References of "de Leval, Laurence"
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See detailRaloxifene-induced myeloma cell apoptosis: a study of nuclear factor-kappaB inhibition and gene expression signature.
Olivier, Sabine ULg; Close, Pierre ULg; Castermans, Emilie ULg et al

in Molecular Pharmacology (2006), 69(5), 1615-1623

Because multiple myeloma remains associated with a poor prognosis, novel drugs targeting specific signaling pathways are needed. The efficacy of selective estrogen receptor modulators for the treatment of ... [more ▼]

Because multiple myeloma remains associated with a poor prognosis, novel drugs targeting specific signaling pathways are needed. The efficacy of selective estrogen receptor modulators for the treatment of multiple myeloma is not well documented. In the present report, we studied the antitumor activity of raloxifene, a selective estrogen receptor modulator, on multiple myeloma cell lines. Raloxifene effects were assessed by tetrazolium salt reduction assay, cell cycle analysis, and Western blotting. Mobility shift assay, immunoprecipitation, chromatin immunoprecipitation assay, and gene expression profiling were performed to characterize the mechanisms of raloxifene-induced activity. Indeed, raloxifene, as well as tamoxifen, decreased JJN-3 and U266 myeloma cell viability and induced caspase-dependent apoptosis. Raloxifene and tamoxifen also increased the cytotoxic response to vincristine and arsenic trioxide. Moreover, raloxifene inhibited constitutive nuclear factor-kappaB (NF-kappaB) activity in myeloma cells by removing p65 from its binding sites through estrogen receptor alpha interaction with p65. It is noteworthy that microarray analysis showed that raloxifene treatment decreased the expression of known NF-kappaB-regulated genes involved in myeloma cell survival and myeloma-induced bone lesions (e.g., c-myc, mip-1alpha, hgf, pac1,...) and induced the expression of a subset of genes regulating cellular cycle (e.g., p21, gadd34, cyclin G2,...). In conclusion, raloxifene induces myeloma cell cycle arrest and apoptosis partly through NF-kappaB-dependent mechanisms. These findings also provide a transcriptional profile of raloxifene treatment on multiple myeloma cells, offering the framework for future studies of selective estrogen receptor modulators therapy in multiple myeloma. [less ▲]

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See detailUse of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus
de Leval, Laurence ULg; Waltregny, David ULg; Boniver, Jacques ULg et al

in American Journal of Surgical Pathology (2006), 30(3), 319-327

Uterine smooth muscle tumors (SMTs) are usually recognized on the basis of their routine morphologic features; however, their distinction from endometrial stromal tumors (ESTs), the second most common ... [more ▼]

Uterine smooth muscle tumors (SMTs) are usually recognized on the basis of their routine morphologic features; however, their distinction from endometrial stromal tumors (ESTs), the second most common mesenchymal tumor of the uterus, is sometimes problematic. Histone deacetylases (HDACs) were originally identified as nuclear enzymes regulating histone acetylation. We have recently shown that in normal human tissues, HDAC8 is exclusively expressed in the cytoplasm of cells showing smooth muscle differentiation. In this study, we examined HDAC8 expression in SMTs and ESTs of the uterus to determine whether HDAC8 may be a useful diagnostic tool in the classification of problematic uterine mesenchymal tumors. HDAC8 immunohistochemical staining was performed in 15 leiomyomas (LMs), 9 highly cellular leiomyomas (HCLs), 8 epithelioid SMTs, 13 leiomyosarcomas (LMSs), and 17 ESTs, including 3 with sex-cord differentiation and 5 with smooth muscle differentiation. All tumors were also stained for other smooth muscle markers (desmin, h-caldesmon, smooth muscle actin [SMA], smooth muscle myosin heavy chain) and for CD 10. All LMs had moderate to strong expression of all smooth muscle markers. HDAC8 was detected in 8 of 9 HCLs and in all epithelioid SMTs (8 of 8); however, it was weak in 4 epithelioid SMTs. In contrast, desmin, h-caldesmon and smooth muscle myosin were positive in only 2 of 8, 1 of 8 and 4 of 8 epithelioid SMTs, respectively. All smooth muscle markers had similar frequency of staining in LMSs; however, HDAC8 showed overall moderate intensity compared with other smooth muscle markers, which showed stronger staining. HDAC8, h-caldesmon, and smooth muscle myosin did not stain conventional areas of ESTs or ESTs with sex-cord differentiation, whereas SMA and desmin were positive in those areas in 4 of 12 and 3 of 12 ESTs, respectively. Areas of smooth muscle differentiation in ESTs were positive for HDAC8 in all cases, but they were less constantly positive for the other smooth muscle markers. CD10 was expressed in most ESTs (14 of 17), but it was also positive in 15 of 45 SMTs. In conclusion: 1) HDAC8 seems to be a specific marker of SM differentiation because conventional ESTs and ESTs with sex-cord differentiation are negative for HDAC8, whereas areas of smooth muscle differentiation in these tumors are consistently positive; 2) HDAC8 gives similar results to those obtained with desmin, h-caldesmon, and smooth muscle myosin in both LMs and LMSs, although the staining for HDAC8 in LMSs tends to be less intense; 3) HDAC8 may be a more sensitive marker than desmin and h-caldesmon in epithelioid SMTs. Thus, HDAC8 detection may be useful in helping the differential diagnosis of uterine mesenchymal tumors. [less ▲]

