References of "Noël, Agnès"
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See detailInfluence of mouse strain on ovarian tissue recovery after engraftment with angiogenic factor.
Fransolet, Maïté ULg; Henry, Laurie ULg; Labied, Soraya et al

in Journal of Ovarian Research (2015), 8(1), 14

BACKGROUND: For women facing gonadotoxic treatment, cryopreservation of ovarian tissue with subsequent retransplantation during remission is a promising technique for fertility preservation. However ... [more ▼]

BACKGROUND: For women facing gonadotoxic treatment, cryopreservation of ovarian tissue with subsequent retransplantation during remission is a promising technique for fertility preservation. However, follicle loss within grafted ovarian tissue can be caused by ischemia and progressive revascularization. Several xenograft models using different immunodeficient rodent lines are suitable for studying ovarian tissue survival and follicular viability after frozen-thawed ovarian cortex transplantation. SCID mice, which are deficient for functional B and T cells, are the most commonly used mice for ovarian xenograft studies. However, due to incomplete immunosuppression, NOD-SCID mice displaying low NK cell function and an absence of circulating complement might be more appropriate. The present study aims to define the most appropriate immunodeficient mouse strain for ovarian tissue xenotransplantation by comparing ovarian graft recovery in SCID and NOD-SCID mice following engraftment in the presence of isoform 111 of vascular endothelial growth factor. METHODS: Sheep ovarian cortex fragments were embedded in a collagen matrix, with or without VEGF111, before being stitched onto the ovaries of SCID and NOD-SCID mice. Transplants were recovered after 3 days to study early revascularization or after 3 weeks to evaluate follicle preservation and tissue fibrosis through histological analyses. RESULTS: At day 3, vessels were largely reorganized in the ovarian grafts of both mouse strains. After 3 weeks, the cortical tissue was clearly identifiable in SCID mice but not in NOD-SCID mice. Upon VEGF111 treatment, vascularization was significantly improved 3 days after transplantation in SCID mice. This increase in vessel density was correlated with better follicular preservation in SCID mice 3 weeks after transplantation. Fibrosis was not decreased by VEGF treatment in either mouse strain. CONCLUSIONS: Tissue architecture and follicular morphology were better preserved in ovarian tissues grafted in SCID mice in comparison with NOD-SCID mice. Moreover, tissue revascularization was improved in SCID mice by VEGF111 graft treatment. Thus, we consider SCID mice to be the best murine model for studying ovarian tissue xenografts. [less ▲]

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See detailIsoform 165 of vascular endothelial growth factor in collagen matrix improves ovine cryopreserved ovarian tissue revascularisation after xenotransplantation in mice.
Henry, Laurie ULg; LABIED, Soraya ULg; Fransolet, Maïté ULg et al

in Reproductive biology and endocrinology (2015), 13(1), 15

BACKGROUND: Aggressive anti-cancer treatments can result in ovarian failure. Ovarian cryopreservation has been developed to preserve the fertility of young women, but early graft revascularisation still ... [more ▼]

BACKGROUND: Aggressive anti-cancer treatments can result in ovarian failure. Ovarian cryopreservation has been developed to preserve the fertility of young women, but early graft revascularisation still requires improvement. METHODS: Frozen/thawed sheep ovarian cortical biopsies were embedded in collagen matrix with or without isoform 165 of vascular endothelial growth factor (VEGF165) and transplanted into ovaries of immunodeficient mice. Ovaries were chosen as transplantation sites to more closely resemble clinical conditions in which orthotopic transplantation has previously allowed several spontaneous pregnancies. RESULTS: We found that VEGF165 significantly increased the number of Dextran-FITC positive functional vessels 3 days after grafting. Dextran- fluorescein isothiocyanate (FITC) positive vessels were detectable in 53% and 29% of the mice in the VEGF-treated and control groups, respectively. Among these positive fragments, 50% in the treated group displayed mature smooth-muscle-actin-alpha (alpha-SMA) positive functional vessels compared with 0% in the control group. CD31 positive murine blood vessels were observed in 40% of the VEGF165 transplants compared with 21% of the controls. After 3 weeks, the density of murine vessels was significantly higher in the VEGF165 group. CONCLUSION: The encapsulation of ovarian tissue in collagen matrix in the presence of VEGF165 before grafting has a positive effect on functional blood vessel recruitment. It can be considered as a useful technique to be improved and further developed before human clinical applications in female cancer patients in the context of fertility preservation. [less ▲]

