References of "Willems, Luc"
     in
Bookmark and Share    
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 29 (5 ULg)
Full Text
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 ▲]

Detailed reference viewed: 28 (14 ULg)
Full Text
See detailViruses and Cancer
Barez, Pierre-Yves ULg; Carpentier, Alexandre ULg; Willems, Luc ULg

Conference (2013, February 08)

Detailed reference viewed: 42 (14 ULg)
Full Text
See detailThe role of TGF­alpha in the resistance to mesothelioma chemotherapy
Neelature Sriramareddy, Sathyanarayana ULg; Vandermeer, Fabian; costa, christostome et al

in GIGA-Day 2013 (2013)

Detailed reference viewed: 27 (9 ULg)
See detailInteraction of HTLV-­1 Tax with minichromosome maintenance proteins accelerates the replication timing program
Carpentier, Alexandre ULg; Barez, Pierre-Yves ULg; Willems, Luc ULg

Conference (2013, January 28)

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most common are the ... [more ▼]

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most common are the adult T-cell leukemia (ATL) and a neurodegenerative disorder called HAM/TSP (Human associated myelopathy/ Tropical spastic paraparesis). A key parameter of HTLV-1 pathogenesis is faster replication of provirus-carrying lymphocytes allowing clonal expansion of infected cell populations. The virally-encoded Tax oncoprotein plays an essential role in this process by interacting with DNA replication origins and accelerating S phase progression. By reprogramming the timing of origin firing, Tax also creates a replicative stress leading to DNA double strand breaks. This mechanism further triggers the DNA damage response (DDR) that induces cell cycle arrest and initiates either apoptosis or senescence. However, HTLV-1 infected cells have developed strategies to interfere with the DDR and are adapted to checkpoint control. These cells are thus able to proliferate despite occurrence of DNA damage. Based on these observations, we now propose a novel therapeutic approach based on the principle of synthetic lethality. [less ▲]

Detailed reference viewed: 67 (18 ULg)
Full Text
Peer Reviewed
See detailIdentification of microRNA-based signatures for response and survival for non-small cell lung cancer treated with cisplatin-vinorelbine A ELCWP prospective study
Berghmans, T; Ameye, L; Willems, Luc ULg et al

in Lung Cancer (2013), 82

Clinical variables, like stage and performance status (PS), have predictive and prognostic values in advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy, not allowing adequate ... [more ▼]

Clinical variables, like stage and performance status (PS), have predictive and prognostic values in advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy, not allowing adequate individual prediction. MicroRNA (miRNA) are non-coding RNAs regulating gene expression. In a prospective study, we assessed the predictive value for response and survival of tumour miRNA in NSCLC patients treated by 1st line cisplatin and vinorelbine. miRNA expression was analysed on a biopsy obtained during the diagnostic bronchoscopy, using TaqMan Low Density Arrays. The signature for response was derived using logistic regression with stepwise variable selection. The associations between overall survival and miRNA expression levels were estimated by using the Kaplan–Meier method, log-rank test, and Cox proportional hazard regression models to estimate the hazard ratios. In total, 38 patients with adequate tumour biopsies, treated with cisplatin-vinorelbine were included: male (n = 27), 80–100 Karnofsky PS (n = 27), adenocarcinoma (n = 20), stage IV (n = 30). One patient was considered not assessable for response but remained included in the survival analyses. Out of the 37 patients assessable for response, 16 partial responses (43%) were observed. A two miRNA signature (miR-149 and miR-375) was found predictive for response and was also associated to progression-free survival (p = 0.05). Using a linear combination of the miR CT values with Cox’s regression coefficients as weights, we constructed a prognostic score for overall survival including four miRNA (miR-200c, miR-424, miR-29c and miR-124). The signature distinguished patients with good (n = 18) and poor (n = 20) prognosis with respective median survival times of 47.3 months (95% CI 29.8–52.4) and 15.5 months (95% CI 9.1–22.8) (p < 0.001; hazard ratio 21.1, 95% CI 4.7–94.9). Conclusions: miRNA signature allows predicting response and is of prognostic value for survival in patients with NSCLC treated with first line cisplatin and vinorelbine. [less ▲]

