References of "Malaise, Michel"
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See detailCEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes
DEROYER, Céline ULiege; CHARLIER, Edith ULiege; NEUVILLE, Sophie ULiege et al

in Cell Death and Disease (2019)

CEMIP (for “Cell migration-inducing protein” also called KIAA1199 and Hybid for “Hyaluronan-binding protein”) expression is increased in cancers and described as a regulator of cell survival, growth and ... [more ▼]

CEMIP (for “Cell migration-inducing protein” also called KIAA1199 and Hybid for “Hyaluronan-binding protein”) expression is increased in cancers and described as a regulator of cell survival, growth and invasion. In rheumatoid arthritis, CEMIP is referred to as an angiogenic marker and participates in hyaluronic acid degradation. In this study, CEMIP expression is investigated in healthy and osteoarthritis (OA) cartilage from human and mouse. Its role in OA physiopathology is deciphered, specifically in chondrocytes proliferation and dedifferentiation and in the extracellular matrix remodeling. To this end, CEMIP, αSMA and types I and III collagen expressions were assessed in human OA and non-OA cartilage. CEMIP expression was also investigated in a mouse OA model. CEMIP expression was studied in vitro using a chondrocyte dedifferentiation model. High-throughput RNA sequencing was performed on chondrocytes after CEMIP silencing. Results showed that CEMIP was overexpressed in human and murine OA cartilage and along chondrocytes dedifferentiation. Most of genes deregulated in CEMIP-depleted cells were involved in cartilage turnover (e.g., collagens), mesenchymal transition and fibrosis. CEMIP regulated β-catenin protein level. Moreover, CEMIP was essential for chondrocytes proliferation and promoted αSMA expression, a fibrosis marker, and TGFβ signaling towards the p-Smad2/3 (Alk5/PAI-1) pathway. Interestingly, CEMIP was induced by the pSmad1/5 (Alk1) pathway. αSMA and type III collagen expressions were overexpressed in human OA cartilage and along chondrocytes dedifferentiation. Finally, CEMIP was co-expressed in situ with αSMA in all OA cartilage layers. In conclusion, CEMIP was sharply overexpressed in human and mouse OA cartilage and along chondrocytes dedifferentiation. CEMIP-regulated transdifferentiation of chondrocytes into “chondro-myo-fibroblasts” expressing α-SMA and type III collagen, two fibrosis markers. Moreover, these “chondro-myo-fibroblasts” were found in OA cartilage but not in healthy cartilage. [less ▲]

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See detailEFFICACY OF BIO-OPTIMISED CURCUMA EXTRACT (FLEXOFYTOL®) FOR PAINFUL KNEE OSTEOARTHRITIS: DATA FROM COPRA, A MULTICENTER RANDOMISED CONTROLLED STUDY
Henrotin, Yves ULiege; Malaise, Michel ULiege; Wittoek, R et al

in Annals of the Rheumatic Diseases (2018, June), 77(supplement 2), 790

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See detailHYALURONAN DERIVATIVE HYMOVIS® INCREASES CARTILAGE VOLUME AND TYPE II COLLAGEN TURNOVER IN OSTEOARHRITIC KNEE: DATA FROM MOKHA STUDY
Henrotin, Yves ULiege; Bannuru, R; Malaise, Michel ULiege et al

in Annals of the Rheumatic Diseases (2018, June), 77(supplement 2), 1614

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See detailSerum starvation raises turnover of phosphorylated p62/SQSTM1 (Serine 349), reveals expression of proteasome and N-glycanase1 interactive protein RAD23B and sensitizes human synovial fibroblasts to BAY 11-7085-induced cell death.
RELIC, Biserka ULiege; CHARLIER, Anne ULiege; DEROYER, Céline ULiege et al

in Oncotarget (2018), 9(88), 35830-35843

Phosphorylation of p62/SQSTM1 (p62) on Serine 349 (P-Ser349 p62) as well as proteasome dysfunction have been shown to activate the cell protective Keap1/Nrf2 pathway. We showed previously that BAY 11-7085 ... [more ▼]

