References of "Fillet, Marianne"
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See detailImmune Recovery after Allogeneic Hematopoietic Stem Cell Transplantation following Flu-TBI versus TLI-ATG Conditioning
HANNON, Muriel ULg; BEGUIN, Yves ULg; Ehx, Grégory ULg et al

in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (2015), 21(14), 3131-9

Purpose: A conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) combining total lymphoid irradiation (TLI) plus anti-thymocyte globulin (ATG) has been develop to induce graft ... [more ▼]

Purpose: A conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) combining total lymphoid irradiation (TLI) plus anti-thymocyte globulin (ATG) has been develop to induce graft-versus-tumor effects without graft-versus-host disease (GVHD). Experimental Design: We compared immune recovery in 53 patients included in a phase II randomized study comparing nonmyeloablative HCT following either fludarabine plus 2 Gy total body irradiation (TBI arm, n=28) or 8 Gy TLI plus anti-thymocyte globulin (TLI arm, n=25). Results: In comparison to TBI patients, TLI patients had a similarly low 6-month incidence of grade II-IV acute GVHD, a lower incidence of moderate/severe chronic GVHD (P=0.02), a higher incidence of CMV reactivation (P<0.001), and a higher incidence of relapse (P=0.01). While recovery of total CD8+ T cells was similar in the two groups, with median CD8+ T cell counts reaching the normal values 40-60 days after allo-HCT, TLI patients had lower percentages of naïve CD8 T cells. Median CD4+ T cell counts did not reach the lower limit of normal values the first year after allo-HCT in the two groups. Further, CD4+ T cell counts were significantly lower in TLI than in TBI patients the first 6 months after transplantation. Interestingly, while median absolute regulatory T cell (Treg) counts were comparable in TBI and TLI patients, Treg/naïve CD4+ T cell ratios were significantly higher in TLI than in TBI patients the 2 first years after transplantation. Conclusions: Immune recovery differs substantially between these two conditioning regimens possibly explaining the different clinical outcomes observed (NCT00603954). [less ▲]

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See detailFULLY AUTOMATED ELECTROPHORETICALLY MEDIATED MICROANALYSIS SYSTEM FOR CYP1A1 ACTIVITY MONITORING
Farcas, Elena ULg; Servais, Anne-Catherine ULg; Lamalle, Caroline ULg et al

Poster (2015, June 23)

Introduction Since the efficacy and toxicity of drugs are closely related to their pharmacokinetics, a good understanding of metabolic pathways is important at an early stage of development. The ... [more ▼]

Introduction Since the efficacy and toxicity of drugs are closely related to their pharmacokinetics, a good understanding of metabolic pathways is important at an early stage of development. The identification of the enzymes involved in drug metabolism is thus of critical importance for the design of further clinical studies. The availability of specifically expressed human CYPs, namely supersomes, allows the investigation of the contribution of a single metabolic enzyme to the biotransformation pathway of the compound under investigation. CYP1A1, a member of the cytochrome P450 superfamily, was studied in this project. Interestingly, it has been described to be over expressed in various types of cancer. Consequently, CYP1A1 has emerged as a particularly interesting target for cancer therapy. Methods All the experiments were carried out on a HP3DCE system equipped with an on-column DAD. The EMMA procedure was performed by injecting a plug containing CYP1A1 supersomes, followed by a plug that contained the co-factor and the substrate, then another plug of CYP1A1 supersomes. The reaction was triggered by the application of a voltage switch. The voltage was then turned off to allow the metabolic reaction to occur. The separation of the components was then performed at -25 kV. Results The present study describes the development of a fully automatized in-capillary method to follow metabolization of 7-hydroxycoumarin and screen CYP1A1 inhibitors. After preliminary studies, satisfying results were obtained using CYP1A1 at a concentration of 200 pmol/mL, while the incubation time was settled to 15 min. Equal reactant plugs were injected at -50 mbar for 6 sec. The short-end injection performed gave rise to a baseline separation of the molecules (substrate, product, CYP1A1 and NADPH) in less than 2 minutes. Adequate plugs overlap was obtained using electrophoretic mixing. The DoE performed highlighted that the voltage switch has a great impact on the metabolite formation. The amount of product obtained in the optimal conditions was found to be comparable to the one detected after conventional off-line metabolization. Besides the interest of developing an automatized CE approach for metabolisation studies, we also wanted to investigate the potentiality of this approach to screen CYP1A1 inhibitors. The ability of our system to monitor CYP1A1 inhibition was undertaken with apigenin, a well-known inhibitor. It is noteworthy that the compatibility of our system with MEKC ensures its applicability to a large variety of molecules. Novel aspect Monitoring CYP1A1 activity using a rapid and fully automated EMMA method that could be used for new anticancer agents screening. [less ▲]

