References of "Delvenne, Philippe"
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See detailComprehensive Approach for Monitoring Human Tissue Degradation
Dubois, Lena ULiege; Stefanuto, Pierre-Hugues ULiege; Perrault, Katelynn ULiege et al

in Chromatographia (2019)

In recent years, comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC × GC–TOFMS) has been reported as a suitable tool for the determination of volatile organic ... [more ▼]

In recent years, comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC × GC–TOFMS) has been reported as a suitable tool for the determination of volatile organic compounds (VOCs) emitted during the process of cadaveric decomposition. The main aim of the present study was to investigate temporal changes in VOC patterns during the decomposition process of various human tissues. The focus of previous research was mainly on the analysis of VOCs produced by whole cadavers. However, this study aimed to identify whether the VOCs produced during decomposition differ between specific organs, and further, to determine the extent of the variation between cadavers. The sampling process developed for this project allowed inter- and intra-cadaveric comparison. The headspace of heart, lung, liver, kidney and blood was monitored during the decomposition process. Tissue samples from five different cadavers were sampled regularly by dynamic pumping onto sorbent tubes that were further thermally desorbed onto a GC × GC–TOFMS system. A large amount of data (n = 774) was obtained, leading to challenges in the integration, interpretation and representation of the results. Eventually, multivariate statistical methods, such as principal components analysis (PCA) and hierarchical cluster analysis (HCA) were applied to the dataset to evaluate trends and differences in subgroups. It was demonstrated that there were subtle differences between the sets of compounds produced from each organ due to the different functions they carry out within the body. However, VOC profiles were more similar among organs from the same cadaver than when comparing samples from different cadavers. Various reasons may cause the differences between the analyzed cadavers, ranging from the individual diet and lifestyle to the time since death. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature. [less ▲]

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See detailTGFBI, an ECM interacting protein, enhances glycolysis and promotes pancreatic cancer cell migration
Costanza, Brunella; Rademaker, Gilles ULiege; Tiamiou, Assia ULiege et al

in International Journal of Cancer (2019)

Pancreatic cancer (PDAC) remains a deadly malignancy with no efficient therapy available up-to-date. Glycolysis is the main provider of energetic substrates to sustain cancer dissemination of PDAC ... [more ▼]

Pancreatic cancer (PDAC) remains a deadly malignancy with no efficient therapy available up-to-date. Glycolysis is the main provider of energetic substrates to sustain cancer dissemination of PDAC. Accordingly, altering the glycolytic pathway is foreseen as a sound approach to trigger pancreatic cancer regression. Here, we show for the first time that high TGFBI expression in PDAC patients is associated with a poor outcome. We demonstrate that, although usually secreted by stromal cells, PDAC cells synthesize and secrete TGFBI in quantity correlated with their migratory capacity. Mechanistically, we show that TGFBI activates FAK signaling pathway through its binding to integrin αVβ5, leading to a significant enhancement of glycolysis and to the acquisition of an invasive phenotype. Finally, we show that TGFBI silencing significantly inhibits PDAC tumor development in a chick chorioallantoic membrane assay model. Our study highlights TGFBI as an oncogenic ECM interacting protein that bears the potential to serve as a target for new anti-PDAC therapeutic strategies. [less ▲]

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See detailUnveiling of a new role for DPF3 protein in cancer biology
Verrillo, Giulia ULiege; Hanache, Sarah ULiege; Duchemin, Amandine ULiege et al

Poster (2019, February)

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See detailHuman colon cancer cells highly express myoferlin to maintain a fit mitochondrial network and escape p53-driven apoptosis.
Rademaker, Gilles ULiege; Costanza, Brunella; Bellier, Justine ULiege et al

in Oncogenesis (2019)

Colon adenocarcinoma is the third most commonly diagnosed cancer and the second deadliest one. Metabolic reprogramming, described as an emerging hallmark of malignant cells, includes the predominant use ... [more ▼]

