Karim Zouaoui Boudjeltia

Université Libre de Bruxelles, Bruxelles, Brussels Capital, Belgium

Are you Karim Zouaoui Boudjeltia?

Claim your profile

Publications (123)544.49 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate changes in red blood cell (RBC) rheology over time in critically ill patients with sepsis and their relationship with outcome. In this prospective, non-interventional study, RBC rheology was assessed using the Laser-assisted Optical Rotational Cell Analyzer in a convenience sample of intensive care unit (ICU) patients with (n=64) and without (n=160) sepsis. Results were compared to measures in healthy volunteers (n=20). RBC rheology was also assessed on days 1 and 3 of the ICU stay in 32 of the non-septic and 19 of the septic patients. RBC deformability was determined by the elongation index (EI) in relation to the shear stress (0.3 to 50 Pa) applied to the RBC membrane. An aggregation index (AI) was assessed simultaneously with the same device. The ICU mortality rate of the septic patients was 31%. RBC deformability was already reduced in septic patients at ICU admission, an effect that persisted during the study period and worsened in the non-survivors for the large majority of shear stresses studied (e.g., EI for 50 Pa of shear stress was 0.527±0.064 in non-survivors vs 0.566±0.034 in survivors, p<0.05). These changes were not observed in non-septic patients. The AI was more elevated in septic than in non-septic patients at ICU admission, but had no prognostic value. Alterations in RBC rheology, including reduced deformability and increased aggregation, occur early in septic patients and reductions in RBC deformability over time are associated with a poor outcome. Copyright © 2015. Published by Elsevier Inc.
    Microvascular Research 05/2015; 101. DOI:10.1016/j.mvr.2015.05.001 · 2.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Myeloperoxidase (MPO) is a pro-oxidant enzyme involved in inflammation and its activity measurement in biological samples has emerged essential for laboratory and clinical investigations. We will describe a new method which combines the SIEFED (specific immunological extraction followed by enzymatic detection) and an ELISA (ELISAcb) to measure the active and total amounts of MPO on the same human sample and with the same calibration curve, as well as defining an acurate ratio between both the active and total forms of the enzyme. The SIEFED/ELISAcb method consists of the MPO extraction from aqueous or biological samples by immobilized anti-MPO antibodies coated onto microplate wells. After a washing step to eliminate unbound material, the activity of MPO is measured in situ by adding a reaction solution (SIEFED). Following aspiration of the reaction solution, a secondary anti-MPO antibody is added into the wells and the ELISAcb test is carried out in order to measure the total MPO content. To validate the combined method, a comparison was made with SIEFED and ELISA experiments performed separately on plasma samples isolated from human whole blood after a neutrophil stimulation. The SIEFED/ELISAcb provides a suitable tool for the measurement of specific MPO activity in biological fluids and for the estimation of the inhibitory potential of a fluid. The method can also be used as a pharmacological tool to make the distinction between a catalytic inhibitor, which binds to MPO and inhibits its activity and a steric inhibitor, which hinders the enzyme and prevents its immunodetection.
    Free Radical Research 05/2015; 49(6):1-30. DOI:10.3109/10715762.2015.1027197 · 2.99 Impact Factor
  • Pierre Van Antwerpen, Karim Zouaoui Boudjeltia
    [Show abstract] [Hide abstract]
    ABSTRACT: Rational drug design is a general approach using protein-structure technique in which the discovery of a ligand can be driven either by chance, screening, or rational theory. Myeloperoxidase was rapidly identified as a therapeutical target because of its involvement in chronic inflammatory syndromes. In this context, the research of MPO inhibitors was intensified and development of new chemical entities was rationally driven by the research of ligands that enter into the MPO catalytic pocket. Actually, as soon as crystallography data of myeloperoxidase (MPO) have become available and its structure was virtually designed, the rational drug design has been applied to this peroxidase. Pharmaceutical industries and academic laboratories apply rational drug design on MPO by either optimizing known inhibitors or searching new molecules by high throughput virtual screening. By these ways, they were able to find efficient MPO inhibitors and understand their interactions with the enzyme. During this quest of MPO inhibition, it appears that Glu268 is a crucial residue in order to optimize ligand-target interaction. This amino acid should be carefully considered by medicinal chemist when they design inhibitors interfering with MPO activity.