Phosphorylation of p62/SQSTM1 (p62) on Serine 349 (P-Ser349 p62) as well as proteasome dysfunction have been shown to activate the cell protective Keap1/Nrf2 pathway. We showed previously that BAY 11-7085-induced human synovial fibroblast cell death includes autophagy and p62 downregulation. In this work, we have studied expression of P-Ser349 p62 in human synovial fibroblasts. Results showed that P-Ser349 p62 was not detected in synovial cell extracts unless cells were cultured in the presence of proteasome inhibitor (MG132). MG132 revealed P-Ser349 p62 turnover, that was further increased by concomitant autophagy inhibition and markedly enhanced in serum starved cells. Starvation sensitized synovial fibroblasts to BAY 11-7085 while MG132 protected both non-starved and starved cells from BAY 11-7085-induced cell death. Lentivirus mediated overexpression of phosphorylation-mimetic p62 mutant S349E markedly protected synovial fibroblasts from BAY 11-7085. Inhibitor of Keap1-P-S349 p62 interaction, K67, had synergistic effect with MG132. Starvation increased p62 molecular weight, that was reversed by serum and bovine serum albumin re-feeding. Furthermore, starvation markedly induced RAD23B. Increased endo-beta-N-acetylglucosaminidase (ENGase) turnover was detected in starved synovial fibroblasts. PNGase F treatment produced faster migration p62 form in human synovial tissue extracts but starvation-like p62 form of higher molecular weight in synovial cell extracts. Co-transfection of NGLY1, with p62 or p62 mutants S349A and S349E markedly stabilized p62 expressions in HEK293 cells. Tunicamycin upregulated p62 and protected synovial fibroblasts from BAY 11-7085-induced cell death. These results showed that P-Ser349 p62 has pro-survival role in human synovial fibroblasts and that de-glycosylation events are involved in p62 turnover. [less ▲]

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See detailInefficacy of autologous bone marrow concentrate in stage three osteonecrosis: a randomized controlled double-blind trial
HAUZEUR, Jean-Philippe ULiege; De Maertelaer, Viviane ; BAUDOUX, Etienne ULiege et al

in International Orthopaedics (2018), 42

Purpose The fracture stage of non-traumatic osteonecrosis (ON stage 3) of the femoral head (ONFH) has an unfavourable prognosis frequently requiring total hip replacement (THR). The percentage could be ... [more ▼]

Purpose The fracture stage of non-traumatic osteonecrosis (ON stage 3) of the femoral head (ONFH) has an unfavourable prognosis frequently requiring total hip replacement (THR). The percentage could be lowered after core decompression. In earlier non-fracture ON stages, implantation of autologous bone marrow aspirate concentrate (BMAC) improved the effect of core decompression. The purpose was to evaluate the effect of BMAC in addition to core decompression in stage 3 ONFH. Methods A double blind RCT was conducted comparing two groups: core decompression plus saline injection or core decompression plus BMAC implantation. Both patients and assessors were blinded to the treatment assignments. Evaluations were done at baseline, three, six, 12, and 24 months, including pain (VAS), WOMAC, side-effects, radiological evolution including ARCO subclassifications, together with possible THR requirement. The primary endpoint was the need for THR. The second endpoints included the clinical symptoms such as pain and functional ability and the progression of the ON lesions as well as the appearance of osteoarthritis features (ARCO stage 4). Both groups included 23 hips (19 patients). Results No differences were found between the groups for THR requirements, clinical tests, and radiological evolution. In both groups, 15/23 hips needed THR. The radiological evolution of the ONFH lesions in term of location, extension, surface collapse, and dome depression was moderate in both groups and was not correlated with the need of THR. Conclusions Implantation of BMAC after core decompression did not produce any improvement of the evolution of ONFH stage 3. [less ▲]

