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See detailMT4-MMP (MMP17) as a therapeutic target in metastatic solid tumors
Noël, Agnès ULg

Poster (2015)

Others and we have identified the glycosylphosphatidyl inositol (GPI) anchored MMP called MT4-MMP or MMP-17 as a main driver of cancer cell metastasis in breast (1-3), head and neck (4) and colon cancers ... [more ▼]

Others and we have identified the glycosylphosphatidyl inositol (GPI) anchored MMP called MT4-MMP or MMP-17 as a main driver of cancer cell metastasis in breast (1-3), head and neck (4) and colon cancers (5). More recently, we demonstrated a functional link between MT4-MMP and EGFR signaling in promoting breast cancer cell proliferation in vivo and in 3D culture models. We found that MT4-MMP is a key partner of EGFR activation and signaling (6), which is independent of its enzymatic activity. In triple negative breast cancer (TNBC) cells, MT4-MMP promotes primary tumor growth and lung metastases (1,2). Herein, we investigated the clinical relevance of our finding by immunohistochemical (IHC) study of MT4-MMP and EGFR expression in human samples of several breast cancer subtypes including lobular and ductal carcinoma in situ, invasive carcinoma, triple negative ductal carcinoma and normal tissue. IHC staining of normal breast tissues with MT4-MMP antibody show no signal, whereas breast carcinomas are positives for MT4-MMP. Of note, a strong staining for MT4-MMP was observed in the triple negative breast cancer (TNBC), the most aggressive breast cancer subtype. TNBC are known to express high level of EGFR and treatment options are limited due to the non-response of the TNBC patients to the EGFR targeted therapy. By investigating 86 TNBC tumors, we found a strong correlation between MT4-MMP and EGFR expression in a 68 % of TNBC tumors. In parallel to the human study, by exploring the mechanism of MT4-MMP trafficking and internalization, we found for the first time that MT4-MMP can be recycled at the cell surface. Mechanistically, MT4-MMP uses a unique endocytic pathway, which relies on CLIC/GEEC route. In addition to deeply investigating its internalization dynamics, we also explored the mode of its oligomerization and dimerization at the cell surface. Altogether, we are providing mechanistic insights on how MT4-MMP availability is regulated and revealing unique features of this MT-MMP among other MT-MMPs. These findings can be useful for designing therapeutics to block its presence at the cell surface, rather than merely blocking its enzymatic activity to block its pro-tumor effects. (1) Chabottaux et al., 2006, Cancer Res 66, 5165-5172; (2) Host et al., 2012, Int. J. Cancer 131(7):1537-48; (3) Rizki et al., 2008, Cancer Res 68, 1378-1387), (4) Huang et al., 2009, Neoplasia 11, 1371-1382) (5) Nimri et al., 2013, Mol Carcinog 52, 859-870 (6) Paye et al., 2014, Cancer Res. 74(23):6758-70 [less ▲]

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See detailMT4-MMP, a potential prognostic factor in triple negative breast cancer
Yip, Cassandre ULg; FOIDART, Pierre ULg; SOMJA, Joan ULg et al

Scientific conference (2015, December 03)

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See detailMT4-MMP, a potential therapeutic target in triple negative breast cancer
Yip, Cassandre ULg; FOIDART, Pierre ULg; SOMJA, Joan ULg et al

Poster (2015, September)

MT4-MMP and EGFR axis may have a significant role in patient outcome and response to EGFR targeted therapy. This axis is clinically relevant in TNBC, the most aggressive breast cancer subtype. TNBC are ... [more ▼]

MT4-MMP and EGFR axis may have a significant role in patient outcome and response to EGFR targeted therapy. This axis is clinically relevant in TNBC, the most aggressive breast cancer subtype. TNBC are known to express high level of EGFR and treatment options are limited due to the non response of to the EGFR targeted therapy. Expression levels of MT4-MMP and EGFR in TNBC may be used as prognosis factor for the selection of patient who may respond or not to EGFR targeted therapy. Also, our data shed light and the potential therapeutic option of targeting both MT4-MMP and EGFR in TNBC. [less ▲]