    Free Radical Research 03/2015; 49(6):1-41. DOI:10.3109/10715762.2015.1027201 · 2.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Human peroxidasin 1 (hsPxd01) is a multidomain heme peroxidase that uses bromide as a cofactor for the formation of sulfilimine crosslinks. The latter confer critical structural reinforcement to collagen IV scaffolds. Here hsPxd01 and various truncated variants lacking non-enzymatic domains were recombinantly expressed in HEK cell lines. The N-glycosylation site occupancy and disulfide pattern, the oligomeric structure and unfolding pathway are reported. The homotrimeric ironprotein contains a covalently-bound ferric high-spin heme per subunit with a standard reduction potential of the Fe(III)/Fe(II) couple of -233 mV at pH 7.0. Despite sequence homology at the active site and biophysical properties similar to human peroxidases, the catalytic efficiency of bromide oxidation (kcat/KM) of full-length hsPxd01 is rather low but increased upon truncation. This is discussed with respect to its structure and proposed biosynthetic function in collagen IV crosslinking. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    Journal of Biological Chemistry 02/2015; 290(17). DOI:10.1074/jbc.M114.632273 · 4.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the last decades, proteomics has largely progressed. Mass spectrometry and liquid chromatography (LC) are generally used in proteomics. These techniques enable proper separation of peptides and good identification and/or quantification of them. Later, nano-scaled liquid chromatography, improvements of mass spectrometry resolution and sensitivity brought huge advancements. Enhancements in chemistry of chromatographic columns also brought interesting results. In the present work, the potency of identification of proteins by different nano-chip columns was studied and compared with classical LC column. The present study was applied to cardiovascular field where proteomics has shown to be highly helpful in research of new biomarkers. Protein extracts from atheroma plaques were used and proteomics data were compared. Results show that fewer spectra were acquired by the mass spectrometer when nano-chip columns were used instead of the classical ones. However, approximately 40% more unique peptides were identified by the recently optimized chip named Polaris-HR-chip-3C18 column, and 20% more proteins were identified. This fact leads to the identification of more low-abundance proteins. Many of them are involved in atheroma plaque development such as apolipoproteins, ceruloplasmin, etc. In conclusion, present data shows that recent developments of nanoLC column chemistry and dimensions enabled the improved detection and identification of low-abundance proteins in atheroma plaques. Several of them are of major interest in the field of cardiovascular disease. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Chromatography A 01/2015; 1385. DOI:10.1016/j.chroma.2015.01.038 · 4.26 Impact Factor
  • Critical Care 01/2015; 19(Suppl 1):P35. DOI:10.1186/cc14115 · 5.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cardiovascular disease linked to atherosclerosis is the leading cause of death worldwide. Atherosclerosis is mainly linked to dysfunction in vascular endothelial cells and subendothelial accumulation of oxidized forms of LDL. In the present study, we investigated the role of myeloperoxidase oxidized LDL (Mox-LDL) in endothelial cell dysfunction. We studied the effect of proinflammatory Mox-LDL treatment on endothelial cell motility, a parameter essential for normal vascular processes such as angiogenesis and blood vessel repair. This is particularly important in the context of an atheroma plaque, where vascular wall integrity is affected and interference with its repair could contribute to progression of the disease. We investigated in vitro the effect of Mox-LDL on endothelial cells angiogenic properties and we also studied the signalling pathways that could be affected by analysing Mox-LDL effect on the expression of angiogenesis-related genes. We report that Mox-LDL inhibits endothelial cell motility and tubulogenesis through an increase in miR-22 and heme oxygenase 1 expression. Our in vitro data indicate that Mox-LDL interferes with parameters associated with angiogenesis. They suggest that high LDL levels in patients would impair their endothelial cell capacity to cope with a damaged endothelium contributing negatively to the progression of the atheroma plaque.
