References of "Noël, Agnès"
     in
Bookmark and Share    
See detailInvolvement of microenvironment modulations in lung metastasis formation
Donati, Kim ULiege; Sepult, Christelle ULiege; Noël, Agnès ULiege et al

Conference (2016, May 11)

Detailed reference viewed: 21 (5 ULiège)
Full Text
Peer Reviewed
See detailEstetrol, a natural SERM exhibiting combined estrogenic and antiestrogenic properties on mammary gland and breast cancer
Gérard, Céline ULiege; Gallez, Anne ULiege; Blacher, Silvia ULiege et al

Conference (2016, May 09)

The increased risk of breast cancer and thromboembolism in women who take Hormone Replacement Therapy (HRT) currently is a major public health problem. The discovery of novel molecules with better safety ... [more ▼]

The increased risk of breast cancer and thromboembolism in women who take Hormone Replacement Therapy (HRT) currently is a major public health problem. The discovery of novel molecules with better safety profile would provide useful advances for patient care. Estretrol (E4) appears as a promising candidate for HRT. Indeed, in contrast to current treatment containing ethinyl estradiol or estradiol (E2), E4 has a minimal impact on liver cells activity supporting a decreased incidence on thromboembolic events. In preclinical studies, E4 has been effective against the main symptoms of menopause such as hot flushes, vaginal atrophy, and osteoporosis, from a starting dose of 0.3 mg/kg/day. The aim of this study was to define the impact of E4 on mammary gland and breast cancer development when it is used at concentrations effective for menopause symptom relief. We report preclinical data showing that E4 is less efficient than E2 to induce mammary gland growth. Treatment of estrogen receptor (ER)-positive breast cancer with several concentrations of E4 has shown that 0.3 mg/kg/day E4 did not increase tumor development. However, at 3mg/kg/day, E4 increased the growth of hormone-dependent tumors and their metastatic dissemination in ovariectomized and intact mice. This effect was similar to the one observed with E2 used at 0.08 mg/kg/day. E4 presents also some anti-estrogenic effects on mammary gland and antitumor activity on breast cancer by decreasing the strong proliferative effect of E2. While ERα is the predominant receptor mediating its effects, the dual weak-estrogenic/anti-estrogenic feature of E4 results from differential signaling pathways activation. Both nuclear and rapid extranuclear signaling pathways are necessary for a complete estrogenic effect of E4. However, the antitumor action of E4 is not due to a capacity to antagonize E2-induced nuclear activity. In conclusion, our results support that E4, if it is used in strictly controlled clinical applications, could have no or only limited impact on breast and breast cancer. [less ▲]

Detailed reference viewed: 46 (1 ULiège)
Full Text
Peer Reviewed
See detailNeonatal Hypoxic-Ischemic Encephalopathy: a new view of an old problem
Tskitishvili, Ekaterine ULiege; VIELLEVOYE, Renaud ULiege; Gérard, Céline et al

in Références en Gynécologie Obstétrique (2016), 17(1-1),

Neonatal hypoxic-ischemic encephalopathy (HIE) remains a challenge of perinatal medicine. It is an important cause of long term morbidity, including motor and behavioral deficits, mental retardation ... [more ▼]

Neonatal hypoxic-ischemic encephalopathy (HIE) remains a challenge of perinatal medicine. It is an important cause of long term morbidity, including motor and behavioral deficits, mental retardation, seizures and cerebral palsy, and mortality in newborns. This paper reviews the pathophysiology and current concepts of the management of neonatal HIE as well as the future potential neuroprotective strategies for attenuation of this disease. [less ▲]

Detailed reference viewed: 179 (9 ULiège)
Peer Reviewed
See detailFrom Metabolomics Study of Age-Related Macular Degeneration (AMD) to the Development of New Pyruvate Dehydrogenase Kinase Inhibitors (PDK)
Arslan, Deniz ULiege; Schoumacher, Matthieu ULiege; Pirotte, Bernard ULiege et al

Poster (2016, May)

