References of "Delvenne, Philippe"
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See detailClinical significance of MT4-MMP and EGFR expression in Breast Cancer
Yip, Cassandre ULg; PAYE, Alexandra ULg; Truong, Alice ULg et al

Scientific conference (2015, January 31)

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See detailGrille de correction: déclinaisons de la perception et des réalisations
Bonnet, Pierre ULg; Delvenne, Philippe ULg; Defaweux, Valérie ULg et al

Conference (2015, January 29)

Un outil disponible on-line pour la correction des questions ouvertes à réponse courte ou longue (QROC et QROL) est utilisé depuis plusieurs années au sein de l’ULg. Les copies réponse des étudiants sont ... [more ▼]

Un outil disponible on-line pour la correction des questions ouvertes à réponse courte ou longue (QROC et QROL) est utilisé depuis plusieurs années au sein de l’ULg. Les copies réponse des étudiants sont scannées et corrigées sur un écran d’ordinateur. L’enseignant fournit l’énoncé de la question et une grille de correction suivant un canevas prédéfini. La correction évalue une série de critères regroupés par 4 à l’écran. Chaque critère défini est évalué au moyen d’une échelle horizontale allant de 0 à 100% suivant que le critère n’est pas rencontré (0%) ou qu’il est totalement développé (100%) par l’étudiant. L’enseignant peut graduer cette échelle en y indiquant des repères (indices). La pondération des différents critères est définie à priori ou à posteriori. Sur cette base de travail commune, nous analysons la façon dont cette grille est utilisée pour corriger des questions relatives à des matières médicales différentes enseignées par différents professeurs : histologie, anatomie, physiologie et anatomopathologie. L’analyse fait ressortir que malgré un canevas commun, les modalités de correction sont variables ce qui témoigne de la différence existant entre les matières, les compétences évaluées et, probablement, la sensibilité des enseignants. A l’inverse, ceci démontre la souplesse de l’outil adaptable à des types d’évaluations différents. [less ▲]

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See detailAsporin Is a Fibroblast-Derived TGF-beta1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer.
Maris, Pamela; Blomme, Arnaud; Palacios, Ana Perez et al

in PLoS medicine (2015), 12(9), 1001871

BACKGROUND: Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-beta1 has been identified as a key ... [more ▼]

BACKGROUND: Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-beta1 has been identified as a key driving force behind metastatic breast cancer, with promising therapeutic implications. METHODS AND FINDINGS: Employing immunohistochemistry (IHC) analysis, we report, to our knowledge for the first time, that asporin is overexpressed in the stroma of most human breast cancers and is not expressed in normal breast tissue. In vitro, asporin is secreted by breast fibroblasts upon exposure to conditioned medium from some but not all human breast cancer cells. While hormone receptor (HR) positive cells cause strong asporin expression, triple-negative breast cancer (TNBC) cells suppress it. Further, our findings show that soluble IL-1beta, secreted by TNBC cells, is responsible for inhibiting asporin in normal and cancer-associated fibroblasts. Using recombinant protein, as well as a synthetic peptide fragment, we demonstrate the ability of asporin to inhibit TGF-beta1-mediated SMAD2 phosphorylation, epithelial to mesenchymal transition, and stemness in breast cancer cells. In two in vivo murine models of TNBC, we observed that tumors expressing asporin exhibit significantly reduced growth (2-fold; p = 0.01) and metastatic properties (3-fold; p = 0.045). A retrospective IHC study performed on human breast carcinoma (n = 180) demonstrates that asporin expression is lowest in TNBC and HER2+ tumors, while HR+ tumors have significantly higher asporin expression (4-fold; p = 0.001). Assessment of asporin expression and patient outcome (n = 60; 10-y follow-up) shows that low protein levels in the primary breast lesion significantly delineate patients with bad outcome regardless of the tumor HR status (area under the curve = 0.87; 95% CI 0.78-0.96; p = 0.0001). Survival analysis, based on gene expression (n = 375; 25-y follow-up), confirmed that low asporin levels are associated with a reduced likelihood of survival (hazard ratio = 0.58; 95% CI 0.37-0.91; p = 0.017). Although these data highlight the potential of asporin to serve as a prognostic marker, confirmation of the clinical value would require a prospective study on a much larger patient cohort. CONCLUSIONS: Our data show that asporin is a stroma-derived inhibitor of TGF-beta1 and a tumor suppressor in breast cancer. High asporin expression is significantly associated with less aggressive tumors, stratifying patients according to the clinical outcome. Future pre-clinical studies should consider options for increasing asporin expression in TNBC as a promising strategy for targeted therapy. [less ▲]

