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See detailEpigenetic regulation of angiogenesis
Shiva Shankar, Thammadihalli Veerasangaiah ULg; Sulka, Béatrice ULg; Willems, Luc ULg

Speech (2011)

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 designed a family of twin drugs with intrinsic HDAC and DNMT inhibitory activities and tested 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 (EPI) affecting global histone acetylation and having quantifiable anti-angiogenic action without cytotoxic and apoptotic effect. In order to elucidate its anti-angiogenic mechanism, we characterized gene expression pattern simultaneously with the methylation profile of HUVEC cells treated with EPI and reference epigenetic modulators. This approach based on parallel microarray analyses permitted us to underscore a list of genes exclusively affected by EPI but not by other HDAC or DNMT inhibitors. These genes were then analyzed using the Ingenuity Pathway Analysis software revealing potential involvement of a subset of genes in angiogenesis. Our present aim is to validate the expression levels of a series of genes with respect to epigenetic mechanisms (histone modifications and DNA methylation). Finally, the biological relevance of the target genes will be explored by RNA silencing. Hence, 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 ▲]

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See detailEpigenetic Therapy of Lung Cancers: Anti-tumoral effect of valproate on small cell lung cancer
Hubaux, Roland ULg

Doctoral thesis (2011)

Lung cancer is the leading cause of cancer-related death worldwide. Among lung carcinomas, the outcome of small cell lung carcinoma (SCLC) patients is the poorest of any histological subtype with five ... [more ▼]

Lung cancer is the leading cause of cancer-related death worldwide. Among lung carcinomas, the outcome of small cell lung carcinoma (SCLC) patients is the poorest of any histological subtype with five-year survival rate of less than 20 and 5 % for limited and extensive stage respectively. Based on increasing evidence that inhibitors of histones deacetylases (HDAC) have anticancer properties, the goal of this study was to evaluate the ability of valproate (VPA) to improve efficacy of chemotherapeutic regimen in SCLC. We show that VPA directly induces apoptosis of SCLC cell lines at concentrations relevant for clinical uses. Furthermore, VPA synergizes with two chemotherapeutic regimen used in first (cisplatin + etoposide) and second line (cyclophosphamid + vindesine + doxorubicin) treatments. Both mitochondrial and death receptor pathways are involved in VPA-induced apoptosis. Although VPA promotes production of reactive oxygen species, free radical scavenger N-acetylcystein is not sufficient to inhibit apoptosis. As expected, VPA triggers hyperacetylation of histone H3 and increases expression of p21. VPA reduces levels of BclxL, induces cleavage of Bid, translocation of Bax to mitochondria, release of cytochrome c into cytosol and phosphorylation of Erk and H2AX. Transcriptomic analyses by microarrays and quantitative RT-PCR have underscored a series of genes candidates potentially implicated into sensitivity of SCLC to VPA. Among these, the Fzd7 receptor of the WNT pathway is essential for VPA proapoptotic activity. Efficiency of VPA combined to first and second line chemotherapeutic agents is supported by preclinical models of SCLC cells engrafted into SCID mice. The second line combination is presently tested in a clinical trial with patients presenting with refractory or relapsing small cell lung cancer (protocol 01081 at http://www.elcwp.org). [less ▲]

Detailed reference viewed: 35 (10 ULg)
See detailEpigenetics and local adaptation
Hanikenne, Marc ULg

Conference (2014, January 22)

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See detailEpigenetics, sirtuins and osteoarthritis.
Gabay, Odile; Sanchez, Christelle ULg

in Joint, bone, spine : revue du rhumatisme (2012), 79(6), 570-3

Epigenetics, modifications of the DNA other than changes on the DNA sequences, is frequently studied in cancer research and aging. DNA methylation, mi-RNA, and histones deacetylation are investigated in ... [more ▼]

Epigenetics, modifications of the DNA other than changes on the DNA sequences, is frequently studied in cancer research and aging. DNA methylation, mi-RNA, and histones deacetylation are investigated in different pathologies, including inflammatory diseases and age-related diseases such as osteoarthritis (OA). In this review, we focus on the chromatin-modifying enzymes in arthritic pathologies, and more particularly on Sirtuins. We also review the role of Sirt1 in OA, which has been highlighted in recent publications, and examine the possible protective role Sirt1 could play in this disease. Moreover, we discuss the possible therapeutic target of such a protein, reviewing the potential inhibitors/activators of this enzyme and their properties. [less ▲]

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See detailEpigenetique, interface entre environnement et genes: ro1e dans les maladies complexes.
SCHEEN, André ULg; Junien, C.

in Revue Médicale de Liège (2012), 67(5-6), 250-7

Epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. Epigenetics is one of the major mechanisms ... [more ▼]

Epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. Epigenetics is one of the major mechanisms explaining the "Developmental Origin of Health and Diseases" (DOHaD). Besides genetic background inherited from parents, which confers susceptibility to certain pathologies, epigenetic changes constitute the memory of previous events, either positive or negative, along the life cycle, including at the in utero stage. The later exposition to hostile environment may reveal such susceptibility, with the development of various pathologies, among them numerous chronic complex diseases. The demonstration of such a sequence of events has been shown for metabolic diseases as obesity, metabolic syndrome and type 2 diabetes, cardiovascular disease and cancer. In contrast to genetic predisposition, which is irreversible, epigenetic changes are potentially reversible, thus giving targets not only for prevention, but possibly also for the treatment of certain complex diseases. [less ▲]