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See detailA Membrane-Type-1 Matrix Metalloproteinase (MT1-MMP) - Discoidin Domain Receptor 1 Axis Regulates Collagen-Induced Apoptosis in Breast Cancer Cells.
Assent, Delphine; Bourgot, Isabelle ULg; Hennuy, Benoît ULg et al

in PloS one (2015), 10(3), 0116006

During tumour dissemination, invading breast carcinoma cells become confronted with a reactive stroma, a type I collagen-rich environment endowed with anti-proliferative and pro-apoptotic properties. To ... [more ▼]

During tumour dissemination, invading breast carcinoma cells become confronted with a reactive stroma, a type I collagen-rich environment endowed with anti-proliferative and pro-apoptotic properties. To develop metastatic capabilities, tumour cells must acquire the capacity to cope with this novel microenvironment. How cells interact with and respond to their microenvironment during cancer dissemination remains poorly understood. To address the impact of type I collagen on the fate of tumour cells, human breast carcinoma MCF-7 cells were cultured within three-dimensional type I collagen gels (3D COL1). Using this experimental model, we have previously demonstrated that membrane type-1 matrix metalloproteinase (MT1-MMP), a proteinase overexpressed in many aggressive tumours, promotes tumour progression by circumventing the collagen-induced up-regulation of BIK, a pro-apoptotic tumour suppressor, and hence apoptosis. Here we performed a transcriptomic analysis to decipher the molecular mechanisms regulating 3D COL1-induced apoptosis in human breast cancer cells. Control and MT1-MMP expressing MCF-7 cells were cultured on two-dimensional plastic plates or within 3D COL1 and a global transcriptional time-course analysis was performed. Shifting the cells from plastic plates to 3D COL1 activated a complex reprogramming of genes implicated in various biological processes. Bioinformatic analysis revealed a 3D COL1-mediated alteration of key cellular functions including apoptosis, cell proliferation, RNA processing and cytoskeleton remodelling. By using a panel of pharmacological inhibitors, we identified discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase specifically activated by collagen, as the initiator of 3D COL1-induced apoptosis. Our data support the concept that MT1-MMP contributes to the inactivation of the DDR1-BIK signalling axis through the cleavage of collagen fibres and/or the alteration of DDR1 receptor signalling unit, without triggering a drastic remodelling of the transcriptome of MCF-7 cells. [less ▲]

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See detailEstetrol is a weak estrogen antagonizing estradiol-dependent mammary gland proliferation.
Gérard, Céline ULg; Blacher, Silvia ULg; Communal, Laudine et al

in Journal of Endocrinology (2015), 224(1), 86-95

Estetrol (E4) is a natural estrogen produced exclusively by the human fetal liver during pregnancy. Its physiological activity remains unknown. In contrast to ethinyl estradiol (EE) and estradiol (E2), E4 ... [more ▼]

Estetrol (E4) is a natural estrogen produced exclusively by the human fetal liver during pregnancy. Its physiological activity remains unknown. In contrast to ethinyl estradiol (EE) and estradiol (E2), E4 has a minimal impact on liver cells activity and could provide a better safety profile in contraception or hormone therapy. The aim of this study was to delineate if E4 exhibits an activity profile distinct from that of E2 on mammary gland. Compared to E2, E4 acted as a low affinity estrogen in both, human in vitro and murine in vivo, models. E4 was 100 times less potent than E2 to stimulate the proliferation of human breast epithelial (HBE) cells and murine mammary gland in vitro and in vivo, respectively. This effect was prevented by fulvestrant and by tamoxifen supporting the notion that ERalpha is the main mediator of the estrogenic effect of E4 on the breast. Interestingly, when E4 was administered along with E2, it significantly antagonized the strong stimulatory effect of E2 on HBE cells proliferation and on the growth of mammary ducts. This study characterizes for the first time the impact of E4 on mammary gland. Our results highlight that E4 is less potent than E2 and exhibits antagonistic properties towards the proliferative effect of E2 on breast epithelial cells. These data support E4 as a potential new estrogen for clinical use with a reduced impact on breast proliferation. [less ▲]

