56 results on '"Dousset C"'
Search Results
2. Index
- Author
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Dousset, C. and Grand-Clément, A.
- Published
- 2005
3. 4th International Symposium on Biological Control of Bacterial Plant Diseases
- Author
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Poliakoff F., Legendre B., Dousset C., Paillard S., Molusson D., Sainte-Luce A., Juteau. V., Forveille A., Rivoal C., Cunty A., and Olivier V.
- Subjects
0303 health sciences ,03 medical and health sciences ,biology ,030306 microbiology ,Xanthomonas vesicatoria ,Biological pest control ,Plant Science ,biology.organism_classification ,Streptomyces ,Clavibacter michiganensis ,030304 developmental biology ,Microbiology - Published
- 2019
4. Transcranial Direct Current Stimulation combined with cognitive training induces response inhibition facilitation through distinct neural responses according to the stimulation site: a follow-up event-related potentials study
- Author
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Dousset, C., Ingels, A., Schroder, E., Angioletti, Laura, Balconi, Michela, Kornreich, C., Campanella, S., Angioletti Laura (ORCID:0000-0002-3027-2272), Balconi Michela (ORCID:0000-0002-8634-1951), Dousset, C., Ingels, A., Schroder, E., Angioletti, Laura, Balconi, Michela, Kornreich, C., Campanella, S., Angioletti Laura (ORCID:0000-0002-3027-2272), and Balconi Michela (ORCID:0000-0002-8634-1951)
- Abstract
Objective: We investigated whether the mid-term impact (1 week posttraining) of a “combined cognitive rehabilitation (CRP)/transcranial direct current stimulation (tDCS) program” on the performance of a Go/No-go task was enhanced compared with isolated CRP and whether it varied according to the stimulation site (right inferior frontal gyrus [rIFG] vs right dorsolateral prefrontal cortex [rDLPFC]). Methods: A total of 150 healthy participants were assigned to (1) an Inhibition Training (IT) group, (2) a group receiving active tDCS over the rIFG in combination with IT (IT + IF), (3) a group receiving active tDCS over the rDLPFC in combination with IT (IT + DL), (4) a group receiving IT with sham tDCS (ITsham), and (5) a No-Training (NT) group to control for test-retest effects. Each group undertook 3 sessions of a Go/No-go task concomitant with the recording of event-related potentials (T0, before training; T1, at the end of a 4-day training session [20 minutes each day]; T2, 1 week after T1). Results: With the exception of the NT participants, all the groups exhibited improved performances at T2. The IT + DL group exhibited the best improvement profile, indexed by faster response times (RTs) (T0 > T1 = T2), with a reduced rate of errors at the posttraining sessions compared with both T0 and T1. This “inhibitory learning effect” was neurophysiologically indexed by shorter No-go N2d latencies and enhanced No-go P3d amplitudes. Conclusion: CRP combined with active tDCS over the rDLPFC appears to be optimal for boosting long-term (one week) inhibitory skills as it induced specific and robust neural changes.
- Published
- 2021
5. The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma
- Author
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Touzeau, C, Dousset, C, Le Gouill, S, Sampath, D, Leverson, J D, Souers, A J, Maïa, S, Béné, M C, Moreau, P, Pellat-Deceunynck, C, and Amiot, M
- Published
- 2014
- Full Text
- View/download PDF
6. A propos de deux nouvelles collections de Poissons récoltées en Terre Adélie (Antarctique) en 1964 et 1965
- Author
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Hureau, J C, Arnaud, P, Dousset, C, and BioStor
- Published
- 1965
7. 2015-2019: Four years of Xylella fastidiosa surveillance in France
- Author
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Olivier, V., Legendre, B., Dousset, C., Paillard, S., Juteau, V., Forveille, A., Molusson, D., Sainte-Luce, A., Rivoal, C., Cunty, A., and Poliakoff, F.
