References of "Kustermans, Gaëlle"
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See detailUnique recurrence patterns of cervical intraepithelial neoplasia following excision of the squamo-columnar junction.
Herfs, Michael ULg; SOMJA, Joan ULg; Howitt, Brooke E. et al

in International journal of cancer. Journal international du cancer (2014)

Recent studies have identified a putative cell of origin for cervical intraepithelial neoplasia (CIN) and cervical cancer at the squamo-columnar junction (SCJ) and suggest that these cells may not ... [more ▼]

Recent studies have identified a putative cell of origin for cervical intraepithelial neoplasia (CIN) and cervical cancer at the squamo-columnar junction (SCJ) and suggest that these cells may not regenerate following excision (LEEP). This study addressed the impact of SCJ excision on the temporal dynamics, histologic and viral (HPV) characteristics of recurrent CIN. One hundred thirty one consecutive patients treated by excision and attending follow-up visits were enrolled. We compared recurrent and initial CIN with attention to excision margins, timing of recurrence, CIN grade, HPV types, p16 immunophenotype, and SCJ immunophenotype. During the follow-up period (up to four years), sixteen (12.2%) recurrences were identified. Four (25%) were identified at the first follow-up visit, closely resembled the initial CIN 2/3 in grade and HPV type, and were typically SCJ marker positive [SCJ(+)], suggesting non-excised (residual) disease. Twelve (75%) manifested after the first postoperative visit and all were in the ectocervix or in mature metaplastic epithelium. All of the 12 delayed recurrences were classified as CIN 1 and were SCJ (-). Nine of 11 SCJ (-) recurrences (82%) followed regressed spontaneously. Taken together, these results show that new lesions developing from any HPV infection are delayed and occur within the ectocervix or metaplastic epithelium. This dramatically lower risk of CIN 2/3 following successful SCJ excision suggests that removal of the SCJ could be a critical variable in reducing the risk of subsequent CIN 2/3 and cervical cancer. (c) 2014 Wiley Periodicals, Inc. [less ▲]

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See detailNovel association between vasoactive intestinal peptide and CRTH2 receptor in recruiting eosinophils: a possible biochemical mechanism for allergic eosinophilic inflammation of the airways.
EL SHAZLY, Amr ULg; Begon, Dominique ULg; KUSTERMANS, Gaëlle ULg et al

in Journal of Biological Chemistry (2013), 288(2), 1374-84

We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and ... [more ▼]

We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and eosinophils cell line (Eol-1 cells) was up-regulated by VIP treatment. This was functional and resulted into exaggerated migratory response of cells against PGD2. Nasal challenge of AR patients resulted into significant increase of VIP contents in nasal secretion (ELISA), and the immunohistochemical studies of allergic nasal tissues, showed significant expression of VIP in association with intense eosinophil recruitment. Biochemical assays showed that VIP-induced eosinophils chemotaxis from AR patients and Eol-1 cells, was mediated through CRTH2 receptor. Cells migration against VIP was sensitive to protein kinase C (PKC) and protein kinase A (PKA) inhibition, but not to tyrosine kinase or P38 MAP-kinase inhibition, or calcium chelation. Western blot demonstrated a novel CRTH2 mediated cytosol to membrane translocation of PKC-epsilon, PKC-delta and PKA-alpha, gamma and IIalpha reg in Eol-1 cells upon stimulation with VIP. Confocal images and FACS demonstrated a strong association and co-localization between VIP peptide and CRTH2 molecules. Further, VIP induced PGD2 secretion from eosinophils. Our results demonstrate the first evidence of association between VIP and CRTH2 in recruiting eosinophils. [less ▲]

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See detailThe L1 major capsid protein of HPV16 differentially modulates APC trafficking according to the vaccination or natural infection context.
Herman, Ludivine ULg; Hubert, Pascale ULg; Herfs, Michael ULg et al

in European Journal of Immunology (2010), 40(11), 3075-84

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix. The progression of cervical lesions suggests that viral antigens are not adequately ... [more ▼]

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix. The progression of cervical lesions suggests that viral antigens are not adequately presented to the immune system. The aim of this study was to determine whether HPV16 viral particles can influence the trafficking of human DC/Langerhans cells (LC), either by direct interactions with DC or following incubation with human normal keratinocytes that are in close contact with LC in the squamous epithelium. We first demonstrated that HPV16 L1 major capsid protein, when self-assembled into virus-like particles (VLP), is able to induce in DC an over-expression of CXC receptor 4 (CXCR4) via the activation of the NF-kappaB signaling pathway and to enhance DC motility in the presence of CXCL12, suggesting an ability to migrate towards lymph nodes. We also showed that conditioned media of HPV16 VLP-treated keratinocytes induce a lower LC migration than those from untreated keratinocytes and that prostaglandin E2 (PGE(2)), detected in HPV16 VLP-treated keratinocyte supernatants, may reduce LC recruitment into the squamous epithelium. Taken together, our data demonstrate that HPV16 VLP may differentially regulate the immune protective response according to their target cells. [less ▲]