    Mediators of Inflammation 11/2014; 2014:134635. DOI:10.1155/2014/134635 · 2.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this pilot study was to explore the risk of metabolic abnormalities in steel workers employed in different shift-work rotations. Male workers in a steel factory [16 employed in a fast clockwise rotation (CW), 18 in slow counterclockwise rotation (CC), 9 day workers (DW); mean age 43.3 ± SD 6.8 years] with at least 5 years experience in their current work schedule participated. All workers provided fasting blood samples between 06:00 and 08:00 h for plasma glucose, insulin, apo-lipoproteins A and B (ApoA, ApoB), high- and low-density lipoproteins (HDL and LDL), total cholesterol (tCH), triglycerides (TG), minimally oxidized (mox) LDL, C-reactive protein (CRP), interleukin-8 (IL-8) and serum 25-hydroxyvitamin D (25(OH)D). HOMA index (homeostatic model assessment) was calculated to evaluate insulin resistance, beta cell function and risk of diabetes. Information on demographics, health, stimulants, sleep, social and work life, chronotype (phase of entrainment) and social jetlag (difference between mid-sleep on workdays and free days) as a surrogate for circadian disruption was collected by questionnaire. Neither chronotype nor social jetlag was associated with any of the metabolic risk blood markers. There were no significant differences in 25(OH)D, ApoA, ApoB, CRP, HDL, IL-8, insulin, LDL, mox-LDL, mox-LDL/ApoB ratio, tCH and TG levels between the three work groups. Although we did observe absolute differences in some of these markers, the small sample size of our study population might prevent these differences being statistically significant. Fasting glucose and HOMA index were significantly lower in CW compared to DW and CC, indicating lower metabolic risk. Reasons for the lower fasting glucose and HOMA index in CW workers remains to be clarified. Future studies of workers in different shift rotations are warranted to understand better the differential effects of shift-work on individual workers and their health indices.
    Chronobiology International 09/2014; Sep 4:1-7.(10). DOI:10.3109/07420528.2014.957295 · 2.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Seeds and aerial parts of Peganum harmala L. (P. harmala) are widely used in Algeria as anti-inflammatory remedies. Evaluation of P. harmala total alkaloids extracts and pure β-carboline compounds as an anti-inflammatory treatment by the inhibition of an enzyme key of inflammatory, myeloperoxidase (MPO) and HPLC quantification of the alkaloids from the different parts of plant. MPO inhibition was tested using taurine chloramine test. The inhibition of LDL oxidation induced by MPO was carried out. The molecular docking analysis of P. harmala alkaloids on MPO was performed using the Glide XP docking protocol and scoring function and the redox potential of alkaloids was determined using an Epsilon potentiostat. The concentration of harmala alkaloids was determined using HPLC analysis. The HPLC profiling of theactive total alkaloids indicates that β-carboline e.g. harmine, harmaline, harmane, harmol and harmalol are major components. As β-carbolines resemble tryptamine, of which derivatives are efficient inhibitors of MPO, the harmala alkaloids were tested for their activity on this enzyme. Total alkaloids of the seeds and of the aerial parts strongly inhibited MPO at 20µg/ml (97±5 and 43±4%, respectively) whereas, at the same concentration, those of the roots showed very low inhibition (15±6%). Harmine, harmaline and harmane demonstrated a significant inhibition of MPO at IC50 of 0.26, 0.08 and 0.72µM respectively. These alkaloids exerted a similar inhibition effects on MPO-induced LDL oxidation. Molecular docking analysis of P. harmala alkaloids on MPO showed