References of "Boniver, Jacques"
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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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See detailCharacterization of an antibody panel for immunohistochemical analysis of canine muscle cells
Gofflot, Stéphanie ULg; Kischel, Philippe ULg; Thielen, Caroline ULg et al

in Veterinary Immunology and Immunopathology (2008), 125(3-4), 225-33

Immunohistochemistry is an indispensable tool in the assessment and characterization of lineage-specific differentiation of grafted cells in cell-based-therapy. This strategy is under investigation for ... [more ▼]

Immunohistochemistry is an indispensable tool in the assessment and characterization of lineage-specific differentiation of grafted cells in cell-based-therapy. This strategy is under investigation for the treatment of many muscle disorders and different animals such as dogs are used as models to study the tissue regeneration. The aim of the present study was to characterize an antibody panel for the analysis of canine muscle cells, useful in routinely processed formalin-fixed paraffin-embedded tissues. Overall, 12 antibodies (8 mouse monoclonal and 4 goat polyclonal), validated for use on human tissues tested for cross-reactivity on canine smooth muscle (bladder, intestine, and uterus), skeletal muscle and heart. Specific staining was achieved with eight antibodies, of which six were cytoplasmic markers (desmin, HDAC8, MHC, SMA, Troponin I and Troponin T) and two were cardiac nuclear markers (GATA-4 and Nkx-2.5). This antibody panel may be useful not only for the evaluation of cell-based therapies in muscle disorders, but also for the evaluation of canine soft tissue neoplasms in veterinary pathology. [less ▲]

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See detailThe prevention of spontaneous apoptosis of follicular lymphoma B cells by a follicular dendritic cell line: involvement of caspase-3, caspase-8 and c-FLIP.
Goval, Jean-Jacques; Thielen, Caroline ULg; Bourguignon, Caroline et al

in Haematologica (2008), 93(8), 1169-77

BACKGROUND: Follicular lymphoma, the neoplastic counterpart of germinal center B cells, typically recapitulates a follicular architecture. Several observations point to the crucial role of the cellular ... [more ▼]

BACKGROUND: Follicular lymphoma, the neoplastic counterpart of germinal center B cells, typically recapitulates a follicular architecture. Several observations point to the crucial role of the cellular microenvironment in the development and/or progression of follicular lymphoma cells in vivo. The aim of our study was to characterize the spontaneous apoptosis of follicular lymphoma cells in vitro, and the modulation of this apoptosis by follicular dendritic cells. DESIGN AND METHODS: We used a cell line derived from follicular dendritic cells to model the functional interactions of these cells and lymphoma cells in co-culture. Follicular lymphoma cells were isolated from tissue biopsies. Apoptosis was quantified by flow cytometry and apoptotic pathways were investigated by western blotting. RESULTS: The spontaneous apoptosis of follicular lymphoma cells in vitro involves the activation of caspases-3 and -8 but not of caspase-9, occurs despite persistent high levels of BCL-2 and MCL-1, and is associated with down-regulation of c-FLIP(L). Spontaneous apoptosis of follicular lymphoma cells is partially prevented by co-culture with the follicular dendritic cells, which prevents activation of caspase-8, caspase-3 and induces an upregulation of c-FLIP(L). Using neutralizing antibodies, we demonstrated that interactions involving CD54 (ICAM-1), CD106 (VCAM-1) and CD40 are implicated in this biological process. CONCLUSIONS: Follicular dendritic cells constitute a useful tool to study the functional interactions between follicular lymphoma cells and follicular dendritic cells in vitro. Understanding the molecular mechanisms involved in these protective interactions may lead to the identification of therapeutic agents that might suppress the survival and growth of follicular lymphoma cells. [less ▲]

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See detailTransforming growth factor-beta1-mediated Slug and Snail transcription factor up-regulation reduces the density of Langerhans cells in epithelial metaplasia by affecting E-cadherin expression
Herfs, Michael ULg; Hubert, Pascale ULg; Kholod, Natalia et al

in 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 ▲]

