References of "Frankenne, F"
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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 detailMixed origin of neovascularization of human endometrial grafts in immunodeficient mouse models
Alvarez Gonzalez, Maria-Luz ULg; Frankenne, F.; Galant, C. et al

in Human Reproduction (2009), 24(9), 2217-24

BACKGROUND: In vivo mouse models have been developed to study the physiology of normal and pathologic endometrium. Although angiogenesis is known to play an important role in endometrial physiology and ... [more ▼]

BACKGROUND: In vivo mouse models have been developed to study the physiology of normal and pathologic endometrium. Although angiogenesis is known to play an important role in endometrial physiology and pathology, the origin of neovasculature in xenografts remains controversial. The aim of this study was to assess the origin of the neovasculature of endometrial grafts in different mouse models. METHODS: Human proliferative endometrium (n = 19 women) was grafted s.c. in two immunodeficient mouse strains: nude (n = 8) and severely compromised immunodeficient (SCID; n = 20). Mice were also treated with estradiol, progesterone or levonorgestrel. Fluorescence in-situ hybridization using a centromeric human chromosome X probe, immunohistochemistry (von Willebrand factor and collagen IV) and lectin perfusion were performed to identify the origin of the vessels. RESULTS: More than 90% of vessels within xenografts were of human origin 4 weeks after implantation. Some vessels (9.67 +/- 2.01%) were successively stained by human or mouse specific markers, suggesting the presence of chimeric vessels exhibiting a succession of human and murine portions. No difference in staining was observed between the two strains of mouse or different hormone treatments. Furthermore, erythrocytes were found inside human vessels, confirming their functionality. CONCLUSION: This article shows that human endometrial grafts retain their own vessels, which connect to the murine vasculature coming from the host tissue and become functional. [less ▲]

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See detailDevelopment of an animal experimental model to study the effects of levonorgestrel on the human endometrium.
Alvarez Gonzalez, Maria-Luz ULg; Galant, C.; Frankenne, F. et al

in Human Reproduction (2009), 24(3), 697-704

BACKGROUND: This study was designed to develop an animal model to test the response of endometrium to local progestin delivery. METHODS: Proliferative human endometrium was subcutaneously grafted in two ... [more ▼]

BACKGROUND: This study was designed to develop an animal model to test the response of endometrium to local progestin delivery. METHODS: Proliferative human endometrium was subcutaneously grafted in two groups of SCID mice that received, 2 days before, a subcutaneous estradiol (E2) pellet and, for half of them, an additional implant of levonorgestrel (LNG). Mice were sacrificed 1, 2, 3 or 4 weeks after endometrial implantation and grafts were histologically analysed. Proliferation, steroid hormone receptors, blood vessels and stromal decidualization in both groups (E2 and LNG) were immunohistologically evaluated and compared with proliferative endometrium and endometrium from women with an LNG intrauterine device. RESULTS: Grafts presented normal morphological endometrial characteristics. The expression of progesterone receptors was significantly decreased in glands and stroma of the LNG group as compared with the E2 group at all times. A significant decrease was also observed in the stromal expression of estrogen receptor- in the LNG group. At 4 weeks, the mean cross-sectional area of vessels was significantly higher after LNG treatment. CONCLUSIONS: These morphological and immunohistochemical characteristics are similar to those observed in women treated with local LNG. This mouse model might facilitate further investigations needed to understand the mechanisms responsible for the breakthrough bleeding frequently observed in progestin users. [less ▲]

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See detailDifferential elevation of matrix metalloproteinase expression in women exposed to levonorgestrel-releasing intrauterine system for a short or prolonged period of time
Labied, Soraya ULg; Galant, C.; Nisolle, Michelle ULg et al

in Human Reproduction (2009), 24(1), 113-121

BACKGROUND: The levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective contraceptive and has many non-contraceptive health benefits. However, it is commonly associated with irregular ... [more ▼]

