated to density classes from an annotated dataset
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Frémondière, Pierre. "L'évolution de l'accouchement dans la lignée humaine. Estimation de la contrainte fœto-pelvienne par deux méthodes complémentaires : la simulation numérique de l'accouchement et l'analyse discriminante des modalités d'accouchement au sein d'un échantillon obstétrical." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM5013.
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Notre objectif est d’étudier les modalités d’accouchement au sein de la lignée humaine. Pour cela, nous utilisons deux approches complémentaires : la simulation numérique de l’accouchement et l’analyse discriminante des modalités d’accouchement au sein d’un échantillon obstétrical. Dans un premier temps, nous construisons des maillages de bassins et de crânes de foetus fossiles grâce à une méthode d’interpolation : le krigeage. Les groupes fossiles considérés sont les Australopithèques, les premiers représentants du genre Homo (PRGH) et les représentants du genre Homo au Pléistocène moyen et supérieur (RPMS). Les dimensions des crânes juvéniles sont utilisées pour estimer « à rebours » les dimensions néonatales à l’aide de courbes de croissance humaine et de chimpanzé. Nous réalisons une simulation numérique de l’accouchement à partir des maillages de ces dyades « virtuelles ». Puis nous réalisons des analyses discriminantes avec un jeu de données issu de mesures réalisées sur le pelviscanner de femmes et sur les mesures du crâne de leur nouveau-né afin de séparer les modalités d’accouchement grâce aux variables foeto-pelviennes. Ces mêmes variables foeto-pelviennes sont mesurées chez les dyades fossiles afin d’identifier, par les analyses discriminantes, leurs modalités d’accouchement les plus probables. Nos résultats suggèrent un accouchement eutocique sans rotation intra-pelvienne chez les Australopithèques, eutocique avec rotation intrapelvienne chez les PRGH, dystocique ou eutocique chez les RPMS, l’accouchement eutocique est caractérisé par une rotation et une incurvation de la trajectoire de descenteThe purpose of this thesis is to estimate delivery outcomes for extinct hominids. We therefore use two complementary methods : numerical simulation of childbirth and discriminant analysis of delivery outcomes from an obstetrical sample. First, we use kriging to construct meshes of pelves and neonatal skulls. Fossil hominid specimens included in the study are Australopithecines, early Homo (EH) and middle to early Pleistocene Homo (MEPH). We estimate fetal cranial dimensions with chimpanzee or human cranial growth curve that we reversly use and apply on juveniles skull measurements. “Virtual” dyads are formed from pelves and neonatal skulls. Then, we simulate childbirth of these « virtual » dyads. Different levels of laxity of the sacro-iliac junction and different positions of the fetal head are considered. Finally, we use an obstetrical sample: delivery outcome is noted, CT-scans are used to obtain maternal pelvic measurements and diameters of the fetal head were also measured after delivery. A discriminant analysis is performed using this obstetrical sample to separate delivery outcomes thanks to fetal-pelvic measurements. Fossil dyads were subsequently added in the discriminant analysis to assess delivery outcomes to which they belong. Results suggest small fetal-pelvic constraint for Austalopithecines. This constraint is moderate for EH. Fetal-pelvic constraint is more important for MEPH. We suggest that rotational birth appears with EH. The curved trajectory of the fetal head appears with MEPH. Emergence of rotational birth and curved trajectory of fetal head are probably explained by two major increases in brain size during late and middle Pleistocene
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Nevesny, Gérard. "Typage histologique et mammographie dans les mastopathies à risque : approche plurifactorielle : à propos de 162 cas." Montpellier 1, 1991. http://www.theses.fr/1991MON11171.
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Ramos, José Leonardo Gualberto. "Desenvolvimento uterino em cadelas do nascimento aos seis meses de idade:análise histomorfométrica." Universidade Federal do Espírito Santo, 2012. http://repositorio.ufes.br/handle/10/5852.
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Previous issue date: 2012-08-21The development of research aimed at better understanding the formation and functioning of the female reproductive system as a basis for development of contraceptive methods has become increasingly relevant. Furthermore, characterization of uterine development, mainly endometrial glands in dogs has not yet the description as observed in other species. The objective of this study was to evaluate the chronology of the uterine development in prepubertal bitches (endometrium, myometrium and perimetrium) with emphasis on the development of endometrial glands. We evaluated uteri of 32 bitches with a prepubertal and 180 days postnatal (DPN). These animals were divided into eight groups of four animals each: G1 = 1DPN, G2 = 15DPN, G3 = 30DPN, 45DPN = G4, G5 = 60DPN, 90DPN = G6, G7 and G8 = 120DPN = 180DPN. We evaluated the type of epithelium, the presence of endometrial glands and quantity, the measurement of the total thickness of the uterine wall (mM), thickness of the myometrium (mM), endometrial thickness (mM), diameter (mm) and number (n°/mm2) of endometrial glands. The histoarchitecture uterus with 1 DPN revealed rudimentary feature supported with simple cubic cells in the stroma in organization, with lamina propria devoid of glands, with 15 DPN observed presence of rudimentary structures, starting from invaginations (endometrial folding) from 30 to 45 days was observed discrete branching glands that became more evident; DPN at 60 and from this period, there was an increase of glandular development in an ongoing process until the last period evaluated (180 DPN). All structures evaluated had low coefficient of variation (<10%) demonstrating homogeneity of data evaluated, as well as significant correlations (P <0.0001) between all variables with age animal [total uterine wall (R2 = 97, 4%), endometrial total (R2 = 99.4%), total myometrium (R2 = 95.8%), number of endometrial glands (R2 = 92.3%); diameters of endometrial glands (R2 = 94.1% ) and epithelial height (R2 = 72.2%). We conclude that the uterus of bitches is devoid of endometrial glands at birth and they begin continuous development from birth to 15 days and 60 days after birth are already fully formed
