References of "Cosse, Jean-Philippe"
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See detailThe role of epigenetics in malignant pleural mesothelioma
Vandermeers, Fabian; Neelature Sriramareddy, Sathya; Chrisostome, Costa et al

in Lung Cancer (2013), 81

Malignant pleural mesothelioma (MPM) is an almost invariably fatal cancer of the pleura due to asbestos exposure. Increasing evidence indicates that unresponsiveness to chemotherapy is due to epigenetic ... [more ▼]

Malignant pleural mesothelioma (MPM) is an almost invariably fatal cancer of the pleura due to asbestos exposure. Increasing evidence indicates that unresponsiveness to chemotherapy is due to epigenetic errors leading to inadequate gene expression in tumor cells. The availability of compounds that modulate epigenetic modifications, such as histone acetylation or DNA methylation, offers new prospects for treatment of MPM. Here, we review latest findings on epigenetics in mesothelioma and present novel strategies for promising epigenetic thérapies. [less ▲]

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See detailNovel phenolic glycolipids: antioxidant activity and effect on membrane models
Sainvitu, Pauline ULg; Nasir, Mehmet Nail ULg; Draguet, Florian et al

Poster (2013, May 30)

Aromatic glycolipids are of both medical as well as pharmaceutical interest. Antimicrobial, antiviraland antiinflammatory activities have been reported (Otto, 2000, Journal of Molecular Catalysis B ... [more ▼]

Aromatic glycolipids are of both medical as well as pharmaceutical interest. Antimicrobial, antiviraland antiinflammatory activities have been reported (Otto, 2000, Journal of Molecular Catalysis B: Enzymatic). Moreover, they are expected to have interesting antioxidant properties when they contain phenolic groups. The alkyl chain should enhance their ability to penetrate into the cellular membrane (Nicolosi, 2002, Journal of Molecular Catalysis B: Enzymatic). The presence of a sugar unit could also be useful to target specific cells. In this study, novel aromatic glycolipids were synthesized as useful models for studying the structure–activity relationship, in particular as regards to their aromatic group.Theireffect on cell viability when an oxidative stress is induced was tested. In parallel, their interaction with cell models (liposomes) was studied through membrane fusion and permeability experiments. [less ▲]

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See detailBiophysical characterization of the interaction of novel aromatic glycolipid surfactants with membrane models.
Sainvitu, Pauline ULg; Nasir, Mehmet Nail ULg; Draguet, Florian et al

Poster (2013, May 15)

Aromatic glycolipids are of both medical and pharmaceutical interest. Antimicrobial, antiviral and anti-inflammatory activities have been reported (Otto, 2000, Journal of Molecular Catalysis B: Enzymatic ... [more ▼]

Aromatic glycolipids are of both medical and pharmaceutical interest. Antimicrobial, antiviral and anti-inflammatory activities have been reported (Otto, 2000, Journal of Molecular Catalysis B: Enzymatic). Moreover, they are expected to have interesting antioxidant properties when they contain phenolic groups. The alkyl chain should enhance their ability to penetrate into the cellular membrane (Nicolosi, 2002, Journal of Molecular Catalysis B: Enzymatic). The presence of a sugar unit could also be useful to target specific cells. In this study, novel aromatic glycolipids were synthesized as useful models for studying the structure–activity relationship, in particular as a function of their aromatic group. Their interaction with membranes was studied with monolayer models and was predicted by a computational approach. The relationships between these data and their cytotoxicity and antioxidant properties evaluated on cell cultures are discussed. [less ▲]

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See detailBiophysical characterization of the interaction of novel aromatic glycolipid surfactants with membrane models.
Sainvitu, Pauline ULg; Nasir, Mehmet Nail ULg; Nott, Katherine ULg et al

in World Academy of Science, Engineering and Technology (2013, May), 77

Aromatic glycolipids are of both medical and pharmaceutical interest. Antimicrobial, antiviral and anti-inflammatory activities have been reported (Otto, 2000, Journal of Molecular Catalysis B: Enzymatic ... [more ▼]

Aromatic glycolipids are of both medical and pharmaceutical interest. Antimicrobial, antiviral and anti-inflammatory activities have been reported (Otto, 2000, Journal of Molecular Catalysis B: Enzymatic). Moreover, they are expected to have interesting antioxidant properties when they contain phenolic groups. The alkyl chain should enhance their ability to penetrate into the cellular membrane (Nicolosi, 2002, Journal of Molecular Catalysis B: Enzymatic). The presence of a sugar unit could also be useful to target specific cells. In this study, novel aromatic glycolipids were synthesized as useful models for studying the structure–activity relationship, in particular as a function of their aromatic group. Their interaction with membranes was studied with monolayer models and was predicted by a computational approach. The relationships between these data and their cytotoxicity and antioxidant properties evaluated on cell cultures are discussed. [less ▲]

