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See detailMechanisms underlying resistance to cetuximab in the HNSCC cell line: role of AKT inhibition in bypassing this resistance.
Rebucci, Magali; Peixoto, Paul ULg; Dewitte, Amelie et al

in International Journal of Oncology (2011), 38(1), 189-200

EGFR is frequently overexpressed in head and neck squamous cell cancer (HNSCC). Cetuximab is a monoclonal antibody designed to interact with EGFR, block its activation, reduce the downstream signaling ... [more ▼]

EGFR is frequently overexpressed in head and neck squamous cell cancer (HNSCC). Cetuximab is a monoclonal antibody designed to interact with EGFR, block its activation, reduce the downstream signaling pathways and induce EGFR internalization. This study aims to investigate the role of the EGFR signaling pathway and EGFR internalization in a cetuximab-resistant cell line and to propose a new therapeutic strategy to optimize treatment of HNSCC. The HNSCC cell line, CAL33 was sensitive to gefitinib but resistant to cetuximab. Cetuximab induces an unexpected EGFR phosphorylation in CAL33 cells similarly to EGF but this EGFR activation does not trigger EGFR internalization/degradation, the process currently implicated in the response to cetuximab. Cetuximab inhibits ERK and AKT phosphorylation in cetuximab-sensitive A431 cells, whereas the level of AKT phosphorylation is unmodified in cetuximab-resistant cells. Interestingly, CAL33 cells harbor a PIK3CA mutation. The treatment of CAL33 cells with PI3K inhibitor and cetuximab restores the inhibition of AKT phosphorylation and induces growth inhibition. Our results indicate that EGFR internalization is impaired by cetuximab treatment in CAL33 cells and that the AKT pathway is a central element in cetuximab resistance. The combination of cetuximab with a PI3K inhibitor could be a good therapeutic option in PIK3CA-mutated HNSCC. [less ▲]

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See detailMechanisms underlying the toxicity of lactone aroma compounds towards the producing yeast cells
Aguedo, Mario ULg; Beney, L.; Waché, Y. et al

in Journal of Applied Microbiology (2003), 94(2), 258-265

Aims: To study the fundamental mechanisms of toxicity of the fruity aroma compound γ-decalactone, that lead to alterations in cell viability during its biotechnological production by yeast cells; Yarrowia ... [more ▼]

Aims: To study the fundamental mechanisms of toxicity of the fruity aroma compound γ-decalactone, that lead to alterations in cell viability during its biotechnological production by yeast cells; Yarrowia lipolytica that is able to produce high amounts of this metabolite was used here as a model. Methods and Results: Lactone concentrations above 150 mg l-1 inhibited cell growth, depolarized the living cells and increased membrane fluidity. Infrared spectroscopic measurements revealed that the introduction of the lactone into model phospholipid bilayers, decreased the phase transition temperature. Moreover, the H+-ATPase activity in membrane preparations was strongly affected by the presence of the lactone. On the other hand, only a slight decrease in the intracellular pH occurred. Conclusions: We propose that the toxic effects of γ-decalactone on yeast may be initially linked to a strong interaction of the compound with cell membrane lipids and components. Significance and Impact of the Study: These findings may enable the elaboration of strategies to improve yeast cell viability during the process of lactones bioproduction. [less ▲]

See detailMechanisms underlying the toxicity of lactone aroma compounds towards Yarrowia lipolytica
Aguedo, Mario ULg; Waché, Y.; Beney, L. et al

Poster (2002, July)

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See detailMechanisms, causes, investigation, and management of vomiting disorders in cats: a literature review
Batchelor, Daniel J.; Devauchelle, Patrick; Elliott, Jonathan et al

in Journal of Feline Medicine and Surgery (2013), 15(4), 237-265

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See detailMechanisms, causes, investigation, and management of vomiting disorders in cats: a literature review
Batchelor, Daniel J.; Devauchelle, Patrick; Elliott, Jonathan et al

in Journal of Feline Medicine and Surgery (2013), 15(4), 237-265

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See detailA mechanistic basis for potent, glycoprotein B-directed gammaherpesvirus neutralization.
Glauser, Daniel L; Kratz, Anne*-Sophie; Gillet, Laurent ULg et al

in Journal of General Virology (The) (2011), 92(Pt 9), 2020-33

Glycoprotein B (gB) is a conserved, essential component of gammaherpes virions and so potentially vulnerable to neutralization. However, few good gB-specific neutralizing antibodies have been identified ... [more ▼]