O desenvolvimento de pesquisas que visam o melhor entendimento da formação e funcionamento do sistema reprodutor da fêmea como embasamento para desenvolvimento de métodos contraceptivos tem se tornado cada vez mais relevante. Além disso, a caracterização do desenvolvimento uterino, principalmente das glândulas endometriais na cadela ainda não se tem à descrição como observado em outras espécies. Objetivou-se com este estudo avaliar a cronologia do desenvolvimento uterino em cadelas pré-púberes (endométrio, miométrio e perimétrio) com ênfase no desenvolvimento das glândulas endometriais. Foram avaliados úteros de 32 cadelas pré-púberes com um a 180 dias pós-nascimento (DPN). Estes animais foram distribuídos em oito grupos com quatro animais cada, sendo: G1=1DPN, G2=15DPN, G3=30DPN, G4=45DPN, G5=60DPN, G6=90DPN, G7=120DPN e G8=180DPN. Foram avaliados o tipo de epitélio, presença e quantidade de glândulas endometriais, a mensuração da espessura total da parede uterina (μm), espessura do miométrio (μm), espessura do endométrio (μm), diâmetro (μm) e número (n°/mm2) de glândulas endometriais. A histoarquitetura do útero com 1 DPN revelou característica rudimentar com células cúbicas simples apoiadas em estroma em organização, com lâmina própria desprovida de glândulas; com 15 DPN observou-se presença de estruturas rudimentares, com início das invaginações (pregueamento endometrial); dos 30 aos 45 dias observou-se discreta ramificação das glândulas que se tornaram mais evidentes; aos 60 DPN e a partir deste período, observou-se aumento do desenvolvimento glandular num processo contínuo até o último período avaliado (180 DPN). Todas as estruturas avaliadas apresentaram baixo coeficiente de variação (<10%) demonstrando uma homogeneidade nos dados avaliados, bem como correlações significativa (P<0,0001) entre todas as variáveis analisadas com a idade animal [parede uterina total (R2=97,4%), endométrio total (R2=99,4%), miométrio total (R2=95,8%), número de glândulas endometriais (R2=92,3%); diâmetro das glândulas endometriais (R2=94,1%) e altura do epitélio (R2=72,2%). Conclui-se que o útero de cadelas é desprovido de glândulas endometriais ao nascimento e que estas iniciam desenvolvimento contínuo a partir dos 15 dias de nascimento e aos 60 dias pósnascimento já estão completamente formadas
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RAMOS, J. L. G. "Desenvolvimento Uterino em Cadelas do Nascimento aos Seis Meses de Idade: Análise Histomorfométrica." Universidade Federal do Espírito Santo, 2012. http://repositorio.ufes.br/handle/10/5112.
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tese_6110_DISSERTAÇÃO JOSÉ LEONARDO.pdf: 793119 bytes, checksum: 967bf88af9499eeb42b0f5f48284e2f0 (MD5)
Previous issue date: 2012-08-21O desenvolvimento de pesquisas que visam o melhor entendimento da formação e funcionamento do sistema reprodutor da fêmea e que propiciam conhecimentos para o desenvolvimento de métodos contraceptivos tem se tornado cada vez mais relevante. Além disso, não se tem descrição da caracterização do desenvolvimento uterino na cadela, como observado em outras espécies, principalmente em relação as glândulas endometriais. Assim, objetivou-se caracterizar o desenvolvimento uterino em cadelas do nascimento aos seis meses de idade. Foram avaliados úteros de 32 cadelas pré-púberes com um a 180 dias pós-nascimento (DPN), distribuídas em oito grupos com quatro animais cada, sendo: G1=1DPN, G2=15DPN, G3=30DPN, G4=45DPN, G5=60DPN, G6=90DPN, G7=120DPN e G8=180DPN. Foram avaliados o tipo de epitélio, presença e quantidade de glândulas endometriais, realizou-se mensuração da espessura da parede uterina total (μm), espessura do miométrio (μm), espessura do endométrio (μm), diâmetro (μm) e número (n°/mm2) de glândulas endometriais. A histoarquitetura do útero com 1 DPN revelou característica rudimentar com células cúbicas simples apoiadas em estroma em organização, lâmina própria desprovida de glândulas endometriais; miométrio rudimentar e presença de perimétrio; aos 15 DPN observou-se presença de estruturas glandulares rudimentares, com início das invaginações (pregueamento endometrial); dos 30 aos 45 dias observou-se discreta ramificação das glândulas que se tornaram mais evidentes; aos 60 DPN observaram-se glândulas endometriais em lâmina própria com ramificações e discreto pregueamento endometrial; de 90 a 180 DPN todas as estruturas uterinas apresentaram histoarquitetura de um animal maduro, com maior número de glândulas endometriais em lâmina própria.Todas as variáveis avaliadas apresentaram baixo coeficiente de variação (<10%) demonstrando uma homogeneidade nos dados avaliados, bem como correlações significativas (P<0,0001) entre todas as variáveis analisadas com a idade animal [parede uterina total (R2=97,4%), endométrio total (R2=99,4%), miométrio total (R2=95,8%), número de glândulas endometriais (R2=92,3%); diâmetro das glândulas endometriais (R2=94,1%) e altura do epitélio (R2=72,2%). Conclui-se que o útero de cadelas é desprovido de glândulas endometriais ao nascimento; que ele se desenvolve continuamente do nascimento aos 180 dias; que as glândulas endometriais iniciam desenvolvimento contínuo a partir dos 15 dias; e que após 60 dias do nascimento a cadela apresenta conformação histológica uterina de um animal adulto.
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Suedam, Ivy Kiemle Trindade [UNESP]. "Estudo comparativo dos resultados de enxertos de vidro bioativo e osso autógeno, associados ou não ao plasma rico em plaquetas, em seio maxilar de coelho: análise fractal, densitométrica e histomorfométrica." Universidade Estadual Paulista (UNESP), 2007. http://hdl.handle.net/11449/104740.