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See detailUterine tumors resembling ovarian sex-cord tumors: A study of 14 cases showing a diverse phenotypic profile
de Leval, Laurence ULg; Waltregny, David ULg; Dupuis, Léon-Marie et al

in Laboratory Investigation : Journal of Technical Methods & Pathology (2006, January), 86(Suppl. 1), 176

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See detailUterine tumors resembling ovarian sex-cord tumors: A study of 14 cases showing a diverse phenotypic profile
de Leval, Laurence ULg; Waltregny, David ULg; Dupuis, Léon-Marie et al

in Modern Pathology (2006, January), 19(Suppl. 1), 176

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See detailCloning of the genome of Alcelaphine herpesvirus 1 as an infectious and pathogenic bacterial artificial chromosome.
Dewals, Benjamin G ULg; Boudry, Christel ULg; Gillet, Laurent ULg et al

in Journal of General Virology (The) (2006), 87(Pt 3), 509-17

Alcelaphine herpesvirus 1 (AlHV-1), carried asymptomatically by wildebeest, causes malignant catarrhal fever (MCF) following cross-species transmission to a variety of susceptible species of the order ... [more ▼]

Alcelaphine herpesvirus 1 (AlHV-1), carried asymptomatically by wildebeest, causes malignant catarrhal fever (MCF) following cross-species transmission to a variety of susceptible species of the order Artiodactyla. The study of MCF pathogenesis has been impeded by an inability to produce recombinant virus, mainly due to the fact that AlHV-1 becomes attenuated during passage in culture. In this study, these difficulties were overcome by cloning the entire AlHV-1 genome as a stable, infectious and pathogenic bacterial artificial chromosome (BAC). A modified loxP-flanked BAC cassette was inserted in one of the two large non-coding regions of the AlHV-1 genome. This insertion allowed the production of an AlHV-1 BAC clone stably maintained in bacteria and able to regenerate virions when transfected into permissive cells. The loxP-flanked BAC cassette was excised from the genome of reconstituted virions by growing them in permissive cells stably expressing Cre recombinase. Importantly, BAC-derived AlHV-1 virions replicated comparably to the virulent (low-passage) AlHV-1 parental strain and induced MCF in rabbits that was indistinguishable from that of the virulent parental strain. The availability of the AlHV-1 BAC is an important advance for the study of MCF that will allow the identification of viral genes involved in MCF pathogenesis, as well as the production of attenuated recombinant candidate vaccines. [less ▲]

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See detailCloning of the genome of Alcelaphine herpesvirus 1 as an infectious and pathogenic bacterial artificial chromosome
Dewals, Benjamin G ULg; Boudry, Christel; Gillet, Laurent ULg et al

Poster (2006)

Alcelaphine herpesvirus 1 (AlHV-1), carried asymptomatically by wildebeest, causes malignant catarrhal fever (MCF) following cross-species transmission to a variety of susceptible species of the order ... [more ▼]