Colon adenocarcinoma is the third most commonly diagnosed cancer and the second deadliest one. Metabolic reprogramming, described as an emerging hallmark of malignant cells, includes the predominant use of glycolysis to produce energy. Recent studies demonstrated that mitochondrial electron transport chain inhibitor reduced colon cancer tumour growth. Accumulating evidence show that myoferlin, a member of the ferlin family, is highly expressed in several cancer types, where it acts as a tumour-promoter and participates in the metabolic rewiring towards oxidative metabolism. In this study, we showed that myoferlin expression in colon cancer lesions is associated with low patient survival and is higher than in non-tumoural adjacent tissue. Human colon cancer cells silenced for myoferlin exhibit a reduced oxidative phosphorylation activity associated with mitochondrial fission leading, ROS accumulation, decreased cell growth, and increased apoptosis. We observed the triggering of a DNA damage response culminating to a cell cycle arrest in wild-type p53 cells. The use of a p53 null cell line or a compound able to restore p53 activity (Prima-1) reverted the effects induced by myoferlin silencing, confirming the involvement of p53. The recent identification of a compound interacting with a myoferlin C2 domain and bearing anti-cancer potency identifies, together with our demonstration, this protein as a suitable new therapeutic target in colon cancer. [less ▲]

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See detailMethylglyoxal, a glycolysis metabolite, triggers metastasis through MEK/ERK/SMAD1 pathway activation in breast cancer
Nokin, Marie-Julie ULiege; Bellier, Justine ULiege; Durieux, Florence et al

in Breast Cancer Research (2019), 21(1

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See detailMicroproteomic Profiling of High-Grade Squamous Intraepithelial Lesion of the Cervix: Insight into Biological Mechanisms of Dysplasia and New Potential Diagnostic Markers
Pottier, Charles ULiege; Kriegsmann, M.; Alberts, D. et al

in Proteomics. Clinical Applications (2019), 13(1)

Purpose: High-grade squamous intraepithelial lesion (HSIL) is a known precursor for squamous cell carcinoma of uterine cervix. Although it is known that SILs are associated to infection by human ... [more ▼]

Purpose: High-grade squamous intraepithelial lesion (HSIL) is a known precursor for squamous cell carcinoma of uterine cervix. Although it is known that SILs are associated to infection by human papillomavirus, downstream biological mechanisms are still poorly described. In this study, we compared the microproteomic profile of HSIL to normal tissues: ectocervix (ectoC) and endocervix (endoC). Experimental design: Tissue regions of endoC, ectoC, and HSlL were collected by laser microdissection (3500 cells each) from five patients. Samples were processed and analyzed using our recently developed laser microdissection-based microproteomic method. Tissues were compared in order to retrieve HSIL's proteomic profile. Potentially interesting proteins for pathology were stained by immunohistochemistry. Results: We identified 3072 proteins among the fifteen samples and 2386 were quantified in at least four out of the five biological replicates of at least one tissue type. We found 236 proteins more abundant in HSIL. Gene ontology enrichments revealed mechanisms of DNA replication and RNA splicing. Despite the squamous nature of HSIL, a common signature between HSIL and endoC could be found. Finally, potential new markers could support diagnosis of dysplasia in SILs. Conclusion and clinical relevance: This microproteomic investigation of HSIL gives insights into the biology of cervical precancerous lesions. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim [less ▲]

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See detailP2X1 deficiency causes massive intestinal bleeding along with enhanced neutrophil-dependent thrombosis in colitis
Wéra, Odile ULiege; Servais, Laurence ULiege; Delierneux, Céline et al

Conference (2018, November)

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See detailHuman papillomavirus oncoproteins induce a reorganization of epithelial-associated γδ T cells promoting tumor formation
Van hede, Dorien ULiege; Polese, Barbara ULiege; Humblet, Chantal ULiege et al

Poster (2018, June)