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suedam_ikt_dr_arafo.pdf: 2051837 bytes, checksum: 442046f47964d37176f4cdf82ded3bc6 (MD5)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
O objetivo do presente estudo foi avaliar o efeito da associação de osso autógeno (OA) e de vidro bioativo (VB) ao plasma rico em plaquetas (PRP) como substitutos ósseos no interior de seios maxilares (SM) de coelhos, por meio de análise radiográfica da densidade óssea e da dimensão fractal e análise histomorfométrica. Adicionalmente, pretendeu-se validar os métodos da densidade óssea e dimensão fractal como indicadores da neoformação óssea. Para tanto, 20 coelhos divididos em dois grupos (G1 e G2) foram submetidos à cirurgia de levantamento de SM. No G1, 10 SM esquerdos foram enxertados com OA e 10 SM direitos com VB. No G2, 10 SM esquerdos foram enxertados com uma combinação de OA+PRP e 10 SM direitos com VB+PRP. Após 90 dias, os animais foram sacrificados e radiografias padronizadas dos SMs foram obtidas. Os valores médios (desvio padrão) da densidade óssea, expressa em milímetros equivalentes de alumínio, para os tratamentos OA, VB, OA+PRP e VB+PRP foram, respectivamente, 1,79(0,316), 2,04(0,398), 1,61(0,285) e 1,53(0,309), sendo que diferenças estatisticamente significantes (p<0,05) foram encontradas entre os valores de VB e OA, e, VB+PRP e VB. Na dimensão fractal, os valores encontrados, que podem variar de 1 a 2, foram 1,48(0,040), 1,35(0,084), 1,44(0,043) e 1,44(0,066), respectivamente. Diferenças significantes (p<0,05) foram encontradas entre os valores de VB e OA, e, OA+PRP e VB. Na histometria, expressa em porcentagem de preenchimento ósseo, os valores obtidos foram 63,30l8,609, 52,65(10,415), 55,25(7,018) e 51,07(10,255), respectivamente. Não foram encontradas diferenças estatísticas entre os tratamentos. Não houve correlação estatisticamente significante entre as variáveis densidade óssea, dimensão fractal e porcentagem de osso. Na análise histológica dos SM tratados com OA observou-se tecido ósseo neoformado, ricamente...
The objective of the present study was to evaluate the use of autogenous bone (AB) and bioactive glass (BG) and the association of these materials with platelet-rich plasma (PRP), as bone substitutes in the rabbit maxillary sinus (MS) by means of radiographical bone density and fractal dimension and by histomorphometrical analysis. In addition, the study aimed at validating the two radiographic methods as indicators of bone formation. Twenty rabbits divided into two groups (G1 and G2) were submitted to sinus lift surgery. In G1, 10 left MS were grafted with AB and 10 right MS were grafted with BG. In G2, 10 left MS were grafted with AB+PRP and 10 right MS were grafted with VB+PRP. Ninety days after, the animals were sacrificed and standardized radiographs were taken. Mean values (standard deviation) of bone density, expressed as aluminium equivalent milimeters, in MS grafted with OA, VB, OA+PRP and VB+PRP were 1,79l0,316, 2,04l0,398, 1,61l0,285 and 1,53l0,309, respectively. Statistically significant differences (p <0,05) were observed in bone density between BG and AB, and between BG+PRP and BG. Mean values of fractal dimension, which can vary from 1 to 2, were 1,48l0,040, 1,35l0,084, 1,44l0,043 and 1,44l0,066, respectively. Significant differences were observed between BG and AB and AB+PRP and BG. Mean values of percentage of bone inside MS, assessed by histometrical analysis were, respectively, 63,30l8,609, 52,65l10,415, 55,25l7,018 and 51,07l10,255. Differences were not statistically significant. No correlations were observed among bone density, fractal dimension and percentage of bone. Histological analysis showed that MS treated with AB presented newly formed and mature lamellar bone, with active bone formation presenting several vessels and osteoblasts. The other groups showed minor bone formation, with a diffuse marrow and thin network of newly... (Complete abstract click electronic access below)
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Suedam, Ivy Kiemle Trindade. "Estudo comparativo dos resultados de enxertos de vidro bioativo e osso autógeno, associados ou não ao plasma rico em plaquetas, em seio maxilar de coelho : análise fractal, densitométrica e histomorfométrica /." Araraquara : [s.n.], 2007. http://hdl.handle.net/11449/104740.
