References of "FOIDART, Jean-Michel"
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See detailA dynamic in vivo model of epithelial-to-mesenchymal transitions in circulating tumor cells and metastases of breast cancer.
Bonnomet, Arnaud; Syne, Laïdya ULg; Brysse, Anne ULg et al

in Oncogene (2012), 31(33), 3741-53

Epithelial-to-mesenchymal transition (EMT) processes endow epithelial cells with enhanced migratory/invasive properties and are therefore likely to contribute to tumor invasion and metastatic spread ... [more ▼]

Epithelial-to-mesenchymal transition (EMT) processes endow epithelial cells with enhanced migratory/invasive properties and are therefore likely to contribute to tumor invasion and metastatic spread. Because of the difficulty in following EMT processes in human tumors, we have developed and characterized an animal model with transplantable human breast tumor cells (MDA-MB-468) uniquely showing spontaneous EMT events to occur. Using vimentin as a marker of EMT, heterogeneity was revealed in the primary MDA-MB-468 xenografts with vimentin-negative and vimentin-positive areas, as also observed on clinical human invasive breast tumor specimens. Reverse transcriptase-PCR after microdissection of these populations from the xenografts revealed EMT traits in the vimentin-positive zones characterized by enhanced 'mesenchymal gene' expression (Snail, Slug and fibroblast-specific protein-1) and diminished expression of epithelial molecules (E-cadherin, ZO-3 and JAM-A). Circulating tumor cells (CTCs) were detected in the blood as soon as 8 days after s.c. injection, and lung metastases developed in all animals injected as examined by in vivo imaging analyses and histology. High levels of vimentin RNA were detected in CTCs by reverse transcriptase-quantitative PCR as well as, to a lesser extent, Snail and Slug RNA. Von Willebrand Factor/vimentin double immunostainings further showed that tumor cells in vascular tumoral emboli all expressed vimentin. Tumoral emboli in the lungs also expressed vimentin whereas macrometastases displayed heterogenous vimentin expression, as seen in the primary xenografts. In conclusion, our data uniquely demonstrate in an in vivo context that EMT occurs in the primary tumors, and associates with an enhanced ability to intravasate and generate CTCs. They further suggest that mesenchymal-to-epithelial phenomena occur in secondary organs, facilitating the metastatic growth [less ▲]

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See detailCurcumin-cyclodextrin complexes potentiate gemcitabine effects in an orthotopic mouse model of lung cancer.
Rocks, Natacha ULg; Bekaert, Sandrine ULg; Coia, I et al

in British Journal of Cancer (2012), 107(7), 1083-92

Background:Overall clinical outcome for advanced lung cancer remains very disappointing despite recent advances in treatment. Curcumin has been reported as potentially active against cancer.Methods:Owing ... [more ▼]

Background:Overall clinical outcome for advanced lung cancer remains very disappointing despite recent advances in treatment. Curcumin has been reported as potentially active against cancer.Methods:Owing to poor curcumin solubility, we have used cyclodextrins (CD) as an excipient allowing a considerable increase of aqueous solubility and bioavailability of curcumin. The effects of solubilised curcumin have been evaluated in cell cultures as well as in an in vivo orthotopic lung tumour mouse model.Results:Cell proliferation was reduced while apoptosis rates were increased when lung epithelial tumour cells were cultured in the presence of curcumin-CD complexes. For in vivo experiments, cells were grafted into lungs of C57Bl/6 mice treated by an oral administration of a non-soluble form of curcumin, CDs alone or curcumin-CD complexes, combined or not with gemcitabine. The size of orthotopically implanted lung tumours was reduced upon curcumin complex administration as compared with treatments with placebo or non-solubilised curcumin. Moreover, curcumin potentiated the gemcitabine-mediated antitumour effects.Conclusion:Our data demonstrate that curcumin, when given orally in a CD-solubilised form, reduces lung tumour size in vivo. In vitro experiments show impaired tumour cell proliferation and increased cell apoptosis. Moreover, our data underline a potential additive effect of curcumin with gemcitabine thus providing an efficient therapeutic option for antilung cancer therapy. [less ▲]

