References of "Foidart, Jean-Michel"
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See detailHuman chorionic gonadotrophin (hCG): new pleiotropic functions for an "old" hormone during pregnancy
Gridelet, Virginie ULiege; PERRIER d'HAUTERIVE, Sophie ULiege; Polese, Barbara ULiege et al

in Frontiers in Immunology (2020), 11

Human chorionic gonadotrophin (hCG) is the first specific molecule synthesized by the embryo. hcg RNA is transcribed as early as the 8-cell stage and the blastocyst produces the protein before its ... [more ▼]

Human chorionic gonadotrophin (hCG) is the first specific molecule synthesized by the embryo. hcg RNA is transcribed as early as the 8-cell stage and the blastocyst produces the protein before its implantation. hCG in the uterine microenvironment binds with its cognate receptor LHCGR on the endometrial surface. This binding stimulates LIF production and inhibits IL-6 production by epithelial cells of the endometrium. These effects ensure essential help in the preparation of the endometrium for initial embryo implantation. hCG also effects angiogenic and immunomodulatory actions as reported in many articles by our laboratories and other ones. By stimulating angiogenesis and vasculogenesis, hCG provides the placenta with an adequate maternal blood supply and optimal embryo nutrition during the invasion of the uterine endometrium. The immunomodulatory properties of hCG are numerous and important for programming maternal immune tolerance towards the embryo. The reported effects of hCG on uterine NK, Treg and B cells, three major cell populations for the maintenance of pregnancy, demonstrate the role of this embryonic signal as a crucial immune regulator in the course of pregnancy. Human embryo rejection for hCG-related immunological reasons has been studied in different ways, and a sufficient dose of hCG seems to be necessary to maintain maternal tolerance. Different teams have studied the addition of hCG in patients suffering from recurrent miscarriages or implantation failures. HCG could also have a beneficial or a negative impact on autoimmune diseases during pregnancy. In this review, we will discuss the immunological impacts hCG during pregnancy and if this hormone might be used therapeutically. [less ▲]

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See detailLiposomes and drug-in-cyclodextrin-in-liposomes formulations encapsulating 17β-estradiol: an innovative drug delivery system that prevents the activation of the membrane-initiated steroid signaling (MISS) of estrogen receptor α
Gallez, Anne ULiege; Palazzo, Claudio ULiege; Blacher, Silvia ULiege et al

in International Journal of Pharmaceutics (2020), 573

The encapsulation into liposomes of several types of molecules presents the advantages to protect the activity of these molecules and to target specific tissues. Nevertheless, a major obstacle remains the ... [more ▼]

The encapsulation into liposomes of several types of molecules presents the advantages to protect the activity of these molecules and to target specific tissues. Nevertheless, a major obstacle remains the incomplete understanding of nano-bio interactions. Specifically, the impact that inclusion of drug into liposomes or of drug-in-cyclodextrin-in liposomes (DCL) could have on the molecular and cellular mechanism of drug action is largely unknown. As a proof of concept, we evaluated the impact of 17β-estradiol (E2) included into liposomes or DCL on estrogen receptor (ER)α signaling pathways. Indeed, ERα relays the pleiotropic actions of E2 in physiology and pathophysiology through two major pathways: (1) the genomic/nuclear effects associated to the transcriptional activity of the ERα and (2) the rapid/nongenomic/membrane-initiated steroid signaling (MISS) effects related to the induction of fast signaling pathways occurring when ERα is anchored to the plasma membrane. We evidenced that the inclusion of E2 into liposomes (Lipo-E2) or into DCL (DCL-E2) prevented the activation of the rapid/nongenomic/extranuclear/MISS pathway of ERα, while the activation of the genomic/nuclear pathway was maintained. These results support that Lipo-E2 and DCL-E2 could be a useful tool to delineate the complex molecular mechanisms associated to ERα. In conclusion, this study supports the notion that inclusion of drugs into liposomes or DCL could modify some specific pathways of their molecular and cellular mechanisms of action. These results emphasized that attention should be paid to nano-bio interactions induced by the use of nanovectors in medicine. [less ▲]