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See detailThe combined immunodetection of AP-2alpha and YY1 transcription factors is associated with ERBB2 gene overexpression in primary breast tumors.
Allouche, Abdelkader; Nolens, Gregory ULg; Tancredi, Annalisa ULg et al

in Breast Cancer Research [=BCR] (2008), 10(1), 9

INTRODUCTION: Overexpression of the ERBB2 oncogene is observed in about 20% of human breast tumors and is the consequence of increased transcription rates frequently associated with gene amplification ... [more ▼]

INTRODUCTION: Overexpression of the ERBB2 oncogene is observed in about 20% of human breast tumors and is the consequence of increased transcription rates frequently associated with gene amplification. Several studies have shown a link between activator protein 2 (AP-2) transcription factors and ERBB2 gene expression in breast cancer cell lines. Moreover, the Yin Yang 1 (YY1) transcription factor has been shown to stimulate AP-2 transcriptional activity on the ERBB2 promoter in vitro. In this report, we examined the relationships between ERBB2, AP-2alpha, and YY1 both in breast cancer tissue specimens and in a mammary cancer cell line. METHODS: ERBB2, AP-2alpha, and YY1 protein levels were analyzed by immunohistochemistry in a panel of 55 primary breast tumors. ERBB2 gene amplification status was determined by fluorescent in situ hybridization. Correlations were evaluated by a chi2 test at a p value of less than 0.05. The functional role of AP-2alpha and YY1 on ERBB2 gene expression was analyzed by small interfering RNA (siRNA) transfection in the BT-474 mammary cancer cell line followed by real-time reverse transcription-polymerase chain reaction and Western blotting. RESULTS: We observed a statistically significant correlation between ERBB2 and AP-2alpha levels in the tumors (p < 0.01). Moreover, associations were found between ERBB2 protein level and the combined high expression of AP-2alpha and YY1 (p < 0.02) as well as between the expression of AP-2alpha and YY1 (p < 0.001). Furthermore, the levels of both AP-2alpha and YY1 proteins were inversely correlated to ERBB2 gene amplification status in the tumors (p < 0.01). Transfection of siRNAs targeting AP-2alpha and AP-2gamma mRNAs in the BT-474 breast cancer cell line repressed the expression of the endogenous ERBB2 gene at both the mRNA and protein levels. Moreover, the additional transfection of an siRNA directed against the YY1 transcript further reduced the ERBB2 protein level, suggesting that AP-2 and YY1 transcription factors cooperate to stimulate the transcription of the ERBB2 gene. CONCLUSION: This study highlights the role of both AP-2alpha and YY1 transcription factors in ERBB2 oncogene overexpression in breast tumors. Our results also suggest that high ERBB2 expression may result either from gene amplification or from increased transcription factor levels. [less ▲]

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See detailHigh frequency of RASSF1A and RARb2 gene promoter methylation in morphologically normal endometrium adjacent to endometrioid adenocarinoma
Arafa, M.; Kridelka, Frédéric ULg; Mathias, Valérie ULg et al

in Histopathology (2008), 53(5), 525-532

Aims: To identify a DNA methylation signature of endometrioid carcinoma of the endometrium (EEC) in the early stages of endometrial carcinogenesis. <br />Methods and results: Archival biopsy specimens of ... [more ▼]