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See detailBone Marrow-derived Myofibroblasts Are the Providers of Pro-invasive Matrix Metalloproteinase 13 in Primary Tumor.
Lecomte, Julie ULg; Masset, Anne; Blacher, Silvia ULg et al

in Neoplasia : An International Journal for Oncology Research (2012), 14(10), 943-51

Carcinoma-associated fibroblasts are key contributors of the tumor microenvironment that regulates carcinoma progression. They consist of a heterogeneous cell population with diverse origins, phenotypes ... [more ▼]

Carcinoma-associated fibroblasts are key contributors of the tumor microenvironment that regulates carcinoma progression. They consist of a heterogeneous cell population with diverse origins, phenotypes, and functions. In the present report, we have explored the contribution of bone marrow (BM)-derived cells to generate different fibroblast subsets that putatively produce the matrix metalloproteinase 13 (MMP13) and affect cancer cell invasion. A murine model of skin carcinoma was applied to mice, irradiated, and engrafted with BM isolated from green fluorescent protein (GFP) transgenic mice. We provide evidence that one third of BM-derived GFP(+) cells infiltrating the tumor expressed the chondroitin sulfate proteoglycan NG2 (pericytic marker) or alpha-smooth muscle actin (alpha-SMA, myofibroblast marker), whereas almost 90% of Thy1(+) fibroblasts were originating from resident GFP-negative cells. MMP13producing cells were exclusively alpha-SMA(+) cells and derived from GFP(+) BM cells. To investigate their impact on tumor invasion, we isolated mesenchymal stem cells (MSCs) from the BM of wild-type and MMP13-deficient mice. Wild-type MSC promoted cancer cell invasion in a spheroid assay, whereas MSCs obtained from MMP13-deficient mice failed to. Our data support the concept of fibroblast subset specialization with BM-derived alpha-SMA(+) cells being the main source of MMP13, a stromal mediator of cancer cell invasion. [less ▲]

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See detailNebulized Anti-IL-13 Monoclonal Antibody Fab' Fragment Reduces Allergen-Induced Asthma
Hacha, Jonathan ULg; Tomlinson, K; Maertens, Ludovic ULg et al

in American Journal of Respiratory Cell and Molecular Biology (2012), sous presse

Rationale: Interleukin-13 (IL-13) is a prototypic Th2 cytokine and a central mediator of the complex cascade of events leading to asthmatic phenotype. Indeed, IL-13 plays key roles in IgE synthesis ... [more ▼]

Rationale: Interleukin-13 (IL-13) is a prototypic Th2 cytokine and a central mediator of the complex cascade of events leading to asthmatic phenotype. Indeed, IL-13 plays key roles in IgE synthesis, bronchial hyperresponsiveness, mucus hypersecretion, subepithelial fibrosis and eosinophil infiltration. Objectives: We assessed the potential efficacy of inhaled anti-IL-13 monoclonal antibody Fab' fragment on allergen-induced airway inflammation, hyperresponsiveness and remodeling in an experimental model of allergic asthma. Anti-IL-13 Fab' was administered to mice as a liquid aerosol generated by inExpose® inhalation system in a tower allowing a nose-only exposure. Methods: BALB/c mice were treated by PBS, anti-IL-13 Fab' or A33 Fab' fragment and subjected to ovalbumin (OVA) exposure for 1 and 5 weeks (short term (ST) and long term (LT) protocols). Measurements and Main Results: Our data demonstrate a significant anti-asthma effect following nebulization of anti-IL-13 Fab' in a model of asthma driven by allergen exposure as compared to saline and non-immune Fab fragments. In short and long terms protocols, administration of the anti-IL-13 Fab' by inhalation significantly decreased bronchial responsiveness to methacholine, BALF eosinophilia, inflammatory cell infiltration in lung tissue, and many features of airway remodeling. Levels of pro-inflammatory mediators and matrix metalloprotease levels were significantly lower in lung parenchyma of mice treated with anti-IL-13 Fab'. Conclusions: These data demonstrate that an inhaled anti-IL-13 Fab' significantly reduces airway inflammation, hyperresponsiveness and remodeling. Specific neutralization of IL-13 in the lungs using an inhaled anti-IL-13 Fab' could represent a novel and effective therapy for the treatment of asthma. [less ▲]