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See detailFully automated electrophoretically mediated microanalysis system for CYP1A1 activity monitoring
Farcas, Elena ULg; Servais, Anne-Catherine ULg; Lamalle, Caroline ULg et al

Conference (2015, May 28)

In order to evaluate the potentiality of capillary electrophoresis for CYP1A1 activity monitoring, an in-line method was developed with the well-known 7-ethoxycoumarin substrate. The electrophoretically ... [more ▼]

In order to evaluate the potentiality of capillary electrophoresis for CYP1A1 activity monitoring, an in-line method was developed with the well-known 7-ethoxycoumarin substrate. The electrophoretically mediated microanalysis approach was used with CYP1A1 supersomes to provide a rapid and fully automated method. The in-line homogenous enzyme assay was performed in physiological conditions (pH 7.4), whereas a MEKC buffer was used as background electrolyte. In order to reduce the analysis time, the short end injection was performed. Firstly a plug containing CYP1A1 supersomes was hydrodynamically injected into a fused silica capillary, followed by a plug of co-factor (NADPH) and substrate (7-ethoxycoumarin) and finally another plug of CYP1A1 (sandwich mode). The experimental conditions were finely investigated and tuned by design of experiment methodology. The metabolization rate measured in the optimized conditions was comparable with the one obtained after off-line metabolization. Finally, inhibition studies were conducted and a significant decrease of 7-hydroxycoumarin formation was observed using apigenin as CYP1A1 potent inhibitor. [less ▲]

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See detailSimultaneous determination of insulin and its analogues in pharmaceutical formulations by micellar electrokinetic chromatography
Lamalle, Caroline ULg; Servais, Anne-Catherine ULg; RADERMECKER, Régis ULg et al

in Journal of Pharmaceutical & Biomedical Analysis (2015)

A simple and efficient MEKC method was developed to simultaneously determine human insulin, its five analogues, the main degradation products and the excipients usually present in injection formulations ... [more ▼]

A simple and efficient MEKC method was developed to simultaneously determine human insulin, its five analogues, the main degradation products and the excipients usually present in injection formulations. A very fast method with a total analysis time of 3 min was then successfully validated for the analysis of human insulin and the quality control of different commercial formulations was carried out. [less ▲]

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See detailThe emergence of metabolomics as a key discipline in the drug discovery process
Fillet, Marianne ULg; Frederich, Michel ULg

in Drug Discovery Today: Technologies (2015)

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See detailTSC2 and 14-3-3 proteins down-regulate a RIP3 dependent PDT-induced Necroptosis in Glioblastoma
Fettweis, Grégory ULg; Coupienne, Isabelle; Fillet, Marianne ULg et al

Poster (2014, October)

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See detailComprehensive plasma profiling for the characterization of graft-versus-host disease biomarkers
De Bock, Muriel; BEGUIN, Yves ULg; Leprince, Pierre ULg et al

in Talanta (2014), 125

Acute graft-versus-host disease (aGVHD) remains a life-threatening complication of hematopoietic stem cell transplantation (HSCT), limiting its application. To optimize management of aGVHD and reduce ... [more ▼]