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See detail(18)F- FDG PET/CT joint assessment of early therapeutic response in rheumatoid arthritis patients treated with rituximab.
Fosse, Pacome; KAISER, Marie-Joëlle ULiege; Namur, Gauthier et al

in European Journal of Hybrid Imaging (2018), 2(1), 6

Background: (18)F-FDG PET/CT has been proposed in the evaluation of the disease activity in rheumatoid arthritis (RA). The goals of this study were to evaluate the reproducibility of the technique, to ... [more ▼]

Background: (18)F-FDG PET/CT has been proposed in the evaluation of the disease activity in rheumatoid arthritis (RA). The goals of this study were to evaluate the reproducibility of the technique, to compare metabolic parameters to clinical, biological and ultrasonographic parameters before and after treatment and to evaluate whether the early metabolic response was related to the outcome. (18)F- FDG PET/CT of the hands, wrists and knees was obtained in 15 patients with anti-TNFalpha refractory RA, at baseline and 16 weeks after treatment with rituximab. The number of PET-positive joints (PET+ joints), the cumulative standard uptake value (cSUV) and the composite index (CI) were defined. The composite clinical index DAS28, CRP serum levels and the number of joints positive at ultrasonography (US+ joints) and the cumulative synovial thickness (CST) were also assessed at baseline and week 24. Results: High interobserver agreement was observed, both at baseline and after treatment. The number of PET+ joints was not correlated with the number of joints tender or swollen. The 3 metabolic parameters were strongly correlated with US, CRP and DAS28 at baseline and with US and CRP (CSUV, CI) at week 16, but no longer with the DAS28 index. The metabolic response based on the change in the visual PET/CT joint analysis predicted the outcome with a high negative predictive value of 91%, with a 91% specificity, and an 86% accuracy. Conclusions: These preliminary data suggest that (18)F- FDG PET/CT is a reproducible and accurate tool for evaluating disease activity in refractory rheumatoid arthritis and its non-response to rituximab. The correlation obtained with US joint assessment gives relevance to objective diseased joints through imaging techniques. [less ▲]

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See detailOLFM4, KNG1 and Sec24C identified by proteomics and immunohistochemistry as potential markers of early colorectal cancer stages
QUESADA-CALVO, Florence ULiege; MASSOT, Charlotte ULiege; Bertrand, Virginie ULiege et al

in Clinical Proteomics (2017), 24(9),

Abstract Background: Despite recent advances in colorectal cancer (CRC) diagnosis and population screening programs, the identification of patients with preneoplastic lesions or with early CRC stages ... [more ▼]

Abstract Background: Despite recent advances in colorectal cancer (CRC) diagnosis and population screening programs, the identification of patients with preneoplastic lesions or with early CRC stages remains challenging and is important for reducing CRC incidence and increasing patient’s survival. Methods: We analysed 76 colorectal tissue samples originated from early CRC stages, normal or inflamed mucosa by label-free proteomics. The characterisation of three selected biomarker candidates was performed by immunohisto‑ chemistry on an independent set of precancerous and cancerous lesions harbouring increasing CRC stages. Results: Out of 5258 proteins identified, we obtained 561 proteins with a significant differential distribution among groups of patients and controls. KNG1, OLFM4 and Sec24C distributions were validated in tissues and showed differ‑ ent expression levels especially in the two early CRC stages compared to normal and preneoplastic tissues. Conclusion: We highlighted three proteins that require further investigations to better characterise their role in early CRC carcinogenesis and their potential as early CRC markers. [less ▲]

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See detailProteomic differential distribution of 53BP1 in serrated and conventional adenomas validated by histological characterisation
QUESADA-CALVO, Florence ULiege; Merli, Angela-Maria ULiege; MASSOT, Charlotte ULiege et al

Poster (2017, February 10)

