References of "Bours, Vincent"
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See detailIntegration de la pharmacogenetique dans la pratique medicale
Dideberg, Vinciane ULg; Bours, Vincent ULg

in Revue Médicale de Liège (2005), 60(12), 918-22

Today, the initiation of any medical treatment still raises questions about its efficacy and safety. Indeed, therapeutic responses vary over time and between individuals and are influenced by age, sex ... [more ▼]

Today, the initiation of any medical treatment still raises questions about its efficacy and safety. Indeed, therapeutic responses vary over time and between individuals and are influenced by age, sex, other treatments and the pathology itself. Genetic factors are thought to be responsible for 20 to 95% of these individual variations. Recent advances in biotechnology, molecular genetics and genomics allow a better understanding of drug metabolism and action. Pharmacogenetics, compiling phenotypic and genotypic data, may lead to a more personalized treatment. To allow a better approach of pharmacogenetics and pharmacogenomics, we will define these two terms and describe their actual and future clinical application. [less ▲]

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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 detailDeletions of the 3 ' BCR and 5 ' ABL regions in patients with Philadelphia-positive chronic myeloid leukemia: a one-step process occurring in about 10% of the cases without any evidence of genetic instability in the target cells
Fournier, M.; Lacrosse, S.; Jamar, Mauricette ULg et al

in Cancer Genetics & Cytogenetics (2005), 160(2), 184-187

Deletions of the 5' ABL region adjacent to the t(9;22)(q34;q11) have recently been reported in 8-32.7% of patients with chronic myeloid leukemia (CML). The deletions were visualized with fluorescence in ... [more ▼]

Deletions of the 5' ABL region adjacent to the t(9;22)(q34;q11) have recently been reported in 8-32.7% of patients with chronic myeloid leukemia (CML). The deletions were visualized with fluorescence in situ hybridization using, in the majority of the cases, the Vysis LSI BCR/ABL ES (extra signal) probe. In our series, 10 of 99 CML patients (10.1%) were characterized by a 5'ABL deletion. We show that 3' BCR losses are observed in nearly all the cases with 5' ABL deletions. Moreover, the different genetic events (Philadelphia chromosome formation; 5' ABL and 3' BCR deletions) occur simultaneously in a one-step process without any evidence for genetic instability in the target bone marrow cells. (c) 2005 Elsevier Inc. All rights reserved. [less ▲]

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See detailLow daunomycin concentrations protect colorectal cancer cells from hypoxia-induced apoptosis
Lechanteur, Chantal ULg; Jacobs, Nathalie ULg; Greimers, Roland ULg et al

in Oncogene (2005), 24(10), 1788-1793

Hypoxia, a common feature of solid tumors, is a direct stress that triggers apoptosis in many cell types. Poor or irregular tumor vascularization also leads to a decreased drug diffusion and cancer cells ... [more ▼]

Hypoxia, a common feature of solid tumors, is a direct stress that triggers apoptosis in many cell types. Poor or irregular tumor vascularization also leads to a decreased drug diffusion and cancer cells distant from blood vessels (hypoxic cells) are exposed to low drug concentrations. In this report, we show that low daunomycin concentrations protect HCT116 colorectal cancer cells from hypoxia-induced apoptosis. While hypoxia induced p53 accumulation without expression of its responsive genes (bax and p21), daunomycin treatment restored p53 transactivation activity and cell cycle progression. We also demonstrated a role for Akt activation in daunomycin-induced protection through phosphorylation and inactivation of the Bcl-2 family proapoptotic factor Bad. Our data therefore suggest that chemotherapy could possibly, because of low concentrations in poorly vascularized tumors, protect cancer cells from hypoxia-induced cytotoxicity. [less ▲]

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See detailPhosphorylation of NF-kappa B and I kappa B proteins: implications in cancer and inflammation
Viatour, Patrick ULg; Merville, Marie-Paule ULg; Bours, Vincent ULg et al

in Trends in Biochemical Sciences (2005), 30(1), 43-52

Nuclear factor-kappaB (NF-kappaB) is a transcription factor that has crucial roles in inflammation, immunity, cell proliferation and apoptosis. Activation of NF-kappaB mainly occurs via IkappaB kinase ... [more ▼]

