References of "Bours, Vincent"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailCLEC-2 is required for the activation of mouseplatelets by bacterial DNA mimetics
Delierneux, Céline ULg; Hego, Alexandre ULg; LECUT, Christelle ULg et al

Conference (2015, June 22)

Background: Short nuclease-resistant phosphorothioate synthetic CpG motif-bearing oligonucleotides (CpG ODNs) mimicking bacterial DNA display potent immunostimulatory activity and are therefore being used ... [more ▼]

Background: Short nuclease-resistant phosphorothioate synthetic CpG motif-bearing oligonucleotides (CpG ODNs) mimicking bacterial DNA display potent immunostimulatory activity and are therefore being used in clinical trials as vaccine adjuvants. Cellular uptake and activation depends on the interaction of CpG ODNs with the C-type lectin receptor DEC-205 and subsequent stimulation of the Toll-like receptor 9 (TLR9) and myeloid differentiation primary response 88 (MyD88) signaling cascade. Platelets express TLR9, MyD88, and the C-type lectin-like receptor 2 (CLEC-2). However, the impacts of CpG ODNs on platelet function have been elusive. Aims: To evaluate whether CpG ODNs affect platelet activation and thrombus formation via CLEC-2 and TLR9. Methods: We incubated washed platelets or whole blood from TLR9-, MyD88- or CLEC-2- deficient mice with CpG ODNs. We performed platelet aggregometry, flow cytometric binding and platelet activation assays as well as signal transduction analyses. Thrombus formation and fibrin generation were also analyzed by intravital microscopy in mouse microcirculation upon intravenous injection of CpG ODNs. Results: We show that CpG ODNs bind on platelet surface and are internalized. They activate platelets and induce their aggregation. TLR9- or MyD88-deficient platelets aggregated normally in response to CpG ODN. Interestingly, platelets deficient for the C-type lectin receptor CLEC-2 were unable to capture and internalize CpG ODN. CLEC-2 deficiencyabolished CpG ODN-induced platelet activation and aggregation. CpG ODN stimulated CLEC-2 dependent tyrosine kinase pathway and Syk phosphorylation. In vivo, intravenously injected CpG ODN interacted with platelets adhered to laser injured arteriolar endothelia and promoted fibrin generation and thrombus growth. Conclusion: CLEC-2 mediates CpG ODN uptake and subsequent platelet activation, independently of TLR9, which may serve an important role in the interplay between platelets and immunity. [less ▲]

Detailed reference viewed: 11 (0 ULg)
Full Text
Peer Reviewed
See detailCLEC-2 is required for the activation of mouse platelets by bacterial DNA mimetics
Delierneux, Céline ULg; Hego, Alexandre ULg; LECUT, Christelle ULg et al

Conference (2015, June 22)

Aims: To evaluate whether CpG ODNs affect platelet activation and thrombus formation via CLEC-2 and TLR9. Methods: We incubated washed platelets or whole blood from TLR9-, MyD88- or CLEC-2- deficient mice ... [more ▼]

Aims: To evaluate whether CpG ODNs affect platelet activation and thrombus formation via CLEC-2 and TLR9. Methods: We incubated washed platelets or whole blood from TLR9-, MyD88- or CLEC-2- deficient mice with CpG ODNs. We performed platelet aggregometry, flow cytometric binding and platelet activation assays as well as signal transduction analyses. Thrombus formation and fibrin generation were also analyzed by intravital microscopy in mouse microcirculation upon intravenous injection of CpG ODNs. Results: We show that CpG ODNs bind on platelet surface and are internalized. They activate platelets and induce their aggregation. TLR9- or MyD88-deficient platelets aggregated normally in response to CpG ODN. Interestingly, platelets deficient for the C-type lectin receptor CLEC-2 were unable to capture and internalize CpG ODN. CLEC-2 deficiency abolished CpG ODN-induced platelet activation and aggregation. CpG ODN stimulated CLEC-2 dependent tyrosine kinase pathway and Syk phosphorylation. In vivo, intravenously injected CpG ODN interacted with platelets adhered to laser injured arteriolar endothelia and promoted fibrin generation and thrombus growth. Conclusion: CLEC-2 mediates CpG ODN uptake and subsequent platelet activation, independently of TLR9, which may serve an important role in the interplay between platelets and immunity. [less ▲]

