References of "Poulet, Christophe"
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See detailNatural Antisense Transcripts: Molecular Mechanisms and Implications in Breast Cancers.
Latge, Guillaume ULiege; Poulet, Christophe ULiege; Bours, Vincent ULiege et al

in International Journal of Molecular Sciences (2018), 19(1),

Natural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high ... [more ▼]

Natural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high-throughput sequencing of the antisense transcriptome has only been available for less than a decade, many natural antisense transcripts were first described as long non-coding RNAs. Although the precise biological roles of natural antisense transcripts are not known yet, an increasing number of studies report their implication in gene expression regulation. Their expression levels are altered in many physiological and pathological conditions, including breast cancers. Among the potential clinical utilities of the natural antisense transcripts, the non-coding|coding transcript pairs are of high interest for treatment. Indeed, these pairs can be targeted by antisense oligonucleotides to specifically tune the expression of the coding-gene. Here, we describe the current knowledge about natural antisense transcripts, their varying molecular mechanisms as gene expression regulators, and their potential as prognostic or predictive biomarkers in breast cancers. [less ▲]

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See detailCellular and genomic disease signature of peripheral blood mononuclear cells in patients with malignant pleural mesothelioma
Mallon, Zachary R.; Poulet, Christophe ULiege; Enstrom, Amanda et al

Poster (2017)

Background: Recent data on the incidence malignant pleural mesothelioma (MPM) and the continued large-scale use of asbestos throughout the developing world portends an epidemic of asbestos-related disease ... [more ▼]

Background: Recent data on the incidence malignant pleural mesothelioma (MPM) and the continued large-scale use of asbestos throughout the developing world portends an epidemic of asbestos-related disease. MPM is an aggressive and fatal cancer with few treatment options. Recent advances in large scale genomic and high throughput cellular analyses now provide the tools to more easily attain markers of disease status and potential responsiveness to immunotherapeutics. Materials and Methods: Here we present pre-treatment cellular and genomic biomarker data on a cohort of chemotherapy-naïve MPM patients, and demographically matched healthy donors (HD). MPM patients were enrolled in a Phase 1b study utilizing CRS-207, a live, attenuated Listeria monocytogenes strain engineered to express the tumor-associated antigen, mesothelin. Four different multi-color flow cytometry panels were used to provide resolution on major immune cell populations of T cells, γδ T cells, B Cells, dendritic cells, monocytes, and natural killer cells. Together, these panels provided deeper resolution on 39 distinct subpopulations of major immune cell subsets. RNA from these cells was used to perform multiplex gene expression analysis on 770 genes using the Nanostring nCounter PanCancer Pathway Panel. Results: FACS analysis yielded numerous subpopulations with statistically significant differences between MPM patients and healthy controls. Differences in immune populations were analyzed by median and significant findings included populations of CD4+ T cells, CD8+ T cells, B cells, classical monocytes, and monocytic myeloid derived suppressor cells*. Class comparison and hierarchical clustering of gene expression data revealed genomic markers that were significantly expressed in MPM compared to healthy controls. Immune subset deconvolution of gene expression data provided similar findings as FACS analysis and corroborated this disease signature across experimental platforms. Conclusions: Understanding a patient’s biological disease signature can aide in diagnosis, as well as in making informed choices about therapies amidst the complex and broadening immunotherapeutic landscape. Until recently, existing biomarker data in MPM has been limited to a small number of serological markers and limited immune analysis. Here, we present the first comprehensive report of a MPM disease signature from the cellular and genomic perspectives. Correlation of patient baseline disease signatures with treatment outcome may yield biomarkers predictive of treatment efficacy. Predictive signatures are being investigated in the on-going Phase 1b study of CRS-207 and chemotherapy, as well as in the Phase 2 study of CRS-207 with pembrolizumab in MPM patients who failed prior treatment. *Inclusion of additional subjects confirmed the significance of all immune cell subsets except for MDSCs. [less ▲]