Nuclear factor-kappaB (NF-kappaB) is a transcription factor that has crucial roles in inflammation, immunity, cell proliferation and apoptosis. Activation of NF-kappaB mainly occurs via IkappaB kinase (IKK)-mediated phosphorylation of inhibitory molecules, including IkappaBalpha. Optimal induction of NF-kappaB target genes also requires phosphorylation of NF-kappaB proteins, such as p65, within their transactivation domain by a variety of kinases in response to distinct stimuli. Whether, and how, phosphorylation modulates the function of other NF-kappaB and IkappaB proteins, such as B-cell lymphoma 3, remains unclear. The identification and characterization of all the kinases known to phosphorylate NF-kappaB and IkappaB proteins are described here. Because deregulation of NF-kappaB and IkappaB phosphorylations is a hallmark of chronic inflammatory diseases and cancer, newly designed drugs targeting these constitutively activated signalling pathways represent promising therapeutic tools. [less ▲]

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See detailInterleukin-6 receptor shedding is enhanced by interleukin-1beta and tumor necrosis factor alpha and is partially mediated by tumor necrosis factor alpha-converting enzyme in osteoblast-like cells.
Franchimont, Nathalie; Lambert, Cécile ULg; Huynen, Pascale ULg et al

in Arthritis and Rheumatism (2005), 52(1), 84-93

OBJECTIVE: Interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) activation of gp130 represents an alternative pathway for osteoclast development in inflammatory conditions. The goal of the present ... [more ▼]

OBJECTIVE: Interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) activation of gp130 represents an alternative pathway for osteoclast development in inflammatory conditions. The goal of the present study was to investigate changes in sIL-6R levels in response to the inflammatory cytokines IL-1beta and tumor necrosis factor alpha (TNFalpha) and to determine the role of TNFalpha-converting enzyme (TACE) in this process. METHODS: Levels of sIL-6R in the culture media of MG63 and SAOS-2 osteoblast-like cell lines after exposure to various agents were determined by immunoassay. TACE protein levels were measured by Western immunoblotting. Cells were transfected with small interfering RNA (siRNA) or with an expression plasmid for IL-6R and TACE to determine the potential involvement of TACE in IL-6R shedding. RESULTS: IL-1beta and TNFalpha increased the levels of sIL-6R in the culture media of MG63 osteoblast-like cells. This effect was not influenced by cycloheximide or 5,6-dichlorobenzimidazole riboside but was markedly inhibited by the calcium chelator EGTA and by the TACE and matrix metalloproteinase inhibitor hydroxamate (Ru36156). IL-1beta and TNFalpha had no influence on the alternatively spliced form of IL-6R RNA. Levels of sIL-6R were reduced when MG63 cells were transiently transfected with TACE siRNA. Transfection of SAOS-2 cells with expression plasmids for IL-6R and TACE produced a dose-dependent increase in sIL-6R levels. CONCLUSION: IL-1beta- and TNFalpha-mediated induction of IL-6R shedding in osteoblast-like cells is at least partly dependent on TACE activation. [less ▲]

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See detailDexamethasone inhibits the HSV-tk/ ganciclovir bystander effect in malignant glioma cells.
Robe, Pierre ULg; Nguyen-Khac, Minh-Tuan ULg; Jolois, Olivier ULg et al

in BMC Cancer (2005), 5

BACKGROUND: HSV-tk/ ganciclovir (GCV) gene therapy has been extensively studied in the setting of brain tumors and largely relies on the bystander effect. Large studies have however failed to demonstrate ... [more ▼]

BACKGROUND: HSV-tk/ ganciclovir (GCV) gene therapy has been extensively studied in the setting of brain tumors and largely relies on the bystander effect. Large studies have however failed to demonstrate any significant benefit of this strategy in the treatment of human brain tumors. Since dexamethasone is a frequently used symptomatic treatment for malignant gliomas, its interaction with the bystander effect and the overall efficacy of HSV-TK gene therapy ought to be assessed. METHODS: Stable clones of TK-expressing U87, C6 and LN18 cells were generated and their bystander effect on wild type cells was assessed. The effects of dexamethasone on cell proliferation and sensitivity to ganciclovir were assessed with a thymidine incorporation assay and a MTT test. Gap junction mediated intercellular communication was assessed with microinjections and FACS analysis of calcein transfer. The effect of dexamethasone treatment on the sensitivity of TK-expressing to FAS-dependent apoptosis in the presence or absence of ganciclovir was assessed with an MTT test. Western blot was used to evidence the effect of dexamethasone on the expression of Cx43, CD95, CIAP2 and BclXL. RESULTS: Dexamethasone significantly reduced the bystander effect in TK-expressing C6, LN18 and U87 cells. This inhibition results from a reduction of the gap junction mediated intercellular communication of these cells (GJIC), from an inhibition of their growth and thymidine incorporation and from a modulation of the apoptotic cascade. CONCLUSION: The overall efficacy of HSV-TK gene therapy is adversely affected by dexamethasone co-treatment in vitro. Future HSV-tk/ GCV gene therapy clinical protocols for gliomas should address this interference of corticosteroid treatment. [less ▲]

