References of "CASTERMANS, Emilie"
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See detailDeletion of exons 1-3 of the MEN1 gene in a large Italian family causes the loss of menin expression.
Zatelli, Maria Chiara; Tagliati, Federico; Di Ruvo, Mauro et al

in Familial cancer (2014)

Multiple endocrine neoplasia type 1 (MEN1) syndrome is an autosomal dominant disease, characterized by parathyroid adenomas, endocrine gastroenteropancreatic tumors and pituitary adenomas, due to ... [more ▼]

Multiple endocrine neoplasia type 1 (MEN1) syndrome is an autosomal dominant disease, characterized by parathyroid adenomas, endocrine gastroenteropancreatic tumors and pituitary adenomas, due to inactivating mutations of the MEN1 gene (chromosome 11q13). MEN1 mutations are mainly represented by nonsense, deletions/insertions, splice site or missense mutations that can be detected by direct sequencing of genomic DNA. However, MEN1 patients with large heterozygous deletions may escape classical genetic screening and may be misidentified as phenocopies, thereby hindering proper clinical surveillance. We employed a real-time polymerase chain reaction application, the TaqMan copy number variation assay, to evaluate a family in which we failed to identify an MEN1 mutation by direct sequencing, despite a clear clinical diagnosis of MEN1 syndrome. Using the TaqMan copy number variation assay we identified a large deletion of the MEN1 gene involving exons 1 and 2, in three affected family members, but not in the other nine family members that were to date clinically unaffected. The same genetic alteration was not found in a group of ten unaffected subjects, without family history of endocrine tumors. The MEN1 deletion was further confirmed by multiplex ligation-dependent probe amplification, which showed the deletion extended from exon 1 to exon 3. This new approach allowed us to correctly genetically diagnose three clinical MEN1 patients that were previously considered as MEN1 phenocopies. More importantly, we excluded the presence of genetic alterations in the unaffected family members. These results underline the importance of using a variety of available biotechnology approaches when pursuing a genetic diagnosis in a clinically suggestive setting of inherited endocrine cancer. [less ▲]

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See detailTwo novel mutations of the CLDN16 gene cause familial hypomagnesaemia with hypercalciuria and nephrocalcinosis
Hanssen, Oriane ULg; CASTERMANS, Emilie ULg; BOVY, Christophe ULg et al

in Clinical Kidney Journal (2014), 7

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is an autosomal-recessive disease caused by mutations in the CLDN16 or CLDN19 genes, which encode tight junction-associated proteins ... [more ▼]

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is an autosomal-recessive disease caused by mutations in the CLDN16 or CLDN19 genes, which encode tight junction-associated proteins, claudin-16 and -19. The resultant tubulopathy leads to urinary loss of Mg2+ and Ca2+, with subsequent nephrocalcinosis and end-stage renal disease (ESRD). An 18-year-old boy presented with chronic kidney disease and proteinuria, as well as hypomagnesaemia, hypercalciuria and nephrocalcinosis. A kidney biopsy revealed tubular atrophy, interstitial fibrosis and segmental sclerosis of some glomeruli. Two novel mutations in the CLDN16 gene were identified: c.340C>T (nonsense) and c.427+5G>A (splice site). The patient reached ESRD at 23 and benefited from kidney transplantation. [less ▲]

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See detailA giant treated with growth hormone
Rostomyan, Liliya ULg; Potorac, Iulia ULg; CASTERMANS, Emilie ULg et al

in The 3rd ENEA Workshop : Hypopituitarism - Abstract book (2013, December)

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See detailFIPA : étude clinique et génétique à l'Hôpital "King Edward Memorial", Bombay (Mumbai) Inde
Bothra, N; Daly, Adrian ULg; CASTERMANS, Emilie ULg et al

in Annales d'Endocrinologie (2013, October), 74

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See detailImpact of bone marrow-derived mesenchymal stromal cells on experimental xenogeneic graft-versus-host disease
Bruck, France; Belle, Ludovic ULg; LECHANTEUR, Chantal ULg et al

in Cytotherapy (2013), 15(3), 267-279

Background aims. Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation caused by donor T cells reacting against host tissues. Previous ... [more ▼]