BACKGROUND: The levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective contraceptive and has many non-contraceptive health benefits. However, it is commonly associated with irregular endometrial bleeding. Metalloproteinases contribute to extracellular matrix (ECM) remodelling and regulate bleeding during the menstrual cycle. Enhanced metalloproteinase expression participates in the pathogenesis of breakthrough bleeding. Thus the objective of this study was to compare matrix metalloproteinase (MMP) expression in endometrium during luteal phase and in short-term (1 month) and long-term (> or =6 months) LNG-IUS users. METHODS: MMP expression was analysed by semi-quantitative RT-PCR and immunohistochemistry. Gelatinase activity was determined by gelatin zymography. RESULTS: MMP-1, -2, -3, -7, -9 and -12 mRNAs levels were increased, whereas that of MMP-26 was decreased in the endometrium of LNG-IUS users. MMP-1, -2, -3, -7 and -9 were localized by immunohistochemistry in all biopsies in the short-term group but in only 0-27% in the control group. The incidence of positive immunostaining for MMP-2 and -3 decreased significantly in the long-term compared with short-term LNG-IUS users. MMP-26 was localized in all biopsies from the control group but in only 14 and 25% from the short- and long-term LNG-IUS groups, respectively. In both LNG groups, the numbers of macrophages (the major source of MMP-12) was increased. CONCLUSIONS: MMP-1, active MMP-2, MMP-3, MMP-7, MMP-9 and MMP-12 are more prevalent in the short-term LNG-IUS group, suggesting their important contribution to ECM breakdown and transient bleeding. The decrease in the percentage of women expressing MMP-2 and -3 might contribute to the decreased occurrence of unwanted spotting and bleeding in long-term LNG-IUS users. [less ▲]

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See detailThe IGF system in in-vitro human decidualization
Ganeff, Corinne ULg; Chatel, G.; Munaut, Carine ULg et al

in Molecular Human Reproduction (2009), 15(1), 27-38

Decidualization of endometrial stromal cells (ESCs) is critical for a successful pregnancy but the molecular mechanisms of the process are poorly understood. In this study, we investigated whether the ... [more ▼]

Decidualization of endometrial stromal cells (ESCs) is critical for a successful pregnancy but the molecular mechanisms of the process are poorly understood. In this study, we investigated whether the insulin-like growth factor (IGF) network is involved in this cellular process. Expression kinetics of members of the IGF system was examined at both mRNA and protein levels during in-vitro decidualization of cultured human ESCs. We found a significant up-regulation of IGF-II as well as of IGF-I receptor and the A and B insulin receptor (InsR) isoforms. In addition, levels of the key adaptor proteins insulin receptor substrate 1 (IRS-1) and IRS-2 increased, suggesting a potential involvement of the IGF signalling pathway in the decidualization process. Expression of two IGF binding proteins, IGFBP-1 and IGFBP-4, which can inhibit IGF action, also increased. In order to determine whether IGF signalling was activated during decidualization, the phosphorylation status of the receptors and the adaptor proteins was estimated. Only IRS-2 was slightly phosphorylated in decidualized cells and was further activated by the addition of exogenous IGF-II. These results suggest that the IGF signalling pathway could play a crucial role in the functions of decidualized endometrial cells [less ▲]

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See detailControlled release of drugs from multi-component biomaterials
Zalfen, Alina ULg; Nizet, D.; Jérôme, Christine ULg et al

in Acta Biomaterialia (2008), 4(6), 1788-1796

In order to control their release, drugs are encapsulated into systems which are expected to provide a certain site with a predetermined amount of drug over a well-defined period of time. Here we report ... [more ▼]

