Nuclear Factor-Kappa B, Cancer, and Apoptosis
Bours, Vincent ; ; 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 ▲]Detailed reference viewed: 16 (7 ULg)
A Cell Type-Specific and Gap Junction-Independent Mechanism for the Herpes Simplex Virus-1 Thymidine Kinase Gene/Ganciclovir-Mediated Bystander Effect
; Robe, Pierre ; Lechanteur, Chantal et al
in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (1999), 5(11), 3639-44
Tumor cells expressing the herpes simplex virus type 1 thymidine kinase (HSV-tk) gene are killed by nucleoside analogues such as ganciclovir (GCV). GCV affects not only the cells expressing HSV-tk but ... [more ▼]
Tumor cells expressing the herpes simplex virus type 1 thymidine kinase (HSV-tk) gene are killed by nucleoside analogues such as ganciclovir (GCV). GCV affects not only the cells expressing HSV-tk but also neighboring cells that do not express the gene; this phenomenon commonly is called "bystander effect." GCV metabolites transfer via gap junctional intercellular communication (GJIC) accounts for the bystander effect in different cell lines, but other mechanisms have also been described. In this study, we analyzed the mechanisms of the bystander effect in two cell lines exhibiting different capacities of communication (DHD/K12 and 9L). The 9L cells exhibited a very good bystander effect, which was completely blocked by a long-term inhibitor of GJIC, 18 alpha-glycyrrhetinic acid. DHD/K12 cells exhibited a moderate bystander effect that was not abolished by 18 alpha-glycyrrhetinic acid or 1-octanol, another strong inhibitor of GJIC. Interestingly, we also observed a bystander effect in cultures where HSV-tk-expressing DHD/K12 cells were physically separated from their untransfected counterparts but grown in the same medium. Moreover, the transfer of filtered conditioned medium from GCV-treated HSV-tk-expressing DHD/K12 cells to DHD/K12 parental cells induced a decrease of survival in a concentration-dependent manner, suggesting that the bystander effect in this cell line was mediated by a soluble factor. [less ▲]Detailed reference viewed: 22 (1 ULg)
Posterior epidural migration of sequestered lumbar disc fragments. Report of two cases.
Robe, Pierre ; Martin, Didier ; Lenelle, Jacques et al
in Journal of Neurosurgery (1999), 90(2 Suppl), 264-6
The posterior epidural migration of sequestered lumbar disc fragments is an uncommon event. The authors report two such cases in which patients presented with either intense radicular pain or cauda equina ... [more ▼]
The posterior epidural migration of sequestered lumbar disc fragments is an uncommon event. The authors report two such cases in which patients presented with either intense radicular pain or cauda equina syndrome. The radiological characteristics were the posterior epidural location and the ring enhancement of the mass after injection of contrast material. The major diagnostic pitfalls are discussed. [less ▲]Detailed reference viewed: 95 (7 ULg)
Effects of Schwann Cell Transplantation in a Contusion Model of Rat Spinal Cord Injury
Martin, Didier ; Robe, Pierre ; Franzen, Rachelle et al
in Journal of Neuroscience Research (1996), 45(5), 588-597
Cultured Schwann cells were transplanted at various delays into a spinal cord contusion injury performed at low thoracic level in adult female rats. The Schwann cells were purified from the dorsal root ... [more ▼]
Cultured Schwann cells were transplanted at various delays into a spinal cord contusion injury performed at low thoracic level in adult female rats. The Schwann cells were purified from the dorsal root ganglia of adult syngeneic animals. the transplants were well tolerated, and the transplanted Schwann cells invaded the injured spinal cord. As quantified using video image analysis, the survival and growth of the transplanted cells were poor when the grafting procedure was performed 3-4 days after injury and very good when performed immediately or 10 days after injury, in which cases post-traumatic micro- and macrocavitation were strongly reduced. In animals grafted immediately after injury but not in animals grafted after 10 days, post-traumatic astrogliosis was much reduced. The Schwann cells transplanted area was invaded by numerous regenerating axons, the vast majority of which were, based on the neurotransmitter (CGRP and SP) profile, originating from dorsal root ganglion. No regeneration of the corticospinal tract as assessed after anterograde tracing or of descending aminergic fibers could be demonstrated. [less ▲]Detailed reference viewed: 33 (5 ULg)
Migration épidurale postérieure d'une hernie discale lombaire : a propos de deux cas.
Robe, Pierre ; Martin, Didier ; Lenelle, Jacques et al
Conference (1996, March 16)Detailed reference viewed: 22 (1 ULg)
Alpha-MSH stimulates neurite outgrowth of neonatal rat corticospinal neurons in vitro.
