References of "FOIDART, Jean-Michel"
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See detailIn Search of New First Trimester Biomarkers for Ischemic Placental Disease
Tskitishvili, Ekaterine ULg; Noël, Agnès ULg; Foidart, Jean-Michel ULg

in Austin Journal of Obstetrrics and Gynecology (2014), 1(2), 1-3

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See detailDevice-based controlled local delivery of anastrozol into peritoneal cavity: in vitro and in vivo evaluation
Krier, Fabrice ULg; Riva, Raphaël ULg; Defrère, Sylvie et al

in Journal of Drug Delivery Science and Technology [=JDDST] (2014), 24(2), 198-204

Local treatment using drug loaded implants allows decreasing seric concentrations of the active ingredient with the purpose of limiting side effects and reaching perfect observance. Nowadays, some ... [more ▼]

Local treatment using drug loaded implants allows decreasing seric concentrations of the active ingredient with the purpose of limiting side effects and reaching perfect observance. Nowadays, some diseases are already treated with implants, but generally, by subcutaneous or intra vaginal implantation. In this work, a new implant device dedicated to the intra-peritoneal cavity was developed. For this purpose, a core-membrane polymer implant was selected. We propose an original method to determine the most appropriate membrane to control the release based on the use of Franz cells. The ability of the implant to release a constant quantity of an active ingredient will be assessed by testing implants in vitro. Finally, intra peritoneal cavity and subcutaneous in vivo implantation has been achieved in order to confirm the controlled and local release of the active ingredient. [less ▲]

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See detailAltered alpha-defensin 5 expression in cervical squamocolumnar junction: implication in the formation of a viral/tumour-permissive microenvironment.
Hubert, Pascale ULg; Herman, Ludivine; RONCARATI, Patrick ULg et al

in Journal of Pathology (The) (2014), 234(4), 464-77

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix, which mainly develops at the squamocolumnar (SC) junction. The progression of cervical ... [more ▼]

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix, which mainly develops at the squamocolumnar (SC) junction. The progression of cervical HPV infections into (pre)neoplastic lesions suggests that viral antigens are not adequately recognized by innate immunity or presented to the adaptive immune system. Members of the defensin family have recently been found to inhibit viral and bacterial pathogens, to stimulate the migration of immune cells and to play a role in anticancer responses. In the present study, we focused on the poorly characterized human alpha-defensin 5 (HD-5) and its possible role in these processes. We showed that HD-5 was able to prevent HPV virion entry into cervical keratinocytes and to influence adaptive immunity. Indeed, this peptide specifically induced the chemoattraction and proliferation of both activated T lymphocytes and immature dendritic cells in a CCR2/CCR6-dependent manner and stimulated the infiltration of these professional antigen-presenting cells in a (pre)neoplastic epithelium transplanted in vivo in immunodeficient mice. No chemotactic effect was observed with plasmacytoid dendritic cells, macrophages or natural killer cells. Proliferative and angiogenic effects of HD-5 were also assessed in vitro and in vivo. However there was a striking regional disparity in expression of HD-5, being prominent in ectocervical, vaginal and vulvar neoplasia, while absent, or nearly so, in the cervical SC junction. Taken together, these results suggest one possible explanation for why the SC junction is uniquely vulnerable to both high-risk HPV infection (via reduced HD-5 expression and viral entry) and progression of neoplasia (via altered cell-mediated immune responses and altered microenvironment). Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [less ▲]

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See detailImproved computer-assisted analysis of the global lymphatic network in human cervical tissues.
Balsat, Cédric ULg; Signolle, Nicolas; GOFFIN, Frédéric ULg et al

in Modern Pathology : An Official Journal of the United States & Canadian Academy of Pathology, Inc (2014), 27(6), 887-98

Lymphatic dissemination is a key event in cervical cancer progression and related tumor lymphatic markers are viewed as promising prognostic factor of nodal extension. However, validating such parameters ... [more ▼]