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See detailThe proteolytic activity of MT4-MMP is required for its proangiogenic and pro-metastatic promoting effects
Host, Lorin; Paye, Alexandra ULg; Detry, Benoît ULg et al

in International Journal of Cancer = Journal International du Cancer (2012), 131(7), 1537-1548

MT4-MMP expression in breast adenocarcinoma stimulates tumor growth and metastatic spreading to the lung. However whether these pro-tumorigenic and pro-metastatic effects of MT4-MMP are related to a ... [more ▼]

MT4-MMP expression in breast adenocarcinoma stimulates tumor growth and metastatic spreading to the lung. However whether these pro-tumorigenic and pro-metastatic effects of MT4-MMP are related to a proteolytic action is not known yet. Through site directed mutagenesis MT4-MMP has been inactivated in cancer cells through Glutamic acid 249 substitution by Alanine in the active site. Active MT4-MMP triggered an angiogenic switch at day 7 after tumor implantation and drastically accelerated subcutaneous tumor growth as well as lung colonization in RAG -/- mice. All these effects were abrogated upon MT4-MMP inactivation. In sharp contrast to most MMPs being primarily of stromal origin, we provide evidence that tumor-derived MT4-MMP, but not host-derived MT4-MMP contributes to angiogenesis. A genetic approach using MT4-MMP-deficient mice revealed that the status of MT4-MMP produced by host cells did not affect the angiogenic response. Despite of this tumor intrinsic feature, to exert its tumor promoting effect, MT4-MMP requires a permissive microenvironment. Indeed, tumor-derived MT4-MMP failed to circumvent the lack of an host angio-promoting factor such as lasminogen activator inhibitor (PAI-1). Overall, our study demonstrates the key contribution of MT4-MMP catalytic activity in the tumor compartment, at the interface with host cells. It identifies MT4-MMP as a key intrinsic tumor cell determinant that contributes to the elaboration of a permissive microenvironment for metastatic dissemination [less ▲]

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See detailAbnormal vascular architecture at the placental-maternal interface in placenta increta
CHANTRAINE, Frédéric ULg; Blacher, Silvia ULg; Berndt, Sarah et al

in American Journal of Obstetrics and Gynecology (2012), 207(3), 1881-9

Objective The objective of the study was to characterize the vascular architecture at the placental-maternal interface in pregnancies complicated by placenta increta and normal pregnancies. Study Design ... [more ▼]

Objective The objective of the study was to characterize the vascular architecture at the placental-maternal interface in pregnancies complicated by placenta increta and normal pregnancies. Study Design Vessel numbers and cross-section area density and spatial and area distributions in 13 placenta-increta placental beds were compared with 9 normal placental beds using computer-assisted image analysis of whole-slide CD31 immunolabeled sections. Results The total areas occupied by vessels in normal and placenta-increta placental beds were comparable, but vessels were significantly sparser and larger in the latter. Moreover, placenta-increta–vessel distributions (area and distance from the placental–myometrial junction) were more heterogeneous. Conclusion Size and spatial organization of the placenta-increta vascular architecture at the placental-maternal interface differed from normal and might partially explain the severe hemorrhage observed during placenta-increta deliveries. [less ▲]

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See detailAdverse obstetrical outcomes after treatment of precancerous cervical lesions: a Belgian multicentre study.
Simoens, C; GOFFIN, Frédéric ULg; Simon, P et al

in BJOG : An International Journal of Obstetrics & Gynaecology (2012), 119(10), 1247-1255

Objective  To assess the impact of cervical intraepithelial neoplasia (CIN) treatment on the risk of (spontaneous) preterm delivery (PD) and small for gestational age (SGA) at birth. Design  A multicentre ... [more ▼]

