http://hdl.handle.net/2268/107 Chercher dans ce canal chercher http://orbi.ulg.ac.be/simple-search http://hdl.handle.net/2268/150521 Titre: Human papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion <br/> <br/>Auteur, co-auteur: Renoux, Virginie; Bisig, Bettina; Langers, Inge; Renaud, Bastin; Thiry, Marc; Deroanne, Christophe; Delvenne, Philippe; Jacobs, Nathalie <br/> <br/>Résumé: Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV-infected women clear the virus within two years. However, it remains unclear which immune cells are implicated in this process and no study has evaluated the direct interaction between HPVs and NK cells, a key player in host resistance to viruses and tumors. We demonstrated an NK-cell infiltration in HPV- associated preneoplastic cervical lesions. Since HPVs cannot grow in vitro, virus-like particles (VLPs) were used as a model for studying the NK-cell response against the virus. Interestingly, NK cells displayed higher cytotoxic activity and cytokine production (TNF-a and IFN-g) in the presence of HPV-VLPs. Using flow cytometry and microscopy, we observed that NK-cell stimulation was linked to rapid VLP entry into these cells by macropinocytosis. Using CD16+ and CD16- NK-cell lines and a CD16-blocking antibody, we demonstrated that CD16 is necessary for HPV–VLP internalization, as well as for degranulation and cytokine production. Thus, we show for the first time that NK cells interact with HPVs and can participate in the immune response against HPV-induced lesions. Sat, 15 Jun 2013 03:00:44 GMT http://hdl.handle.net/2268/149333 Titre: Human papillomavirus predicts the outcome following concomitant chemoradiotherapy in patients with head and neck squamous cell carcinomas. <br/> <br/>Auteur, co-auteur: Duray, Anaelle; Descamps, Geraldine; Decaestecker, Christine; Sirtaine, Nicolas; Gilles, Andre; Khalife, Mohamad; Chantrain, Gilbert; Depuydt, Christophe E.; Delvenne, Philippe; Saussez, Sven <br/> <br/>Résumé: We investigated the prevalence of human papillomavirus (HPV) in a clinical series of 72 patients with head and neck squamous cell carcinoma (HNSCC) using a retrospective and prospective study design. The majority of patients were smokers and/or drinkers and were treated with concomitant chemoradiotherapy (CCR). Furthermore, we assessed the impact of HPV positivity on the response to CCR. Paraffin-embedded samples from HNSCC patients (n=72) were evaluated for the presence of HPV DNA using both GP5+/GP6+ consensus PCR and type-specific E6/E7 PCR to detect HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67 and 68. The type-specific E6/E7 PCR demonstrated that 20 out of 69 HNSCC patients (29%) presented with high-risk (HR) HPV types and that 5 of the 69 HNSCC patients (7%) presented with low-risk (LR) HPV types. Using the GP5+/GP6+ PCR, we observed that the rate of response was statistically lower in the HPV+ group (P=0.02). Concerning patient outcomes in terms of recurrence and survival, we observed that the prognosis was poorer for HPV+ patients. We showed for the first time that patients with HPV+ HNSCC present with a worse prognosis after CCR. This observation highlights the need for prospective studies with large numbers of patients and a detailed history of tobacco and alcohol consumption before validating HPV as a marker of prognosis following CCR. Mon, 27 May 2013 12:04:34 GMT http://hdl.handle.net/2268/149218 Titre: In vivo PET/CT in a human glioblastoma chicken chorioallantoic