Maternal plasma soluble endoglin at 11-13 weeks's gestation in pre-eclampsia
Foidart, Jean-Michel ; Munaut, Carine ; Chantraine, Frédéric et al
in Ultrasound in Obstetrics & Gynecology (2010), 35(6), 680-7
Objectives: To examine the performance of screening for preeclampsia (PE) by a combination of maternal factors, soluble endoglin (sEng), pregnancy associated plasma protein A (PAPP-A), placental growth ... [more ▼]
Objectives: To examine the performance of screening for preeclampsia (PE) by a combination of maternal factors, soluble endoglin (sEng), pregnancy associated plasma protein A (PAPP-A), placental growth factor (PlGF) and uterine artery lowest pulsatibility index (L-PI) at 11-13 weeks of gestation. Methods: Uterine artery L-PI, sEng, PAPP-A and PlGF were measured at 11-13 weeks in 90 singleton pregnancies that subsequently developed PE, including 30 that required delivery before 34 weeks (early-PE) and 60 with late-PE, and 180 unaffected controls. Screening performance for PE by maternal factors, sEng, PAPP-A, PlGF and uterine artery L-PI and their combinations was determined. Results: In early-PE, compared to controls, plasma sEng and uterine L-PI were significantly increased and serum PAPP-A and PlGF were decreased. In late-PE, compared to controls, serum PlGF was decreased and uterine L-PI was increased but plasma sEng and serum PAPP-A were not significantly different. In screening for early-PE, the detection rate at a 10% false positive rate was 46.7% for sEng alone and 96.3% for a combination of maternal factors, sEng, PlGF and uterine artery L-PI. Conclusions: Effective screening for early-PE can be provided by a combination of maternal factors, sEng, PlGF and uterine artery L-PI at 11-13 weeks. [less ▲]Detailed reference viewed: 27 (10 ULg)
Does plasminogen activator inhibitor-1 drive lymphangiogenesis?
; ; Blacher, Silvia et al
in PLoS ONE (2010), 5(3), 9653
The purpose of this study is to explore the function of plasminogen activator inhibitor-1 (PAI-1) during pathological lymphangiogenesis. PAI-1, the main physiological inhibitor of plasminogen activators ... [more ▼]
The purpose of this study is to explore the function of plasminogen activator inhibitor-1 (PAI-1) during pathological lymphangiogenesis. PAI-1, the main physiological inhibitor of plasminogen activators is involved in pathological angiogenesis at least by controlling extracellular proteolysis and by regulating endothelial cell survival and migration. Protease system's role in lymphangiogenesis is unknown yet. Thus, based on its important pro-angiogenic effect, we hypothesized that PAI-1 may regulate lymphangiogenesis associated at least with metastatic dissemination of cancer cells. To address this issue, we studied the impact of PAI-1 deficiency in various murine models of tumoral lymphangiogenesis. Wild-type PAI-1 proficient mice were used as controls. We provide for the first time evidence that PAI-1 is dispensable for tumoral lymphangiogenesis associated with breast cancers either induced by mammary carcinoma cell injection or spontaneously appearing in transgenic mice expressing the polyomavirus middle T antigen (PymT) under the control of a mouse mammary tumor virus long-terminal repeat promoter (MMTV-LTR). We also investigated inflammation-related lymphatic vessel recruitment by using two inflammatory models. PAI-1 deficiency did neither affect the development of lymphangioma nor burn-induced corneal lymphangiogenesis. These novel data suggest that vascular remodelling associated with lymphangiogenesis and angiogenesis involve different molecular determinants. PAI-1 does not appear as a potential therapeutic target to counteract pathological lymphangiogenesis. [less ▲]Detailed reference viewed: 83 (22 ULg)
Soluble forms of VEGF receptor-1 and -2 promote vascular maturation via mural cell recruitment.
