Partial trisomy 4q associated with young-onset dopa-responsive parkinsonism.Garraux, Gaëtan ; CABERG, Jean-Hubert ; et alin Archives of Neurology (2012), 69(3), 398-400 OBJECTIVE: To describe a patient who developed a young-onset, dopa-responsive parkinsonism linked to a de novo heterozygous interstitial duplication 4q. DESIGN: Case report. SETTING: Movement Disorder ... [more ▼] OBJECTIVE: To describe a patient who developed a young-onset, dopa-responsive parkinsonism linked to a de novo heterozygous interstitial duplication 4q. DESIGN: Case report. SETTING: Movement Disorder Outpatient Clinic at the University Hospital Centre, Liege, Belgium. Patient A 31-year-old woman. MAIN OUTCOME MEASURES: Clinical, neuroimaging, and genetic data. RESULTS: The duplicated region contains 150 known genes, including the alpha-synuclein (SNCA) gene locus. Motor and 6-[(18)F]fluoro-L-dopa positron emission tomography features are similar to those previously reported in heterozygote SNCA duplication carriers. Altered expression of other genes contained in the duplicated region may contribute to clinical features that are uncommon in the phenotypic spectrum of SNCA multiplications such as delayed developmental psychomotor milestones during infancy and musculoskeletal abnormalities. CONCLUSION: This case report provides new insights on the genetic basis of parkinsonism. [less ▲] Detailed reference viewed: 25 (8 ULg) Surface Mucin-1 does not play a role in dendritic cell migration; Caberg, Jean-Hubert ; et alin Molecular Immunology (2009), 46(4), 738-742 Detailed reference viewed: 20 (3 ULg) Increased migration of Langerhans cells in response to HPV16 E6 and E7 oncogene silencing: role of CCL20Caberg, Jean-Hubert ; Hubert, Pascale ; Herman, Ludivine et alin Cancer Immunology, Immunotherapy (2009), 58(1), 39-47 Detailed reference viewed: 32 (7 ULg) Silencing of E7 oncogene restores functional E-cadherin expression in human papillomavirus 16-transformed keratinocytesCaberg, Jean-Hubert ; Hubert, Pascale ; Begon, Dominique et alin Carcinogenesis (2008), 29(7), 1441-7 Detailed reference viewed: 29 (10 ULg) Transforming growth factor-beta1-mediated Slug and Snail transcription factor up-regulation reduces the density of Langerhans cells in epithelial metaplasia by affecting E-cadherin expressionHerfs, Michael ; Hubert, Pascale ; et alin American Journal of Pathology (2008), 172(5), 1391-402 Epithelial metaplasia (EpM) is an acquired tissue abnormality resulting from the transformation of epithelium into another tissue with a different structure and function. This adaptative process is ... [more ▼] Epithelial metaplasia (EpM) is an acquired tissue abnormality resulting from the transformation of epithelium into another tissue with a different structure and function. This adaptative process is associated with an increased frequency of (pre)cancerous lesions. We propose that EpM is involved in cancer development by altering the expression of adhesion molecules important for cell-mediated antitumor immunity. Langerhans cells (LCs) are intraepithelial dendritic cells that initiate immune responses against viral or tumor antigens on both skin and mucosal surfaces. In the present study, we showed by immunohistology that the density of CD1a LCs is reduced in EpM of the uterine cervix compared with native squamous epithelium and that the low number of LCs observed in EpM correlates with the down-regulation of cell-surface E-cadherin. We also demonstrated that transforming growth factor- 1 is not only overexpressed in metaplastic tissues but also reduces E-cadherin expression in keratinocytes in vitro by inducing the promoter activity of Slug and Snail transcription factors. Finally, we showed that in vitro-generated LCs adhere poorly to keratinocytes transfected with either Slug or Snail DNA. These data suggest that transforming growth factor- 1 indirectly reduces antigenpresenting cell density in EpM by affecting E-cadherin expression, which might explain the increased susceptibility of abnormal tissue differentiation to the development of cancer by the establishment of local immunodeficiency responsible for EpM tumorigenesis. [less ▲] Detailed reference viewed: 58 (18 ULg) The cross-talk between dendritic and regulatory T cells: good or evil?Hubert, Pascale ; Jacobs, Nathalie ; Caberg, Jean-Hubert et alin Journal of Leukocyte Biology (2007), 82(4), 781-94 Immune responses against pathogens require fine regulation in order to avoid excessive inflammation, which could be harmful to the host. Moreover, the immune system must be tolerant to non-pathogenic ... [more ▼] Immune responses against pathogens require fine regulation in order to avoid excessive inflammation, which could be harmful to the host. Moreover, the immune system must be tolerant to non-pathogenic antigens in order to prevent allergy, autoimmunity and transplant rejection. There is accumulating evidence that interactions between dendritic cells (DC) and regulatory T (Treg) cells play a crucial role in the balance between immune response and tolerance. Communications between these cells are complex, bi-directional and mediated by soluble or cell surface molecules. The maturation status