Background aims. Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation caused by donor T cells reacting against host tissues. Previous studies have suggested that mesenchymal stromal cells (MSCs) could exert potent immunosuppressive effects. Methods. The ability of human bone marrow derived MSCs to prevent xenogeneic GVHD in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice and in NOD/SCID/interleukin-2Rg(null) (NSG) mice transplanted with human peripheral blood mononuclear cells (PBMCs) was assessed. Results. Injection of 200 106 human PBMCs intraperitoneally (IP) into sub-lethally (3.0 Gy) irradiated NOD/SCID mice also given anti-asialo GM1 antibodies IP 1 day prior and 8 days after transplantation induced lethal xenogeneic GVHD in all tested mice. Co-injection of 2 106 MSCs IP on day 0 did not prevent lethal xenogeneic GVHD induced by injection of human PBMCs. Similarly, injection of 30 106 human PBMCs IP into sub-lethally (2.5 Gy) irradiated NSG mice induced a lethal xenogeneic GVHD in all tested mice. Injection of 3 106 MSCs IP on days 0, 7, 14 and 21 did not prevent lethal xenogeneic GVHD induced by injection of human PBMCs. Conclusions. Injection of MSCs did not prevent xenogeneic GVHD in these two humanized mice models. [less ▲]

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See detailHigher risk of death among MEN1 patients with mutations in the JunD interacting domain. A Groupe d'étude des Tumeurs Endocrines (GTE) cohort study
Thevenon, Julien; Bourredjem, Abderrahmane; Faivre, Laurence et al

in Human Molecular Genetics (2013)

BackgroundMultiple Endocrine Neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors ... [more ▼]

BackgroundMultiple Endocrine Neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Although genotype-phenotype studies have so far failed to identify any statistical correlations, some families harbor recurrent tumor patterns. The function of MENIN is unclear but has been described through the discovery of its interacting partners. Mutations in the interacting domains of MENIN functional partners have been shown to directly alter its regulation abilities.MethodsWe report on a cohort of MEN1 patients from the Groupe d'etude des Tumeurs Endocrines. Patients with a molecular diagnosis and a clinical follow-up, totalling 262 families and 806 patients were included. Associations between mutation type, location or interacting factors of the MENIN protein and death as well as the occurrence of MEN1-related tumors were tested using a frailty Cox model to adjust for potential heterogeneity across families.ResultsAccounting for the heterogeneity across families, the overall risk of death was significantly higher when mutations affected the JunD interacting domain (adjusted HR=1.88: 95%-CI=1.15- 3.07). Patients had a higher risk of death from cancers of the MEN1 spectrum (HR=2.34; 95%-CI=1.23- 4.43).ConclusionThis genotype-phenotype correlation study confirmed the lack of direct genotype-phenotype correlations. However, patients with mutations affecting the JunD interacting domain had a higher risk of death secondary to a MEN1 tumor and should thus be considered for surgical indications, genetic counseling and follow-up. [less ▲]

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See detailExiste-t-il une predisposition genetique aux addictions ?
CASTERMANS, Emilie ULg; GAILLEZ, Stephanie ULg; BOURS, Vincent ULg

in Revue Médicale de Liège (2013), 68(5-6), 226-32

Is free will the rule in front of drugs, alcohol or gambling? Would interindividual genetic variations influence our behaviour to such a point that addiction susceptibility would be enhanced or decreased ... [more ▼]

Is free will the rule in front of drugs, alcohol or gambling? Would interindividual genetic variations influence our behaviour to such a point that addiction susceptibility would be enhanced or decreased? Addiction predisposition is a complex trait, involving numerous predisposition genes and also environment. Heritability of this trait is 50%, meaning a similar contribution of genes and environment in the setting of this trait. Some genes of the dopaminergic system and some others specific for various drugs metabolism have been associated to addictions. The growth of those findings into promising pilot treatments seems a good future coming in. [less ▲]

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See detailAry Hydrocarbon receptor interacting protein (AIP) on somatotroph adenomas : a molecular target for somatostatin analogues ?
JAFFRAIN-REA, M; ANGELINI, M; OCCHI, G et al

in Endocrine abstracts - May 2012, volume 29 (2012, May)