Detailed reference viewed: 18 (0 ULg)
Full Text
Peer Reviewed
See detailWIP1 deficiency inhibits HTLV-1 Tax oncogenesis: novel therapeutic prospects for treatment of ATL?
Gillet, Nicolas ULg; Carpentier, Alexandre ULg; Barez, Pierre-Yves ULg et al

in Retrovirology (2012), 9(1), 115

Attenuation of p53 activity appears to be a major step in Human T-lymphotropic virus type 1 (HTLV-1) Tax transformation. However, p53 genomic mutations are late and rather infrequent events in HTLV-1 ... [more ▼]

Attenuation of p53 activity appears to be a major step in Human T-lymphotropic virus type 1 (HTLV-1) Tax transformation. However, p53 genomic mutations are late and rather infrequent events in HTLV-1 induced Adult T cell leukemia (ATL). The paper by Zane et al. shows that a mediator of p53 activity, Wild-type p53-induced phosphatase 1 (Wip1), contributes to Tax-induced oncogenesis in a mouse model. Wip1 may therefore be a novel target for therapeutic approaches. [less ▲]

Detailed reference viewed: 37 (27 ULg)
See detailReprogramming of replication origin firing and checkpoint adaptation in adult T cell leukemia
Barez, Pierre-Yves ULg; Carpentier, Alexandre ULg; Willems, Luc ULg

Conference (2012, December 14)

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most common are the ... [more ▼]

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most common are the adult T-cell leukemia (ATL) and a neurodegenerative disorder called HAM/TSP (Human associated myelopathy/ Tropical spastic paraparesis). A key parameter of HTLV-1 pathogenesis is faster replication of provirus-carrying lymphocytes allowing clonal expansion of infected cell populations. The virally-encoded Tax oncoprotein plays an essential role in this process by interacting with DNA replication origins and accelerating S phase progression. By reprogramming the timing of origin firing, Tax also creates a replicative stress leading to DNA double strand breaks. This mechanism further triggers the DNA damage response (DDR) that induces cell cycle arrest and initiates either apoptosis or senescence. However, HTLV-1 infected cells have developed strategies to interfere with the DDR and are adapted to checkpoint control. These cells are thus able to proliferate despite occurrence of DNA damage. Based on these observations, we now propose a novel therapeutic approach based on the principle of synthetic lethality. [less ▲]

Detailed reference viewed: 51 (2 ULg)
Full Text
Peer Reviewed
See detailTransformation by deltaretroviruses: mechanisms and therapies
Willems, Luc ULg

in Proceedings of the Belgian Royal Academies of Medicine (2012), 1

Human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) are two closely related deltaretroviruses inducing hematological diseases in human and ruminants. HTLV-1 infects about 25 million ... [more ▼]

Human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) are two closely related deltaretroviruses inducing hematological diseases in human and ruminants. HTLV-1 infects about 25 million subjects worldwide and causes Adult T-cell leukemia-lymphoma (ATLL) or HAM/TSP (HTLV-induced myelopathy - tropical spastic paraparesis). BLV is the etiological agent of enzootic bovine leukemia. HTLV-1 and BLV have developed strategies to subvert hosts' immune surveillance. Understanding these mechanisms has allowed development of novel therapeutic approaches. [less ▲]

Detailed reference viewed: 21 (1 ULg)
Full Text
Peer Reviewed
See detailTransformation by deltaretroviruses: mechanisms and therapies
Willems, Luc ULg

in Proceedings of the Belgian Royal Academies of Medicine (2012), 1

Human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) are two closely related deltaretroviruses inducing hematological diseases in human and ruminants. HTLV-1 infects about 25 million ... [more ▼]

Human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) are two closely related deltaretroviruses inducing hematological diseases in human and ruminants. HTLV-1 infects about 25 million subjects worldwide and causes Adult T-cell leukemia-lymphoma (ATLL) or HAM/TSP (HTLV-induced myelopathy - tropical spastic paraparesis). BLV is the etiological agent of enzootic bovine leukemia. HTLV-1 and BLV have developed strategies to subvert hosts' immune surveillance. Understanding these mechanisms has allowed development of novel therapeutic approaches. [less ▲]

Detailed reference viewed: 10 (2 ULg)
Full Text
Peer Reviewed
See detailTransformation by deltaretroviruses: mechanisms and therapies
Willems, Luc ULg

in Proceedings of the Belgian Royal Academies of Medicine (2012), 1

Human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) are two closely related deltaretroviruses inducing hematological diseases in human and ruminants. HTLV-1 infects about 25 million ... [more ▼]