that all active P. harmala alkaloids have a high affinity on the active site of MPO (predicted free energies of binding up to -3.1kcal/mol). Measurement of redox potentials versus the normal hydrogen electrode clearly differentiated (i) the high MPO inhibitory activity of harmine, harmaline and harmane (+1014, 1014 and 1003mV, respectively); and (ii) the low activity of harmalol and harmol (+ 629/778 and 532/644mV, respectively).A reverse phase HPLC method has been developed to determine simultaneously five alkaloids of P. harmala. Seeds contained all five β-carboline derivatives with the main active alkaloids, harmaline and harmine, being up to 3.8 and 2.9%, respectively. Up to 3.2% of harmine was determined in the roots. The four β-carboline derivatives, harmine, harmaline, harmane and harmalol were identified in the aerial parts. The highest inhibitory effect observed in seeds and the moderate effect of aerial parts could be explained by their harmine and harmaline content. In contrast, the very weak inhibition of the root extract, despite the presence of harmine, may tentatively be explained by the high concentration of harmol which can reduce Compound II of MPO to the native form. The inhibition of MPO by P. harmala β-carboline alkaloids, herein reported for the first time, may explain the anti-inflammatory effect traditionally attributed to its herbal medicine.
    Journal of ethnopharmacology 04/2014; DOI:10.1016/j.jep.2014.03.070 · 2.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Oxidation of low-density lipoprotein (LDL) by myeloperoxidase (MPO)-H2O2-chloride system is a key event in the development of atherosclerosis. The present study aimed at investigating the interaction of MPO with native and modified LDL and at revealing post-translational modifications on apolipoprotein-B-100 (the unique apolipoprotein of LDL) in vitro and in vivo. Using amperometry we demonstrate that MPO activity increases up to 90% when it is adsorbed at the surface of LDL. This phenomenon is apparently reflected by local structural changes in MPO observed by circular dichroism. Using mass spectrometry we further analyzed in vitro modifications of apolipoprotein-B-100 by HOCl generated by the MPO-H2O2-chloride system or added as a reagent. A total of 97 peptides containing modified residues could be identified. Furthermore, differences were observed between LDL oxidized by reagent HOCl or HOCl generated by the MPO-H2O2-chloride system. Finally, LDL was isolated from patients with high cardiovascular risk to confirm that our in vitro findings are also relevant in vivo. We show that several of HOCl-mediated modifications of apolipoprotein-B-100 identified in vitro were also present on LDL isolated from patients who have increased levels of plasma MPO and MPO-modified LDL. In conclusion, these data emphasize the specificity of MPO to oxidize LDL.
    The Journal of Lipid Research 02/2014; DOI:10.1194/jlr.M047449 · 4.73 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Because propolis contains many types of antioxidant compounds such as polyphenols and flavonoids, it can be useful in preventing oxidative damages. Ethyl acetate extracts of propolis from several Algerian regions show high activity by scavenging free radicals, preventing lipid peroxidation and inhibiting myeloperoxidase (MPO). By fractioning and assaying ethyl acetate extracts, it was observed that both polyphenols and flavonoids contribute to these activities. A correlation was observed between the polyphenol content and the MPO inhibition. However, it seems that kaempferol, a flavonoid, contributes mainly to the MPO inhibition. This molecule is in a high amount in the ethyl acetate extract and demonstrates the best efficiency towards the enzyme with an inhibiting concentration at 50% of 4 ± 2 µM.