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See detailBiophysical characterization of the interaction of novel aromatic glycolipid surfactants with membrane models.
Sainvitu, Pauline ULg; Nasir, Mehmet Nail ULg; Nott, Katherine ULg et al

in World Academy of Science, Engineering and Technology (2013, May), 77

Aromatic glycolipids are of both medical and pharmaceutical interest. Antimicrobial, antiviral and anti-inflammatory activities have been reported (Otto, 2000, Journal of Molecular Catalysis B: Enzymatic ... [more ▼]

Aromatic glycolipids are of both medical and pharmaceutical interest. Antimicrobial, antiviral and anti-inflammatory activities have been reported (Otto, 2000, Journal of Molecular Catalysis B: Enzymatic). Moreover, they are expected to have interesting antioxidant properties when they contain phenolic groups. The alkyl chain should enhance their ability to penetrate into the cellular membrane (Nicolosi, 2002, Journal of Molecular Catalysis B: Enzymatic). The presence of a sugar unit could also be useful to target specific cells. In this study, novel aromatic glycolipids were synthesized as useful models for studying the structure–activity relationship, in particular as a function of their aromatic group. Their interaction with membranes was studied with monolayer models and was predicted by a computational approach. The relationships between these data and their cytotoxicity and antioxidant properties evaluated on cell cultures are discussed. [less ▲]

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See detailSynthesis and physico-chemical characterization of fatty esters
Sainvitu, Pauline ULg; Nott, Katherine ULg; Nicks, Francois ULg et al

Poster (2012, November 16)

Specific antioxidant molecules (e.g. phenolics) help to prevent oxidation reaction of the cell membrane. A fatty chain grafted on these compounds should enhance their capacity to interact with the ... [more ▼]

Specific antioxidant molecules (e.g. phenolics) help to prevent oxidation reaction of the cell membrane. A fatty chain grafted on these compounds should enhance their capacity to interact with the membrane lipids. In our study, three fatty esters comprising an aromatic part were synthesized. They differentiate the aromatic substituent and the number of carbons between the aromatic ring and the ester function. A structure-function relationships study was performed to identify the structural pattern affecting the interfacial properties and the membrane interaction properties. The behavior of their monolayer film at an air-water interface was studied. The interactions with membrane were assessed on living cells and were predicted by a computational approach. In the future, we will investigate the effect of the presence of a sugar unit on these molecules. [less ▲]

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See detailEffet de l’hypoxie sur la résistance des cellules cancéreuses à l’étoposide : Etude de l’apoptose et de l’autophagie
Cosse, Jean-Philippe ULg

Doctoral thesis (2010)

L’hypoxie tumorale est une caractéristique du microenvironnement de la plupart des tumeurs solides. Elle correspond à la faible tension en oxygène observée au niveau de certaines zones de la tumeur et est ... [more ▼]