Detailed reference viewed: 14 (0 ULg)
See detailLiposomes entrapping apigenin for the treatment of glioblastoma
Karim, Reatul ULg; Palazzo, Claudio ULg; Dubois, Nadège ULg et al

Poster (2015, April 17)

Detailed reference viewed: 30 (16 ULg)
Full Text
Peer Reviewed
See detailBRCA1 germline mutation and glioblastoma development: report of cases
Boukerroucha, Meriem ULg; Josse, Claire ULg; SEGERS, Karin ULg et al

in BMC Cancer (2015), 15

Background Germline mutations in breast cancer susceptibility gene 1 (BRCA1) increase the risk of breast and ovarian cancers. However, no association between BRCA1 germline mutation and glioblastoma ... [more ▼]

Background Germline mutations in breast cancer susceptibility gene 1 (BRCA1) increase the risk of breast and ovarian cancers. However, no association between BRCA1 germline mutation and glioblastoma malignancy has ever been highlighted. Here we report two cases of BRCA1 mutated patients who developed a glioblastoma (GBM). Cases presentation Two patients diagnosed with triple negative breast cancer (TNBC) were screened for BRCA1 germline mutation. They both carried a pathogenic mutation introducing a premature STOP codon in the exon 11 of the BRCA1 gene. Few years later, both patients developed a glioblastoma and a second breast cancer. In an attempt to clarify the role played by a mutated BRCA1 allele in the GBM development, we investigated the BRCA1 mRNA and protein expression in breast and glioblastoma tumours for both patients. The promoter methylation status of this gene was also tested by methylation specific PCR as BRCA1 expression is also known to be lost by this mechanism in some sporadic breast cancers. Conclusion Our data show that BRCA1 expression is maintained in glioblastoma at the protein and the mRNA levels, suggesting that loss of heterozygosity (LOH) did not occur in these cases. The protein expression is tenfold higher in the glioblastoma of patient 1 than in her first breast carcinoma, and twice higher in patient 2. In agreement with the high protein expression level in the GBM, BRCA1 promoter methylation was not observed in these tumours. In these two cases, despite of a BRCA1 pathogenic germline mutation, the tumour-suppressor protein expression is maintained in GBM, suggesting that the BRCA1 mutation is not instrumental for the GBM development. [less ▲]

Detailed reference viewed: 23 (2 ULg)
Full Text
See detailA tale of two anomalies. A paternal duplication and a maternal deletion of 15q13
BULK, Saskia ULg; Decortis, Thierry ULg; Rondia, G et al

Poster (2015, March 06)

Detailed reference viewed: 14 (1 ULg)
Full Text
See detailCongenital gigantism in a girl with anterior pituitary hyperplasia : a new genes for a new disease
Lysy, PA; Daly, Adrian ULg; Brunelle, C et al

in Abstract book - 43ème Congrès Annuel de la Société Belge de Pédiatrie (2015, March)

Detailed reference viewed: 23 (0 ULg)
Full Text
See detailX-Linked acro-gigantism (X-LAG) syndrome : a new form of infant-onset pituitary gigantism
Stratakis, CA; Trivellin, G; Rostomyan, Liliya ULg et al

in Abstract book - 14th International Pituitary Congress (2015, March)

Detailed reference viewed: 20 (0 ULg)
Full Text
See detailDisease characteristics of patients with X-linked acrogigantism (X-LAG) syndrome
Daly, Adrian ULg; Lodish, MB; Trivellin, G et al

in Abstract book - ENDO 2015 (2015, March)