    International Journal of Molecular Sciences 02/2014; 15(2):2327-45. DOI:10.3390/ijms15022327 · 2.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT Objective Plasma and synovial myeloperoxidase (MPO) and its products were strongly associated with osteoarthritis (OA) and rheumatoid arthritis (RA). In addition, it is well known that there is a link between oxidative stress and cytokines. The present study aims at investigating the link between synovial MPO (and its products), IL-18, which is involved in the degradation of articular cartilage in RA, and IL-8, which is involved in recruitment and activation of neutrophils during inflammation. Effects of the treatment of RA on the biological parameters were also investigated. Methods Patients (n=105) were studied including 39 patients with OA, 33 with RA and 33 with RA receiving a specific treatment. DAS-28 was calculated whereas MPO antigen/activity, neutrophils, chloro-tyrosine, homocitrulline, IL-8 and IL-18 were measured in synovial fluid (SF) and CRP was measured in serum. Results DAS-28 and CRP level were not significantly different between groups. MPO activity, and MPO, chloro-tyrosine and homocitrulline levels were significantly higher in SF of RA patients than OA patients. MPO specific activity (MPO activity/antigen ratio) was significantly lower in treated than in untreated RA patients as was IL-8. MPO activity and concentration were correlated with IL-8 and IL-18 in untreated but not in treated RA patients. Conclusions MPO level is related to IL-8 and IL-18 levels in untreated RA patients. A link has been shown between treatment and decrease of IL-8, MPO specific activity and homocitrulline in SF. The causal role of MPO in SF inflammation and how treatment can affect MPO specific activity need further investigations.
    Free Radical Research 01/2014; DOI:10.3109/10715762.2014.886327 · 2.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Low-grade systemic inflammation was suggested to participate to the decline of physiological functions and increased vulnerability encountered in older patients. Geriatric syndromes encompass various features such as functional dependence, polymorbidity, depression and malnutrition. There is a strong prevalence of cardiovascular diseases and related risk factors and chronic cytomegalovirus infections in the geriatric population. As these underlying conditions were proposed to influence the inflammatory state, the aim of this study was to assess their potential contribution to the association of geriatric syndromes with inflammatory parameters. We recruited 100 subjects in the general population or hospitalized for chronic medical conditions (age, 23-96 years). We collected information on clinical status (medical history, ongoing comorbidities, treatments and geriatric scales), biological parameters (hematological tests, cytomegalovirus serology) and cytokines production (basal and alum-induced interleukin (IL)-1β and IL-6 levels). Using stepwise backward multivariate analyses, we defined which set of clinical and biological variables could be predictive for increased inflammatory markers. We confirmed the age-associated increase of circulating IL-6 levels. In contrast to geriatric scales, we found history of cardiovascular diseases to be strongly associated for this parameter as for high IL-6 production upon ex vivo stimulation with alum. Association between low-grade inflammation and geriatric conditions could be linked to underlying cardiovascular diseases.
    PLoS ONE 11/2013; 8(11):e81911. DOI:10.1371/journal.pone.0081911 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Infection is often difficult to recognize in critically ill patients because of the marked coexisting inflammatory process. Lack of early recognition prevents timely resuscitation and effective antimicrobial therapy, resulting in increased morbidity and mortality. Measurement of a biomarker, such as C-reactive protein (CRP) concentration, in addition to history and physical signs, could facilitate diagnosis. Although frequently measured in clinical practice, few studies have reported on the pathophysiological role of this biomarker and its predictive value in critically ill patients. In this review, we discuss the pathophysiological role of CRP and its potential interpretation in the inflammatory processes observed in critically ill patients.