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See detailGenomic Studies of Multiple Myeloma Reveal an Association between X Chromosome Alterations and Genomic Profile Complexity.
Sticca, Tiberio ULiege; CABERG, Jean-Hubert ULiege; Wenric, Stéphane ULiege et al

in Genes, Chromosomes & Cancer (2017), 56

The genomic profile of multiple myeloma (MM) has prognostic value by dividing patients into a good prognosis hyperdiploid group and a bad prognosis non-hyperdiploid group with a higher incidence of IgH ... [more ▼]

The genomic profile of multiple myeloma (MM) has prognostic value by dividing patients into a good prognosis hyperdiploid group and a bad prognosis non-hyperdiploid group with a higher incidence of IgH translocations. This classification, however, is inadequate and many other parameters like mutations, epigenetic modifications and genomic heterogeneity may influence the prognosis. We performed a genomic study by array-based comparative genomic hybridization (aCGH) on a cohort of 162 patients to evaluate the frequency of genomic gains and losses. We identified a high frequency of X chromosome alterations leading to partial Xq duplication, often associated with Xi deletion in female patients. This partial X duplication could be a cytogenetic marker of aneuploidy as it is correlated with a high number of chromosomal breakages. Patient with high level of chromosomal breakage had reduced survival regardless the region implicated. A higher transcriptional level was shown for genes with potential implication in cancer and located in this altered region. Among these genes, IKBKG and IRAK1 are members of the NFKB pathway which plays an important role in MM and is a target for specific treatments. [less ▲]

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See detailInvolvement of Ikbζ in glioblastomas and its potential implication in radioresistance
Dubois, Nadège ULiege; Willems, Marie; Kroonen, Jérôme et al

Poster (2016, November 29)

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See detailInvolvement of Ikbζ in glioblastomas and its potential implication in radioresistance
Dubois, Nadège; Willems, Marie; Kroonen, Jérôme et al

Poster (2016, September 09)

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See detailPrognostic relevance of epilepsy at presentation in glioblastoma patients.
Berendsen, Sharon; Varkila, Meri; Kroonen, Jerome et al

in Neuro-oncology (2016)

BACKGROUND: Epileptogenic glioblastomas are thought to convey a favorable prognosis, either due to early diagnosis or potential antitumor effects of antiepileptic drugs. We investigated the relationship ... [more ▼]

BACKGROUND: Epileptogenic glioblastomas are thought to convey a favorable prognosis, either due to early diagnosis or potential antitumor effects of antiepileptic drugs. We investigated the relationship between survival and epilepsy at presentation, early diagnosis, and antiepileptic drug therapy in glioblastoma patients. METHODS: Multivariable Cox regression was applied to survival data of 647 consecutive patients diagnosed with de novo glioblastoma between 2005 and 2013 in order to investigate the association between epilepsy and survival in glioblastoma patients. In addition, we quantified the association between survival and valproic acid (VPA) treatment. RESULTS: Epilepsy correlated positively with survival (HR: 0.75 (95% CI: 0.61-0.92), P < .01). This effect is independent of age, sex, performance status, type of surgery, adjuvant therapy, tumor location, and tumor volume, suggesting that this positive correlation cannot be attributed solely to early diagnosis. For patients who presented with epilepsy, the use of the antiepileptic drug VPA did not associate with survival when compared with patients who did not receive VPA treatment. CONCLUSION: Epilepsy is an independent prognostic factor for longer survival in glioblastoma patients. This prognostic effect is not solely explained by early diagnosis, and survival is not associated with VPA treatment. [less ▲]

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See detailInvolvement of Ikbζ in glioblastomas and its potential implication in radioresistance
Dubois, Nadège ULiege; Willems, Marie; Kroonen, Jérôme et al

Poster (2016)

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See detailConnexin 30 expression inhibits growth of human malignant gliomas but protects them against radiation therapy.
Artesi, Maria ULiege; Kroonen, Jerome; Bredel, Markus et al

in Neuro-oncology (2014)

BACKGROUND: Glioblastomas remain ominous tumors that almost invariably escape treatment. Connexins are a family of transmembrane, gap junction-forming proteins, some members of which were reported to act ... [more ▼]