Lymphatic dissemination is a key event in cervical cancer progression and related tumor lymphatic markers are viewed as promising prognostic factor of nodal extension. However, validating such parameters requires an objective characterization of the lymphatic vasculature. Here, we performed a global analysis of the lymphatic network using a new computerized method applied on whole uterine cervical digital images. Sixty-eight cases of cervical neoplasia (12 CIN3, 10 FIGO stage 1A and 46 stage IB1) and 10 cases of normal cervical tissue were reacted with antibodies raised against D2-40, D2-40/p16 and D2-40/Ki67. Immunostained structures were automatically detected on whole slides. The lymphatic vessel density (D2-40), proliferating lymphatic vessel density (D2-40/ki67) and spatial lymphatic distribution in respect to the adjacent epithelium were assessed from normal cervix to early cervical cancer and correlated with lymphovascular space invasion and lymph node status. Prominent lymphatic vessel density and proliferating lymphatic vessel density are detected under the transformation zone of benign cervix and no further increase is noted during cancer progression. Notably, a shift of lymphatic vessel distribution toward the neoplastic edges is detected. In IB1 cervical cancer, although intra- and peritumoral lymphatic vessel density are neither correlated with lymphovascular space invasion nor with lymph node metastasis, a specific spatial distribution with more lymphatic vessels in the vicinity of tumor edges is predictive of lymphatic dissemination. Herein, we provide a new computerized method suitable for an innovative detailed analysis of the lymphatic network. We show that the transformation zone of the benign cervix acts as a baseline lymphangiogenic niche before the initiation of neoplastic process. During cancer progression, this specific microenvironment is maintained with lymphatic vessels even in closer vicinity to tumor cells.Modern Pathology advance online publication, 6 December 2013; doi:10.1038/modpathol.2013.195. [less ▲]

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See detailThe uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor alpha modulation, uncoupling nuclear and membrane activation.
Abot, Anne; Fontaine, Coralie; Buscato, Melissa et al

in EMBO molecular medicine (2014), 6(10), 1328-46

Estetrol (E4) is a natural estrogen with a long half-life produced only by the human fetal liver during pregnancy. The crystal structures of the estrogen receptor alpha (ERalpha) ligand-binding domain ... [more ▼]

Estetrol (E4) is a natural estrogen with a long half-life produced only by the human fetal liver during pregnancy. The crystal structures of the estrogen receptor alpha (ERalpha) ligand-binding domain bound to 17beta-estradiol (E2) and E4 are very similar, as well as their capacity to activate the two activation functions AF-1 and AF-2 and to recruit the coactivator SRC3. In vivo administration of high doses of E4 stimulated uterine gene expression, epithelial proliferation, and prevented atheroma, three recognized nuclear ERalpha actions. However, E4 failed to promote endothelial NO synthase activation and acceleration of endothelial healing, two processes clearly dependent on membrane-initiated steroid signaling (MISS). Furthermore, E4 antagonized E2 MISS-dependent effects in endothelium but also in MCF-7 breast cancer cell line. This profile of ERalpha activation by E4, uncoupling nuclear and membrane activation, characterizes E4 as a selective ER modulator which could have medical applications that should now be considered further. [less ▲]

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See detailEstetrol and neuroprotection against perinatal ischemic insult
Tskitishvili, Ekaterine ULg; Nisolle, Michelle ULg; Noël, Agnès ULg et al

in Estetrol attenuates neonatal hypoxic-ischemic brain injury (2014)

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See detailChanges in elastin density in different locations of the vaginal wall in women with pelvic organ prolapse.
DE LANDSHEERE, Laurent ULg; Blacher, Silvia ULg; Munaut, Carine ULg et al

in International Urogynecology Journal & Pelvic Floor Dysfunction (2014)

INTRODUCTION AND HYPOTHESIS: The purpose of this study was to analyze the histomorphometric properties of the vaginal wall in women with pelvic organ prolapse (POP). METHODS: In 15 women undergoing ... [more ▼]