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See detailOestrogènes, progestérone, progestatifs et sein
Pequeux, Christel ULiege; Gérard, Céline ULiege; Gallez, Anne ULiege et al

in Espié, Marc (Ed.) Le SEIN, du Normal au Pathologique: état de l'art (2020)

Ce chapitre explique le développement de la glande mammaire, le rôle des oestrogènes, les mécanismes d'action des récepteurs aux oestrogènes, la signalisation paracrine via le récepteur aux oestrogènes ... [more ▼]

Ce chapitre explique le développement de la glande mammaire, le rôle des oestrogènes, les mécanismes d'action des récepteurs aux oestrogènes, la signalisation paracrine via le récepteur aux oestrogènes alpha, les effets de l'estétrol, le rôle de la progestérone, la signalisation intrinsèque et paracrine du récepteur à la progestérone chez l'adulte, l'effet des la progestérone sur les cellules souches mammaires, les cellules senseurs, les effets hormonaux sur le risque de cancer du sein, les traitements anti-hormonaux. [less ▲]

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See detailA paracrine interaction between granulosa cells and leukocytes in the preovulatory follicle causes the increase in follicular G-CSF levels
NOEL, Laure ULiege; Fransolet, Maïté ULiege; Jacobs, Nathalie ULiege et al

in J Assist Reprod Genet (2020)

OBJECTIVE: Follicular granulocyte colony-stimulating factor (G-CSF) is a new biomarker of oocyte quality and embryo implantation in in vitro fertilization (IVF) cycles. Its role in reproduction is poorly ... [more ▼]

OBJECTIVE: Follicular granulocyte colony-stimulating factor (G-CSF) is a new biomarker of oocyte quality and embryo implantation in in vitro fertilization (IVF) cycles. Its role in reproduction is poorly understood. Our study aimed to investigate the mechanisms and cells responsible for G-CSF production in the preovulatory follicle. DESIGN: Laboratory research study. SETTING: Single-center study. INTERVENTIONS: Granulosa cells and leukocytes were isolated from the follicular fluids (FF) or the blood of women undergoing IVF and from the blood of a control group of women with spontaneous ovulatory cycles to perform cocultures. MAIN OUTCOME MEASURE: G-CSF-secreted protein was quantified in the conditioned media of cocultures. RESULTS: G-CSF secretion was considerably increased in cocultures of granulosa cells and leukocytes. This effect was maximal when leukocytes were isolated from the blood of women in the late follicular phase of the menstrual cycle or from the FF of women undergoing IVF. The leukocyte population isolated from the FF samples of women undergoing IVF had a higher proportion of granulocytes than that isolated from the corresponding blood samples. Leukocytes induced the synthesis and secretion of G-CSF by granulosa cells. Among a range of other FF cytokines/chemokines, only growth-regulated oncogene alpha (GROalpha) was also increased. CONCLUSION: The notable rise in G-CSF at the time of ovulation coincides with the accumulation of follicular granulocytes, which stimulate G-CSF production by granulosa cells via paracrine interactions. High follicular G-CSF concentrations may occur in follicles with optimal granulosa-leukocyte interactions, which could explain the increased implantation rate of embryos arising from these follicles. [less ▲]

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See detailAbsence of correlation between follicular fluid volume and follicular granulocyte colony-stimulating factor, a predictor of embryo implantation and successful delivery.
NOEL, Laure ULiege; Donneau, Anne-Françoise ULiege; JOUAN, Caroline ULiege et al

in Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology (2019)

Follicular granulocyte colony-stimulating factor (G-CSF) is a documented marker of embryo implantation potential. The primary objective was to determine whether follicular G-CSF levels correlate with ... [more ▼]