Alcelaphine herpesvirus 1 (AlHV-1), carried asymptomatically by wildebeest, causes malignant catarrhal fever (MCF) following cross-species transmission to a variety of susceptible species of the order Artiodactyla. The study of MCF pathogenesis has been impeded by an inability to produce recombinant virus, mainly due to the fact that AlHV-1 becomes attenuated during passage in culture. In this study, these difficulties were overcome by cloning the entire AlHV-1 genome as a stable, infectious and pathogenic bacterial artificial chromosome (BAC). A modified loxP-flanked BAC cassette was inserted in one of the two large non-coding regions of the AlHV-1 genome. This insertion allowed the production of an AlHV-1 BAC clone stably maintained in bacteria and able to regenerate virions when transfected into permissive cells. The loxP-flanked BAC cassette was excised from the genome of reconstituted virions by growing them in permissive cells stably expressing Cre recombinase. Importantly, BAC-derived AlHV-1 virions replicated comparably to the virulent (low-passage) AlHV-1 parental strain and induced MCF in rabbits that was indistinguishable from that of the virulent parental strain. The availability of the AlHV-1 BAC is an important advance for the study of MCF that will allow the identification of viral genes involved in MCF pathogenesis, as well as the production of attenuated recombinant candidate vaccines. [less ▲]

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See detailIdentification of accessible proteins expressed in human breast cancer
Castronovo, Vincenzo ULg; Kischel, Philippe; Guillonneau, François et al

Scientific conference (2006)

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See detailSERMs-induced myeloma cell apoptosis: A study of NF-kappa B inhibition and gene expression signature
Olivier, Sabine ULg; Close, Patricia ULg; Castermans, Emilie ULg et al

in Journal of Bone and Mineral Research (2005, September), 20(9, Suppl. 1), 213

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See detailLe cas clinique du mois: traitement d'un kyste hydatique hepatique par hepatectomie laparoscopique (Bisegmentectomie II-III)
Detry, Olivier ULg; Leonard, Philippe ULg; Delwaide, Jean ULg et al

in Revue Médicale de Liège (2005), 60(9), 700-2

Most of the echinococcosis cases treated in Belgium are contracted in African and Mediterranean countries. In this paper the authors describe the case of a Mediterranean patient suffering from a hepatic ... [more ▼]

Most of the echinococcosis cases treated in Belgium are contracted in African and Mediterranean countries. In this paper the authors describe the case of a Mediterranean patient suffering from a hepatic hydatid cyst treated by oral albendazole and laparoscopic liver resection. [less ▲]

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See detailTransmission of an undiagnosed sarcoma to recipients of kidney and liver grafts procured in a non-heart beating donor
Detry, Olivier ULg; De Roover, Arnaud ULg; de Leval, Laurence ULg et al

in Liver Transplantation (2005), 11(6), 696-699

Transmission of an undiagnosed cancer with solid organ transplantation is a rare but dreadful event. In this paper the authors report the transmission of an undiagnosed sarcoma to recipients of kidney and ... [more ▼]

Transmission of an undiagnosed cancer with solid organ transplantation is a rare but dreadful event. In this paper the authors report the transmission of an undiagnosed sarcoma to recipients of kidney and liver grafts procured in a Maastricht category 3 non-heart beating donor. To the authors' knowledge this case is the first report of such a transmission with a liver graft procured in a non-heart beating donor. The cancer transferal was diagnosed I year after transplantation in the recipients of the liver and of one kidney. The liver recipient died from multiple organ failure after a failed attempt of tumor resection. The kidney recipient underwent immunosuppression withdrawal and transplantectomy. Non-heart beating donors should not be particularly at risk for undiagnosed cancer transmission if the procurement is performed according to the same rules of careful inspection of the abdominal and thoracic organs. After diagnosis of donor cancer transmission, kidney recipients should have the graft removed, and immunosuppression should be interrupted. The management of liver graft recipients is very difficult in this setting, and long-term survival was very rarely reported. [less ▲]

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See detailAbdominal aortic aneurysm due to Brucella melitensis
Quaniers, Janine ULg; DURIEUX, Rodolphe ULg; de Leval, Laurence ULg et al

in Acta Chirurgica Belgica (2005), 105(1), 93-95

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See detailBovine herpesvirus 4 induces apoptosis of human carcinoma cell lines in vitro and in vivo
Gillet, Laurent ULg; Dewals, Benjamin G ULg; Farnir, Frédéric ULg et al

in Cancer Research (2005), 65(20), 9463-9472

The idea of using oncolytic viruses for the treatment of cancers was proposed a century ago. During the last two decades, viruses able to replicate specifically in cancer cells and to induce their lysis ... [more ▼]

