References of "Willems, Luc"
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See detailGrasshoppers as a food source? A review
Paul, Aman ULg; Frederich, Michel ULg; Uyttenbroeck, Roel ULg et al

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment (in press), 20(AgricultureIsLife),

Description of the subject. Current trends suggest an increasing future demand for conventional meats, which indicates a strong need to shift this dependency to other alternative protein sources such as ... [more ▼]

Description of the subject. Current trends suggest an increasing future demand for conventional meats, which indicates a strong need to shift this dependency to other alternative protein sources such as insects. Literature. From a nutritional point of view, of all the insects consumed globally, grasshoppers are particularly important as a human food. Data from the literature regarding the nutrient composition, amino acid profile, fatty acid profile, mineral composition and vitamin content of grasshoppers as reviewed in this paper, suggest that a number of grasshopper species are a good source of nutrients. It also highlights some of the health related aspects that might arise from the consumption of grasshoppers, mostly linked to agricultural practices and the allergic response of sensitive individuals. The paper also summarizes some religious, social and economic factors that are associated with grasshopper consumption. Conclusions. The success of introducing grasshoppers as a novel food in western countries depends on changes in consumer attitudes. It would be interesting to develop food products derived from grasshoppers in a form acceptable to consumers. Furthermore, it is important to explore the food potential of some grasshopper species native to western countries and to develop their rearing methodologies to enhance availability. [less ▲]

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See detailPhysiological and bio-functional properties of gum arabic: a notable interest for certain human diseases
Eloundou Mballa, Pierre; Goffin, Dorothée ULg; Destain, Jacqueline ULg et al

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (in press)

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See detailStructural basis for recognition of histone H3K36me3 nucleosome by human de novo DNA methyltransferases 3A and 3B
Rondelet, Grégoire; Dal Maso, Thomas; Willems, Luc ULg et al

in Journal of Structural Biology (2016), 194

DNA methylation is an important epigenetic modification involved in chromatin organization and gene expression. The function of DNA methylation depends on cell context and is correlated with histone ... [more ▼]

DNA methylation is an important epigenetic modification involved in chromatin organization and gene expression. The function of DNA methylation depends on cell context and is correlated with histone modification patterns. In particular, trimethylation of Lys36 on histone H3 tail (H3K36me3) is associated with DNA methylation and elongation phase of transcription. PWWP domains of the de novo DNA methyltransferases DNMT3A and DNMT3B read this epigenetic mark to guide DNA methylation. Here we report the first crystal structure of the DNMT3B PWWP domain–H3K36me3 complex. Based on this structure, we propose a model of the DNMT3A PWWP domain–H3K36me3 complex and build a model of DNMT3A (PWWP-ADD-CD) in a nucleosomal context. The trimethylated side chain of Lys36 (H3K36me3) is inserted into an aromatic cage similar to the ‘‘Royal” superfamily domains known to bind methylated histones. A key interaction between trimethylated Lys36 and a conserved water molecule stabilized by Ser270 explains the lack of affinity of mutated DNMT3B (S270P) for the H3K36me3 epigenetic mark in the ICF (Immunodeficiency, Centromeric instability and Facial abnormalities) syndrome. The model of the DNMT3A-DNMT3L heterotetramer in complex with a dinucleosome highlights the mechanism for recognition of nucleosome by DNMT3s and explains the periodicity of de novo DNA methylation. [less ▲]

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See detailFrom Valeriana officinalis to cancer therapy: the success of a bio-sourced compound
Hamaïdia, Malik ULg; Barez, Pierre-Yves ULg; Carpentier, Alexandre ULg et al

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment (2016), 20

Over the centuries, bio-sourced compounds isolated from plants, insects and microorganisms have been a potent source of drugs for the treatment of human diseases. In this review, we recapitulate the story ... [more ▼]

Over the centuries, bio-sourced compounds isolated from plants, insects and microorganisms have been a potent source of drugs for the treatment of human diseases. In this review, we recapitulate the story of one of these compounds, 2-propylpentanoic acid, derived from the Valeriana officinalis flowering plant and its path to validation as a cancer treatment. [less ▲]

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See detailViruses within animal genome
De Brogniez, Alix ULg; Willems, Luc ULg

in Revue scientifique et technique - Office international des épizooties (2016)

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See detailImprovement of malignant pleural mesothelioma immunotherapy by epigenetic modulators
Hamaïdia, Malik ULg; Staumont, Bernard ULg; DUYSINX, Bernard ULg et al

in Current Topics in Medicinal Chemistry (2016), 16

In the absence of a satisfactory treatment of malignant pleural mesothelioma (MPM), novel therapeutic strategies are urgently needed. Among these, immunotherapy offers a series of advantages such as tumor ... [more ▼]