Background: γδ T cells have been shown to protect against the formation of squamous cell carcinoma (SCC) in several models. Yet, the role of γδ T cells in human papillomavirus (HPV) associated uterine ... [more ▼]

Background: γδ T cells have been shown to protect against the formation of squamous cell carcinoma (SCC) in several models. Yet, the role of γδ T cells in human papillomavirus (HPV) associated uterine cervical SCC, the third cause of death by cancer in women, is unknown. Method: We investigated the impact of γδ T cells in a transgenic mouse model of carcinogenesis induced by HPV16-oncoproteins. Human uterine cervical biopsies of women infected by HPV were also analyzed. Results: Surprisingly, γδ T cells promoted the development of HPV16 oncoprotein-induced lesions. HPV16-oncoproteins induced a decrease in epidermal Skint1 expression and the associated anti-tumor Vγ5+ γδ T cells, which were replaced by γδ T cell subsets (mainly Vγ6+ γδlowCCR2+CCR6-) actively producing IL-17A. Consistent with a proangiogenic role, γδ T cells promoted the formation of blood vessels in the dermis underlying the HPV-induced lesions. In human cervical biopsies, IL-17A+ γδ T cells could be only observed at the cancer stage (SCC), where HPV-oncoproteins are highly expressed, supporting the clinical relevance of our observations in mice. Overall, our results suggest that HPV16-oncoproteins induce a reorganization of the local epithelial-associated γδ T cell subpopulations thereby promoting angiogenesis and cancer development. [less ▲]

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See detailDeciphering the radiosensitivity of HPV-positive tumors
Bruyère, Diane ULiege; Lebeau, Alizée ULiege; RONCARATI, Patrick ULiege et al

Poster (2018, May 30)

The increased radiosensitivity of HPV positive tumors (compared to HPV negative ones) is widely known in clinical settings. However, the mechanisms by which this phenomenon occurs are still to be ... [more ▼]

The increased radiosensitivity of HPV positive tumors (compared to HPV negative ones) is widely known in clinical settings. However, the mechanisms by which this phenomenon occurs are still to be elucidated. A few hypotheses have been suggested regarding this differential radiosensitivity like, for example, an altered microtumoral environment or virus-host protein interactions. In this study, we focused on interactions between DNA repair proteins and virus oncoproteins. A large panel of 147 proteins implicated in DNA repair pathways was tested for potential interaction with HPV16 E6 and/or E7 oncoproteins using the GPCA method (Gaussia Princeps Complementation Assay). The proteins highlighted by the screening were validated by co-IP. The functional experiments, realized on HPV negative head and neck cancer (UPCI-SCC-111, FaDu, UPCI-SCC-40), vulva cancer (C33a) and control keratinocytes (HaCaT) stably transduced with E6 and/or E7, are in progress. [less ▲]

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See detailDeciphering the radiosensitivity of HPV-positive tumors
Bruyère, Diane ULiege; Lebeau, Alizée ULiege; RONCARATI, Patrick ULiege et al

Poster (2018, May 28)

The increased radiosensitivity of HPV positive tumors (compared to HPV negative ones) is widely known in clinical settings. However, the mechanisms by which this phenomenon occurs are still to be ... [more ▼]

The increased radiosensitivity of HPV positive tumors (compared to HPV negative ones) is widely known in clinical settings. However, the mechanisms by which this phenomenon occurs are still to be elucidated. A few hypotheses have been suggested regarding this differential radiosensitivity like, for example, an altered microtumoral environment or virus-host protein interactions. In this study, we focused on interactions between DNA repair proteins and virus oncoproteins. A large panel of 147 proteins implicated in DNA repair pathways was tested for potential interaction with HPV16 E6 and/or E7 oncoproteins using the GPCA method (Gaussia Princeps Complementation Assay). The proteins highlighted by the screening were validated by co-IP. The functional experiments, realized on HPV negative head and neck cancer (UPCI-SCC-111, FaDu, UPCI-SCC-40), vulva cancer (C33a) and control keratinocytes (HaCaT) stably transduced with E6 and/or E7, are in progress. [less ▲]

