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See detailNatural killer and dendritic cells collaborate in the immune response induced by the vaccine against uterine cervical cancer.
Langers, Inge ULg; Renoux, Virginie; Reschner, Anca et al

in European journal of immunology (in press)

Virus-like particles (VLPs) of human papillomavirus (HPV) are used as a vaccine against HPV-induced cancer, and recently we have shown that these VLPs are able to activate natural killer (NK) cells. Since ... [more ▼]

Virus-like particles (VLPs) of human papillomavirus (HPV) are used as a vaccine against HPV-induced cancer, and recently we have shown that these VLPs are able to activate natural killer (NK) cells. Since NK cells collaborate with dendritic cells (DCs) to induce an immune response against viral infections and tumors, we studied the impact of this crosstalk in the context of HPV vaccination. NK cells in the presence of HPV-VLPs enhanced DC maturation as shown by an upregulation of CD86 and HLA-DR and an increased production of IL-12p70, but not of the immunosuppressive cytokine IL-10. This activation was bi-directional. Indeed, in the presence of HPV-VLPs, DCs further activated NK cells by inducing the upregulation of cell surface activation markers (CD69 and HLA-DR). The function of NK cells was also improved as shown by an increase in IFN-gamma secretion and cytotoxic activity against an HPV+ cell line. This crosstalk between NK cells and DCs needed CD40 interaction and IL-12p70 secretion, whereas NKG2D was not implicated. Our results provide insight into how VLPs interact with innate immune cells and how NK cells and DCs play a role in the immune response induced by this vaccine agent. This article is protected by copyright. All rights reserved. [less ▲]

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See detailUse of lipid probes as matrices for MALDI Imaging applications
Longuespée, Rémi ULg; Alberts, Deborah ULg; Pottier, Charles et al

Poster (2014, November 07)

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See detailOrigin and immunoescape of uterine cervical cancer
Van hede, Dorien ULg; Langers, Inge ULg; DELVENNE, Philippe ULg et al

in Presse Médicale (2014)

Human papillomavirus associated uterine cervical cancer is an important public health problem since it is classified as the fourth most common cancer in women worldwide with more than 500 000 recorded ... [more ▼]

Human papillomavirus associated uterine cervical cancer is an important public health problem since it is classified as the fourth most common cancer in women worldwide with more than 500 000 recorded cases. This review is focused on where and why HPV infection induces cervical cancers and how this virus avoids the host immune response. Immunological therapeutic approaches are also addressed. [less ▲]

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See detailEGFR activation and signaling in cancer cells are enhanced by the membrane-bound metalloprotease MT4-MMP.
Paye, Alexandra ULg; Truong, Alice ULg; Yip, Cassandre ULg et al

in Cancer research (2014)

MT4-MMP (MMP-17) is a GPI-anchored matrix metalloprotease expressed on the surface of cancer cells which promotes tumor growth and metastasis. In this report, we identify MT4-MMP as an important driver of ... [more ▼]

MT4-MMP (MMP-17) is a GPI-anchored matrix metalloprotease expressed on the surface of cancer cells which promotes tumor growth and metastasis. In this report, we identify MT4-MMP as an important driver of cancer cell proliferation through CDK4 activation and retinoblastoma protein (Rb) inactivation. We also determine a functional link between MT4-MMP and the growth factor receptor EGFR. Mechanistic experiments revealed direct association of MT4-MMP and its positive effects on EGFR phosphorylation in response to TGF- and EGF in cancer cells. Notably, the effects of MT4-MMP on proliferation and EGFR activation did not rely on metalloprotease activity. Clinically, MT4-MMP and EGFR expression were correlated in human triple negative breast cancer specimens. Altogether our results identify MT4-MMP as a positive modifier of EGFR outside-in signaling that acts to cooperatively drive cancer cell proliferation. [less ▲]