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly population of industrialized countries. This blindness results from the deterioration of the macula, a small part of ... [more ▼]

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly population of industrialized countries. This blindness results from the deterioration of the macula, a small part of the retina specialized for the high-acuity vision. Exudative AMD, called “wet”, is characterized by the formation of new blood vessels growing under the retina according to a process named choroidal neovascularization (CNV). Currently, the aetiology and pathogenesis of AMD remain unclear. Nevertheless, a recent metabolomics study performed on the serum of “wet” AMD patients and on a CNV murine model, that mimics the effect of “wet” AMD, have demonstrated that lactate level is clearly involved in the severity of the pathology as well as the relationship between lactate, CNV and AMD. According to this result, we suggest a new therapeutic approach of AMD based on the normalization of blood lactate level. The modulation of the lactate plasma concentration by treatment of the animals with synthetic compounds and more specifically Pyruvate Dehydrogenase Kinase (PDK) inhibitors significantly decrease the CNV. PDK and its four isoforms (PDK1-4) regulate the activity of the pyruvate dehydrogenase complex (PDH), a mitochondrial enzyme that plays a major role in the metabolic pathway of glucose, by reversible phosphorylation. Starting from these results, development of new PDK inhibitors could open the way to innovative treatment opportunities in AMD disease. Different analogues of (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide (fig.1) have been already synthetized and pharmacological evaluation is currently in progress. According to the results obtained, various pharmacomodulations will be investigated [less ▲]

Detailed reference viewed: 86 (27 ULiège)
Peer Reviewed
See detailFrom Metabolomics to Identification of a new therapeutic approach for Age-Related Macular Degeneration (AMD)
Schoumacher, Matthieu ULiege; De Tullio, Pascal ULiege; LAMBERT, Vincent ULiege et al

Poster (2016, May)

Age-related macular degeneration (AMD) is the leading cause of vision loss in the western world among people aged 50 or older. 90% of all vision loss due to AMD result from the exudative form, which is ... [more ▼]

Age-related macular degeneration (AMD) is the leading cause of vision loss in the western world among people aged 50 or older. 90% of all vision loss due to AMD result from the exudative form, which is characterized by choroidal neovascularization (CNV). Age-related changes that induce pathologic CNV are incompletely understood and critical issues remain to be addressed. Metabolomics is defined as the comprehensive study of endogenous metabolites changes in various biological systems. This newly emerging “omic” science provides a unique opportunity to correlate variation of the metabolome with pathological occurrence or progression and/or to identify metabolites that are implicated in the disease. We apply a 1H NMR metabolomics approach on sera collected from AMD patient and healthy volunteers and form a mice model of laser-induced CNV which mimics the effect of exudative AMD. After post-processing treatments, the different spectra were analyzed by statistical discriminant methodologies (PCA, ICA, PLS-DA, O-PLS-DA). These approaches allow the differentiation between control and AMD patients and between laser-induced mice and the control mice group. Moreover, the same discriminating spectral zones have been identified in human and mice model, leading to the emergence of different putative biomarkers. Among these markers, lactate emerges as a key metabolite in both settings. Mechanistically, lactate produced locally and by inflammatory cells, plays a critical role in the onset of the inflammatory and angiogenic phases. In mice model of laser-induced CNV, normalization of circulating lactate by dichloroacetate a pyruvate dehydrogenase kinase (PDK) inhibitor, decreases CNV development. Our data support the innovative concept of lactate as a parainflammation- and angio-metabolite associated to AMD and CNV progression. Moreover, control of blood lactate level via inhibition of PDK provides new options for the treatment of exudative AMD. This study demonstrates the ability of metabolomics for drug target discovery and opens new perspectives for AMD treatment and patient follow-up. [less ▲]