Objective  To assess the impact of cervical intraepithelial neoplasia (CIN) treatment on the risk of (spontaneous) preterm delivery (PD) and small for gestational age (SGA) at birth. Design  A multicentre cohort study. Setting  Maternity wards of four academic hospitals in Belgium. Population  Ninety-seven exposed pregnant women (with a CIN treatment history) and 194 nonexposed pregnant women (without a history of CIN treatment). Methods  A questionnaire and check of obstetrical files included socio-demographic characteristics, risk factors for PD, obstetrical history for all women and characteristics of the CIN treatment for exposed women. Pregnancy outcomes were recorded after delivery. The influence of previous treatment of CIN on pregnancy outcomes, adjusted for confounding variables, was assessed by Cox regression and lifetables (for the outcome gestational age at birth) and by logistic regression (for the outcomes PD and SGA at birth). Main outcome measures  Occurrence of PD and SGA at birth. Results  Seventy-nine per cent of the women in the database were multiparous; 16.3% of women with a previous excisional treatment spontaneously delivered preterm, compared with 8.1% of unexposed women [odds ratio (OR), 2.19; 95% confidence interval (CI), 0.97-4.99]. When adjusting for confounding factors (ethnicity, HIV status, education, age, smoking and parity), the OR for PD was 2.33 (95% CI, 0.99-5.49). Excisional treatment did not have an impact on SGA at birth (OR, 0.94; 95% CI,0.41-2.15). The depth of the cone was >10 mm in 63.5% of the documented cases. Large cones, more than 10 mm deep, were associated with a significantly increased risk of PD (adjusted OR, 4.55; 95% CI, 1.32-15.65) compared with untreated women, whereas smaller cones (≤10 mm) were not significantly associated with PD (OR, 2.77; 95% CI, 0.28-27.59). The associations seen for PD with respect to the cone size did not hold for SGA at birth. Conclusions  There was an increased risk of (spontaneous) PD after excision of CIN, in particular when the cone depth exceeded 10 mm. [less ▲]

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See detailRegulation of CXCL8/IL-8 expression by Zonula Occludens-1 in human breast cancer cells.
Brysse, Anne ULg; Mestdagt, Mélanie ULg; Polette, Myriam et al

in Molecular Cancer Research (2012), 10(1), 121-32

Accumulating data now suggest that ZO-1, once delocalized from tight junctions, could be implicated in the regulation of tumor promoting genes. Because of their major implication in different steps of ... [more ▼]

Accumulating data now suggest that ZO-1, once delocalized from tight junctions, could be implicated in the regulation of tumor promoting genes. Because of their major implication in different steps of tumor progression, we investigated here the influence of ZO-1 on chemokines expression in breast cancer cells. Using GeneArray analysis to compare chemokine mRNA expression in breast tumor cells transfected with a siRNA against ZO-1, we identified CXCL-8/IL-8 as a major potential target of ZO-1 signaling, being strongly downregulated following ZO-1 siRNA transfection. Examining further the relationship between ZO-1 and IL-8, we first demonstrated that CXCL8/IL-8 expression correlates with a relocalization of ZO-1 in several breast cancer cell lines. Moreover, CXCL8/IL-8 is downregulated in invasive BT549 cells transfected with 3 different ZO-1 siRNA and overexpressed in non-invasive BT20 and SKBR3 cells transfected with vectors expressing ZO-1. We also provide evidence for an activation of the CXCL8/IL-8 promoter by ZO-1. Finally, we demonstrate that the regulation of CXCL8/IL-8 by ZO-1 is independent of the beta-catenin pathway. Our results thus clearly demonstrate an implication of ZO-1 in CXCL8/IL-8 regulation. Because of the major implications of CXCL8/IL-8 in tumor invasion, such a regulation could play an important role in breast cancer progression. [less ▲]

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See detailTibolone increases bone mineral density but also relapse in breast cancer survivors: LIBERATE Trial Bone Sub-study.
Bundred, N. J.; Kenemans, P.; Yip, C. H. et al

in Breast Cancer Research [=BCR] (2012), 14(1), 13

INTRODUCTION: Livial Intervention Following Breast Cancer; Efficacy, Recurrence and Tolerability Endpoints (LIBERATE - ClinicalTrials.gov number NCT00408863), a randomized, placebo controlled, double ... [more ▼]