L’hypoxie tumorale est une caractéristique du microenvironnement de la plupart des tumeurs solides. Elle correspond à la faible tension en oxygène observée au niveau de certaines zones de la tumeur et est la conséquence de la prolifération rapide des cellules tumorales et de la structure désordonnée de la tumeur et de sa vascularisation. L’hypoxie tumorale est souvent corrélée à un mauvais pronostic de guérison des patients car c’est un phénomène qui renforce l’agressivité des cellules cancéreuses et leur résistance à des thérapies anticancéreuses telles que la radiothérapie et la chimiothérapie. La résistance à la chimiothérapie est due à un effet direct de l’hypoxie, car les agents utilisés en chimiothérapie nécessitent souvent l’oxygène pour exercer leur cytotoxicité, et à un effet indirect de l’hypoxie qui induit une série d’adaptations au niveau de la cellule. L’hypoxie modifie le métabolisme de la cellule, stimule l’angiogenèse, l’érythropoïèse et régule la survie cellulaire en participant à la régulation de l’apoptose. La régulation de l’apoptose par l’hypoxie est complexe car en fonction de sa sévérité, l’hypoxie peut stimuler ou au contraire, inhiber l’apoptose. La compréhension de la régulation de l’apoptose par l’hypoxie est importante car l’apoptose participe à la sélection des cellules tumorales les plus agressives et conditionne l’efficacité des agents cytotoxiques utilisés au cours de la chimiothérapie. Ce travail a pour objectif d’étudier les mécanismes de régulation de l’apoptose par l’hypoxie. Dans un premier temps, nous avons comparé l’effet de l’hypoxie sur l’apoptose induite par l’étoposide, qui est un agent cytotoxique utilisé pour traiter certains types de cancers, au niveau de trois lignées cancéreuses humaines provenant de trois organes différents. Nous avons montré que l’effet de l’hypoxie sur l’apoptose induite par l’étoposide était dépendant de la lignée cellulaire car l’hypoxie stimule l’apoptose induite par l’étoposide dans les cellules MCF7 alors qu’elle inhibe l’apoptose induite par l’étoposide dans les cellules HepG2. Ceci montre que la régulation de l’apoptose par l’hypoxie est un mécanisme complexe, qui ne dépend pas uniquement de la sévérité de l’hypoxie, mais également d’autres paramètres tels que la lignée cellulaire. Dans la suite du travail, nous avons étudié comment l’hypoxie était capable de protéger les cellules HepG2 de l’apoptose induite par l’étoposide. Pour cela, nous avons évalué l’implication de plusieurs facteurs de transcription. Les résultats ont mis en évidence que l’hypoxie protège les cellules HepG2 de l’apoptose induite par l’étoposide en inhibant le facteur de transcription p53 et en activant le facteur de transcription c-jun. Nous avons également évalué l’implication de l’autophagie qui est un processus cellulaire impliqué dans le recyclage des protéines de longue durée de vie et des organites ainsi que dans la survie et la mort cellulaire. En condition d’hypoxie, l’autophagie peut être induite par un mécanisme impliquant la protéine BNIP3. Nous avons montré que, dans les cellules HepG2, l’autophagie était induite par l’étoposide mais pas par l’hypoxie. Cependant, l’autophagie induite par l’étoposide a des conséquences différentes en fonction de la tension en oxygène puisque les résultats ont montré que l’autophagie favorise l’apoptose induite par l’étoposide en normoxie mais pas en hypoxie. Enfin, nous avons montré que BNIP3 n’influençait pas l’autophagie mais participait à la protection contre l’apoptose induite par l’étoposide en hypoxie. En conclusion, les résultats obtenus montrent que la régulation de l’apoptose par l’hypoxie est un phénomène complexe qui est dépendant de plusieurs paramètres dont la lignée cellulaire. De plus, ces résultats indiquent que, lorsque l’hypoxie protège de l’apoptose, cette protection résulte de plusieurs adaptations mises en place par l’hypoxie. Ces résultats sont importants car ils améliorent notre compréhension des phénomènes de résistance observés chez les patients. [less ▲]

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See detailBNIP3 protects HepG2 cells against etoposide-induced cell death under hypoxia by an autophagy-independent pathway
Cosse, Jean-Philippe ULg; Rommelaere, Guillaume; Ninane, Noelle et al

in Biochemical Pharmacology (2010), 80

Tumor hypoxia is a common characteristic of most solid tumors and is correlated with poor prognosis for patients partly because hypoxia promotes resistance to cancer therapy. Hypoxia selects cancer cells ... [more ▼]

Tumor hypoxia is a common characteristic of most solid tumors and is correlated with poor prognosis for patients partly because hypoxia promotes resistance to cancer therapy. Hypoxia selects cancer cells that are resistant to apoptosis and allows the onset of mechanisms that promote cancer cells survival including autophagy. Previously, we showed that human hepatoma HepG2 cells were protected under hypoxia against the etoposide-induced apoptosis. In this study, respective putative contribution of autophagy and BNIP3 in the protection conferred by hypoxia against the etoposide-induced apoptosis was investigated. We report that autophagy is induced by etoposide, a process that is not affected by hypoxic conditions. Using Atg5 siRNA, we show that etoposide-induced autophagy promotes apoptotic cell death under normoxia but not under hypoxia. Then, we investigated whether the hypoxia-induced protein BNIP3 could explain the different effect of autophagy on cell death under hypoxia or normoxia. We show that the silencing of BNIP3 does not affect autophagy whatever the pO2 but participates in the protective effect of hypoxia against etoposide-induced apoptosis. Together, these results suggest that autophagy might be involved in etoposide-induced cell death only under normoxia and that BNIP3 is a major effector of the protective mechanism conferred by hypoxia to protect cancer cells against etoposide-induced apoptotic cell death. [less ▲]