    10/2013; 2013:124021. DOI:10.1155/2013/124021
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aging is associated with progressive alterations of immune functions, leading to higher susceptibility to bacterial and viral infections and reduced vaccine responses. Data concerning cytokine production in response to Toll-like receptor (TLR) ligands are highly variable in old people, reflecting the heterogeneity of the geriatric population. The aim of our study was to define the relative contribution of age and clinical status on TLR-induced interleukin (IL)-12p70 and IL-23 production as these cytokines play an important role in the protection against intracellular and extracellular pathogens, respectively. For this purpose, we recruited 100 subjects (aged 23-96 years) in the general population or hospitalized for chronic diseases. We collected information on clinical status (medical history, ongoing comorbidities, treatments and geriatric scales), biological parameters (biochemical and hematological tests, telomere length determination, cytomegalovirus serology). Whole blood samples were stimulated with a combination of TLR4 and TLR7/8 ligands. We performed univariate and stepwise backward multivariate analyses regression to define which set of clinical variables could be predictive for IL-12p70 and IL-23 production in these conditions. Our results indicated that age was not correlated with TLR-mediated IL-12p70 and IL-23 production. In contrast, poor nutritional status and frailty in subjects >75 years were associated with decreased IL-12p70 and IL-23 production. By intracytoplasmic staining, we confirmed that production of IL-12/23p40 by conventional dendritic cells (DCs) upon TLR ligation was decreased in frail patients. However, proportion of DCs and monocytes subsets, phenotypic maturation and proximal signaling events were found to be comparable in frail and healthy old subjects. These results suggest the importance of age-associated clinical parameters and not age by itself in the alteration of innate immune responses in old individuals and emphasis the importance of innate immune responses in the susceptibility of frail geriatric patients to infections.
    PLoS ONE 06/2013; 8(6):e65325. DOI:10.1371/journal.pone.0065325 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Due to its production of potent antimicrobial oxidants including hypochlorous acid, human myeloperoxidase (MPO) plays a critical role in innate immunity and inflammatory diseases. Thus MPO is an attractive target in drug design. Aminoalkyl-fluoroindole derivatives were detected to be very potent MPO inhibitors; however, they also promote inhibition of the serotonin reuptake transporter (SERT) at the same concentration range. Using structure-based drug design, a new series of MPO inhibitors derived from 3-alkylindole were synthesized and their effects were assessed on the MPO-mediated taurine chlorination and LDL oxidation as well as on inhibition of SERT. The fluoroindole compound with 3 carbons in the side chain and one amide group exhibited a selectivity index of 35 (Ki/IC50) with a high inhibition of MPO activity (IC50= 18 nM) whereas its effect on SERT was in the micromolar range. Structure-function relationships, mechanism of action and safety of the molecule were discussed in the manuscript.
    Journal of Medicinal Chemistry 04/2013; 56(10). DOI:10.1021/jm4001538 · 5.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Due to its production of potent antimicrobial oxidants including hypochlorous acid, human myeloperoxidase (MPO) plays a critical role in innate immunity and inflammatory diseases. Thus MPO is an attractive target in drug design. Aminoalkyl-fluoroindole derivatives were detected to be very potent MPO inhibitors; however, they also promote inhibition of the serotonin reuptake transporter (SERT) at the same concentration range. Using structure-based drug design, a new series of MPO inhibitors derived from 3-alkylindole were synthesized and their effects were assessed on the MPO-mediated taurine chlorination and LDL oxidation as well as on inhibition of SERT. The fluoroindole compound with 3 carbons in the side chain and one amide group exhibited a selectivity index of 35 (Ki/IC50) with a high inhibition of MPO activity (IC50= 18 nM) whereas its effect on SERT was in the micromolar range. Structure-function relationships, mechanism of action and safety of the molecule were discussed in the manuscrip
    Journal of Medicinal Chemistry 04/2013; · 5.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intermittent hypoxia (hypoxia-reoxygenation) is often associated with cardiovascular morbidity and mortality. We describe a new device which can be used to submit cohorts of mice to controlled and standardised hypoxia-normoxia cycles at an individual level. Mice were placed in individual compartments to which similar gas flow parameters were provided using an open loop strategy. Evaluations made using computational fluid dynamics were confirmed by studying changes in haemoglobin oxygen saturation in vivo. We also modified the parameters of the system and demonstrated its ability to generate different severities of cyclic hypoxemia very precisely, even with very high frequency cycles of hypoxia-reoxygenation. The importance of the parameters on reoxygenation was shown. This device will allow investigators to assess the effects of hypoxia–reoxygenation on different pathological conditions, such as obstructive sleep apnoea or chronic obstructive pulmonary disease.