INTRODUCTION: Livial Intervention Following Breast Cancer; Efficacy, Recurrence and Tolerability Endpoints (LIBERATE - ClinicalTrials.gov number NCT00408863), a randomized, placebo controlled, double-blind trial which demonstrated that tibolone (Livial), a tissue selective hormone replacement therapy (HRT) increased breast cancer (BC) recurrence HR 1.40 (95% CI 1.14-1.70; p=0.001) entered a subgroup of women into a study of Bone Mineral Density (BMD). METHODS: Women with surgically excised primary BC (T1-3, N0-2, M0) within the last 5 years complaining of vasomotor symptoms, were assigned to tibolone 2.5mg daily or placebo treatment for a maximum of 5 years. The BMD sub-study enrolled 763 patients utilizing dual-energy X-ray absorptiometry (DXA) scanning at baseline and at 2 years. RESULTS: In the bone sub-study 699 out of 763 women were eligible (345 allocated to tibolone and 354 to placebo) after undergoing DXA scans, 300 (43%) women had normal BMD, 317 (45%) osteopenia and 82 (11.7%) osteoporosis. Low body mass index (<0.001), Asian race (p<0.001) and late age at menarche (p<0.04) predicted for low bone mass at baseline. Tibolone increased BMD by 3.2% at the lumbar spine and 2.9% at the hip compared to placebo (both p<0.001). The majority of fractures (55%) occurred in osteopaenic patients. Women with normal BMD had increased recurrence on tibolone 15.6% (22/141) compared to placebo 6.9% (11/159) p=0.016, whereas no increased BC recurrence was seen in women with low BMD; 7.4% (15/204) on tibolone versus (6.7% (13/195) on placebo. CONCLUSIONS: Tibolone is contraindicated after BC treatment as it increases BMD and BC recurrence. Risk of BC recurrence was elevated in BC women with normal BMD (compared to low) who took tibolone. [less ▲]

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See detailSurgical intervention after transvaginal Prolift mesh repair: retrospective single-center study including 524 patients with 3 years' median follow-up
DE LANDSHEERE, Laurent ULg; Ismail, Sharif; Lucot, Jean-Philippe et al

in American Journal of Obstetrics and Gynecology (2012), 206(1), 831-837

Objective The aim of this study was to explore the nature and rate of surgical intervention after transvaginal Prolift mesh repair for pelvic organ prolapse. Study Design This was a retrospective study of ... [more ▼]

Objective The aim of this study was to explore the nature and rate of surgical intervention after transvaginal Prolift mesh repair for pelvic organ prolapse. Study Design This was a retrospective study of all patients who underwent Prolift mesh repair between January 2005 and January 2009. Patient data were obtained from medical records, and patients were telephoned to check if they had surgery in other hospitals. Results A total of 600 consecutive patients were identified. Of these, 524 patients (87.3%) were included in the study, with a median follow-up duration of 38 months (range, 15–63). Global reoperation rate was 11.6%. Indications of intervention were surgery for urinary incontinence (6.9%), mesh-related complications (3.6%), or prolapse recurrence (3%). Conclusion The global reoperation rate after transvaginal Prolift mesh repair was 11.6%, with urinary incontinence surgery being the most common indication. Rates of mesh complications and prolapse recurrence are relatively low in an experienced team. [less ▲]

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See detailFetal nuchal translucency thickness in different cut-off points for aneuploidy screening in the south of Vietnam
To, Hong ULg; Schaaps, Jean-Pierre ULg; Foidart, Jean-Michel ULg

in Journal of Obstetrics and Gynaecology Research (2011), 37(10), 1327-1334

Aims: The purpose of this study was to define the most suitable cut-off point for fetal nuchal translucency thickness in a screening program for aneuploidy and trisomy 21 in the south of Vietnam. <br ... [more ▼]

Aims: The purpose of this study was to define the most suitable cut-off point for fetal nuchal translucency thickness in a screening program for aneuploidy and trisomy 21 in the south of Vietnam. <br />Material & Methods: Two thousand and five hundred cases of singleton pregnancies were followed prospectively from the first trimester to the delivery. The rate of aneuploidy was calculated by seeking a relationship to increased fetal nuchal translucency thickness then calculating the sensitivity and specificity of different cut-off points in thickness measurement to find the most suitable point for screening. <br />Results: The prevalence of fetal abnormality was 1.5% (95% CI 1.1–2.1), and 1.2% (95% CI 0.8–1.7) of aneuploidy cases found and the commonest was trisomy 21. A cut-off point at 2.4 mm showed the highest level of sensitivity and specificity for the detection of aneuploidy (65.5 and 95.7%) and trisomy 21 (75.0 and 95.1%), with a false-positive rate of 4.3 and 4.9%, respectively. <br />Conclusion: Using a cut-off point of nuchal translucency at 2.4 mm has potential for aneuploidy and trisomy 21 screening in the south of Vietnam. [less ▲]