Detailed reference viewed: 76 (14 ULiège)
Full Text
Peer Reviewed
See detailImpacts of Ionizing Radiation on the Different Compartments of the Tumor Microenvironment
Leroi, Natacha ULiege; LALLEMAND, François ULiege; COUCKE, Philippe ULiege et al

in Frontiers in Pharmacology (2016), 7

During the last decade, the initial cancer cell-centered view of tumors has greatly evolved to an integrated vision of tumor biology taking into account the key contribution of the TME. Obviously, the ... [more ▼]

During the last decade, the initial cancer cell-centered view of tumors has greatly evolved to an integrated vision of tumor biology taking into account the key contribution of the TME. Obviously, the different compartments of TME are closely related and contribute not only to tumor progression, but also to its response to treatments. Importantly, the TME evolves over time during the different steps of cancer development and is also affected by different therapeutic modalities. Although, improvements have been achieved regarding RT delivery to the primary tumor, ionizing radiation also target nontumor cells that influence tumor growth and metastatic dissemination. Different approaches have been proposed to overcome the radioresistance of cancer cells. The TME-mediated radioresistance is now the object of researches, which has been elegantly reviewed recently by Barker et al. (2015) and severalarticles pointed out the importance of treatments that modify the TME and likely radiosensitize tumor (Ansiaux et al., 2005; Crokart et al., 2005b; Frérart et al., 2008). However, the impact of anti-cancer treatments on the TME and consequently on the tumor phenotype, response to treatment and metastases, is often neglected. Here we pointed out the impact of RT on the TME. Recent findings emphasize the interest to optimize RT (i.e., dose per fraction) and timing of surgery (Leroi et al., 2015; Surace et al., 2015) in order to prevent metastatic spreading. The future challenge in RT will be to define the most appropriate combinations between RT, and other therapeutic modalities with the optimal sequence and timing of treatments. In this context, investigation of the TME-related acquired resistance will be essential and will provide important innovative data. [less ▲]

Detailed reference viewed: 54 (14 ULiège)
Full Text
See detailFeasibility study of repetitive diffusion MRI after Neoadjuvant radiotherapy for following tumor microenvironment.
LALLEMAND, François ULiege; Leroi, Natacha ULiege; Bahri, Mohamed Ali ULiege et al

Conference (2016, March 22)

Purpose/Objective. Neoadjuvant radiotherapy (NeoRT) improves tumor local control and tumor resection in many cancers. The timing between the end of the NeoRT and surgery is mostly driven by the occurrence ... [more ▼]

Purpose/Objective. Neoadjuvant radiotherapy (NeoRT) improves tumor local control and tumor resection in many cancers. The timing between the end of the NeoRT and surgery is mostly driven by the occurrence of side effects or the tumor downsizing. We previously demonstrated in an in vivo model that the timing of surgery and the schedule of NeoRT influenced the tumor dissemination. Here, our aim is to evaluate with functional MRI (fMRI) the impact of the radiation treatment on the tumor microenvironment and subsequently to identify non-invasive markers helping to determine the best timing to perform surgery for avoiding tumor spreading. First, we needed to demonstrate the feasibility of repetitive MRI imaging after NeoRT in mice. Material/methods. We used two models of NeoRT we previously developed in mice: MDA-MB 231 and 4T1 cells implanted in the flank of mice. When tumors reached the planned volume, they are irradiated with 2x5 Gy and then surgically removed at different time points after RT. In the mean time between the end of RT and the surgical procedure, mice were imaged in a 9,4T Agilent® MRI. Diffusion Weighted (DW) -MRI was performed every 2 days between RT and surgery. For each tumors we acquired 8 slices of 1 mm thickness and 0.5 mm gap with an “in plane voxel resolution” of 0.5 mm. For DW-MRI, we performed FSEMS (Fast Spin Echo MultiSlice) sequences, with 9 different B-values (from 40 to 1000) and B0, in the 3 main directions. We also performed IVIM (IntraVoxel Incoherent Motion) analysis, in the aim to obtain information on intravascular diffusion, related to perfusion (F: perfusion factor) and subsequently tumor vessels perfusion. Results. As preliminary results, with the MBA-MB 231 we observed a significant increase of F at day 6 after irradiation than a decrease and stabilization until surgery. No other modifications of the MRI signal, ADC, D or D* were observed. We observed similar results with 4T1 cells, F increased at day 3 than returned to initial signal. The difference in the timing of the peak of F can be related to the difference in tumor growth between MBA-MB 231 and 4T1 (four weeks vs one week). Conclusion. For the first time, we demonstrate the feasibility of repetitive fMRI imaging in mice models after NeoRT. With these models, we show a significant peak of the perfusion factor (F) at day 6 or day 3. This change occurs between the two previous time points of surgery demonstrating a difference in the metastatic spreading. Indeed, after a NeoRT of 2X5Gy we observed more metastases in the lung when MDA-MB 231 tumor bearing mice are operated 4 days after RT compared to 11 days. These preliminary results are very promising for identifying noninvasive markers for determining the best timing for surgery. [less ▲]

