References of "Cataldo, Didier"
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See detailExposure to Bacterial CpG DNA Protects from Airway Allergic Inflammation by Expanding Regulatory Lung Interstitial Macrophages.
Sabatel, Catherine ULg; Radermecker, Coraline ULg; Fievez, Laurence ULg et al

in Immunity (2017), 46(3), 457-473

Living in a microbe-rich environment reduces the risk of developing asthma. Exposure of humans or mice to unmethylated CpG DNA (CpG) from bacteria reproduces these protective effects, suggesting a major ... [more ▼]

Living in a microbe-rich environment reduces the risk of developing asthma. Exposure of humans or mice to unmethylated CpG DNA (CpG) from bacteria reproduces these protective effects, suggesting a major contribution of CpG to microbe-induced asthma resistance. However, how CpG confers protection remains elusive. We found that exposure to CpG expanded regulatory lung interstitial macrophages (IMs) from monocytes infiltrating the lung or mobilized from the spleen. Trafficking of IM precursors to the lung was independent of CCR2, a chemokine receptor required for monocyte mobilization from the bone marrow. Using a mouse model of allergic airway inflammation, we found that adoptive transfer of IMs isolated from CpG-treated mice recapitulated the protective effects of CpG when administered before allergen sensitization or challenge. IM-mediated protection was dependent on IL-10, given that Il10-/- CpG-induced IMs lacked regulatory effects. Thus, the expansion of regulatory lung IMs upon exposure to CpG might underlie the reduced risk of asthma development associated with a microbe-rich environment. [less ▲]

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See detailProtean proteases: at the cutting edge of lung diseases.
Taggart, Clifford; Mall, Marcus A.; Lalmanach, Gilles et al

in European Respiratory Journal (2017), 49(2),

Proteases were traditionally viewed as mere protein-degrading enzymes with a very restricted spectrum of substrates. A major expansion in protease research has uncovered a variety of novel substrates, and ... [more ▼]

Proteases were traditionally viewed as mere protein-degrading enzymes with a very restricted spectrum of substrates. A major expansion in protease research has uncovered a variety of novel substrates, and it is now evident that proteases are critical pleiotropic actors orchestrating pathophysiological processes. Recent findings evidenced that the net proteolytic activity also relies upon interconnections between different protease and protease inhibitor families in the protease web.In this review, we provide an overview of these novel concepts with a particular focus on pulmonary pathophysiology. We describe the emerging roles of several protease families including cysteine and serine proteases.The complexity of the protease web is exemplified in the light of multidimensional regulation of serine protease activity by matrix metalloproteases through cognate serine protease inhibitor processing. Finally, we will highlight how deregulated protease activity during pulmonary pathogenesis may be exploited for diagnosis/prognosis purposes, and utilised as a therapeutic tool using nanotechnologies.Considering proteases as part of an integrative biology perspective may pave the way for the development of new therapeutic targets to treat pulmonary diseases related to intrinsic protease deregulation. [less ▲]

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See detailA Belgian survey on the diagnosis of asthma-COPD overlap syndrome.
Cataldo, Didier ULg; Corhay, Jean-Louis ULg; Derom, Eric et al

in International Journal of Chronic Obstructive Pulmonary Disease (2017), 12

INTRODUCTION: Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma-COPD overlap syndrome (ACOS). Recommendations on their diagnosis are diffuse ... [more ▼]

INTRODUCTION: Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma-COPD overlap syndrome (ACOS). Recommendations on their diagnosis are diffuse and inconsistent. This survey aimed to identify consensus on criteria for diagnosing ACOS. METHODS: A Belgian expert panel developed a survey on ACOS diagnosis, which was completed by 87 pulmonologists. Answers chosen by >/=70% of survey respondents were considered as useful criteria for ACOS diagnosis. The two most frequently selected answers were considered as major criteria, others as minor criteria. The expert panel proposed a minimal requirement of two major criteria and one minor criterion for ACOS diagnosis. Respondents were also asked which criteria are important for considering inhaled corticosteroids prescription in a COPD patient. RESULTS: To diagnose ACOS in COPD patients, major criteria were "high degree of variability in airway obstruction over time (change in forced expiratory volume in 1 second >/=400 mL)" and "high degree of response to bronchodilators (>200 mL and >/=12% predicted above baseline)". Minor criteria were "personal/family history of atopy and/or IgE sensitivity to >/=1 airborne allergen", "elevated blood/sputum eosinophil levels and/or increased fractional exhaled nitric oxide", "diagnosis of asthma <40 years of age"; "symptom variability", and "age (in favor of asthma)". To diagnose ACOS in asthma patients, major criteria were "persistence of airflow obstruction over time (forced expiratory volume in 1 second/forced vital capacity ratio <0.7)" and "exposure to noxious particles/gases, with >/=10 pack-years for (ex-)smokers"; minor criteria were "lack of response on acute bronchodilator test"; "reduced diffusion capacity"; "limited variability in airway obstruction"; "age >40 years"; "emphysema on chest computed tomography scan". CONCLUSION: Specific criteria were identified that may guide physicians to a more uniform diagnostic approach for ACOS in COPD or asthma patients. These criteria are largely similar to those used to prescribe inhaled corticosteroids in COPD. [less ▲]