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See detailEstetrol attenuates neonatal hypoxic–ischemic brain injury
Tskitishvili, Ekaterine ULg; Nisolle, Michelle ULg; Munaut, Carine ULg et al

in Experimental Neurology (2014), 261

Estetrol (E4) is a recently described natural estrogen with four hydroxyl-groups that is synthesized exclusively during pregnancy by the human fetal liver. It has important antioxidative activity. The aim ... [more ▼]

Estetrol (E4) is a recently described natural estrogen with four hydroxyl-groups that is synthesized exclusively during pregnancy by the human fetal liver. It has important antioxidative activity. The aim of the present study was to define the importance of E4 in the attenuation of neonatal hypoxic-ischemic encephalopathy. Antioxidative effect of 650μM, 3.25mM and 6.5mM E4 on primary hippocampal cell cultures was studied before/after H202-induced oxidative stress. To examine oxidative stress and cell viability, lactate dehydrogenase activity and cell proliferation colorimetric assays were performed. To study the neuroprotective and therapeutic effects of E4 in vivo neonatal hypoxic-ischemic encephalopathy model of 7-day-old newborn rat pups was used. The neuroprotective and therapeutic effects of estetrol before/after hypoxic-ischemic insult was studied in 1mg/kg/day, 5mg/kg/day, 10mg/kg/day, 50mg/kg/day E4 pretreated/treated groups and compared with the sham and the vehicle treated groups. The body temperature of the rat pups was 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 microtubule-associated protein-2, doublecortin and vascular-endothelial growth factor were evaluated by histo- and immunohistochemistry. ELISAs were performed on blood samples to detect concentrations of S100B and glial fibrillary acidic protein as brain damage markers. This work reveals for the first time that E4 significantly decreases LDH activity and enhances cell proliferation in primary hippocampal neuronal cell cultures in vitro, and decreases the early gray matter loss and promotes neuro- and angiogenesis in vivo. [less ▲]

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See detailEGFR activation and signaling in cancer cells are enhanced by the membrane-bound metalloprotease MT4-MMP.
Paye, Alexandra ULg; Truong, Alice ULg; Yip, Cassandre ULg et al

in Cancer Research (2014), 74(23), 6758-70

MT4-MMP (MMP-17) is a GPI-anchored matrix metalloprotease expressed on the surface of cancer cells which promotes tumor growth and metastasis. In this report, we identify MT4-MMP as an important driver of ... [more ▼]

MT4-MMP (MMP-17) is a GPI-anchored matrix metalloprotease expressed on the surface of cancer cells which promotes tumor growth and metastasis. In this report, we identify MT4-MMP as an important driver of cancer cell proliferation through CDK4 activation and retinoblastoma protein (Rb) inactivation. We also determine a functional link between MT4-MMP and the growth factor receptor EGFR. Mechanistic experiments revealed direct association of MT4-MMP and its positive effects on EGFR phosphorylation in response to TGF- and EGF in cancer cells. Notably, the effects of MT4-MMP on proliferation and EGFR activation did not rely on metalloprotease activity. Clinically, MT4-MMP and EGFR expression were correlated in human triple negative breast cancer specimens. Altogether our results identify MT4-MMP as a positive modifier of EGFR outside-in signaling that acts to cooperatively drive cancer cell proliferation. [less ▲]

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See detailAGE-RELATED MACULAR DEGENERATION (AMD): FROM METABOLOMICS APPROACH TO THE INHIBITION OF PDK AS A NEW THERAPEUTIC TARGET
Arslan, Deniz ULg; Pirotte, Bernard ULg; De Tullio, Pascal ULg et al

Poster (2014, September 09)

