References of "Hubert, Pascale"
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See detailDefensins: « simple » antimicrobial peptides or broad-spectrum molecules ?
Suarez-Carmona, Meggy ULg; Hubert, Pascale ULg; Delvenne, Philippe ULg et al

in Cytokine & Growth Factor Reviews (in press)

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See detailDevelopment and optimization of pegylated lipoplexes for vaginal application
Lechanteur, Anna ULg; Furst, Tania ULg; Kanber, Erdem et al

Conference (2014, October 04)

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See detailAltered alpha-defensin 5 expression in cervical squamocolumnar junction: implication in the formation of a viral/tumour-permissive microenvironment.
Hubert, Pascale ULg; Herman, Ludivine; RONCARATI, Patrick ULg et al

in Journal of Pathology (The) (2014), 234(4), 464-77

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix, which mainly develops at the squamocolumnar (SC) junction. The progression of cervical ... [more ▼]

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix, which mainly develops at the squamocolumnar (SC) junction. The progression of cervical HPV infections into (pre)neoplastic lesions suggests that viral antigens are not adequately recognized by innate immunity or presented to the adaptive immune system. Members of the defensin family have recently been found to inhibit viral and bacterial pathogens, to stimulate the migration of immune cells and to play a role in anticancer responses. In the present study, we focused on the poorly characterized human alpha-defensin 5 (HD-5) and its possible role in these processes. We showed that HD-5 was able to prevent HPV virion entry into cervical keratinocytes and to influence adaptive immunity. Indeed, this peptide specifically induced the chemoattraction and proliferation of both activated T lymphocytes and immature dendritic cells in a CCR2/CCR6-dependent manner and stimulated the infiltration of these professional antigen-presenting cells in a (pre)neoplastic epithelium transplanted in vivo in immunodeficient mice. No chemotactic effect was observed with plasmacytoid dendritic cells, macrophages or natural killer cells. Proliferative and angiogenic effects of HD-5 were also assessed in vitro and in vivo. However there was a striking regional disparity in expression of HD-5, being prominent in ectocervical, vaginal and vulvar neoplasia, while absent, or nearly so, in the cervical SC junction. Taken together, these results suggest one possible explanation for why the SC junction is uniquely vulnerable to both high-risk HPV infection (via reduced HD-5 expression and viral entry) and progression of neoplasia (via altered cell-mediated immune responses and altered microenvironment). Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [less ▲]

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See detailHMGB1 secretion during cervical carcinogenesis promotes the acquisition of a tolerogenic functionality by plasmacytoid dendritic cells
Demoulin, Stéphanie ULg; Herfs, Michael ULg; SOMJA, Joan ULg et al

in International Journal of Cancer = Journal International du Cancer (2014)

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See detailNF-kappaB-induced KIAA1199 promotes survival through EGFR signalling.
Shostak, Kateryna ULg; Zhang, Xin; Hubert, Pascale ULg et al

in Nature communications (2014), 5

Constitutive activation of EGFR- and NF-kappaB-dependent pathways is a hallmark of cancer, yet signalling proteins that connect both oncogenic cascades are poorly characterized. Here we define KIAA1199 as ... [more ▼]

Constitutive activation of EGFR- and NF-kappaB-dependent pathways is a hallmark of cancer, yet signalling proteins that connect both oncogenic cascades are poorly characterized. Here we define KIAA1199 as a BCL-3- and p65-dependent gene in transformed keratinocytes. KIAA1199 expression is enhanced on human papillomavirus (HPV) infection and is aberrantly expressed in clinical cases of cervical (pre)neoplastic lesions. Mechanistically, KIAA1199 binds Plexin A2 and protects from Semaphorin 3A-mediated cell death by promoting EGFR stability and signalling. Moreover, KIAA1199 is an EGFR-binding protein and KIAA1199 deficiency impairs EGF-dependent Src, MEK1 and ERK1/2 phosphorylations. Therefore, EGFR stability and signalling to downstream kinases requires KIAA1199. As such, KIAA1199 promotes EGF-mediated epithelial-mesenchymal transition (EMT). Taken together, our data define KIAA1199 as an oncogenic protein induced by HPV infection and constitutive NF-kappaB activity that transmits pro-survival and invasive signals through EGFR signalling. [less ▲]

