References of "Bours, Vincent"
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See detailRadiofrequency ablation of liver tumors: short term evaluation
Detry, Olivier ULg; Detroz, Bernard ULg; Preud'Homme, Laurence ULg et al

in Acta Gastro-Enterologica Belgica (2001, January), 64(1), 11

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See detailOzone adaptation in calves is associated with impaired accumulation of granulocytes in the lung
Fievez, Laurence ULg; Kirschvink, Nathalie; Dogné, S. et al

in Proceedings: Comparative Respiratory Society Meeting (2001)

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See detailConstitutive NF-kappaB activity preserves homeostasis of quiescent mature lymphocytes and granulocytes by controlling the expression of distinct Bcl-2 family proteins
Bureau, Fabrice ULg; Vanderplasschen, Alain ULg; Jaspar, F. et al

in Proceedings: International Symposium: NF-kappaB: Regulation, Gene Expression & Disease (2001)

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See detailRoles of Nuclear Factor-Kappab, P53, and P21/Waf1 in Daunomycin-Induced Cell Cycle Arrest and Apoptosis
Hellin, A. C.; Bentires-Alj, M.; Verlaet, Myriam ULg et al

in Journal of Pharmacology and Experimental Therapeutics (The) (2000), 295(3), 870-8

Daunomycin is a potent inducer of p53 and NF-kappaB transcription factors. It is also able to increase the amount of the p21 cyclin-dependent kinase inhibitor. The human p21 promoter harbors p53 ... [more ▼]

Daunomycin is a potent inducer of p53 and NF-kappaB transcription factors. It is also able to increase the amount of the p21 cyclin-dependent kinase inhibitor. The human p21 promoter harbors p53-responsive elements and an NF-kappaB binding site. [less ▲]

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See detailNf-Kappab Activation in Response to Toxical and Therapeutical Agents: Role in Inflammation and Cancer Treatment
Bours, Vincent ULg; Bonizzi, Giuseppina; Bentires-Alj, Mohamed et al

in Toxicology (2000), 153(1-3), 27-38

The NF-kappaB transcription factor is ubiquitously expressed and controls the expression of a large number of genes. Experimental data clearly indicate that NF-kappaB is a major regulator of the ... [more ▼]

The NF-kappaB transcription factor is ubiquitously expressed and controls the expression of a large number of genes. Experimental data clearly indicate that NF-kappaB is a major regulator of the inflammatory reaction by controlling the expression of pro-inflammatory molecules in response to cytokines, oxidative stress and infectious agents. We demonstrated that NF-kappaB activation by IL-1beta follows three distinct cell-specific pathways. Moreover, our studies indicated that in one model of inflammatory diseases, horse recurrent airway obstruction (RAO), the extent of NF-kappaB basal activity correlates with pulmonary dysfunction. Another role of NF-kappaB activity protects cancer cells against apoptosis and could participate in the resistance to cancer treatment. However, we did not observe any increased cytotoxicity after treatment with anticancer drugs or TNF-alpha of cells expressing a NF-kappaB inhibitor. Therefore, we can conclude that the inhibition of apoptosis by NF-kappaB is likely to be cell type and stimulus-dependent. Further studies are required to determine whether NF-kappaB could be a target for anticancer treatments. [less ▲]

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See detailMechanisms of Persistent Nf-Kappa B Activity in the Bronchi of an Animal Model of Asthma
Bureau, Fabrice ULg; Delhalle, Sylvie; Bonizzi, Giuseppina et al

in Journal of Immunology (2000), 165(10), 5822-5830

In most cells trans-activating NF-kappaB induces many inflammatory proteins as well as its own inhibitor, IkappaB-alpha, thus assuring a transient response upon stimulation. However, NF-kappaB-dependent ... [more ▼]