- Subjects
Xylella fastidiosa ,validation ,detection ,surveillance ,identification ,Philaenus spumarius - Abstract
The surveillance of Xylella fastidiosa in France is implemented with detection methods validated by Anses - Plant Health Laboratory in plants and in Philaenus spumarius. Since 2015, improvements of protocols allowed to detect outbreaks and to identify the subspecies with a good efficiency. Xylella fastidiosa strains detected outdoors in France, identified with official methods, are mainly belonging to the subspecies multiplex (ST6 and ST7). The subspecies pauca (ST53) was only found in one outbreak (Menton on French Riviera).
- Published
- 2019
8. Current situation in France regarding Xylella fastidiosa: recent developments and validation of detection method on plants and vector Philaenus spumarius
- Author
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Poliakoff F., Legendre B., Juteau V., Molusson D., Dintheer A., Sainte-Luce A., Dousset C., Audusseau A., Paillard S., Cunty A., and Olivier V.
- Subjects
Xylella fastidiosa ,Detection ,Identification ,Validation ,Subspecies ,Philaenus spumarius - Abstract
The validated method (MA039) used in France to detect Xylella fastidiosa in plant samples in the framework of regulated surveillance is based on a Real-Time PCR (Harper et al., 2010) applied on plant DNA extracted with the QuickPick SML kit (Bio-Nobile). The MLST (Multi Locus Sequence Typing) (Yuan et al., 2010, EPPO PM7/24) scheme is applied to identify the sequence types and the subspecies. Until now the bacterium X. fastidiosa subspecies multiplex was mostly detected on about forty plant species, mainly ornamental of the Mediterranean area. These methods were optimized to improve their sensitivity on plant matrices such as olive tree, oak and on the insect vector Philaenus spumarius. They should contribute to the revision of the EPPO protocol.
- Published
- 2018
9. Improvements for better detection, isolation and characterization of X. fastidiosa
- Author
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Poliakoff, F., Legendre,B., Olivier, V. and Dousset , C., Paillard, S., Molusson., D., Sainte- Luce , A.
- Subjects
Detection - Abstract
Since the first outbreak of Xylella fastidiosa (Xf) on Polygala myrtifolia in natural settings in 2015 in France, Xf has been detected on more than thirty plant species with a validated method based on Real-Time PCR (Harper et al, 2010) associated to DNA extraction with QuickPick™ Plant DNA kit (Bio-Nobile) and KingFisher™ automate (Thermo Fisher Scientific). The sample preparation and isolation performed on modified PWG medium (EPPO, 2016) have been optimized and more than 40 Xf strains were isolated from Coffee plants, various ornamentals and trees. Critical reagents used for characterization of isolates directly on plant and on isolated strains according to a multilocus sequence typing (MLST) (http://pubmlst.org/xfastidiosa/) following the amplification protocol of Yuan et al. (2010) were evaluated to optimize EPPO protocol PM 7/24. Thus isolates in France were mostly allocated to sequence types ST6 and ST7 (subspecies multiplex) although other subspecies were identified punctually (Denancé et al., 2017). Philaenus spumarius, known as vector in Apulia is widespread in mainland France and Corsica. A detection method of X f in insects was validated based on Real-Time PCR (Harper et al., 2010) performed in duplex with internal controls 18S (Ioos et al., 2009), after DNA extraction using the same commercial kit (Bio-Nobile). The rate of contaminated insects based on individual insect testing varied, according to the outbreak locations in Corsica, from 4% to 25%.This research is financially supported by the Project H2020 PONTE.
- Published
- 2017
- Full Text
- View/download PDF
10. Xylella fastidiosa in France: current situation in Corsica and in the region
- Author
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Poliakoff F.*, Legendre B., Olivier V. and Dousset C., Paillard S., Molusson D., Sainte- Luce A., Juteau V.