LORQUET, Sophie ; ; Blacher, Silvia et al
in FASEB Journal (2010), 24(10), 3782-95
Two soluble forms of vascular endothelial growth factor (VEGF) receptors, sVEGFR-1 and sVEGFR-2, are physiologically released and overproduced in some pathologies. They are known to act as anti-VEGF ... [more ▼]
Two soluble forms of vascular endothelial growth factor (VEGF) receptors, sVEGFR-1 and sVEGFR-2, are physiologically released and overproduced in some pathologies. They are known to act as anti-VEGF agents. Here, we report that these soluble receptors contribute to vessel maturation by mediating a dialogue between endothelial cells (EC) and mural cells that leads to blood vessel stabilization. Through a multidisciplinary approach, we provide evidences that these soluble VEGF receptors promote mural cell migration through a paracrine mechanism involving interplay in EC between VEGF/VEGFR-2 and sphingosine-1- phosphate type-1 (S1P)/S1P1 pathways that leads to endothelial nitric oxyde synthase (eNOS) activation. This new paradigm is supported by the finding that sVEGFR-1 and -2: 1) induce an eNOS-dependent outgrowth of a mural cell network in an ex vivo model of angiogenesis, 2) increase the mural cell coverage of neovessels in vitro and in vivo, 3) promote mural cell migration towards EC, 4) stimulate endothelial S1P1 overproduction and eNOS activation that promote the migration and the recruitment of neighboring mural cells. These findings provide new insights into mechanisms regulating physiological and pathological angiogenesis and vessel stabilization. [less ▲]Detailed reference viewed: 144 (44 ULg)
Higher sensitivity of Adamts12-deficient mice to tumor growth and angiogenesis.
El Hour, Mehdi ; ; Blacher, Silvia et al
in Oncogene (2010), 29(20), 3025-32
ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) constitute a family of endopeptidases related to matrix metalloproteinases. These proteases have been largely implicated in ... [more ▼]
ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) constitute a family of endopeptidases related to matrix metalloproteinases. These proteases have been largely implicated in tissue remodeling and angiogenesis associated with physiological and pathological processes. To elucidate the in vivo functions of ADAMTS-12, we have generated a knockout mouse strain (Adamts12−/−) in which Adamts12 gene was deleted. The mutant mice had normal gestations and no apparent defects in growth, life span and fertility. By applying three different in vivo models of angiogenesis (malignant keratinocyte transplantation, Matrigel plug and aortic ring assays) to Adamts12−/− mice, we provide evidence for a protective effect of this host enzyme toward angiogenesis and cancer progression. In the absence of Adamts-12, both the angiogenic response and tumor invasion into host tissue were increased. Complementing results were obtained by using medium conditioned by cells overexpressing human ADAMTS-12, which inhibited vessel outgrowth in the aortic ring assay. This angioinhibitory effect of ADAMTS-12 was independent of its enzymatic activity as a mutated inactive form of the enzyme was similarly efficient in inhibiting endothelial cell sprouting in the aortic ring assay than the wild-type form. Altogether, our results show that ADAMTS-12 displays antiangiogenic properties and protect the host toward tumor progression. [less ▲]Detailed reference viewed: 141 (36 ULg)
Défaut d'observance et inertie therapeutique en obstétrique.
Masson, Véronique ; Petit, Philippe ; Foidart, Jean-Michel
in Revue Médicale de Liège (2010), 65(5-6), 395-8
Observance around pregnancy includes two parts: what can be done before conception and what must be done during pregnancy. Preconception care, if efficaciously performed, offerss real benefits for foetal ... [more ▼]
Observance around pregnancy includes two parts: what can be done before conception and what must be done during pregnancy. Preconception care, if efficaciously performed, offerss real benefits for foetal and child development. Its efficacy will depends on the involvement and motivation of physicians and particularly also on the patient's observance. In this article we summarize essential pieces of advice to be given to each patient before pregnancy. Therapeutic inertia in obstetrics presents two differents aspects: on the one hand, the delay to initiate a therapeutic strategy when a complication arises such as a postpartum hemorrhage; on the other hand, the continuation of obsolete practices, such as the therapy of uterine hypersystolia. [less ▲]Detailed reference viewed: 66 (3 ULg)
L'inertie thérapeutique en contraception.
Pintiaux, Axelle ; Bouüaert, Corine ; Habay, Nathalie et al
in Revue Médicale de Liège (2010), 65(5-6), 391-4
The efficiency of contraception is linked to the method and the patient's compliance. The advice given by the physician about contraception use is essential to avoid unintended pregnancy. The accuracy of ... [more ▼]
The efficiency of contraception is linked to the method and the patient's compliance. The advice given by the physician about contraception use is essential to avoid unintended pregnancy. The accuracy of contraceptive choice and the individualized adaptation over time contribute to safe contraception. [less ▲]Detailed reference viewed: 103 (3 ULg)
Ultrasound assessment of the intima and media layers on the carotid arteries in peri- and postmenopausal women
Chantraine, Frédéric ; ; Coudoux, Elodie et al
in European Journal of Ultrasound (2010), 31(S 01), 906Detailed reference viewed: 13 (0 ULg)
Local applications of GM-CSF induce the recruitment of immune cells in cervical low-grade squamous intraepithelial lesions.