Glycoprotein B (gB) is a conserved, essential component of gammaherpes virions and so potentially vulnerable to neutralization. However, few good gB-specific neutralizing antibodies have been identified. Here, we show that murid herpesvirus 4 is strongly neutralized by mAbs that recognize an epitope close to one of the gB fusion loops. Antibody binding did not stop gB interacting with its cellular ligands or initiating its fusion-associated conformation change, but did stop gB resolving stably to its post-fusion form, and so blocked membrane fusion to leave virions stranded in late endosomes. The conservation of gB makes this mechanism a possible general route to gammaherpesvirus neutralization. [less ▲]

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See detailMechanistic Diversity of Beta-Lactamases
Frère, Jean-Marie ULg; Dubus, Alain; Galleni, Moreno ULg et al

in Biochemical Society Transactions (1999), 27(2), 58-63

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See detailMechanistic Insight into the Staudinger Reaction Catalyzed by N-Heterocyclic Carbenes
Hans, Morgan ULg; Wouters, J.; Demonceau, Albert ULg et al

in Chemistry : A European Journal (2013), 19(19), 9668-9676

Four zwitterions were prepared by treating 1,3-dimesitylimidazolin-2-ylidene (SIMes) or 1,3-dimesitylimidazol-2-ylidene (IMes) with either N-tosyl benzaldimine or diphenylketene. They were isolated in ... [more ▼]

Four zwitterions were prepared by treating 1,3-dimesitylimidazolin-2-ylidene (SIMes) or 1,3-dimesitylimidazol-2-ylidene (IMes) with either N-tosyl benzaldimine or diphenylketene. They were isolated in high yields and characterized by IR and NMR spectroscopy. The molecular structures of three of them were determined by using X-ray crystallography and their thermal stability was monitored by using thermogravimetric analysis. The imidazol(in)ium-2-amides were rather labile white solids that did not show any tendency to tautomerize into the corresponding 1,2,2-triaminoethene derivatives. They displayed a mediocre catalytic activity in the Staudinger reaction of N-tosyl benzaldimine with diphenylketene. In contrast, the imidazol(in)ium-2-enolates were orange-red crystalline materials that remained stable over extended periods of time. Despite their greater stability, these zwitterions turned out to be efficient promoters for the model cycloaddition under scrutiny. As a matter of fact, their catalytic activity matched those recorded with the free carbenes. Altogether, these results provide strong experimental insight into the mechanism of the Staudinger reaction catalyzed by N-heterocyclic carbenes. They also highlight the superior catalytic activity of the imidazole-based carbene IMes compared with its saturated analogue SIMes in the reaction under consideration. [less ▲]

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See detailMechanistic Insights into the Cobalt-Mediated Radical Polymerization (CMRP) of Vinyl Acetate with Cobalt(Iii) Adducts as Initiators
Debuigne, Antoine ULg; Champouret, Yohan; Jérôme, Robert ULg et al

in Chemistry : A European Journal (2008), 14(13), 4046-4059

Over the past few years, cobalt-mediated radical polymerization (CMRP) has proved efficient in controlling the radical polymerization of very reactive monomers, such as vinyl acetate (VAc). However, the ... [more ▼]

Over the past few years, cobalt-mediated radical polymerization (CMRP) has proved efficient in controlling the radical polymerization of very reactive monomers, such as vinyl acetate (VAc). However, the reason for this success and the intimate mechanism remained basically speculative. Herein, two mechanisms are shown to coexist: the reversible termination of the growing poly(vinyl acetate) chains by the Co(acac)(2) complex (acac: acetylacetonato), and a degenerative chain-transfer process. The importance of one contribution over the other strongly depends on the polymerization conditions, including complexation of cobalt by ligands, such as water and pyridine. This significant progress in the CMRP mechanism relies on the isolation and characterization of the very first cobalt adducts formed in the polymerization medium and their use as CMRP initiators. The structure proposed for these adducts was supported by DFT calculations. Beyond the control of the VAc polymerization, which is the best ever achieved by CMRP, extension to other monomers and substantial progress in macromolecular engineering are now realistic forecasts. [less ▲]

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See detailMechanistic investigation and selectivity of the grafting onto C60 of macroradicals prepared by cobalt-mediated radical polymerization
Hurtgen, Marie ULg; Debuigne, Antoine ULg; Gigmes, Didier et al

in Polymer (2012), 53(20), 4353-4358

The grafting mechanism of poly(vinyl acetate) macroradicals prepared by cobalt-mediated radical polymerization onto C60 is investigated. The experimental conditions directly impact the nature and ... [more ▼]