In order to control their release, drugs are encapsulated into systems which are expected to provide a certain site with a predetermined amount of drug over a well-defined period of time. Here we report on a multi-component drug delivery biomaterial that consists of a hydrogel matrix in which drug-loaded biodegradable microcarriers are dispersed, and whose potential applications could be found in the design of implantable devices with long-term activity, as required by contraceptive and hormone replacement treatments. The release profile of the drug can actually be tuned by the complex interplay of several release mechanisms, including the permeability and eventually the degradation rate of the microcarriers and the diffusion through the hydrogel. The hydrogel consisted of 2-hydroxyethyl methacrylate cross-linked by ethylene glycol dimethacrylate. The microcarriers were biodegradable poly-ε-caprolactone (PCL) microspheres in which active molecules, such as levonorgestrel (LNG), were encapsulated. The hydrogels were characterized by water swelling, thermal properties, LNG diffusion through drug-free and drug-depleted hydrogel membranes and LNG release from devices with drug dispersed in the hydrogel. The PCL microspheres were observed by scanning electron microscopy; their size distribution, LNG loading and release were also investigated. The hydrogel-microsphere assemblies were characterized in terms of the distribution of the microspheres within the hydrogel, water swelling and the release of the encapsulated molecules. The developed device, due to its composite structure, has the ability to combine several release mechanisms, leading to drug release obeying zero-order kinetics for most of the time. [less ▲]

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See detailDesign, synthesis and anticancer activity of novel hydroxylated coumarin derivatives
Hemmer, Marc ULg; De Tullio, Pascal ULg; Bernard, Y. et al

Conference (2007, October)

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See detailPlasminogen activator inhibitor type 1 (PAI-1) controls bone marrow-dependent and independent vascularization
Jost, M; Maillard, C; Lecomte, J et al

Poster (2006)

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See detailSynthesis, quality control and in vivo evaluation of [I-123] rhTIMP-2, a potential tumour-imaging agent
Oltenfreiter, R.; Burvenich, I.; Staelens, L. et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2005), 48(5), 387-396

Matrix metalloproteinases (MMPs) are enzymes involved in the turnover of the extracellular matrix. Their overexpression in tumours may provide a target for diagnostic imaging by using labelled MMP ... [more ▼]

Matrix metalloproteinases (MMPs) are enzymes involved in the turnover of the extracellular matrix. Their overexpression in tumours may provide a target for diagnostic imaging by using labelled MMP inhibitors. MMPs are inhibited by endogenous tissue inhibitors of metalloproteinases (TIMPs). The enhanced production of MT1-MMP, located on the surface of cells within or in the direct vicinity of the tumour, and the high affinity interaction between TIMP-2 and MT1-MMP suggested that TIMP-2 could be a potential agent for non-invasive monitoring of cancer MMP levels, diagnosis of primary and secondary tumours and tumour response to MMP inhibitor therapy. There is also evidence that I-125-rhTIMP-2 internalizes, which is an important feature for its possible use as a radiotherapeuticum if labelled with I-131. Labelling of rhTIMP-2 was performed using the iodogen method resulting in a radiochemical yield of 51.1 +/- 11.8% (n = 5) and a radiochemical purity of > 98%. The trichloroacetic acid (TCA) precipitability of I-123 rhTIMP-2 was 95.2%. SDS-PAGE confirmed the correct size (21 kDa) of the purified I-123 rhTIMP-2 without degradation. HPLC showed one radioactive peak with a retention time corresponding to the nonlabelled rhTIMP-2. In vivo biodistribution showed no long-term accumulation in organs and the possibility to accumulate in the tumour. These results show the potential of I-123 rhTIMP-2 as tumour-imaging agent. Copyright (c) 2005 John Wiley [less ▲]

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See detailCaractérisation par analyse d’images de l’angiogenèse sur des coupes histologiques
Le Maire, Sophie; Blacher, Silvia ULg; Labied, Soraya ULg et al

Conference (2005)

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See detailImage analysis quantification of the angiogenesis on an embryonic implantation site
Le Maire, Sophie; Blacher, Silvia ULg; Labied, Soraya ULg et al

Conference (2005)

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See detailSynthesis, radiosynthesis, in vitro and preliminary in vivo evaluation of biphenyl carboxylic and hydroxamic matrix metalloproteinase (MMP) inhibitors as potential tumor imaging agents.
Oltenfreiter, R.; Staelens, L.; Hillaert, U. et al

in Applied Radiation & Isotopes (2005), 62(6), 903-13

Excess matrix degradation is one of the hallmarks of cancer and is an important factor in the process of tumor progression. It is implicated in invasion, metastasis, growth, angiogenesis and migration ... [more ▼]

