References of "FOIDART, Jean-Michel"
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See detailNew Biological Investigations on 3-Bromophenyl 6-Acetoxymethyl-2-oxo-2H-1-Benzopyran-3-Carboxylate as Anti-angiogenic Agent
Hemmer, M.; Kempen, Isabelle; De Tullio, Pascal ULg et al

in Drug Development Research (2010), 71

The development of blood vessels inside tumors is required to provide the nutrients and oxygen needed for tumor growth and to allow the spread of cancer cells at a distance to form metastasis ... [more ▼]

The development of blood vessels inside tumors is required to provide the nutrients and oxygen needed for tumor growth and to allow the spread of cancer cells at a distance to form metastasis. Angiogenesis is also implicated in ocular diseases like age-related macular degeneration. The present work describes the potential anti-angiogenic properties of a coumarinic derivative, 3-bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate (IK9), previously described as a potent inhibitor of HT 1080 fibrosarcoma cell invasion in vitro and tumor growth in vivo. In vivo, ex vivo, and in vitro models were used to delineate the anti-angiogenic properties of IK9. The anti-angiogenic effect of IK9 was demonstrated in vivo in a choroidal neovascularization mice model and additionally ex vivo in a rat aortic ring assay where it was more active than the known matrix metalloproteinase inhibitor Ro 28-2653. IK9 did not affect apoptosis, proliferation, or endothelial cell invasiveness in vitro. These findings suggest a complex mechanism of action of the compound via direct or indirect effects on endothelial cell properties. This study identifies IK9 as a new potent inhibitor of angiogenesis and suggests its potential use as a therapeutic agent. [less ▲]

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See detailMMP-19 Deficiency Promotes Tenascin-C Accumulation and Allergen-induced Airway Inflammation.
Guéders, Maud ULg; Hirst, S.; Quesada Calvo, Florence ULg et al

in American Journal of Respiratory Cell and Molecular Biology (2010), 43(3), 286-95

Matrix metalloproteinases (MMPs) recently appeared as key regulators of inflammation, allowing recruitment and clearance of inflammatory cells and modifying the biological activity of many peptidic ... [more ▼]

Matrix metalloproteinases (MMPs) recently appeared as key regulators of inflammation, allowing recruitment and clearance of inflammatory cells and modifying the biological activity of many peptidic mediators by cleavage. MMP-19 is a newly described MMP and preferentially cleaves matrix proteins such as collagens and tenascin-C. The role of MMP-19 in asthma has not been described to date. The purpose of the present study was to assess MMP-19 expression in a murine asthma model and to address biological effects of MMP-19 deficiency in mice. Allergenexposed wild-type (WT) mice displayed an increased expression of MMP-19 mRNA and an increased number of MMP-19-positive cells in the lungs detected by immunohistochemistry. After allergen challenge of MMP-19 knockout (MMP-19-/-) mice, an exacerbated eosinophilic inflammation was detected in bronchoalveolar lavage fluid and bronchial tissue along with an increased airway responsiveness to methacholine. A shift towards increased Th2-driven inflammation in MMP-19-/- mice was demonstrated by 1) increased numbers of cells expressing the IL-33 receptor T1/ST2 in lung parenchyma, 2) increased IgG1 levels in serum and 3) higher levels of IL-13 and CCL11 in lung extracts. Tenascin-C was found accumulated in peribronchial areas of MMP-19-/- after allergen challenges as assessed by Western blot and immunohistochemistry analysis. We conclude that MMP-19 is a new mediator in asthma, preventing tenascin-C accumulation and directly or indirectly controlling Th2-driven airway eosinophilia and airway hyperreactivity. Our data suggest that MMP-19 might act on Th2 inflammation homeostasis through preventing tenascin protein accumulation. [less ▲]