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See detailL'amiodarone et la thyroïde
Brescia, Lionel ULg; Benoit, Arnaud ULg; BETEA, Daniela ULg et al

in Revue Médicale de Liège (2014), 69(10), 549-554

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See detailIn vivo skin fluorescence imaging in young Caucasian adults with early malignant melanomas
PIERARD, Gérald ULg; Hermanns-Lê, Trinh ULg; Pierard, Sébastien ULg et al

in Clinical, Cosmetic and Investigational Dermatology (2014), 7

Background: Human cutaneous malignant melanoma (CMM) is an aggressive cancer showing a dramatic worldwide increase in incidence over the past few decades. The most prominent relative epidemiological ... [more ▼]

Background: Human cutaneous malignant melanoma (CMM) is an aggressive cancer showing a dramatic worldwide increase in incidence over the past few decades. The most prominent relative epidemiological increase has been disclosed in young women. The aim of the study was to assess the effects of chronic sun exposures in order to rate the extend of melanocytic stimulations in the vicinity of CMM. Methods: The study was designed to evaluate the melanin distribution and density using ultraviolet light illumination. The present study was performed on surgical excision specimens of thin CMM lesion removed from the upper limbs of 55 Caucasian adults (37 women and 18 men). Two control groups comprised 23 men and 21 women of similar ages who had medium-size congenital melanocytic nevi, also present on the upper limbs. The peritumoral skin was scrutinized using a Visioscan® VC98 device, revealing the faint mosaic melanoderma (FMM) pattern that grossly indicates early signs of chronic photodamage in epidermal melanin units. Results: The median extent of relative FMM was significantly higher in the CMM male group. By contrast, the CMM female group showed a reverse bimodal distribution in FMM size. Only 12/37 (32.5%) of the CMM female group had an increased FMM size, whereas 25/37 (67.5%) of females with CMM had a global FMM extent in the normal range, relative to the controls. Conclusion: Thin CMM supervening in young women appear unrelated to repeat photoexposure. Other mechanisms are possibly involved. [less ▲]

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See detailTriple negative tumors accumulate significantly less methylglyoxal specific adducts than other human breast cancer subtypes
Chiavarina, Barbara ULg; Nokin, Marie-Julie; Durieux, Florence ULg et al

in Oncotarget (2014)

Metabolic syndrome and type 2 diabetes are associated with increased risk of breast cancer development and progression. Methylglyoxal (MG), a glycolysis by- product, is generated through a non-enzymatic ... [more ▼]

Metabolic syndrome and type 2 diabetes are associated with increased risk of breast cancer development and progression. Methylglyoxal (MG), a glycolysis by- product, is generated through a non-enzymatic reaction from triose-phosphate intermediates. This dicarbonyl compound is highly reactive and contributes to the accumulation of advanced glycation end products. In this study, we analyzed the accumulation of Arg-pyrimidine, a MG-arginine adduct, in human breast adenocarcinoma and we observed a consistent increase of Arg-pyrimidine in cancer cells when compared with the non-tumoral counterpart. Further immunohistochemical comparative analysis of breast cancer subtypes revealed that triple negative lesions exhibited low accumulation of Arg-pyrimidine compared with other subtypes. Interestingly, the activity of glyoxalase 1 (Glo-1), an enzyme that detoxifies MG, was significantly higher in triple negative than in other subtype lesions, suggesting that these aggressive tumors are able to develop an efficient response against dicarbonyl stress. Using breast cancer cell lines, we substantiated these clinical observations by showing that, in contrast to triple positive, triple negative cells induced Glo-1 expression and activity in response to MG treatment. This is the first report that Arg- pyrimidine adduct accumulation is a consistent event in human breast cancer with a differential detection between triple negative and other breast cancer subtypes. [less ▲]

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See detailInfusion of clinical-grade enriched regulatory T cells delays experimental xenogeneic graft-versus-host disease
Hannon, Muriel ULg; LECHANTEUR, Chantal ULg; Lucas, Sophie et al

in Transfusion (2014), 54(February), 353-363

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See detailTGF-B induced protein IG-H3 is essential for the growth of human liver metastases
Castronovo, Vincenzo ULg; Blomme, Arnaud; Delvenne, Philippe ULg et al

in Acta Gastro-Enterologica Belgica (2014, March), 77(1), 05

Introduction : Transforming growth factor-beta-induced protein ig-h3 (TGFBI) is extracellular matrix component known to be important for cell-collagen interaction. We and others have reported elevated ... [more ▼]