- Subjects
Xylella fastidiosa ,detection ,identification ,survey - Abstract
Since the first outbreak of X. fastidiosa on Polygala myrtifolia (Pm) in natural settings in 2015 in France, the national survey showed that disease is present in many ornamental host plant in environment of Corsica and French Riviera (PACA). X. fastidiosa has been detected on around forty plant species with a validated method based on Real-Time PCR (Harper et al., 2010) associated to DNA extraction with QuickPick™ Plant DNA kit (Bio-Nobile) and KingFisher™ automate (Thermo Fisher Scientific). The sample preparation and isolation performed on modified PWG medium (EPPO, 2016) have been optimized and more than 40 X. fastidiosa strains were isolated from various ornamentals and trees. The characterization of isolates directly on plant or on pure strains is performed according to a multilocus sequence typing (MLST) (http://pubmlst.org/X. fastidiosa/). Following EPPO protocol PM 7/24 isolates were mostly allocated to sequence types ST6 and ST7 (subspecies multiplex). Modifications of the amplification protocol (Yuan et al., 2010) proposed by Denancé et al.(2017) revealed infections linked to the subspecies pauca, sandyi, one recombinant and some mixed infections. EPPO protocol MLST confirmed four isolates in Polygala myrtifolia from PACA contaminated with subsp. pauca but not the identification of other contaminants. These contaminations could not be observed again in the immediate environment after plant eradication. Subspecies assignation directly from plant material is not always successful linked to PCR inhibitors depending of host plants. This study confirms the diversity of subspecies of X. fastidiosa in France. Nevertheless subspecies multiplex was found in the great majority., {"references":["Denance N, Legendre B, Briand M, Olivier V, de Boisseson C, Poliakoff F & Jacques M-A. 2017. Several","Harper SJ, Ward LI, & Clover GRG, 2010. Development of LAMP and Real-Time PCR methods for the","Yuan X., Morano L., Bromley R., Spring-Pearson S., Stouthamer R., & Nunney, L. (2010). Multilocus"]}
- Published
- 2017
- Full Text
- View/download PDF
11. CLAVIBACTER MICHIGANENSIS SUBSP. MICHIGANENSIS: OPTIMIZATION OF DETECTION IN SEED AND EFFECT OF SEED TREATMENT ON EFFICIENCY OF DETECTION METHODS
- Author
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Mathis, R., primary, Fricot, C., additional, Larenaudie, M., additional, Quillévéré, A., additional, Rolland, M., additional, Grimault, V., additional, Olivier, V., additional, Dousset, C., additional, Gentit, P., additional, Germain, R., additional, and Baldwin, T., additional
- Published
- 2015
- Full Text
- View/download PDF
12. Combination of lenalidomide with vitamin D3 induces apoptosis in mantle cell lymphoma via demethylation of BIK
- Author
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Brosseau, C, primary, Dousset, C, additional, Touzeau, C, additional, Maïga, S, additional, Moreau, P, additional, Amiot, M, additional, Le Gouill, S, additional, and Pellat-Deceunynck, C, additional
- Published
- 2014
- Full Text
- View/download PDF
13. The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma
- Author
-
Touzeau, C, primary, Dousset, C, additional, Le Gouill, S, additional, Sampath, D, additional, Leverson, J D, additional, Souers, A J, additional, Maïga, S, additional, Béné, M C, additional, Moreau, P, additional, Pellat-Deceunynck, C, additional, and Amiot, M, additional
- Published
- 2013
- Full Text
- View/download PDF
14. Etude de l'élevage porcin extensif en Espagne. Etude des facteurs race et alimentation sur la composition de la carcasse et la composition en acides gras du tissu musculaire du jambon, frais et sec
- Author
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Dousset, C.