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See detailMétaplasie osseuse de l'endomètre: deux cas rapportés
Mutsers, Emilie ULg; Chantraine, Frédéric ULg; Delbecque, Katty ULg et al

in Gunaïkeia (2010), 15(4),

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See detailDiabete et grossesse: impact de l'inertie medicale et de l'observance therapeutique.
Pintiaux, Axelle ULg; Chabbert-Buffet, N.; Philips, Jean-Christophe ULg et al

in Revue Médicale de Liège (2010), 65(5-6), 399-404

Pregnancy and infant outcomes are related to maternal blood glucose profile. Managing preexisting diabetes and achieving euglycaemia before and during the pregnancy reduce the risk for complications ... [more ▼]

Pregnancy and infant outcomes are related to maternal blood glucose profile. Managing preexisting diabetes and achieving euglycaemia before and during the pregnancy reduce the risk for complications. Screening, diagnosis and treatment of gestational diabetes are important issues from a public health point of view, more particularly because of the progression of this disease due to obesity epidemics among young people. Pregnancy in a diabetic woman is a critical situation where neither clinical inertia nor patient's non-compliance could be accepted. [less ▲]

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See detailLes indications de l'androgénothérapie chez la femme
DE GOTTAL, Emilie ULg; PINTIAUX, Axelle ULg; BELIARD, Aude ULg et al

in Réalités en Gynécologie-Obstétrique (2009), 138

Les taux d’androgènes peuvent être diminués dans de nombreuses situations pathologiques et iatrogènes, mais également physiologiquement chez la femme âgée. La déficience androgénique affecte de nombreux ... [more ▼]

Les taux d’androgènes peuvent être diminués dans de nombreuses situations pathologiques et iatrogènes, mais également physiologiquement chez la femme âgée. La déficience androgénique affecte de nombreux systèmes. La supplémentation androgénique améliorerait les fonctions cognitives, l’humeur, la libido, la qualité osseuse, la force et la fonction musculaire. Toutefois, ce traitement, n’est actuellement pas recommandé en routine par les Guidelines de l’Endocrine Society. Les androgènes peuvent entraîner de l’acné, une augmentation de la pilosité, une raucité de la voix et une clitorimégalie, ces deux derniers effets indésirables étant rares. Ils influencent également le système cardiovasculaire en modifiant le profil lipidique, mais les données restent controversées. La supplémentation par DHEA a été étudiée chez des femmes atteintes d’insuffisance surrénalienne. Il semblerait que 50 mg/j de DHEA soit la dose adéquate pour restaurer des taux d’androgènes physiologiques et améliorer ainsi les symptômes sans observer d’effets secondaires majeurs. Il est toutefois recommandé de poursuivre les recherches parmi les groupes de patientes atteintes de déficience androgénique afin d’en définir précisément le syndrome clinique et d’étudier les effets de l’androgénothérapie. [less ▲]

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See detailNew asthma biomarkers: lessons from murine models of acute and chronic asthma.
Di Valentin, Emmanuel ULg; Crahay, Céline; Garbacki, Nancy ULg et al

in American Journal of Physiology - Lung Cellular and Molecular Physiology (2009), 296(2), 185-97

Many patients suffering from asthma are not fully controlled by currently available treatments, and some of them display an airway remodeling leading to exaggerated lung function decline. The aim of the ... [more ▼]

Many patients suffering from asthma are not fully controlled by currently available treatments, and some of them display an airway remodeling leading to exaggerated lung function decline. The aim of the present study was to unveil new mediators in asthma to better understand pathophysiology and propose or validate new potential therapeutic targets. A mouse model of asthma mimicking acute or chronic asthma disease was used to select genes undergoing a modulation in both acute and chronic conditions. Mice were exposed to ovalbumin or PBS for 1, 5, and 10 wk [short-, intermediate-, and long-term model (ST, IT, and LT)], and gene expression in the lung was studied using an Affymetrix 430 2.0 genome-wide microarray and further confirmed by RT-PCR and immunohistochemistry for selected targets. We report that 598, 1,406, and 117 genes were upregulated and 490, 153, 321 downregulated at ST, IT, and LT, respectively. Genes related to mucous secretion displayed a progressively amplified expression during the allergen exposure protocol, whereas genes corresponding to growth and differentiation factors, matrix metalloproteinases, and collagens were mainly upregulated at IT. By contrast, genes related to cell division were upregulated at ST and IT and were downregulated at LT. In this study, besides confirming that Arg1, Slc26a4, Ear11, and Mmp12 genes are highly modulated throughout the asthma pathology, we show for the first time that Agr2, Scin, and Cd209e genes are overexpressed throughout the allergen exposure and might therefore be considered as suitable new potential targets for the treatment of asthma. [less ▲]