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See detailDeltaNp63 isoform-mediated beta-defensin family up-regulation is associated with (lymph)angiogenesis and poor prognosis in patients with squamous cell carcinoma.
Suarez-Carmona, Meggy ULg; Hubert, Pascale ULg; Gonzalez, Arnaud ULg et al

in Oncotarget (2014), 5(7), 1856-1868

Beside a role in normal development/differentiation, high p63 immunoreactivity is also frequently observed in squamous cell carcinoma (SCC). Due to the complexity of the gene, the role of each p63 isotype ... [more ▼]

Beside a role in normal development/differentiation, high p63 immunoreactivity is also frequently observed in squamous cell carcinoma (SCC). Due to the complexity of the gene, the role of each p63 isotype in tumorigenesis is still confusing. Constitutively produced or induced in inflammatory conditions, human beta-defensins (HbetaDs) are cationic peptides involved in host defenses against bacteria, viruses and fungi. Here, we investigated both the role of p63 proteins in the regulation of HbetaDs and the implication of these antimicrobial peptides in tumor (lymph)angiogenesis. Thus, in contrast to TAp63 isotypes, we observed that DeltaNp63 proteins (alpha, beta, gamma) induce HbetaD1, 2 and 4 expression. Similar results were observed in cancer tissues and cell lines. We next demonstrated that DeltaNp63-overexpressing SCC are associated with both a poor prognosis and a high tumor vascularisation and lymphangiogenesis. Moreover, we showed that HbetaDs exert a chemotactic activity for (lymphatic) endothelial cells in a CCR6-dependent manner. The ability of HbetaDs to enhance (lymph)angiogenesis in vivo was also evaluated. We observed that HbetaDs increase the vessel number and induce a significant increase in relative vascular area compared to negative control. Taken together, the results of this study suggest that DeltaNp63-regulated HbetaD could promote tumor (lymph)angiogenesis in SCC microenvironment. [less ▲]

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See detailUnique recurrence patterns of cervical intraepithelial neoplasia following excision of the squamo-columnar junction.
Herfs, Michael ULg; SOMJA, Joan ULg; Howitt, Brooke E. et al

in International journal of cancer. Journal international du cancer (2014)

Recent studies have identified a putative cell of origin for cervical intraepithelial neoplasia (CIN) and cervical cancer at the squamo-columnar junction (SCJ) and suggest that these cells may not ... [more ▼]

Recent studies have identified a putative cell of origin for cervical intraepithelial neoplasia (CIN) and cervical cancer at the squamo-columnar junction (SCJ) and suggest that these cells may not regenerate following excision (LEEP). This study addressed the impact of SCJ excision on the temporal dynamics, histologic and viral (HPV) characteristics of recurrent CIN. One hundred thirty one consecutive patients treated by excision and attending follow-up visits were enrolled. We compared recurrent and initial CIN with attention to excision margins, timing of recurrence, CIN grade, HPV types, p16 immunophenotype, and SCJ immunophenotype. During the follow-up period (up to four years), sixteen (12.2%) recurrences were identified. Four (25%) were identified at the first follow-up visit, closely resembled the initial CIN 2/3 in grade and HPV type, and were typically SCJ marker positive [SCJ(+)], suggesting non-excised (residual) disease. Twelve (75%) manifested after the first postoperative visit and all were in the ectocervix or in mature metaplastic epithelium. All of the 12 delayed recurrences were classified as CIN 1 and were SCJ (-). Nine of 11 SCJ (-) recurrences (82%) followed regressed spontaneously. Taken together, these results show that new lesions developing from any HPV infection are delayed and occur within the ectocervix or metaplastic epithelium. This dramatically lower risk of CIN 2/3 following successful SCJ excision suggests that removal of the SCJ could be a critical variable in reducing the risk of subsequent CIN 2/3 and cervical cancer. (c) 2014 Wiley Periodicals, Inc. [less ▲]

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See detailDevelopment of anti-HPV lipoplexes for the treatment of cervical cancer
Lechanteur, Anna ULg; Furst, Tania ULg; Evrard, Brigitte ULg et al

Conference (2013, December 03)

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