In most cells trans-activating NF-kappaB induces many inflammatory proteins as well as its own inhibitor, IkappaB-alpha, thus assuring a transient response upon stimulation. However, NF-kappaB-dependent inflammatory gene expression is persistent in asthmatic bronchi, even after allergen eviction. In the present report we used bronchial brushing samples (BBSs) from heaves-affected horses (a spontaneous model of asthma) to elucidate the mechanisms by which NF-kappaB activity is maintained in asthmatic airways. NF-kappaB activity was high in granulocytic and nongranulocytic BBS cells. However, NF-kappaB activity highly correlated to granulocyte percentage and was only abrogated after granulocytic death in cultured BBSs. Before granulocytic death, NF-kappaB activity was suppressed by simultaneous addition of neutralizing anti-IL-1beta and anti-TNF-alpha Abs to the medium of cultured BBSs. Surprisingly, IkappaB-beta, whose expression is not regulated by NF-kappaB, unlike IkappaB-alpha, was the most prominent NF-kappaB inhibitor found in BBSs. The amounts of IkappaB-beta were low in BBSs obtained from diseased horses, but drastically increased after addition of the neutralizing anti-IL-1beta and anti-TNF-alpha Abs. These results indicate that sustained NF-kappaB activation in asthmatic bronchi is driven by granulocytes and is mediated by IL-1beta and TNF-alpha. Moreover, an imbalance between high levels of IL-1beta- and TNF-alpha-mediated IkappaB-beta degradation and low levels of IkappaB-beta synthesis is likely to be the mechanism preventing NF-kappaB deactivation in asthmatic airways before granulocytic death. [less ▲]

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See detailNuclear Factor-Kappa B, Cancer, and Apoptosis
Bours, Vincent ULg; Bentires-Alj, M.; Hellin, A. C. et al

in Biochemical Pharmacology (2000), 60(8), 1085-9

The role of nuclear factor (NF)-kappa B in the regulation of apoptosis in normal and cancer cells has been extensively studied in recent years. Constitutive NF-kappa B activity in B lymphocytes as well as ... [more ▼]

The role of nuclear factor (NF)-kappa B in the regulation of apoptosis in normal and cancer cells has been extensively studied in recent years. Constitutive NF-kappa B activity in B lymphocytes as well as in Hodgkin's disease and breast cancer cells protects these cells against apoptosis. It has also been reported that NF-kappa B activation by tumor necrosis factor (TNF)-alpha, chemotherapeutic drugs, or ionizing radiations can protect several cell types against apoptosis, suggesting that NF-kappa B could participate in resistance to cancer treatment. These observations were explained by the regulation of antiapoptotic gene expression by NF-kappa B. However, in our experience, inhibition of NF-kappa B activity in several cancer cell lines has a very variable effect on cell mortality, depending on the cell type, the stimulus, and the level of NF-kappa B inhibition. Moreover, in some experimental systems, NF-kappa B activation is required for the onset of apoptosis. Therefore, it is likely that the NF-kappa B antiapoptotic role in response to chemotherapy is cell type- and signal-dependent and that the level of NF-kappa B inhibition is important. These issues will have to be carefully investigated before considering NF-kappa B as a target for genetic or pharmacological anticancer therapies. [less ▲]

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See detailAdditive Effect between Nf-Kappab Subunits and P53 Protein for Transcriptional Activation of Human P53 Promoter
Benoit, V.; Hellin, A. C.; Huygen, S. et al

in Oncogene (2000), 19(41), 4787-94

The tumor suppressor p53 plays a pivotal role in the cellular response to DNA damage as it controls DNA repair, cell cycle arrest and apoptosis. We studied the autoregulation of human p53 gene ... [more ▼]

The tumor suppressor p53 plays a pivotal role in the cellular response to DNA damage as it controls DNA repair, cell cycle arrest and apoptosis. We studied the autoregulation of human p53 gene transcription in colon cancer cell lines. Wild-type p53 has been shown to autoregulate its own transcription either positively or negatively and probably in a cell-type-specific manner. Indeed, a p53 binding site has been described in the human and murine p53 promoters, but a direct binding of wild-type p53 protein to this site has never been reported. In this study, we demonstrated a transactivation of human p53 promoter by wild-type p53 in human colon cancer cells. We identified in the human p53 promoter a novel potential p53-responsive element that binds wild-type p53. Moreover, wild-type p53 protein transactivated a reporter plasmid containing a luciferase gene driven by a minimal promoter harboring this p53 binding site. Finally, as the p53 promoter contains an NF-kappaB binding site, we demonstrated an additive effect when NF-kappaB subunits and p53 protein combined to transactivate the human p53 promoter. [less ▲]