The grafting mechanism of poly(vinyl acetate) macroradicals prepared by cobalt-mediated radical polymerization onto C60 is investigated. The experimental conditions directly impact the nature and stability of the PVAc/C60 adducts. In the presence of residual initiating radicals that can compete with PVAc! macroradicals for addition onto C60, mixtures of PVAc/C60 adducts having between one and eight polymer chains per C60 are formed. PVAc/C60 adducts prepared with low [PVAc]:[C60] ratios may contain weak C60-C60 bonds that further dissociate and account for the instability of the products. The formation of such dimers can be lessened by increasing the temperature from 30 !C to 100 !C. The temperature increase also allows a complete dissociation of the PVAc-Co dormant species into PVAc! macroradicals and an almost quantitative grafting of eight PVAc chains onto C60, leading to well-de!ned C60(PVAc)8 octa-adducts. These results might shed new light on the grafting onto C60 of macroradicals prepared by other CRP techniques. [less ▲]

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See detailA mechanistic study on the degradation of highly ordered, non-ionic surfactant templated aluminosilicate mesoporous materials Al-CMI-1 in boiling water
Léonard, Alexandre ULg; Su, B.-L.

in Zhao, Dongyuan; Qiu, Shilun; Tang, Yi (Eds.) et al Recent Progress in Mesostructured Materials, Proceedings of the 5 International Mesostructured Materials Symposium (IMMS2006) (2007)

A detailed account of the evolution of aluminosilicate mesoporous materials in boiling water is described. After erosion of the surface silicate layer covering the inner side of the channel walls by ... [more ▼]

A detailed account of the evolution of aluminosilicate mesoporous materials in boiling water is described. After erosion of the surface silicate layer covering the inner side of the channel walls by hydrolysis, Al atoms become exposed and confer a remarkable resistance to these materials. [less ▲]

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See detailA mechanobiological model of orthodontic tooth movement.
Van Schepdael, A; Vander Sloten, J; Geris, Liesbet ULg

in Biomechanics & Modeling in Mechanobiology (2013)

Orthodontic tooth movement is achieved by the process of repeated alveolar bone resorption on the pressure side and new bone formation on the tension side. In order to optimize orthodontic treatment, it ... [more ▼]

Orthodontic tooth movement is achieved by the process of repeated alveolar bone resorption on the pressure side and new bone formation on the tension side. In order to optimize orthodontic treatment, it is important to identify and study the biological processes involved. This article presents a mechanobiological model using partial differential equations to describe cell densities, growth factor concentrations, and matrix densities occurring during orthodontic tooth movement. We hypothesize that such a model can predict tooth movement based on the mechanobiological activity of cells in the PDL. The developed model consists of nine coupled non-linear partial differential equations, and two distinct signaling pathways were modeled: the RANKL-RANK-OPG pathway regulating the communication between osteoblasts and osteoclasts and the TGF-beta pathway mediating the differentiation of mesenchymal stem cells into osteoblasts. The predicted concentrations and densities were qualitatively validated by comparing the results to experiments reported in the literature. In the current form, the model supports our hypothesis, as it is capable of conceptually simulating important features of the biological interactions in the alveolar bone-PDL complex during orthodontic tooth movement. [less ▲]

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See detailMechanobiological modeling can explain orthodontic tooth movement: three case studies.
Van Schepdael, An ULg; Vander Sloten, J.; Geris, Liesbet ULg

in Journal of Biomechanics (2013), 46(3), 470-7

Progress in medicine and higher expectation of quality of life has led to a higher demand for several dental and medical treatments. This increases the occurrence of situations in which orthodontic ... [more ▼]

Progress in medicine and higher expectation of quality of life has led to a higher demand for several dental and medical treatments. This increases the occurrence of situations in which orthodontic treatment is complicated by pathological conditions, medical therapies and drugs. Together with experiments, computer models might lead to a better understanding of the effect of pathologies and medical treatment on tooth movement. This study uses a previously presented mechanobiological model of orthodontic tooth displacement to investigate the effect of pathologies and (medical) therapies on the result of orthodontic treatment by means of three clinically relevant case studies looking at the effect of estrogen deficiency, the effect of OPG injections and the influence of fluoride intake. When less estrogen was available, the model predicted bone loss and a rise in the number of osteoclasts present at the compression side, and a faster bone resorption. These effects were also observed experimentally. Experiments disagreed on the effect of estrogen deficiency on bone formation, while the mechanobiological model predicted very little difference between the pathological and the non-pathological case at formation sites. The model predicted a decrease in tooth movement after OPG injections or fluoride intake, which was also observed in experiments. Although more experiments and model analysis is needed to quantitatively validate the mechanobiological model used in this study, its ability to conceptually describe several pathological conditions is an important measure for its validity. [less ▲]

