References of "Gonzalez, Arnaud"
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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 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 detailIn Ovo PET Imaging Of A Human Colorectal Carcinoma Model In Chicken Chorioallantoic Membrane
Warnock, Geoffrey ULg; Turtoi, Andrei ULg; Blomme, Arnaud ULg et al

Poster (2012, October)

Aim. The objective of this study was to use in vivo PET/CT imaging as a validation tool for a novel human colorectal carcinoma model being developed in chicken chorioallantoic membrane (CAM). For this ... [more ▼]

Aim. The objective of this study was to use in vivo PET/CT imaging as a validation tool for a novel human colorectal carcinoma model being developed in chicken chorioallantoic membrane (CAM). For this initial pilot study a cell line modeling colon cancer was selected and imaged using [18F]fluorodeoxyglucose (FDG). <br />Materials and methods. A window was made in the shell of fertilized chicken eggs and 3x106 SW1222 human colorectal carcinoma cells were implanted at day 10 post-fertilization. On day 17 the shell window was enlarged to allow direct injection of FDG (12.2 ± 4.5 MBq/egg) into a CAM blood vessel. During injection the egg was warmed on a heating pad. A mixture of ketamine/medetomidine (50 :1 mg/ml, 0.2 ml/egg) was injected into the albumin in some eggs to assess the effect of anesthesia. After FDG injection the egg was returned to the incubator for a 45 min uptake period before imaging. Imaging was performed on a Siemens Focus 120 microPET with structural CT on a General Electric eXplore CT120. A Minerve cell system allowed reproducible positioning between modalities. PET data was acquired in list mode before histogramming into a single 10 min frame for reconstruction using a 3D maximum a posteriori (MAP) method with all corrections except scatter. A standard 100 µm (theoretical) image resolution protocol (70 kV, 50 mA, 32 ms, 220 views) was used to obtain structural CT data. Image coregistration was performed in PMOD version 3.3. In a separate egg, the influence of added contrast on the CT data was investigated by adding iodinated contrast agent (Iobitridol 35 mgI/ml) to the albumin. <br />Results. FDG uptake was clear in chick and tumor, with notably high uptake at the major joints. Tumors were identified by localization of FDG uptake on the surface of the CAM. A lack of soft tissue contrast between tumor, CAM and albumin made precise structural identification of the tumor difficult. Anesthesia was crucial to image quality in both PET and CT. CT contrast between the soft tissues of the chick and surrounding albumin/structures was improved by addition of contrast agent. <br />Conclusion. For the first time we demonstrate successful imaging of FDG uptake in a human colorectal carcinoma chicken CAM model in ovo. Methods to improve structural data are under investigation and will be used in further studies. With such improvement, this model could be of great value to PET oncology imaging. [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 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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