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Resumo: O objetivo do presente estudo foi avaliar o efeito da associação de osso autógeno (OA) e de vidro bioativo (VB) ao plasma rico em plaquetas (PRP) como substitutos ósseos no interior de seios maxilares (SM) de coelhos, por meio de análise radiográfica da densidade óssea e da dimensão fractal e análise histomorfométrica. Adicionalmente, pretendeu-se validar os métodos da densidade óssea e dimensão fractal como indicadores da neoformação óssea. Para tanto, 20 coelhos divididos em dois grupos (G1 e G2) foram submetidos à cirurgia de levantamento de SM. No G1, 10 SM esquerdos foram enxertados com OA e 10 SM direitos com VB. No G2, 10 SM esquerdos foram enxertados com uma combinação de OA+PRP e 10 SM direitos com VB+PRP. Após 90 dias, os animais foram sacrificados e radiografias padronizadas dos SMs foram obtidas. Os valores médios (desvio padrão) da densidade óssea, expressa em milímetros equivalentes de alumínio, para os tratamentos OA, VB, OA+PRP e VB+PRP foram, respectivamente, 1,79(0,316), 2,04(0,398), 1,61(0,285) e 1,53(0,309), sendo que diferenças estatisticamente significantes (p<0,05) foram encontradas entre os valores de VB e OA, e, VB+PRP e VB. Na dimensão fractal, os valores encontrados, que podem variar de 1 a 2, foram 1,48(0,040), 1,35(0,084), 1,44(0,043) e 1,44(0,066), respectivamente. Diferenças significantes (p<0,05) foram encontradas entre os valores de VB e OA, e, OA+PRP e VB. Na histometria, expressa em porcentagem de preenchimento ósseo, os valores obtidos foram 63,30l8,609, 52,65(10,415), 55,25(7,018) e 51,07(10,255), respectivamente. Não foram encontradas diferenças estatísticas entre os tratamentos. Não houve correlação estatisticamente significante entre as variáveis densidade óssea, dimensão fractal e porcentagem de osso. Na análise histológica dos SM tratados com OA observou-se tecido ósseo neoformado, ricamente... (Resumo completo, clicar acesso eletrônico abaixo)Abstract: The objective of the present study was to evaluate the use of autogenous bone (AB) and bioactive glass (BG) and the association of these materials with platelet-rich plasma (PRP), as bone substitutes in the rabbit maxillary sinus (MS) by means of radiographical bone density and fractal dimension and by histomorphometrical analysis. In addition, the study aimed at validating the two radiographic methods as indicators of bone formation. Twenty rabbits divided into two groups (G1 and G2) were submitted to sinus lift surgery. In G1, 10 left MS were grafted with AB and 10 right MS were grafted with BG. In G2, 10 left MS were grafted with AB+PRP and 10 right MS were grafted with VB+PRP. Ninety days after, the animals were sacrificed and standardized radiographs were taken. Mean values (standard deviation) of bone density, expressed as aluminium equivalent milimeters, in MS grafted with OA, VB, OA+PRP and VB+PRP were 1,79l0,316, 2,04l0,398, 1,61l0,285 and 1,53l0,309, respectively. Statistically significant differences (p <0,05) were observed in bone density between BG and AB, and between BG+PRP and BG. Mean values of fractal dimension, which can vary from 1 to 2, were 1,48l0,040, 1,35l0,084, 1,44l0,043 and 1,44l0,066, respectively. Significant differences were observed between BG and AB and AB+PRP and BG. Mean values of percentage of bone inside MS, assessed by histometrical analysis were, respectively, 63,30l8,609, 52,65l10,415, 55,25l7,018 and 51,07l10,255. Differences were not statistically significant. No correlations were observed among bone density, fractal dimension and percentage of bone. Histological analysis showed that MS treated with AB presented newly formed and mature lamellar bone, with active bone formation presenting several vessels and osteoblasts. The other groups showed minor bone formation, with a diffuse marrow and thin network of newly... (Complete abstract click electronic access below)
Orientador: Gulnara Scaf
Coorientador: Elcio Marcantonio Junior
Banca: Maria Lúcia Rubo de Rezende
Banca: Eduardo Sant'Ana
Banca: Eduardo Hochuli Vieira
Banca: Joni Augusto Cirelli
Doutor
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Sehn, Felipe Perraro. "Influência da associação de osso bovino mineral com osso alógeno fresco congelado em enxertos para levantamento de seio maxilar. Estudo clínico, histológico e histomorfométrico em humanos." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/58/58136/tde-13062014-162825/.
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O osso alógeno fresco congelado e o Bio-Oss® (OBM) são materiais conhecidos como substitutos ao osso autógeno em cirurgias de levantamento de seio maxilar. O objetivo deste estudo foi avaliar clínica, histológica e histomorfometricamente o processo de reparo de enxertos alógenos com e sem a utilização de OBM, utilizados em técnicas de levantamento de seio maxilar em humanos. Neste estudo do tipo prospectivo, randomizado, tipo série de casos, comparativo, foram operados 34 seios maxilares de pacientes de ambos os sexos, que apresentavam um rebordo ósseo residual com altura máxima de 5 mm na região de seios maxilares para reconstrução em altura para cirurgias de levantamento de seio maxilar prévia à reabilitação por implantes. Os pacientes foram divididos em a) Grupo Controle: Dezessete (17) seios maxilares enxertados somente com a utilização de osso alógeno e b) Grupo Teste: 17 seios maxilares reabilitados com osso alógeno e OBM, na proporção de 2:1. Seis meses após a enxertia, no momento da instalação dos implantes, amostras ósseas foram coletadas por meio de trefinas para análise histológica e histomorfométrica. Os dados da investigação foram submetidos ao teste t de Student para amostras independentes empregado para comparações entre os dois grupos, Mann-Whitney e testes de correlação foram aplicados. 29 pacientes com uma média de idade de 51,32 anos (± 6,44), foram divididos em grupos controle (17) e teste (12), sendo 34 seios avaliados no total. Não houve diferença estatística entre os grupos com relação à idade (p = 0,23) e ao gênero (p = 0,56). Mediana do torque de inserção dos implantes foi de 32N para o grupo controle, e 45N para o grupo teste (p < 0,0001). Taxa de sucesso no grupo controle foi de 93,02% e 100% no grupo teste. Análise histológica apresentou no grupo controle osso alógeno residual com lacunas osteocíticas vazias e padrão lamelar; osso neoformado com lacunas osteocíticas com osteócitos viáveis e padrão imaturo; osteoblastos em íntimo contato matriz osteóide, formando pontes entre os blocos de osso alógeno e osso neoformado; osteoclastos em proximidade às áreas remodelação óssea; ausência de sinais de infiltrado inflamatório; tecido conjuntivo; e no grupo teste, todos os ítens acima e osso bovino mineral. Histomorfometria: material enxertado remanescente (p = 0,74); osso alógeno remanescente (35.78% ± 6.21% grupo controle, 19.72% ± 10.42% grupo teste; p < 0,0001); OBM remanescente no grupo teste (14,78% ± 8,67); osso neoformado (11.94% ± 1.71% grupo controle, 25.79% ± 8.76% grupo teste; p < 0,001); osso total (47.72% ± 5.6% grupo controle, 58.96% ± 8.1% grupo teste; p < 0,001); tecido conjuntivo (52.27% ± 5.6% grupo controle, 41.45% ± 8.4% grupo