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

Age-related Macular Degeneration (AMD) is a leading cause of vision loss in the western world among people aged 50 or older. 90% of all vision loss due to AMD results from the exudative form, which is characterized by choroidal neovascularization (CNV). Age-related changes that induce pathologic CNV are incompletely understood. A successful application of anti-VEGF approaches in the clinic is obviously a turning point in AMD treatment. Nevertheless, despite such important advances, critical issues remain to be addressed. To better understand the aetiology of this pathology, we used and improved a murine model of laser-induced choroidal neovascularization and applied a 1H NMR metabolomics study. This approach leads to the emergence of different putative biomarkers and to the validation of the CNV model for an experimental study of AMD. Among these “biomarkers”, lactate appears to be clearly involved in the development of AMD. The modulation of their plasma concentration by treatment of the animals with synthetic compounds and more specifically Pyruvate Dehydrogenase Kinase inhibitors (PDK) significantly decrease the impact of laser induced CNV. Starting from these results, the development of new PDHK inhibitors could open the way to innovative treatment opportunities in AMD disease [less ▲]

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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 detailNMR in the Pharmaceutical and Biomedical areas for identification and quantification of drugs and metabolomics applications
LAMBERT, Vincent ULg; Dufour, Gilles ULg; Chiap, Patrice ULg et al

Conference (2014, June 23)

Nuclear Magnetic Resonance (NMR) is probably, with mass spectrometry, the most powerful analytical tool for the structural determination of organic compounds. For a long time and due to technical ... [more ▼]

Nuclear Magnetic Resonance (NMR) is probably, with mass spectrometry, the most powerful analytical tool for the structural determination of organic compounds. For a long time and due to technical limitations, the main applications of NMR were focused on chemistry (organic, inorganic and medicinal chemistry) or biochemistry (i.e. proteins and proteins ligands analysis). Indeed, despite of very interesting potential in terms of structural information, reproducibility, specificity, quantification, NMR suffered of a lack of sensitivity and sometime of resolution in the case of complex mixture analysis in comparison with other technics. However, since several years, important technical improvements such as huge increase in sensitivity, hyphenation of NMR with LC system, automation and development of 2D and presaturation sequences have opened new putative applications for NMR, specifically in the pharmaceutical and biomedical areas. Then, beside the mass and chromatographic technics classically used for drug analysis, NMR represents an interesting and complementary tool for many applications. In this presentation, we will describe some NMR applications related to the pharma area. Starting from the identification of xenobiotic metabolites by coupling LC-SPE-NMR data with LC-MS/MS results, quantification of cyclodextrines in complex media, identification of illicit compounds, we will finish with our recent metabolomics NMR developments. [less ▲]

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See detailTumor Angiogenesis and Lymphangiogenesis: Microenvironmental Soil for Tumor Progression and Metastatic Dissemination
Paupert, Jenny ULg; Van De Velde, Maureen ULg; Kridelka, Frédéric ULg et al

in Feige, Jean-Jacques; Pagès, Gilles; Soncin, Fabrice (Eds.) Molecular Mechanisms of Angiogenesis (2014)

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See detailInhibition of PDH Kinase as a new therapeutic target for Age-related Macular Degeneration (AMD)
Arslan, Deniz ULg; Pirotte, Bernard ULg; De Tullio, Pascal ULg et al

Poster (2014, June)

Metabolomics is one of the most recent technologies in the world of Omics sciences. It aims at studying metabolome, which is composed of small molecular weight organic molecules (called metabolites) of a ... [more ▼]