membrane model: A new tool for oncology and radiotracer development. <br/> <br/>Auteur, co-auteur: Warnock, Geoffrey; Turtoi, Andrei; Blomme, Arnaud; Bretin, Florian; Bahri, Mohamed Ali; Lemaire, Christian; Libert, Lionel; Seret, Alain; Luxen, André; Castronovo, Vincenzo; Plenevaux, Alain <br/> <br/>Résumé: For many years the laboratory mouse has been used as the standard model for in vivo oncology research, particularly in the development of novel PET tracers, but the growth of tumors on chicken chorioallantoic membrane (CAM) provides a more rapid, low cost and ethically sustainable alternative. For the first time, we demonstrate the feasibility of in vivo PET and CT imaging in a U87 glioblastoma tumor model on chicken chorioallantoic membrane (CAM), with the aim of applying this model for screening of novel PET tracers. Methods: U87 glioblastoma cells were implanted on the CAM at day 11 post-fertilization and imaged at day 18. A small animal imaging cell was used to maintain incubation and allow anesthesia using isoflurane. Radiotracers were injected directly into the exposed CAM vasculature. Sodium [18F]fluoride was used to validate the imaging protocol, demonstrating that image-degrading motion can be removed with anesthesia. Tumor glucose metabolism was imaged using [18F]fluorodeoxyglucose and tumor protein synthesis was imaged using 2-[18F]fluoro-L-tyrosine. Anatomical images were obtained by contrast enhanced CT, facilitating clear delineation of the tumor, delineation of tracer uptake in tumor versus embryo and accurate volume measurements. Results: PET imaging of tumor glucose metabolism and protein synthesis was successfully demonstrated in the CAM U87 glioblastoma model. Catheterization of CAM blood vessels facilitated dynamic imaging of glucose metabolism with [18F]fluorodeoxyglucose and demonstrated the ability to study PET tracer uptake over time in individual tumors, while CT imaging improved the accuracy of tumor volume measurements. Conclusion: In summary, we describe the novel application of PET/CT in the CAM tumor model, with optimization of typical imaging protocols. PET imaging in this valuable tumor model could prove particularly useful for rapid, high-throughput screening of novel radiotracers. Sun, 26 May 2013 12:35:09 GMT http://hdl.handle.net/2268/149011 Titre: Expression of type 2 orexin receptor in human endometrium and its epigenetic silencing in endometrial cancer. <br/> <br/>Auteur, co-auteur: Dehan, Pierre; Canon, C.; Trooskens, G.; Rehli, M.; Munaut, Carine; Van Criekinge, W.; Delvenne, Philippe <br/> <br/>Résumé: CONTEXT: Orexins A and B are neuropeptides that bind and activate 2 types of receptors. In addition to direct action in the brain, the orexinergic system has broader implications in peripheral organs, and it has been proposed to have a role in the induction of apoptosis. There are very few data on the endometrium. OBJECTIVE: The expression and epigenetic regulation of type 2 orexin receptor (OX2R) was investigated in the human endometrium as well as in endometrial endometrioid carcinoma (EEC). METHODS: OX2R localization was studied by immunohistochemistry in normal endometrium (n = 24) and in EEC (n = 32). The DNA methylation status of a CpG island located in the first exon of OX2R was analyzed by bisulfite sequencing in normal (n = 18), EEC (n = 34), and 3 endometrial cell lines. On the latter, mRNA expression and Western blotting as well as in vitro induction with orexin were performed. RESULTS: Expression of the OX2R protein was detected in normal endometrial epithelia, whereas it was frequently lacking in EEC. This loss was associated with hypermethylation of OX2R in EEC in comparison with normal endometrium (median CpG methylation percentages of 48.85% and 5.85%, respectively). In cell lines, hypermethylation correlated with weak OX2R expression. Additionally, in vitro treatment of the 3 EEC cell lines with orexins A and B did not result in proliferation change CONCLUSIONS: Altogether our data provide evidence for the epigenetic silencing of OX2R in EEC. The implication of the OX2R loss in tumoral progression remains to be elucidated. Thu, 23 May 2013 09:23:24 GMT http://hdl.handle.net/2268/147505 Titre: Confrontation anatomo-clinique. Cancer thyroidin après irradiation: revue de la littérature à propos d'un cas <br/> <br/>Auteur, co-auteur: Leonard, Philippe; Delvenne, Philippe; Collignon, Jacques; Ghaye, Benoît; Merchie, G.; Deneufbourg, Jean-Marie; Boniver, Jacques Sun, 28 Apr 2013 19:43:37 GMT http://hdl.handle.net/2268/147260 Titre: Comparing duration of response and duration of clinical benefit between fulvestrant treatment groups in the CONFIRM trial: application of new methodology. <br/> <br/>Auteur, co-auteur: Garnett, Sally Anne; Martin, Miguel; JERUSALEM, Guy; Petruzelka, Lubos; Torres, Roberto; Bondarenko, Igor N.; Khasanov, Rustem; Verhoeven, Didier; Pedrini, Jose L.; Smirnova, Iva; Lichinitser, Mikhail R.; Pendergrass, Kelly; Lindemann, Justin P. O.; Di Leo, Angelo <br/> <br/>Résumé: Comparisons of duration of response (DoR) and duration of clinical benefit (DoCB) within clinical trials are prone to biases. To address these biases, we used new methodology to prospectively analyze expected DoR and expected DoCB. Objective response rate and clinical benefit rate were calculated for fulvestrant 500 and 250 mg, and used to calculate expected DoR and expected DoCB for each dose group. The ratios for expected DoR and expected DoCB (expected DoR500/expected DoR250 and expected DoCB500/expected DoCB250) were then calculated, thereby allowing statistical comparisons of these endpoints between each arm of the COmparisoN of Faslodex In Recurrent or Metastatic breast cancer (CONFIRM) trial. Expected DoRs for fulvestrant 500 and 250 mg were 3.2 and 3.6 months, respectively. The expected DoR ratio between fulvestrant 500 and 250 mg was not statistically significant (0.89; 95 % CI, 0.48-1.67, P = 0.724). The expected DoCBs for fulvestrant 500 and 250 mg were 9.8 and 7.2 months, respectively. The expected DoCB ratio showed that the expected DoCB for fulvestrant 500 mg was significantly improved compared with the expected DoCB for fulvestrant 250 mg (1.36; 95 % CI, 1.07-1.73, P = 0.013). Analysis of the expected DoR and expected DoCB showed fulvestrant 500 mg significantly increased expected DoCB compared with fulvestrant 250 mg in the CONFIRM trial. Tue, 23 Apr 2013 14:20:11 GMT http://hdl.handle.net/2268/146351 Titre: Preliminary results of [18F]FPRGD2 PET/CT imaging of integrin αvβ3 levels in patients with locally advanced rectal carcinoma <br/> <br/>Auteur, co-auteur: WITHOFS, Nadia; MARTINIVE, Philippe; SCAGNOL, Irène; THONON, David; Giacomelli, Fabrice; Mievis, Frédéric; COUCKE, Philippe; CATALDO, Didier; Sanjiv, Gambhir; HUSTINX, Roland Mon, 08 Apr 2013 03:01:01 GMT http://hdl.handle.net/2268/146350 Titre: FDG PET/CT for radiotherapy treatment planning. Comparison of functional volume delineation algorithms <br/> <br/>Auteur, co-auteur: WITHOFS, Nadia; Bernard, Claire; VAN DER REST, Catherine; MARTINIVE, Philippe; HATT, Mathieu; Dimitris, Visvikis; COUCKE, Philippe; HUSTINX, Roland Mon, 08 Apr 2013 03:00:41 GMT http://hdl.handle.net/2268/145257 Titre: Transposition en réseau des trajets cliniques d’un Service de Radiothérapie dans le modèle de Reason pour la prévention et la gestion des évènements indésirables <br/> <br/>Auteur, co-auteur: DELGAUDINE, Marie; LENAERTS, Eric; RENARD, André; PRINCEN, Fabienne; COUCKE, Philippe Fri, 22 Mar 2013 04:00:09 GMT http://hdl.handle.net/2268/144749 Titre: Dendritic cells in Barrett's esophagus carcinogenesis: an inadequate microenvironment for antitumor immunity? <br/> <br/>Auteur, co-auteur: Somja, Joan; Demoulin, Stéphanie; RONCARATI, Patrick; Herfs, Michael; BLETARD, Noëlla; Delvenne, Philippe; Hubert, Pascale Thu, 14 Mar 2013 09:02:20 GMT http://hdl.handle.net/2268/144747 Titre: Dendritic cells in Barrett's carcinogenesis: an inadequate environment for antitumor immunity? <br/> <br/>Auteur, co-auteur: Somja, Joan; Demoulin, Stéphanie; RONCARATI, Patrick; Herfs, Michael; BLETARD, Noëlla; Delvenne, Philippe; Hubert, Pascale Thu, 14 Mar 2013 08:28:14 GMT http://hdl.handle.net/2268/144508 Titre: Disruption of COX-2 modulates gene expression and the cardiac injury response to doxorubicin <br/> <br/>Auteur, co-auteur: Neilan, Tomas; Doherty, Glen; Chen, Gang; Deflandre, Catherine; McAllister, Hester; Butler, Ryan; McClelland, Sarah; Kay, Elaine; Ballou, Leslie; Fitzgerald <br/> <br/>Résumé: To determine the role of cyclooxygenase (COX)-2 in anthracycline-induced cardiac toxicity, we administered doxorubicin (Dox) to mice with genetic disruption of COX-2 (COX-2−/−). After treatment with Dox, COX-2−/− mice had increased cardiac dysfunction and cardiac cell apoptosis compared with Dox-treated wild-type mice. The expression of the death-associated protein kinase-related apoptosis-inducing protein kinase-2 was also increased in Dox-treated COX-2−/− animals. The altered gene expression, cardiac injury, and dysfunction after Dox treatment in COX-2−/− mice was attenuated by a stable prostacyclin analog, iloprost. Wild-type mice treated with Dox developed cardiac fibrosis that was absent in COX-2−/− mice and unaffected by iloprost. These results suggest that genetic disruption of COX-2 increases the cardiac dysfunction after treatment with Dox by an increase in cardiac cell apoptosis. This Dox-induced cardiotoxicity in COX-2−/− mice was attenuated by a prostacyclin analog, suggesting a protective role for prostaglandins in this setting. Sun, 10 Mar 2013 23:56:14 GMT http://hdl.handle.net/2268/144477 Titre: Risk Of Malignancies In A Single Center Cohort Of IBD-Patients Treated with Immunosuppressives and Anti-TNF-antibodies <br/> <br/>Auteur, co-auteur: Steinborn, A; Beigel, F; Breiteneicher, S; Van Steen, Kristel; Schnitzler, F; Göke, B; Weidinger, M; Brand, S; Ochsenkühn, T; Seiderer, J Sat, 09 Mar 2013 18:12:04 GMT http://hdl.handle.net/2268/144476 Titre: Risk Of Malignancies In A Single Center Cohort Of IBD-Patients Treated with Immunosuppressives and Anti-TNF-antibodies <br/> <br/>Auteur, co-auteur: Steinborn, A; Beigel, F; Breiteneicher, S; Van Steen, Kristel; Schnitzler, F; Göke, B; Weidinger, M; Brand, S; Ochsenkühn, T; Seiderer, J Sat, 09 Mar 2013 17:59:53 GMT http://hdl.handle.net/2268/144475 Titre: Rate of Malignancies and Infections in a Large Single Center Cohort of IBD Patients Treated With Thiopurines and