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See detailHypoxia-Induced Decrease in p53 Protein Level and Increase in c-jun DNA Binding Activity Results in Cancer Cell Resistance to Etoposide
Cosse, Jean-Philippe ULg; Ronvaux, Marie; Ninane, Noelle et al

in Neoplasia : An International Journal for Oncology Research (2009), 11

Tumor hypoxia is one of the features of tumor microenvironment that contributes to chemoresistance in particular by cellular adaptations that modulate the apoptotic process. However, the mechanisms ... [more ▼]

Tumor hypoxia is one of the features of tumor microenvironment that contributes to chemoresistance in particular by cellular adaptations that modulate the apoptotic process. However, the mechanisms involved in this resistance still need deeper understanding. In this study, we investigated the involvement of four transcription factors, c-Myc, nuclear factor κB (NF-κB), p53, and c-jun/activator protein 1 (AP-1) in the hypoxia-induced resistance to etoposide in HepG2 cells. Whereas the profile of c-Myc and NF-κB activity did not fit the effect of hypoxia on caspase 3 activity, hypoxia decreased basal p53 abundance and DNA binding activity as well as p53 etoposide-induced activation. Short interfering RNA (siRNA) silencing evidenced that p53 was required for etoposide-induced apoptosis under normoxia. An inhibition of its activity under hypoxia could thus be responsible at least in part for the protection observed under hypoxic conditions. Moreover, p53 was found to induce the expression of Bak1. We showed that Bak1 was involved in the etoposide-induced apoptosis because Bak1 siRNA decreased it. Conversely, hypoxia increased c-jun DNA binding activity in the presence of etoposide. siRNA-mediated silencing of c-jun increased the responsiveness of cells to etoposide under hypoxia, as shown by an increase in caspase 3 activity and lactate dehydrogenase release. These effects occurred in a p53-independent manner. These data evidenced that hypoxia decreased the responsiveness of HepG2 cells to etoposide at least by two independent pathways involving p53 inhibition and c-jun activation. [less ▲]

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See detailInvolvement of autophagic pathway in the hypoxia-induced resistance to etoposide in HepG2
Cosse, Jean-Philippe ULg; Sermeus, Audrey; Flamant, Lionel et al

Poster (2009)

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See detailTumour Hypoxia Affects the Responsiveness of Cancer Cells to Chemotherapy and Promotes Cancer Progression
Cosse, Jean-Philippe ULg; Michiels, Carine

in Anti-Cancer Agents in Medicinal Chemistry (2008), 8

A solid tumour forms an organ-like structure that is comprised of cancer cells as well as stroma cells (fibroblasts, inflammatory cells) that are embedded in an extracellular matrix and are nourished by ... [more ▼]

A solid tumour forms an organ-like structure that is comprised of cancer cells as well as stroma cells (fibroblasts, inflammatory cells) that are embedded in an extracellular matrix and are nourished by vascular network. However, tumoral microenvironment is heterogeneous due to the abnormal vasculature network and high proliferation rate of cancer cells. Because of these features, some regions are starved from oxygen, a phenomenon called hypoxia. Transient hypoxia is associated with inadequate blood flow while chronic hypoxia is the consequence of the increased oxygen diffusion distance due to tumour expansion. Both types of hypoxia are correlated with poor outcome for patients. Moreover, hypoxia also enhances chemoresistance of cancer cells. Firstly, the delivery of drugs in hypoxic area and cellular uptake of it are affected by hypoxia or associated acidity. Secondly, some chemotherapeutic drugs require oxygen to generate free radicals that contribute to cytotoxicity. Last, hypoxia induces cellular adaptations that compromise the effectiveness of chemotherapy. In response to nutrient deprivation due to hypoxia, the rate of proliferation of cancer cells decreases but chemotherapeutic drugs are more effective against proliferating cells. On the other hand, hypoxia induces adaptation by post-translational and transcriptional changes that promote cell survival and resistance to chemotherapy. Through these changes, hypoxia promotes angiogenesis, shift to glycolytic metabolism, expression of ABC transporters, cell survival by inducing the expression of genes encoding growth factors and the modulation of apoptotic process. The aim of this review is to provide a description of known hypoxia-induced mechanisms of chemoresistance at a cellular level. [less ▲]

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See detailHypoxia promotes resistance to etoposide by regulating p53 stability and c-jun DNA-binding activity
Cosse, Jean-Philippe ULg; Ronvaux, Marie; Ninane, Noelle et al

Conference (2008)

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See detailHypoxia promotes resistance to etoposide by regulating p53 stability and c-jun DNA-binding activity
Cosse, Jean-Philippe ULg; Ronvaux, Marie; Ninane, Noelle et al