In the absence of a satisfactory treatment of malignant pleural mesothelioma (MPM), novel therapeutic strategies are urgently needed. Among these, immunotherapy offers a series of advantages such as tumor specificity and good tolerability. Unfortunately, MPM immunotherapy is frequently limited by incomplete cell differentiation or feedback loop regulatory mechanisms. In this review, we describe different components of the innate immune system and discuss strategies to improve MPM immunotherapy by using epigenetic modulators. [less ▲]

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See detailRecent advances in BLV research
Barez, Pierre-Yves ULg; De Brogniez, Alix ULg; Carpentier, Alexandre ULg et al

in Viruses (2015), 7(11), 6080-6088

Different animal models have been proposed to investigate the mechanisms of HTLV-induced pathogenesis: rats, transgenic and NOD-SCID/γcnull (NOG) mice, rabbits, squirrel monkeys, baboons and macaques ... [more ▼]

Different animal models have been proposed to investigate the mechanisms of HTLV-induced pathogenesis: rats, transgenic and NOD-SCID/γcnull (NOG) mice, rabbits, squirrel monkeys, baboons and macaques. These systems indeed provide useful information but have intrinsic limitations such as lack of disease relevance, species specificity or inadequate immune response. Another strategy based on a comparative virology approach is to characterize a related pathogen and to speculate on possible shared mechanisms. In this perspective, bovine leukemia virus (BLV), another member of the deltaretrovirus genus, is evolutionary related to HTLV-1. BLV induces lymphoproliferative disorders in ruminants providing useful information on the mechanisms of viral persistence, genetic determinants of pathogenesis and potential novel therapies. [less ▲]

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See detailValproic acid improves second-line regimen of small cell lung carcinoma in preclinical models
Hubaux, Roland; Vandermeers, Fabian; Cosse, Jean-Philippe et al

in European Respiratory Society (2015), 1(2), 00028

With 5-year survival rates below 5%, small cell lung carcinoma (SCLC) has very poor prognosis and requires improved therapies. Despite an excellent overall response to first-line therapy, relapses are ... [more ▼]

With 5-year survival rates below 5%, small cell lung carcinoma (SCLC) has very poor prognosis and requires improved therapies. Despite an excellent overall response to first-line therapy, relapses are frequent and further treatments are disappointing. The goal of the study was to improve secondline therapy of SCLC. The effect of chemotherapeutic agents was evaluated in cell lines (apoptosis, reactive oxygen species, and RNA and protein expression) and in mouse models (tumour development). We demonstrate here that valproic acid, a histone deacetylase inhibitor, improves the efficacy of a second-line regimen (vindesine, doxorubicin and cyclophosphamide) in SCLC cells and in mouse models. Transcriptomic profiling integrating microRNA and mRNA data identifies key signalling pathways in the response of SCLC cells to valproic acid, opening new prospects for improved therapies. [less ▲]

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See detailVAC chemotherapy with valproic acid for refractory/relapsing small cell lung cancer: a phase II study
Berghmans, Thierry; Lafitte, Jean-Jacques; Scherpereel, Arnaud et al

in European Respiratory Society Open Research (2015), 1(2),

Salvage chemotherapy (CT) for relapsing or refractory small cell lung cancer (SCLC) remains disappointing. In vitro experiments showed that valproic acid increases apoptosis of SCLC cell lines exposed to ... [more ▼]

Salvage chemotherapy (CT) for relapsing or refractory small cell lung cancer (SCLC) remains disappointing. In vitro experiments showed that valproic acid increases apoptosis of SCLC cell lines exposed to doxorubicin, vindesine and bis(2-chloroethyl)amine. The primary objective of this phase II study was to determine whether epigenetic modulation with valproic acid in addition to a doxorubicin, vindesine and cyclophosphamide (VAC) regimen improves 6-month progression-free survival (PFS). Patients with pathologically proven SCLC refractory to prior platinum derivatives and etoposide were eligible. After central registration, patients received VAC plus daily oral valproic acid. 64 patients were registered, of whom six were ineligible. Seven patients did not receive any CT, leaving 51 patients assessable for the primary end-point. The objective response rate was 19.6%. Median PFS was 2.8 months (95% CI 2.5–3.6 months) and 6-month PFS was 6%. Median survival time was 5.9 months (95% CI 4.7–7.5 months). Toxicity was mainly haematological, with 88% and 26% grade 3–4 neutropenia and thrombopenia, respectively. Despite an interesting response rate, the addition of valproic acid to VAC did not translate into adequate PFS in relapsing SCLC or SCLC refractory to platinum–etoposide. [less ▲]