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See detailMyoferlin controls mitochondrial structure and activity in pancreatic ductal adenocarcinoma, and affects tumor aggressiveness
Rademaker, Gilles ULiege; Hennequière, Vincent ULiege; Nokin, Marie-Julie ULiege et al

in Oncogene (2018)

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death. Therapeutic options remain very limited and are based on classical chemotherapies. Energy metabolism ... [more ▼]

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death. Therapeutic options remain very limited and are based on classical chemotherapies. Energy metabolism reprogramming appears as an emerging hallmark of cancer and is considered a therapeutic target with considerable potential. Myoferlin, a ferlin family member protein overexpressed in PDAC, is involved in plasma membrane biology and has a tumor-promoting function. In the continuity of our previous studies, we investigated the role of myoferlin in the context of energy metabolism in PDAC. We used selected PDAC tumor samples and PDAC cell lines together with small interfering RNA technology to study the role of myoferlin in energetic metabolism. In PDAC patients, we showed that myoferlin expression is negatively correlated with overall survival and with glycolytic activity evaluated by 18F-deoxyglucose positron emission tomography. We found out that myoferlin is more abundant in lipogenic pancreatic cancer cell lines and is required to maintain a branched mitochondrial structure and a high oxidative phosphorylation activity. The observed mitochondrial fission induced by myoferlin depletion led to a decrease of cell proliferation, ATP production, and autophagy induction, thus indicating an essential role of myoferlin for PDAC cell fitness. The metabolic phenotype switch generated by myoferlin silencing could open up a new perspective in the development of therapeutic strategies, especially in the context of energy metabolism. [less ▲]

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See detailMurine stroma adopts a human-like metabolic phenotype in the PDX model of colorectal cancer and liver metastases
Blomme, A.; van Simaeys, G.; Doumont, G. et al

in Oncogene (2018), 37(9), 1237-1250

Cancer research is increasingly dependent of patient-derived xenograft model (PDX). However, a major point of concern regarding the PDX model remains the replacement of the human stroma with murine ... [more ▼]

Cancer research is increasingly dependent of patient-derived xenograft model (PDX). However, a major point of concern regarding the PDX model remains the replacement of the human stroma with murine counterpart. In the present work we aimed at clarifying the significance of the human-to-murine stromal replacement for the fidelity of colorectal cancer (CRC) and liver metastasis (CRC-LM) PDX model. We have conducted a comparative metabolic analysis between 6 patient tumors and corresponding PDX across 4 generations. Metabolic signatures of cancer cells and stroma were measured separately by MALDI-imaging, while metabolite changes in entire tumors were quantified using mass spectrometry approach. Measurement of glucose metabolism was also conducted in vivo using [18F]-fluorodeoxyglucose (FDG) and positron emission tomography (PET). In CRC/CRC-LM PDX model, human stroma was entirely replaced at the second generation. Despite this change, MALDI-imaging demonstrated that the metabolic profiles of both stromal and cancer cells remained stable for at least four generations in comparison to the original patient material. On the tumor level, profiles of 86 water-soluble metabolites as well as 93 lipid mediators underlined the functional stability of the PDX model. In vivo PET measurement of glucose uptake (reflecting tumor glucose metabolism) supported the ex vivo observations. Our data show for the first time that CRC/CRC-LM PDX model maintains the functional stability at the metabolic level despite the early replacement of the human stroma by murine cells. The findings demonstrate that human cancer cells actively educate murine stromal cells during PDX development to adopt the human-like phenotype. © 2017 Macmillan Publishers Limited, part of Springer Nature [less ▲]

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See detailUnveiling a New Role of DPF3 Protein in Cancer Biology
Verrillo, Giulia ULiege; Hanache, Sarah; Duchemin, Amandine ULiege et al

Poster (2018, February 01)

Detailed reference viewed: 40 (5 ULiège)