Hubert, Pascale ; Doyen, Jean ; Capelle, Xavier et al
in American Journal of Reproductive Immunology (2010), 64(2), 126-136
Abstract Problem Quantitative alterations of antigen-presenting cells (APC) in (pre)neoplastic lesions of the uterine cervix associated with human papillomavirus (HPV) infection suggest a diminished ... [more ▼]
Abstract Problem Quantitative alterations of antigen-presenting cells (APC) in (pre)neoplastic lesions of the uterine cervix associated with human papillomavirus (HPV) infection suggest a diminished capacity to capture viral antigens and to induce a protective immune response. Method of study To test if a cervical application of GM-CSF could restore an immune response against HPV in women with cervical low-grade squamous intraepithelial lesions (LSIL). We performed two clinical trials with11 healthy women and 15 patients with LSIL. Results GM-CSF applications were well tolerated in all enrolled women and no difference in toxicity between the treated and placebo groups was observed during the follow up (until 30 months). Interestingly, in the GM-CSF treated group, a significant increased APC and cytotoxic T lymphocyte infiltration was observed in the cervical biopsies with no change in regulatory T cell numbers. All the HPV16+ patients exhibited an immune response against HPV16 after GM-CSF applications, as shown by NK and/or T cells producing IFN-γ whereas no cellular immune response was observed before the treatment. Moreover, the anti-VLP antibody titers also increased after the treatment. Conclusion These encouraging results obtained from a limited number of subjects justify further study on the therapeutic effect of APC in cervical (pre)neoplastic lesions. [less ▲]Detailed reference viewed: 129 (52 ULg)
Human Chorionic Gonadotropin: a hormone with immunological and angiogenic properties.
; Gridelet, Virginie ; Berndt, Sarah et al
in Journal of Reproductive Immunology (2010), 85(1), 93-8
The success of implantation depends on a receptive endometrium, a normal blastocyst and synchronized cross-talk at the maternal–fetal interface. The progression of pregnancy then requires immunological ... [more ▼]
The success of implantation depends on a receptive endometrium, a normal blastocyst and synchronized cross-talk at the maternal–fetal interface. The progression of pregnancy then requires immunological tolerance which allows conceptus survival. A cascade of cytokines mediates this dialogue and is crucial in the cross-talk between the immune and endocrine systems. The first known human embryo-derived signal is chorionic gonadotropin (hCG) by which the embryo profoundly influences immunological tolerance and angiogenesis at the maternal–fetal interface. hCG levels coincide with the development of trophoblast tolerance. Indeed, it increases the number of uterine natural killer cells that play a key role in the establishment of pregnancy. hCG also intervenes in the development of local immune tolerance through the cellular system of apoptosis via Fas/Fas-Ligand. It modulates the Th1/Th2 balance and acts on complement C3 and C4A/B factors modulating decidual immunity. The transient tolerance evident during gestation is at least partially achieved via the presence of regulatory T cells which are attracted by hCG at the fetal–maternal interface. Finally, hCG treatment of activated dendritic cells results in an up-regulation of MHC class II, IL-10 and IDO expression, reducing the ability to stimulate T cell proliferation. Successful implantation requires an extensive endometrial angiogenesis in the implantation site. Recent data demonstrate angiogenic effects of hCG via its interaction with endometrial and endothelial LH/hCG receptors. Our review focuses on these functions of hCG, giving new insight into the endocrine–immune dialogue that exists between the conceptus and immune cells within the receptive endometrium at the time of implantation. [less ▲]Detailed reference viewed: 62 (19 ULg)
Performance evaluation of microbead and ELISA assays for follicular G-CSF: a non-invasive biomarker of oocyte developmental competence for embryo implantation.