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See detailModes of Human T Cell Leukemia Virus Type 1 Transmission, Replication and Persistence
Carpentier, Alexandre ULg; Barez, Pierre-Yves ULg; Hamaïdia, Malik ULg et al

in Viruses (2015), 7

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes cancer (Adult T cell Leukemia, ATL) and a spectrum of inflammatory diseases (mainly HTLV-associated myelopathy—tropical spastic ... [more ▼]

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes cancer (Adult T cell Leukemia, ATL) and a spectrum of inflammatory diseases (mainly HTLV-associated myelopathy—tropical spastic paraparesis, HAM/TSP). Since virions are particularly unstable, HTLV-1 transmission primarily occurs by transfer of a cell carrying an integrated provirus. After transcription, the viral genomic RNA undergoes reverse transcription and integration into the chromosomal DNA of a cell from the newly infected host. The virus then replicates by either one of two modes: (i) an infectious cycle by virus budding and infection of new targets and (ii) mitotic division of cells harboring an integrated provirus. HTLV-1 replication initiates a series of mechanisms in the host including antiviral immunity and checkpoint control of cell proliferation. HTLV-1 has elaborated strategies to counteract these defense mechanisms allowing continuous persistence in humans. [less ▲]

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See detailN-Hydroxy-6-(5-Nitro- Naphtalimide)-Hexanamide Inhibits Lysine Deacetylation, Mitigates Angiogenesis and Reduces Tumor Growth
Shankar, T.V. Shiva; Sulka, B.; Hubert, P. et al

in Journal of Cancer Sciences (2015), 2(1),

In this report, we present a novel histone deacetylase inhibitor (HDACi) (N-Hydroxy-6-(5-nitro-naphtalimide)-hexanamide: ES8) that efficiently inhibits angiogenesis in relevant ex vivo models (Human ... [more ▼]

In this report, we present a novel histone deacetylase inhibitor (HDACi) (N-Hydroxy-6-(5-nitro-naphtalimide)-hexanamide: ES8) that efficiently inhibits angiogenesis in relevant ex vivo models (Human umbilical vein endothelial cells (HUVEC), 3D aortic ring assay) and in vivo (chick chorioallantoic membrane (CAM), Zebrafish). Transcriptomic profiling reveals a set of ES8 specific genes that are not affected by the prototypical HDACi suberoylanilide hydroxamic acid (SAHA). Finally, ES8 also reduced tumor growth in mouse models of small cell lung cancer. Availability of a novel compound not centered exclusively on inhibition of angiogenic factors and inducing a characteristic transcription profile may be of interest to overcome resistance to currently used chemotherapies. [less ▲]

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See detailAPOBEC3 Interference during Replication of Viral Genomes
Willems, Luc ULg; Gillet, Nicolas ULg

in Viruses (2015)

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See detailCheckpoints modulation by the human T-lymphotropic virus type 1 (HTLV-1) Tax protein : towards new therapeutic approaches
Carpentier, Alexandre ULg; Barez, Pierre-Yves ULg; Boxus, Mathieu et al

Poster (2015, May 13)

HTLV-1 infects approximately 15 million people worldwide and causes several diseases. This virus is responsible for the adult T-cell leukemia (ATL) and for a chronic neuropathology (TSP/HAM). There is ... [more ▼]

HTLV-1 infects approximately 15 million people worldwide and causes several diseases. This virus is responsible for the adult T-cell leukemia (ATL) and for a chronic neuropathology (TSP/HAM). There is currently no satisfactory treatment for these diseases. Among the proteins encoded by HTLV-1, Tax appears to play an important role in the mechanisms leading to pathogenicity. We are interested in the mechanisms of cell transformation by the Tax viral oncoprotein. In particular, we aim at understanding the interplay between Tax and the DNA damage response (DDR). We show that transient expression of Tax results in DNA damage, cell cycle arrest and activation of the DDR. In fibroblasts, cell cycle arrest occurs at the G1 and G2 phases depending on the p53 background. In contrast, HTLV-1 infected lymphocytes proliferate continuously and appear to be adapted to the checkpoints. This mechanism of checkpoint adaptation thus allows ongoing proliferation despite the presence of genomic lesions. Quantification of the rates of NHEJ and homologous recombination indicates that HTLV-1 infected cells require very efficient DNA repair for survival. Therefore, we propose a novel therapeutic approach based on the principle of synthetic lethality using inhibitors of DNA repair. [less ▲]

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