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See detailMechanobiology and cell tensegrity: the root of ethnic hair curling?
Pierard-Franchimont, Claudine; PAQUET, Philippe ULg; QUATRESOOZ, Pascale ULg et al

in Journal of Cosmetic Dermatology (2011), 10(2), 163-7

BACKGROUND: The hair shape, either straight, crimp, or curly, is basically under genetic influence. It is possibly altered by some drugs such as cytostatic agents. In addition, specific innate molecular ... [more ▼]

BACKGROUND: The hair shape, either straight, crimp, or curly, is basically under genetic influence. It is possibly altered by some drugs such as cytostatic agents. In addition, specific innate molecular characteristics are modulated by some cosmetic procedures to reshape the hair shafts. AIM: To revisit the possible implication of mechanobiology and cell tensegrity in shaping ethnic hair. MATERIALS AND METHODS: Optical and scanning electron microscopy of hairs. RESULTS: It is generally held that the cross-section shape of hair is related to differences in the global aspect of the hair shaft. A possible biologic link between these features may rely on shaping cell tensegrity at any portion of the hair shaft. Cell tensegrity encompasses all intrinsic and extrinsic forces responsible for the three-dimensional arrangement of intracellular macromolecules. CONCLUSION: We offer as a hypothesis that the hair shape in part depends on the organization of the cell proliferation in the hair matrix. This review gathers observations supporting the involvement of cell tensegrity in shaping the hair shaft. [less ▲]

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See detailMechanobiology and force transduction in scars developed in darker skin types.
Quatresooz, Pascale ULg; Hermanns, Jean-François ULg; Paquet, Philippe ULg et al

in Skin Research & Technology (2006), 12(4), 279-82

BACKGROUND: Scarring is a complex process involving many cell types, cytokines and biological pathways including mechanobiology. Some subtle mechanical properties of skin can be assessed by measuring the ... [more ▼]

BACKGROUND: Scarring is a complex process involving many cell types, cytokines and biological pathways including mechanobiology. Some subtle mechanical properties of skin can be assessed by measuring the speed of ultrasound shear wave propagation. The orientation of abnormal skin tension forces can be visualized, particularly in darker skin types, using dermoscopy showing distinct patterns of rete ridges' conformation. AIM: To assess some mechanobiological features of scars in darker skin types. PATIENTS AND METHODS: Large atrophic and hypertrophic surgical scars were examined on the trunk of 35 darker skin subjects. The surrounding skin was used as a comparator. Dermoscopic aspects were recorded. Resonance running time measurements (RRTM) were performed using a shear wave propagation device (Reviscometer). They were performed in four specific directions at given angles with regard to the long axis of the scar. The minimum, maximum and mean RRTM values were recorded at each site. RESULTS: Dermoscopy revealed patterns of melanin deposits in scars distinct from the normal honeycomb network seen in the surrounding skin. Hypertrophic scars showed a patchy pattern of large macular melanoderma dispersed in a lighter background. In these cases, low RRTM values were obtained with little variations according to the orientation of the measurements. By contrast, atrophic scars showed a streaky laddering melanotic pattern under dermoscopy. Higher RRTM values were often obtained, particularly in the transversal direction of the scars. Mechanical anisotropy was greater in the atrophic scars compared with the normal skin. DISCUSSION: Darker skin types represent a model for visualizing the main orientation of the epidermal rete ridges. A correlation was found between the pattern of melanized rete ridges of scars and the main orientation of the intrinsic forces in the skin. [less ▲]

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See detailMechanobiology of bone regeneration and bone adaptation to achieve stable long-term fixation of endosseous implants
Geris, Liesbet ULg; Van Oosterwyck, Hans; Duyck, Joke et al

in Zeman, M. E.; Cerrolaza, M. (Eds.) Computational Modeling of Tissue Surgery (2005)

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See detailThe mechanobiology of tissue differentiation around immediately loaded implants: a bone chamber experiment
Geris, Liesbet ULg; Van Oosterwyck, Hans; Duyck, Joke et al

in Proceedings of the 14th conference of the European Society of Biomechanics (2004)

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See detailA mechanobioregulatory model for the study of bone fracture healing
Geris, Liesbet ULg; Gerisch, A.; Weiner, R. et al

in Proceedings of the European Conference on Mathematical and Theoretical Biology (2008)

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See detailMechanochemical Study of a Single Polypeptide Molecule: Force-Induced Conformational Transition
Willet, Nicolas ULg; Hinterdorfer, Peter; Lecommandoux, Sébastien et al

Conference (2011, June)

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