The idea of using oncolytic viruses for the treatment of cancers was proposed a century ago. During the last two decades, viruses able to replicate specifically in cancer cells and to induce their lysis were identified and were genetically modified to improve their viro-oncolytic properties. More recently, a new approach consisting of inducing selective apoptosis in cancer cells through viral infection has been proposed; this approach has been called viro-oncoapoptosis. In the present study, we report the property of bovine herpesvirus-4 (BoHV-4) to induce, in vitro and in vivo, apoptosis of some human carcinomas. This conclusion relies on the following observations: (a) In vitro, BoHV-4 infection induced apoptosis of A549 and OVCAR carcinoma cell lines in a time- and dose-dependent manner. (b) Apoptosis was induced by the expression of an immediate-early or an early BoHV-4 gene, but did not require viral replication. (c) Cell treatment with caspase inhibitors showed that apoptosis induced by BoHV-4 relied mainly on caspase-10 activation. (d) Infection of cocultures of A549 or OVCAR cells mixed with human 293 cells (in which BoHV-4 does not induce apoptosis) showed that BoHV-4 specifically eradicated A549 or OVCAR cancer cells from the cocultures. (e) Finally, in vivo experiments done with nude mice showed that BoHV-4 intratumoral injections reduced drastically the growth of preestablished A549 xenografts. Taken together, these results suggest that BoHV-4 may have potential as a viro-oncoapoptotic agent for the treatment of some human carcinomas. Moreover, further identification of BoHV-4 proapoptotic gene(s) and the cellular pathways targeted by this or these gene(s) could lead to the design of new cancer therapeutic strategies. [less ▲]

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See detailExpression of histone deacetylase 8, a class I histone deacetylase, is restricted to cells showing smooth muscle differentiation in normal human tissues
Waltregny, David ULg; de Leval, Laurence ULg; Glenisson, Wendy et al

in American Journal of Pathology (2004), 165(2), 553-564

Histone deacetylases (HDACs) were originally identified as nuclear enzymes involved in gene transcription regulation. Until recently, it was thought that their activity was restricted within the nucleus ... [more ▼]

Histone deacetylases (HDACs) were originally identified as nuclear enzymes involved in gene transcription regulation. Until recently, it was thought that their activity was restricted within the nucleus, with histones as unique substrates. The demonstration that specific HDACs deacetylate nonhistone proteins, such as p53 and alpha-tubulin, broadened the field of activity of these enzymes. HDAC8, a class I HDAC, is considered to be ubiquitously expressed, as suggested by results of Northern blots performed on tissue RNA extracts, and transfection experiments using various cell lines have indicated that this enzyme may display a prominent nuclear localization. Using immunohistochemistry, we unexpectedly found that, in normal human tissues, HDAC8 is exclusively expressed by cells showing smooth muscle differentiation, including visceral and vascular smooth muscle cells, myoepithelial cells, and myofibroblasts, and is mainly detected in their cytosol. These findings were confirmed in vitro by nucleo-cytoplasmic fractionation and immunoblot experiments performed on human primary smooth muscle cells, and by the cytosolic detection of epitope-tagged HDAC8 overexpressed in fibroblasts. Immunocytochemistry strongly suggested a cytoskeleton-like distribution of the enzyme. Further double-immunofluorescence staining experiments coupled with confocal microscopy analysis showed that epitope-tagged HDAC8 overexpressed in murine fibroblasts formed cytoplasmic stress fiber-like structures that co-localized with the smooth muscle cytoskeleton protein smooth muscle alpha-actin. Our works represent the first demonstration of the restricted expression of a class I HDAC to a specific cell type and indicate that HDAC8, besides being a novel marker of smooth muscle differentiation, may play a role in the biology of these contractile cells. [less ▲]

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See detailLuminal contact with University of Wisconsin solution improves human small bowel preservation
De Roover, Arnaud ULg; de Leval, Laurence ULg; Gilmaire, Julie ULg et al

in Transplantation Proceedings (2004), 36(2), 273-275

AIM: Under clinical conditions small bowel mucosa is stored without any contact between the mucosa and the preservation solution. We evaluated the impact of luminal contact with University of Wisconsin ... [more ▼]