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See detailBiomarker discovery in asthma-related inflammation and remodeling.
Quesada Calvo, Florence ULg; Fillet, Marianne ULg; De Seny, Dominique ULg et al

in Proteomics (2009), 9(8), 2163-2170

Asthma is a complex inflammatory disease of airways. A network of reciprocal interactions between inflammatory cells, peptidic mediators, extracellular matrix components, and proteases is thought to be ... [more ▼]

Asthma is a complex inflammatory disease of airways. A network of reciprocal interactions between inflammatory cells, peptidic mediators, extracellular matrix components, and proteases is thought to be involved in the installation and maintenance of asthma-related airway inflammation and remodeling. To date, new proteic mediators displaying significant activity in the pathophysiology of asthma are still to be unveiled. The main objective of this study was to uncover potential target proteins by using surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) on lung samples from mouse models of allergen-induced airway inflammation and remodeling. In this model, we pointed out several protein or peptide peaks that were preferentially expressed in diseased mice as compared to controls. We report the identification of different five proteins: found inflammatory zone 1 or RELM (FIZZ-1), calcyclin (S100A6), clara cell secretory protein 10 (CC10), Ubiquitin, and Histone H4. [less ▲]

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See detailTraitement de la prééclampsie sévère: jusqu'où, et pour quels risques/bénéfices?
PETIT, Philippe ULg; Top, Marlene; CHANTRAINE, Frédéric ULg et al

in Revue Médicale de Liège (2009), 64(12), 620-625

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See detailRole of ADAM and ADAMTS metalloproteinases in airway diseases
Paulissen, Geneviève ULg; Rocks, Natacha ULg; Guéders, Maud ULg et al

in Respiratory Research (2009), 10(1), 127

Lungs are exposed to the outside environment and therefore to toxic and infectious agents or allergens. This may lead to permanent activation of innate immune response elements. A Disintegrin And ... [more ▼]

Lungs are exposed to the outside environment and therefore to toxic and infectious agents or allergens. This may lead to permanent activation of innate immune response elements. A Disintegrin And Metalloproteinases (ADAMs) and ADAMs with Thrombospondin motifs (ADAMTS) are proteinases closely related to Matrix Metalloproteinases (MMPs). These multifaceted molecules bear metalloproteinase and disintegrin domains endowing them with features of both proteinases and adhesion molecules. Proteinases of the ADAM family are associated to various physiological and pathological processes and display a wide spectrum of biological effects encompassing cell fusion, cell adhesion, "shedding process", cleavage of various substrates from the extracellular matrix, growth factors or cytokines... This review will focus on the putative roles of ADAM/ADAMTS proteinases in airway diseases such as asthma and COPD. [less ▲]

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See detailVEGF-D deficiency in mice does not affect embryonic or postnatal lymphangiogenesis but reduces lymphatic metastasis.
Koch, M.; Dettori, D.; Van Nuffelen, A. et al

in Journal of Pathology (The) (2009), 219(3), 356-364

Vascular endothelial growth factor-D (VEGF-D) is one of the two ligands of the VEGFR-3 receptor on lymphatic endothelial cells. Gene-silencing studies in mice and Xenopus tadpoles recently showed that the ... [more ▼]