teste; p < 0,01). Adicionar OBM ao osso alógeno em cirurgias de levantamento de seio maxilar mostrou-se uma técnica de enxertia eficaz para a instalação de implantes. Resultou em maior torque de inserção, porcentagens maiores de osso neoformado e osso total, permitindo a instalação de implantes e reabilitação protética funcional.Allograft fresh frozen bone and Bio-Oss are knows as autogenous bone materials substitutes in maxillary sinus lifting. The aim of this study was to evaluate clinical, histological and histomorphometrically the process of repair with and without the association of BBM in maxillary sinus augmentation. In this prospective, randomized, comparative case series study, 34 maxillary sinuses were augmented, which had a residual bone ridge with a maximum height of 5 mm in maxillary sinus reconstruction region at the time for surgery of maxillary sinus prior to rehabilitation by implants. Patients were divided into a) control group: seventeen (17) grafted maxillary sinuses with only allograft bone and b) test group: 17 maxillary sinuses rehabilitated with allograft bone and BBM in a 2:1 ratio. Six months after grafting, at time of implant placement, bone samples were collected using a trephine burr for histological and histomorphometrical analysis. The research data were subjected to Student\'s t test for independent samples used for comparisons between two groups, Mann - Whitney and correlation tests were applied. 29 patients with a mean age of 51.32 years (± 6.44), were divided into control group (17) and test (12), with 34 maxillary sinuses evaluated in total. There was no statistical difference between the groups regarding to age (p = 0.23) and gender (p = 0.56). Median insertion torque of the implants was 32N for the control group and 45N for the test group (p < 0.0001). Survival rate in the control group was 93.02% and 100% in the test group. Histological analysis showed, at the control group, residual allograft bone with empty osteocytic lacunae and lamellar pattern; newly formed bone with osteocytic lacunae with viable osteocytes and immature pattern; osteoblasts in close contact with osteoid matrix, forming bridges between the blocks of allograft bone and new bone formation; osteoclasts in bone remodeling surrounding areas; no evidence of inflammatory infiltrate; connective tissue; and in the test group, all the items above and bovine bone mineral. Histomorphometry: graft remaining material (p = 0.74); remaining allogenous bone (35.78% ± 06.21% control group, 19.72% ± 10:42% test group, p < 0.0001); BBM remaining in the test group (14.78% ± 8.67); newly formed bone (11.94% ± 1.71% control group, 25.79% ± 8.76% test group, p < 0.001); total bone (47.72% ± 5.6% control group, 58.96% ± 8.1% test group, p < 0.001); connective tissue (52.27% ± 5.6% control group, 41.45% ± 8.4% test group, p < 0.01). Adding bovine bone mineral to allogenous bone in maxillary sinus surgery proved to be an effective technique of grafting for implant placement. It resulted in higher insertion torque, higher percentages of new bone formation and total bone, allowing installation of implants and functional loading.
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Guiu, Lahaye Séverine. "Facteurs pronostiques et prédictifs dans le cancer du sein infiltrant." Thesis, Besançon, 2015. http://www.theses.fr/2015BESA3012/document.
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Le traitement systémique adjuvant du cancer du sein infiltrant repose sur la chimiothérapie et l’hormonothérapie. Certains facteurs sont connus pour être pronostiques (âge, taille tumorale, statut ganglionnaire, grade tumoral, emboles vasculaires, statut des récepteurs hormonaux (RH) et de HER2) ou prédictifs de réponse aux traitements (RH et HER2) et influent sur nos décisions thérapeutiques. Cependant, certaines patientes récidivent malgré un traitement complet alors que d’autres vont recevoir un traitement qui aurait pu être évité de par leur bon pronostic « intrinsèque ». Nous avons cherché à identifier dans ce travail d’autres facteurs pronostiques et / ou prédictifs dans le cancer du sein infiltrant en situation néoadjuvante / adjuvante. Premièrement, nous montrons que le type histologique lobulaire, réputé pour être une histologie de cancer du sein de bon pronostic et peu chimiosensible, ne doit pas être un facteur décisionnel quant aux traitements systémiques. En situation adjuvante et concernant la chimiothérapie, la validité et l’utilité cliniques des tests génomiques nécessitent d’être évaluées spécifiquement dans ce sous-groupe. Ensuite, nous avons étudié la validité analytique, la validité clinique et l’utilité clinique de 2 classifications moléculaires des cancers du sein selon PAM50 et l’analyse immunohistochimique de biomarqueurs : récepteur œstrogène, HER2 et Ki67 avec un cut-off à 14%. Selon nos conclusions, il n’y a actuellement pas de données suffisamment robustes pour que ces 2 classifications modifient les décisions de traitement systémique. Nous avons mis en évidence un sous-groupe de tumeurs triples négatives exprimant le récepteur androgène et FOXA1 et se comportant comme des tumeurs luminales. Enfin, nous avons montré sur une large série néoadjuvante que la réponse histologique complète est un critère substitutif de survie pour les tumeurs RH négatifsThe adjuvant systemic treatment of invasive breast cancer is based on chemotherapy and endocrine therapy. Several prognostic factors (age, tumoral size, nodal status, tumoral grade, vascular embols, hormonal receptors (HR), HER2) and predictive factors of response to treatment (HR and HER2) are described and have an impact on our therapeutic decisions. However, recurrences are frequent after a complete treatment and patients could avoid such treatment because of the good “intrinsic” prognosis. In this work, we aimed to identify other prognostic and / or predictive factors for the invasive breast cancer in the neoadjuvant / adjuvant settings. Firstly, we showed that the lobular histology, considered as histology of good prognosis and low chemo sensitive, should not be a decisive factor regarding systemic therapy. In the adjuvant setting, regarding chemotherapy, clinical validity and utility of the genomic tests need to be specifically evaluated in this subgroup. Then, we studied analytical validity, clinical validity and clinical utility of 2 molecular classification of breast cancer: PAM50 and a panel of 3 biomarkers in immunohistochemistry (estrogen receptor, HER2 and Ki-67 with a cut-off of 14%). We concluded that the data were not strong enough and that the therapeutic decisions should not be influenced by these classifications. We identified a subgroup of triple negative breast cancer that express androgen receptor and FOXA1 and which behave like luminal tumors. At last, we showed in a large neoadjuvant population, that the pathological complete response is a surrogate marker of survival in RH negative tumors
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Filho, Bernardo Cunha Araújo. "Estudo da anatomia do seio esfenoidal através da dissecção endoscópica em cadáveres." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5143/tde-10072008-160428/.