Excess matrix degradation is one of the hallmarks of cancer and is an important factor in the process of tumor progression. It is implicated in invasion, metastasis, growth, angiogenesis and migration. Many characteristics of matrix metalloproteinases (MMPs) make them attractive therapeutic and diagnostic targets. MMP expression is upregulated at the tumor site, with localization of activity in the tumor or the surrounding stroma, providing a target for medical imaging techniques. Radioiodinated carboxylic and hydroxamic MMP inhibitors 2-(4′-[123I] iodo-biphenyl-4-sulfonylamino)-3-methyl-butyric acid (9) and 2-(4′-[123I] iodo-biphenyl-4-sulfonylamino)-3-methyl-butyramide (11), their unlabelled standards and precursors were synthesized. Radioiodination was conducted by electrophilic aromatic substitution of the tributylstannyl precursors and resulted in radiochemical yields of 70±5% (n=6) and 60±5% (n=4), respectively. In vitro zymography and enzyme assays showed for both hydroxamic acid and carboxylic acid compounds a good inhibition activity and a high selectivity for MMP-2. In vivo biodistribution in NMRI mice showed no long-term accumulation in organs and the possibility to accumulate in the tumor in a later phase of this study. [less ▲]

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See detailTryptophane-based biphenylsulfonamide matrix metalloproteinase inhibitors as tumor imaging agents
Oltenfreiter, R.; Staelens, L.; Labied, Soraya ULg et al

in Cancer Biotherapy & Radiopharmaceuticals (2005), 20(6), 639-47

Aim: As a part of our efforts to use small organic matrix metalloproteinase (MMP) inhibitors with improved characteristics for the diagnosis and treatment of different kinds of tumor tissues ... [more ▼]

Aim: As a part of our efforts to use small organic matrix metalloproteinase (MMP) inhibitors with improved characteristics for the diagnosis and treatment of different kinds of tumor tissues, biphenylsulfonamide analogues were synthesized. This study reports on the in vivo biodistribution of iodine-123-labeled biphenylsulfonide and analogues in A549 lung carcinoma inoculated into athymic mice and the evaluation of their suitability as imaging agents using a single photon emission computed tomography (SPECT) camera. Methods: The radioiodinated carboxylic and hydroxamic MMP inhibitors 2-(4′- [123I]iodobiphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid (1′) and 2-(4′-[123I]iodobiphenyl-4- sulfonylamino)-3-(1H-indol-3-yl)-propionamide (2′) were synthesized by electrophilic aromatic substitution of the tributylstannyl derivatives. Planar gamma camera imaging was performed in nu/nu athymic mice bearing an A549 tumor using a Toshiba GCA-9300A/hg SPECT camera in planar mode equipped with a high-resolution, parallel-hole collimator. Results: Radiosynthesis of (1′) and (2′) resulted in radiochemical yields of 60 ± 5% (n ± 3) and 70 ± 5% (n = 6), respectively. Evaluation of tumors induced in athymic mice by the inoculation of non-small cell lung A549 carcinoma cells, showed a tumor uptake of 0.27–0.01 percent injected dose per gram (%ID/g) (3 hours–48 hours p.i.), a tumor-blood ratio of 0.7, a tumor-muscle ratio of 1.6, and a tumor-fat ratio of 0.5 at 24 hours (p.i.) for compound 1′. For compound 2′ a tumor uptake of 0.7–0.04 %ID/g (3 hours–48 hours p.i.), a postinjection tumor-blood ratio of 1.2, a tumor-muscle ratio of 3.2, and a tumor-fat ratio of 2.4 at 48 hours p.i. was observed. SPECT evaluation confirmed the results obtained from biodistribution. Conclusion: In vivo evaluation of these radioiodinated carboxylic and hydroxamic MMP inhibitor tracers revealed that they do not appear suitable as tumor-imaging agents. [less ▲]

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See detailDesign and pharmacological evaluation of recently developed 6-substituted 3-bromophenyl 2-oxo-2H-1-benzopyran 3-carboxylate derivatives as putative inhibitors of cell invasion
Kempen, I.; Frankenne, F.; Telliez, A. et al

in Fundamental & Clinical Pharmacology (2004)

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