Vascular endothelial growth factor-D (VEGF-D) is one of the two ligands of the VEGFR-3 receptor on lymphatic endothelial cells. Gene-silencing studies in mice and Xenopus tadpoles recently showed that the role of endogenous VEGF-D in lymphatic development is moderate. By contrast, exogenous VEGF-D is capable of stimulating lymphangiogenesis. Nonetheless, its endogenous role in pathological conditions remains largely unknown. Hence, we reassessed its role in disease, using Vegf-dnull mice. Vegf-dnull mice were generated that, under physiological conditions, displayed normal embryonic and postnatal lymphangiogenesis and lymphatic remodelling, efficient lymphatic functioning and normal health. Vegf-dnull mice also reponded normally in models of skin wound healing and healing of infarcted myocardium, despite enhanced expression of VEGF-D in these models in wild-type mice. In contrast, Vegf-dnull mice displayed reduced peritumoral lymphangiogenesis and lymph node metastasis in an orthotopic pancreatic tumour model. Together, our data indicate that endogenous VEGF-D in mice is dispensible for lymphangiogenesis during development, in postnatal and adult physiology and in several pathological conditions, but significantly contributes to lymphatic metastasis. [less ▲]

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See detailMembrane-Type 4 Matrix Metalloproteinase (MT4-MMP) induces lung metastasis by alteration of primary breast tumor vascular architecture
Chabottaux, Vincent; Ricaud, Stéphanie; Host, Lorin et al

in Journal of Cellular & Molecular Medicine (2009)

The present study aims at investigating the mechanism by which MT4-MMP, a membrane-anchored MMP expressed by human breast tumor cells promotes the metastatic dissemination into lung. We applied ... [more ▼]

The present study aims at investigating the mechanism by which MT4-MMP, a membrane-anchored MMP expressed by human breast tumor cells promotes the metastatic dissemination into lung. We applied experimental (intravenous) and spontaneous (subcutaneous) models of lung metastasis using human breast adenocarcinoma MDA-MB-231 cells overexpressing or not MT4-MMP. We found that MT4-MMP does not affect lymph node colonization nor extravasation of cells from the bloodstream, but increases the intravasation step leading to metastasis. Ultrastructural and fluorescent microscopic observations coupled with automatic computer-assisted quantifications revealed that MT4-MMP expression induces blood vessel enlargement and promotes the detachment of mural cells from the vascular tree, thus causing an increased tumor vascular leak. On this basis, we propose that MT4-MMP promotes lung metastasis by disturbing the tumor vessel integrity and thereby facilitating tumor cell intravasation. [less ▲]

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See detailChorionic Gonadotropin Stimulation of Angiogenesis and Pericyte Recruitment
Berndt, Sarah; Blacher, Silvia ULg; PERRIER d'HAUTERIVE, Sophie ULg et al

in Journal of Clinical Endocrinology and Metabolism (2009), 94(11), 4567-74

During the periimplantation period, human chorionic gonadotropin (hCG) plays a key role by increasing the uterine blood flow through uterine vessel vasodilatation but also through angiogenesis. Indeed, we ... [more ▼]

During the periimplantation period, human chorionic gonadotropin (hCG) plays a key role by increasing the uterine blood flow through uterine vessel vasodilatation but also through angiogenesis. Indeed, we previously demonstrated that hCG contributes to endothelial cell recruitment and vessel formation. OBJECTIVE: In this study, hCG was proposed as an arteriogenic factor that could promote perivascular cell recruitment and vessel stabilization. DESIGN: The aortic ring assay, a three-dimensional ex vivo angiogenesis system mimicking all the steps of the angiogenesis process was used to study the impact of hCG on pericyte recruitment and vessel maturation. SETTING: The study was conducted at a university hospital laboratory. MAIN OUTCOME MEASURES: Perivascular cell proliferation, migration, and apposition were quantified by computerized image analysis. RESULTS: Physiological concentrations of hCG (10-400 IU/ml) significantly enhanced pericyte sprouting and migration and gave rise to the maturation and coverage of endothelial capillaries. In a three-dimensional coculture model of endothelial and perivascular cells, hCG enhanced vessel tube formation and endothelial/mural cell adhesion. In addition, hCG stimulated the proliferation of human umbilical vein endothelial cells and smooth muscle cells. The specificity of these effects was determined by using an anti-hCG blocking antibody. Signaling pathways implicated on this hCG effect is protein kinase A and phospholipase C/protein kinase C dependent for the proliferative effect but only phospholipase C/protein kinase C for the migrative process. CONCLUSIONS: Our findings highlight a novel paracrine role of this early embryonic signal in vessel maturation by stimulating perivascular cell recruitment, migration, and proliferation. [less ▲]