Acute graft-versus-host disease (aGVHD) remains a life-threatening complication of hematopoietic stem cell transplantation (HSCT), limiting its application. To optimize management of aGVHD and reduce therapy-related toxicity, early specific markers are needed. The main objective of this study was thus to uncover diagnostic biomarkers comparing plasma protein profiles of patients at the time of acute GVHD diagnosis and of patients undergoing HSCT without aGVHD. Additional analysis of samples taken 15 days before aGVHD diagnosis was also performed to evaluate the potential of the newly discovered biomarkers for early diagnosis. To extract a maximum of information from plasma samples, we used three complementary proteomic approaches, namely 2D-DIGE, SELDI-TOF-MS and 2D-LC-MSE. We identified and confirmed by means of a independent techniques, the differential expression of several proteins indicating significantly increased inflammation response and disturbance in the coagulation cascade. The variation of these proteins was already observed 15 days before GVHD diagnosis, suggesting the potential early detection of the disease before symptoms appearance. Finally, logistic regression analysis determines a composite biomarker panel comprising fibrinogen, fragment of fibrinogen beta chain, SAA, prothrombin fragments, apolipoprotein A1 and hepcidin that optimally discriminated patients with and without GVHD. The area under the receiver operating characteristic curve distinguishing these 2 groups was 0.95. [less ▲]

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See detailGalectin-3: a new promising cardiac biomarker in sports endurance?
LE GOFF, Caroline ULg; Devaux, Séverine; BREVERS, Eric ULg et al

in Cardiovascular Research (2014, July), 103(Supplement 1), 255

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See detailDéveloppement de méthodes séparatives pour détecter la contrefaçon de molécules biosynthétiques comme l'insuline et les GHRP
Lamalle, Caroline ULg; Baptiste, Emeline; Marini Djang'Eing'A, Roland ULg et al

in Spectra Analyse (2014), 43

Counterfeiting is a widespread problem in the world. The medicines, like insulin or GHRP, need a strict quality control. Capillary electrophoresis and liquid chromatography methods were developed to ... [more ▼]

Counterfeiting is a widespread problem in the world. The medicines, like insulin or GHRP, need a strict quality control. Capillary electrophoresis and liquid chromatography methods were developed to analyze these peptides. The human insulin and its different analogues (lispro, aspart, glulisin, glargin and detemir) were separated by MEKC within 15 minutes. The GHRP-2 and -6 were separated by HPLC also in 15 minutes. Several samples of GHRP-6 were analyzed and non-compliances were reported. These analytical approaches seem to be promising to fight against the counterfeiting of such medicines. [less ▲]

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See detailCardiac troponins and natriuretic peptides in runners: useful for cardiac risk screening ?
LE GOFF, Caroline ULg; Kaux, Jean-François ULg; Fillet, Marianne ULg et al

in British Journal of Sports Medicine (2014, April), 48(7), 173

Background Cardiac troponins (cTn) are considered as the best biomarkers for detection of myocardial cell injury and NT-proBNP as the best for the cardiac insufficiency. Objective Our aim was to compare ... [more ▼]

Background Cardiac troponins (cTn) are considered as the best biomarkers for detection of myocardial cell injury and NT-proBNP as the best for the cardiac insufficiency. Objective Our aim was to compare cTnT and NT-proBNP levels before and after the stress tests, in sportive subjects. Design Prospective, cohort study. Setting Amateur marathon runners and ultrarunners. Patients 28 subjects (26 men, 42.5±11 yrs) were enrolled. Interventions Subjects ran the Maasmarathon (42.195 kilometers) and 33 subjects (33 men, 45.7±9.3 yrs) ran the Ultratour of Liège (Belgium; 67 km). All subjects gave their informed consent. We took blood sample before (T0), just after (T1) and 3 hours after the race (T3). Main outcome measurements cTnT concentrations were measured by high sensitive methods (hsTnT, Roche Diagnostics) on heparin plasma. The NT-proBNP was also determined with the kit Roche on heparin plasma. All statistical analyses were performed using Medcalc version 8.1 for Windows. P-value <.01 was regarded as statistically significant. Results A significant difference between hsTnT concentrations at T0 and T1 (P<.001), and between T0 and T3 (P<.001) for NT-proBNP have been observed, but not between T1 and T3. This observation appeared only after a strenuous exercise. However, up to now this type of exercise is not reproducible easily in a laboratory. Moreover, nobody knows if these observations would have cardiac consequences at long terms. Conclusion Measurement of cardiac troponins by high sensitive methods allows detecting significant release of biomarkers from the heart during exercise. The value of NT-proBNP are also significant but less than TnThs. We think that the TnThs could be an interesting tool in the future to help sport medicine to detect risk of developing a cardiac problem in the future or a sudden death. [less ▲]