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See detailCyclin dependent kinase inhibitor (CDKN1B) gene variants in AIP mutation-negative familial isolated pituitary adenomas (FIPA) kindreds
Tichomirowa, M.; Lee, M.; Barlier, A. et al

in Endocrine-Related Cancer (2012), 19

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See detailBone marrow-derived mesenchymal stromal cells failed to prevent experimental xenogeneic graft-versus-host disease
Bruck, France; de Leval, Laurence; Belle, Ludovic ULg et al

Poster (2012)

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See detailCharacterization of CD8+ T-cell response in acute and resolved hepatitis A virus infection.
Schulte, I.; Hitziger, T.; Giugliano, S. et al

in Journal of Hepatology (2011), 54(2), 201-208

Abstract BACKGROUND & AIMS: In contrast to the infection with other hepatotropic viruses, hepatitis A virus (HAV) always causes acute self-limited hepatitis, although the role for virus-specific CD8 T ... [more ▼]

Abstract BACKGROUND & AIMS: In contrast to the infection with other hepatotropic viruses, hepatitis A virus (HAV) always causes acute self-limited hepatitis, although the role for virus-specific CD8 T cells in viral containment is unclear. Herein, we analyzed the T cell response in patients with acute hepatitis by utilizing a set of overlapping peptides and predicted HLA-A2 binders from the polyprotein. METHODS: A set of 11 predicted peptides from the HAV polyprotein, identified as potential binders, were synthesized. Peripheral blood mononuclear cells (PBMCs) from patients were tested for IFNγ secretion after stimulation with these peptides and ex vivo with HLA-A2 tetramers. Phenotyping was carried out by staining with the activation marker CD38 and the memory marker CD127. RESULTS: Eight out of 11 predicted HLA-A2 binders showed a high binding affinity and five of them were recognized by CD8+ T cells from patients with hepatitis A. There were significant differences in the magnitude of the responses to these five peptides. One was reproducibly immunodominant and the only one detectable ex vivo by tetramer staining of CD8+ T cells. These cells have an activated phenotype (CD38hi CD127lo) during acute infection. Three additional epitopes were identified in HLA-A2 negative patients, most likely representing epitopes restricted by other HLA-class I-alleles (HLA-A11, B35, B40). CONCLUSIONS: Patients with acute hepatitis A have a strong multi-specific T cell response detected by ICS. With the tetramer carrying the dominant HLA-A2 epitope, HAV-specific and activated CD8+ T cells could be detected ex vivo. This first description of the HAV specific CTL-epitopes will allow future studies on strength, breadth, and kinetics of the T-cell response in hepatitis A. [less ▲]

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See detailParallel detection of antigen-specific T-cell responses by multidimensional encoding of peptide-Major Histocompatibility Complexes
Reker Hadrup, Sine; Bakker, Arnold H; Shu, Chengyi J. et al

in Nature Methods (2009), 6((7)), 520-526

Abstract The use of fluorescently labeled MHC multimers has become an essential technique for the analysis of disease- and therapy-induced T cell immunity. While classical MHC multimer analyses are well ... [more ▼]

Abstract The use of fluorescently labeled MHC multimers has become an essential technique for the analysis of disease- and therapy-induced T cell immunity. While classical MHC multimer analyses are well-suited for the detection of immune responses against a few epitopes, limitations on patient sample size preclude a comprehensive analysis of T cell immunity. To address this issue, we have developed a combinatorial encoding strategy that allows the parallel detection of a multitude of different T cell populations within a single sample. Detection of antigen-specific T cells from peripheral blood by combinatorial encoding is as efficient as detection with conventional PE labeled multimers, but results in a significantly increased sensitivity, and most importantly, allows comprehensive screens to be performed on patient material. Proof of principle for the feasibility of large-scale screening of patient material was obtained by analysis of HLA-A3 restricted T cell responses against known and potential melanoma-associated antigens in peripheral blood from melanoma patients. 2 [less ▲]