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See detail18F-FDG PET/CT in the Management of Aortitis.
Bruls, Samuel; Courtois, Audrey ULg; Nusgens-Richelle, Betty ULg et al

in Clinical nuclear medicine (2015)

BACKGROUND: Aortitis is a generic term defined as an inflammatory condition involving the aortic wall, of infectious or noninfectious origin. This inflammatory process may deteriorate the aortic wall ... [more ▼]

BACKGROUND: Aortitis is a generic term defined as an inflammatory condition involving the aortic wall, of infectious or noninfectious origin. This inflammatory process may deteriorate the aortic wall, resulting in potentially life-threatening vascular complications. Therefore, it is important to establish a diagnosis as early as possible. PATIENTS AND METHODS: During a 4-year period, 428 consecutive patients referred to our department for aortic diseases underwent FDG PET/CT examinations. Among these, 18 patients (4.2%) were suspected to have aortitis. All of them had an initial positive FDG PET/CT uptake occurring in the aorta and major branches as evaluated by visual analysis of images and assessed with the final diagnosis of aortitis. During follow-up, after surgery and/or upon immunosuppressive treatment, each of these patients underwent a second PET/CT that was compared with the initial evaluation. In all cases, normalization of FDG uptake was correlated with clinical improvement. CONCLUSIONS: Our study aimed to illustrate the potential clinical value of functional monitoring with PET/CT in the management of aortitis. FDG PET/CT constitutes a valuable imaging modality to establish an early diagnosis, monitor disease progression and treatment, and evaluate vascular complication and relapse. We highlight the importance of an early detection of inflammatory large-vessel pathology, which may represent a major threat. [less ▲]

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See detailHedgehog- and mTOR-targeted therapies for advanced basal cell carcinomas.
FRANCHIMONT, Claudine ULg; Hermanns-Lê, Trinh ULg; PAQUET, Philippe ULg et al

in Future Oncology (2015), 11

Basal cell carcinomas (BCCs) are the most frequent human cancer. Over 90% of all BCCs have a mutation in patched homologue 1 (PTCH 1) or smoothened (SMO), two conducting proteins of the Hedgehog (Hh ... [more ▼]

Basal cell carcinomas (BCCs) are the most frequent human cancer. Over 90% of all BCCs have a mutation in patched homologue 1 (PTCH 1) or smoothened (SMO), two conducting proteins of the Hedgehog (Hh) pathway. They rarely progress deeply and metastasize; however, if they do, these advanced BCC become amenable to treatment by inhibiting the Hedgehog and the P13K–mTOR pathways. Such innovative drugs include vismodegib, cyclopamine, itraconazole, everolimus and a few other agents that are in early clinical development. [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 (2015), 137

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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 (2015), 26

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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 (2015), 136

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 detail[F]FPRGD PET/CT imaging of integrin alphabeta levels in patients with locally advanced rectal carcinoma.
WITHOFS, Nadia ULg; Martinive, Philippe ULg; VANDERICK, Jean ULg et al

in European journal of nuclear medicine and molecular imaging (2015)

PURPOSE: Our primary objective was to determine if [18F]FPRGD2 PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal ... [more ▼]