; Munaut, Carine ; et al
in Journal of Reproductive Immunology (2010), 86(2), 126-32
G-CSF in individual follicular fluids correlates with the potential of the corresponding embryo to result in a live birth after transfer in IVF. To evaluate the requirements for routine follicular fluid G ... [more ▼]
G-CSF in individual follicular fluids correlates with the potential of the corresponding embryo to result in a live birth after transfer in IVF. To evaluate the requirements for routine follicular fluid G-CSF quantification, we compared follicular fluid G-CSF measurements made with two multiplexed microbead assays purchased from Bio-Rad Laboratories and R&D Systems, and a commercial G-CSF ELISA (R&D Systems). Individual follicular fluids (n=139) associated with transferred embryos were analysed to determine cytokine profile and the fate of each transferred embryo was recorded. The effect of multiplexing as well as comparison of the respective performances of the microbead assay with a flow cytometry assay was explored. Multivariable logistic regression analysis was performed and receiver operating characteristic (ROC) analysis was used to determine the performance and sensitivity/specificity of each method for individual follicular fluids. Covariate factors known to influence IVF outcome such as age, serum oestradiol and embryo score were systematically integrated in each analysis. The quantification of follicular fluid G-CSF using microbead assay methodologies, but not ELISA, yielded results showing the utility of follicular fluid G-CSF as a biomarker predictive of a successful delivery (Au(roc): 0.77 [0.68-0.84] (p=0.003) and 0.75 [0.66-0.82] (p=0.004) for Bio-Rad and R&D Systems microbead assays respectively), whereas follicular fluid G-CSF values quantified by ELISA were not predictive (Au(roc):0.61 [0.52-0.70] p=0.84). Microbead assay and flow cytometry appeared similarly efficient for quantifying follicular fluid G-CSF and multiplex versus single-plex assays did not influence the reliability of quantification. [less ▲]Detailed reference viewed: 48 (16 ULg)
Maternal plasma soluble fms-like tyrosine kinase-1 and free vascular endothelial growth factor at 11 to 13 weeks of gestation in preeclampsia.
; ; Foidart, Jean-Michel et al
in Prenatal Diagnosis (2010), 30(3), 191-7
Objective To investigate the maternal plasma concentration of soluble fms-like tyrosine kinase-1 (sFlt-1) and free vascular endothelial growth factor (free-VEGF) at 11 to 13 weeks of gestation in patients ... [more ▼]
Objective To investigate the maternal plasma concentration of soluble fms-like tyrosine kinase-1 (sFlt-1) and free vascular endothelial growth factor (free-VEGF) at 11 to 13 weeks of gestation in patients destined to develop preeclampsia (PE) and to examine whether any possible differences in maternal plasma levels are related to uterine artery pulsatility index (PI) and maternal serum placental growth factor (PlGF). Methods Plasma free-VEGF, plasma sFlt-1, serum PlGF and uterine artery PI were measured at 11 to 13 weeks in 90 cases that subsequently developed PE and in 180 unaffected controls. Results In the majority of cases of PE and controls the levels of free-VEGF were undetectable. In the pregnancies that developed PE, compared to unaffected controls, uterine artery PI was higher, serum PlGF was lower but there was no significant difference in levels of sFlt-1. Conclusion Measurement of free-VEGF and sFlt-1 in maternal blood at 11 to 13 weeks of gestation is not useful in the prediction of pregnancies destined to develop PE [less ▲]Detailed reference viewed: 22 (5 ULg)
Management of severe preeclampsia
Brichant, Géraldine ; Dewandre, Pierre-Yves ; Foidart, Jean-Michel et al
in Acta Clinica Belgica (2010), 65(3), 163-169
Features of severe preeclampsia include severe proteinuric hypertension and symptoms of central nervous system dysfunction, hepatocellular injury, thrombocytopenia, oliguria, pulmonary oedema ... [more ▼]
Features of severe preeclampsia include severe proteinuric hypertension and symptoms of central nervous system dysfunction, hepatocellular injury, thrombocytopenia, oliguria, pulmonary oedema, cerebrovascular accident and severe intrauterine growth restriction. Women with severe preeclampsia must be hospitalized to confirm the diagnosis, to assess the severity of the disease, to monitor the progression of the disease and to try to stabilize the disease. Severe preeclampsia may be managed expectantly, in selected cases. The objective of expectant management in these patients is to improve neonatal outcome. Expectant management is based on antihypertensive treatment and prevention of end organ dysfunction. Antihypertensive treatment improves maternal outcome but has the potential to be deleterious for the foetus. Plasma volume expansion has been suggested for severe preeclampsia but trials failed to show any benefit. Magnesium sulfate is the anticonvulsivant of choice to treat or prevent eclampsia when indicated. Antenatal corticosteroids are recommended in severely preeclamptic women with 26-34 weeks gestation. Timing of delivery is based upon gestational age, severity of preeclampsia, maternal and foetal risks. [less ▲]Detailed reference viewed: 55 (16 ULg)
Membrane type 1 matrix metalloproteinase detection in tumors, using the iodinated endogenous [123I]-tissue inhibitor 2 of metalloproteinases as imaging agent.
