Effets des polyphénols de vin rouge sur la prolifération cellulaire et sur le métabolisme du resvératrol

Il est connu qu une consommation modérée de vin rouge protégerait contre de nombreuses pathologies, du fait notamment de ses polyphénols. Nous avons étudié en particulier l effet de ces polyphénols sur le cancer colorectal, l un des cancers les plus fréquents dans les pays industrialisés. Certains polyphénols purifiés de vin rouge, comme le resvératrol et la quercétine, montrent des effets antiprolifératifs contre les cellules de cancer colorectal.Notre première approche a consisté à utiliser des extraits polyphénoliques de vins rouges de Bourgogne. Nous avons alors étudié d une part, leurs effets in vitro sur la prolifération cellulaire de lignées tumorales colorectales humaines SW480 et les interactions entre ces polyphénols et le transport et le métabolisme du resvératrol ; et d autre part, les effets in vivo chez la souris CF-1 d une consommation régulière de ces polyphénols dans l alimentation sur la survenue de lésions pré-néoplasiques chimio-induites par l azoxyméthane au niveau du colon.Notre deuxième approche s est orientée vers les modifications de la structure chimique du resvératrol. Par l ajout de groupements méthoxyles et hydroxyles, et par l isomérisation de sa structure (cis ou trans), nous avons cherché à dégager des relations structures-fonctions du resvératrol et à créer des dérivés plus bioactifs.Nous montrons que les polyphénols du vin rouge inhibent la prolifération de cellules cancéreuses coliques, en bloquant le cycle cellulaire. Certains polyphénols du vin tel que la quercétine sont capables d augmenter la capacité des cellules SW480 à accumuler le resvératrol. [Nous montrons que] chez les souris, la prise régulière de polyphénols de vin rouge dans l alimentation diminue le nombre global de lésions pré-néoplasiques, et surtout les lésions de grande taille dont dérivent les polypes intestinaux. Les modifications chimiques de la structure du resvératrol montrent que les analogues méthoxylés du cis-resvératrol sont de puissants antiprolifératifs par blocage de la mitose, alors que le mécanisme d action des dérivés du trans-resvératrol bloque le cycle cellulaire au niveau de la phase S.Ce travail supporte l idée que le recours aux polyphénols du vin dans la prévention des adénocarcinomes coliques est possible et que ce champs de recherche est une voie prometteuse. Concernant des visées thérapeutiques, la recherche d analogues du resvératrol présentant une biodisponibilité accrue est une piste à poursuivreIt is known that moderate consumption of red wine may protect against many diseases, in particular because of its polyphenols. We studied in particular the effect of these polyphenols on colorectal cancer, one of the most common cancers in industrialized countries. Some purified polyphenols from red wine, like resveratrol and quercetin, showed antiproliferative effects against colorectal cancer cells.Our first approach was to use polyphenolic extracts from Burgundy red wine. We then studied their in vitro effects on human colorectal tumor cell lines SW480 s proliferation and the interactions between the polyphenols and the transport and metabolism of resveratrol; and secondly, the effects on CF-1 mice of regular consumption of these polyphenols in the diet on the occurrence of chemically induced pre-neoplastic lesions by azoxymethane in the colon.Our second approach was directed towards changes in the chemical structure of resveratrol. By the addition of hydroxyl and methoxyl groups, and the isomerization of its structure (cis or trans), we wanted to identify structure-function relationships of resveratrol and create more bioactive derivatives.We show that the red wine polyphenols inhibit proliferation of colon cancer cells by blocking the cell cycle. Some wine polyphenols such as quercetin are able to increase the ability of SW480 cells to accumulate resveratrol. [We show that] in mice, the regular intake of red wine polyphenols in the diet reduces the overall number of pre-neoplastic lesions, especially large lesions which may become intestinal polyps. The chemical changes in the structure of resveratrol show that the methoxylated analogues of cis-resveratrol are potent antiproliferatives by blocking mitosis, while the mechanism of action of derivatives of trans-resveratrol blocks the cell cycle at the S phase.This work supports the idea that the use of wine polyphenols in the prevention of colon adenocarcinomas is possible and that this field of research is a promising way. Concerning therapeutic purposes, the search for analogues of resveratrol with improved bioavailability is a way to pursueDIJON-BU Doc.électronique (212319901) / SudocSudocFranceF