; ; Martin, Didier et al
in Brain Research (1996), 736(1-2), 91-8
Peptides related to melanocortin (alpha MSH) and corticotropin (ACTH), collectively termed melanocortins, exert trophic effects on the outgrowth of neurites from peripheral and central nervous system in ... [more ▼]
Peptides related to melanocortin (alpha MSH) and corticotropin (ACTH), collectively termed melanocortins, exert trophic effects on the outgrowth of neurites from peripheral and central nervous system in vitro. Here we study the neurite outgrowth promoting effect of alpha-MSH on corticospinal (CS) neurons in vitro. Corticospinal neurons were identified in cell culture of neonatal rat cortex by immunostaining of cholera toxin subunit B (CTB), retrogradely transported from the cervical parts of the spinal cord. The CTB-immunoreactive neurons represent a small percentage (3-5%) of the total cell population after 72 h in vitro. The axons or dendrites of cortical and CTB-labelled layer V neurons were visualized using antibodies against axon- or dendrite-specific markers and measured using a semi-automatic quantification device. Here we report that alpha-MSH stimulates axonal as well as dendrite outgrowth from both total and CTB-labelled neurons with a bell-shape response curve. Axonal outgrowth of CTB-labelled neurons was dose-dependently stimulated with a maximal effect of 50% at 10(-10) M alpha-MSH. The maximal effect for stimulation of axon outgrowth for the total cortex population was observed at 10(-8) M alpha-MSH. In addition dendrite outgrowth of both total and CTB-labelled neurons is stimulated in a dose-dependent manner with maximal effects (varying between 46 and 48%) at 10(-8) M alpha-MSH. Explanations in the shift for the optimal alpha-MSH concentration for stimulation of axonal outgrowth of CTB-labelled layer V neurons as compared to total cortex neurons are discussed. [less ▲]Detailed reference viewed: 30 (0 ULg)
Quantitative assessment by western-blot of proteins expressed by different cell types involved in inhibition and promotion of regeneration in the lesioned spinal cord.
; Martin, Didier ; Leprince, Pierre et al
Conference (1995, September 21)Detailed reference viewed: 3 (0 ULg)
A model of spinal cord injury: the balloon-compressive model
Martin, Didier ; ; Robe, Pierre et al
Conference (1995, September 03)Detailed reference viewed: 3 (0 ULg)
Les transplantations de cellules de Schwann syngéniques dans les lésions médullaires : résultats, limitations et perspectives
Martin, Didier ; Schoenen, Jean ; Robe, Pierre et al
Conference (1994, November 06)Detailed reference viewed: 8 (1 ULg)
Transplants of syngenic cultured, DRG-derived Schwann cells into the injured adult rat spinal cord.
Martin, Didier ; Robe, Pierre ; Schoenen, Jean et al
Conference (1993, June 18)Detailed reference viewed: 21 (1 ULg)
Les transplantations de cellules de Schwann syngéniques dans les lésions médullaires : Résultats, limites et perspectives.
Martin, Didier ; Robe, Pierre ; Malgrange, Brigitte et al
Conference (1993, June 08)Detailed reference viewed: 3 (1 ULg)
Les transplantations de cellules de Schwann syngéniques dans les lésions médullaires : Résultats, limitations et perspectives.
Martin, Didier ; Schoenen, Jean ; Robe, Pierre et al
Conference (1993)Detailed reference viewed: 4 (0 ULg)
In Vitro and in Vivo Modulation of 5-Hydroxytryptamine-, Thyrotropin-Releasing Hormone- and Calcitonin-Gene Related Peptide-Like Immunoreactivities in Adult Rat Sensory Neurons
; Martin, Didier ; Sadzot-Delvaux, Catherine et al
in Neuroscience (1992), 51(2), 401-10
In a previous work we have shown that culturing adult rat dorsal root ganglia neurons modifies their neurotransmitter phenotype in such a way that cultured neurons synthesize transmitters that are not ... [more ▼]
In a previous work we have shown that culturing adult rat dorsal root ganglia neurons modifies their neurotransmitter phenotype in such a way that cultured neurons synthesize transmitters that are not found in situ, while several other transmitters are expressed in a much higher percentage of neurons in culture than in situ [Schoenen J. et al. (1989) J. Neurosci. Res. 22, 473-487]. The aim of the present study was to investigate the origin and the nature of the relevant environmental signals that allow this plasticity to be expressed, focusing on three neurotransmitters: 5-hydroxytryptamine, thyrotropin-releasing hormone and calcitonin-gene related peptide. The main results can be summarized as follows: (1) culturing cells in fetal calf serum or on feeder layers of astrocytes, Schwann cells or fibroblasts partially inhibits the serotoninergic phenotype of dorsal root ganglia neurons; (2) in vivo disconnection of dorsal root ganglia from their spinal targets but not from their peripheral or supraspinal targets induces a significant increase of the percentage of 5-hydroxytryptamine- and thyrotropin-releasing hormone-positive neurons in disconnected ganglia; (3) growth factors such as ciliary neuronotrophic factor or basic fibroblast growth factor but not nerve growth factor repress 5-hydroxytryptamine and calcitonin gene-related peptide immunoreactivity in cultured sensory neurons. In conclusion, neurotransmitter gene expression of adult dorsal root ganglia neurons is controlled by complex influences. Our data suggest that thyrotropin-releasing hormone and 5-hydroxytryptamine gene expression are tonically repressed in vivo by factors originating from the spinal segmental level and that growth factors such as ciliary neurotrophic factor or basic fibroblast growth factor could be potential vectors of this repressing effect. [less ▲]Detailed reference viewed: 45 (25 ULg)