    PLoS ONE 04/2013; 8(4):e59973. DOI:10.1371/journal.pone.0059973 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Over 90% of head and neck cancers are squamous cell carcinomas (HNSCC) and the overall 5-year survival rate is up to 50%. The redox status of these cancers is an important factor in carcinogenesis and plays a role in radioresistance and therefore locoregional recurrences. However, knowledge of the redox status is rather limited. Glutathione is the major reactive oxygen species scavenger in normal cells. We compared the levels of tissue redox potential in HNSCC tumor tissue and compared them with those of the adjacent, histologically cancer-free, mucosa. A total of 36 patients with HNSCC were included in the study. The redox status of tumor and normal adjacent tissue was measured by the oxidized/reduced glutathione (GSSG/GSH) ratio in capillary electrophoresis. The GSSG/GSH ratio in the tumor tissue was lower compared with adjacent normal tissue in 38% of the patients. Pretherapy HNSCC tumor tissue has variable GSH levels compared with adjacent cancer-free mucosa. This difference was not related to clinical and pathological parameters. Further studies are required to determine whether the GSSG/GSH ratio plays a role in carcinogenesis and could predict radioresistance.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 03/2013; 22(6). DOI:10.1097/CEJ.0b013e32836056dc · 2.76 Impact Factor
  • D. Dequanter, M. Shahla, K. Zouaoui Boudjeltia, P. Paulus, P. Lothaire
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Nous avons cherché à déterminer la nécessité du curage médiastinal supérieur (MS) et son importance pronostique en cas de carcinome épidermoïde (CE) avancé des voies aéro-digestives supérieures. Méthodes Une analyse rétrospective a été faite des dossiers de 31 patients ayant subi une (pharyngo-)laryngectomie pour un CE avancé. L’analyse statistique a recherché une corrélation entre la présence de métastases ganglionnaires MS et les facteurs cliniques ; le seuil de signification statistique retenu est p < 0,05. Résultats Des ganglions positifs ont été retrouvés chez 20 des patients, dont six avec des ganglions positifs uniquement au niveau du MS. Les ganglions positifs au niveau du MS n’ont été trouvés dans aucun des cas de CE laryngé, mais dans six des 13 cas d’atteinte hypopharyngée, et toujours associés aux tumeurs de plus de 35 mm. On observe une forte association entre la présence de métastases ganglionnaires et la localisation de la tumeur primitive (laryngée ou hypopharyngée), bien que celle-ci ne soit pas statistiquement significative (p = 0,08). Conclusions Dans cette série, les CE laryngés avancés n’ont jamais été associés à des ganglions positifs du MS, alors que les CE hypopharyngés avancés ont montré une tendance à impliquer les ganglions du MS.
    02/2013; 130(1):4–7. DOI:10.1016/j.aforl.2012.10.001

Publication Stats

1k Citations
544.49 Total Impact Points

Institutions

  • 2002–2015
    • Université Libre de Bruxelles
      • • Laboratory of Experimental Medicine (LME)
      • • Faculty of Medicine
      • • Laboratory of Experimental Medicine (LABOMEDEX)
      Bruxelles, Brussels Capital, Belgium
  • 2003–2013
    • University Hospital Brussels
      Bruxelles, Brussels Capital, Belgium
  • 2012
    • Centre Hospitalier Universitaire de Charleroi
      Charleroi, Walloon Region, Belgium
  • 2011
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain
  • 2009
    • Centre Hospitalier Universitaire Tivoli
      Louvierre, Walloon Region, Belgium
  • 2004–2009
    • Vrije Universiteit Brussel
      • Department of Intensive Care Medicine
      Bruxelles, Brussels Capital Region, Belgium
  • 2006
    • Université de Neuchâtel
      Neuenburg, Neuchâtel, Switzerland