References of "Doyen, Jean"
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See detailVulvar Skin Disorders throughout Lifetime: About Some Representative Dermatoses
DOYEN, Jean ULg; Demoulin, Stéphanie ULg; DELBECQUE, Katty ULg et al

in BioMed Research International (2014)

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See detailFrom the Clinics to the Bench and back to the Clinics: design of a medical treatment for Cervical Intraepithelial Neoplasia (CIN)
Jost, Maud; Frankenne, Francis; Maillard, Catherine ULg et al

Conference (2011, May 20)

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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 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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See detailPhase I/II trial of immunogenicity of a human papillomavirus (HPV) type 16 E7 protein-based vaccine in women with oncogenic HPV-positive cervical intraepithelial neoplasia
Hallez, Sophie; Simon, Philippe; Maudoux, Frédéric et al

in Cancer Immunology, Immunotherapy (2004), 53(7), 642-650

Purpose: Infection with oncogenic human papillomavirus (HPV) and HPV-16 in particular is a leading cause of anogenital neoplasia. High-grade intraepithelial lesions require treatment because of their ... [more ▼]

Purpose: Infection with oncogenic human papillomavirus (HPV) and HPV-16 in particular is a leading cause of anogenital neoplasia. High-grade intraepithelial lesions require treatment because of their potential to progress to invasive cancer. Numerous preclinical studies have demonstrated the therapeutic potential of E7-directed vaccination strategies in mice tumour models. In the present study, we tested the immunogenicity of a fusion protein (PD-E7) comprising a mutated HPV-16 E7 linked to the first 108 amino acids of Haemophilus influenzae protein D, formulated in the GlaxoSmithKline Biologicals adjuvant AS02B, in patients bearing oncogenic HPV-positive cervical intraepithelial neoplasia (CIN). Methods: Seven patients, five with a CIN3 and two with a CIN1, received three intramuscular injections of adjuvanted PD-E7 at 2-week intervals. Three additional CIN1 patients received a placebo. CIN3 patients underwent conization 8 weeks postvaccination. Cytokine flow cytometry and ELISA were used to monitor antigen-specific cellular and antibody responses from blood taken before and after vaccine or placebo injection. Results: Some patients had preexisting systemic IFN-gamma CD4(+) (1/10) and CD8(+) (5/10) responses to PD-E7. Vaccination, not placebo injection, elicited systemic specific immune responses in the majority of the patients. Five vaccinated patients (71%) showed significantly increased IFN-gamma CD8(+) cell responses upon PD-E7 stimulation. Two responding patients generated long-term T-cell immunity toward the vaccine antigen and E7 as well as a weak H. influenzae protein D (PD)-directed CD4(+) response. All the vaccinated patients, but not the placebo, made significant E7- and PD-specific IgG. Conclusions: The encouraging results obtained from this study performed on a limited number of subjects justify further analysis of the efficacy of the PD-E7/AS02B vaccine in CIN patients. [less ▲]

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See detailLe depistage du cancer du col de l'uterus en Belgique: le point en 2003
Delvenne, Philippe ULg; Jacobs, Nathalie ULg; Lambert, Chantal ULg et al

in Revue Médicale de Liège (2003), 58(5), 316-8

Squamous cell cancer of the uterine cervix is associated with a high morbidity and mortality worldwide and in Belgium. Its development is related to the infection by oncogenic human papillomavirus (HPV ... [more ▼]

Squamous cell cancer of the uterine cervix is associated with a high morbidity and mortality worldwide and in Belgium. Its development is related to the infection by oncogenic human papillomavirus (HPV) types. Cervical cancer is preceded by dysplasic stages (squamous intraepithelial lesions) which can be detected by a Pap smear. The goal of this paper is to review the screening of uterine cervical cancer in Belgium. [less ▲]

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See detailDistinct T cell subsets and cytokine production in cultures derived from transformation zone and squamous intraepithelial lesion biopsies of the uterine cervix.
Jacobs, Nathalie ULg; Renard, Isabelle; Al-Saleh, Walid et al

in American Journal of Reproductive Immunology (2003), 49(1), 6-13

PROBLEM: The characterization of lymphocytes issued from squamous intraepithelial lesions (SIL) and from the transformation zone (TZ), where the majority of SIL occur, is important to understand the role ... [more ▼]

PROBLEM: The characterization of lymphocytes issued from squamous intraepithelial lesions (SIL) and from the transformation zone (TZ), where the majority of SIL occur, is important to understand the role of immunity in SIL development. METHOD OF STUDY: We compared lymphocyte populations of the TZ and SIL with those of normal exocervix, using a technique allowing for the isolation of lymphocytes, either from the epithelium or from the underlying stroma of small biopsies. RESULTS: The majority of cells derived from the epithelium of all biopsies were CD8+ T cells. Some SIL-derived cultures were characterized by an increased proportion of activated TCRgammadelta+. The production of the immunosuppressive cytokine IL10 was significantly higher in lymphocyte cultures from the normal TZ in comparison with the exocervix. A decreased percentage of effector T cells was observed in cultures derived from the stroma of normal TZ (TCRgammadelta+) or SIL (CD8+) in comparison with the exocervix. CONCLUSIONS: Our results suggest that a low proportion of effector T cells and IL10 production could contribute to the predisposition of the TZ to the development of SIL and to the progression of SIL to cervical cancer. [less ▲]

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See detailInfluence of the mucosal epithelium microenvironment on Langerhans cells: implications for the development of squamous intraepithelial lesions of the cervix
Giannini, Sandra ULg; Hubert, Pascale ULg; Doyen, Jean ULg et al

in International Journal of Cancer = Journal International du Cancer (2002), 97(5), 654-659