Detailed reference viewed: 25 (6 ULg)
Full Text
See detailX-Linked acro-gigantism (X-LAG) due to microduplications of chromosome Xq26 : A new disorder and implications for acromegaly
Trivellin, G; Daly, AF; Faucz, FR et al

in Abstract book - ENDO 2015 (2015, March)

Detailed reference viewed: 17 (2 ULg)
Full Text
Peer Reviewed
See detailClinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients.
Rostomyan, Liliya ULg; Daly, Adrian ULg; PETROSSIANS, Patrick ULg et al

in Endocrine-related cancer (2015)

Despite being a classical growth disorder, pituitary gigantism has not been studied previously in a standardized way. We performed a retrospective, multicenter, international study to characterize a large ... [more ▼]

Despite being a classical growth disorder, pituitary gigantism has not been studied previously in a standardized way. We performed a retrospective, multicenter, international study to characterize a large series of pituitary gigantism patients. We included 208 patients (163 males; 78.4%) with growth hormone excess and current/previous abnormal growth velocity for age or final height >2SD above country normal means. The median onset of rapid growth was 13.0 years and occurred significantly earlier in females than in males; pituitary adenomas were diagnosed earlier in females than males (15.8 vs. 21.5 years, respectively). Adenomas were >/=10 mm (i.e. macroadenomas) in 84%, of which extrasellar extension occurred in 77% and invasion in 54%. GH/IGF-1 control was achieved in 39% during long-term follow-up. Final height was greater in those with younger age of onset, with larger tumors and higher GH levels. Later disease control was associated with a greater difference from mid-parental height (r=0.23, P=0.02). AIP mutations occurred in 29%; microduplication at Xq26.3 -X-linked acro-gigantism (X-LAG)- occurred in two familial isolated pituitary adenoma (FIPA) kindreds and in ten sporadic patients. Tumor size was not different in X-LAG, AIP mutated and genetically-negative patient groups. AIP-mutated and X-LAG patients had significantly younger age at onset and diagnosis, but disease control was worse in genetically-negative cases. Pituitary gigantism patients are characterized by male predominance and large tumors that are difficult to control. Treatment delay increases final height and symptom burden. AIP mutations and X-LAG explain many cases, but no genetic etiology is seen in >50% of cases. [less ▲]

Detailed reference viewed: 30 (2 ULg)
Full Text
Peer Reviewed
See detailEndothelial exosomes contribute to the antitumor response during breast cancer neoadjuvant chemotherapy via microRNA transfer.
Bovy, Nicolas ULg; Blomme, Benoît ULg; Freres, Pierre ULg et al

in Oncotarget (2015)

The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for ... [more ▼]

The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for the development of new anti-cancer therapies. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression. They are secreted into the extracellular medium in vesicles called exosomes, which allow communication between cells via the transfer of their cargo. Consequently, we hypothesized that circulating endothelial miRNAs could be transferred to tumor cells and modify their phenotype. Using exogenous miRNA, we demonstrated that endothelial cells can transfer miRNA to tumor cells via exosomes. Using miRNA profiling, we identified miR-503, which exhibited downregulated levels in exosomes released from endothelial cells cultured under tumoral conditions. The modulation of miR-503 in breast cancer cells altered their proliferative and invasive capacities. We then identified two targets of miR-503, CCND2 and CCND3. Moreover, we measured increased plasmatic miR-503 in breast cancer patients after neoadjuvant chemotherapy, which could be partly due to increased miRNA secretion by endothelial cells. Taken together, our data are the first to reveal the involvement of the endothelium in the modulation of tumor development via the secretion of circulating miR-503 in response to chemotherapy treatment. [less ▲]

Detailed reference viewed: 59 (19 ULg)
Full Text
Peer Reviewed
See detailCancer du sein : de la thérapie ciblée à la médecine personnalisée
JERUSALEM, Guy ULg; COLLIGNON, Joëlle ULg; Josse, Claire ULg et al

in Revue Médicale de Liège (2015), 70(5-6), 269-276

Dans cet article, les auteurs passent en revue les grands principes de prise en charge du traitement systémique du cancer du sein et posent la question suivante : jusqu'où réellement aujourd'hui ce ... [more ▼]