Follicular granulocyte colony-stimulating factor (G-CSF) is a documented marker of embryo implantation potential. The primary objective was to determine whether follicular G-CSF levels correlate with follicular fluid volume. The secondary objectives were to assess whether follicular G-CSF is associated with oocyte maturity at the time of harvest and with delivery rate after fresh or frozen embryo transfer. Thirty-two patients undergoing intracytoplasmic sperm injection (ICSI) cycles were recruited (Centre de Procreation Medicalement Assistee (CPMA), University of Liege, Belgium). A total of 211 follicular fluid (FF) samples were individually collected at the time of oocyte harvest. FF volume was recorded, and G-CSF concentration was assessed by ELISA. The embryos were individually cultured in vitro. Their implantation and live birth rates were recorded after fresh and frozen embryo transfers. The follicular fluid volume did not correlate with the follicular G-CSF concentration. There were no differences in follicular G-CSF levels between mature and immature oocytes. The probability of successful implantation and delivery was increased for embryos with FF containing a high G-CSF concentration. There was a trend toward lower follicular G-CSF levels in cases of miscarriage. Therefore, follicular fluid volume cannot be a substitute for follicular G-CSF as a marker of embryo implantation ability. [less ▲]

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See detailClinical performance of a specific granulocyte colony stimulating factor ELISA to determine its concentration in follicular fluid as a predictor of implantation success during in vitro fertilization.
Tournaye, H; D'Hooghe, T.; Verheyen, G. et al

in Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology (2019)

This study aimed to demonstrate the clinical performance of an ultra-sensitive follicular fluid (FF) granulocyte colony stimulating factor (G-CSF) immunoassay to confirm previous work, indicating a ... [more ▼]

This study aimed to demonstrate the clinical performance of an ultra-sensitive follicular fluid (FF) granulocyte colony stimulating factor (G-CSF) immunoassay to confirm previous work, indicating a correlation between FF G-CSF concentration and live birth potential of the corresponding embryo after in vitro fertilization. This study was a noninterventional, prospective, diagnostic clinical multicentric study conducted between August 2012 and January 2014 with 396 single embryo transfers (SETs) from 278 subjects. During oocyte retrieval, FF was individually collected. Embryo morphology and implantation success were evaluated. The implantation success rate in the high G-CSF group (32.3%) was higher than the overall rate (27.5%). Similarly, for embryos with optimal morphology, implantation success rates were highest among those in the high G-CSF concentration category (34.5%) compared with low (19.6%) and intermediate (29.8%) G-CSF concentration categories. Significant differences in mean G-CSF concentrations were observed between the study sites. To minimize bias, analyses were repeated using data from the center with the largest number of SETs. In alignment with the overall analysis, this center demonstrated a 43% greater probability of implantation for optimal embryos with high G-CSF compared to the general implantation rate among optimal embryos and a 327% increase compared with the implantation rate of optimal embryos with low G-CSF. [less ▲]

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See detailEstetrol and its effects on the damaged brain
Tskitishvili, Ekaterine ULiege; Foidart, Jean-Michel ULiege

in Diaz Brinton, Roberta; Genazzani, Andrea R.; Simoncini, Tomasso (Eds.) et al Sex Steroids' Effects on Brain, Heart and Vessels (2019)

Estrogens play an important role not only in reproductive system but in the central nervous system as well. Major events of ontogenesis occur earlier in pregnancy are connected to the formation of ... [more ▼]

Estrogens play an important role not only in reproductive system but in the central nervous system as well. Major events of ontogenesis occur earlier in pregnancy are connected to the formation of estrogen receptors and expression of estrogens leading to the normal physiological development of the central nervous system, though development of brain by itself is a complex process and lasts during the whole pregnancy. Estetrol (E4) is a recently described natural estrogen with four hydroxyl-groups that is synthesized exclusively during pregnancy by the human fetal liver. Its role in the central nerovus system is not fully understood. Our studies showed for the first time and proved impressive antioxidative effects of E4 in vitro and proved its tremendous neuroprotective, promyelinating, neurogenic and cerebro-angiogenic properties in vivo. E4 dicreases brain damage markers (S100B and GFAP) in blood assuming that E4 attenuates neonatal hypoxic-ischemic encephalopathy in vivo. We have also shown that the combined use of E4 with other steroids do not have any priority over the signle use of E4. E4’s antioxidative actions mostly depend on ERα and ERβ, whereas neurogenesis and possibly promyelinating activities might be realized through ERβ. Taken together our studies suggest importance of E4 treatment possibly not only in neonates but in adults with different neurological diseases like that that opening new directions for the use of E4 in clinical practice in neurological diseases. [less ▲]