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See detailDry powder of budesonide/hydroxypropyl-beta-cyclodextrin complex for inhalation as a new potential antiasthmatic treatment
Bigazzi, William ULg; Dufour, Gilles; Mingeot-Leclercq, Marie-Paule et al

Conference (2016, October 17)

Asthma is a respiratory disease characterized by chronic airway inflammation which can lead, if not correctly managed, to tissue remodeling associated with an irreversible decline in lung function ... [more ▼]

Asthma is a respiratory disease characterized by chronic airway inflammation which can lead, if not correctly managed, to tissue remodeling associated with an irreversible decline in lung function. Hypersensitivity of the respiratory tract to non-specific stimuli, which causes triggering of asthma attacks, is also observed. Despite medical advances, asthma remains an important socio-economic and public health concern since this condition affects 300 million people and causes more than 300 000 deaths worldwide every year. Furthermore its annual cost is estimated at over 30 billion euros in Europe. These issues can be partially linked to an inadequate control of asthma due to undesirable effects of existing medication such as corticosteroids. Hence, the development of new medications with improved effectiveness and reduced adverse effects could allow a better management of the disease. It has been recently discovered that inhaled solution of hydroxylpropyl-beta-cyclodextrin (HPBCD) is able to reduce allergen-induced bronchoconstriction in asthmatic patients, with no toxicity observed in healthy patients further to administration. Based on these results, our project seeks to develop new antiasthmatic medication containing an association of HPBCD and budesonide, a widely used corticosteroid in long-term treatment of asthma. Thus, we investigated complexation between the two molecules. Interestingly, it was observed that when budesonide is complexed with HPBCD, its permeability across a Calu-3 cell layer is reduced. Several experiments in mouse models confirmed that HPBCD acts as a sustained delivery system which progressively releases budesonide into the lung parenchyma, leading to a prolonged anti-inflammatory effect. Due to high Peclet number of HPBCD, the spray dried complex exhibited wrinkled particles whose interest in dry powder for inhalation is well known. Thanks to its anti-inflammatory effect and its sustained release potential, HPBCD could significantly reduce corticosteroids needed doses for management of asthma. However, a clinical study has to be performed to determine the optimal budesonide/HPBCD ratio and the minimal effective dose of complex. Further investigations are also needed to exploit the potential of spray dried HPBCD and develop a powder for inhalation by particle engineering. [less ▲]

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See detailADAMTS3 activity is mandatory for embryonic lymphangiogenesis and regulates placental angiogenesis.
Dupont, Laura ULg; Janssen, Lauriane; Bekhouche, Mourad et al

Conference (2016, June)

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See detailStimulated release and functional activity of surface expressed metalloproteinase ADAM17 in exosomes.
Groth, Esther; Pruessmeyer, Jessica; Babendreyer, Aaron et al

in Biochimica et Biophysica Acta (2016), 1863(11), 2795-2808

By mediating proteolytic shedding on the cell surface the disintegrin and metalloproteinases ADAM10 and ADAM17 function as critical regulators of growth factors, cytokines and adhesion molecules. We here ... [more ▼]

