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See detailCross talk between dendritic and natural killer cells in the presence of vaccine agent against cervical cancer
Langers, Inge ULg; Renoux, Virginie ULg; Reschner, Anca ULg et al

in Belgian Journal of Medical Oncology [=BJMO] (2010, January 30), 4

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See detailRegulation of p63 Isoforms by Snail and Slug Transcription Factors in Human Squamous Cell Carcinoma.
Herfs, Michael ULg; Hubert, Pascale ULg; Suarez-Carmona, Meggy ULg et al

in American Journal of Pathology (2010), 176(4), 1941-1949

TP63 is a p53-related gene that contains two alternative promoters, which give rise to transcripts that encode proteins with (TAp63) or without (DeltaNp63) an amino-transactivating domain. Whereas the ... [more ▼]

TP63 is a p53-related gene that contains two alternative promoters, which give rise to transcripts that encode proteins with (TAp63) or without (DeltaNp63) an amino-transactivating domain. Whereas the expression of p63 is required for proper development of epithelial structures, the role of p63 in tumorigenesis remains unclear. Here, we investigated the role of Snail and Slug transcription factors, known to promote epithelial-to-mesenchymal transitions during development and cancer, in the regulation of p63 isoforms in human squamous cell carcinoma (SCC). In the present study, we observed that the expressions of DeltaN and TAp63 isoforms were, respectively, down- and up-regulated by both Snail and Slug. However, the induction of TAp63 was not directly caused by these two transcription factors but resulted from the loss of DeltaNp63, which acts as dominant-negative inhibitor of TAp63. In SCC cell lines and cancer tissues, high expression of Snail and Slug was also significantly associated with altered p63 expression. Finally, we showed that DeltaNp63 silencing reduced cell-cell adhesion and increased the migratory properties of cancer cells. These data suggest that the disruption of p63 expression induced by Snail and Slug plays a crucial role in tumor progression. Therefore, p63 and its regulating factors could constitute novel prognosis markers in patients with SCC and attractive targets for the therapeutic modulation of neoplastic cell invasiveness. [less ▲]

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See detailFish and chips
DELVENNE, Philippe ULg; Deprez, Manuel ULg; BISIG, Bettina ULg et al

in Revue Médicale de Liège (2010), 65 Spec no.

Academic hospital laboratories should offer patients the possibility to have the most accurate diagnosis by the development of new analyses, such as molecular biology tests including FISH (Fluorescent In ... [more ▼]

Academic hospital laboratories should offer patients the possibility to have the most accurate diagnosis by the development of new analyses, such as molecular biology tests including FISH (Fluorescent In Situ Hybridization) and chips (microarrays,...). The purpose of this article is to describe the principles and the potential applications of these techniques. [less ▲]

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See detailHyperacute graft rejection during heart transplantation for giant cell myocarditis: A case report.
Mutijima, E.; Delbecque, Katty ULg; Defraigne, Jean-Olivier ULg et al

in Pathology - Research & Practice (2010), 15(206), 411-4

We report the case of a patient with giant cell myocarditis who was bridged to transplantation with mechanical circulatory support and developed a fatal perioperative hyperacute rejection. The patient had ... [more ▼]

We report the case of a patient with giant cell myocarditis who was bridged to transplantation with mechanical circulatory support and developed a fatal perioperative hyperacute rejection. The patient had received abundant transfusions that had raised her anti-HLA antibody titers. The cross-match test was positive. No pre-transplantation immunosuppressive therapy had been administered given concomitant infection. The severity and acuteness of the rejection in this case likely reflect the combined effect of preformed anti-HLA antibodies in the context of an active organ-specific immune process at the time of transplantation. This case raises the questions of the need for intensive immunosuppressive therapy before transplantation in giant cell myocarditis and of the management of patients with positive cross-match in the context of a giant cell myocarditis. [less ▲]

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See detailLocal applications of GM-CSF induce the recruitment of immune cells in cervical low-grade squamous intraepithelial lesions.
Hubert, Pascale ULg; Doyen, Jean ULg; Capelle, Xavier ULg et al

in American Journal of Reproductive Immunology (2010), 64(2), 126-136

Abstract Problem Quantitative alterations of antigen-presenting cells (APC) in (pre)neoplastic lesions of the uterine cervix associated with human papillomavirus (HPV) infection suggest a diminished ... [more ▼]