Aims: To identify a DNA methylation signature of endometrioid carcinoma of the endometrium (EEC) in the early stages of endometrial carcinogenesis. <br />Methods and results: Archival biopsy specimens of 39 EECs, 14 cases of atypical hyperplasia (AH), 11 histologically normal endometrial tissues adjacent to EECs and 24 normal control endometrial samples were retrieved. The cases were tested by quantitative methylation-specific polymerase chain reaction with primers hybridizing in the promoter regions of five genes frequently methylated in human cancer (RASSF1A, RARb2, P16, MGMT and GSTPi). Twenty-nine of 39 (74%) EECs and 7/14 (50%) AHs were methylated for the RASSF1A gene, whereas 17/39 (44%) EECs and 6/14 (43%) AHs were positive for the methylation of the RARb2 gene. No significant results were obtained for the other genes (P16, MGMT and GSTPi). Interestingly, 4/11 (36%) and 6/11 (55%) histologically normal endometrial tissues adjacent to EEC showed, respectively, RASSF1A and RARb2 gene methylation. Furthermore, these 11 specimens were microsatellite stable and showed similar proliferative, cell cycle and apoptotic mean labelling indices as the normal endometrial control tissues. <br />Conclusions: Promoter region methylation of RASSF1A and RARb2 genes is an early event in endometrial carcinogenesis. [less ▲]

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See detailTCRγδ cells in HPV-associated cervical cancer
Renoux, Virginie ULg; de Leval, Laurence ULg; Waroux, Olivier ULg et al

in Acta Clinica Belgica (2008), 63

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See detailFactors influencing physicians' detection of cancer patients' and relatives distress : can a communication skills training program improve physicians' detection?
Merckaert, I.; Libert, Y.; Delvaux, N. et al

in Psycho-oncology (2008), 17

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See detailIn vivo administration of a PKA type I inhibitor (Rp-8-Br-cAMPS) restores T-cell responses in retrovirus-infected mice
Nayjib, Btissam ULg; Zeddou, Mustapha ULg; Drion, Pierre ULg et al

in Open Immunol journal (2008), 1

Murine AIDS (MAIDS) is caused by infection with the murine leukemia retrovirus RadLV-Rs and is characterized by T-cell anergy and severe immunodeficiency with increased susceptibilty to several ... [more ▼]

Murine AIDS (MAIDS) is caused by infection with the murine leukemia retrovirus RadLV-Rs and is characterized by T-cell anergy and severe immunodeficiency with increased susceptibilty to several experimental opportunistic infections as observed in HIV infection. T cell anergy is associated with an increase of intracellular cAMP level, triggering a multistep pathway involving activation of PKA type I and resulting in inhibition of proximal TCR signaling. We have reviously demonstrated that blocking PKA type I using the selective inhibitor Rp-8-Br-cAMPS, restores T-cell function in vitro in MAIDS as well as in HIV infection. In the present report, we investigated the effect of parenteral administration of Rp-8-Br-cAMPS in mice with MAIDS. We show that the compound is not toxic and partially restores the ex vivo proliferative responses to anti-CD3 mAb, but that it has no effect on the lymphadenopathy and splenomegaly characterizing the MAIDS syndrome. [less ▲]

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See detailInteraction between virus like particles (VLP) and natural killer (NK) cells
Renoux, Virginie ULg; Dortu, Estelle ULg; Provenzano, Fabian et al

in Acta Clinica Belgica (2008), 2

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See detailInnate lymphocyte and dendritic cell cross-talk: a key factor in the regulation of the immune response.
Reschner, Anca ULg; Hubert, Pascale ULg; Delvenne, Philippe ULg et al

in Clinical & Experimental Immunology (2008), 152(2), 219-26

Dendritic cells (DC) are specialized in the presentation of antigens and the initiation of specific immune responses. They have been involved recently in supporting innate immunity by interacting with ... [more ▼]

Dendritic cells (DC) are specialized in the presentation of antigens and the initiation of specific immune responses. They have been involved recently in supporting innate immunity by interacting with various innate lymphocytes, such as natural killer (NK), NK T or T cell receptor (TCR)-gammadelta cells. The functional links between innate lymphocytes and DC have been investigated widely and different studies demonstrated that reciprocal activations follow on from NK/DC interactions. The cross-talk between innate cells and DC which leads to innate lymphocyte activation and DC maturation was found to be multi-directional, involving not only cell-cell contacts but also soluble factors. The final outcome of these cellular interactions may have a dramatic impact on the quality and strength of the down-stream immune responses, mainly in the context of early responses to tumour cells and infectious agents. Interestingly, DC, NK and TCR-gammadelta cells also share similar functions, such as antigen uptake and presentation, as well as cytotoxic and tumoricidal activity. In addition, NK and NK T cells have the ability to kill DC. This review will focus upon the different aspects of the cross-talk between DC and innate lymphocytes and its key role in all the steps of the immune response. These cellular interactions may be particularly critical in situations where immune surveillance requires efficient early innate responses. [less ▲]