Detailed reference viewed: 36 (21 ULiège)
Full Text
See detailEstetrols’ Potential for Neuroprotection Following the injury to the Developing Brain: Preclinical Studies
Tskitishvili, Ekaterine ULiege; Nisolle, Michelle ULiege; Noël, Agnès ULiege et al

in The 17th World Congress of Gynecological Endocrinology, Florence 2-5 March 2016 (2016, March)

Context: Hypoxic-Ischemic encephalopathy (HIE) remains a major cause of perinatal brain injury. The brain rapidly increases in size, shape and complexity during the second and third trimesters. A sentinel ... [more ▼]

Context: Hypoxic-Ischemic encephalopathy (HIE) remains a major cause of perinatal brain injury. The brain rapidly increases in size, shape and complexity during the second and third trimesters. A sentinel event in late pregnancy or the intrapartum period may have an acute profound effect on a previously neurologically intact fetus, leading to the development of (HIE). The nature of the deficits is dependent on the gestational age and severity of the insult, though it is seldom reported in preterm infants. Studies in animal models of HIE may provide important information for the development of treatment for this pathological condition. Estetrol (E4) is a recently described estrogen with four hydroxyl-groups that is synthesized exclusively during pregnancy by the human fetal liver. Objective: In this study, we evaluated E4’s neuroprotective and therapeutic potency in neonatal (in vivo) HIE model of the immature 7-day-old newborn rat. Methods: Rat pups body temperatures were examined along with their body and brain weights. Brains were studied at the level of the hippocampus and cortex. Intact cell counting and expressions of markers for neuronal early grey matter damage (microtubule-associated protein-2 (MAP-2)), neurogenesis (doublecortin (DCX)) and angiogenesis (vascular-endothelial growth factor (VEGF)) were evaluated by histo- and immunohistochemistry. The serum levels of two markers of brain damage (S100B and glial fibrillary acidic protein (GFAP)) were measured by ELISA. Results: Our results demonstrate that E4 has a significant neuroprotective and therapeutic effects. Estetrol decreases the early gray matter loss, and promotes neuro- and angiogenesis in vivo. Estetrol treatment has no effects on body weight, brain weight or body temperature. Conclusion: Taken together, E4 might become an important safe and physiological substance to treat neonatal HIE. [less ▲]

Detailed reference viewed: 67 (3 ULiège)
Full Text
Peer Reviewed
See detailDynamics of Internalization and Recycling of the Pro-Metastatic Membrane Type 4-Matrix Metalloproteinase (MT4-MMP) in Breast Cancer Cells
Truong, Alice ULiege; Yip, Cassandre ULiege; PAYE, Alexandra ULiege et al

in FEBS Journal (2016), 283(4), 704-22

MT4-MMP (MMP17) is a glycosylphosphatidyl inositol (GPI)-anchored membrane-type MMP expressed on the cell surface of human breast cancer cells. In triple negative breast cancer cells, MT4-MMP promotes ... [more ▼]