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Peer Reviewed
See detailMtDNA haplogroups define two phenotypes of osteoarthritis
Rego-Perez, I; Fernandez-Moreno, M; DEBERG, Michelle ULg et al

in Arthritis and Rheumatism (2010), 62

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See detailMTHFR C677T polymorphism and susceptibility to migraine with aura
Magis, Delphine ULg; Coppola, Gianluca; Allena, Marta et al

in Cephalalgia : An International Journal of Headache (2005, October), 25(10), 863-864

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See detailmTOR inhibitors in advanced breast cancer: ready for prime time?
Martin, Lesley-Ann; Andre, Fabrice; Campone, Mario et al

in Cancer Treatment Reviews (2013), 39(7), 742-52

Current therapeutic approaches for advanced breast cancer frequently target receptors mediating cell survival and proliferation, such as the estrogen receptor and/or progesterone receptor and human ... [more ▼]

Current therapeutic approaches for advanced breast cancer frequently target receptors mediating cell survival and proliferation, such as the estrogen receptor and/or progesterone receptor and human epidermal growth factor receptor-2. Although these approaches are effective for many patients, treatment resistance is common. Therefore, new treatment approaches are needed for patients with advanced breast cancer. Mammalian target of rapamycin is a highly conserved serine-threonine kinase that acts as a major signaling hub that integrates and synergizes with cellular proliferation, survival, and/or motility signals mediated by estrogen receptor, human epidermal growth factor receptor-2, and other receptor tyrosine kinases. Dysregulation of mammalian target of rapamycin signaling occurs in various tumor types, including breast cancer, and has been associated with cancer pathogenesis, disease progression, and treatment resistance. Recent clinical trials show that combined inhibition of mammalian target of rapamycin and estrogen receptor represents an effective strategy for treating hormone receptor-positive advanced breast cancer progressing on nonsteroidal aromatase inhibitor therapy, and data from ongoing trials combining mammalian target of rapamycin inhibition with human epidermal growth factor receptor-2-targeted therapy are awaited. This review focuses on the molecular rationale underlying strategies to enhance sensitivity to treatment in hormone receptor-positive and human epidermal growth factor receptor-2-positive advanced breast cancer, the clinical efficacy of such approaches, and future perspectives. [less ▲]

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See detailA much lower density for the transiting extrasolar planet WASP-7 (Research Note)
Southworth, J.; Dominik, M.; Jorgensen, U~G et al

in Astronomy and Astrophysics (2011), 527

We present the first high-precision photometry of the transiting extrasolar planetary system WASP-7, obtained using telescope defocussing techniques and reaching a scatter of 0.68 mmag per point. We find ... [more ▼]

We present the first high-precision photometry of the transiting extrasolar planetary system WASP-7, obtained using telescope defocussing techniques and reaching a scatter of 0.68 mmag per point. We find that the transit depth is greater and that the host star is more evolved than previously thought. The planet has a significantly larger radius (1.330 +/- 0.093 Rjup versus 0.915 +0.046 -0.040 Rjup) and much lower density (0.41 +/- 0.10 rhojup versus 1.26 +0.25 -0.21 rhojup) and surface gravity (13.4 +/- 2.6 m/s2 versus 26.4 +4.4 -4.0 m/s2) than previous measurements showed. Based on the revised properties it is no longer an outlier in planetary mass--radius and period--gravity diagrams. We also obtain a more precise transit ephemeris for the WASP-7 system. [less ▲]

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See detailA much lower density for the transiting extrasolar planet WASP-7.
Southworth, J.; Dominik, M.; Jorgensen, U~G et al

Textual, factual or bibliographical database (2011)

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See detailMucilage and polysaccharides in the halophyte plant species Kosteletzkya virginica : Localozation and composition in relation to salt stress
Ghanem, Michel Edmond; Han, Rui-Ming; Classen, Birgit et al

in Journal of Plant Physiology (2010), 167

Detailed reference viewed: 51 (2 ULg)
See detailA mucin-enriched fermentation model to assess prebiotic potential of new indigestible carbohydrates
Boudry, Christelle ULg; Tran, Thi Hanh Tham ULg; Blaise, Yannick ULg et al

in 64th Annual Meeting of the European Federation of Animal Science (2013, August 29)