Abstract Problem Quantitative alterations of antigen-presenting cells (APC) in (pre)neoplastic lesions of the uterine cervix associated with human papillomavirus (HPV) infection suggest a diminished capacity to capture viral antigens and to induce a protective immune response. Method of study To test if a cervical application of GM-CSF could restore an immune response against HPV in women with cervical low-grade squamous intraepithelial lesions (LSIL). We performed two clinical trials with11 healthy women and 15 patients with LSIL. Results GM-CSF applications were well tolerated in all enrolled women and no difference in toxicity between the treated and placebo groups was observed during the follow up (until 30 months). Interestingly, in the GM-CSF treated group, a significant increased APC and cytotoxic T lymphocyte infiltration was observed in the cervical biopsies with no change in regulatory T cell numbers. All the HPV16+ patients exhibited an immune response against HPV16 after GM-CSF applications, as shown by NK and/or T cells producing IFN-γ whereas no cellular immune response was observed before the treatment. Moreover, the anti-VLP antibody titers also increased after the treatment. Conclusion These encouraging results obtained from a limited number of subjects justify further study on the therapeutic effect of APC in cervical (pre)neoplastic lesions. [less ▲]

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See detailProgression model tissue microarray (TMA) for the study of uterine carcinomas.
Arafa, Mohammad; Boniver, Jacques ULg; Delvenne, Philippe ULg

in Disease Markers (2010), 28(5), 267-72

Cervical and endometrial uterine carcinomas are heterogeneous groups of cancers, which are preceded by preneoplastic lesions. More accurate tools are needed to improve the diagnosis and to define markers ... [more ▼]

Cervical and endometrial uterine carcinomas are heterogeneous groups of cancers, which are preceded by preneoplastic lesions. More accurate tools are needed to improve the diagnosis and to define markers which may be relevant for the diagnosis, prediction of disease progression and therapeutic response.High throughput technologies for testing and validating molecular targets in cancer lesions and in their precursors are presently available. Among them, the tissue microarray (TMA) presents the advantage of a morphological control of the analyzed tissue fragment. In this article, we review the different aspects of the TMA technology with a special consideration to a uterine carcinogenesis model. [less ▲]

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See detailCurrent concepts in the pathology and epigenetics of endometrial carcinoma.
Arafa, Mohammad; Somja, Joan ULg; Dehan, Pierre ULg et al

in Pathology (2010), 42(7), 613-7

In the Western world, endometrial carcinoma is the most common malignant tumour of the female genital tract and is the fourth most common cancer in women. Two different clinicopathological subtypes are ... [more ▼]

In the Western world, endometrial carcinoma is the most common malignant tumour of the female genital tract and is the fourth most common cancer in women. Two different clinicopathological subtypes are recognised: the oestrogen-related (type I, endometrioid) and the non-oestrogen related (type II, non-endometrioid). This article reviews the epidemiology, risk factors, genetic alterations during endometrial carcinogenesis, features of tumours and precursors and early detection of the disease. Insights into the epigenetic alterations, with emphasis on DNA methylation during endometrial carcinogenesis, and their diagnostic value are also provided. [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 detailHuman Papillomavirus Virus-Like particles and NK cell interactions:role of CD16
Renoux, Virginie ULg; Langers Inge; Clémenceau Béatrice et al

in International Immunology (2010), 22(suppl Pt 5), 17

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See detailReasoning versus knowledge retention and ascertainment throughout a problem-based learning curriculum
Collard, Anne ULg; Gelaes, Sabine ULg; Vanbelle, Sophie ULg et al

in Medical Education (2009), 43

CONTEXT: Since 2000, problem-based learning (PBL) seminars have been introduced into the curriculum of medical studies at the University of Liège. We aimed to carry out a cross-sectional investigation of ... [more ▼]

CONTEXT: Since 2000, problem-based learning (PBL) seminars have been introduced into the curriculum of medical studies at the University of Liège. We aimed to carry out a cross-sectional investigation of the maturational increase in biomedical reasoning capacity in comparison with factual knowledge retention throughout the curriculum. METHODS: We administered a factual knowledge test (i.e. a true ⁄ false test with ascertainment degree) and a biomedical reasoning test (i.e. an adapted script concordance test [SCT]) to 104 students (Years 3–6) and a reference panel. The selected topic was endocrinology. RESULTS: On the SCT, the students obtained higher scores in Years 5 and 6 than in Years 3 and 4. In Year 3, the scores obtained on SCT questions in a new context indicated transfer of reasoning skills. On the true ⁄ false test, the scores of Year 3 students were significantly higher than those of students in the other three year groups. A positive correlation between SCT scores and true ⁄ false test scores was observed only for students in Years 3 and 4. In each group, the ascertainment degree scores were higher for correct than for incorrect responses and the difference was calculated as an index of self-estimation of core knowledge. This index was found to be positively correlated to SCT scores in the four year groups studied. CONCLUSIONS: Biomedical reasoning skills are evidenced early in a curriculum involving PBL and further increase during training. This is accompanied by a decrease in factual knowledge retention. The self-estimation of core knowledge appears to be related to reasoning capacity, which suggests there is a link between the two processes. [less ▲]