MT4-MMP (MMP17) is a glycosylphosphatidyl inositol (GPI)-anchored membrane-type MMP expressed on the cell surface of human breast cancer cells. In triple negative breast cancer cells, MT4-MMP promotes primary tumor growth and lung metastases. Although trafficking and internalization of the transmembrane MT1-MMP have been extensively investigated, little is known about the regulatory mechanisms of the GPI-anchored MT4-MMP. Here, we investigated the fate and cellular trafficking of MT4-MMP by analyzing its homophilic complex interactions, internalization and recycling dynamics compared to an inert form, MT4-MMP-E249A. Oligomeric and dimeric complexes were analyzed by co-transfection of cells with FLAG- or Myc-tagged MT4-MMP by reducing and non-reducing immunoblots and co-immunoprecipitation experiments. The trafficking of MT4-MMP was studied using an antibody feeding assay and confocal microscopy analysis or cell surface protein biotinylation and Western blot analysis. We demonstrate that MT4-MMP forms homophilic complexes at the cell surface, internalizes in early endosomes, and some of the enzyme is either auto-degraded or recycled to the cell surface. Our data indicate that MT4-MMP is internalized by the CLIC/GEEC pathway, a mechanism that differs from other MT-MMP members. Although MT4-MMP localizes with caveolin-1, MT4-MMP internalization was not affected by inhibitors of caveolin-1 or clathrin endocytosis pathways but was reduced by cdc42 or RhoA silencing with siRNA. We provide a new mechanistic insight into the regulatory mechanisms of MT4-MMP, which may have implications in the design of novel therapeutic strategies for metastatic breast cancer. This article is protected by copyright. All rights reserved. [less ▲]

Detailed reference viewed: 142 (20 ULiège)
Peer Reviewed
See detailAdult exposure to BPA causes activational disruption of estrous cycle and folliculogenesis
Lopez Rodriguez, David ULiege; Franssen, Delphine ULiege; GERARD, Arlette ULiege et al

Conference (2016)

Our society is facing a public health challenge caused by the increasing presence of endocrine disrupting chemicals (EDCs). Bisphenol A (BPA) is a widespread EDC used in the manufacture of PVC and epoxy ... [more ▼]

Our society is facing a public health challenge caused by the increasing presence of endocrine disrupting chemicals (EDCs). Bisphenol A (BPA) is a widespread EDC used in the manufacture of PVC and epoxy resins. While early postnatal exposure to BPA disrupts sexual maturation andpubertal timing, , its effects on fertility after adult exposure have not yet been studied. Female Wistar rats were exposed for 15 days to corn oil or a low (25ng/kg/d) or a high (5mg/kg/d) BPA dose subcutateouslyat 90 days of age. Animals exposed to both doses showed a disruption of the estrous cyclicity characterized by a decrease in the average time spent in proestrus. We observed a disruption on folliculogenesis characterized by a significant decrease of antral follicles and increase of atretic follicles. The exposed females showed a regular cycle one month after the last dose of BPAWe did not observe any difference in the frequency or amplitude of GnRH secretion 24h after the end of exposure. We also observed that early postnatal exposure to BPA for 15 days disrupted estrous cycle during adulthood with a decrease in time spent in proestrus. In conclusion, exposure to BPA neonatally or during adulthood disrupts the estrous cycle and folliculogenesis. The effects of exposure to BPA during adulthood might be independent of GnRH secretion. Moreover, the effects of early postnatal exposure to BPA are persistent while exposure to BPA during adulthood appears to causeeactivational, non persistent alteration of the oestrus cycle. [less ▲]

Detailed reference viewed: 11 (1 ULiège)
Peer Reviewed
See detailActivational and organizational disruption of folliculogenesis and estrous cycle after an exposure to Bisphenol A (BPA) during early postnatal or adult window of exposure
Lopez Rodriguez, David ULiege; Franssen, Delphine ULiege; GERARD, Arlette ULiege et al

Poster (2016)

The increasing presence of endocrine disruption chemicals (EDCs) has been link with a reduction in fertility rate and alterations of pubertal timing. Bisphenol A (BPA) is a ubiquitous EDC used in the ... [more ▼]