INTRODUCTION AND HYPOTHESIS: The purpose of this study was to analyze the histomorphometric properties of the vaginal wall in women with pelvic organ prolapse (POP). METHODS: In 15 women undergoing surgery for POP, full-thickness biopsies were collected at two different sites of location from the anterior and/or posterior vaginal wall. Properties of the precervical area (POP-Q point C/D) were compared with the most distal portion of the vaginal wall (POP-Q point Ba/Bp) using histological staining and immunohistochemistry. The densities of total collagen fibers, elastic fibers, smooth muscle cells, and blood vessels were determined by combining high-resolution virtual imaging and computer-assisted digital image analysis. RESULTS: The mean elastin density was significantly decreased in the lamina propria and muscularis layer of the vaginal wall from the most distal portion of the prolapsed vaginal wall compared with the precervical area. This difference was statistically significant in the lamina propria for both anterior (8.4 +/- 1.2 and 12.1 +/- 2.0, p = 0.048) and posterior (6.8 +/- 0.5 and 10.1 +/- 1.4, p = 0.040) locations, and in the muscularis for the anterior (5.2 +/- 0.4 and 8.4 +/- 1.2, p = 0.009) vaginal wall. There were no statistically significant differences in the mean densities of collagen fibers, smooth muscle cells or blood vessels between the two locations. CONCLUSIONS: In this study, we observed changes in elastin density in two different locations of the vaginal wall from women with POP. The histomorphometric properties of the vaginal wall can be variable from one place to another in the same patient. This result supports the existence of most vulnerable locations within the vaginal wall and the potential benefit of site-specific prolapse surgery. [less ▲]

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See detailEffects of varying antigens and adjuvant systems on the immunogenicity and safety of investigational tetravalent human oncogenic papillomavirus vaccines: Results from two randomized trials.
Van Damme, Pierre; Leroux-Roels, Geert; Simon, Philippe et al

in Vaccine (2014)

BACKGROUND: A prophylactic human papillomavirus (HPV) vaccine targeting oncogenic HPV types in addition to HPV-16 and -18 may broaden protection against cervical cancer. Two Phase I/II, randomized ... [more ▼]

BACKGROUND: A prophylactic human papillomavirus (HPV) vaccine targeting oncogenic HPV types in addition to HPV-16 and -18 may broaden protection against cervical cancer. Two Phase I/II, randomized, controlled studies were conducted to compare the immunogenicity and safety of investigational tetravalent HPV L1 virus-like particle (VLP) vaccines, containing VLPs from two additional oncogenic genotypes, with the licensed HPV-16/18 AS04-adjuvanted vaccine (control) in healthy 18-25 year-old women. METHODS: In one trial (NCT00231413), subjects received control or one of 6 tetravalent HPV-16/18/31/45 AS04 vaccine formulations at months (M) 0,1,6. In a second trial (NCT00478621), subjects received control or one of 5 tetravalent HPV-16/18/33/58 vaccines formulated with different adjuvant systems (AS04, AS01 or AS02), administered on different schedules (M0,1,6 or M0,3 or M0,6). RESULTS: One month after the third injection (Month 7), there was a consistent trend for lower anti-HPV-16 and -18 geometric mean antibody titers (GMTs) for tetravalent AS04-adjuvanted vaccines compared with control. GMTs were statistically significantly lower for an HPV-16/18/31/45 AS04 vaccine containing 20/20/10/10mug VLPs for both anti-HPV-16 and anti-HPV-18 antibodies, and for an HPV-16/18/33/58 AS04 vaccine containing 20/20/20/20mug VLPs for anti-HPV-16 antibodies. There was also a trend for lower HPV-16 and -18-specific memory B-cell responses for tetravalent AS04 vaccines versus control. No such trends were observed for CD4+ T-cell responses. Immune interference could not always be overcome by increasing the dose of HPV-16/18 L1 VLPs or by using a different adjuvant system. All formulations had acceptable reactogenicity and safety profiles. Reactogenicity in the 7-day post-vaccination period tended to increase with the introduction of additional VLPs, especially for formulations containing AS01. CONCLUSIONS: HPV-16 and -18 antibody responses were lower when additional HPV L1 VLPs were added to the HPV-16/18 AS04-adjuvanted vaccine. Immune interference is a complex phenomenon that cannot always be overcome by changing the antigen dose or adjuvant system. [less ▲]

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See detailHistology of the vaginal wall in women with pelvic organ prolapse: a literature review.
DE LANDSHEERE, Laurent ULg; Munaut, Carine ULg; Richelle, Betty ULg et al

in International Urogynecology Journal (2013), 24(12), 2011-20

INTRODUCTION AND HYPOTHESIS: The pathophysiology of pelvic organ prolapse (POP) is incompletely understood. The purpose of this study is to describe the current knowledge about histology of the vaginal ... [more ▼]