By mediating proteolytic shedding on the cell surface the disintegrin and metalloproteinases ADAM10 and ADAM17 function as critical regulators of growth factors, cytokines and adhesion molecules. We here report that stimulation of lung epithelial A549 tumor cells with phorbol-12-myristate-13-acetate (PMA) leads to the downregulation of the surface expressed mature form of ADAM17 without affecting ADAM10 expression. This reduction could not be sufficiently explained by metalloproteinase-mediated degradation, dynamin-mediated internalization or microdomain redistribution of ADAM17. Instead, surface downregulation of ADAM17 was correlated with the presence of its mature form in exosomes. Exosomal ADAM17 release was also observed in monocytic and primary endothelial cells where it could be induced by stimulation with lipopolysaccharide. Antibody-mediated surface labelling of ADAM17 revealed that at least part of exosomal ADAM17 was oriented with the metalloproteinase domain outside and had been expressed on the cell surface. Suppression of iRHOM2-mediated ADAM17 maturation prevented surface expression and exosomal release of ADAM17. Further, deletion of the protease's C-terminus or cell treatment with a calcium chelator diminished exosomal release as well as surface downregulation of ADAM17, underlining that both processes are closely associated. Co-incubation of ADAM17 containing exosomes with cells expressing the ADAM17 substrates TGFalpha or amphiregulin lead to increased shedding of both substrates. This was prevented when exosomes were prepared from cells with shRNA-mediated ADAM17 knockdown. These data indicate that cell stimulation can downregulate expression of mature ADAM17 from the cell surface and induce release of exosomal ADAM17, which can then distribute and contribute to substrate shedding on more distant cells. [less ▲]

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See detail[18F]FPRGD2 PET/CT imaging of integrin αvβ3 levels in patients with locally advanced rectal carcinoma
WITHOFS, Nadia ULg; Martinive, Philippe ULg; VANDERICK, Jean ULg et al

in European journal of nuclear medicine and molecular imaging (2016)

PURPOSE: Our primary objective was to determine if [18F]FPRGD2 PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal ... [more ▼]

PURPOSE: Our primary objective was to determine if [18F]FPRGD2 PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal cancer (LARC). Secondary objectives were to compare baseline [18F]FPRGD2 and [18F]FDG uptake, to evaluate the correlation between posttreatment [18F]FPRGD2 uptake and tumour microvessel density (MVD) and to determine if [18F]FPRGD2 and FDG PET/CT could predict disease-free survival. METHODS: Baseline [18F]FPRGD2 and FDG PET/CT were performed in 32 consecutive patients (23 men, 9 women; mean age 63 +/- 8 years) with LARC before starting any therapy. A posttreatment [18F]FPRGD2 PET/CT scan was performed in 24 patients after the end of CRT (median interval 7 weeks, range 3 - 15 weeks) and before surgery (median interval 4 days, range 1 - 15 days). RESULTS: All LARC showed uptake of both [18F]FPRGD2 (SUVmax 5.4 +/- 1.5, range 2.7 - 9) and FDG (SUVmax 16.5 +/- 8, range 7.1 - 36.5). There was a moderate positive correlation between [18F]FPRGD2 and FDG SUVmax (Pearson's r = 0.49, p = 0.0026). There was a moderate negative correlation between baseline [18F]FPRGD2 SUVmax and the TRG (Spearman's r = -0.37, p = 0.037), and a [18F]FPRGD2 SUVmax of >5.6 identified all patients with a complete response (TRG 0; AUC 0.84, 95 % CI 0.68 - 1, p = 0.029). In the 24 patients who underwent a posttreatment [18F]FPRGD2 PET/CT scan the response index, calculated as [(SUVmax1 - SUVmax2)/SUVmax1] x 100 %, was not associated with TRG. Post-treatment [18F]FPRGD2 uptake was not correlated with tumour MVD. Neither [18F]FPRGD2 nor FDG uptake predicted disease-free survival. CONCLUSION: Baseline [18F]FPRGD2 uptake was correlated with the pathological response in patients with LARC treated with CRT. However, the specificity was too low to consider its clinical routine use. [less ▲]

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See detailImplication of adamalysin proteases in mesothelioma
Sepult, Christelle ULg; Rocks, Natacha ULg; Bekaert, Sandrine et al

Conference (2015, September 30)

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See detailInvolvement of adamalysin proteases in modulations of tumor microenvironment and premetastatic niches
Donati, Kim ULg; Bekaert, Sandrine; Sepult, Christelle ULg et al

in European Respiratory Journal (2015, September), 46(59),

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See detailInvolvement of adamalysin proteases in modulations of tumor microenvironment and premetastatic niches.
Donati, Kim ULg; Bekaert, Sandrine; Sepult, Christelle ULg et al

Poster (2015, September)

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See detailMethod for increasing the bioavailability of inhaled compounds
Vanbever, Rita; Koussoroplis, Salomé; Cataldo, Didier ULg et al

Patent (2015)

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