The increasing presence of endocrine disruption chemicals (EDCs) has been link with a reduction in fertility rate and alterations of pubertal timing. Bisphenol A (BPA) is a ubiquitous EDC used in the manufacture of polyvinyl chloride (PVC) and epoxy resins that we can find in food containers and plastics. Our previous studies have shown that an early postnatal exposure to a low dose of BPA disrupts sexual maturation and pubertal timing. However, its long-term and adult effects on fertility have not yet been studied. Daily s.c injections of BPA were administered for 15 days to 1 and 90 day-old female Wistar rats at two different doses: a low dose of 25ng/kg/d and a high dose of 5mg/kg/d. The early postnatal exposure to both BPA doses produces a decrease in the percentage of female with a regular cycle characterized by a decrease on the time spend in proestrus (BPA-25ng 13,6±3,4; BPA-5mg 12,2±3,1%; OIL 18,7±3,2%). During exposure at adulthood, both doses caused a disruption of the estrous cycle characterized by a significant decrease in the average time spent in proestrus (BPA-25ng 18,9±2,2%; BPA-5mg 16,9±1,3%; OIL 23,3±0,9%). This effect was We also observed a disruption of folliculogenesis characterized by a significant decrease of antral follicles (BPA-25ng 21,4±2.1%; BPA-5mg 20,94±2%; OIL 35,6±1,6%) and increase of atretic follicles (BPA-25ng 24,2±3,9%; BPA-5mg 26,2±6,3%; OIL 15,5±0,8%). The exposed females showed a regular cycle one month after the last dose of BPA. In conclusion, both BPA doses have been found to produce a disruption of oestrus cycle and folliculogenesis depending on the window of exposure. While BPA produces persistent effects after early postnatal exposure, exposure during adulthood appears to cause activational, non-persistent alterations. [less ▲]

Detailed reference viewed: 17 (0 ULiège)
Full Text
Peer Reviewed
See detailElastin density: Link between histological and biomechanical properties of vaginal tissue in women with pelvic organ prolapse?
DE LANDSHEERE, Laurent ULiege; Brieu, Mathias; Blacher, Silvia ULiege et al

in International Urogynecology Journal & Pelvic Floor Dysfunction (2016)

INTRODUCTION AND HYPOTHESIS: The aim of the study was to correlate histological and biomechanical characteristics of the vaginal wall in women with pelvic organ prolapse (POP). METHODS: Tissue samples ... [more ▼]

INTRODUCTION AND HYPOTHESIS: The aim of the study was to correlate histological and biomechanical characteristics of the vaginal wall in women with pelvic organ prolapse (POP). METHODS: Tissue samples were collected from the anterior [point Ba; POP Questionnaire (POP-Q)] and/or posterior (point Bp; POP-Q) vaginal wall of 15 women who underwent vaginal surgery for POP. Both histological and biomechanical assessments were performed from the same tissue samples in 14 of 15 patients. For histological assessment, the density of collagen and elastin fibers was determined by combining high-resolution virtual imaging and computer-assisted digital image analysis. For biomechanical testing, uniaxial tension tests were performed to evaluate vaginal tissue stiffness at low (C0) and high (C1) deformation rates. RESULTS: Biomechanical testing highlights the hyperelastic behavior of the vaginal wall. At low strains (C0), vaginal tissue appeared stiffer when elastin density was low. We found a statistically significant inverse relationship between C0 and the elastin/collagen ratio (p = 0.048) in the lamina propria. However, at large strain levels (C1), no clear relationship was observed between elastin density or elastin/collagen ratio and stiffness, likely reflecting the large dispersion of the mechanical behavior of the tissue samples. CONCLUSION: Histological and biomechanical properties of the vaginal wall vary from patient to patient. This study suggests that elastin density deserves consideration as a relevant factor of vaginal stiffness in women with POP. [less ▲]

Detailed reference viewed: 42 (5 ULiège)