of DC, which may be influenced by different microenvironmental factors, is considered as an important checkpoint for the induction of peripheral tolerance through modifications of the activation status of T cells. Moreover, several lines of experimental evidence suggest that different subsets or the functional status of DC are also involved in the promotion of Treg cell differentiation. A better knowledge of the regulatory mechanisms of the immune response induced or inhibited by DC via their interactions with Treg cells could be relevant for the development of new immunotherapeutic approaches. [less ▲] Detailed reference viewed: 59 (13 ULg) MIP3 alpha stimulates the migration of Langerhans cells in models of human papillomavirus (HPV)-associated (pre)neoplastic epitheliumHerman, Ludivine ; Hubert, Pascale ; Caberg, Jean-Hubert et alin Cancer Immunology, Immunotherapy (2007), 56(7), 1087-1096 Detailed reference viewed: 42 (4 ULg) Le cancer du col de l'utérus: du virus au traitementDelvenne, Philippe ; Goffin, Frédéric ; Kridelka, Frédéric et alin Revue Médicale de Liège (2007), 62(S1) Squamous cell cancer of the uterine cervix is associated with a high morbidity and mortality worldwide and in Belgium. New therapeutic approaches have been recently proposed. The development of this ... [more ▼] Squamous cell cancer of the uterine cervix is associated with a high morbidity and mortality worldwide and in Belgium. New therapeutic approaches have been recently proposed. The development of this cancer is related to the infection by oncogenic human papillomavirus (HPV) types. The link between cervical cancer and HPV has, in recent years, generated, a great interest for studies aiming to better understand the role of the immune system in the control of these infections and for the development of prophylactic anti-HPV vaccines. [less ▲] Detailed reference viewed: 164 (22 ULg) Role of hormone cofactors in the human papillomavirus-induced carcinogenesis of the uterine cervixDelvenne, Philippe ; Herman, Ludivine ; et alin Molecular & Cellular Endocrinology (2007), 264(1-2), 1-5 If human papillomavirus (HPV) is necessary for the development of (pre)neoplastic lesions of the uterine cervix, it is not sufficient. Among the cofactors involved in the malignant transformation of cells ... [more ▼] If human papillomavirus (HPV) is necessary for the development of (pre)neoplastic lesions of the uterine cervix, it is not sufficient. Among the cofactors involved in the malignant transformation of cells infected by HPV, sex hormones may facilitate the cervical carcinogenesis by different mechanisms, including the induction of squamous metaplasia in the transformation zone of the cervix, interactions between steroid hormones and HPV gene expression and alterations of the local immune microenvironment. [less ▲] Detailed reference viewed: 40 (10 ULg) Defensis induce the recruitment of dendritic cells in cervical human papillomavirus-associated (pre)neoplastic lesions formed in vitro and transplanted in vivoHubert, Pascale ; Herman, Ludivine ; Maillard, Catherine et alin FASEB Journal (2007), 21(11), 2765-75 In addition to their direct antimicrobial activity, defensins might also influence adaptive immunity by attracting immature dendritic cells (DC). As these cells have been shown to be deficient in uterine ... [more ▼] In addition to their direct antimicrobial activity, defensins might also influence adaptive immunity by attracting immature dendritic cells (DC). As these cells have been shown to be deficient in uterine cervix carcinogenesis, we evaluated the ability of -defensin (HNP-2, human neutrophil defensin 2) and ß-defensin (HßD2, human beta defensin 2) to stimulate their migration in human papillomavirus (HPV)-associated (pre)cancers. We first observed, using RT-PCR and immunohistology, that HßD2 is absent in HPV-transformed keratinocytes and that it is weakly expressed in cervical (pre)neoplastic lesions in comparison with normal keratinocytes. We next demonstrated that defensins exert a chemotactic activity for DC in a Boyden Chamber assay and stimulate their infiltration in an in vitro-formed (pre)neoplastic epithelium (organotypic culture of HPV-transformed keratinocytes). To evaluate the ability of defensins also to recruit DC in vivo, we developed a model of immunodeficient mice grafted with organotypic cultures of HPV+ keratinocytes, which form an epithelium similar to a high-grade neoplastic lesion, with tumoral invasion and neovascularization. Intravenously injected human DC were able to infiltrate grafts of HPV+ keratinocytes after administration of HNP-2 in the transplantation chamber. Taken together, these results suggest that defensins could reverse a frequent immune alteration observed in cancer development. [less ▲] Detailed reference viewed: 43 (17 ULg) E-cadherin-dependent adhesion of dendritic and Langerhans cells to keratinocytes is defective in cervical human papillomavirus-associated (pre)neoplastic lesionsHubert, Pascale ; Caberg, Jean-Hubert ; Gilles, Christine et alin Journal of Pathology (The) (2005), 206(3), 346-355 Detailed reference viewed: 31 (6 ULg) |
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