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Introdução: O seio esfenoidal apresenta relações anatômicas extremamente importantes com estruturas neurovasculares. Estas podem apresentar diversas variações, tornando as suas relações com seio esfenoidal bastante complexas e potencialmente associadas a graves lesões durante sua abordagem. Objetivo: O objetivo deste estudo prospectivo foi descrever, através da dissecção endoscópica em cadáveres, os detalhes das variações anatômicas do SE, avaliando a concordância entre os lados e as diferenças dessas variações entre o gênero e a cor da pele. Casuística e Métodos: Quarenta e cinco cadáveres (90 fossas nasais) de ambos os sexos com idade no óbito entre 30 e 83 anos foram submetidos à dissecção endoscópica meticulosa do seio esfenoidal. A distância da parede anterior do SE à espinha nasal anterior; a localização e o formato do óstio do SE, o grau de pneumatização do SE, a presença de células de Onodi, a dominância entre os lados, a inserção de septo interssinusal e de cristas, a presença de proeminências e/ou deiscências da artéria carótida interna, do nervo óptico, do nervo maxilar e do nervo vidiano, assim como a presença de recessos óptico-carotídeo, pterigóide e lateral foram descritos. As prevalências foram comparadas entre o gênero e diferentes cor da pele. Também foi analisada a simetria entre os lados direito e esquerdo. Resultados: O óstio estava localizado medialmente à inserção póstero-inferior da concha superior em 85,6% das fossas nasais estudadas e em 50% apresentava-se com formato arredondado. A distância média do óstio do seio esfenoidal à espinha nasal anterior foi de 68 mm (+- 4,6mm) para ambos os lados. Não havia dominância dos lados direito ou esquerdo em 21 (46,7%) dos cadáveres. Em 17 cadáveres (37,8%) o seio esquerdo se apresentou mais pneumatizado e em 7 (15,6%), o seio esfenoidal direito apresentou dominância em relação ao esquerdo. O tipo selar foi o mais prevalente (53%) seguido do pré-selar (38%). O recesso mais prevalente foi o pterigóide (47,8%). As cristas estivaram presentes em 22,7% dos lados. O septo intersinusal se inseriu no trajeto da artéria carótida interna e do nervo óptico, respectivamente, em 16,7% e 2,2%. A artéria carótida interna esteve proeminente em 48,9% e deiscente em 31,1% das fossas estudadas. O nervo óptico estava proeminente e deiscente em 35,6% e 8,9%, respectivamente. O nervo vidiano foi a estrutura com proeminência mais prevalente (50%). O nervo maxilar esteve deiscente em 5,6% dos lados estudados. Uma célula de Onodi esteve presente em 23 (25,6%) dos lados dissecados. A análise da simetria mostrou concordância perfeita com relação ao grau de pneumatização e se apresentou bastante variável de acordo com a estrutura estudada. Cadáveres do sexo feminino apresentaram de forma estatisticamente significante maior prevalência de deiscência de carótida interna (p=0,002) e do nervo maxilar (p=0,02), assim como proeminência do nervo óptico (p < 0,001). Conclusão: Os dados demonstram a complexa anatomia interna do seio esfenoidal, e o conhecimento desta anatomia é de grande importância para evitar as potenciais complicações cirúrgicas nesta região.Introduction: There are extremely important anatomic relationships between the sphenoid sinus (SS) and neurovascular structures. These structures may have several anatomic variations, which makes their relationship with the sphenoid sinus complex and carries risks of severe injuries during surgery. Objective: This prospective study used endoscopic cadaver dissection to describe details of SS anatomic variations and to evaluate agreement between sides and differences between sexes and ethnic groups. Casuistic and Methods: Fourty-five cadavers (90 nasal fossae) of both sexes ageing between 30 and 83 years underwent careful dissection of the sphenoid sinus. Distance from the SS anterior wall to the anterior nasal spine, the position and shape of the SS, the degree of SS pneumatization, the presence of Onodi cells, the dominance between sides, the insertion of the intersinus septum and crests, the presence of dehiscence and protrusions of the internal carotid artery (ICA), optic nerve (ON), maxillary and vidian nerves, and the presence of optic-carotid, pterygoid and lateral recesses were described. Data were analyzed according to sex, skin color and symmetry between nasal fossae of each cadaver. Results: Ostia were located medially to the posteroinferior insertion of the superior turbinate in 85.6% of the nasal fossae, and were circular in 50% of the cases. The mean distance from the ostium to the anterior nasal spine was 68 mm (+- 4.6 mm) for both sides. No dominance of right or left side was found in 21 (46.7%) of the cadavers. In 17 cadavers (37.8%), the left sinus was more pneumatized, and in 7 (15.6%), the right sphenoid sinus showed dominance over the left sinus. The sellar type was the most prevalent (53%), followed by the presellar type (38%). Pterygoid recesses were the most prevalent (47.8%). Crests were found in 22.7% of the sides. The intersinus septum was inserted on the course of the internal carotid artery and optic nerve in 16.7% and 2.2 % of the cases. ICA protrusions were found in 48.9% of the cases, and dehiscence in 31.1% of the fossae under study. Dehiscence and protrusion of the ON were found in 35.6% and 8.9% of the cases. The vidian nerve was the structure with the most prevalent protrusion (50%). Dehiscence over the maxillary nerve was found in 5.6% of the sides. Onodi cells were found in 23 (25.6%) of the dissected sides. The analysis of symmetry revealed perfect agreement of the degree of pneumatization and was greatly variable depending on the structure analyzed. Female cadavers had a statistically greater prevalence of dehiscence over the internal carotid artery (p = 0.002) and over the maxillary nerve (p = 0.02), as well as greater prevalence of optic nerve protrusion (p < 0.001). Conclusion: Our data showed that the SS internal anatomy is complex, and its knowledge is essential during surgical approaches to the sphenoid sinus.