; ; et al
in Cancer Biotherapy & Radiopharmaceuticals (2010), 25(5), 511-20
Matrix metalloproteinases (MMPs) are principal participants in tumor development. In addition to serve as a useful biochemical marker, MMP expression may also provide a target for the diagnostic in vivo ... [more ▼]
Matrix metalloproteinases (MMPs) are principal participants in tumor development. In addition to serve as a useful biochemical marker, MMP expression may also provide a target for the diagnostic in vivo imaging of tumors, using a radiolabeled inhibitor. This study investigates the use of membrane type 1 (MT1)-MMP as target for in vivo tumor diagnosis. Specific binding of the endogenous tissue inhibitor of metalloproteinase-2 (TIMP-2) to MT1-MMP has been previously described. In this study, biodistribution and imaging experiments were performed on MT1-MMP-overexpressing (S.1.5) and control (C.IV.3) tumor-inoculated mice using [(123)I]-recombinant human TIMP-2 (rhTIMP-2) as radioligand and [(123)I]-rhTIMP-1 as control. The expression profile was controlled in vitro and on tumor extracts. rhTIMP-2 as well as rhTIMP-1 were labeled using the Iodogen method and characterized. Biodistribution of [(123)I]-rhTIMP-2 showed a tumor uptake of 2.87% +/- 1.58% ID/g at 3 hours postinjection in S.1.5. Tumor values of [(123)I]-rhTIMP-1 and [(123)I]-rhTIMP-2 evaluated in S.1.5 and C.IV.3, respectively, were significantly lower. Planar imaging revealed significant uptake of [(123)I]-rhTIMP-2 in S.1.5 compared with contralateral background areas. This could not be observed in C.IV.3 and with [(123)I]-rhTIMP-1 in S.1.5. All tumors were well established (200-800 mg). These results suggest that rhTIMP-2 holds potential for development of radiotracers for in vivo imaging in overexpressing MT1-MMP but not in similar tumors that do not express this protease. [less ▲]Detailed reference viewed: 19 (5 ULg)
Manifestations hemodynamiques et respiratoires de la preeclampsie.
Brichant, Jean-François ; Brichant, Géraldine ; Dewandre, Pierre-Yves et al
in Annales Françaises d'Anesthésie et de Réanimation (2010), 29
The hemodynamic and cardiovascular changes seen during PE vary according to the natural history of the disease, its severity and eventual therapeutic measures taken. In the early stages of pregnancy ... [more ▼]
The hemodynamic and cardiovascular changes seen during PE vary according to the natural history of the disease, its severity and eventual therapeutic measures taken. In the early stages of pregnancy, patients who will eventually develop PE, present with a blood pressure which even though within normal limits, is higher than in other women. Similarly, their cardiac output is higher with a normal or decreased peripheral vascular resistance. As soon as the clinical signs of the disease appear, the hemodynamic picture usually shifts toward that of a high peripheral resistance with low cardiac output. Sometimes however, a clinically hyperkinetic circulation may be demonstrated. In PE patients, cardiac preload pressures are usually normal even though the circulatory volumes are lower by 600 to 800ml when compared to those found in normal pregnancy. The cardiac function is however usually preserved during PE. PE induces an exaggerated capillary permeability. This results in the worsening of the airway edema which may render the intubation very difficult. The increased capillary permeability contributes, among other factors, to the heightened risk of acute pulmonary edema. It is not justified to administer an anti-hypertensive treatment to PE women presenting with only moderate hypertension. An anti-hypertensive treatment must only be initiated whenever the hypertension is severe (i.e. SBP>/=160mmHg and/or DBP>/=110mmHg) in order to reduce the risk of maternal complications. In the absence of objective comparative data assessing anti-hypertensive agents for the PE patient, the choice of therapy relies predominantly on the practitioners' own experience. Systematic circulatory volume expansion has not been proven to improve the maternal nor the neonatal prognosis. Such treatment is to be reserved solely for situations in which correcting a hypo-volemia is absolutely necessary. The treatment of acute pulmonary edema in a PE patient is symptomatic and includes the administration of vasodilating agents and of diuretics. A benefit in setting-up an invasive monitoring of the pulmonary artery occlusive pressure has not been demonstrated. The sonographic surveillance of the hemodynamic state can however be useful in these circumstances. [less ▲]Detailed reference viewed: 41 (4 ULg)