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See detailGrowth Regulation of Astrocytes and C6 Cells by Tgfbeta1: Correlation with Gap Junctions
Robe, Pierre ULg; Rogister, Bernard ULg; Merville, Marie-Paule ULg et al

in Neuroreport (2000), 11(13), 2837-41

Transforming growth factor (TGF) beta1 enhanced in vitro [3H]thymidine incorporation into C6 cells and reduced that of astrocytes in the presence of a high serum concentration. It concomitantly raised the ... [more ▼]

Transforming growth factor (TGF) beta1 enhanced in vitro [3H]thymidine incorporation into C6 cells and reduced that of astrocytes in the presence of a high serum concentration. It concomitantly raised the gap junction intercellular communication (GJIC) in normal astrocytes but reduced the coupling of C6 cells, and respectively increased or decreased the proportion of P2-phosphorylated connexin (Cx) 43 isoform in these cells. Finally, octanol, which inhibited GJIC in both cell types, increased the thymidine incorporation in C6 cells, but neither altered the proliferation of astrocytes nor their response to TGFbeta1. These data indicate that an inhibition of gap junction intercellular communication, due to an altered phosphorylation of connexin 43, may contribute to the proliferative response of C6 glioblastoma cells to TGFbeta1. [less ▲]

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See detailCombined Suicide and Cytokine Gene Therapy for Peritoneal Carcinomatosis
Lechanteur, Chantal ULg; Delvenne, Philippe ULg; Princen, Frédéric et al

in Gut (2000), 47(3), 343-8

BACKGROUND: Gene therapy is a novel approach for the treatment of cancers, and tumours disseminated in the peritoneal cavity are suitable for in situ delivery of a therapeutic gene. AIMS: The efficacy of ... [more ▼]

BACKGROUND: Gene therapy is a novel approach for the treatment of cancers, and tumours disseminated in the peritoneal cavity are suitable for in situ delivery of a therapeutic gene. AIMS: The efficacy of a therapy combining a suicide gene (herpes simplex virus type I thymidine kinase (HSV-TK)) and cytokine genes was investigated in a model of peritoneal carcinomatosis induced by colon carcinoma cells in syngeneic rats. MATERIAL AND METHODS: Pre-established macroscopic tumours in BDIX rats were treated by intraperitoneal injections of retrovirus producing cells (FLYA13 TK, FLYA13 granulocyte macrophage-colony stimulating factor (GM-CSF), FLYA13 interleukin 12 (IL-12)) and ganciclovir (GCV). RESULTS: TK/GCV treated animals showed a slight increase in survival time (72 days) compared with the control group (63 days) while the association of cytokine and TK/GCV gene therapy resulted in significantly improved survival, with a large proportion of animals remaining tumour free on day 480 (60% and 40% for TK/GCV/GM-CSF and TK/GCV/IL-12 treated animals, respectively). Histological analysis of treated animals showed that the remaining tumour nodes were infiltrated by mononuclear cells but no major differences were observed between the various treatments. Immunohistochemical analysis revealed that lymphoid CD4(+) and CD8(+) T cells as well as macrophages accumulated outside untreated tumour nodes while CD8(+) and CD25(+) activated T cells and macrophages heavily infiltrated the tumours after the different treatments. CONCLUSIONS: Our data indicate that combined suicide and cytokine gene therapy is a powerful approach for the treatment of macroscopic peritoneal carcinomatosis. [less ▲]

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See detailPharmacological Modulation of the Bystander Effect in the Herpes Simplex Virus Thymidine Kinase/Ganciclovir Gene Therapy System: Effects of Dibutyryl Adenosine 3',5'-Cyclic Monophosphate, Alpha-Glycyrrhetinic Acid, and Cytosine Arabinoside
Robe, Pierre ULg; Princen, Frédéric; Martin, Didier ULg et al

in Biochemical Pharmacology (2000), 60(2), 241-9

The herpes simplex virus type 1 thymidine kinase (HSV1-tk) suicide gene/ganciclovir system was first applied to the treatment of glioblastoma tumors, but was hampered by the low gene transfection yield ... [more ▼]