PURPOSE: Our primary objective was to determine if [18F]FPRGD2 PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal cancer (LARC). Secondary objectives were to compare baseline [18F]FPRGD2 and [18F]FDG uptake, to evaluate the correlation between posttreatment [18F]FPRGD2 uptake and tumour microvessel density (MVD) and to determine if [18F]FPRGD2 and FDG PET/CT could predict disease-free survival. METHODS: Baseline [18F]FPRGD2 and FDG PET/CT were performed in 32 consecutive patients (23 men, 9 women; mean age 63 +/- 8 years) with LARC before starting any therapy. A posttreatment [18F]FPRGD2 PET/CT scan was performed in 24 patients after the end of CRT (median interval 7 weeks, range 3 - 15 weeks) and before surgery (median interval 4 days, range 1 - 15 days). RESULTS: All LARC showed uptake of both [18F]FPRGD2 (SUVmax 5.4 +/- 1.5, range 2.7 - 9) and FDG (SUVmax 16.5 +/- 8, range 7.1 - 36.5). There was a moderate positive correlation between [18F]FPRGD2 and FDG SUVmax (Pearson's r = 0.49, p = 0.0026). There was a moderate negative correlation between baseline [18F]FPRGD2 SUVmax and the TRG (Spearman's r = -0.37, p = 0.037), and a [18F]FPRGD2 SUVmax of >5.6 identified all patients with a complete response (TRG 0; AUC 0.84, 95 % CI 0.68 - 1, p = 0.029). In the 24 patients who underwent a posttreatment [18F]FPRGD2 PET/CT scan the response index, calculated as [(SUVmax1 - SUVmax2)/SUVmax1] x 100 %, was not associated with TRG. Post-treatment [18F]FPRGD2 uptake was not correlated with tumour MVD. Neither [18F]FPRGD2 nor FDG uptake predicted disease-free survival. CONCLUSION: Baseline [18F]FPRGD2 uptake was correlated with the pathological response in patients with LARC treated with CRT. However, the specificity was too low to consider its clinical routine use. [less ▲]

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See detailSimulants of malignant melanoma
Pierard, Gérald ULg; Pierard-Franchimont, Claudine ULg; Delvenne, Philippe ULg

in Oncology Reviews (2015), 9

During the recent period, dermoscopy has yielded improvement in the early disclosure of various atypical melanocytic neoplasms (AMN) of the skin. Beyond this clinical procedure, AMN histopathology remains ... [more ▼]

During the recent period, dermoscopy has yielded improvement in the early disclosure of various atypical melanocytic neoplasms (AMN) of the skin. Beyond this clinical procedure, AMN histopathology remains mandatory for establishing their precise diagnosis. Of note, panels of experts in AMN merely report moderate agreement in various puzzling cases. Divergences in opinion and misdiagnosis are likely increased when histopathological criteria are not fine-tuned and when facing a diversity of AMN types. Furthermore, some AMN have been differently named in the literature including atypical Spitz tumor, metastasizing Spitz tumor, borderline and intermediate melanocytic tumor, malignant Spitz nevus, pigmented epithelioid melanocytoma or animal-type melanoma. Some acronyms have been further suggested such as MELTUMP (after melanocytic tumor of uncertain malignant potential) and STUMP (after Spitzoid melanocytic tumor of uncertain malignant potential). In this review, such AMN at the exclusion of cutaneous malignant melanoma (MM) variants, are grouped under the tentative broad heading skin melanocytoma. Such set of AMN frequently follows an indolent course, although they exhibit atypical and sometimes worrisome patterns or cytological atypia. Rare cases of skin melanocytomas progress to loco regional clusters of lesions (agminate melanocytomas), and even to regional lymph nodes. At times, the distinction between a skin melanocytoma and MM remains puzzling. However, multipronged immunohistochemistry and emerging molecular biology help profiling any malignancy risk if present. [less ▲]

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See detailThe importance of the tumor microenvironment in the therapeutic management of cancer
Pottier, Charles ULg; Wheatherspoon, Alodie; RONCARATI, Patrick ULg et al

in Expert Review of Anticancer Therapy (2015), 15

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See detailCarcinogenic HPV infection in the cervical squamo-columnar junction
Mirkovic, Jelena; Howitt, Brooke; RONCARATI, Patrick ULg et al

in Journal of Pathology (The) (2015), 236

Recent studies have suggested the involvement of a unique population of cells at the cervical squamo-columnar junction (SCJ) in the pathogenesis of early (squamous intraepithelial lesion or SIL) and ... [more ▼]