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See detailCytokine Expression in Squamous Intraepithelial Lesions of the Uterine Cervix: Implications for the Generation of Local Immunosuppression
Giannini, Sandra; Al-Saleh, Walid; Piron, Hélène ULg et al

in Clinical & Experimental Immunology (1998), 113(2), 183-9

We have addressed the notion that the progression of cancer of the uterine cervix is associated with a preferential constraint on the development of a type 1 cellular mediated response, which is necessary ... [more ▼]

We have addressed the notion that the progression of cancer of the uterine cervix is associated with a preferential constraint on the development of a type 1 cellular mediated response, which is necessary to efficiently eliminate (pre)neoplastic cells. Based on the importance of cytokines in the regulation of an appropriate immune response, we have evaluated the expression of IL-12p40, IL-10 and transforming growth factor-beta 1 (TGF-beta1). Using reverse transcriptase-polymerase chain reaction (RT-PCR), the expression of these three cytokines was evaluated in both low-grade (LG) and high-grade (HG) cervical squamous intraepithelial lesions (SIL) and in normal exocervix and transformation zone biopsies. Our results show that the average level of IL-12 increases within both the LG and HG SIL, compared with both control groups. Interestingly, the percentage of HG SIL expressing IL-12p40 was lower compared with LG SIL. In contrast, the expression of IL-10 increased in parallel with the severity of the lesion to a maximal level in HG SIL. Using immunohistochemistry, we ascertained the presence of IL-12 protein in SIL and IL-10 protein in the transformation zone and SIL biopsies. Both IL-12- and IL-10-producing cells were localized in the stroma, not within the SIL. Furthermore, in this study we also observed that the region of the cervix the most sensitive to lesion development, the transformation zone, was associated with higher average levels of the immunosuppressive cytokines IL-10 and TGF-beta1. [less ▲]

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See detailCorrelation of T-Helper Secretory Differentiation and Types of Antigen-Presenting Cells in Squamous Intraepithelial Lesions of the Uterine Cervix
al-Saleh, W.; Giannini, S. L.; Jacobs, Nathalie ULg et al

in Journal of Pathology (The) (1998), 184(3), 283-90

This study addressed the notion that the progression of cervical cancer is associated with a T-helper 2 (TH2) immunodeviation by analysing cytokine expression in 60 cervical biopsy specimens, spanning the ... [more ▼]

This study addressed the notion that the progression of cervical cancer is associated with a T-helper 2 (TH2) immunodeviation by analysing cytokine expression in 60 cervical biopsy specimens, spanning the spectrum from normal cervical tissue to high-grade squamous intraepithelial lesions (SILs). The biopsies were analysed by immunohistochemistry for the expression of TH1 [interleukin-2 (IL2), interferon gamma (IFN gamma)] and of TH2-type cytokines (IL4, IL6). Positive cells were usually observed in the subepithelial connective tissue, where most CD4+ cells were also detected. The density of IL2+ cells was significantly lower in high-grade SILs than in normal tissues taken either from the ectocervix or from the transformation zone. In contrast, significantly higher densities of IL4+ cells and, to a lesser degree, IL6+ cells were found in SIL biopsies compared with histologically normal tissues taken from the adjacent ectocervical region. A significantly higher IL4+/CD4+ cell ratio was also found in high-grade SILs (82 per cent) than in normal cervical biopsies taken from the transformation zone of healthy women showing squamous metaplasia (27 per cent). The elevated density of TH2+ cells in SIL biopsies was associated with both the expression of HLA-DR by keratinocytes and a diminished number of intraepithelial Langerhans' cells (CD1a+). In conclusion, the increased TH2+/CD4+ cell ratio in SIL biopsies suggest the presence, during cervical carcinogenesis, of a TH2 immunodeviation that could participate in the immunoescape of preneoplastic cervical keratinocytes. [less ▲]

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See detailInverse Modulation of Il-10 and Il-12 in the Blood of Women with Preneoplastic Lesions of the Uterine Cervix
Jacobs, Nathalie ULg; Giannini, Sandra L; Doyen, Jean ULg et al

in Clinical & Experimental Immunology (1998), 111(1), 219-24

It has been postulated that an impaired immune response may contribute to the progression of human papillomavirus (HPV)-associated preneoplastic lesions. Based on this hypothesis, we evaluated the ... [more ▼]

It has been postulated that an impaired immune response may contribute to the progression of human papillomavirus (HPV)-associated preneoplastic lesions. Based on this hypothesis, we evaluated the cytokine production in the blood of patients with squamous intraepithelial lesions (SIL) of the uterine cervix. The levels of type-1 (interferon-gamma (IFN-gamma) and IL-12) and type-2(IL-4 and IL-10) cytokines were measured in whole blood culture supernatants of patients with low- and high-grade SIL and control women. There was no difference in IL-4 and IFN-gamma levels between patients with SIL and the control group. In contrast, the ratio of IL-12/IL-10 levels was significantly lower in patients with SIL compared with the control group. A lower IL-12/IL-10 ratio in women with SIL was also observed when peripheral blood mononuclear cell (PBMC) culture supernatants and plasma samples were analysed. In patients, neither the lower expression of the CD3epsilon chain nor the higher frequency of HLA-DRB1*1501 expression could be correlated with abnormal cytokine production. These results suggest that a part of the cytokine network, namely IL-10 and IL-12, is perturbed in patients with SIL. A better knowledge of the role of these cytokines in regulating the growth of HPV-associated SIL might have practical implications for the development of vaccines or immunomodulatory strategies in the treatment of cervical cancers. [less ▲]

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