INTRODUCTION: Sessile serrated adenoma/polyp (SSA/p) is a precancerous lesion, mostly located in the right side of the colon (cecum, ascending and transverse colon). The difficulty is to visualize this ... [more ▼]

INTRODUCTION: Sessile serrated adenoma/polyp (SSA/p) is a precancerous lesion, mostly located in the right side of the colon (cecum, ascending and transverse colon). The difficulty is to visualize this lesion during colonoscopy because of its subtle appearance. MATERIAL AND METHOD: We compared proteomes of serrated polyps (SSA/p) and conventional adenomas using residual human formalin fixed paraffin embedded (FFPE) samples. FFPE-FASP method was applied on samples before label free proteomic analysis. Immunohistochemistry (IHC) characterisation of one candidate marker was performed for tissue validation on an independent set of samples including: conventional adenomas (low and high-grade dysplasia), serrated polyps (hyperplastic polyps, SSA/p and traditional serrated adenoma) and finally normal colon (taken at the margin of colorectal cancer (CRC) or of diverticular disease). RESULTS: Proteomics provided 765 proteins (out of 5992 proteins identified) significantly discriminating conventional adenomas from serrated lesions. We selected 53BP1 (Tumor suppressor p53-binding protein 1) among these for IHC validation, because of its tumor suppressor gene function and role as a mediator of DNA damage checkpoint. 53BP1 appeared significantly up-regulated in proteomes of low and high grade adenomas compared to these of normal tissue and SSA/p. 53BP1 IHC signal was located in the nucleus and the percentage of positive nucleus decreased in serrated polyps, especially in crypts and in the border epithelium, confirming part of the proteomic results. CONCLUSION: This study highlights potential marker proteins, including 53BP1 from which IHC signal was strongly decreased in some serrated polyps. The loss of 53BP1 has been associated with tumour progression and poor prognosis, while little is currently known about its involvement in precancerous CRC lesions. 53BP1 decrease of expression in the nucleus and therefore possible loss of function in some epithelial cells could reflect important changes occurring during dysplasia to neoplasia progression in serrated lesions. [less ▲]

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See detailIdentification of proteins discriminating inflammation induced dysplasia from simple inflammation in ulcerative colitis by laser capture microdissection and label free proteomics – a pilot study
Merli, Angela-Maria ULiege; QUESADA-CALVO, Florence ULiege; MASSOT, Charlotte ULiege et al

Conference (2017, February 09)

Chronic colonic inflammation in ulcerative colitis (UC) may induce dysplasia, which can itself progress and transform into neoplasia. Diagnosis of dysplasia in UC remains difficult particularly when ... [more ▼]

Chronic colonic inflammation in ulcerative colitis (UC) may induce dysplasia, which can itself progress and transform into neoplasia. Diagnosis of dysplasia in UC remains difficult particularly when tissue inflammation is present. The aim of this retrospective pilot study was to highlight proteins specifically associated with inflammation induced dysplasia in UC. We performed a pilot experiment on 15 Formalin-Fixed, Paraffin-Embedded (FFPE) samples isolated from 5 cases of UC patients with a Polypoïd Pedunculated dysplasia (UC-PP). We compared the proteomes of the UC-PP, the inflammatory (UC-I) and the normal (UC-NL) tissues of each patient. We performed Laser Capture Microdissection (LCM) in order to collect only epithelial cells, avoiding inflammatory infiltrating ones. Label free proteomic analysis using a 2D-nanoUPLC coupled with a hybrid Quadrupole-Orbitrap was applied, as well as differential analysis on the paired samples. Immunohistochemistry (IHC) characterisation of one of the selected proteins of interest was used for validation. Out of 985 quantified proteins, 7 were found significantly more abundant in UC-PP compared to UC-I tissues, with 6 being only detected in UC-PP using proteomics. One of these is Solute Carrier Family 12 member 2 (SLC12A2), also known as Na-K-2Cl co-transporter 1 (NKCC1), a protein involved in ionic balance, in T-cell migration promotion and in some features involved in cancer development like proliferation, migration or invasion. IHC results obtained were in correlation with proteomic results and showed that SLC12A2 was more abundant in UC-PP tissue than in UC-I and UC-NL tissues, with a signal clearly delimiting the dysplastic region from the surrounding inflammatory tissue. This pilot experiment shows a different proteomic profile in inflammation-associated dysplasia and simple inflammation. This should be replicated using other types of dysplasia in IBD. SLC12A2 could be a potential biomarker of inflammation-associated dysplasia. [less ▲]