Dans cet article, les auteurs passent en revue les grands principes de prise en charge du traitement systémique du cancer du sein et posent la question suivante : jusqu'où réellement aujourd'hui ce traitement est-il individualisé ? Les nouvelles technologies permettent une analyse détaillée des anomalies génomiques au niveau des cellules cancéreuses. Malheureusement, nous n'avons pas encore compris comment utiliser au mieux ces données au bénéfice du patient. La majorité des modifications du génome sont des évènements relativement rares compliquant le développement de nouveaux médicaments dans le cadre d'une médecine de précision. De plus, les tumeurs présentent une grande hétérogénéité temporelle et spatiale dont il faudra tenir compte lors de ce développement. Une collaboration internationale intensive est en cours pour tenter de confirmer que la médecine de précision permet d'optimiser les résultats du traitement systémique dans le cancer du sein. [less ▲]

Detailed reference viewed: 98 (2 ULg)
Full Text
Peer Reviewed
See detailX-linked acrogigantism (X-LAG) syndrome : Clinical Profile and Therapeutic responses
Beckers, Albert ULg; Lodish, MB; Trivellin, G et al

in Endocrine-Related Cancer (2015), 22

Detailed reference viewed: 10 (4 ULg)
Full Text
Peer Reviewed
See detailModulating effect of COMT Val158Met polymorphism on interference resolution during a working memory task
Jaspar, Mathieu ULg; DIDEBERG, Vinciane ULg; Bours, Vincent ULg et al

in Brain & Cognition (2015), 95

Genetic variability related to the catechol-O-methyltransferase (COMT) gene has received increasing attention in the last 15 years, in particular as a potential modulator of the neural substrates ... [more ▼]

Genetic variability related to the catechol-O-methyltransferase (COMT) gene has received increasing attention in the last 15 years, in particular as a potential modulator of the neural substrates underlying inhibitory processes and updating in working memory (WM). In an event-related functional magnetic resonance imaging (fMRI) study, we administered a modified version of the Sternberg probe recency task (Sternberg, 1966) to 43 young healthy volunteers, varying the level of interference across successive items. The task was divided into two parts (high vs. low interference) to induce either proactive or reactive control processes. The participants were separated into three groups according to their COMT Val158Met genotype [Val/Val (VV); Val/Met (VM); Met/Met (MM)]. The general aim of the study was to determine whether COMT polymorphism has a modulating effect on the neural substrates of interference resolution during WM processing. Results indicate that interfering trials were associated with greater involvement of frontal cortices (bilateral medial frontal gyrus, left precentral and superior frontal gyri, right inferior frontal gyrus) in VV homozygous subjects (by comparison to Met allele carriers) only in the proactive condition of the task. In addition, analysis of peristimulus haemodynamic responses (PSTH) revealed that the genotype-related difference observed in the left SFG was specifically driven by a larger increase in activity from the storage to the recognition phase of the interfering trials in VV homozygous subjects. These results confirm the impact of COMT genotype on inhibitory processes during a WM task, with an advantage for Met allele carriers. Interestingly, this impact on frontal areas is present only when the level of interference is high, and especially during the transition from storage to recognition in the left superior frontal gyrus. [less ▲]

Detailed reference viewed: 61 (5 ULg)
Full Text
Peer Reviewed
See detailMutation of the iron-sulfur cluster assembly gene IBA57 causes fatal infantile leukodystrophy.
DEBRAY, François-Guillaume ULg; Stumpfig, Claudia; Vanlander, Arnaud V. et al

in Journal of inherited metabolic disease (2015)

Leukodystrophies are a heterogeneous group of severe genetic neurodegenerative disorders. A multiple mitochondrial dysfunctions syndrome was found in an infant presenting with a progressive ... [more ▼]