Screening the prebiotic potential of novel indigestible carbohydrates (ICH) is a challenge for feed and food industry and in vitro models are increasingly used for such purposes. Recently extracellular ... [more ▼]

Screening the prebiotic potential of novel indigestible carbohydrates (ICH) is a challenge for feed and food industry and in vitro models are increasingly used for such purposes. Recently extracellular binding proteins responsible for the adherence to intestinal mucus were described for several Lactobacillus species. As this genus is known for its beneficial effect on gut health, we enriched the in vitro gas fermentation model with mucin in order to evaluate the prebiotic potential of 5 ICH. Mucin-coated microcosms (MCM) were prepared as described by Van den Abbeele et al. (2012, Microbial Biotechnology, 5, 106-115) and introduced in the fermentation bottles with an inoculum prepared from fresh faeces of 3 sows mixed with a nutritive buffer solution. Fermentation was performed at 39°C, using 200 mg of substrate, 30 ml of inoculum and 6 MCM, yielding approx. 20 mg mucin each, in 140 ml glass bottles. A first study was performed with inulin and cellulose as substrates, with and without mucus in the bottles. A second study was performed with 5 substrates (inulin, IMO, beet pulp POS, cellobiose and gluconate) in presence of mucus. After 8 and 72h, SCFA and the microflora of fermentation broth was analysed as well as the microflora on the MCM. The comparison of the microflora evolution with and without mucus showed a better development of the Lactobacillus in the fermentation broth, mainly in presence of inulin. The development of the Lactobacillus genus allowed the classification of the 5 substrates tested in the second study (Inulin > IMO > Gluconate > Cellobiose > POS)(P < 0.05) which was not possible without mucus (P > 0.05). Inulin and IMO showed also the highest development of Bifidobacteria (P < 0.05) and the highest levels of butyrate production (P < 0.05) compared to the three other substrates, indicating a high prebiotic potential. [less ▲]

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See detailMucoadhesive cellulosic derivative sponges as drug delivery system for vaginal application
Furst, Tania ULg; Piette, Marie ULg; Lechanteur, Anna ULg et al

in European Journal of Pharmaceutics & Biopharmaceutics (2015)

Vaginal delivery of active drugs has been largely studied for local and systemic applications. It is well known that vagina is a complex route, due to physiological and non-physiological changes ... [more ▼]

Vaginal delivery of active drugs has been largely studied for local and systemic applications. It is well known that vagina is a complex route, due to physiological and non-physiological changes. Therefore, in order to achieve a prolonged local effect, these variations have to be considered. The aim of this study was to formulate and to characterize a solid system, called sponges, obtained by lyophilization of cellulosic derivative (HEC 250M) hydrogels. These sponges have to meet particular criteria to be adapted for vaginal application: they have to adhere to the vaginal cavity and to be rehydrated by the small amount of vaginal fluids. Moreover, they have to be easily manipulated and to be stable. Three freezing temperatures have been tested to prepare sponges ( 15 C, 25 C, 35 C). By SE analyzes, it was observed that the pores into the sponges were smaller and numerous as the freezing temperature decreases. However, this temperature did not have any influence on the rehydration speed that was rather influenced by the HEC concentration. Viscosity and mucoadhesive strength of hydrogels and corresponding sponges were also measured. It appeared that these parameters are mainly dépendent on the HEC concentration. These mucoadhesive sponges can be considered as potential drug delivery systems intended for vaginal application. [less ▲]

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Peer Reviewed
See detailMucociliary function testing in dogs.
Peeters, Dominique ULg; Clercx, Cécile ULg; Mc Entee, Kathleen ULg et al

in Proceedings of the 11th Annual Congress of the ESVIM (2001)

Detailed reference viewed: 4 (1 ULg)