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See detailUnique Vascular Benefits of Estetrol, a Native Fetal Estrogen with Specific Actions in Tissues (NEST)
Foidart, Jean-Michel ULiege; GASPARD, Ulysse ULiege; Pequeux, Christel ULiege et al

in Diaz Brinton, Roberta; Genazzani, Andrea; Simoncini, Tommaso (Eds.) et al Sex Steroids' Effects on Brain, Heart and Vessels: Volume 6: Frontiers in Gynecological Endocrinology (2019)

Estrogens (E), in combination with oral contraceptives (COCs) and hormone replacement therapy (HRT) drugs used for the relief of climacteric symptoms of menopause, increase the synthesis of clotting ... [more ▼]

Estrogens (E), in combination with oral contraceptives (COCs) and hormone replacement therapy (HRT) drugs used for the relief of climacteric symptoms of menopause, increase the synthesis of clotting factors, decrease the levels of coagulation inhibitors, and increase the risk of venous thromboembolic events (VTE). Ischemic stroke incidence in postmenopausal women during HRT use is also increased and is probably due to a thrombotic event. This suggests that a safer estrogen may reduce stroke and VTE incidence, with lower impact on hemostasis. Estetrol (E4) is a relatively recently described new human-specific E produced exclusively by the fetal liver during pregnancy. This Native (human and natural) E has Selective actions in Tissues (NEST). Nest activities of E4 are the consequence of its unique dual role. It activates the nuclear estrogen receptor alpha (ERα) but antagonizes the membrane ERα in contrast to other E, which activate both types of receptors. Most beneficial effects of E on the vascular system have been ascribed to the activation of the membrane ERα of vascular endothelial cells, including enhancement of nitric oxide (NO) production, vasodilation, and prevention of atherosclerosis, of neointimal proliferation, and of hypertension. In a series of papers reviewed here, the INSERM team in Toulouse has demonstrated, by the combined use of pharmacological tools and of transgenic mice lacking either the nuclear ERα, the membrane ERα, or both, that the nuclear ERα plays a major role in controlling E activities in vessels. E4 is able to elicit the important vasculoprotective actions mediated by estradiol (E2). Furthermore, phase 1 and 2 clinical studies of E4 in a contraceptive indication (in combination with drospirenone) or in postmenopausal women for the relief of climacteric complaints demonstrate that E4 has a minimal impact on hemostasis, coagulation factors, coagulation inhibitors, fibrinolysis, angiotensinogen, triglycerides, and cholesterol. Altogether, preclinical studies and phase 1 and 2 clinical data indicate that E4 could be a new E with a better safety/efficacy profile than other E for women’s healthcare. [less ▲]

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See detailDevelopment of injectable liposomes and drug-in-cyclodextrin-in-liposome formulations encapsulating estetrol to prevent cerebral ischemia of premature babies.
Palazzo, Claudio ULiege; Laloy, Julie; Delvigne, Anne Sophie et al

in European Journal of Pharmaceutical Sciences (2019), 9(127), 52-59

Neonatal Hypoxic-Ischemic Encephalopathy (HIE), a brain disease due to brain hypoxia along with ischemia and reduced cerebral blood flow, is one of the primary reasons of severe injury among babies ... [more ▼]

Neonatal Hypoxic-Ischemic Encephalopathy (HIE), a brain disease due to brain hypoxia along with ischemia and reduced cerebral blood flow, is one of the primary reasons of severe injury among babies prematurely born. No efficacy treatment is available to the present day. Estetrol (E4), a major estradiol metabolite, has an important role in the brain development and protection. The aim of this study is to develop new injectable liposome and drug-in-cyclodextrin-in-liposome (DCL) formulations, encapsulating E4 in order to enhance its crossing through the blood-brain barrier (BBB). Liposome and DCL formulations were prepared and were physiochemically characterized. Stability in foetal bovine serum (FBS) was evaluated. LDH and MTS tests on endothelial, neuronal and BBB model cells, as well as hemocompatibility of the nanovectors were performed in vitro. In vitro BBB passage was evaluated using human BBB cell line (hCMEC/D3). All the formulations had average particle size below 150 nm, polydispersity index below 0.10 and ζ potential around + 30 mV. The encapsulation efficacy for liposomes was between 3% and 10% while those of DCL are between 15% and 35%. The effect of liposome and DCL formulations on cell viability and integrity was evaluated. The results showed no toxic effects on all the tested cell lines. Hemocompatibility tests showed no hemolysis, platelet aggregation or effects on coagulation, confirming the possibility of the formulations to be intravenously administrated. BBB passage tests highlighted the capability of the formulations to pass the BBB and reach the brain. Therefore, the formulations are promising drug delivery system to target estrogens to the brain, due to their physiochemical characteristics. [less ▲]