Human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) are two closely related deltaretroviruses inducing hematological diseases in human and ruminants. HTLV-1 infects about 25 million subjects worldwide and causes Adult T-cell leukemia-lymphoma (ATLL) or HAM/TSP (HTLV-induced myelopathy - tropical spastic paraparesis). BLV is the etiological agent of enzootic bovine leukemia. HTLV-1 and BLV have developed strategies to subvert hosts' immune surveillance. Understanding these mechanisms has allowed development of novel therapeutic approaches. [less ▲]

Detailed reference viewed: 9 (0 ULg)
Full Text
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 ▲]

Detailed reference viewed: 30 (7 ULg)
Full Text
Peer Reviewed
See detailChemoresistance to Valproate Treatment of Bovine Leukemia Virus-Infected Sheep; Identification of Improved HDAC Inhibitors
Gillet, Nicolas ULg; Vandermeers, Fabian ULg; De Brogniez, Alix ULg et al

in Pathogens (2012), (2012-1), 65-82

We previously proved that a histone deacetylase inhibitor (valproate, VPA) decreases the number of leukemic cells in bovine leukemia virus (BLV)-infected sheep. Here, we characterize the mechanisms ... [more ▼]

We previously proved that a histone deacetylase inhibitor (valproate, VPA) decreases the number of leukemic cells in bovine leukemia virus (BLV)-infected sheep. Here, we characterize the mechanisms initiated upon interruption of treatment. We observed that VPA treatment is followed by a decrease of the B cell counts and proviral loads (copies per blood volume). However, all sheep eventually relapsed after different periods of time and became refractory to further VPA treatment. Sheep remained persistently infected with BLV. B lymphocytes isolated throughout treatment and relapse were responsive to VPA-induced apoptosis in cell culture. B cell proliferation is only marginally affected by VPA ex vivo. Interestingly, in four out of five sheep, ex vivo viral expression was nearly undetectable at the time of relapse. In two sheep, a new tumoral clone arose, most likely revealing a selection process exerted by VPA in vivo. We conclude that the interruption of VPA treatment leads to the resurgence of the leukemia in BLV-infected sheep and hypothesize that resistance to further treatment might be due to the failure of viral expression induction. The development of more potent HDAC inhibitors and/or the combination with other compounds can overcome chemoresistance. These observations in the BLV model may be important for therapies against the related Human T-lymphotropic virus type 1. [less ▲]

Detailed reference viewed: 29 (9 ULg)
Full Text
See detailUnderstanding angiogenesis through novel epigenetic modulators
Shiva Shankar, Thammadihalli Veerasangaiah ULg; Sulka, Béatrice; Blacher, Silvia ULg et al

Scientific conference (2012, June 22)

DNA methylation and histone deacetylation are two key epigenetic modifications that play central role in regulation of gene expression. Several studies have shown that histone deacetylases (HDAC) and DNA ... [more ▼]

DNA methylation and histone deacetylation are two key epigenetic modifications that play central role in regulation of gene expression. Several studies have shown that histone deacetylases (HDAC) and DNA methyltransferases (DNMT) inhibitors are potent anti-angiogenic compounds. Though combination of HDAC and DNMT inhibitors are now being examined in clinical trials of hematological malignancies, little work has been done to understand the effect of this combination on physiological and tumoral angiogenesis. We have designed and tested a family of twin drugs with intrinsic HDAC and DNMT inhibitory activities in relevant models of angiogenesis in vitro (Human Umbilical Vein Endothelial Cells – HUVEC and aortic ring) and in vivo (chick chorioallantoic membrane and Zebrafish). We have identified a lead compound having quantifiable anti-angiogenic effect without cytotoxicity affecting global histone acetylation and DNA methylation levels. In order to elucidate its anti-angiogenic mechanism, we characterized gene expression pattern simultaneously with the methylation profile of HUVEC cells treated with the lead compound and reference epigenetic modulators. This approach based on parallel microarray analyses permitted us to underscore a list of genes exclusively affected by the lead compound but not by other HDAC or DNMT inhibitors. These genes were then analyzed using the Ingenuity Pathway software revealing potential involvement of a subset of genes in angiogenesis. Our present work is focused on exploring the exact role of these genes on angiogenesis using RNA silencing and vectors cloned with genes of interest. We are using these novel epigenetic modulators as a tool to understand the regulatory mechanism of angiogenesis and to develop effective approaches to treat cancer. [less ▲]