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See detailTwo biomarkers for the screening of cardiac risk among runners ?
LE GOFF, Caroline ULg; Kaux, Jean-François ULg; Fillet, Marianne ULg et al

in British Journal of Sports Medicine (2014, April), 48(7), 174

Background Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight protein involved in the intracellular uptake and buffering of long chain fatty in the myocardium. Troponin T is a ... [more ▼]

Background Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight protein involved in the intracellular uptake and buffering of long chain fatty in the myocardium. Troponin T is a component of the contractile apparatus of the striated musculature. Both are early markers for acute coronary syndrome. Objective The aim of our study was to compare the results obtained with the H-FABP and the highly sensitive cardiac troponins (hsTnT) and to test their cardiospecificity in healthy runners. Design Prospective, cohort study. Setting Amateur marathon runners. Patients 23 runners (marathon) were enrolled. Interventions We drowned blood samples at three times: just before (T0), just after (T1), and three hours after the end of the race (T3). Main outcome measurements H-FABP and hs-TnT were performed according to the manufacturer's instructions. A linear regression was calculated to observe if there is any correlation between the two biomarkers. Values above the 95th percentile for H-FABP (2.5 ng/mL) and the 99th percentile for hsTnT (14 ng/L) were considered as positive. Results At T0, none of the subjects were positive for hsTnT but 35% were positive for H-FABP; at T1, 83% for hsTnT and 100% for H-FABP; at T3, 83% for hsTnT and 96% for H-FABP. At T0, the regression equation was H-FABP T0=3.9454–0.1001×hsTnT T0; at T1: H-FABP T1=51.838–1.7026×hsTnT T1; at T3: H-FABP T3=47.977–1.6193×hsTnT T3. No correlation was observed between the 2 biomarkers. Conclusion We observed a significant increase of H-FABP and hsTnT in runners. These markers are independent to each other. These values could biologically correspond to a heart ischemia. These biomarkers could be helpful for the screening of cardiac risk among runners. [less ▲]

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See detailMicellar electrokinetic chromatography against the counterfeiting of insulin formulations
Lamalle, Caroline ULg; Servais, Anne-Catherine ULg; Crommen, Jacques ULg et al

Poster (2014)

Insulin plays an important role in the homeostasis of blood glucose concentration. A deficiency of this hormone causes diabetes, which can be treated by subcutaneous injection of synthetic insulin ... [more ▼]

Insulin plays an important role in the homeostasis of blood glucose concentration. A deficiency of this hormone causes diabetes, which can be treated by subcutaneous injection of synthetic insulin. Besides human regular insulin, several modified analogues have been developed to accelerate (Lispro, Aspart, Glulisin) or delay (Glargin, Detemir) its absorption. Moreover, protamine is sometimes associated with human, Lispro or Aspart insulin to give a crystalline form, which delays the action of insulin, providing it with a prolonged absorption profile after injection. Diabetes is one of the most common metabolic diseases in the world; its prevalence increases continuously. A lot of patients are therefore concerned with the treatment, which is relatively expensive and requires a prescription. Some pharmaceutical formulations can sometimes be found without prescription on the parallel market but the risk of drug counterfeiting is then considerably increased. The poor quality of these drugs can lead to harmful consequences for the public health. It is therefore essential to develop a suitable method for the identification and quantification of human insulin and its analogues inside formulations. Ortner et al. [1] have already proposed micellar electrokinetic chromatography (MEKC) methods to detect simultaneously human insulin and its five analogues but no quantitative applications were presented. Furthermore, formulations containing protamine were not tested so we included them in our study. The first optimisation step involved the sample preparation procedure. An acidic sample solution (10 mM HCl) was finally selected to solubilise protamine and Glargin. Then the background electrolyte composition was investigated to separate the components present in the formulations. A basic buffer (50 mM ammonium acetate pH 9) was selected, providing an important and stable electroosmotic flow, a negative charge to the insulins and avoiding any adsorption to the capillary wall. The addition of sodium dodecylsulfate (SDS) and acetonitrile (ACN) was also found crucial for selectivity. With 50 mM SDS and 15% ACN the six insulins and the two major excipients (phenol and meta-cresol) were fully separated within 15 minutes. This method was then entirely validated for the human insulin and the quality control of related formulations was performed. The next step will be the validation and the quantification of the other analogues. [less ▲]