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See detailEstetrol, a newly designated orphan drug, for attenuation of neonatal Hypoxic-Ischemic Encephalopathy (HIE)
Tskitishvili, Ekaterine ULiege; Pequeux, Christel ULiege; VIELLEVOYE, Renaud ULiege et al

Poster (2018, November 13)

Estetrol, a newly designated orphan drug, for attenuation of neonatal Hypoxic-Ischemic Encephalopathy (HIE) Ekaterine Tskitishvili1*, Christel Pequeux1, Renaud Viellevoye2, Michelle Nisolle3, Agnes Noël1 ... [more ▼]

Estetrol, a newly designated orphan drug, for attenuation of neonatal Hypoxic-Ischemic Encephalopathy (HIE) Ekaterine Tskitishvili1*, Christel Pequeux1, Renaud Viellevoye2, Michelle Nisolle3, Agnes Noël1 and Jean-Michel Foidart1 1Laboratory of Development Biology and Tumor, University of Liege, Liege, Belgium; 2Department of Pediatrics, University of Liege, Liege, Belgium; 3Department of Ob/Gyn, University of Liege, Liege, Belgium Estetrol (E4) is a fetal estrogen synthesized only during human pregnancy. We aimed to study its role in attenuation of neonatal HIE. In vitro we defined antioxidative and cell viability effects of E4 on primary hippocampal cell cultures in oxidative stress condition by using lactate dehydrogenase (LDH) activity and cell survival (MTS) assays. To study the neuroprotective and therapeutic effects of E4 in vivo neonatal HIE model of 7-day-old newborn rat pups was used. Brains were studied at the level of the hippocampus and cortex. Intact cell counting and expressions of markers for gray and white matter (MAP-2 and MBP), neurogenesis (DCX) and angiogenesis (VEGF) were evaluated by histo- and immunohistochemistry. The serum levels of brain damage markers (S100B and GFAP) were measured by ELISA. Our results demonstrate that E4 has significant antioxidative and cell survival properties along with neuroprotective and therapeutic effects. It decreases the early gray and white matter loss and promotes neuro- and angiogenesis in vivo. Combined use of E4 with other steroids does not have priority over the single use of E4. We also defined that E4's antioxidative actions mostly depend on ERα and ERβ, whereas neurogenesis and possibly promyelinating activities might be realized through ERβ. Treatment by E4 has no effects on body weight, brain weight or body temperature. E4 might become an important safe and physiological substance to treat neonatal HIE. Based on our data EMA granted orphan drug designation to E4. References 1.Tskitishvili E, Nisolle M, Munaut C, Pequeux C, Gerard C, Noel A, Foidart JM.Estetrol attenuates Neonatal Hypoxic-Ischemic brain injury. Exp Neurol 2014; 261:298-307. 2. Tskitishvili E , Pequeux C, Munaut C, Viellevoye R, Nisolle M, Noel A, Foidart JM. Use of Estetrol with other Steroids for Attenuation of Neonatal Hypoxic-Ischemic brain injury: to combine or not to combine? Oncotarget 2016; 7(23):33722-43. 3. Tskitishvili E,Viellevoye R, Gerard C, Pequeux C, Munaut C, Nisolle M, Noel A, Foidart JM. Neonatal Hypoxic-Ischemic Encephalopathy: a new view of an old problem. Références en Gynécologie Obstetrique. 2016 17;1-4 4. Tskitishvili E, Pequeux C, Munaut C, Viellevoye R, Nisolle M, Noël A, Foidart JM. Estrogen receptors and estetrol-dependent neuroprotective actions: a pilot study. J Endocrinol. 2017; 232(1):85-95. 5.Foidart JM, Tskitishvili E. International patent application. Estrogenic components for use in the treatment of neurological disorders. [less ▲]