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See detailDetection of HPV-induced cervical (pre)neoplastic lesions: a tissue microarray (TMA) study
Arafa, Mohammad Mahmoud Mohammad ULg; Boniver, Jacques ULg; Delvenne, Philippe ULg

in Applied Immunohistochemistry & Molecular Morphology (2008), 16(5), 422-432

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See detailCervix carcinoma is associated with an up-regulation and nuclear localization of the dual-specificity protein phosphatase VHR.
Henkens, Rachel ULg; Delvenne, Philippe ULg; Arafa, Mohammad et al

in BMC Cancer (2008), 8

BACKGROUND: The 21-kDa Vaccinia virus VH1-related (VHR) dual-specific protein phosphatase (encoded by the DUSP3 gene) plays a critical role in cell cycle progression and is itself regulated during the ... [more ▼]

BACKGROUND: The 21-kDa Vaccinia virus VH1-related (VHR) dual-specific protein phosphatase (encoded by the DUSP3 gene) plays a critical role in cell cycle progression and is itself regulated during the cell cycle. We have previously demonstrated using RNA interference that cells lacking VHR arrest in the G1 and G2 phases of the cell cycle and show signs of beginning of cell senescence. METHODS: In this report, we evaluated successfully the expression levels of VHR protein in 62 hysterectomy or conization specimens showing the various (pre) neoplastic cervical epithelial lesions and 35 additional cases of hysterectomy performed for non-cervical pathologies, from patients under 50 years of age. We used a tissue microarray and IHC technique to evaluate the expression of the VHR phosphatase. Immunofluorescence staining under confocal microscopy, Western blotting and RT-PCR methods were used to investigate the localization and expression levels of VHR. RESULTS: We report that VHR is upregulated in (pre) neoplastic lesions (squamous intraepithelial lesions; SILs) of the uterine cervix mainly in high grade SIL (H-SIL) compared to normal exocervix. In the invasive cancer, VHR is also highly expressed with nuclear localization in the majority of cells compared to normal tissue where VHR is always in the cytoplasm. We also report that this phosphatase is highly expressed in several cervix cancer cell lines such as HeLa, SiHa, CaSki, C33 and HT3 compared to primary keratinocytes. The immunofluorescence technique under confocal microscopy shows that VHR has a cytoplasmic localization in primary keratinocytes, while it localizes in both cytoplasm and nucleus of the cancer cell lines investigated. We report that the up-regulation of this phosphatase is mainly due to its post-translational stabilization in the cancer cell lines compared to primary keratinocytes rather than increases in the transcription of DUSP3 locus. CONCLUSION: These results together suggest that VHR can be considered as a new marker for cancer progression in cervix carcinoma and potential new target for anticancer therapy. [less ▲]

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See detailHuman bone marrow adipocytes block granulopoiesis through neuropilin-1-induced granulocyte colony-stimulating factor inhibition.
Belaid-Choucair, Zakia ULg; Lepelletier, Yves; Poncin, Géraldine ULg et al

in Stem Cells (2008), 26(6), 1556-64

Adipocytes are part of hematopoietic microenvironment, even though up to now in humans, their role in hematopoiesis is still questioned. We have previously shown that accumulation of fat cells in femoral ... [more ▼]