Poster (2008)

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See detailHypoxia induces protection against etoposide-induced apoptosis: molecular profiling of changes in gene expression and transcription factor activity
Sermeus, Audrey; Cosse, Jean-Philippe ULg; Crespin, Marianne et al

in Molecular Cancer (2008), 7

Background: it is now well established that hypoxia renders tumor cells resistant to radio- but also chemotherapy. However, few elements are currently available as for the mechanisms underlying this ... [more ▼]

Background: it is now well established that hypoxia renders tumor cells resistant to radio- but also chemotherapy. However, few elements are currently available as for the mechanisms underlying this protection. Results: in this study, physiological hypoxia was shown to inhibit apoptosis induced in HepG2 cells by etoposide. Indeed, hypoxia reduced DNA fragmentation, caspase activation and PARP cleavage. The DNA binding activity of 10 transcription factors was followed while the actual transcriptional activity was measured using specific reporter plasmids. Of note is the inhibition of the etoposideinduced activation of p53 under hypoxia. In parallel, data from low density DNA microarrays indicate that the expression of several pro- and anti-apoptotic genes was modified, among which are Bax and Bak whose expression profile paralleled p53 activity. Cluster analysis of data unravels several possible pathways involved in the hypoxia-induced protection against etoposide-induced apoptosis: one of them could be the inhibition of p53 activity under hypoxia since caspase 3 activity parallels Bax and Bak expression profile. Moreover, specific downregulation of HIF-1α by RNA interference significantly enhanced apoptosis under hypoxia possibly by preventing the hypoxia mediated decrease in Bak expression without altering Bax expression. Conclusion: these results are a clear demonstration that hypoxia has a direct protective effect on apoptotic cell death. Moreover, molecular profiling points to putative pathways responsible for tumor growth in challenging environmental conditions and cancer cell resistance to chemotherapeutic agents. [less ▲]

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See detailDifferential effects of hypoxia on etoposide-induced apoptosis according to the cancer cell lines
Cosse, Jean-Philippe ULg; Sermeus, Audrey; Vannuvel, Kayleen et al

in Molecular Cancer (2007)

Background: It is more and more recognized that hypoxia plays a role in the resistance of cancer cells to chemotherapy. However, the mechanisms underlying this resistance still need deeper understanding ... [more ▼]

Background: It is more and more recognized that hypoxia plays a role in the resistance of cancer cells to chemotherapy. However, the mechanisms underlying this resistance still need deeper understanding. The aim of this study was to investigate the effect of hypoxia on this process since hypoxia is one of the hallmarks of tumor environment. Results: The effect of hypoxia on the apoptosis induced by etoposide, one drug commonly used in chemotherapy, was investigated using three different cancer cell lines. Gene expression changes were also studied in order to delineate the mechanisms responsible for the hypoxia-induced chemoresistance. We observed that hypoxia differentially influenced etoposide-induced cell death according to the cancer cell type. While hypoxia inhibited apoptosis in hepatoma HepG2 cells, it had no influence in lung carcinoma A549 cells and further enhanced it in breast cancer MCF-7 cells. Etoposide increased p53 activity in all cell lines while hypoxia alone decreased it only in HepG2 cells. Hypoxia had no influence on the etoposide-induced p53 activity in A549, increased p53 abundance in MCF-7 cells but markedly decreased p53 activity in HepG2 cells. Using low density DNA arrays to detect the expression of genes involved in the regulation of apoptosis, etoposide and hypoxia were shown to each influence the expression of numerous genes, many of the ones influenced by etoposide being p53 target genes. Again, the influence of hypoxia on the etoposideinduced changes was different according to the cell type. Conclusion: These results evidenced that there was a striking parallelism between the effect of hypoxia on the etoposide-induced p53 stabilization as well as p53 target gene expression and its effect on the etoposide-induced apoptosis according to the cell type. They are very interesting not only because they provide one possible mechanism for the induction of chemoresistance under hypoxic conditions in cells like HepG2 but also because they indicate that not all cell types respond the same way. This knowledge is of importance in designing adequate treatment according to the type of tumors. [less ▲]

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See detailDifferential effects of hypoxia on étoposide induced apoptosis according to the cancer cell lines
Cosse, Jean-Philippe ULg; Sermeus, Audrey; Vannuvel, Kayleen et al

Poster (2006)

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See detailDifferential effects of hypoxia on étoposide induced apoptosis according to the cancer cell lines
Cosse, Jean-Philippe ULg; Sermeus, Audrey; Vannuvel, Kayleen et al

Poster (2006)

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