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See detailLa souris, le patient, et le faux expert. Décryptage d'une mystification.
Bakker, Julie ULiege; Balthazart, Jacques ULiege; Baron, Frédéric ULiege et al

Article for general public (2018)

La recherche sur animaux est actuellement encadrée de façon stricte en Wallonie comme dans toute l'Union Européenne (voir l'article de Marc Vandenheede publié dans le Vif). Cette législation et les ... [more ▼]

La recherche sur animaux est actuellement encadrée de façon stricte en Wallonie comme dans toute l'Union Européenne (voir l'article de Marc Vandenheede publié dans le Vif). Cette législation et les contrôles qui y sont associés induisent de nombreuses contraintes pratiques, des charges administratives et des coûts financiers importants que les chercheurs seraient certainement heureux d'éviter s'il existait une alternative à l'expérimentation animale. [less ▲]

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See detailAnalyse détaillée de la seconde version de l’avant-projet de Code du bien-être animal wallon. Lecture commentée au 21/03/2018 du Chapitre 8 (Expérimentation animale)
Drion, Pierre ULiege; Corhay, Albert ULiege; Haubruge, Eric ULiege et al

Report (2018)

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par ... [more ▼]

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par les décrets du Gouvernement wallon). Certains éléments sont repris tels quels de la Directive 2010/63. Cela est nécessaire car la Directive européenne en tant que telle n’a pas de force obligatoire en Belgique. Elle doit être transcrite par un instrument législatif (avant, la Loi de 1984 et ses modifications, aujourd’hui, le projet de code pour la Région wallonne). Certains aspects semblent flous, mais renvoient à des dispositions que le Gouvernement doit encore prendre (au travers d’arrêtés du Gouvernement wallon, comme le faisaient avant les nombreux arrêtés royaux et du gouvernement qui réglementent la matière). Les arrêtés d’exécution devront obligatoirement tenir compte de la Directive européenne et s’inspirer de dispositions actuellement en vigueur. [less ▲]

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See detailHeterogeneity of estrogen receptor alpha and progesterone receptor distribution in lesions of deep infiltrating endometriosis of untreated women or during exposure to various hormonal treatments.
BRICHANT, Géraldine ULiege; NERVO, Patricia ULiege; Albert, Adelin ULiege et al

in Gynecological Endocrinology (2018)

Deep infiltrating endometriosis (DIE) responds variably to hormonal therapy. Mutations in cancer driver genes have been identified in a fraction of the ectopic endometrial epithelial cells, suggesting a ... [more ▼]

Deep infiltrating endometriosis (DIE) responds variably to hormonal therapy. Mutations in cancer driver genes have been identified in a fraction of the ectopic endometrial epithelial cells, suggesting a functional heterogeneity of these lesions. To evaluate the phenotype heterogeneity of cells in DIE, we measured the expression of estrogen receptor alpha (ERalpha) and of progesterone receptor (PR) in DIE of untreated women or under various treatments. We analyzed the luminal epithelial height (LEH), immunoreactive epithelial staining (IRS) and stromal staining intensity (SSI) of ERalpha and PR. We observed a high variability in the same gland, among distinct glands in the same sample and among distinct patients receiving the same treatment. LEH variability was primarily due to epithelial cells heterogeneity in a gland, secondarily to the glands randomly evaluated on the same section, and tertiary to the patient category. Variability in IRS and SSI scores was primarily the consequence of their heterogeneity in the same woman and to a lesser extent to variability among patients. LEH and SSI were not modified according to treatment. IRS for PR was lower in treated patients. This heterogeneity of ERalpha and PR distribution could explain why endocrine treatments are unable to cure this condition. [less ▲]

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See detailERα- and dose-dependent effect of estetrol on angiogenesis and tumor growth
Gallez, Anne ULiege; BLACHER, Silvia ULiege; Gérard, Céline et al