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See detailDigging deeper into lymphatic vessel formation in vitro and in vivo
Detry, Benoît ULg; Bruyère, F.; Erpicum, Charlotte ULg et al

in BMC Cell Biology (2011), 12

Background Abnormal lymphatic vessel formation (lymphangiogenesis) is associated with different pathologies such as cancer, lymphedema, psoriasis and graft rejection. Lymphatic vasculature displays ... [more ▼]

Background Abnormal lymphatic vessel formation (lymphangiogenesis) is associated with different pathologies such as cancer, lymphedema, psoriasis and graft rejection. Lymphatic vasculature displays distinctive features than blood vasculature, and mechanisms underlying the formation of new lymphatic vessels during physiological and pathological processes are still poorly documented. Most studies on lymphatic vessel formation are focused on organism development rather than lymphangiogenic events occurring in adults. We have here studied lymphatic vessel formation in two in vivo models of pathological lymphangiogenesis (corneal assay and lymphangioma). These data have been confronted to those generated in the recently set up in vitro model of lymphatic ring assay. Ultrastructural analyses through Transmission Electron Microscopy (TEM) were performed to investigate tube morphogenesis, an important differentiating process observed during endothelial cell organization into capillary structures. [less ▲]

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See detailFrom the Clinics to the Bench and back to the Clinics: design of a medical treatment for Cervical Intraepithelial Neoplasia (CIN)
Jost, Maud; Frankenne, Francis; Maillard, Catherine ULg et al

Conference (2011, May 20)

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See detailInvolvement of z-MMP-2 in Zebrafish lymphangiogenesis
Paupert, Jenny ULg; Pendeville, Hélène; Detry, Benoît ULg et al

Poster (2011, May)

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See detailDe l'utilité d'une consultation conjointe de gynécologie- endocrinologie pédiatrique : étude rétrospective des motifs de consultation et approche pratique
HARVENGT, Julie ULg; Retz, M.-C.; Foidart, Jean-Michel ULg et al

in Revue Médicale de Liège (2011), 66(11), 581-8

The gynaecological issues encountered in children and teenagers lay at the intersection of paediatric endocrinology and gynaecology. More than ten years ago, an outpatient clinic in paediatric ... [more ▼]

The gynaecological issues encountered in children and teenagers lay at the intersection of paediatric endocrinology and gynaecology. More than ten years ago, an outpatient clinic in paediatric endocrinology and gynaecology has been created. Here, we review the last 6 years. 214 girls were included, considering only the first visit for each patient. Collected data are initial concern for this consultation, age at first consultation and confirmed or suspected diagnosis. A classification is done according to the initial concern of patients in six categories. Principal queries concern pubertal development, precocious pilosity or abnormalities in menstrual cycles. Vulvovaginitis and morphologic abnormalities are also frequently encountered. This consultation suggests a paediatric approach with a child feeling confident and a gynaecological examination with a specialist knowing the anatomy particularities and the development of the children. This article focuses on the importance of specific gynaecological examination in children and reviews the main diseases encountered. [less ▲]

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See detailInvasion and metastatic dissemination in breast cancer: mechanisms
Noël, Agnès ULg; Gilles, Christine ULg; Foidart, Jean-Michel ULg

in Revue Médicale de Liège (2011), 66(5-6), 274-278

Metastases formation is a complex process involving genetic and epigenetic modifications leading to several molecular pathway dysfunctions and alterations in the production and fonction of a panel of ... [more ▼]