AIM: Under clinical conditions small bowel mucosa is stored without any contact between the mucosa and the preservation solution. We evaluated the impact of luminal contact with University of Wisconsin solution (UW) on the structural quality of small bowel preservation. METHODS: Segments of ileum harvested from stable multi-organ donors were flushed with UW. For each donor, ileal segments were placed in UW without any contact between the mucosa and the preservation solution (group A), as is practiced in clinical conditions. Adjacent segments were cut on their antimesenteric side and placed in UW so that their mucosa was widely in contact with the solution (group B). The grafts preserved in ice were removed from the preservation fluid at different times (0, 3, 6, or 12 hours). Tissues were studied by optical microscopy after H [less ▲]

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See detailA new model for human intestinal preservation: Comparison of University of Wisconsin and Celsior preservation solutions
De Roover, Arnaud ULg; de Leval, Laurence ULg; Gilmaire, Julie ULg et al

in Transplantation Proceedings (2004), 36(2), 270-272

AIM: We compared University of Wisconsin (UW) and Celsior preservation solutions using a new model of human intestinal preservation that mimics the clinical conditions of small bowel procurement. METHODS ... [more ▼]

AIM: We compared University of Wisconsin (UW) and Celsior preservation solutions using a new model of human intestinal preservation that mimics the clinical conditions of small bowel procurement. METHODS: Intestinal grafts were harvested from four multiorgan donors. After classic warm dissection for organ procurement, an ileal segment of 50 cm was immediately flushed with Celsior. After the perfusion of the abdominal organs with UW, a second segment of adjacent ileum was harvested. The two intestinal grafts were then divided into segments by stapling, before immersion into the corresponding preservation solution (Celsior or UW) for 0-, 6-, 12-, or 24-hour incubation at 4 degrees C. A histological score was graded after blinded examination of three random specimens within each ileal graft for each duration of preservation. RESULTS: Control specimens showed normal histology. After 6 hours of preservation, most villi showed complete epithelial detachment although the crypts appeared intact. After 12 hours of preservation, a larger proportion of the villi showed extensive epithelial sloughing. After 24 hours, the damage involved the entire mucosa with the crypt epithelium largely detached from the basal membrane. No statistical difference in histological score was observed between the two preservation solutions. CONCLUSION: This study showed severe histological alterations of graft mucosa after short periods of preservation by UW or Celsior solutions. This model may be useful to evaluate improvements in the quality of preservation of human intestinal transplants. [less ▲]

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See detailRegulation of HER-2 oncogene expression by cyclooxygenase-2 and prostaglandin E2
Benoit, Valérie; Relic, Biserka ULg; de Leval, Laurence ULg et al

in Oncogene (2004), 23(8), 1631-1635

The oncoprotein HER-2/neu is a prosurvival factor and its overexpression has been correlated with adverse prognosis in breast cancers. High levels of the cyclooxygenase-2 (COX-2), a proinflammatory and ... [more ▼]

The oncoprotein HER-2/neu is a prosurvival factor and its overexpression has been correlated with adverse prognosis in breast cancers. High levels of the cyclooxygenase-2 (COX-2), a proinflammatory and antiapoptotic enzyme, were detected in HER-2-positive tumors and this observation was linked to an HER-2-mediated induction of COX-2 gene transcription. Here, we report that COX-2 expression, and synthesis of its major enzymatic product, PGE2, leads in turn to an enhanced HER-2 expression. Moreover, COX-2 enzymatic inhibition dramatically reduced HER-2 protein levels, efficiently increased the cancer cells sensitility to chemotherapeutic treatment and acted in synergy with HER-2 inhibitor, trastuzumab. Therefore, we propose an original model where HER-2 and COX-2 transcriptionally regulate each other in a positive loop. [less ▲]

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See detailLuminal contact improves human small bowel preservation
DE ROOVER, Arnaud ULg; de Leval, Laurence ULg; GILMAIRE, Julie ULg et al

in Acta Gastro-Enterologica Belgica (2004), 67

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See detailBack pain and renal failure
Delanaye, Pierre ULg; Bovy, Christophe ULg; de Leval, Laurence ULg et al

in Lancet (2004), 364(9449), 1992

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