BACKGROUND: Glioblastomas remain ominous tumors that almost invariably escape treatment. Connexins are a family of transmembrane, gap junction-forming proteins, some members of which were reported to act as tumor suppressors and to modulate cellular metabolism in response to cytotoxic stress. METHODS: We analyzed the copy number and expression of the connexin (Cx)30 gene gap junction beta-6 (GJB6), as well as of its protein immunoreactivity in several public and proprietary repositories of glioblastomas, and their influence on patient survival. We evaluated the effect of the expression of this gap junction protein on the growth, DNA repair and energy metabolism, and treatment resistance of these tumors. RESULTS: The GJB6 gene was deleted in 25.8% of 751 analyzed tumors and mutated in 15.8% of 158 tumors. Cx30 immunoreactivity was absent in 28.9% of 145 tumors. Restoration of Cx30 expression in human glioblastoma cells reduced their growth in vitro and as xenografts in the striatum of immunodeficient mice. Cx30 immunoreactivity was, however, found to adversely affect survival in 2 independent retrospective cohorts of glioblastoma patients. Cx30 was found in clonogenic assays to protect glioblastoma cells against radiation-induced mortality and to decrease radiation-induced DNA damage. This radioprotection correlated with a heat shock protein 90-dependent mitochondrial translocation of Cx30 following radiation and an improved ATP production following this genotoxic stress. CONCLUSION: These results underline the complex relationship between potential tumor suppressors and treatment resistance in glioblastomas and single out GJB6/Cx30 as a potential biomarker and target for therapeutic intervention in these tumors. [less ▲]

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See detailCx30 (GJB6) inhibits cell growth in human malignant gliomas but mediates radiation resistance
Artesi, Maria ULiege; Kroonen, Jerome; Poulet, Christophe ULiege et al

in Neuro-Oncology (2014)

Connexins (Cxs) are potentially key players in the control of tumor cell proliferation. Normal astrocytes express large amounts of connexin30 and we have previously demonstrated its underexpression in rat ... [more ▼]

Connexins (Cxs) are potentially key players in the control of tumor cell proliferation. Normal astrocytes express large amounts of connexin30 and we have previously demonstrated its underexpression in rat glioma cells. Here we report that a Cx30 gene deletion occurs in approximately 30% of human glioblastomas (GBMs). Cx30 mRNA levels are decreased in these tumors compared to glial tumors of lower grade and to non tumoral tissues. At the protein level, Cx30 is lost in approximately one third of the tumors in our cohort of 230 glioblastoma biopsies. Restoration of Cx30 in U87 glioma cell lines and in glioma primary cultures (GM1), effectively retards cell proliferation in vitro and inhibits tumor growth in vivo. This correlates with a decrease in TCF, CK2 and NFkappaB activity and with altered expression levels of cell cycle control proteins such as cyclin D1, P27, P21 and c-myc. In patient biopsies, Cx30 expression was found in tumor regions displaying a lower Ki-67 proliferative index. Interestingly, in our cohort of malignant glioma patients, Cx30 expression proved to be an adverse prognostic factor. Here, we demonstrate its role in mediating cell survival and a hypermetabolic state after radiation treatment in human glioma cells. Mechanistically, we propose that a HSP90- mediated Cx30 translocation into mitochondria occurs after radiation treatment. The inhibition of the HSP90 molecular chaperone with geldamycin inhibits the radiation- induced translocation of Cx30 into mitochondria, decreasing the hypermetabolic state and restoring radiation sensitivity in those cells. These results demonstrate the central regulatory role of connexin30 in the biology of human gliomas. [less ▲]

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See detailExpression pattern of synaptic vesicle protein 2 (SV2) isoforms in patients with temporal lobe epilepsy and hippocampal sclerosis
CREVECOEUR, Julie ULiege; Kaminski, RM; Rogister, Bernard ULiege et al

in Neuropathology & Applied Neurobiology (2014), 40(2), 191-204

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See detailExome sequencing of tumors: relevance in copy-number alteration (CNA) analysis and fixed tissue samples.
Wenric, Stéphane ULiege; JOSSE, Claire ULiege; Fasquelle, Corinne ULiege et al

Poster (2013, March 15)