INTRODUCTION AND HYPOTHESIS: The pathophysiology of pelvic organ prolapse (POP) is incompletely understood. The purpose of this study is to describe the current knowledge about histology of the vaginal wall and its possible involvement in the pathogenesis of pelvic organ prolapse. METHODS: Eligible studies were selected through a MEDLINE search covering January 1986 to December 2012. The research was limited to English-language publications. RESULTS: Investigations of changes in the vaginal tissue that occur in women with genital prolapse are currently still limited and produced contrary results. The heterogeneity of the patients and the control groups in terms of age, parity and hormonal status, of the localization of biopsies and the histological methods as well as the lack of validation of the quantification procedures do not allow clear and definitive conclusions to be drawn. CONCLUSIONS: This review shows that current knowledge of the histological changes observed in women with POP are inconclusive and relatively limited. More studies are needed in this specific field to better understand the mechanisms that lead to POP. [less ▲]

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See detailEstrogenic components for use in the treatment of neurological disorders
Foidart, Jean-Michel ULg; Tskitishvili, Ekaterine ULg

Patent (2013)

The invention relates to the prophylactic and therapeutic applications of certain estrogenic components such as estetrol in neurological disorders such as neonatal hypoxic-ischemic encephalopathy (HIE).

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See detailMolecular mechanisms of type I collagen-induced apoptosis in breast carcinoma cells
Maquoi, Erik ULg; Assent, Delphine ULg; Foidart, Jean-Michel ULg et al

Poster (2013, September 27)

Objective: As invading breast carcinoma cells breach the underlying basement membrane, they become confronted with a dense three-dimensional reactive stroma dominated by type I collagen. To develop ... [more ▼]

Objective: As invading breast carcinoma cells breach the underlying basement membrane, they become confronted with a dense three-dimensional reactive stroma dominated by type I collagen. To develop metastatic capabilities, invading tumour cells must acquire the capacity to negotiate this hostile microenvironment. By enmeshing cells in a dense fibrillar network, type I collagen acts as a physical barrier for cell migration as well as an endogenous antigrowth signal, partly by inducing apoptosis in epithelial cells. Aberrant cell survival resulting from an acquired resistance toward apoptosis represents a prominent hallmark of cancers. However, the molecular mechanisms implicated in collagen-induced apoptosis remain poorly defined. Here, we investigate the molecular mechanisms by which type I collagen induces apoptosis in breast carcinoma cells and identify MMP-14, a membrane-anchored matrix metalloproteinase, as a key anti-apoptotic factor. Methods: To investigate the induction of apoptosis by collagen, human breast adenocarcinoma MCF-7 cells overexpressing or not MMP-14 were plated on plastic plates or embedded within three dimensional type I collagen gels (Col3D). Cell death was evaluated by measuring cytoplasmic histone-associated DNA fragments (Cell Death Detection ELISA). The percentage of cells with an apoptotic nuclear morphology was also determined. The interactions between cancer cells and Col3D were analyzed by confocal microscopy and the impact of Col3D on the transcriptome of cancer cells was investigated using Illumina HT-12 BeadArrays. Results: When cultured within Col3D gels, MCF-7 cells displayed a round morphology and a cell death characterized by a Z-VAD-FMK-dependent chromatin condensation, nuclear segmentation and oligonucleosomal DNA fragmentation was induced. Transfection of MCF-7 cells with MMP-14 cDNA promoted the interactions between cells and collagen and prevented apoptosis. A transcriptomic analysis revealed that culturing MCF-7 cells within Col3D altered the expression of about 700 genes, irrespective of MMP-14 expression. Col3D modulated the expression of several apoptosis-related genes. Interestingly, MMP-14 activity was sufficient to prevent the Col3D-dependent induction of Bcl2-Interacting Killer (BIK), a pro-apoptotic member of the Bcl-2 family. Conclusions: Our results shed light on the molecular mechanisms by which a collagen-rich microenvironment triggers apoptosis in invading breast cancer cells. Furthermore, we demonstrate that MMP-14 promotes tumour progression by circumventing apoptosis. [less ▲]

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