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See detailDiscovery of new rheumatoid arthritis biomarkers using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry ProteinChip approach.
De Seny, Dominique ULg; Fillet, Marianne ULg; Meuwis, Marie-Alice ULg et al

in Arthritis and Rheumatism (2005), 52(12), 3801-12

OBJECTIVE: To identify serum protein biomarkers specific for rheumatoid arthritis (RA), using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology ... [more ▼]

OBJECTIVE: To identify serum protein biomarkers specific for rheumatoid arthritis (RA), using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology. METHODS: A total of 103 serum samples from patients and healthy controls were analyzed. Thirty-four of the patients had a diagnosis of RA, based on the American College of Rheumatology criteria. The inflammation control group comprised 20 patients with psoriatic arthritis (PsA), 9 with asthma, and 10 with Crohn's disease. The noninflammation control group comprised 14 patients with knee osteoarthritis and 16 healthy control subjects. Serum protein profiles were obtained by SELDI-TOF-MS and compared in order to identify new biomarkers specific for RA. Data were analyzed by a machine learning algorithm called decision tree boosting, according to different preprocessing steps. RESULTS: The most discriminative mass/charge (m/z) values serving as potential biomarkers for RA were identified on arrays for both patients with RA versus controls and patients with RA versus patients with PsA. From among several candidates, the following peaks were highlighted: m/z values of 2,924 (RA versus controls on H4 arrays), 10,832 and 11,632 (RA versus controls on CM10 arrays), 4,824 (RA versus PsA on H4 arrays), and 4,666 (RA versus PsA on CM10 arrays). Positive results of proteomic analysis were associated with positive results of the anti-cyclic citrullinated peptide test. Our observations suggested that the 10,832 peak could represent myeloid-related protein 8. CONCLUSION: SELDI-TOF-MS technology allows rapid analysis of many serum samples, and use of decision tree boosting analysis as the main statistical method allowed us to propose a pattern of protein peaks specific for RA. [less ▲]

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See detailSodium nitroprusside-induced osteoblast apoptosis is mediated by long chain ceramide and is decreased by raloxifene.
Olivier, Sabine ULg; Fillet, Marianne ULg; Malaise, Michel ULg et al

in Biochemical Pharmacology (2005), 69(6), 891-901

Release of high levels of nitric oxide (NO) is associated with osteoblastic cell death. The mechanisms of NO-induced cytotoxicity are not well documented and it is presently not known if estrogenic ... [more ▼]

Release of high levels of nitric oxide (NO) is associated with osteoblastic cell death. The mechanisms of NO-induced cytotoxicity are not well documented and it is presently not known if estrogenic compounds prevent this effect. We studied the role of ceramides in cell death induced by the NO donor sodium nitroprusside (SNP) and we tested the possibility that 17beta-estradiol, the anti-estrogen ICI 182.780 and two selective estrogen receptor modulators raloxifene and tamoxifen modify osteoblastic cell apoptosis. SNP dose-dependently decreased MC3T3-E1 osteoblast viability, increased NO production in the culture media and enhanced the release of intracellular ceramides C22 and C24. Cell death induced by SNP was partially inhibited when MC3T3-E1 cells were pretreated with raloxifene and tamoxifen but was not modified when the cells were pretreated with 17beta-estradiol or ICI 182.780. Cell death induced by SNP resulted from apoptosis as demonstrated by Annexin-V and propidium iodide labeling and a reduction of SNP-induced MC3T3-E1 apoptosis was confirmed in the presence of raloxifene and tamoxifen. SNP induction of C22 and C24 production was inhibited by a pretreatment with raloxifene but not with 17beta-estradiol. Moreover, the synthetic ceramide C24 (0.75 and 1microM) decreased MC3T3-E1 cell viability and osteoblast cell death induced by C24 was partially decreased by raloxifene and to a lesser extent by 17beta-estradiol. These data demonstrate that SNP-induced cell death is mediated by the long chain ceramides C22 and C24 and that raloxifene protected osteoblast from apoptosis induced by SNP, an effect that might be relevant to its pharmacological properties on bone remodeling. [less ▲]