Genomic DNA has been extracted from both cryopreserved and formalin-fixed paraffin-embedded forms of 2 different tumor samples (triple negative, and Her2+). Exome sequencing has been performed on all 4 ... [more ▼]

Genomic DNA has been extracted from both cryopreserved and formalin-fixed paraffin-embedded forms of 2 different tumor samples (triple negative, and Her2+). Exome sequencing has been performed on all 4 forms, as well as SNP and CNA detection. A comparison of the various metrics and results related to the sequencing, mapping, and variants detection has been done, outlining what can, and can’t be done with exome data sequenced from cryopreserved and FFPE tissue. [less ▲]

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See detailLung function and airway inflammation monitoring after hematopoietic stem cell transplantation.
Moermans, Catherine ULiege; Poulet, Christophe ULiege; HENKET, Monique ULiege et al

in Respiratory Medicine (2013), 107

Background Induced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the ... [more ▼]

Background Induced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the context of hematopoietic stem cell transplantation (HSCT). Methods We monitored lung function in 182 patients who underwent HSCT and measured airway inflammation by sputum induction in 80 of them. We prospectively measured FEV1, FVC, DLCO, KCO, TLC, RV, exhaled nitric oxide (FeNO) as well as sputum cell counts before and 3, 6, 12, 24 and 36 months after HSCT. Results For the whole cohort there was a progressive decrease in TLC, which was significant after 3 years (p < 0.01). By contrast, there was no change in other lung functions parameters or in FeNO. Baseline sputum analysis revealed increased neutrophil counts in patients {Median (IQR): 63% (38–79)} compared to healthy subjects matched for age {Median (IQR): 49% (17–67), p < 0.001} but there was no significant change in any type of sputum cell counts over the three years. When comparing myeloablative (MA) vs non-myeloablative (NMA) conditioning, falls in FEV1, FVC and DLCO, and rise in RV and sputum neutrophils were more pronounced over the first year of observation in those receiving MA. Conclusions There was a progressive loss in lung function after HSCT, featuring a restrictive pattern. Myeloablative conditioning was associated with early rise of sputum neutrophils and greater alteration in lung function over the first year. [less ▲]

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See detailIn Vivo Tumorigenesis Was Observed after Injection of In Vitro Expanded Neural Crest Stem Cells Isolated from Adult Bone Marrow
Wislet, Sabine ULiege; Poulet, Christophe ULiege; Neirinckx, Virginie ULiege et al

in PLoS ONE (2012), 7(10), 46425

Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells ... [more ▼]

Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC) as mixed populations of cells including mesenchymal (MSC) and neural crest stem cells (NCSC). Here, we report the transformation of NCSC into tumorigenic cells, after in vitro long-term passaging. Indeed, the characterization of 6 neural crest-derived clones revealed the presence of one tumorigenic clone. Transcriptomic analyses of this clone highlighted, among others, numerous cell cycle checkpoint modifications and chromosome 11q down-regulation (suggesting a deletion of chromosome 11q) compared with the other clones. Moreover, unsupervised analysis such as a dendrogram generated after agglomerative hierarchical clustering comparing several transcriptomic data showed important similarities between the tumorigenic neural crest-derived clone and mammary tumor cell lines. Altogether, it appeared that NCSC isolated from adult bone marrow represents a potential danger for cellular therapy, and consequently, we recommend that phenotypic, functional and genetic assays should be performed on bone marrow mesenchymal and neural crest stem cells before in vivo use, to demonstrate whether their biological properties, after ex vivo expansion, remain suitable for clinical application. [less ▲]

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See detailMesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences.
Wislet, Sabine ULiege; Laudet, Emerence ULiege; Neirinckx, Virginie ULiege et al

in Cellular and Molecular Life Sciences : CMLS (2012), 69(15), 2593-2608

The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The ... [more ▼]