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Gallien-landriau, Isabelle. "Étude de l'altération fonctionnelle du système reproducteur par les perturbateurs endocriniens : caractérisation des effets, identification des xéno-estrogènes impliqués et conséquences sur les populations de poissons en estuaire et Baie de Seine." Le Havre, 2003. http://www.theses.fr/2003LEHA0009.
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Une étude du développement et de la reproduction du flet a été entreprise en Estuaire de Seine. Différentes perturbations ont été identifiées : (i) au niveau individuel, des réductions significatives de la masse des gonades, une vitellogenèse précoce chez 10% des femelles et 4% d'intersexués ne produisant pas d'ovocytes matures ont été constatés ; (ii) au niveau populationnel, une faible représentation des mâles de plus de 4 ans a conduit à un déséquilibre du sex-ratio observé (1 : 4). Des dérégulations du système endocrinien pourraient expliquer ces observations. Ainsi, la mesure de vitellogénine plasmatique révèle une forte induction (124 ± 43 æg. ML-1), qui touche 67% des mâles. De plus, l'analyse des contenus biliaires par le test YES montre la présence de composés estrogéno-mimétiques chez 50% des individus. L'analyse chimique (GC-MS) de ces composés révèle la contribution significative à la réponse mesurée d'estradiol, éthynylestradiol et alkylphénol- polyéthoxylatesA study of the development and reproduction of the flounder was undertaken in the Seine Estuary. Various disturbances were identified: (i) at the individual level, significant gonadal mass reductions, premature vitellogenesis in 10% of females, and 4% of intersex were observed, (ii) at the population level, a weak representation of males older than 4 years led to a biased sex-ratio (1 : 4). Spermatogenesis in the intersex fish was synchronous with normal fish but oocytes generally became cystic and subsequently degenerated. Disturbances of the endocrine status may partly explain these observations. Vitellogenin synthesis was induced in 67% of the males (mean plasma level : 124 ± 43 æg. ML-1) and 50% of the fish samples led to gene reporter induction in the yeast test (YES). Chemical analysis of these bile revealed that E2, EE2 and NPEO contributed significantly to observed reponse
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Rocha, Regina Furbino Villefort. "Análises epidemiológica, histopatológica e imuno-histoquímica de ameloblastomas : casuística de seis anos." Universidade Federal do Espírito Santo, 2012. http://repositorio.ufes.br/handle/10/5866.
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Previous issue date: 2012-07-04Ameloblastomas são tumores odontogênicos (TOs) de origem epitelial e etiologia desconhecida. Porém, estudos recentes identificaram alterações moleculares associadas ao desenvolvimento e progressão dos TOs, dentre elas as móleculas de adesão celular E-caderina e beta catenina. Objetivos: realizar um levantamento epidemiológico dos casos de ameloblastomas pertencentes ao arquivo do Serviço de Anatomia Patológica da Universidade Federal do Espírito Santo (SAPB-UFES), analisar suas características histopatológicas e a expressão de beta catenina nas diferentes variantes de ameloblastomas. Método: estudo retrospectivo dos casos de ameloblastomas registrados no SAPB-UFES, no período compreendido entre março de 2004 e dezembro de 2010. Foram coletados dados sociodemográficos, clinicorradiográficos, dados sobre acesso, diagnóstico, tratamento e seguimento desses pacientes. As análises histopatológicas foram baseadas nos critérios de Vickers e Gorlin, Waldron e El-Mofty e da Organização Mundial da Saúde. Para análise imuno-histoquímica foi utilizada a técnica indireta de imuno-peroxidase, com anticorpo primário anti beta catenina monoclonal de camundongo. Foram avaliados a intensidade e a localização da marcação. Para análise semiquantitativa foram adotados os escores: negativo, postividade focal, positividade variável e uniformidade positiva. Resultados: foram encontrados 13 ameloblastomas, classificados histopatologicamente como sólidos (06), unicísticos (03) e desmoplásicos (03). Todos foram imunomarcados. A intensidade de marcação variou de fraca a forte (1 a 3). A média de marcação variou de 10,82% a 13,38% no núcleo; de 39,93% a 47,61% na membrana; e de 90,01% a 98,53% no citoplasma. Entretanto não foi encontrada diferença significante de expressão de beta catenina entre os três diferentes tipos de ameloblastomas. Conclusão: os resultados epidemiológicos foram semelhantes a outros estudos. A expressão citoplasmática de beta catenina evidencia o acúmulo da mesma no citoplasma e sugere alteração na via de sinalização de Wnt. Por outro lado, a redução da expressão na membrana sugere alteração na adesão celular
Ameloblastomas are odontogenic tumors (OTs) derived from epithelium which etiology remains unknown. However, recent studies have identified molecular changes associated with the development and progression of OTs, including cell adhesion molecules like E-cadherin and beta-catenin. Objectives: to conduct an epidemiological investigation of ameloblastomas cases from files of the Anatomical Pathology Service at Federal University of Espírito Santo (SAPB-UFES), analyze their histopathological features and the expression of beta-catenin in different variants of ameloblastomas. Methods: a retrospective study of ameloblastomas registered at SAPB-UFES between March 2004 and December 2010. Sociodemographic, clinical and imaginological data were collected, as well as data about access, diagnosis, treatment and follow up of these patients. The histopathological analyzes were based on Vickers and Gorlin, Waldron and El-Mofty and the World Health Organization criteria. Primary antibody anti beta-catenin mouse monoclonal and indirect immuno-peroxidase technique was employed for immunohistochemical analysis. Intensity and location of the immunostaining were analysed. For semiquantitative analysis the scores were: negative, focal, variable and uniformity positivity. Results: there were 13 ameloblastomas, histopathologically classified as solid (06), unicystic (03) and desmoplastic (03). All of them were immunostained. The intensity of immunostaining ranged from weak to strong (1-3). The mean of immunostaining ranged from 10.82% to 13.38% in the nucleus; from 39.93% to 47.61% in the membrane; and from 90.01% to 98.53% in the cytoplasm. However, there was no significant difference in expression of beta-catenin between three different types of ameloblastomas. Conclusion: The results were similar to other epidemiological studies. The cytoplasmic expression of beta-catenin shows accumulation in the cytoplasm and suggests changes in the Wnt signaling pathway. Moreover, the reduction of membrane expression suggests changes in cell adhesion
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Charloux, Anne. "L'adénocarcinome au sein des cancers bronchiques primitifs non à petites cellules : étude rétrospective du rôle pronostique de ce type histologique sur une série de 376 patients." Strasbourg 1, 1992. http://www.theses.fr/1992STR1M200.