The herpes simplex virus type 1 thymidine kinase (HSV1-tk) suicide gene/ganciclovir system was first applied to the treatment of glioblastoma tumors, but was hampered by the low gene transfection yield. Fortunately, the gap junction-dependent diffusion of phosphorylated ganciclovir metabolites from transfected cells to their neighbors proved to enhance the overall benefit of this strategy. However, as tumor cells are often gap junction-deficient, we sought to restore this property pharmacologically and hence to improve the efficacy of the treatment. We demonstrated that this approach was feasible in glioblastoma cells using dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) (100 microM) as a pharmacological inducer of gap junctions. alpha-Glycyrrhetinic acid (25 microM), on the other hand, strongly inhibited both gap junction-mediated intercellular communication and the bystander effect, thus confirming the role of gap junctions in HSV-tk-mediated bystander killing. Using cytosine arabinoside as a growth inhibitor, we underlined the role of tumor cell proliferation in the sensitivity of HSV-tk-transfected cells to ganciclovir and demonstrated its correlation with the importance of the bystander effect. [less ▲]

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See detailRecommandations en matiere de traitement du cancer rectal
Gast, Pierrette ULg; Bours, Vincent ULg; Detroz, Bernard ULg et al

in Revue Médicale de Liège (2000), 55(5), 350-5

Curative resection of primary tumor and metastases is the only way to obtain a prolonged survival. Several additional treatments are under evaluation; some are already routinely proposed, in order to ... [more ▼]

Curative resection of primary tumor and metastases is the only way to obtain a prolonged survival. Several additional treatments are under evaluation; some are already routinely proposed, in order to reduce the tumor size and to allow surgery, to reduce the recurrence rate, and to give a better survival in case of unresectable metastases. Even in case of unresectable metastases, resection of the primary tumor should be envisaged, as quality of life with an evolving rectal tumor is very poor. [less ▲]

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See detailAntitumoral Vaccination with Granulocyte-Macrophage Colony-Stimulating Factor or Interleukin-12-Expressing Dhd/K12 Colon Adenocarcinoma Cells
Lechanteur, Chantal ULg; Moutschen, Michel ULg; Princen, Frederic et al

in Cancer Gene Therapy (2000), 7(5), 676-82

Immunomodulating gene therapy for the treatment of malignant diseases is under extensive investigation. In this study, we induced an antitumoral immune response with murine interleukin-12 (mIL-12) and ... [more ▼]

Immunomodulating gene therapy for the treatment of malignant diseases is under extensive investigation. In this study, we induced an antitumoral immune response with murine interleukin-12 (mIL-12) and murine granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor cells in a model of peritoneal carcinomatosis. Intraperitoneal injection of DHD/K12 tumoral cells engineered to produce IL-12 or GM-CSF did not generate any tumors, whereas untransduced DHD/K12 cells gave rise to peritoneal carcinomatosis. IL-12-expressing DHD/K12 cells also protected against tumors derived from coinjected parental cells. To test whether cytokine-producing cells could elicit a memory antitumoral immune response, animals received a challenge with parental DHD/K12 cells 35 days after the injection of proliferating or irradiated DHD/K12 engineered cells. Under our experimental conditions, irradiated tumor cells did not generate any antitumoral immunity. In contrast, tumor development was delayed and survival increased in the animals vaccinated with cytokine-secreting proliferating cells. A specific cytotoxic T-lymphocyte response against DHD/K12 parental cells was observed after vaccination with GM-CSF-expressing cells. Our results demonstrated that intraperitoneal vaccination with IL-12- or GM-CSF-expressing adenocarcinoma cells induced a systemic immune antitumoral response that may be useful as an adjuvant therapy after surgical resection of colorectal cancer. [less ▲]

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See detailTraitement adjuvant du cancer du sein: meta-analyse et recommandations therapeutiques
Jerusalem, Guy ULg; Bours, Vincent ULg; Fillet, Georges ULg

in Revue Médicale de Liège (2000), 55(5), 356-9

Adjuvant chemotherapy and hormonotherapy have a major impact on relapse-free and overall survival of patients with early-stage breast cancer. Providing effective medical care for these patients is an ... [more ▼]

