References of "Peulen, Olivier"
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See detailTargeting osteopontin suppresses glioblastoma stem-like cell character and tumorigenicity in vivo
Lamour, Virginie; Henry, Aurélie ULg; Kroonen, Jerome et al

in International Journal of Cancer = Journal International du Cancer (2015)

Osteopontin (OPN) is a secreted protein involved in most aspects of tumor progression and metastasis development. Elevated OPN expression has been reported in multiple types of cancer including ... [more ▼]

Osteopontin (OPN) is a secreted protein involved in most aspects of tumor progression and metastasis development. Elevated OPN expression has been reported in multiple types of cancer including glioblastoma (GBM), the highest grade and most aggressive brain tumor. GBMs contain a subpopulation of glioma-initiating cells (GICs) implicated in progression, therapeutic resistance and recurrence. We have previously demonstrated that OPN silencing inhibited GBM cell growth in vitro and in vivo. Moreover, activation of CD44 signaling upon OPN ligation has been recently implicated in the acquisition of a stem cell phenotype by GBM cells. The present study is aimed to explore OPN autocrine function using shRNA silencing strategy in GICs enriched from GBM cell lines and a human primary GBM grown in EGF and bFGF defined medium. The removal of these growth factors and addition of serum induced a significant loss of OPN expression in GICs. We showed that OPN-silenced GICs were unable to grow as spheres and this capacity was restored by exogenous OPN. Importantly, the expression of Sox2, Oct3/4 and Nanog, key stemness transcription factors, was significantly decreased in GICs upon OPN targeting. We identified Akt/mTOR/p70S6K as the main signaling pathway triggered following OPN-mediated EGFR activation in GICs. Finally, in an orthotopic xenograft mouse model, the tumorigenic potential of U87-MG sphere cells was completely abrogated upon OPN silencing. Our demonstration of endogenous OPN major regulatory effects on GICs stemness phenotype and tumorigenicity implies a greater role than anticipated for OPN in GBM pathogenesis from initiation and progression to probable recurrence. [less ▲]

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See detailImpact of the Structure of Biocompatible Aliphatic Polycarbonates on siRNA Transfection Ability
Frère, Antoine ULg; Kawalec, Michal; Tempelaar, Sarah et al

in Biomacromolecules (2015)

RNAi therapeutics are promising therapeutic tools that have sparked the interest of many researchers. In an effort to provide a safe alternative to PEI, we have designed a series of new guanidinium and/or ... [more ▼]

RNAi therapeutics are promising therapeutic tools that have sparked the interest of many researchers. In an effort to provide a safe alternative to PEI, we have designed a series of new guanidinium and/or morpholino functionalized biocompatible and biodegradable polycarbonate vectors. The impact of different functions (morpholino-, guanidinium-, hydrophobic groups), of the architecture (linear homopolymer to dumbbell-shape) and of the molecular weight of these copolymers on their capacity to form polyplexes and to decrease the expression of two epigenetic regulators of gene expression, HDAC7 and HDAC5 was evaluated. The use of one of these polymers combining morpholine and guanidine functions at the ratio >1 and hydrophobic trimethylene carbonate groups showed a significant decrease of mRNA and protein level in HeLa cells, similar to PEI. These results highlight the potential of polycarbonate vectors for future in vivo application as an anti-cancer therapy. [less ▲]

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See detailPolyplex based on polycarbonate polymesr for an efficient delivery of an anti-angiogenic siRNA
Frère, Antoine ULg; Tempelaar, Sarah; Peixoto, Paul ULg et al

Conference (2014, August 28)

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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 detailImpact of the Structure of Biocompatible Aliphatic Polycarbonate on siRNA Transfection Ability
Frère, Antoine ULg; Kawalec, Michal; Tempelaar, Sarah et al

Poster (2014, May 26)

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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 detailPolyplex Based On Polycarbonate Polymers For An Efficient Delivery Of An Anti-Angiogenic siRNA
Frère, Antoine ULg; Kawalec, Michal; Tempelaar, Sarah et al

Poster (2014)

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See detailThe Anti-Tumor Effect of HDAC Inhibition in a Human Pancreas Cancer Model Is Significantly Improved by the Simultaneous Inhibition of Cyclooxygenase 2
Peulen, Olivier ULg; Gonzalez, Arnaud; Peixoto, Paul ULg et al

in PLoS ONE (2013), 8(9), 75102

Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer death worldwide, with no satisfactory treatment to date. In this study, we tested whether the combined inhibition of cyclooxygenase-2 ... [more ▼]

Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer death worldwide, with no satisfactory treatment to date. In this study, we tested whether the combined inhibition of cyclooxygenase-2 (COX-2) and class I histone deacetylase (HDAC) may results in a better control of pancreatic ductal adenocarcinoma. The impact of the concomitant HDAC and COX-2 inhibition on cell growth, apoptosis and cell cycle was assessed first in vitro on human pancreas BxPC-3, PANC-1 or CFPAC-1 cells treated with chemical inhibitors (SAHA, MS-275 and celecoxib) or HDAC1/2/3/7 siRNA. To test the potential antitumoral activity of this combination in vivo, we have developed and characterized, a refined chick chorioallantoic membrane tumor model that histologically and proteomically mimics human pancreatic ductal adenocarcinoma. The combination of HDAC1/3 and COX-2 inhibition significantly impaired proliferation of BxPC-3 cells in vitro and stalled entirely the BxPC-3 cells tumor growth onto the chorioallantoic membrane in vivo. The combination was more effective than either drug used alone. Consistently, we showed that both HDAC1 and HDAC3 inhibition induced the expression of COX-2 via the NF-kB pathway. Our data demonstrate, for the first time in a Pancreatic Ductal Adenocarcinoma (PDAC) model, a significant action of HDAC and COX-2 inhibitors on cancer cell growth, which sets the basis for the development of potentially effective new combinatory therapies for pancreatic ductal adenocarcinoma patients. [less ▲]

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See detailConcomitant inhibition of class I HDAC and COX-2 exerts a antitumor effect in a human pancreatic cancer model
Gonzalez, Arnaud ULg; Peixoto, Paul ULg; Turtoi, Andrei ULg et al

Poster (2013, July 11)

- Introduction : Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in developed countries. Early-stage pancreatic cancer is usually clinically silent, and disease only ... [more ▼]

- Introduction : Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in developed countries. Early-stage pancreatic cancer is usually clinically silent, and disease only becomes apparent after the tumor invades surrounding tissues or metastatises to distant organs. Moreover, the current chemotherapeutic treatments have no or few effects on this type of cancer, increasing only slightly the median survival of the patients. The survival rate at 5-years is only 3%. There is a need to develop new effective therapies for PDAC patients together with a robust and fast in vivo model allowing drug screening. In this study, We tested whether the combined inhibition of cyclooxygenase-2 (COX-2) and class I histone deacetylase (HDAC) may result in a better control of PDAC. We improved the formation of pancreatic tumor on Chorioallantoic membrane (CAM), an alternative to murine model. - Methods : The impact of the concomitant HDAC and COX-2 inhibition on cell growth, apoptosis and cell cycle was assessed in vitro on human pancreas BxPC-3 cells treated with chemical inhibitors (SAHA, MS-275 and celecoxib) or HDAC1/3/7 siRNA. To test the potential antitumoral activity of this combination in vivo, we improved, characterized and used model of pancreas tumors growing on chick chorioallantoic membrane. - Results : The inhibition of HDAC1/3 by SiRNA or MS-275 treatment reduced significantly the growth of BxPC-3 cells in vitro. Furthermore, we showed by QPCR and immunoblotting that both HDAC1 and HDAC3 inhibition induced the expression of COX-2 at least via the NF-kB pathway. Based on this observation, we decided to test the effect of MS-275 combined with celecoxib a COX-2 inhibitor. This combination was more effective then either drug used alone to reduce the growth of BxPC-3 cells. By FACS analysis we showed that MS-275/celecoxib combination decreased significantly the proportion of cells in S phase and increased significantly and drastically the proportion in G0/G1 at 24, 48 and 72h. By immunobloting this GO/G1 arrest was confirmed by accumulation of cell cycle repressors (P21, P27) and disappearance of hyper phosphorylated form of RB protein. Following a procedure development, we produced on CAM 60 mm3 functionally vascularized tumors mimicking human pancreatic tumors on CAM model. The clinical relevance of this model is supported by the CK7+/CK19+/CK20-/CEA+/Ki67+/CD56- immunolabeling. Recently we have discovered several novel biomarkers of human PDAC: MYOF, TGFBI, LTBP2. These antigens were expressed in tumors grown on CAM, reaffirming its clinical relevance. The concept of the co-treatment by MS-275 and celecoxib was validated using this model. We showed that celecoxib alone did not significantly reduce tumor growth. MS-275 alone decreased tumor growth by 50% and combination of celecoxib and MS-275 stalled entirely the tumor growth. - Conclusions : Our data demonstrate a significant synergic anti-tumoral action of HDAC and COX-2 inhibitors, which set a basis for the development of potentially effective new combinatory therapies for PDAC patients. [less ▲]

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See detailOrganized Proteomic Heterogeneity in Colorectal Cancer Liver Metastases and Implications for Therapies
Turtoi, Andrei ULg; Blomme, Arnaud; Debois, Delphine et al

in Hepatology (Baltimore, Md.) (2013)

Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems ... [more ▼]

Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Because to date no similar information is available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image-guided proteomics and explored the heterogeneity of extracellular and membrane subproteome in a unique collection of eight fresh human colorectal carcinoma (CRC) liver metastases. Monitoring the spatial distribution of over 1,000 proteins, we found unexpectedly that all liver metastasis lesions displayed a reproducible, zonally delineated pattern of functional and therapeutic biomarker heterogeneity. The peritumoral region featured elevated lipid metabolism and protein synthesis, the rim of the metastasis dis- played increased cellular growth, movement, and drug metabolism, whereas the center of the lesion was characterized by elevated carbohydrate metabolism and DNA-repair activity. From the aspect of therapeutic targeting, zonal expression of known and novel biomarkers was evident, reinforcing the need to select several targets in order to achieve optimal coverage of the lesion. Finally, we highlight two novel antigens, LTBP2 and TGFBI, whose expression is a consistent feature of CRC liver metastasis. We demon- strate their in vivo antibody-based targeting and highlight their potential usefulness for clinical applications. Conclusion: The proteome heterogeneity of human CRC liver metastases has a distinct, organized pattern. This particular hallmark can now be used as part of the strategy for developing rational therapies based on multiple sets of target- able antigens. [less ▲]

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See detailDifferential proteomic analysis of a human breast tumor and its matched bone metastasis identifies cell membrane and extracellular proteins associated with bone metastasis
Dumont, Bruno ULg; Castronovo, Vincenzo ULg; Peulen, Olivier ULg et al

in Journal of Proteome Research (2012)

The classical fate of metastasizing breast cancer cells is to seed and form secondary colonies in bones. The molecules closely associated with these processes are predominantly present at the cell surface ... [more ▼]

The classical fate of metastasizing breast cancer cells is to seed and form secondary colonies in bones. The molecules closely associated with these processes are predominantly present at the cell surface and in the extracellular space, establishing the first contacts with the target tissue. In this study, we had the rare opportunity to analyze a bone metastatic lesion and its corresponding breast primary tumor obtained simultaneously from the same patient. Using mass spectrometry, we undertook a proteomic study on cell surface and extracellular protein-enriched material. We provide a repertoire of significantly modulated proteins, some with yet unknown roles in the bone metastatic process as well as proteins notably involved in cancer cell invasiveness and in bone metabolism. The comparison of these clinical data with those previously obtained using a human osteotropic breast cancer cell line highlighted an overlapping group of proteins. Certain differentially expressed proteins are validated in the present study using immunohistochemistry on a retrospective collection of breast tumors and matched bone metastases. Our exclusive set of selected proteins supports the set-up of further investigations on both clinical samples and experimental bone metastasis models that will help to reveal the finely coordinated expression of proteins that favor the development of metastases in the bone microenvironment. [less ▲]

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See detailIntestinal Growth and Pathology og Giardia duodenalis assemblage subtype AI, AII, B end E in the gerbil model
Bénéré, Ely; Van Assche, Tim; Van Ginneken, Chris et al

in Parasitology (2012), 139

This study investigated the significance of the genetic differences between assemblages A, B and E on intestinal growth and virulence. Intestinal growth and virulence were studied in 2 laboratory (AI: WB ... [more ▼]

This study investigated the significance of the genetic differences between assemblages A, B and E on intestinal growth and virulence. Intestinal growth and virulence were studied in 2 laboratory (AI: WB and B: GS/M-83-H7) and 6 field isolates of assemblage subtype AI, AII, B and EIII. Intestinal trophozoite burdens, body weight and faecal consistency were monitored until day 29 post-infection (p.i.), morphological (mucosal architecture and inflammation) and functional (disaccharidase and alkaline phosphatase enzyme activity) damage to the small intestine were evaluated on days 7 and 18 p.i. The assemblage subtypes AI and B were more infectious and produced higher trophozoite loads for a longer period compared to the subtypes AII and EIII. The body weight of infected gerbils was significantly reduced compared to uninfected controls, but did not differ between the assemblage subtypes. Consistent softening of the faeces was only observed with assemblage B. Assemblage B next to assemblage subtype AI elicited relatively higher pathogenicity, characterized by more extensive damage to mucosal architecture, decreased brush-border enzyme function and infiltration of inflammatory cells. Assemblage EIII and AII isolates showed relatively low virulence. The Giardia assemblage subtypes exhibit different levels of growth and virulence in the gerbil model. [less ▲]

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See detailHDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells
Peixoto, Paul ULg; Castronovo, Vincenzo ULg; Matheus, Nicolas ULg et al

in Cell Death & Differentiation (2012)