Detailed reference viewed: 86 (14 ULg)
Full Text
See detailInteraction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program
Barez, Pierre-Yves ULg; Willems, Luc ULg

Poster (2012, June 22)

First human retrovirus discovered, HTLV-1 infects approximately twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most important are the adult T ... [more ▼]

First human retrovirus discovered, HTLV-1 infects approximately twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most important are the adult T-cell leukemia (ATL) and a neurodegenerative disorder called HAM/TSP (Human associated myelopathy/ Tropical spastic paraparesis). We are interested in the mechanisms of transformation by the viral Tax oncoprotein. Recently, we showed that Tax interacts with the minichromosome maintenance MCM2-7 helicase and binds to origins of DNA replication (Boxus et al, 2012 Blood 119:151). Thereby, Tax modulates the spatiotemporal program of origin activation during the S phase of cell cycle. In fact, Tax accelerates S phase progression by inducing early firing of late replication origins. Concomitantly, Tax-MCM2-7 interplay also modulates viral transcription. Together, our data demonstrates that interaction between Tax and MCM2-7 is involved in replication reprogramming and viral transcription. [less ▲]

Detailed reference viewed: 30 (12 ULg)
Full Text
Peer Reviewed
See detailInteraction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program
Boxus, Mathieu ULg; Twizere, Jean-Claude ULg; Legros, Sébastien et al

in Blood (2012), 119

The Tax oncoprotein encoded by the Human T-cell leukemia virus type 1 (HTLV-1) plays a pivotal role in viral persistence and pathogenesis. HTLV-1 infected cells proliferate faster than normal lymphocytes ... [more ▼]

The Tax oncoprotein encoded by the Human T-cell leukemia virus type 1 (HTLV-1) plays a pivotal role in viral persistence and pathogenesis. HTLV-1 infected cells proliferate faster than normal lymphocytes, expand through mitotic division and accumulate genomic lesions. Here, we show that Tax associates with the minichromosome maintenance MCM2-7 helicase complex and localizes to origins of replication. Tax modulates the spatiotemporal program of origin activation and fires supplementary origins at the onset of S phase. Thereby, Tax increases the DNA replication rate, accelerates S phase progression but also generates a replicative stress characterized by the presence of genomic lesions. Mechanistically, Tax favors p300 recruitment and histone hyperacetylation at late replication domains advancing their replication timing in early S phase. [less ▲]

Detailed reference viewed: 29 (9 ULg)
Full Text
Peer Reviewed
See detailHow the DNA damage response determines the fate of HTLV-1 Tax-expressing cells
Boxus, Mathieu ULg; Willems, Luc ULg

in Retrovirology (2012), 9(2),

How the Human T lymphotropic virus type 1 (HTLV-1) Tax protein stimulates proliferation while triggering cell cycle arrest and senescence remains puzzling. There is also a debate about the ability of Tax ... [more ▼]

How the Human T lymphotropic virus type 1 (HTLV-1) Tax protein stimulates proliferation while triggering cell cycle arrest and senescence remains puzzling. There is also a debate about the ability of Tax to activate or inhibit the DNA damage response. Here, we comment on these different activities and propose a conceptual rationale for the apparently conflicting observations. [less ▲]

Detailed reference viewed: 15 (3 ULg)
Full Text
Peer Reviewed
See detailViral expression directs the fate of B cells in BLV-infected sheep.
Florins, Arnaud-Francois ULg; De Brogniez, Alix ULg; Elemans, M. et al

in Journal of Virology (2012), 86(1), 621-624

The host immune response is believed to tightly control viral replication of deltaretroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV). However, this assumption ... [more ▼]

The host immune response is believed to tightly control viral replication of deltaretroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV). However, this assumption has not been definitely proven in vivo. In order to further evaluate the importance of immune response in the BLV model, we studied the fate of cells in which viral expression was transiently induced. Using a dual fluorochrome labeling approach, we show that ex vivo induction of viral expression induces higher death rates of B cells in vivo. Furthermore, cyclosporine treatment of these animals indicated that an efficient immune response is required to control virus expressing cells. [less ▲]

Detailed reference viewed: 39 (9 ULg)