Metastases formation is a complex process involving genetic and epigenetic modifications leading to several molecular pathway dysfunctions and alterations in the production and fonction of a panel of molecular mediators. Recent studies have shed light on the importance of multiple interactions occuring between tumor cells and host cells involved in the elaboration of a microenvironment permissive for tumor cell survival and growth. These tumor-host interactions are decisive, not only in the primary tumor, but also in secondary sites colonized by tumor cells. Cancer appears more and more as a sytemic disease in which tumor cell is one of the pawn in the game. System of defense are rapidly overwhelmed and tumor cells hijack host cells to promote their dissemination that likely occurs at earlier stages than initially anticipated. In the present review, we describe the novel concepts of metastases formation based on recent transcriptomic analyses and new insights acquired on the tumor microenvironment in the primary tumor and in secondary foci. [less ▲]

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See detailTGFbeta-receptor-dependent angiostimulation through the hyperglycosylated isoform of human chorionic gonadotropin.
Berndt, Sarah; Detilleux, Julien; Blacher, Silvia et al

in Placenta (2011), 32(9), 44

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See detailTransient reduction of placental angiogenesis in PAI-1 deficient mice
Labied, Soraya ULg; Blacher, Silvia ULg; Carmeliet, P. et al

in Physiological Genomics (2011), 43(4), 188-98

Murine placentation is associated with the invasion of maternal endometrium by trophoblasts and an extensive maternal and foetal angiogenesis. Plasminogen activator inhibitor-1 (PAI-1) is transiently ... [more ▼]

Murine placentation is associated with the invasion of maternal endometrium by trophoblasts and an extensive maternal and foetal angiogenesis. Plasminogen activator inhibitor-1 (PAI-1) is transiently produced by spongiotrophoblasts and trophoblast giant cells at 10.5-11.5 day post-coitum (dpc). Knowing the key contribution of PAI-1 in the regulation of angiogenesis, we have now analyzed the consequence of PAI-1 deficiency on murine placentation. Morphological and quantitative computer-assisted image analysis revealed abnormal placental morphology in PAI-1 (-/-) mice at 10.5 and 12.5 dpc. At 10.5 dpc, the genetic ablation of PAI-1 resulted in a transient reduction of both maternal and foetal vascularizations in the placenta and increased trophoblast cell density. This was associated with a poorer development of the labyrinth and an extension of the decidua. A larger spongiotrophoblast layer appeared at 12.5 dpc in PAI-1 deficient mice. Placental morphology was normalized at 14,5 dpc. Microarray analyses performed on laser capture microdissected labyrinths revealed that 46 genes were differentially expressed at 10.5 dpc between the two genotypes. However, only 11 genes were still differently modulated at 14.5 dpc when normalization of placental morphology had take place. This transcriptomic profiling highlighted a dysregulation in the expression of placenta-related cathepsin family members. All together our data provide evidence for a transient impaired placental morphology in PAI-1-deficient mice which is then normalized leading to normal embryonic development. [less ▲]

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See detailDeterminants of high, median and low rates of caesarean deliveries in Belgium
Absil, Gaëtan ULg; Van Parys, A. S.; Bednarek, Stéphanie et al

Report (2011)

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See detailWhole Slide Quantification of Stromal Lymphatic Vessel Distribution and Peritumoral Lymphatic Vessel Density in Early Invasive Cervical Cancer: A Method Description
Balsat, Cédric ULg; Blacher, Silvia ULg; Signolle, Nicolas et al

in ISRN Obstetrics and Gynecology (2011), 2011

Peritumoral Lymphatic Vessel Density (LVD) is considered to be a predictive marker for the presence of lymph node metastases in cervical cancer. However, when LVD quantification relies on conventional ... [more ▼]

Peritumoral Lymphatic Vessel Density (LVD) is considered to be a predictive marker for the presence of lymph node metastases in cervical cancer. However, when LVD quantification relies on conventional optical microscopy and the hot spot technique, interobserver variability is significant and yields inconsistent conclusions. In this work, we describe an original method that applies computed image analysis to whole slide scanned tissue sections following immunohistochemical lymphatic vessel staining. This procedure allows to determine an objective LVD quantification as well as the lymphatic vessel distribution and its heterogeneity within the stroma surrounding the invasive tumor bundles. The proposed technique can be useful to better characterize lymphatic vessel interactions with tumor cells and could potentially impact on prognosis and therapeutic decisions. [less ▲]

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