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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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See detailInteraction between the vaccine of cervical cancer associated and natural killer (NK) cells
Renoux, Virginie ULg; Longton, Laurence; Dortu, Estelle ULg et al

Poster (2007, October 11)

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See detailInteraction between human papillomavirus (HPV) and natural killer (NK) cells
Renoux, Virginie ULg; Longton, Laurence; Dortu, Estelle ULg et al

Conference (2007, October 10)

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See detailThe cross-talk between dendritic and regulatory T cells: good or evil?
Hubert, Pascale ULg; Jacobs, Nathalie ULg; Caberg, Jean-Hubert ULg et al

in 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 ▲]

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See detailPhysicians are different when they learn communication skills: influence of the locus of control
Libert, Yves; Merckaert, I.; Reynaert, C. et al

in Psycho-Oncology (2007), 16(6), 553-562

Purpose: Although it is widely recognised that educational interventions may be more effective for people with an 'internal' Locus of Control (who believe that life outcomes are controlled by their own ... [more ▼]

Purpose: Although it is widely recognised that educational interventions may be more effective for people with an 'internal' Locus of Control (who believe that life outcomes are controlled by their own characteristics or actions) compared to people with an 'external' Locus of Control (who believe that life outcomes are controlled by external forces such as luck, fate or others), no study has yet assessed the influence of physicians' Locus of Control (LOC) on communication skills learning. This study aims to test the hypothesis that, in a communication skills training program, physicians with an 'internal' LOC would demonstrate communication skills acquisition to a greater degree than those with an 'external' LOC. Methods: A non-randomised longitudinal intervention study was conducted between January 1999 and April 2001. Sixty-seven volunteer physicians from private and institutional practice in Belgium participated in a learner-centred, skills-focused, practice-oriented communication skills training program. Communication skills changes were assessed in 2 standardised simulated interviews before and after training (one two-person and one three-person interview). Communication skills were assessed using the Cancer Research Campaign Workshop Evaluation Manual. Physicians' LOC was assessed using the Rotter I-E scale. Communication skills changes of the upper and lower third of physicians in respect of their scores on this scale were compared using group by time repeated measures of variance. Results: In the two-person and three-person interviews, changes in the use of open directive questions were more important among physicians with an "internal" LOC compared with changes observed among physicians with an 'external' LOC (P = 0.066 and P = 0.004, respectively). In the three-person interview, changes in the use of directive questions, assessing functions and moderate feelings stated explicitly were more important among physicians with an 'internal' LOC compared with changes observed among physicians with an 'external' LOC (P = 0.001; P = 0.002 and P = 0.011 respectively). Conclusion: This study shows that physicians' LOC is a psychological characteristic that could influence the efficacy of a communication skills training program. This evidence supports the idea that a psychological characteristic such as 'internal' LOC may facilitate communication skills acquisition through physicians' belief that communication with patients may be controlled by physicians themselves. Copyright (c) 2006 John Wiley [less ▲]

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See detailNK CELLS AND NKG2D LIGANDS IN HPV-ASSOCIATED CERVICAL CANCER
Jacobs, Nathalie ULg; Renoux, Virginie ULg; Dortu, Estelle ULg et al

Poster (2007, April 12)

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See detailAssociation between Epstein-Barr virus and Hodgkin's lymphoma in Belgium: A pathological and virological study
Trimeche, M.; Bonnet, Christophe ULg; Korbi, S. et al

in Leukemia & Lymphoma (2007), 48(7), 1323-1331

The association between Epstein-Barr virus (EBV) and classical Hodgkin's lymphoma (cHL) varies according to the geographic location. In this work we sought to characterize EBV involvement in a series of ... [more ▼]

The association between Epstein-Barr virus (EBV) and classical Hodgkin's lymphoma (cHL) varies according to the geographic location. In this work we sought to characterize EBV involvement in a series of 111 cHL cases diagnosed in Belgium. The overall prevalence of EBV infection detected by in situ hybridization in Reed-Sternberg cells was 33%. EBV positivity correlated with older age at diagnosis (454 years; p = 0.01), mixed cellularity subtype (p = 0.000001), male gender (p = 0.004) and tended to be associated with higher clinical stage (III/IV; p = 0.02). The molecular features of the virus in EBV-positive cHL were studied by comparison with a series of reactive tonsils. A 30-bp deletion within the LMP-1 gene was in 15/28 (53.6%) EBV-positive cHL cases, and in 41.7% of reactive tonsil samples. This variant did not correlate with any clinical or pathological feature. The EBV strain was type A in all cHL and reactive samples. [less ▲]

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See detailConfrontation anatomo-clinique: duplication caecale
Scagnol, Irène ULg; Detry, Olivier ULg; de Leval, Laurence ULg et al

in Revue Médicale de Liège (2007), 62(2), 118-21

Enteric duplication cysts, and particularly caecal duplication cysts, are rare and generally benign congenital anomalies for which a diagnosis is difficult to make because they mimic other surgical ... [more ▼]

Enteric duplication cysts, and particularly caecal duplication cysts, are rare and generally benign congenital anomalies for which a diagnosis is difficult to make because they mimic other surgical diseases. A surgical management is the treatment of choice. The diagnosis can then be made or confirmed by histopathologic analysis. [less ▲]