Metabolomics is one of the most recent technologies in the world of Omics sciences. It aims at studying metabolome, which is composed of small molecular weight organic molecules (called metabolites) of a cell, an organism or a biological system. This approach gives rise to a growing number of applications in many areas, such as biomarkers discovery, clinical studies, drug efficacy and toxicity evaluation, diagnostic tools, quality control. One of the most interesting features of metabolomics is its capability to extract biochemical information reflecting biological events and then to be a powerful tool in the knowledge of the aetiology of some pathologies. Indeed, it is clear that every disease could alter more or less drastically the metabolic profile of the patients. Then a metabolomics approach could highlight the biochemical pathways affected and could allow the identification of new putative therapeutic strategies or targets that could be useful in a new drug discovery strategy. As proteomics, metabolomics approach represents a new and powerful tool for Medicinal Chemistry. Age-related Macular Degeneration (AMD) is a leading cause of vision loss in the western world among people aged 50 or older. 90% of all vision loss due to AMD results from the exudative form, which is characterized by choroidal neovascularization (CNV). Age-related changes that induce pathologic CNV are incompletely understood. A successful application of anti-VEGF approaches in the clinic is obviously a turning point in AMD treatment. Nevertheless, despite such important advances, critical issues remain to be addressed. To better understand the aetiology of this pathology, we used and improved a murine model of laser-induced choroidal neovascularization and applied a 1H NMR metabolomics study. This approach leads to the emergence of different putative biomarkers and to the validation of the CNV model for an experimental study of AMD. Among these “biomarkers”, lactate appears to be clearly involved in the development of AMD. The modulation of their plasma concentration by treatment of the animals with synthetic compounds and more specifically Pyruvate DesHydrogenase Kinase inhibitors (PDHK) significantly decrease the impact of laser induced CNV. Starting from these results, the development of new PDHK inhibitors could open the way to innovative treatment opportunities in AMD disease. [less ▲]

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See detailDUSP3/VHR is a pro-angiogenic atypical dual-specificity phosphatase
Amand, Mathieu ULg; Erpicum, Charlotte ULg; BAJOU, Khalid ULg et al

Poster (2014, January 27)

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See detailAn Easy, Convenient Cell and Tissue Extraction Protocol for Nuclear Magnetic Resonance Metabolomics.
Matheus, Nicolas ULg; Hansen, Sylvain ULg; Rozet, Eric ULg et al

in Phytochemical analysis : PCA (2014)

INTRODUCTION: As a complement to the classic metabolomics biofluid studies, the visualisation of the metabolites contained in cells or tissues could be a very powerful tool to understand how the local ... [more ▼]

INTRODUCTION: As a complement to the classic metabolomics biofluid studies, the visualisation of the metabolites contained in cells or tissues could be a very powerful tool to understand how the local metabolism and biochemical pathways could be affected by external or internal stimuli or pathologies. Therefore, extraction and/or lysis is necessary to obtain samples adapted for use with the current analytical tools (liquid NMR and MS). These extraction or lysis work-ups are often the most labour-intensive and rate-limiting steps in metabolomics, as they require accuracy and repeatability as well as robustness. Many of the procedures described in the literature appear to be very time-consuming and not easily amenable to automation. OBJECTIVE: To find a fast, simplified procedure that allows release of the metabolites from cells and tissues in a way that is compatible with NMR analysis. METHODS: We assessed the use of sonication to disrupt cell membranes or tissue structures. Both a vibrating probe and an automated bath sonicator were explored. RESULTS: The application of sonication as the disruption procedure led to reproducible NMR spectral data compatible with metabolomics studies. This method requires only a small biological tissue or cell sample, and a rapid, reduced work-up was applied before analysis. The spectral patterns obtained are comparable with previous, well-described extraction protocols. CONCLUSION: The rapidity and the simplicity of this approach could represent a suitable alternative to the other protocols. Additionally, this approach could be favourable for high- throughput applications in intracellular and intratissular metabolite measurements. Copyright (c) 2014 John Wiley & Sons, Ltd. [less ▲]

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See detailLymphangiogenesis
Paupert, Jenny ULg; Noël, Agnès ULg

in MacGraw-Hill Education Year Book of Sciences and Technology 2014 (2014)

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See detailBone marrow-derived mesenchymal stem cells drive lymphangiogenesis.
Maertens, Ludovic ULg; Erpicum, Charlotte ULg; Detry, Benoît ULg et al

in PLoS ONE (2014), 9(9), 106976

It is now well accepted that multipotent Bone-Marrow Mesenchymal Stem Cells (BM-MSC) contribute to cancer progression through several mechanisms including angiogenesis. However, their involvement during ... [more ▼]