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See detailWhat Is The Role For Regulatory T-Cells After Nonmyeloablative Conditioning?
Humblet-Baron, S.; CASTERMANS, Emilie ULg; Vanbellinghen, J.-F. et al

in Biology of Blood & Marrow Transplantation (2009, February), 15(2), 122-123

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See detailReconstitution du système immunitaire après allogreffe de cellules souches hématopoïétiques
Castermans, Emilie ULg; Hannon, Muriel ULg; Drion, Pierre ULg et al

in Revue Médicale de Liège (2009), 64(S1), 2-8

Allogeneic hematopoietic stem cell transplantation (alloHCT) is frequently used as treatment for patients with hematological malignancies. Its efficacy depends in part on the destruction of recipient ... [more ▼]

Allogeneic hematopoietic stem cell transplantation (alloHCT) is frequently used as treatment for patients with hematological malignancies. Its efficacy depends in part on the destruction of recipient tumors cells by donor immune cells contained in the graft (graft-versus-tumor effects), underlying the interest of stydying donor immune recovery after alloHCT. Further, donor immune cells play an important role in the prevention and treatment of infections after allHCT, and are the cause of graft-versus-host disease (GVHD). This article reviews the mechanisms of immune recovery after allogeneic hematopoietic cell transplantation (alloHCT), as well as techniques currently used to monitor immune function following allHCT. [less ▲]

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See detailWhat is the Role for Regulatory T-Cells after Nonmyeloablative conditioning
Humblet-Baron, S.; CASTERMANS, Emilie ULg; Vanbellighen, J.-F. et al

in Biology of Blood & Marrow Transplantation (2008, February), 14(2), 136-137

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See detailEvidence for neo-generation of T cells by the thymus after non-myeloablative conditioning.
Castermans, Emilie ULg; Baron, Frédéric ULg; Willems, Evelyne ULg et al

in Haematologica (2008), 93(2), 240-7

BACKGROUND: Background and objective. We investigated immune recovery in 50 patients given either unmanipulated or CD8-depleted allogeneic peripheral blood stem cells after non-myeloablative conditioning ... [more ▼]

BACKGROUND: Background and objective. We investigated immune recovery in 50 patients given either unmanipulated or CD8-depleted allogeneic peripheral blood stem cells after non-myeloablative conditioning. DESIGN AND METHODS: Fifty patients were randomized to receive either CD8-depleted (n=22) or non-manipulated (n=28) peripheral blood stem cells. The median patients age was 57 (range 36-69) years. The conditioning regimen consisted of 2 Gy total body irradiation with or without added fludarabine. Twenty patients received grafts from related donors, 14 from 10/10 HLA-allele matched unrelated donors, and 16 from HLA-mismatched unrelated donors. Graft-versus-host disease pro-phylaxis consisted of mycophenolate mofetil and cyclosporine. Immune recovery during the first year after hematopoietic cell transplantation was assessed by flow cytometry phenotyping, analyses of the diversity of the TCRBV repertoire, and quantification of signal-joint T-cell receptor excision circles (sjTREC). RESULTS: CD8-depletion of the graft reduced the recovery of CD8(+) T-cell counts in the first 6 months following transplantation (p<0.0001) but had no significant impact on the restoration of other T-cell subsets. Both sjTREC concentration and CD3(+) T-cell counts increased significantly between day 100 and 365 (p=0.010 and p=0.0488, respectively) demonstrating neo-production of T cells by the thymus. Factors associated with high sjTREC concentration 1 year after transplantation included an HLA-matched unrelated donor (p=0.029), a high content of T cells in the graft (p=0.002), and the absence of chronic graft-versus-host disease (p<0.0001). CONCLUSIONS: Our data suggest that while immune recovery is mainly driven by peripheral expansion of the graft-contained mature T cells during the first months after non-myeloablative transplantation, T-cell neo-generation by the thymus plays an important role in long term immune reconstitution in transplanted patients. [less ▲]

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See detailEvaluation clinique de la fonction du thymus.
Castermans, Emilie ULg; Morrhaye, Gabriel ULg; Marchand, S. et al

in Revue Médicale de Liège (2007), 62(11), 675-8

The essential role of the thymus is to install an extremely diverse repertoire of T lymphocytes that are self-tolerant and competent against non-self, as well as to generate self-antigen specific ... [more ▼]