Recent studies have suggested the involvement of a unique population of cells at the cervical squamo-columnar junction (SCJ) in the pathogenesis of early (squamous intraepithelial lesion or SIL) and advanced (squamous cell and adeno-carcinomas) cervical neoplasia. However, there is little evidence to date showing that SCJ cells harbour carcinogenic HPV or are instrumental in the initial phases of neoplasia. This study was designed to 1) determine if normal-appearing SCJ cells contained evidence of carcinogenic HPV infection and 2) trace their transition to early SIL. Sections of cervix from high-risk reproductive age women were selected and SCJ cells were analyzed by using several techniques which increasingly implicated HPV infection: HPV DNA (genotyping and in situ hybridization)/RNA (PCR), immunostaining for HPV16 E2 (an early marker of HPV infection), p16ink4, Ki67 and HPV L1 protein. In 22 cases with a history of SIL and no evidence of preneoplastic lesion in the excision specimen, HPV DNA was isolated from 8 of 10 with visible SCJ cells, 6 of which were HPV16/18 DNA positive. In 5 of these latter cases, the SCJ cells were positive for p16ink4 and/or HPV E2. Transcriptionally active HPV infection (E6/E7 mRNAs) was also detected in micro-dissected SCJ cells. Early squamous atypia associated with the SCJ cells demonstrated in addition diffuse p16ink4 immunoreactivity, elevated proliferative index and rare L1 antigen positivity. We present for the first time direct evidence that normal-appearing SCJ cells can be infected by carcinogenic HPV. They initially express HPV E2 and their progression to SIL is heralded by an expanding metaplastic progeny with increased proliferation and p16ink4 expression. Whether certain SCJs are more vulnerable than others to carcinogenic HPV genotypes and what variables determine transition to high grade SIL remain unresolved, but the common event appears to be a vulnerable cell at the SCJ. [less ▲]

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See detailSoluble factors regulated by epithelial-mesenchymal transition mediate tumour angiogenesis and myeloid cell recruitment.
Suarez-Carmona, Meggy ULg; Bourcy, Morgane ULg; LESAGE, J et al

in Journal of Pathology (The) (2015)

Epithelial-to-mesenchymal transition (EMT) programs provide cancer cells with invasive and survival capacities that might favor metastatic dissemination. Whilst signaling cascades triggering EMT have been ... [more ▼]

Epithelial-to-mesenchymal transition (EMT) programs provide cancer cells with invasive and survival capacities that might favor metastatic dissemination. Whilst signaling cascades triggering EMT have been extensively studied, the impact of EMT on the crosstalk between tumor cells and the tumor microenvironment remains elusive. We aimed to identify EMT-regulated soluble factors that facilitate the recruitment of host cells in the tumor. Our findings indicate that EMT phenotypes relate to the induction of a panel of secreted mediators, namely IL-8, IL-6, sICAM-1, PAI-1 and GM-CSF, and implicate the EMT-transcription factor Snail as a regulator of this process. We further show that EMT-derived soluble factors are pro-angiogenic in vivo (in the mouse ear sponge assay), ex vivo (in the rat aortic ring assay) and in vitro (in a chemotaxis assay). Additionally, conditioned medium from EMT-positive cells stimulates the recruitment of myeloid cells. In a bank of 40 triple-negative breast cancers, tumors presenting features of EMT were significantly more angiogenic and infiltrated by a higher quantity of myeloid cells compared to tumors with little or no EMT. Taken together, our results show that EMT programs trigger the expression of soluble mediators in cancer cells that stimulate angiogenesis and recruit myeloid cells in vivo, which might in turn favor cancer spread. [less ▲]

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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 (2014), 44

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 detailPrognosis of HPV-positive head and neck cancers : implication of smoking and immunosuppression
Duray, Anaëlle; LACREMANS, Daniel ULg; Demoulin, Stéphanie ULg et al

in Advances in Cellular and Molecular Otolaryngology (2014), 2

Detailed reference viewed: 14 (4 ULg)