- Subjects
Élevage extensif ,L01 - Élevage - Considérations générales ,Composition chimique ,L40 - Anatomie et morphologie des animaux ,Race (animal) ,Acide gras ,Porcin ,Jambon ,Carcasse ,Alimentation des animaux - Abstract
L'élevage du Porc Ibérique est lié à l'utilisation d'un espace agro-sylvo-past oral, la Dehesa et conduit à la production de porcs lourds, donnant des produits dérivés de charcuterie de haute qualité. Cette étude s'intègre dans le projet de Recherche qui se déroule à l'ETSIAM de Cordoba, dont le but est de connaître l'influence des facteurs de production sur les produits dérivés du Porc Ibérique. Elle s'intérèsse à l'effet des facteurs race et alimentation sur la composition du jambon, frais et sec, ainsi que sur la composition en acides gras des gras intramusculaires du jambon frais et des gras intra et intermusculaires du jambon sec. Elle montre que les jambons de Porc Ibérique et ceux de porcs finis aux glands (Bellota) subissent moins de pertes à la transformation que ceux des porcs croisés et des porcs finis à l'aliment composé (Pienso). Ils sont également plus gras et contiennent moins d'os et de maigre. Les résultats font apparaître que l'effet race sur la composition en acides gras est moins significatif que ne l'est l'effet alimentation. Ce dernier joue sur l'insaturation des gras et sur la teneur en C18 : 1, supérieure chez le Porc alimenté à la Bellota et en C18 : 2 supérieure chez le porc alimenté au Pienso.
- Published
- 1991
15. Objectifs et stratégies des éleveurs de petits ruminants au Sénégal (Résumé du document PPR n° 36)
- Author
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Faugère, Olivier, Dousset, C., Faugère, B., and Moulin, Christine
- Subjects
L01 - Elevage - Considérations générales ,Ovin ,Sociologie rurale ,Élevage ,Analyse économique ,E16 - Economie de la production ,E10 - Economie et politique agricoles ,Système d'exploitation agricole ,Caprin - Published
- 1991
16. Facteurs de variation de la composition chimique des tissus adipeux et musculaires chez le porc. Conséquences sur l'aptitude à l'emploi
- Author
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Dousset, C.
- Subjects
Tissu adipeux ,Composition chimique ,Facteur du milieu ,L40 - Anatomie et morphologie des animaux ,Poids à l'abattage ,Acide gras ,Sexe ,Porcin ,Muscle ,Alimentation des animaux - Abstract
L'influence des conditions de production sur la composition chimique des deux principaux tissus (adipeux et musculaires) chez le porc a été étudiée. Les trois principaux facteurs de variation de la composition chimique de ces tissus semblent être la race, le sexe et l'alimentation. L'âge et le poids d'abattage dans les domaines habituellement considérés n'ont pas d'effet concluant. Il en est de même pour les facteurs environnementaux, exceptée la température. L'effet sexe se traduit essentiellement au niveau du gras intramusculaire. L'effet racial se traduit surtout sur le tissu adipeux. On remarque que les animaux à adiposité élevée et à croissance rapide déposent des gras externes plus riches en lipides, moins en eau. Ces lipides sont plus saturés. Quant à l'alimentation, elle a un effet trés marqué au niveau du tissu adipeux (la bardière) et sur sa composition en acides gras qui reflète la composition en acides gras de la ration.
- Published
- 1991
17. Objectifs et stratégies des éleveurs de petits ruminants au Sénégal
- Author
-
Dousset, C.
- Subjects
Ovin ,Sociologie rurale ,Élevage ,Analyse économique ,Système d'exploitation agricole ,Caprin ,E10 - Économie et politique agricoles - Abstract
Une étude des flux d'entrées et de sorties d'animaux enregistrés sur l'exercice agricole 88/89 dans les troupeaux de trois communautés rurales du Sénégal (Louga, dans la zone sahélienne, Kaymor, dans le Sine Saloum, Kolda, en Haute Casamance) a permis de dégager les principales pratiques d'exploitation et d'acquisition à savoir : les abattages (25 à 30 p. 100 des exploitations), les ventes (40 à 70 p. 100 des exploitations) et le troc, pratique propre à la seule zone de Kolda; les pratiques d'immigration tel que l'achat ou le troc, peu répandues, excepté dans les troupeaux des éleveurs Wolof de la zone de Louga. Une pratique particulière le confiage, a également été étudiée. L'analyse de ces pratiques et des prix de vente au niveau du producteur permet de dégager les objectifs et stratégies des éleveurs : assurer la sécurisation du système de production par des ventes de petits ruminants au moment voulu, répondre aux obligations sociales en procurant des animaux à l'occasion des cérémonies religieuses ou familiales. Une analyse des évolutions des taux d'exploitation et d'immigration dans le temps a permis de montrer l'adaptabilité des stratégies des éleveurs aux conjonctures, ainsi que la souplesse du système de production des petits ruminants, souplesse qui lui confère un rôle de "tampon" dans le système de production.