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See detailDNA methylation and cancer diagnosis: new methods and applications.
Dehan, Pierre ULg; Kustermans, Gaëlle ULg; Guénin, Samuel ULg et al

in Expert Review of Molecular Diagnostics (2009), 9(7), 651-7

Methylation of cytosines in cytosine-guanine (CpG) dinucleotides is one of the most important epigenetic alterations in animals. The presence of methylcytosine in the promoter of specific genes has ... [more ▼]

Methylation of cytosines in cytosine-guanine (CpG) dinucleotides is one of the most important epigenetic alterations in animals. The presence of methylcytosine in the promoter of specific genes has profound consequences on local chromatin structure and on the regulation of gene expression. Changes in DNA methylation play a central role in carcinogenesis. Hypermethylation and consecutive transcriptional silencing of tumor-suppressor genes has been documented in numerous cancers. The identification of target genes silenced by this modification has a great impact on diagnosis, classification, definition of risk groups and prognosis of cancer patients. Here we outline genome-wide techniques aiming at the identification of relevant methylated promoters. Methods and applications allowing clinicians to monitor the methylation of target genes will be also reviewed. [less ▲]

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See detailActin-targeting natural compounds as tools to study the role of actin cytoskeleton in signal transduction.
Kustermans, Gaëlle ULg; Piette, Jacques ULg; Legrand, Sylvie ULg

in Biochemical Pharmacology (2008), 76(11)

Actin cytoskeleton controls a vast range of cellular processes such as motility, cytokinesis, differentiation, vesicle transport, phagocytosis, muscle contraction. A growing literature clearly ... [more ▼]

Actin cytoskeleton controls a vast range of cellular processes such as motility, cytokinesis, differentiation, vesicle transport, phagocytosis, muscle contraction. A growing literature clearly demonstrated that actin cytoskeleton can play a regulating role in several signalling pathways. Cells tightly regulate actin dynamics through numerous specific proteins in order to rapidly and locally respond to various stimuli. An obvious approach to determine the involvement of actin cytoskeleton in signalling pathways is the use of actin-targeting natural compounds. These drugs modulate actin dynamics, accelerating either polymerization or depolymerization, through various mechanisms. This review focus on the use of these actin-targeting drugs as tools to demonstrate the role of actin cytoskeleton in several signal transduction pathways such as those initiated from antigen receptor in T and B cells or those involving mitogen-activated protein kinases (MAPKs) or transcription factors NF-kB and SRF (serum response factor). In this last case (SRF), the use of various actin-targeting drugs participated in the elucidation of the molecular mechanism by which actin regulates SRF-mediated transcription. [less ▲]

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See detailActin cytoskeleton differentially modulates NF-κB-mediated IL-8 expression in myelomonocytic cells
Kustermans, Gaëlle ULg; El Mjiyad, Nadia ULg; Horion, Julie ULg et al

in Biochemical Pharmacology (2008), 76(10)

Many physiopathological events such as phagocytosis, pathogen invasion, cellular adhesion and chemotaxis governed by actin-based cytoskeleton are often accompanied by nuclear factor kB (NF-kB) activation ... [more ▼]

Many physiopathological events such as phagocytosis, pathogen invasion, cellular adhesion and chemotaxis governed by actin-based cytoskeleton are often accompanied by nuclear factor kB (NF-kB) activation and expression of pro-inflammatory genes. In the present study, we demonstrated that reorganization of actin cytoskeleton induced by Cytochalasin D (CytD), an actin-polymerization inhibitor, enhanced il-8 gene expression induced by TNFa and LPS in HL-60 monocyte-like cells. Both transcriptional and post-transcriptional mechanisms were involved. CytD potentiated NF-kB-mediated transcription induced by both TNFa and LPS but via different mechanisms. In the case of LPS, the perturbation of actin dynamics increased the TLR4 levels at the cell membrane and consequently enhanced the IKK complex activation and NF-kB nuclear translocation. However, the canonical pathway involving the IKK complex and leading to the NF-kB translocation into the nucleus was not affected by actin remodelling in the case of TNFa. Interestingly, actin disruption primed p65 phosphorylation induced by TNFa and LPS, on Ser276 and Ser536, respectively, which suggested actin cytoskeleton could also modulate p65 transactivating activity. [less ▲]