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See detailIdentification of proteins discriminating inflammation induced dysplasia from simple inflammation in ulcerative colitis by laser capture microdissection and label free proteomics – a pilot study
Merli, Angela-Maria ULiege; QUESADA-CALVO, Florence ULiege; MASSOT, Charlotte ULiege et al

Poster (2017, February 01)

Chronic colonic inflammation in ulcerative colitis (UC) may induce dysplasia, which can itself progress and transform into neoplasia. Diagnosis of dysplasia in UC remains difficult particularly when ... [more ▼]

Chronic colonic inflammation in ulcerative colitis (UC) may induce dysplasia, which can itself progress and transform into neoplasia. Diagnosis of dysplasia in UC remains difficult particularly when tissue inflammation is present. The aim of this retrospective pilot study was to highlight proteins specifically associated with inflammation induced dysplasia in UC. We performed a pilot experiment on 15 Formalin-Fixed, Paraffin-Embedded (FFPE) samples isolated from 5 cases of UC patients with a Polypoïd Pedunculated dysplasia (UC-PP). We compared the proteomes of the UC-PP, the inflammatory (UC-I) and the normal (UC-NL) tissues of each patient. We performed Laser Capture Microdissection (LCM) in order to collect only epithelial cells, avoiding inflammatory infiltrating ones. Label free proteomic analysis using a 2D-nanoUPLC coupled with a hybrid Quadrupole-Orbitrap was applied, as well as differential analysis on the paired samples. Immunohistochemistry (IHC) characterisation of one of the selected proteins of interest was used for validation. Out of 985 quantified proteins, 7 were found significantly more abundant in UC-PP compared to UC-I tissues, with 6 being only detected in UC-PP using proteomics. One of these is Solute Carrier Family 12 member 2 (SLC12A2), also known as Na-K-2Cl co-transporter 1 (NKCC1), a protein involved in ionic balance, in T-cell migration promotion and in some features involved in cancer development like proliferation, migration or invasion. IHC results obtained were in correlation with proteomic results and showed that SLC12A2 was more abundant in UC-PP tissue than in UC-I and UC-NL tissues, with a signal clearly delimiting the dysplastic region from the surrounding inflammatory tissue. This pilot experiment shows a different proteomic profile in inflammation-associated dysplasia and simple inflammation. This should be replicated using other types of dysplasia in IBD. SLC12A2 could be a potential biomarker of inflammation-associated dysplasia. [less ▲]

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See detailValidation of a new method by nano-liquid chromatography on chip tandem mass spectrometry for combined quantitation of C3f and the V65 vitronectin fragment as biomarkers of diagnosis and severity of osteoarthritis.
Cobraiville, Gael; Fillet, Marianne ULiege; Sharif, Mohammed et al

in Talanta (2017), 169

Microfluidic liquid chromatography coupled to a nanoelectrospray source ion trap mass spectrometry was used for the absolute and simultaneous quantitation of C3f and the V65 vitronectin fragment in serum ... [more ▼]