Anti-TNF-Antibodies. <br/> <br/>Auteur, co-auteur: Ochsenkühn, T; Steinborn, A; Beigel, F; Mahachie John, Jestinah; Van Steen, Kristel; Schnitzler, S; Tillack, C; Göke, B; Weidinger, M; Brand, S; Seiderer, J Sat, 09 Mar 2013 17:53:52 GMT http://hdl.handle.net/2268/144474 Titre: Rate of Malignancies and Infections in a Large Single Center Cohort of IBD Patients Treated With Thiopurines and Anti-TNF-Antibodies. <br/> <br/>Auteur, co-auteur: Ochsenkühn, T; Steinborn, A; Beigel, F; Breiteneicher, S; Mahachie John, Jestinah; Van Steen, Kristel; Schnitzler, F; Tillack, C; Göke, B; Weidinger, M; Brand, S; Seiderer, J Sat, 09 Mar 2013 17:43:43 GMT http://hdl.handle.net/2268/144473 Titre: Rate of Malignancies and Infections in a Large Single Center Cohort of IBD Patients Treated With Thiopurines and Anti-TNF-Antibodies. <br/> <br/>Auteur, co-auteur: Ochsenkühn, T; Steinborn, A; Beigel, F; Breiteneicher, S; Mahachie John, Jestinah; Van Steen, Kristel; Schnitzler, F; Tillack, C; Göke, B; Weidinger, M; Seiderer, S; Seiderer, J Sat, 09 Mar 2013 17:34:31 GMT http://hdl.handle.net/2268/143585 Titre: Elaboration d’un plan de formation continue à partir de l’approche processus dans un service de Radiothérapie <br/> <br/>Auteur, co-auteur: LENAERTS, Eric; DELGAUDINE, Marie; COUCKE, Philippe Fri, 22 Feb 2013 09:14:40 GMT http://hdl.handle.net/2268/143584 Titre: VEGF111, a new VEGF-A isoform induced by genotoxic agents; resistance to proteolytic <br/> <br/>Auteur, co-auteur: MINEUR, P.; Colige, Alain; DELGAUDINE, Marie; Deroanne, Christophe; KESTELOOT, F.; Dubail, Johanne; GOTHOT, André; LAPIERE, Ch.; NOEL, A.; VOO, S.; Waltenberger; Nusgens; Lambert, Charles Fri, 22 Feb 2013 09:14:03 GMT http://hdl.handle.net/2268/143440 Titre: Expression of matrix metalloproteinase-2 and mutant p53 is increased in hydatidiform mole as compared with normal placenta <br/> <br/>Auteur, co-auteur: Petignat, P.; Laurini, R.; Goffin, Frédéric; Bruchim, I.; Bischof, P. <br/> <br/>Résumé: Matrix metalloproteinases (MMPs) are group of enzymes thought to play an important role in trophoblastic and tumor invasion. The aim of our study was to investigate the trophoblastic expression of MMPs and p53 in normal trophoblast and hydatidiform moles (HM). Paraffin sections of 45 specimens, including 14 complete hydatidiform moles (CM), 15 partial hydatidiform moles (PM), 8 atypical partial hydatidiform moles (aPM), and 8 controls were selected. Classification of HM was established on histologic criteria and supported by the DNA ploidy results. Tissue sections from each case were immunostained with monoclonal antibodies, cytokeratin-7, MMP-2, MMP-9, tissue inhibitors of metalloproteinases (TIMP)-1, and p53 wild type (p53wt) and mutant types (mutp53). Staining for cytokeratin-7 revealed a positive reaction in 93% of the samples. MMP-2 was mainly expressed in the syncytiotrophoblast of HM and found in 62% of aPM, 60% PM, and 93% CM. The mutp53 was mainly and focally expressed in syncytiotrophoblastic cells and was found in 63% of aPM, 80% PM, and 93% CM. Expression of MMP-2 and mutp53 was both significantly greater in HM vs control group (P < 0.05) and greater in CM vs PM and aPM (P < 0.05). No significant difference was observed for cytokeratin-7, MMP-9, TIMP-1, and p53wt between the HM subgroups and between HM and control group. MMP-2 and mutp53 are overexpressed in HM as compared with normal trophoblast and might participate in the invasive behavior of the HM. Thu, 21 Feb 2013 10:36:37 GMT