Leukodystrophies are a heterogeneous group of severe genetic neurodegenerative disorders. A multiple mitochondrial dysfunctions syndrome was found in an infant presenting with a progressive leukoencephalopathy. Homozygosity mapping, whole exome sequencing, and functional studies were used to define the underlying molecular defect. Respiratory chain studies in skeletal muscle isolated from the proband revealed a combined deficiency of complexes I and II. In addition, western blotting indicated lack of protein lipoylation. The combination of these findings was suggestive for a defect in the iron-sulfur (Fe/S) protein assembly pathway. SNP array identified loss of heterozygosity in large chromosomal regions, covering the NFU1 and BOLA3, and the IBA57 and ABCB10 candidate genes, in 2p15-p11.2 and 1q31.1-q42.13, respectively. A homozygous c.436C > T (p.Arg146Trp) variant was detected in IBA57 using whole exome sequencing. Complementation studies in a HeLa cell line depleted for IBA57 showed that the mutant protein with the semi-conservative amino acid exchange was unable to restore the biochemical phenotype indicating a loss-of-function mutation of IBA57. In conclusion, defects in the Fe/S protein assembly gene IBA57 can cause autosomal recessive neurodegeneration associated with progressive leukodystrophy and fatal outcome at young age. In the affected patient, the biochemical phenotype was characterized by a defect in the respiratory chain complexes I and II and a decrease in mitochondrial protein lipoylation, both resulting from impaired assembly of Fe/S clusters. [less ▲]

Detailed reference viewed: 9 (4 ULg)
Full Text
See detailLe cancer thyroïdien papillaire familial (FNMTC): études cliniques et génétiques chez 8 familles
VALDES SOCIN, Hernan Gonzalo ULg; Daly, Adrian ULg; Burlacu, C et al

in Abstract book - Annales d'Endocrinologie : 31ème Congrès de la Société Française d'Endocrinologie, Lyon 5-8 novembre 2014 (2014, October)

Detailed reference viewed: 28 (6 ULg)
Full Text
Peer Reviewed
See detailNeoadjuvant chemotherapy in breast cancer induces miR-34a and miR-122 expression
FRERES, Pierre ULg; JOSSE, Claire ULg; Bovy, Nicolas ULg et al

in Journal of Cellular Physiology (2014)

Circulating microRNAs (miRNAs) have been extensively studied in cancer as biomarkers but little is known regarding the influence of anti-cancer drugs on their expression levels. In this article, we ... [more ▼]

Circulating microRNAs (miRNAs) have been extensively studied in cancer as biomarkers but little is known regarding the influence of anti-cancer drugs on their expression levels. In this article, we describe the modifications of circulating miRNAs profile after neoadjuvant chemotherapy (NAC) for breast cancer. The expression of 188 circulating miRNAs was assessed in the plasma of 25 patients before and after NAC by RT-qPCR. Two miRNAs, miR- 34a and miR-122, that were significantly increased after NAC, were measured in tumor tissue before and after chemotherapy in 7 patients with pathological partial response (pPR) to NAC. These 2 chemotherapy-induced miRNAs were further studied in the plasma of 22 patients with adjuvant chemotherapy (AC) as well as in 12 patients who did not receive any chemotherapy. Twenty-five plasma miRNAs were modified by NAC. Among these miRNAs, miR-34a and miR-122 were highly upregulated, notably in pPR patients with aggressive breast cancer. Furthermore, miR-34a level was elevated in the remaining tumor tissue after NAC treatment. Studying the kinetics of circulating miR-34a and miR-122 expression during NAC revealed that their levels were especially increased after anthracycline-based chemotherapy. Comparisons of the plasma miRNA profiles after NAC and AC suggested that chemotherapy-induced miRNAs originated from both tumoral and non-tumoral compartments. This study is the first to demonstrate that NAC specifically induces miRNA expression in plasma and tumor tissue, which might be involved in the anti-tumor effects of chemotherapy in breast cancer patients. [less ▲]

Detailed reference viewed: 77 (28 ULg)