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See detailEpigraphes alphabétiques du pays de la Mer
Colonna d'Istria, Laurent ULg

in Nouvelles Assyriologiques Brèves et Utilitaires (2012)

Detailed reference viewed: 42 (3 ULg)
See detailL'épigraphie au service de l'histoire médicale
Nissen, Cécile ULg

Scientific conference (2010, March 19)

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See detailEpigraphie latine
Dubuisson, Michel; Famerie, Etienne ULg

Learning material (2009)

Detailed reference viewed: 37 (4 ULg)
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See detailEpigraphique grecque. Bibliographie
Famerie, Etienne ULg

Learning material (2009)

Detailed reference viewed: 32 (4 ULg)
See detailEpilepsie
Martin, Didier ULg

Scientific conference (2005, March)

Detailed reference viewed: 23 (5 ULg)
See detailEpilepsie a paroxysmes rolandiques de l'enfant
CARLIER, Gérard; Misson, Jean-Paul ULg; Dubru, Jean-Marie ULg

in Comptes Rendus de la Société Belge de Neurologie Infantile (1983)

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See detailEpilepsie chez des enfants infirmes moteurs-cérébraux
Peduzzi, M.; Defontaine, E.; Misson, Jean-Paul ULg

in Revue Médicale de Liège (2006), 61(4), 237-239

The incidence of epilepsy in 110 patients with cerebral palsy (the majority with spastic tetraplegia) was 46,4%. Almost half of the patients with spastic tetraplegia (45%) and hemiplegia (52%) had ... [more ▼]

The incidence of epilepsy in 110 patients with cerebral palsy (the majority with spastic tetraplegia) was 46,4%. Almost half of the patients with spastic tetraplegia (45%) and hemiplegia (52%) had epilepsy. The incidence was lower in patients with spastic diplegia (32%). Half of epilepsy in spastic hemiplegia were partial seizures and the other half consisted of generalized seizures, while generalized tonic-clonic episodes predominated in all other forms of C.P. A high incidence of West syndrome was observed in patients with spastic tetraplegia. Etiological factors of C.P. were perinatal in 75%. 16,65% had neonatal antecedents of convulsions; most of them had spastic tetraplegia (75%) and a significant mental retardation. A low intelligence quotient (I.Q.) was seen in most of the children with epilepsy, and patients with tetraplegia had significantly lower intelligence quotient than other groups. [less ▲]

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See detailL'épilepsie de Vincent VAN GOGH
Blumer, Dietrich; Stassart, Martine ULg

in Cahiers du CEP (Centre d'Etudes Pathoanalytiques) (1994), 4(4), 3-10

Though he never had typical "grand mal" crisis, Vincent VAN GOGH was really epileptic. The symptomatology of epileptic seizures was better known in the XIXd Century than today.

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See detailL'épilepsie essentielle au Rorschach et au Szondi
Stassart, Martine ULg

in Cahiers du CEP (Centre d'Etudes Pathoanalytiques) (1994), 4

Twenty essential epileptics were examined with help of the Rorschach and Szonditests.The results show that the classical signs of "épileptoïdie" are present by all the subjects. There is thus a specifical ... [more ▼]

Twenty essential epileptics were examined with help of the Rorschach and Szonditests.The results show that the classical signs of "épileptoïdie" are present by all the subjects. There is thus a specifical pattern of personnality by this seizure of epilepsy. [less ▲]

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See detailL'épilepsie essentielle aux tests de Szondi et Rorschach
Stassart, Martine ULg

Conference (1999, July 18)

Twenty essential epileptics were examined with help of Szondi and Rorschachtests. The results show that the classical signs of "epileptoïdie" are actually present by all the subjects. There is thus a ... [more ▼]

Twenty essential epileptics were examined with help of Szondi and Rorschachtests. The results show that the classical signs of "epileptoïdie" are actually present by all the subjects. There is thus a specifical pattern of personnality by this seizure of epiepsy. [less ▲]

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See detailEpilepsie et tests projectifs
Stassart, Martine ULg

Scientific conference (2011, November 11)

Twenty essential epileptics and twelve secondary ( focal) epileptics were examined with help of Rorschach and Szondi tests. The focal epileptics are less structured than the essential ones. These show a ... [more ▼]

Twenty essential epileptics and twelve secondary ( focal) epileptics were examined with help of Rorschach and Szondi tests. The focal epileptics are less structured than the essential ones. These show a lot of "epileptoid" signs, as classicaly described by Françoise Minkowska:high sensoriality, simultaneous production of both "bound" and "explosion" answers. This article is illustrated by a lot of significant examples. [less ▲]

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See detailEpilepsie frontale et trouble du comportement: diagnostic, exploration et traitement
Misson, Jean-Paul ULg; Reynaers, A.; Ernould, C. et al

in 30ème Congrès de l'Association des Pédiatres de Langue Française (1993)

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See detailLes épilepsies : de la molécule aux symptômes
Martin, Didier ULg

Conference (2003, March 15)

Detailed reference viewed: 6 (0 ULg)