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See detailIncreased expression of receptor activator of NF-kappa B ligand (RANKL), its receptor RANK and its decoy receptor osteoprotegerin in the colon of Crohn's disease patients
Franchimont, N.; Reenaers, Catherine ULg; Lambert, Chantal ULg et al

in Clinical & Experimental Immunology (2004), 138(3), 491-498

Crohn's disease (CD) is associated with low bone mass due to chronic inflammation and other factors. Receptor activator of NF-kappaB ligand (RANKL), its receptor RANK and its decoy receptor ... [more ▼]

Crohn's disease (CD) is associated with low bone mass due to chronic inflammation and other factors. Receptor activator of NF-kappaB ligand (RANKL), its receptor RANK and its decoy receptor osteoprotegerin (OPG) are potentially involved in this process as they regulate osteoclastogenesis and are influenced by pro-inflammatory cytokines. The aim of this study was to determine the levels of soluble RANKL (sRANKL), RANK and OPG expression both in the serum and in the colon of CD patients. Levels of sRANKL and OPG were assessed in the serum and the supernatants of cultured colonic biopsies in patients with CD and controls by ELISA. RANK expression was explored by immunostaining and immunofluorescence of fixed colonic samples. OPG and sRANKL levels were higher in the serum of CD patients as compared to age- and sex-matched controls. Levels of sRANKL and OPG were significantly enhanced in cultured colonic biopsies from CD, and OPG levels correlated with histological inflammation, and pro- and anti-inflammatory cytokine levels. No significant correlation was found for sRANKL. RANK(+) cells were increased in the colon of CD, particularly in inflamed areas. These cells were positive for CD68 or S100 protein. We conclude that serum and local levels of sRANKL and OPG are increased in CD. Moreover, RANK is expressed in the colonic mucosa by subpopulations of activated macrophages or dendritic cells at higher levels in CD compared to normal colon. [less ▲]

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See detailProtein phosphorylation as a key mechanism for the regulation of BCL-3 activity
Viatour, Patrick ULg; Merville, Marie-Paule ULg; Bours, Vincent ULg et al

in Cell Cycle (Georgetown, Tex.) (2004), 3(12), 1498-1501

Constitutive NF-kappaB activation, a hallmark of many human cancers, upregulates anti-apoptotic gene expression and therefore disrupts the balance between apoptosis and proliferation. In some lymphomas ... [more ▼]

Constitutive NF-kappaB activation, a hallmark of many human cancers, upregulates anti-apoptotic gene expression and therefore disrupts the balance between apoptosis and proliferation. In some lymphomas, this constitutive NF-kappaB activity is the result of point mutations or translocations of the genes coding for NF-kappaB inhibitors, namely IkappaBalpha or p100. The BCL-3 protein is another member of the IkappaB family and is overexpressed in a subset of human B-cell chronic lymphocytic leukemias because of a chromosomal translocation. This oncoprotein is phosphorylated by multiple kinases including GSK3 and this phosphorylation regulates BCL-3 function by modulating its oncogenic potential and by regulating the expression of a subset of its target genes. Therefore, deciphering the NF-kappaB/IkappaB protein phosphorylations is critical in order to better understand the molecular mechanisms of NF-kappaB-mediated oncogenesis. [less ▲]

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See detailGSK3-Mediated BCL-3 phosphorylation modulates its degradation and its oncogenicity
Viatour, Patrick ULg; Dejardin, Emmanuel ULg; Warnier, Michael et al

in Molecular Cell (2004), 16(1), 35-45

The oncoprotein BCL-3 is a nuclear transcription factor that activates NF-kappaB target genes through formation of heterocomplexes with p50 or p52. BCL-3 is phosphorylated in vivo, but specific BCL-3 ... [more ▼]

The oncoprotein BCL-3 is a nuclear transcription factor that activates NF-kappaB target genes through formation of heterocomplexes with p50 or p52. BCL-3 is phosphorylated in vivo, but specific BCL-3 kinases have not been identified so far. In this report, we show that BCL-3 is a substrate for the protein kinase GSK3 and that GSK3-mediated BCL-3 phosphorylation, which is inhibited by Akt activation, targets its degradation through the proteasome pathway. This phosphorylation modulates its association with HDAC1, -3, and -6 and attenuates its oncogenicity by selectively controlling the expression of a subset of newly identified target genes such as SLPI and CxcI1. Our results therefore suggest that constitutive BCL-3 phosphorylation by GSK3 regulates BCL-3 turnover and transcriptional activity. [less ▲]