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Silva, Fabricio Moreira Serra e. "Avaliação clinica e histologica da eficacia de enxerto heterogeno organico bovino associado a proteina ossea morfogenetica de embrião bovino em cirurgia de levantamento de seio maxilar." [s.n.], 2005. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288704.
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Orientador: Renato MazzonettoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: O presente estudo teve como objetivo avaliar clinica e histologicamente o comportamento da associação entre uma matriz óssea orgânica bovina (Gen-Ox@) e uma proteína óssea morfogenética (BMP) derivada de embrião bovino (Gen-Pro@), quando comparada com enxerto ósseo autógeno em cirurgias para levantamento bilateral de seio maxilar. Foram operados 10 pacientes não-fumantes e sem alterações sistêmicas, que necessitavam de enxerto bilateral do seio maxilar para futura colocação de implantes osseointegráveis. Em todos os pacientes, foi selecionado um lado como teste e o contra-lateral como controle. Após um período de 6 a 11 meses, foi realizada avaliação clínica da área enxertada e biópsia com broca trefina de 2mm, em região adjacente ao eixo do implante a ser inserido. Os espécimes foram armazenados em formol a 10% e levados para processamento laboratorial para coloração das peças com hematoxilina-eosina e confecção das lâminas. A análise histológica foi realizada por meio de microscopia óptica. Clinicamente, pôde-se observar que a qualidade e quantidade óssea formada no lado preenchido com enxerto autógeno apresentaram um aspecto mais favorável à instalação dos implantes, podendo-se observar uma formação óssea mais completa. Histologicamente, pôde-se observar um padrão de neoformação óssea diferente, com o osso autógeno apresentando um aspecto mais organizado. Com o presente estudo, pôde-se concluir que, clinica e histologicamente, o padrão de formação óssea das áreas enxertadas com a associação de osso heterógeno bovino e proteína óssea morfogenética bovina apresenta um trabeculado ósseo menos compacto e menos organizado do que o osso autógeno
Abstract: The present study aimed to evaluate clinically and histologically the behavior of the association between bovine organic osseous matrix (Gen-Ox@) and bone morphogenetic protein (BMP) (Gen-Pro@), when compared with autogenous bone graft in bilateral maxillary sinus lift procedures. Ten non-smoking and systemically healthy patients who needed bilateral maxillary sinus grafting for the placement of osseointegrated implants were operated. In ali patients, one side was selected as test and the other as control. In a second surgical intervention, the implant placement was preceded by clinical evaluation and biopsy of the lateral sinus wall using with a 2 mm trefine bur, in the region of the bone wall created in the sinus lift procedure. The specimens were stored in 10% formalin and taken to laboratorial processing for hematoxicilin-eosin dying and section preparation. The histological analysis was performed through optical microscopy. Clinically, a better bone formation pattern could be observed in the side grafted with autogenous bone. Histologically, the bone neoformation pattern was different in both sides. In the present study, the association with BMP as a growth factor showed different results when compared to autogenous graft. With the present study, it was possible to conclude that clinically the bone formation pattern is better and more full when autogenous bone is used. Histologically, less compact and less organized bone pattern than with the autogenous bone were found
Mestrado
Cirurgia e Traumatologia Buco-Maxilo-Faciais
Mestre em Clínica Odontológica
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Jolicoeur, Francine. "Caractérisation de la cellule myoépithéliale du sein foetal, adulte normal et pathologique." Thèse, 2004. http://hdl.handle.net/1866/14633.
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García, de la Fuente Isabel. "Caractérisation du carcinome mammaire de phénotype basal." Thèse, 2006. http://hdl.handle.net/1866/15753.
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Boa, Olivier. "Analyse in vivo du remodelage à long terme de la peau reconstruite endothélialisée et de son réseau vasculaire et Étude in vitro de la pseudo-vasculogénèse lors du développement tumoral au sein de la peau reconstruite endothélialisée /." 2007. http://www.theses.ulaval.ca/2007/24705/24705.pdf.
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"Avaliação clinica e histologica da eficacia de enxerto heterogeno organico bovino associado a proteina ossea morfogenetica de embrião bovino em cirurgia de levantamento de seio maxilar." Tese, Biblioteca Digital da Unicamp, 2005. http://libdigi.unicamp.br/document/?code=vtls000352882.
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