Engineering vascular networks in porous polymer matrices

Enhanced vascularization is critical to the treatment of ischemic tissues and the engineering of new tissues and organs. We have investigated whether sustained and localized delivery of vascular endothelial growth factor (VEGF) combined with transplantation of human microvascular endothelial cells (HMVECs) can be used to engineer new vascular networks. VEGF was incorporated and released in a sustained manner from porous poly(lactic- co -glycolic acid) (PLG) matrices to promote angiogenesis at the transplantation site. VEGF could be incorporated and released in a biologically active form from PLG matrices, with the majority of VEGF release (64%) occurring within 2 weeks. These matrices promoted a 260% increase in the density of host SCID mouse-derived capillaries invading the matrices after 7 days of implantation, confirming the activity of the released VEGF. HMVECs were transplanted into SCID mice on PLG matrices, and organized to form immature human-derived vessels within 3 days. Functional vessels were observed within 7 days. Importantly, when HMVECs were transplanted on VEGF-releasing matrices, a 160% increase in the density of human-derived blood vessels was observed after 14 days. These findings suggest that combining elements of vasculogenesis and angiogenesis provides a viable and novel approach to enhancing local vascularization. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 668–678, 2002Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34425/1/10134_ftp.pd

Erythroid Promoter Confines FGF2 Expression to the Marrow after Hematopoietic Stem Cell Gene Therapy and Leads to Enhanced Endosteal Bone Formation

Fibroblast growth factor-2 (FGF2) has been demonstrated to be a promising osteogenic factor for treating osteoporosis. Our earlier study shows that transplantation of mouse Sca-1+ hematopoietic stem/progenitor cells that are engineered to express a modified FGF2 leads to considerable endosteal/trabecular bone formation, but it also induces adverse effects like hypocalemia and osteomalacia. Here we report that the use of an erythroid specific promoter, β-globin, leads to a 5-fold decrease in the ratio of serum FGF2 to the FGF2 expression in the marrow cavity when compared to the use of a ubiquitous promoter spleen focus-forming virus (SFFV). The confined FGF2 expression promotes considerable trabeculae bone formation in endosteum and does not yield anemia and osteomalacia. The avoidance of anemia in the mice that received Sca1+ cells transduced with FGF2 driven by the β-globin promoter is likely due to attenuation of high-level serum FGF2-mediated stem cell mobilization observed in the SFFV-FGF2 animals. The prevention of osteomalacia is associated with substantially reduced serum Fgf23/hypophosphatemia, and less pronounced secondary hyperparathyroidism. Our improved stem cell gene therapy strategy represents one step closer to FGF2-based clinical therapy for systemic skeletal augmentation

Par-dessus le Rhin, Au delà du Rhin : l'Eurodistrict Strasbourg-Ortenau ou les usages de la coopération transfrontalière à Strasbourg et autour de Strasbourg

Le 17 octobre 2005, la convention de création de l’Eurodistrict Strasbourg-Ortenau est ratifiée par les représentants de la CUS, de l’Ortenaukreis et des villes de l’Ortenau. Cette structure transfrontalière a pour but de faciliter l’émergence d’une intercommunalité transfrontalière. L’Eurodistrict Strasbourg-Ortenau constitue ainsi le vecteur privilégié de la coopération transfrontalière de proximité entre Strasbourg et l’Ortenau. Pourquoi l’Eurodistrict a-t-il trouvé un fort écho auprès des acteurs locaux strasbourgeois et de l’Ortenau ? En considérant successivement l’Eurodistrict comme un outil mis au service des acteurs et des politiques publiques locales, ce mémoire s’intéresse aux usages de la coopération transfrontalière à Strasbourg et autour de Strasbourg. C’est donc une analyse sociologique de la coopération transfrontalière qui se dessine en filigrane à travers l’exemple de l’Eurodistrict Strasbourg-Ortenau

Information transfer in fish shoals: The use of information during social foraging, navigation and decision making.

Living in groups is a widespread strategy among animals and conveys significant benefits to group members. The proximity of conspecifics provides access to valuable information which individuals use to enhance their foraging success, reduce predation risks, or just facilitate their navigation. Hence, information transfer among group members plays a salient role in the behaviour of animal groups but much of its function is still unknown. In this thesis, I investigate different aspects of information use in social animals during foraging, decision making and navigation contexts, using fish shoals as biological model. I start with a general introduction providing the context with which I developed each of my empirical studies presented in the four following chapters. First, I examine how individual movement characteristics change as individuals reinforce their knowledge about the spatial distribution of prey. Then I investigate the effect of the quality of social information on the foraging success of uninformed individuals. Next, I pursue this line of work by testing whether information transfer affects two important aspects of collective decision making: group accuracy and the likelihood to reaching consensus. Finally, I investigate how information flow within navigating fish schools is affected by the structural properties of the group. This thesis concludes with a review of presented results and a broader discussion on the important role of information transfer on the performance of animal groups

Dépistage du cancer du col de l'utérus en territoire rural (état des lieux et perspectives d'avenir)

DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF