References of "Bours, Vincent"
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See detailModulation of the HSV-TK/ganciclovir bystander effect by n-butyrate in glioblastoma: correlation with gap-junction intercellular communication.
Robe, Pierre ULg; Jolois, Olivier ULg; Nguyen Khac, Minh-Tuan ULg et al

in International Journal of Oncology (2004), 25(1), 187-92

The efficacy of HSV-TK/ganciclovir gene therapy largely relies on the bystander effect, i.e. the ability of transfected cells to kill the adjacent, untrasfected cells. This mechanism itself depends ... [more ▼]

The efficacy of HSV-TK/ganciclovir gene therapy largely relies on the bystander effect, i.e. the ability of transfected cells to kill the adjacent, untrasfected cells. This mechanism itself depends chiefly on the transfer via gap junctions of phosphorylated ganciclovir between cells, and is often deficient in glioblastomas. In this report, we demonstrate that n-butyrate markedly enhances the gap junction intercellular communication of GJIC-deficient glioma cells, and significantly increases the bystander effect in such cells. This effect of n-butyrate appears to be independent from its HDAC inhibitory effect, since trichostatin A does not reproduce it. [less ▲]

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See detailIn vitro and in vivo activity of the nuclear factor-kappa B inhibitor sulfasalazine in human glioblastomas.
Robe, Pierre ULg; Bentires-Alj, Mohamed; Bonif, Marianne et al

in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (2004), 10(16), 5595-603

Glioblastomas, the most common primary brain cancers, respond poorly to current treatment modalities and carry a dismal prognosis. In this study, we demonstrated that the transcription factor nuclear ... [more ▼]

Glioblastomas, the most common primary brain cancers, respond poorly to current treatment modalities and carry a dismal prognosis. In this study, we demonstrated that the transcription factor nuclear factor (NF)-kappaB is constitutively activated in glioblastoma surgical samples, primary cultures, and cell lines and promotes their growth and survival. Sulfasalazine, an anti-inflammatory drug that specifically inhibits the activation of NF-kappaB, blocked the cell cycle and induced apoptosis in several glioblastoma cell lines and primary cultures, as did gene therapy with a vector encoding a super-repressor of NF-kappaB. In vivo, sulfasalazine also significantly inhibited the growth of experimental human glioblastomas in nude mice brains. Given the documented safety of sulfasalazine in humans, these results may lead the way to a new class of glioma treatment. [less ▲]

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See detailCytoplasmic I kappa B alpha increases NF-kappa B-independent transcription through binding to histone deacetylase (HDAC) 1 and HDAC3
Viatour, Patrick ULg; Legrand-Poels, Sylvie; van Lint, Carine et al

in Journal of Biological Chemistry (2003), 278(47), 46541-46548

IkappaBalpha is an inhibitory molecule that sequesters NF-kappaB dimers in the cytoplasm of unstimulated cells. Upon stimulation, NF-kappaB moves to the nucleus and induces the expression of a variety of ... [more ▼]

IkappaBalpha is an inhibitory molecule that sequesters NF-kappaB dimers in the cytoplasm of unstimulated cells. Upon stimulation, NF-kappaB moves to the nucleus and induces the expression of a variety of genes including IkappaBalpha. This newly synthesized IkappaBalpha also translocates to the nucleus, removes activated NF-kappaB from its target genes, and brings it back to the cytoplasm to terminate the phase of NF-kappaB activation. We show here that IkappaBalpha enhances the transactivation potential of several homeodomain-containing proteins such as HOXB7 and Pit-1 through a NF-kappaB-independent association with histone deacetylase (HDAC) 1 and HDAC3 but not with HDAC2, -4, -5, and -6. IkappaBalpha bound both HDAC proteins through its ankyrin repeats, and this interaction was disrupted by p65. Immunofluorescence experiments demonstrated further that IkappaBalpha acts by partially redirecting HDAC3 to the cytoplasm. At the same time, an IkappaBalpha mutant, which lacked a functional nuclear localization sequence, interacted very efficiently with HDAC1 and -3 and intensively enhanced the transactivation potential of Pit-1. Our results support the hypothesis that the NF-kappaB inhibitor IkappaBalpha regulates the transcriptional activity of homeodomain-containing proteins positively through cytoplasmic sequestration of HDAC1 and HDAC3, a mechanism that would assign a new and unexpected role to IkappaBalpha. [less ▲]

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See detailDeletion (6)(p22p25) is a recurrent anomaly of thymoma: report of a second case and review of the literature
Herens, Christian ULg; Radermecker, Maurice ULg; Servais, Anne-Marie ULg et al

in Cancer Genetics & Cytogenetics (2003), 146(1), 66-69

A patient with type AB thymoma and del(6)(p22p25) as the sole cytogenetic anomaly is described. This is the second report of a del(6)(p22p25) in a thymoma. The same deletion was previously found in ... [more ▼]

A patient with type AB thymoma and del(6)(p22p25) as the sole cytogenetic anomaly is described. This is the second report of a del(6)(p22p25) in a thymoma. The same deletion was previously found in association with a type A thymoma. Both patients presented with benign tumors. These data suggest that partial deletion of the short arm of chromosome 6 is a nonrandom change associated with benign thymomas. (C) 2003 Elsevier Inc. All rights reserved. [less ▲]

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See detailThe antiangiogenic factor 16K human prolactin induces caspase-dependent apoptosis by a mechanism that requires activation of nuclear factor-kappa B
Tabruyn, Sébastien ULg; Sorlet, C. M.; Rentier-Delrue, Françoise ULg et al

in Molecular Endocrinology (2003), 17(9), 1815-1823

We have previously shown that the 16-kDa N-terminal fragment of human prolactin (16K hPRL) has antiangiogenic properties, including the ability to induce apoptosis in vascular endothelial cells. Here, we ... [more ▼]

We have previously shown that the 16-kDa N-terminal fragment of human prolactin (16K hPRL) has antiangiogenic properties, including the ability to induce apoptosis in vascular endothelial cells. Here, we examined whether the nuclear factor-kappaB (NF-kappaB) signaling pathway was involved in mediating the apoptotic action of 16K hPRL in bovine adrenal cortex capillary endothelial cells. In a dose-dependent manner, treatment with 16K hPRL induced inhibitor kappaB-alpha degradation permitting translocation of NF-kappaB to the nucleus and reporter gene activation. Inhibition of NF-kappaB activation by overexpression of a nondegradable inhibitor kappaB-alpha mutant or treatment with NF-kappaB inhibitors blocked 16K hPRL-induced apoptosis. Treatment with 16K hPRL activated the initiator caspases-8 and -9 and the effector caspase-3, all of which were essential for stimulation of DNA fragmentation. This activation of the caspase cascade by 16K hPRL was also NF-kappaB dependent. These findings support the conclusion that NF-kappaB signaling plays a central role in 16K hPRL-induced apoptosis in vascular endothelial cells. [less ▲]

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See detailPotentiation of tumor necrosis factor-induced NF-kappa B activation by deacetylase inhibitors is associated with a delayed cytoplasmic reappearance of I kappa B alpha
Adam, Emmanuelle; Quivy, Vincent; Bex, Françoise et al

in Molecular and Cellular Biology (2003), 23(17), 6200-6209

Previous studies have implicated acetylases and deacetylases in regulating the transcriptional activity of NF-kappaB. Here, we show that inhibitors of deacetylases such as trichostatin A (TSA) and sodium ... [more ▼]

Previous studies have implicated acetylases and deacetylases in regulating the transcriptional activity of NF-kappaB. Here, we show that inhibitors of deacetylases such as trichostatin A (TSA) and sodium butyrate (NaBut) potentiated TNF-induced expression of several natural NF-kappaB-driven promoters. This transcriptional synergism observed between TNF and TSA (or NaBut) required intact kappaB sites in all promoters tested and was biologically relevant as demonstrated by RNase protection on two instances of endogenous NF-kappaB-regulated gene transcription. Importantly, TSA prolonged both TNF-induced DNA-binding activity and the presence of NF-kappaKB in the nucleus. We showed that the p65 subunit of NF-kappaB was acetylated in vivo. However, this acetylation was weak, suggesting that other mechanisms could be implicated in the potentiated binding and transactivation activities of NF-kappaB after TNF plus TSA versus TNF treatment. Western blot and immunofluorescence confocal microscopy experiments revealed a delay in the cytoplasmic reappearance of the IkappaBalpha inhibitor that correlated temporally with the prolonged intranuclear binding and presence of NF-kappaB. This delay was due neither to a defect in IkappaBalpha mRNA production nor to a nuclear retention of IkappaBalpha but was rather due to a persistent proteasome-mediated degradation of IkappaBalpha. A prolongation of IkappaB kinase activity could explain, at least partially, the delayed IkappaBalpha cytoplasmic reappearance observed in presence of TNF plus TSA. [less ▲]

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See detailRaloxifene protects Osteoblasts from apoptosis induced by sodium nitroprusside: Potential involvement of ceramide
Olivier, Sabine ULg; Fillet, Marianne ULg; Malaise, Michel ULg et al

in Journal of Bone and Mineral Research (2003, September), 18(Suppl. 2), 136

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See detailIdentification of the signalling pathways required for interleukin-1 beta stimulation of osteoprotegerin synthesis in osteoblastic cells
Lambert, Cecile; Ribbens, Clio ULg; Bours, Vincent ULg et al

in Journal of Bone and Mineral Research (2003, September), 18(Suppl. 2), 142

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See detailInterleukin-1beta and tumor necrosis factor-alpha enhance the shedding of Interleukin-6 receptor in osteoblastic cells: Involvement of tumor necrosis factor-alpha converting enzyme
Franchimont, N. M.; Lambert, Cecile; Ribbens, Clio ULg et al

in Arthritis and Rheumatism (2003, September), 48(9, Suppl. S), 482

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See detailNF-kappa B2/p100 induces Bcl-2 expression
Viatour, Patrick ULg; Bentires-Alj, Mohamed; Chariot, Alain ULg et al

in Leukemia (2003), 17(7), 1349-1356

The NF-kappaB2/p100 and bcl-3 genes are involved in chromosomal translocations described in chronic lymphocytic leukemias (CLL) and non-Hodgkin's lymphomas, and nuclear factor kappaB (NF-kappaB) protects ... [more ▼]

The NF-kappaB2/p100 and bcl-3 genes are involved in chromosomal translocations described in chronic lymphocytic leukemias (CLL) and non-Hodgkin's lymphomas, and nuclear factor kappaB (NF-kappaB) protects cancer cells against apoptosis. Therefore, we investigated whether this transcription factor could modulate the expression of the Bcl-2 antiapoptotic protein. Bcl-2 promoter analysis showed multiple putative NF-kappaB binding sites. Transfection assays of bcl-2 promoter constructs in HCT116 cells showed that NF-kappaB can indeed transactivate bcl-2. We identified a kappaB site located at position -180 that can only be bound and transactivated by p50 or p52 homodimers. As p50 and p52 homodimers are devoid of any transactivating domains, we showed that they can transactivate the bcl-2 promoter through association with Bcl-3. We also observed that stable overexpression of p100 and its processed product p52 can induce endogenous Bcl-2 expression in MCF7AZ breast cancer cells. Finally, we demonstrated that, in breast cancer and leukemic cells ( CLL), high NF-kappaB2/p100 expression was associated with high Bcl-2 expression. Our data suggest that Bcl-2 could be an in vivo target gene for NF-kappaB2/p100. [less ▲]

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See detailIsostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, induces cell cycle arrest and apoptosis in human colon cancer cells
Frederich, Michel ULg; Bentires-Alj, M.; Tits, Monique ULg et al

in Journal of Pharmacology and Experimental Therapeutics (2003), 304(3), 1103-1110

Isostrychnopentamine (ISP) is an indolomonoterpenic alkaloid that is present in the leaves of Strychnos usambarensis, a well known African shrub or little tree. The roots contain quaternary alkaloids ... [more ▼]

Isostrychnopentamine (ISP) is an indolomonoterpenic alkaloid that is present in the leaves of Strychnos usambarensis, a well known African shrub or little tree. The roots contain quaternary alkaloids, which are used to make a curare-like arrow poison. However, tertiary alkaloids isolated from the same plant possess cytotoxic activities against mammalian cells and protozoa. The effect of ISP has been investigated on the growth and viability of HCT-116 colon cancer cells during their exponentially growing phase. ISP induced apoptotic cell death as shown by the translocation of phosphatidylserine from the inner layer to the outer layer of the plasma membrane, chromatin condensation, DNA fragmentation, and caspase-3 and -9 activation. ISP provoked also cell cycle arrest in the G(2)-M phase. We also showed that the expression of p53 was not modified in ISP-treated cells, but that p21 was induced in a p53-independent manner. Finally, we demonstrated that ISP did not affect the catalytic activity of human topoisomerases I and II. In conclusion, ISP, which promotes cell death by a p53-independent apoptotic pathway, could be an interesting lead for cancer chemotherapy. [less ▲]

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See detailMechanisms involved in exogenous C2- and C6-ceramide-induced cancer cell toxicity.
Fillet, Marianne ULg; Bentires-Alj, Mohamed; Deregowski, Valérie et al

in Biochemical Pharmacology (2003), 65(10), 1633-42

Ceramides are important intracellular second messengers that play a role in the regulation of cell growth, differentiation, and programmed cell death. To determine whether ceramides can mediate the ... [more ▼]

Ceramides are important intracellular second messengers that play a role in the regulation of cell growth, differentiation, and programmed cell death. To determine whether ceramides can mediate the apoptosis of HCT116 and OVCAR-3 cancer cells, exogenous C2-, C6-, and C16-ceramides were used to mimic the endogenous lipid increase that follows a large variety of stresses. C2- and C6-ceramides (cell-permeable ceramide analogs), but not C16-ceramide, induced nuclear factor-kappaB (NF-kappaB) DNA-binding, caspase-3 activation, poly(ADP-ribose) polymerase degradation, and mitochondrial cytochrome c release, indicating that apoptosis occurs through the caspase cascade and the mitochondrial pathway. No difference in survival was observed between control cells and cells expressing mutated IkappaBalpha and treated with the permeable ceramides. This suggests that, at least in these cell lines, stable NF-kappaB inhibition did not modify the ceramide-induced cytotoxicity pathway. C6-ceramide also induced a double block in G1 and G2, thus emptying the S phase. [less ▲]

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See detailT-cell reconstitution after unmanipulated, CD8-depleted or CD34-selected nonmyeloablative peripheral blood stem-cell transplantation.
Baron, Frédéric ULg; Schaaf-Lafontaine, Nicole ULg; Humblet-Baron, Stéphanie ULg et al

in Transplantation (2003), 76(12), 1705-13

BACKGROUND: We have previously shown that CD8 depletion or CD34 selection of peripheral blood stem cells (PBSC) reduced the incidence of acute graft-versus-host disease (GvHD) after nonmyeloablative stem ... [more ▼]

BACKGROUND: We have previously shown that CD8 depletion or CD34 selection of peripheral blood stem cells (PBSC) reduced the incidence of acute graft-versus-host disease (GvHD) after nonmyeloablative stem-cell transplantation (NMSCT). In this study, we analyze the effect of CD8 depletion or CD34 selection of the graft on early T-cell reconstitution. METHODS: Nonmyeloablative conditioning regimen consisted in 2 Gy total-body irradiation (TBI) alone, 2 Gy TBI and fludarabine, or cyclophosphamide and fludarabine. Patients 1 to 18 received unmanipulated PBSC, patients 19 to 29 CD8-depleted PBSC, and patients 30 to 35 CD34-selected PBSC. RESULTS: T-cell counts, and particularly CD4+ and CD4CD45RA+ counts, remained low the first 6 months after nonmyeloablative stem-cell transplantation (NMSCT) in all patients. CD34 selection (P<0.0001) but not CD8 depletion of PBSC significantly decreased T-cell chimerism. Donor T-cell count was similar in unmanipulated compared with CD8-depleted PBSC recipients but was significantly lower in CD34-selected PBSC recipients (P=0.0012). T cells of recipient origin remained stable over time in unmanipulated and CD8-depleted PBSC patients but expanded in some CD34-selected PBSC recipients between day 28 and 100 after transplant. Moreover, whereas CD8 depletion only decreased CD8+ counts (P<0.047), CD34 selection reduced CD3+(P<0.001), CD8+(P<0.016), CD4+ (P<0.001), and CD4+CD45RA+ (P<0.001) cell counts. T-cell repertoire was restricted in all patients on day 100 after hematopoietic stem-cell transplantation but was even more limited after CD34 selection (P=0.002). CONCLUSIONS: Despite of the persistence of a significant number of T cells of recipient origin, T-cell counts were low the first 6 months after NMSCT. Moreover, contrary with CD8 depletion of the graft that only affects CD8+ lymphocyte counts, CD34 selection dramatically decreased both CD8 and CD4 counts. [less ▲]

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See detailA low rate of trisomy 21 in twin-pregnancies: A cytogenetics retrospective study of 278 cases
Jamar, Mauricette ULg; Lemarchal, C.; Koulischer, Lucien ULg et al

in Genetic Counseling (2003), 14(4), 395-400

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See detailNF-κB transcription factor induces drug resistance through MDR1 expression in cancer cells
Bentires-Alj, Mohamed; Barbu, Véronique; Fillet, Marianne ULg et al

in Oncogene (2003), 22

The ubiquitous NF-kappaB transcription factor has been reported to inhibit apoptosis and to induce drug resistance in cancer cells. Drug resistance is the major reason for cancer therapy failure and ... [more ▼]

The ubiquitous NF-kappaB transcription factor has been reported to inhibit apoptosis and to induce drug resistance in cancer cells. Drug resistance is the major reason for cancer therapy failure and neoplastic cells often develop multiple mechanisms of drug resistance during tumor progression. We observed that NF-kappaB or P-glycoprotein inhibition in the HCT15 colon cancer cells led to increased apoptotic cell death in response to daunomycin treatment. Interestingly, NF-kappaB inhibition through transfection of a plasmid coding for a mutated IkappaB-alpha inhibitor increased daunomycin cell uptake. Indeed, the inhibition of NF-kappaB reduced mdr1 mRNA and P-glycoprotein expression in HCT15 cells. We identified a consensus NF-kappaB binding site in the first intron of the human mdr1 gene and demonstrated that NF-kappaB complexes could bind with this intronic site. Moreover, NF-kappaB transactivates an mdr1 promoter luciferase construct. Our data thus demonstrate a role for NF-kappaB in the regulation of the mdr1 gene expression in cancer cells and in drug resistance. [less ▲]

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See detailClonal chromosome aberrations in Philadelphia-negative cells from chronic myelocytic leukemia patients treated with imatinib mesylate: report of two cases.
Herens, Christian ULg; Baron, Frédéric ULg; Croisiau, Christiane et al

in Cancer Genetics & Cytogenetics (2003), 147(1), 78-80

Imatinib mesylate (tested as STI571), an abl kinase inhibitor, induces sustained, complete hematologic and cytogenetic responses in chronic myelocytic leukemia (CML) patients; however, emergence of clonal ... [more ▼]

Imatinib mesylate (tested as STI571), an abl kinase inhibitor, induces sustained, complete hematologic and cytogenetic responses in chronic myelocytic leukemia (CML) patients; however, emergence of clonal chromosomal aberrations in Philadelphia-negative (Ph-) cells during treatment has been reported. We describe two CML patients in chronic phase who presented with complete cytogenetic responses during imatinib mesylate therapy but developed new clonal chromosomal rearrangements in Ph- cells. The first patient presented with a duplication of chromosome 1, dup(1)(q21q42), and the second showed two new clonal aberrations consisting of inv(1)(q12q32) and del(7)(q22) in the same clone. [less ▲]

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