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See detailLe cancer du col de l'utérus: du virus au traitement
Delvenne, Philippe ULg; Goffin, Frédéric ULg; Kridelka, Frédéric ULg et al

in 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 ▲]

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See detailRole of hormone cofactors in the human papillomavirus-induced carcinogenesis of the uterine cervix
Delvenne, Philippe ULg; Herman, Ludivine ULg; Kholod, Natalia et al

in 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 ▲]

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See detailDefensis induce the recruitment of dendritic cells in cervical human papillomavirus-associated (pre)neoplastic lesions formed in vitro and transplanted in vivo
Hubert, Pascale ULg; Herman, Ludivine ULg; Maillard, Catherine ULg et al

in 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 ▲]

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See detailDownregulation of CD94/NKG2A inhibitory receptors on CD8+ T cells in HIV infection is more pronounced in subjects with detected viral load than in their aviraemic counterparts.
Zeddou, Mustapha ULg; Rahmouni, Souad ULg; Vandamme, Arnaud ULg et al

in Retrovirology (2007), 4

The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small ... [more ▼]

The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small fraction of activated CD8+ T lymphocytes. Abnormal upregulation of the CD94/NKG2A inhibitory NKR on cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance in cancer or HIV infection. In this study, CD94/NKG2A receptor expression on CD8+ T lymphocytes and NK cells was assessed in 46 HIV-1-infected patients (24 viraemic, 22 aviraemic) and 10 healthy volunteers. The percentage of CD8+ T lymphocytes expressing the CD94/NKG2A inhibitory heterodimer was very significantly decreased in HIV-1-infected patients in comparison with non-infected controls. Within the HIV infected patients, the proportion of CD8+ T lymphocytes and NK cells expressing CD94/NKG2A was higher in subjects with undetectable viral loads in comparison with their viraemic counterparts. No significant difference was detected in the proportion of CD8+ T lymphocytes expressing the activatory CD94/NKG2C heterodimer between the HIV-1 infected patients and the healthy donors, nor between the vireamic and avireamic HIV-1 infected patients. In conclusion, chronic stimulation with HIV antigens in viraemic patients leads to a decreased rather than increased CD94/NKG2A expression on CD8+ T lymphocytes and NK cells. [less ▲]

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See detailDendritic Cells: More Than Just Adaptive Immunity Inducers?
Jacobs, Nathalie ULg; Boniver, Jacques ULg; Hubert, Pascale ULg et al

in Current Immunology Reviews (2007), 2

Dendritic cells (DC) are well known for their capacity to induce immune responses and there is also accumulating evidence of their ability to interact with various cell types of the innate system, such as ... [more ▼]

Dendritic cells (DC) are well known for their capacity to induce immune responses and there is also accumulating evidence of their ability to interact with various cell types of the innate system, such as NK, NKT or TCR gamma-delta cells. These interactions are bi-directional, mediated by soluble or cell surface molecules and have been mainly described in the context of immune responses to infectious agents and tumors. NK, NKT or TCR gamma-delta cells induce the maturation of DC, as shown by the increased expression of CD86, IL12 production and priming of T cell responses. On the other hand, mature DC have the ability to activate NK, NKT or TCR gamma-delta cells for sustained innate immune responses and activated NK cells may kill immature DC. In addition, DC and NK or TCR gamma-delta cells share similar functions such as cytotoxic and antitumor activity, interferon production and antigen presentation capacity. [less ▲]

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See detailPhase I/IIclinical trial of local GM-CSF application in patients with cervical HPV-associated low grade squamous intraepithelial lesions
Hubert, Pascale ULg; Doyen, Jean ULg; Chapelle, X. et al

Conference (2007)

Background: Quantitative and functional alterations of professional antigen-presenting cells (APC) in SIL suggest that these lesions may have a diminished capacity to capture viral antigens. Moreover, GM ... [more ▼]

Background: Quantitative and functional alterations of professional antigen-presenting cells (APC) in SIL suggest that these lesions may have a diminished capacity to capture viral antigens. Moreover, GM-CSF (whose production is decreased in HPV-transformed keratinocytes) is an essential factor for the migration of APC in cervical (pre)neoplastic lesions formed in vitro and transplanted in vivo on mouse. In this study we performed a phase I/II clinical trial in order to determine whether a local application of GM-CSF on cervical low-grade squamous intraepithelial lesions (LSIL) might increase the recruitment of APC into the epithelium and indirectly the viral antigen presentation to the immune system. Methods: Fifteen patients with LSIL (10 GM-CSF and 5 placebo) were enrolled in this study. Patients received 4 GM-CSF applications (or placebo gel) and were followed during 6-7 months. APC infiltration was quantified by immunostaining with anti-CD1a mAb. Cellular immune response was evaluated by using an IFN-gamma intracellular staining on PBMC stimulated in vitro with the E7 HPV16 protein and L1 HPV16 Virus-like particles (VLP). Hybrid capture was performed to semi-quantify the viral DNA in cervical brush specimens. Results: GM-CSF applications were well tolerated in all patients. No difference in the cytological/histological and viral parameters assessed at 2 and 6 months after the last application was observed between the GM-CSF and the placebo group. An increased number of CD1a+ APC was observed in 6/10 patients treated by GM-CSF compared to 1/5 patient in the placebo group. There was an increased immune response against HPV in the GM-CSF group showed by NK and T cells producing IFN-gamma. [less ▲]

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