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See detailDiscovery of new rheumatoid arthritis biomarkers using SELDI-TOF-MS ProteinChip approach
de Seny, D. M.; Fillet, Marianne ULg; Meuwis, Marie-Alice ULg et al

in Arthritis and Rheumatism (2004, September), 50(9, Suppl. S), 124

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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 (vol 23, pg 6200, 2003)
Adam, Emmanuelle; Quivy, Vincent; Bex, Françoise et al

in Molecular and Cellular Biology (2004), 24(15), 6890

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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 detailCaspase-8-dependent HER-2 cleavage in response to tumor necrosis factor alpha stimulation is counteracted by nuclear factor kappa B through c-FLIP-L expression
Benoit, Valérie; Chariot, Alain ULg; Delacroix, Laurence ULg et al

in Cancer Research (2004), 64(8), 2684-2691

The oncoprotein HER-2/neu is a prosurvival factor, and its overexpression has been correlated with poor prognosis in patients with breast cancer. We report that HER-2 is a new substrate for caspase-8 and ... [more ▼]

The oncoprotein HER-2/neu is a prosurvival factor, and its overexpression has been correlated with poor prognosis in patients with breast cancer. We report that HER-2 is a new substrate for caspase-8 and that tumor necrosis factor alpha (TNF-alpha) stimulation leads to an early caspase-8-dependent HER-2 cleavage in MCF7 A/Z breast adenocarcinoma cells defective for nuclear factor kappaB (NFkappaB) activation. We show that the antiapoptotic transcription factor NFkappaB counteracts this cleavage through induction of the caspase-8 inhibitor c-FLIP. Our results also demonstrate that this HER-2 cleavage contributes to the TNF-alpha-induced apoptosis pathway because ectopic expression of an uncleavable HER-2 protects NFkappaB-defective cells against TNF-alpha-mediated cell death. Therefore, we propose an original model in which NFkappaB exerts a new antiapoptotic function by counteracting TNF-alpha-triggered cleavage of the HER-2 survival factor. [less ▲]

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See detail15-deoxy-delta12,14-prostaglandin J2 inhibits Bay 11-7085-induced sustained extracellular signal-regulated kinase phosphorylation and apoptosis in human articular chondrocytes and synovial fibroblasts
Relic, Biserka ULg; Benoit, Valerie; Franchimont, Nathalie et al

in Journal of Biological Chemistry (2004), 279(21), 399-403

We have previously shown that nuclear factor-kappaB inhibition by adenovirus expressing mutated IkappaB-alpha or by proteasome inhibitor increases human articular chondrocytes sensibility to apoptosis ... [more ▼]

We have previously shown that nuclear factor-kappaB inhibition by adenovirus expressing mutated IkappaB-alpha or by proteasome inhibitor increases human articular chondrocytes sensibility to apoptosis. Moreover, the nuclear factor-kappaB inhibitor BAY11-7085, a potent anti-inflammatory drug in rat adjuvant arthritis, is itself a proapoptotic agent for chondrocytes. In this work, we show that BAY 11-7085 but not the proteasome inhibitor MG-132 induced a rapid and sustained phosphorylation of extracellular signal-regulated kinases (ERK1/2) in human articular chondrocytes. The level of ERK1/2 phosphorylation correlated with BAY 11-7085 concentration and chondrocyte apoptosis. 15-Deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) and its precursor prostaglandin (PG) D2 but not PGE2 and PGF2alpha rescued chondrocytes from BAY 11-7085-induced apoptosis. 15d-PGJ2 markedly inhibited BAY 11-7085-induced phosphorylation of ERK1/2. BAY 11-7085 also induced ERK1/2 phosphorylation and apoptosis in human synovial fibroblasts, and these reactions were down-regulated by 15d-PGJ2. Further analysis in synovial fibroblasts showed that only molecules that suppressed BAY 11-7085-induced phosphorylation of ERK1/2 (i.e. 15d-PGJ2, PGD2, and to a lesser extent, MEK1/2 inhibitor UO126, but not prostaglandins E2 and F2alpha or peroxisome proliferator-activated receptor-gamma agonist ciglitazone) were able protect cells from apoptosis. These results suggested that the antiapoptotic effect of 15d-PGJ2 on chondrocytes and synovial fibroblasts might involve inhibition of ERK1/2 phosphorylation. [less ▲]

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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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