Poster (2017, November 07)

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See detailESTROGEN RECEPTORS AND ESTETROL-DEPENDENT NEUROPROTECTIVE ACTIONS: A PILOT STUDY
Tskitishvili, Ekaterine ULiege; Pequeux, Christel ULiege; Munaut, Carine ULiege et al

Conference (2017, October 20)

Context: Estetrol (E4) has strong antioxidative, neurogenic and angiogenic effects in neural system resulting in the attenuation of neonatal hypoxic–ischemic encephalopathy. Objective: We aimed to define ... [more ▼]

Context: Estetrol (E4) has strong antioxidative, neurogenic and angiogenic effects in neural system resulting in the attenuation of neonatal hypoxic–ischemic encephalopathy. Objective: We aimed to define the role of estrogen receptors in E4-dependent actions in neuronal cell cultures and prove the promyelinating effect of E4. Methods: In vitro the antioxidative and cell survival/proliferating effects of E4 on H2O2-induced oxidative stress in primary hippocampal cell cultures were studied using different combinations of specific inhibitors for ERα (MPP dihydrochloride), ERβ (PHTTP), GPR30 (G15) and palmytoilation (2-BR). LDH activity and cell survival assays were performed. In vivo the promyelinating role of different concentrations of E4 (1 mg/kg/day, 5 mg/kg/day, 10 mg/kg/day, 50 mg/kg/day) was investigated using the hypoxic–ischemic brain damage model in the 7-day-old immature rats before/after the induction of hypoxic–ischemic insult. Myelin basic protein (MBP) immunostaining was performed on brain coronal sections. Results: Our results show that LDH activity is significantly upregulated in cell cultures where the E4’s effect was completely blocked by concomitant treatment either with ERα and ERβ inhibitors (MPP and PHTPP, respectively), or ERα and ERβ inhibitors combined with 2-BR. Cell survival is significantly downregulated in cell cultures where the effect of E4 was blocked by ERβ inhibitor (PHTTP) alone. The blockage of GRP30 receptor did affect neither LDH activity nor cell survival. MBP immunostaining is significantly upregulated in E4-pretreated groups at a concentration of 5 mg/kg/day and 50 mg/kg/day E4, whereas the MBP-positive area OD ratio is significantly increased in all the E4-treated groups. Conclusions: E4’s antioxidative actions mostly depend on ERα and ERβ, whereas neurogenesis and possibly promyelinating activities might be realized through ERβ. [less ▲]

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See detailDose-Dependant effect of Estetrol on Angiogenesis and Tumor growth
Gallez, Anne ULiege; BLACHER, Silvia ULiege; Lenfant, Françoise et al

Conference (2017, May 19)

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See detailDose-dependent effect of Estetrol on Angiogenesis and Tumor Growth
Gallez, Anne ULiege; Blacher, Silvia ULiege; Lenfant, Françoise et al

Poster (2017, April 24)

Hormone replacement therapies (HRT) based on estrogen preparations are the most powerful treatments to prevent menopause symptoms. However, they are associated to an increased risk of breast cancer and ... [more ▼]

Hormone replacement therapies (HRT) based on estrogen preparations are the most powerful treatments to prevent menopause symptoms. However, they are associated to an increased risk of breast cancer and they sustain the development of Estrogen Receptor α-positive tumors (ERα+). In addition, we have previously observed that estradiol (E2) can promote the growth of ERα-negative (ERα-) tumors, by increasing tumor angiogenesis that subsequently improves oxygen and nutrients delivery, thereby preventing hypoxia and necrosis. To identify new and safe drugs for the development of HRT presenting a better benefit/risk ratio, it is therefore necessary to evaluate the potential impact of new candidates on both ERα+ and ERα- tumors. In this context, estetrol (E4), a natural estrogen exclusively produced by the fetal liver, is a promising candidate. [less ▲]

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See detailImproved computer-assisted analysis of the global lymphatic network in human cervical tissues.
BALSAT, Cédric ULiege; Signolle, N; Goffin, Frédéric ULiege et al

in Modern Pathology (2017), 30(2), 313

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