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See detailSymptom attribution and radiation thérapy for breast cancer : changes over time and associated psychological factors
Bonamis, O.; Liénard, A.; Coucke, Philippe ULg et al

in Psycho-oncology (2009, June), 18 (Suppl. 2)

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See detailIncreased migration of Langerhans cells in response to HPV16 E6 and E7 oncogene silencing: role of CCL20
Caberg, Jean-Hubert ULg; Hubert, Pascale ULg; Herman, Ludivine ULg et al

in Cancer Immunology, Immunotherapy (2009), 58(1), 39-47

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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 detailMolecular classification of T-cell lymphomas.
De Leval, Laurence ULg; Bisig, Bettina ULg; Thielen, Caroline ULg et al

in Critical Reviews in Oncology/Hematology (2009)

T-cell neoplasms encompass a heterogeneous group of relatively rare disease entities. This review, focused on lymphoblastic tumors (T-ALL/LBL) and nodal-based peripheral T-cell lymphomas (PTCL ... [more ▼]

T-cell neoplasms encompass a heterogeneous group of relatively rare disease entities. This review, focused on lymphoblastic tumors (T-ALL/LBL) and nodal-based peripheral T-cell lymphomas (PTCL), summarizes recent advances in the molecular characterization of these diseases. In T-ALL/LBL, molecular subgroups delineated by gene expression profiling correlate with leukemic arrest at specific stages of normal thymocyte development and different oncogenic pathways, and seem to be of interest for prognosis prediction. Angioimmunoblastic T-cell lymphoma (AITL), one of the most common PTCL entities, comprises neoplastic cells with a molecular signature similar to normal follicular helper T cells, and this cellular derivation might account for several of the peculiar aspects of this disease. Except in ALK-positive anaplastic large cell lymphoma, defined by ALK gene fusions, chromosomal translocations are otherwise rare in PTCLs, but some recurrent rearrangements might be associated with distinct lymphoma subtypes. In PTCL, not otherwise specified (PTCL, NOS), novel molecular biomarkers of potential therapeutic interest have been recently identified. [less ▲]

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See detailBudd-Chiari Syndrome Complicating Hepatic Sarcoidosis: Definitive Treatment by Liver Transplantation: A Case Report.
Delfosse, Vincent ULg; De Leval, Laurence ULg; De Roover, Arnaud ULg et al

in Transplantation Proceedings (2009), 41(8), 3432-3434

Sarcoidotic involvement of the liver is frequent, albeit uncommonly symptomatic. Severe complications are rare, but may seldom require liver transplantation. Budd-Chiari syndrome has been described in a ... [more ▼]

Sarcoidotic involvement of the liver is frequent, albeit uncommonly symptomatic. Severe complications are rare, but may seldom require liver transplantation. Budd-Chiari syndrome has been described in a few patients with hepatic sarcoidosis. Herein we have reported the case of a young woman suffering from hepatic sarcoidosis who developed severe cholestasis and chronic Budd-Chiari syndrome. She successfully underwent orthotopic liver transplantation (OLT) and is asymptomatic with normal liver function at 3 years follow-up. Histopathological assessment of the liver explant demonstrated a florid granulomatous process, with involvement of the large intrahepatic veins, providing an anatomical basis for the vascular flow disturbances. This case adds further evidence that liver transplantation may be the curative treatment for complicated sarcoidotic liver disease. [less ▲]

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See detailPrimary mucosa-associated lymphoid tissue lymphoma of the gallbladder: report of a case harboring API2/MALT1 gene fusion.
Bisig, Bettina ULg; Copie-Bergman, Christiane; Baia, Maryse et al

in Human Pathology (2009), 40(10), 1504-9

The genetic alterations underlying extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue type are heterogeneous and show variation according to the tumor site. Here, we report a ... [more ▼]

The genetic alterations underlying extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue type are heterogeneous and show variation according to the tumor site. Here, we report a case of mucosa-associated lymphoid tissue lymphoma of the gallbladder with genetic characterization. This lymphoma, diagnosed in a 75-year-old woman who underwent cholecystectomy for suspected acute cholecystitis, presented as diffuse thickening of the gallbladder wall. The morphology was typical of mucosa-associated lymphoid tissue lymphoma, and by immunophenotype, the tumor cells were CD20+ CD5- CD10- CD23- CD43- BCL6- BCL2+ IgM+ IgD- lambda+, with moderate nuclear expression of BCL10. Interphase fluorescence in situ hybridization analysis on paraffin sections, using a fusion probe for API2/MALT1, demonstrated 2 fusion signals in most nuclei, bringing the first documentation of a t(11;18)(q21;q21) in this exceptional primary disease location. [less ▲]

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