The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crest stem cells (NCSC) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSC), including their similarities and differences. In this paper, using transcriptomic as well as proteomic technologies, we compared NCSC to MSC and stromal nestin-positive cells, all of them isolated from adult bone marrow. We demonstrated that the nestin-positive cell population, which was the first to be described as able to differentiate into functional neurons, was a mixed population of NCSC and MSC. More interestingly, we demonstrated that MSC shared with NCSC the same ability to truly differentiate into Tuj1-positive cells when co-cultivated with paraformaldehyde-fixed cerebellar granule neurons. Altogether, those results suggest that both NCSC and MSC can be considered as important tools for cellular therapies in order to replace neurons in various neurological diseases. [less ▲]

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See detailWnt1 and BMP2: two factors recruiting multipotent neural crest progenitors isolated from adult bone marrow
Glejzer, Aneta ULiege; Laudet, Emerence ULiege; Leprince, Pierre ULiege et al

in Cellular and Molecular Life Sciences : CMLS (2011), 68/12

Recent studies have shown that neural crestderived progenitor cells can be found in diverse mammalian tissues including tissues that were not previously shown to contain neural crest derivatives, such as ... [more ▼]

Recent studies have shown that neural crestderived progenitor cells can be found in diverse mammalian tissues including tissues that were not previously shown to contain neural crest derivatives, such as bone marrow. The identification of those ‘‘new’’ neural crest-derived progenitor cells opens new strategies for developing autologous cell replacement therapies in regenerative medicine. However, their potential use is still a challenge as only few neural crest-derived progenitor cells were found in those new accessible locations. In this study, we developed a protocol, based on wnt1 and BMP2 effects, to enrich neural crest-derived cells from adult bone marrow. Those two factors are known to maintain and stimulate the proliferation of embryonic neural crest stem cells, however, their effects have never been characterized on neural crest cells isolated from adult tissues. Using multiple strategies from microarray to 2D-DIGE proteomic analyses, we characterized those recruited neural crest-derived cells, defining their identity and their differentiating abilities. [less ▲]

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See detailSubclassification of diffuse glioma tumours based on gene expression and allele copy number variation
Poulet, Christophe ULiege; Hennuy, Benoit; Robe, Pierre ULiege et al

Poster (2010, November 01)

The development of targeted cancer treatment adapted to individual patients requires the identification of different tumour classes according to their biology and prognosis. Gliomas are the most frequent ... [more ▼]

The development of targeted cancer treatment adapted to individual patients requires the identification of different tumour classes according to their biology and prognosis. Gliomas are the most frequent primitive cerebral tumours and in general are divided into 2 histological subtypes: astrocytic and oligodendroglial. Most of these tumours are diffuse and infiltrating. Relapses are inevitable, with a usually fatal outcome. The histological criteria allowing the distinction between glioma tumours remain difficult to use. For about ten years, expression microarrays have been used to refine the diagnosis of gliomas and to develop a new classification. Our work focused on genetic and transcriptomic modifications that could affect the tumour behavior in a set of 30 diffuse gliomas, including astrocytomas, oligodendrogliomas, and mixed gliomas of WHO (World Health Organization) grade II and III. We linked Mapping data from Affymetrix 250k_Nsp arrays and Expression data from Affymetrix HG_U133_Plus2 arrays through a Biological Pathways analysis. The hypothesis is that common chromosomal aberrations should affect gene expression levels in commonly involved pathways. Thus, sub-classes of gliomas are defined based on statistically affected pathways and genes. Mapping studies allowed us to confirm the discriminative status of the chromosomal 1p and 19q regions for the oligodendrogliomas. Most of the chromosomal aberrations are associated with oligodendrogliomas. Astrocytomas only shared an uniparental disomy on chromosome 17p as a common aberration. We found 3 sub-groups of gliomas characterized by distinct signaling pathway alterations (more than 50% of the genes involved in those pathways are differentially ex- pressed, p-value! 0.05). These results are currently under validation by immunohistochemistry. Combining major biological parameters in a single analysis is a powerful way to create a first step of classification. Mapping studies aim to focus on interesting genomic regions. Biological pathways led us to the main genes involved, and by transcriptomics we assessed the statistical relevance of both pathways and groups of samples. These results will lead us to refine the glioma classification based on genetic pattern, and will allow us to discriminate these tumours at a new genetic level. [less ▲]

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