The essential role of the thymus is to install an extremely diverse repertoire of T lymphocytes that are self-tolerant and competent against non-self, as well as to generate self-antigen specific regulatory T cells (Treg) able to inactivate in periphery self-reactive T cells having escaped the thymic censorship. Although indirect, techniques of medical imaging and phenotyping of peripheral T cells may help in the investigation of thymic function. Nowadays however, thymopoiesis is better evaluated through quantification by PCR of T-cell receptor excision circles (TREC) generated by intrathymic random recombination of the gene segments coding for the variable parts of the T-cell receptor for antigen (TCR). The TREC methodology is very valuable in the circumstances not associated with intense proliferation or apoptosis of peripheral T lymphocytes. [less ▲]

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See detailEvaluation de la thymopoiese: applications cliniques.
Castermans, Emilie ULg; Morrhaye, Gabriel ULg; Marchand, S. et al

in Revue Médicale de Liège (2007), 62(12), 725-9

In the precedent article, we have described how T-cell generation in the thymus (thymopoiesis) may be currently evaluated through quantification by PCR of T-cell receptor excision circles (TREC) generated ... [more ▼]

In the precedent article, we have described how T-cell generation in the thymus (thymopoiesis) may be currently evaluated through quantification by PCR of T-cell receptor excision circles (TREC) generated by intrathymic random recombination of the gene segments coding for variable parts of T-cell receptor for antigen (TCR). In hematology, TREC methodology helps in a better understanding of immune reconstitution after graft of hematopoietic stem cells: first there is a proliferation of mature T cells present in the graft, then a differentiation of naive T cells. In geriatrics, the homeostasis of the peripheral T-cell repertoire is maintained through proliferation of peripheral memory T cells rather than through thymic generation of naive T cells. In addition, TREC quantification constitutes a novel major tool for deciphering the tight control of thymopoiesis by the neuroendocrine system. [less ▲]

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See detailRaloxifene-induced myeloma cell apoptosis: a study of nuclear factor-kappaB inhibition and gene expression signature.
Olivier, Sabine ULg; Close, Pierre ULg; Castermans, Emilie ULg et al

in Molecular Pharmacology (2006), 69(5), 1615-1623

Because multiple myeloma remains associated with a poor prognosis, novel drugs targeting specific signaling pathways are needed. The efficacy of selective estrogen receptor modulators for the treatment of ... [more ▼]

Because multiple myeloma remains associated with a poor prognosis, novel drugs targeting specific signaling pathways are needed. The efficacy of selective estrogen receptor modulators for the treatment of multiple myeloma is not well documented. In the present report, we studied the antitumor activity of raloxifene, a selective estrogen receptor modulator, on multiple myeloma cell lines. Raloxifene effects were assessed by tetrazolium salt reduction assay, cell cycle analysis, and Western blotting. Mobility shift assay, immunoprecipitation, chromatin immunoprecipitation assay, and gene expression profiling were performed to characterize the mechanisms of raloxifene-induced activity. Indeed, raloxifene, as well as tamoxifen, decreased JJN-3 and U266 myeloma cell viability and induced caspase-dependent apoptosis. Raloxifene and tamoxifen also increased the cytotoxic response to vincristine and arsenic trioxide. Moreover, raloxifene inhibited constitutive nuclear factor-kappaB (NF-kappaB) activity in myeloma cells by removing p65 from its binding sites through estrogen receptor alpha interaction with p65. It is noteworthy that microarray analysis showed that raloxifene treatment decreased the expression of known NF-kappaB-regulated genes involved in myeloma cell survival and myeloma-induced bone lesions (e.g., c-myc, mip-1alpha, hgf, pac1,...) and induced the expression of a subset of genes regulating cellular cycle (e.g., p21, gadd34, cyclin G2,...). In conclusion, raloxifene induces myeloma cell cycle arrest and apoptosis partly through NF-kappaB-dependent mechanisms. These findings also provide a transcriptional profile of raloxifene treatment on multiple myeloma cells, offering the framework for future studies of selective estrogen receptor modulators therapy in multiple myeloma. [less ▲]

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