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See detailAdditional parameters for the morphometry of angiogenesis and lymphangiogenesis in corneal flatmounts
Blacher, Silvia ULg; Detry, Benoît ULg; Bruyere, Françoise et al

in Experimental Eye Research (2009), 89(2), 274-276

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See detailMixed origin of neovascularization of human endometrial grafts in immunodeficient mouse models
Alvarez Gonzalez, Maria-Luz ULg; Frankenne, F.; Galant, C. et al

in Human Reproduction (2009), 24(9), 2217-24

BACKGROUND: In vivo mouse models have been developed to study the physiology of normal and pathologic endometrium. Although angiogenesis is known to play an important role in endometrial physiology and ... [more ▼]

BACKGROUND: In vivo mouse models have been developed to study the physiology of normal and pathologic endometrium. Although angiogenesis is known to play an important role in endometrial physiology and pathology, the origin of neovasculature in xenografts remains controversial. The aim of this study was to assess the origin of the neovasculature of endometrial grafts in different mouse models. METHODS: Human proliferative endometrium (n = 19 women) was grafted s.c. in two immunodeficient mouse strains: nude (n = 8) and severely compromised immunodeficient (SCID; n = 20). Mice were also treated with estradiol, progesterone or levonorgestrel. Fluorescence in-situ hybridization using a centromeric human chromosome X probe, immunohistochemistry (von Willebrand factor and collagen IV) and lectin perfusion were performed to identify the origin of the vessels. RESULTS: More than 90% of vessels within xenografts were of human origin 4 weeks after implantation. Some vessels (9.67 +/- 2.01%) were successively stained by human or mouse specific markers, suggesting the presence of chimeric vessels exhibiting a succession of human and murine portions. No difference in staining was observed between the two strains of mouse or different hormone treatments. Furthermore, erythrocytes were found inside human vessels, confirming their functionality. CONCLUSION: This article shows that human endometrial grafts retain their own vessels, which connect to the murine vasculature coming from the host tissue and become functional. [less ▲]

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See detailDevelopment of an animal experimental model to study the effects of levonorgestrel on the human endometrium.
Alvarez Gonzalez, Maria-Luz ULg; Galant, C.; Frankenne, F. et al

in Human Reproduction (2009), 24(3), 697-704

BACKGROUND: This study was designed to develop an animal model to test the response of endometrium to local progestin delivery. METHODS: Proliferative human endometrium was subcutaneously grafted in two ... [more ▼]

BACKGROUND: This study was designed to develop an animal model to test the response of endometrium to local progestin delivery. METHODS: Proliferative human endometrium was subcutaneously grafted in two groups of SCID mice that received, 2 days before, a subcutaneous estradiol (E2) pellet and, for half of them, an additional implant of levonorgestrel (LNG). Mice were sacrificed 1, 2, 3 or 4 weeks after endometrial implantation and grafts were histologically analysed. Proliferation, steroid hormone receptors, blood vessels and stromal decidualization in both groups (E2 and LNG) were immunohistologically evaluated and compared with proliferative endometrium and endometrium from women with an LNG intrauterine device. RESULTS: Grafts presented normal morphological endometrial characteristics. The expression of progesterone receptors was significantly decreased in glands and stroma of the LNG group as compared with the E2 group at all times. A significant decrease was also observed in the stromal expression of estrogen receptor- in the LNG group. At 4 weeks, the mean cross-sectional area of vessels was significantly higher after LNG treatment. CONCLUSIONS: These morphological and immunohistochemical characteristics are similar to those observed in women treated with local LNG. This mouse model might facilitate further investigations needed to understand the mechanisms responsible for the breakthrough bleeding frequently observed in progestin users. [less ▲]

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