Management of recurrent or persistent stress urinary incontinence after TVT-O by mesh readjustment
De Landsheere, Laurent ; ; Foidart, Jean-Michel et al
in International Urogynecology Journal & Pelvic Floor Dysfunction (2010), 21(11), 1347-51
Introduction and hypothesis The aim of this study was to evaluate, retrospectively, the place of sub-urethral mesh readjustment when treating recurrent stress urinary incontinence (SUI) after TVT-O ... [more ▼]
Introduction and hypothesis The aim of this study was to evaluate, retrospectively, the place of sub-urethral mesh readjustment when treating recurrent stress urinary incontinence (SUI) after TVT-O. Methods Between August 2006 and August 2008, eight patients had recurrent or persistent SUI. They were treated surgically by tightening the pre-implanted sling. Results Medium delay between first surgery and mesh adjustment was 6 months. One patient needed a second TVT-O for rupture of the pre-implanted mesh during adjustment. Among the seven patients who underwent a mesh readjustment, three were cured, three improved, there was one failure. Mean follow-up was 25 months. Conclusions The sub-urethral mesh readjustment is a simple and safe procedure for patients with recurrent SIU after TVT-O procedure. Success rates are high, surgery minimally invasive but long-term follow-up is needed to evaluate efficiency. [less ▲]Detailed reference viewed: 50 (3 ULg)
Further pharmacological and genetic evidence for the efficacy of PlGF inhibition in cancer and eye disease.
; ; et al
in Cell (2010), 141(1), 178-90
Our findings that PlGF is a cancer target and anti-PlGF is useful for anticancer treatment have been challenged by Bais et al. Here we take advantage of carcinogen-induced and transgenic tumor models as ... [more ▼]
Our findings that PlGF is a cancer target and anti-PlGF is useful for anticancer treatment have been challenged by Bais et al. Here we take advantage of carcinogen-induced and transgenic tumor models as well as ocular neovascularization to report further evidence in support of our original findings of PlGF as a promising target for anticancer therapies. We present evidence for the efficacy of additional anti-PlGF antibodies and their ability to phenocopy genetic deficiency or silencing of PlGF in cancer and ocular disease but also show that not all anti-PlGF antibodies are effective. We also provide additional evidence for the specificity of our anti-PlGF antibody and experiments to suggest that anti-PlGF treatment will not be effective for all tumors and why. Further, we show that PlGF blockage inhibits vessel abnormalization rather than density in certain tumors while enhancing VEGF-targeted inhibition in ocular disease. Our findings warrant further testing of anti-PlGF therapies. [less ▲]Detailed reference viewed: 126 (10 ULg)
New Biological Investigations on 3-Bromophenyl 6-Acetoxymethyl-2-oxo-2H-1-Benzopyran-3-Carboxylate as Anti-angiogenic Agent
; ; De Tullio, Pascal 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 ▲]Detailed reference viewed: 77 (14 ULg)
MMP-19 Deficiency Promotes Tenascin-C Accumulation and Allergen-induced Airway Inflammation.
Guéders, Maud ; ; Quesada Calvo, Florence 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 ▲]Detailed reference viewed: 79 (19 ULg)
Métaplasie osseuse de l'endomètre: deux cas rapportés
Mutsers, Emilie ; Chantraine, Frédéric ; Delbecque, Katty et al
in Gunaïkeia (2010), 15(4),Detailed reference viewed: 276 (7 ULg)
Diabete et grossesse: impact de l'inertie medicale et de l'observance therapeutique.
Pintiaux, Axelle ; ; Philips, Jean-Christophe 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 ▲]Detailed reference viewed: 201 (3 ULg)