Adjuvant chemotherapy and hormonotherapy have a major impact on relapse-free and overall survival of patients with early-stage breast cancer. Providing effective medical care for these patients is an important public health issue. We reviewed the results of the meta-analysis performed by the "Early Breast Cancer Trialists' Cooperative Group". We summarize the recommendations and guidelines proposed by the International Consensus Panel during the St Gallen Conference, 1998. We discussed also the methodology used by the "Federation National des Centres de Lutte Contre le Cancer" in France to establish guidelines for the adjuvant treatment of breast cancer. Faster development and validation of effective treatments will only be possible if participation in clinical trials become more acceptable to the public as well as to the medical community. [less ▲]

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See detailCorrelation between Nuclear Factor-Kappab Activity in Bronchial Brushing Samples and Lung Dysfunction in an Animal Model of Asthma
Bureau, Fabrice ULg; Bonizzi, G.; Kirschvink, N. et al

in American Journal of Respiratory & Critical Care Medicine (2000), 161(4, Pt 1), 1314-1321

Asthma is a chronic inflammatory disease of the airways, in which many inflammatory genes are overexpressed. Transcription factor, nuclear factor-kappaB (NF-kappaB), which is thought to control the ... [more ▼]

Asthma is a chronic inflammatory disease of the airways, in which many inflammatory genes are overexpressed. Transcription factor, nuclear factor-kappaB (NF-kappaB), which is thought to control the transcriptional initiation of inflammatory genes, has been poorly investigated in asthma. In the present report, bronchial cells (BCs), recovered by bronchial brushing in healthy and heaves-affected horses (i.e., an animal model of asthma), were assessed for NF-kappaB activity. Small amounts of active NF-kappaB were present in BCs of healthy horses, whereas high levels of NF-kappaB activity was found during crisis (i.e., acute airway obstruction) in all heaves-affected horses. Three weeks after the crisis, the level of NF-kappaB activity found in BCs of heaves-affected horses was highly correlated (p < 0.01) to the degree of residual lung dysfunction. Unexpectedly, active NF- kappaB complexes found in BCs of heaves-affected horses were mainly p65 homodimers, rather than classic p65-p50 heterodimers. At last, intercellular adhesion molecule-1 (ICAM-1) expression paralleled p65 homodimers activity in these cells. These results demonstrate that the kinetics of NF-kappaB activity is strongly related to the course of the disease and confirm the relevance of NF-kappaB as a putative target in asthma therapy. Moreover, uncommon p65 homodimers could transactivate, in BCs, a subset of genes, such as ICAM-1, characteristic of chronic airway inflammation. [less ▲]

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See detailExiste-t-il des progres dans le traitement du cancer du pancreas metastatique?
Jerusalem, Guy ULg; Bours, Vincent ULg; Fillet, Georges ULg

in Revue Médicale de Liège (2000), 55(3), 146-8

Pancreatic cancer is one of the most lethal cancers in the western world. The authors review the different chemotherapeutic regimens for the palliative approach of this disease. 5-fluorouracil has been ... [more ▼]

Pancreatic cancer is one of the most lethal cancers in the western world. The authors review the different chemotherapeutic regimens for the palliative approach of this disease. 5-fluorouracil has been the only drug with some efficacy for a longtime. Recently a clinical benefit has been obtained with gemcitabine. Polychemotherapy regimens based on gemcitabine, 5-fluorouracil, cisplatin and/or epirubicin have been administered in clinical phase II trials. The superiority of polychemotherapy in terms of palliative benefits or survival is uncertain. Palliative care remains an important issue. [less ▲]

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See detailCell Type-Specific Role for Reactive Oxygen Species in Nuclear Factor-Kappab Activation by Interleukin-1
Bonizzi, G.; Piette, Jacques ULg; Merville, Marie-Paule ULg et al

in Biochemical Pharmacology (2000), 59(1), 7-11

The role of reactive oxygen intermediates (ROIs) in nuclear factor-kappaB (NF-kappaB) activation remains a matter of controversy. We have studied whether ROIs played any role in NF-kappaB induction by ... [more ▼]