Introduction : Transforming growth factor-beta-induced protein ig-h3 (TGFBI) is extracellular matrix component known to be important for cell-collagen interaction. We and others have reported elevated expression of TGFBI in sev- eral human cancers, where its role remains controversial. Aim Current study aims at clarifying the function of TGFBI to date. Methods &Results : CRC-LM and in liver metastases originating from breast, lung and pancreatic tumors. We have next focused on func- tional aspects and have silenced TGFBI expression in SW1222 human colorectal carcinoma cells. The suppression of TGFBI protein led to a marked decrease in cell migration (-70%) and proliferation (-30%) in vitro. To study the effects in vivo we have developed a novel animal model of colorectal carcinoma based on chicken chorioallantoic membrane (CAM) that mimics human CRC-LM. TGFBI silencing resulted in 50% reduction of tumor volume in the CAM tumor model. Notably, the tumors displayed a marked inhibition of vascularization, suggesting an additional anti-angiogenic effect. Indeed, SW1222 cells silenced for TGFBI expression secreted lower levels of VEGFA in vitro. Finally, we have investigated if TGFBI can be used as systemically reachable target for antibody-drug delivery. For this purpose we have The in vivo data demonstrated that TGFBI is an accessible tumor target. Conclusions : Taken together, the present study shows that TGFBI is essential for promoting the development of CRC- LM and therefore represents a promising target for designing novel therapeutic approaches. [less ▲]

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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 detailHMGB1 secretion during cervical carcinogenesis promotes the acquisition of a tolerogenic functionality by plasmacytoid dendritic cells
Demoulin, Stéphanie ULg; SOMJA, Joan ULg; Herfs, Michael 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 detailComparison of two FFPE preparation methods using label-free shotgun proteomics: Application to tissues of diverticulitis patients.
Quesada-Calvo, Florence; Bertrand, Virginie ULg; Longuespée, Rémi ULg et al

in Journal of proteomics (2014), 112C

Formalin-fixed paraffin-embedded (FFPE) specimens of patients are useful sources of materials for clinical research and have recently gained interest for use in the discovery of clinical proteomic ... [more ▼]

Formalin-fixed paraffin-embedded (FFPE) specimens of patients are useful sources of materials for clinical research and have recently gained interest for use in the discovery of clinical proteomic biomarkers. However, the critical step in this field is the ability to obtain an efficient and repeatable extraction using the limited quantities of material available for research in hospital biobanks. This work describes the evaluation of the peptide/protein extraction using FFPE sections treated by the following two methods before shotgun proteomic analysis: a commercial solution (FFPE-FASP) (filter aided sample preparation) and an antigen retrieval-derived protocol (On Slice AR). Their efficiencies and repeatabilities are compared using data-independent differential quantitative label-free analysis. FFPE-FASP was shown to be globally better both qualitatively and quantitatively than On Slice AR. FFPE-FASP was tested on several samples, and differential analysis was used to compare the tissues of diverticulitis patients (healthy and inflammatory tissues). In this differential proteomic analysis using retrospective clinical FFPE material, FFPE-FASP was reproducible and provided a high number of confident protein identifications, highlighting potential protein biomarkers. BIOLOGICAL SIGNIFICANCE: In clinical proteomics, FFPE is an important resource for retrospective analysis and for the discovery of biomarkers. The challenge for FFPE shotgun proteomic analysis is preparation by an efficient and reproducible protocol, which includes protein extraction and digestion. In this study, we analyzed two different methods and evaluated their repeatabilities and efficiencies. We illustrated the reproducibility of the most efficient method, FFPE-FASP, by a pilot study on diverticulitis tissue and on FFPE samples amount accessible in hospital biobanks. These data showed that FFPE is suitable for use in clinical proteomics, especially when the FFPE-FASP method is combined with label-free shotgun proteomics as described in the workflow presented in this work. [less ▲]

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See detailSkin ageprint: the causative factors.
PIERARD, Gérald ULg; Hermanns-Lê, Trinh ULg; Delvenne, Philippe ULg et al

in Paye, M.; Maibach, H.I.; Barel, A.O. (Eds.) Handbook of Cosmetic Science and Technology (2014)

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