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See detailDevelopment and validation of a liquid chromatographic method for the stability study of a pharmaceutical formulation containing voriconazole using cellulose tris(4-chloro-3-methylphenylcarbamate) as chiral selector and polar organic mobile phases.
Servais, Anne-Catherine ULg; Moldovan, Radu-Cristian ULg; Farcas, Elena ULg et al

in Journal of chromatography. A (2014), 1363

The ophthalmic solution of voriconazole, i.e. (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-y l)butan-2-ol, made from an injection formulation which also contains ... [more ▼]

The ophthalmic solution of voriconazole, i.e. (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-y l)butan-2-ol, made from an injection formulation which also contains sulfobutylether-beta-cyclodextrin sodium salt as an excipient (Vfend((R))), is used for the treatment of fungal keratitis. A liquid chromatographic (LC) method using polar organic mobile phase and cellulose tris(4-chloro-3-methylphenylcarbamate) coated on silica as chiral stationary phase was successfully developed to evaluate the chiral stability of the ophthalmic solution. The percentage of methanol (MeOH) in the mobile phase containing acetonitrile (ACN) as the main solvent significantly influenced the retention and resolution of voriconazole and its enantiomer ((2S,3R)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1- yl)butan-2-ol). The optimized mobile phase consisted of ACN/MeOH/diethylamine/trifluoroacetic acid (80/20/0.1/0.1; v/v/v/v). The method was found to be selective not only regarding the enantiomer of voriconazole but also regarding the specified impurities described in the monograph from the European Pharmacopoeia. The LC method was then fully validated applying the strategy based on total measurement error and accuracy profiles. Under the selected conditions, the determination of 0.1% of voriconazole enantiomer could be performed. Finally, a stability study of the ophthalmic solution was conducted using the validated LC method. [less ▲]

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See detailIn-capillary derivatization with (-)-1-(9-fluorenyl)ethyl chloroformate as chiral labeling agent for the electrophoretic separation of amino acids.
Fradi, Ines ULg; Farcas, Elena ULg; Said, Azza Ben et al

in Journal of chromatography. A (2014), 1363

An original micellar electrokinetic chromatography (MEKC) method using in-capillary derivatization with a chiral labeling reagent was developed for the separation of amino acid (AA) derivatives. The ... [more ▼]

An original micellar electrokinetic chromatography (MEKC) method using in-capillary derivatization with a chiral labeling reagent was developed for the separation of amino acid (AA) derivatives. The potential of (-)-1-(9-fluorenyl)-ethyl chloroformate (FLEC) as in-capillary derivatization agent is described for the first time. Several parameters for in-capillary derivatization and subsequent MEKC separation were systematically investigated using experimental designs. Firstly experimental conditions for in-capillary derivatization were optimized using face-centered central composite design (FCCD). Mixing voltage and time as well as concentration of the labeling solution were investigated. Efficient labeling was achieved by sequential injection of AAs and FLEC labeling solution followed by the application of a voltage of 0.2kV for 570s. The background electrolyte (BGE) composition was then optimized in order to achieve selectivity. A FCCD was performed with two factors, namely the sodium dodecyl sulfate (SDS) concentration and the percentage of propan-2-ol (IPA). The separation of 12 pairs of derivatized AA (FLEC-AA) diastereomers was achieved with resolution values comprised between 3 and 20. Furthermore, an efficient derivatization and separation of 29 FLEC-AA derivatives were achieved in a single run using a buffer made up of 40mM sodium tetraborate, 21mM SDS and 8.5% IPA. The method was successfully applied to the analysis of spiked artificial cerebrospinal fluid (aCSF) sample. [less ▲]

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