It is now well accepted that multipotent Bone-Marrow Mesenchymal Stem Cells (BM-MSC) contribute to cancer progression through several mechanisms including angiogenesis. However, their involvement during the lymphangiogenic process is poorly described. Using BM-MSC isolated from mice of two different backgrounds, we demonstrate a paracrine lymphangiogenic action of BM-MSC both in vivo and in vitro. Co-injection of BM-MSC and tumor cells in mice increased the in vivo tumor growth and intratumoral lymphatic vessel density. In addition, BM-MSC or their conditioned medium stimulated the recruitment of lymphatic vessels in vivo in an ear sponge assay, and ex vivo in the lymphatic ring assay (LRA). In vitro, MSC conditioned medium also increased the proliferation rate and the migration of both primary lymphatic endothelial cells (LEC) and an immortalized lymphatic endothelial cell line. Mechanistically, these pro-lymphangiogenic effects relied on the secretion of Vascular Endothelial Growth Factor (VEGF)-A by BM-MSC that activates VEGF Receptor (VEGFR)-2 pathway on LEC. Indeed, the trapping of VEGF-A in MSC conditioned medium by soluble VEGF Receptors (sVEGFR)-1, -2 or the inhibition of VEGFR-2 activity by a specific inhibitor (ZM 323881) both decreased LEC proliferation, migration and the phosphorylation of their main downstream target ERK1/2. This study provides direct unprecedented evidence for a paracrine lymphangiogenic action of BM-MSC via the production of VEGF-A which acts on LEC VEGFR-2. [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 detailA spiked tissue-based approach for quantification of phosphatidylcholines in brain section by MALDI mass spectrometry imaging.
Jadoul, Laure ULg; Longuespée, Rémi ULg; Noël, Agnès ULg et al

in Analytical and Bioanalytical Chemistry (2014), sous presse

In the last few years, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has been successfully used to study the distribution of lipids within tissue sections. However ... [more ▼]

In the last few years, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has been successfully used to study the distribution of lipids within tissue sections. However, few efforts have been made to acquire reliable quantitative data regarding the localized concentrations of these molecules. Here we propose an approach based on brain homogenates for the quantification of phosphatidylcholines (PCs) in brain section by MALDI MSI. Homogenates were spiked with a range of PC(16:0 d31/18:1) concentrations. Sections from homogenates and intact brain were simultaneously prepared before being analyzed by MALDI MSI using a Fourier transform ion cyclotron resonance (FT-ICR) analyzer. Standard curves were generated from the signal intensity of the different PC(16:0 d31/18:1) ionic species ([M+H]+, [M+Na]+ and [M+K]+) detected from the homogenate sections. Localized quantitative data were finally extracted by correlating the standard curves with the signal intensities of endogenous PC (especially PC(16:0/18:1)) ionic species detected on different areas of the brain section. They were consistent with quantitative values found in the literature. This work introduces a new method to take directly into account biological matrix effects for the quantification of lipids as well as other endogenous compounds, in tissue sections by MALDI MSI. [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 detailBlocking lipid synthesis overcomes tumor re-growth and metastasis after anti-angiogenic therapy withdrawal.
Sounni, Nor Eddine ULg; Cimino, Jonathan ULg; BLACHER, Silvia ULg et al

in Cell Metabolism (2014), 20(2), 280-94

The molecular mechanisms responsible for the failure of antiangiogenic therapies and how tumors adapt to these therapies are unclear. Here, we applied transcriptomic, proteomic, and metabolomic approaches ... [more ▼]

The molecular mechanisms responsible for the failure of antiangiogenic therapies and how tumors adapt to these therapies are unclear. Here, we applied transcriptomic, proteomic, and metabolomic approaches to preclinical models and provide evidence for tumor adaptation to vascular endothelial growth factor blockade through a metabolic shift toward carbohydrate and lipid metabolism in tumors. During sunitinib or sorafenib treatment, tumor growth was inhibited and tumors were hypoxic and glycolytic. In sharp contrast, treatment withdrawal led to tumor regrowth, angiogenesis restoration, moderate lactate production, and enhanced lipid synthesis. This metabolic shift was associated with a drastic increase in metastatic dissemination. Interestingly, pharmacological lipogenesis inhibition with orlistat or fatty acid synthase downregulation with shRNA inhibited tumor regrowth and metastases after sunitinib treatment withdrawal. Our data shed light on metabolic alterations that result in cancer adaptation to antiangiogenic treatments and identify key molecules involved in lipid metabolism as putative therapeutic targets. [less ▲]

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