Histone deacetylases (HDACs) form a family of enzymes, which have fundamental roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation, and apoptosis of cancer ... [more ▼]

Histone deacetylases (HDACs) form a family of enzymes, which have fundamental roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation, and apoptosis of cancer cells. In this study, we further investigated the biological function of HDAC5 in cancer cells. We found HDAC5 is associated with actively replicating pericentric heterochromatin during late S phase. We demonstrated that specific depletion of HDAC5 by RNA interference resulted in profound changes in the heterochromatin structure and slowed down ongoing replication forks. This defect in heterochromatin maintenance and assembly are sensed by DNA damage checkpoint pathways, which triggered cancer cells to autophagy and apoptosis, and arrested their growth both in vitro and in vivo. Finally, we also demonstrated that HDAC5 depletion led to enhanced sensitivity of DNA to DNA-damaging agents, suggesting that heterochromatin de-condensation induced by histone HDAC5 silencing may enhance the efficacy of cytotoxic agents that act by targeting DNA in vitro. Together, these results highlighted for the first time an unrecognized link between HDAC5 and the maintenance/assembly of heterochromatin structure, and demonstrated that its specific inhibition might contribute to increase the efficacy of DNA alteration-based cancer therapies in clinic. [less ▲]

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See detailNUCLEAR DELIVERY OF A THERAPEUTIC PEPTIDE BY LONG CIRCULATING pH-SENSITIVE LIPOSOMES: BENEFITS OVER CLASSICAL VESICLES
Ducat, Emilie; Deprez, Juile; Noël, Agnès ULg et al

Poster (2011, December 06)

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See detailNuclear delivery of a therapeutic peptide by long circulating pH-sensitive liposomes: Benefits over classical vesicles.
Ducat, Emilie ULg; Deprez, Julie ULg; Gillet, Aline ULg et al

in International Journal of Pharmaceutics (2011)

The purpose of this study is to propose a suitable vector combining increased circulation lifetime and intracellular delivery capacities for a therapeutic peptide. Long circulating classical liposomes ... [more ▼]

The purpose of this study is to propose a suitable vector combining increased circulation lifetime and intracellular delivery capacities for a therapeutic peptide. Long circulating classical liposomes [SPC:CHOL:PEG-750-DSPE (47:47:6 molar% ratio)] or pH-sensitive stealth liposomes [DOPE:CHEMS:CHOL:PEG(750)-DSPE (43:21:30:6 molar% ratio)] were used to deliver a therapeutic peptide to its nuclear site of action. The benefit of using stealth pH-sensitive liposomes was investigated and formulations were compared to classical liposomes in terms of size, shape, charge, encapsulation efficiency, stability and, most importantly, in terms of cellular uptake. Confocal microscopy and flow cytometry were used to evaluate the intracellular fate of liposomes themselves and of their hydrophilic encapsulated material. Cellular uptake of peptide-loaded liposomes was also investigated in three cell lines: Hs578t human epithelial cells from breast carcinoma, MDA-MB-231 human breast carcinoma cells and WI-26 human diploid lung fibroblast cells. The difference between formulations in terms of peptide delivery from the endosome to the cytoplasm and even to the nucleus was investigated as a function of time. Characterization studies showed that both formulations possess acceptable size, shape and encapsulation efficiency but cellular uptake studies showed the important benefit of the pH-sensitive formulation over the classical one, in spite of liposome PEGylation. Indeed, stealth pH-sensitive liposomes were able to deliver hydrophilic materials strongly to the cytoplasm. Most importantly, when encapsulated in pH-sensitive stealth liposomes, the peptide was able to reach the nucleus of tumorigenic and non tumorigenic breast cancer cells. [less ▲]

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See detailTransferts graisseux au niveau du sein: implications oncologiques.
NIZET, Jean-Luc ULg; Gonzalez, Arnaud ULg; Peulen, Olivier ULg et al

in Revue Médicale de Liège (2011), 66(5-6), 362-6

Autologous fat grafting for breast is increasing dramatically. This fat injection needs accurate technical conditions, and shows very good and long-lasting clinical results. Nevertheless, in breast ... [more ▼]

Autologous fat grafting for breast is increasing dramatically. This fat injection needs accurate technical conditions, and shows very good and long-lasting clinical results. Nevertheless, in breast conservative treatment sequellae, fat injection could lead to difficulties in breast imaging, but also there is some concerns about the potential oncologic risks of these procedures. [less ▲]

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See detailCellular uptake of liposomes monitored by confocal microscopy and flow cytometry
Ducat, Emilie ULg; Evrard, Brigitte ULg; Peulen, Olivier ULg et al

in Journal of Drug Delivery Science and Technology [=JDDST] (2011), 21(6), 469-477

Detailed reference viewed: 121 (29 ULg)