The role of reactive oxygen intermediates (ROIs) in nuclear factor-kappaB (NF-kappaB) activation remains a matter of controversy. We have studied whether ROIs played any role in NF-kappaB induction by interleukin-1beta (IL-1beta) in different cell types. Our studies indicated three different pathways. IL-1beta stimulation of lymphoid cells generates ROIs, which are required for IkappaB-alpha degradation and NF-kappaB activation. The source of these ROIs is the 5-lipoxygenase (5-LOX) enzyme. In monocytic cells, ROIs are also produced in response to IL-1beta and necessary for NF-kappaB induction, but their source appears to be the NADPH oxidase complex. Finally, epithelial cells do not generate ROIs after IL-1beta stimulation, but do rapidly activate NF-kappaB. Interestingly, transfection of epithelial cells with the 5-LOX and 5-LOX activating protein expression vectors restored ROI production and ROI-dependent NF-kappaB activation in response to IL-1beta. Our data thus indicate that ROIs are cell type-specific second messengers for NF-kappaB induction by IL-1beta. [less ▲]

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See detailCytosine Deaminase Suicide Gene Therapy for Peritoneal Carcinomatosis
Bentires-Alj, M.; Hellin, A. C.; Lechanteur, Chantal ULg et al

in Cancer Gene Therapy (2000), 7(1), 20-6

Gene therapy is a novel therapeutic approach that might soon improve the prognosis of some cancers. We investigated the feasibility of cytosine deaminase (CD) suicide gene therapy in a model of peritoneal ... [more ▼]

Gene therapy is a novel therapeutic approach that might soon improve the prognosis of some cancers. We investigated the feasibility of cytosine deaminase (CD) suicide gene therapy in a model of peritoneal carcinomatosis. DHD/K12 colorectal adenocarcinoma cells transfected in vitro with the CD gene were highly sensitive to 5-fluorocytosine (5-FC), and a bystander effect could also be observed. Treating CD+ cells with 5-FC resulted in apoptosis as detected by terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling. In vitro, several human cell lines derived from ovarian or colorectal carcinomas, as well as the rat glioblastoma 9 L cell line, responded to CD/5-FC and showed a very strong bystander effect. 5-FC treatment of peritoneal carcinomatosis generated in syngeneic BDIX rats by CD-expressing DHD/K12 cells led to a complete and prolonged response and to prolonged survival. Our study thus demonstrated the efficacy of CD suicide gene therapy for the treatment of peritoneal carcinomatosis. [less ▲]

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See detailTnp-470, a Potent Angiogenesis Inhibitor, Amplifies Human T Lymphocyte Activation through an Induction of Nuclear Factor-Kappab, Nuclear Factor-at, and Activation Protein-1 Transcription Factors
Locigno, Roberto; Antoine, Nadine ULg; Bours, Vincent ULg et al

in Laboratory Investigation : Journal of Technical Methods & Pathology (2000), 80(1), 13-21

TNP-470, an angiogenesis inhibitor derived from fumagillin, is foreseen as a promising anti-cancer drug. Its effectiveness to restrain tumor growth and its lack of major side effects have been ... [more ▼]

TNP-470, an angiogenesis inhibitor derived from fumagillin, is foreseen as a promising anti-cancer drug. Its effectiveness to restrain tumor growth and its lack of major side effects have been demonstrated in several animal models and have led the drug to reach phase III clinical trials. Beside its antiangiogenesis activities, TNP-470 exhibits several effects on the immune system. We had shown previously that TNP-470 stimulated B lymphocyte proliferation through an action on T cells. In this study, we examined the cellular and molecular modifications induced by TNP-470 in normal human T lymphocytes. Transmission electron microscopic examination of PHA/TNP-470-treated T cells revealed significant morphologic modifications when compared with PHA-treated control T cells. TNP-470 induced indeed an important and significant increase of the nuclear size as well as major nuclear chromatin decondensation. This observation indicated that TNP-470 amplified T-cell activation and led us to investigate its effects on the activation of transcription factors involved in T-cell activation. Using electrophoretic mobility shift assays, we have demonstrated that TNP-470 amplifies and extends the DNA-binding activity of nuclear factor-AT, nuclear factor-KB, and activation protein-1 in T cells. Furthermore, the angioinhibin significantly increased the secretion of IL-2 and IL-4. Our data demonstrate that TNP-470 amplifies the activation of T cells. This effect, whose molecular mechanisms remain to be elucidated, has to be taken into account in the assessment of the antitumor effect of the drug. [less ▲]

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See detailApproches thérapeutiques du cancer ovarien
Bonnet, Christophe ULg; Jerusalem, Guy ULg; Bours, Vincent ULg et al

in Médecine et Hygiène (2000), 58

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