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See detailModulation of Nod2-dependent NF-kappa B signaling by the actin cytoskeleton
Legrand, Sylvie ULg; Kustermans, Gaëlle ULg; Bex, Françoise et al

in Journal of Cell Science (2007), 120(7), 1299-1310

Actin disruption by CytochalasinD (CytD) and LatrunculinB (LatB) induced NF-kappa B activation in myelomonocytic and intestinal epithelial cells. In an attempt to elucidate the mechanism by which actin ... [more ▼]

Actin disruption by CytochalasinD (CytD) and LatrunculinB (LatB) induced NF-kappa B activation in myelomonocytic and intestinal epithelial cells. In an attempt to elucidate the mechanism by which actin disruption induced IKK activation, we studied the human Nod2 protein, which was able to induce NF-kappa B activation and whose expression was restricted to myelomonocytic and intestinal epithelial cells. Nod2 is thought to play key roles in pathogen defence through sensing bacteria and generating an inflammatory immune response. We showed that actin disruption by CytD significantly and specifically increased Nod2-mediated NF-kappa B signaling. Nod2 was fully partitioned in the Triton-X-100-insoluble fraction but translocated into the soluble fraction after CytD treatment, demonstrating that the presence of Nod2 in the detergent-insoluble pellet was specific to actin cytoskeleton. Confocal analysis also revealed a Nod2 colocalization with membrane-associated F-actin. Colocalization and co-immunoprecipitation assays with endogenous Rac1 have shown that Nod2 associated with activated Rac1 in membrane ruffles through both its N-terminal caspase recruitment domains (CARD) and C-terminal leucine-rich repeats (LRRs). Membrane ruffle disruption by a Rac1 dominant negative form primed Nod2-dependent NF-kappa B signaling. The recruitment of Nod2 in Rac-induced dynamic cytoskeletal structures could be a strategy to both repress the Nod2-dependent NF-kappa B signaling in unstimulated cells and rapidly mobilize Nod2 during bacterial infection. [less ▲]

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See detailPerturbation of actin dynamics induces NF-kappa B activation in myelomonocytic cells through an NADPH oxidase-dependent pathway
Kustermans, Gaëlle ULg; El Benna, Jamel; Piette, Jacques ULg et al

in Biochemical Journal (2005), 387(Pt 2), 531-540

Although several reports showed the effect of compounds disrupting microtubules on NF-kappa B (nuclear factor kappa B) activation, nothing is known about agents perturbing actin dynamics. In the present ... [more ▼]

Although several reports showed the effect of compounds disrupting microtubules on NF-kappa B (nuclear factor kappa B) activation, nothing is known about agents perturbing actin dynamics. In the present study, we have shown that actin cytoskeleton disruption induced by actin-depolymerizing agents such as cytochalasin D and latrunculin B and actin-polymerizing compounds such as jasplakinolide induced NF-kappa B activation in myelomonocytic cells. The transduction pathway involved the I kappa B (inhibitory kappa B) kinase complex and a degradation of I kappa B alpha. We have shown that NF-kappa B activation in response to the perturbation of actin dynamics required reactive oxygen species. as demonstrated by the effect of antioxidants. Actin cytoskeleton disruption by cytochalasin D induced O-2(-) release from human monocytes, through the activation of the NADPH oxidase, as confirmed by the phosphorylation and by the membrane translocation of p47(phox). NF-kappa B activation after actin cytoskeleton disruption could be physiologically relevant during monocyte activation and/or recruitment into injured tissues, where cellular attachment, migration and phagocytosis result in cyclic shifts in cytoskeletal organization and disorganization. [less ▲]

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See detailGibberellins and the floral transition in Sinapis alba
Corbesier, Laurent; Kustermans, Gaëlle ULg; Périlleux, Claire ULg et al

in Physiologia Plantarum (2004), 122(1), 152-158

The putative role of gibberellins in the transition to flowering was investigated in Sinapis alba, a caulescent long-day (LD) plant. It was observed that: (1) physiological doses of exogenous gibberellins ... [more ▼]

The putative role of gibberellins in the transition to flowering was investigated in Sinapis alba, a caulescent long-day (LD) plant. It was observed that: (1) physiological doses of exogenous gibberellins (GA(1), GA(3), GA(9)) do not cause the floral shift of the meristem when applied to plants grown in short days but have some positive effect on the flowering response to a suboptimal LD; no inhibition was observed in any case; (2) GA-biosynthesis inhibitors (prohexadione-Ca and paclobutrazol) considerably inhibit stem growth but have some negative effect on flowering only when a suboptimal LD is given; and (3) the floral transition induced by one 22-h LD does not correlate with any detectable change in GA content of the apical bud, of the leaves, and of the phloem exudate reaching the apex. Taken together, these results suggest that GAs do not act as a major signal for photoperiodic flower induction in Sinapis. [less ▲]

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