Microfluidic liquid chromatography coupled to a nanoelectrospray source ion trap mass spectrometry was used for the absolute and simultaneous quantitation of C3f and the V65 vitronectin fragment in serum. The method was first carefully optimized and then validated in serum biological matrix. Stable isotopes for the two biomarkers of interest were used as stable isotope labeled peptide standards. A weighted 1/x2 quadratic regression for C3f and a weighted 1/x quadratic regression for the V65 vitronectin peptide were selected for calibration curves. Trueness (with a relative bias <10%), precision (repeatability and intermediate precision <15%) and accuracy (risk <15%) of the method were successfully demonstrated. The linearity of results was validated in the concentration range of 2.5-200ng/mL for C3f and 2.5-100ng/mL for the V65 vitronectin fragment. Serum samples (n=147) classified in 7 groups [(healthy volunteers, OA with 5 grades of severity and rheumatoid arthritis (RA) patients] were analyzed with our new quantitative method. Our data confirm that C3f and the V65 vitronectin fragment are biomarkers of OA severity, but also that C3f fragment is further related to OA severity whereas the V65 vitronectin fragment is more related to early OA detection. [less ▲]

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See detailInsights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis
CHARLIER, Edith ULiege; RELIC, Biserka ULiege; Deroyer, Céline ULiege et al

in International Journal of Molecular Sciences (2016)

Abstract: Osteoarthritis (OA) is a joint pathology characterized by progressive cartilage degradation. Medical care is mainly based on alleviating pain symptoms. Compelling studies report the presence of ... [more ▼]

Abstract: Osteoarthritis (OA) is a joint pathology characterized by progressive cartilage degradation. Medical care is mainly based on alleviating pain symptoms. Compelling studies report the presence of empty lacunae and hypocellularity in cartilage with aging and OA progression, suggesting that chondrocyte cell death occurs and participates to OA development. However, the relative contribution of apoptosis per se in OA pathogenesis appears complex to evaluate. Indeed, depending on technical approaches, OA stages, cartilage layers, animal models, as well as in vivo or in vitro experiments, the percentage of apoptosis and cell death types can vary. Apoptosis, chondroptosis, necrosis, and autophagic cell death are described in this review. The question of cell death causality in OA progression is also addressed, as well as the molecular pathways leading to cell death in response to the following inducers: Fas, Interleukin-1 (IL-1 ), Tumor Necrosis factor- (TNF- ), leptin, nitric oxide (NO) donors, and mechanical stresses. Furthermore, the protective role of autophagy in chondrocytes is highlighted, as well as its decline during OA progression, enhancing chondrocyte cell death; the transition being mainly controlled by HIF-1 /HIF-2 imbalance. Finally, we have considered whether interfering in chondrocyte apoptosis or promoting autophagy could constitute therapeutic strategies to impede OA progression. [less ▲]

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See detailOstéoblastes autologues (PREOB®) versus concentré de moelle autologue dans l’ostéonécrose de la tête fémorale : étude randomisée
HAUZEUR, Jean-Philippe ULiege; Tungouz, Michel; LECHANTEUR, Chantal ULiege et al

in Revue de Chirurgie Orthopédique et Traumatologie (2016, October), 102

In non-traumatic osteonecrosis of the femoral head (ONFH), implantation of bone marrow concentrate (BMC) containing mesenchymal stem cells (MSC) could delay ONFH progression and improve symptoms (Hernigou ... [more ▼]

In non-traumatic osteonecrosis of the femoral head (ONFH), implantation of bone marrow concentrate (BMC) containing mesenchymal stem cells (MSC) could delay ONFH progression and improve symptoms (Hernigou 2002, Gangji 2004). The next step was to assess the hypothesis that a population of autologous osteoblastic cells (OB) consisting in a more differentiated cell than MSC, could be more efficacious than BMC in early stages ON. [less ▲]

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See detailBiomarkers of inflammation and innate immunity in atrophic nonunion fracture
DE SENY, Dominique ULiege; COBRAIVILLE, Gaël ULiege; Leprince, Pierre ULiege et al

in Journal of Translational Medicine (2016)

Detailed reference viewed: 50 (8 ULiège)