Adipocytes are part of hematopoietic microenvironment, even though up to now in humans, their role in hematopoiesis is still questioned. We have previously shown that accumulation of fat cells in femoral bone marrow (BM) coincides with increased expression of neuropilin-1 (NP-1), while it is weakly expressed in hematopoietic iliac crest BM. Starting from this observation, we postulated that adipocytes might exert a negative effect on hematopoiesis mediated through NP-1. To test this hypothesis, we set up BM adipocytes differentiated into fibroblast-like fat cells (FLFC), which share the major characteristics of primitive unilocular fat cells, as an experimental model. As expected, FLFCs constitutively produced macrophage colony stimulating factor and induced CD34(+) differentiation into macrophages independently of cell-to-cell contact. By contrast, granulopoiesis was hampered by cell-to-cell contact but could be restored in transwell culture conditions, together with granulocyte colony stimulating factor production. Both functions were also recovered when FLFCs cultured in contact with CD34(+) cells were treated with an antibody neutralizing NP-1, which proved its critical implication in contact inhibition. An inflammatory cytokine such as interleukin-1 beta or dexamethasone modulates FLFC properties to restore granulopoiesis. Our data provide the first evidence that primary adipocytes exert regulatory functions during hematopoiesis that might be implicated in some pathological processes. Disclosure of potential conflicts of interest is found at the end of this article. [less ▲]

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See detailTARC and IL-5 expression correlates with tissue eosinophilia in peripheral T-cell lymphomas.
Thielen, Caroline ULg; Radermacher, Vincent ULg; Trimeche, Mounir et al

in Leukemia Research (2008), 32(9), 1431-8

The current study attempts to characterize the eosinophilia associated with T-cell lymphomas and to investigate its possible relationship with the secretion of eosinophil-stimulating factors by lymphoma ... [more ▼]

The current study attempts to characterize the eosinophilia associated with T-cell lymphomas and to investigate its possible relationship with the secretion of eosinophil-stimulating factors by lymphoma cells and/or intra-tumoral surrounding cells. Paraffin-embedded specimens from 50 patients diagnosed with peripheral T-cell lymphomas, either unspecified (PTCL-U, n=30) or angioimmunoblastic (AITL, n=20) were morphologically assessed for intra-tumoral eosinophilia and analyzed by immunohistochemistry using specific antibodies directed against TARC, IL-5, RANTES, and eotaxin. The AITL and PTCL-U cases contained a mean of 147+/-41 and 102+/-37 eosinophils per 10 high power fields, respectively. Thirty-two of 47 cases (68%) showed IL-5-positive lymphoma cells while 15/50 (30%) tumors showed variable staining for TARC in scattered non-lymphoid cells with dendritic morphology. TARC and IL-5-positive cases possessed significantly more eosinophils. Our data indicate that IL-5 and TARC expression highly correlate with eosinophilia in T-cell lymphomas, suggesting that these chemokines are involved in the recruitment of eosinophils into the tumors. [less ▲]

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See detailA New Dimethyl Sulfoxide-Based Method for Gene Promoter Methylation Detection
Kholod, Natalia ULg; Boniver, Jacques ULg; Delvenne, Philippe ULg

in Journal of Molecular Diagnostics (2007), 9(5), 574-81

The identification of gene promoter methylation is a useful tool for the molecular diagnosis of human diseases. We have developed a new PCR-based technique for detecting the methylation status of CpG ... [more ▼]

The identification of gene promoter methylation is a useful tool for the molecular diagnosis of human diseases. We have developed a new PCR-based technique for detecting the methylation status of CpG islands of gene promoters. This new method, named methyl-sensitive dimethyl sulfoxide-PCR (Ms-DMSO-PCR), is based on the finding that methylated and unmethylated DNAs show a different sensitivity to the amount of DMSO used in the PCR reaction. For the amplification of methylated DNA, more DMSO is required in comparison to unmethylated DNA. This finding resulted in the development of a simple PCR screening of CpG islands with addition of DMSO in the range from 0 to 8% (v/v), and the same pair of primers is sufficient for distinguishing hyper- or hypomethylated gene promoters from normally methylated sequences. This new technique is a one-step procedure and does not require any modifications of DNA or expensive equipment. Therefore, Ms-DMSO-PCR has the potential to be widely used for clinical applications as well in basic research. [less ▲]

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