- Published
- 1991
18. Objectifs et stratégies des éleveurs des petits ruminants au Sénégal
- Author
-
Dousset, C.
- Subjects
Ovin ,E50 - Sociologie rurale et sécurité sociale ,Sociologie rurale ,Système de production ,Analyse économique ,Caprin ,Effectif du cheptel - Published
- 1990
19. 2015-2019: Four years of Xylella fastidiosa surveillance in France
- Author
-
Olivier V., Legendre B., Dousset C., Paillard S., Juteau V., Forveille A., Molusson D., Sainte-Luce A., Rivoal C., Cunty A., and Poliakoff F.
- Subjects
Xylella fastidiosa ,validation ,detection ,surveillance ,identification ,3. Good health ,Philaenus spumarius - Abstract
The surveillance of Xylella fastidiosa in France is implemented with detection methods validated by Anses - Plant Health Laboratory in plants and in Philaenus spumarius. Since 2015, improvements of protocols allowed to detect outbreaks and to identify the subspecies with a good efficiency. Xylella fastidiosa strains detected outdoors in France, identified with official methods, are mainly belonging to the subspecies multiplex (ST6 and ST7). The subspecies pauca (ST53) was only found in one outbreak (Menton on French Riviera).
20. 2015-2019: Four years of Xylella fastidiosa surveillance in France
- Author
-
Olivier, V., Legendre, B., Dousset, C., Paillard, S., Juteau, V., Forveille, A., Molusson, D., Sainte-Luce, A., Rivoal, C., Cunty, A., and Poliakoff, F.
- Subjects
Xylella fastidiosa ,validation ,detection ,surveillance ,identification ,3. Good health ,Philaenus spumarius - Abstract
The surveillance of Xylella fastidiosa in France is implemented with detection methods validated by Anses - Plant Health Laboratory in plants and in Philaenus spumarius. Since 2015, improvements of protocols allowed to detect outbreaks and to identify the subspecies with a good efficiency. Xylella fastidiosa strains detected outdoors in France, identified with official methods, are mainly belonging to the subspecies multiplex (ST6 and ST7). The subspecies pauca (ST53) was only found in one outbreak (Menton on French Riviera).
21. TREATMENT OF CANCER OF THE RECTUM (STUDY OF A SERIES OF 127 CASES).
- Author
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Dousset, C
- Published
- 1969
22. Selective pharmacologic targeting of CTPS1 shows single-agent activity and synergizes with BCL2 inhibition in aggressive mantle cell lymphoma.
- Author
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Durand R, Bellanger C, Kervoëlen C, Tessoulin B, Dousset C, Menoret E, Asnagli H, Parker A, Beer P, Pellat-Deceunynck C, and Chiron D
- Subjects
- Animals, Humans, Mice, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Apoptosis drug effects, Bridged Bicyclo Compounds, Heterocyclic, Carbon-Nitrogen Ligases, Cell Line, Tumor, Cell Proliferation drug effects, Molecular Targeted Therapy, Sulfonamides pharmacology, Sulfonamides therapeutic use, Xenograft Model Antitumor Assays, Drug Synergism, Lymphoma, Mantle-Cell drug therapy, Lymphoma, Mantle-Cell pathology, Lymphoma, Mantle-Cell metabolism, Lymphoma, Mantle-Cell genetics, Proto-Oncogene Proteins c-bcl-2 antagonists & inhibitors, Proto-Oncogene Proteins c-bcl-2 metabolism, Proto-Oncogene Proteins c-bcl-2 genetics
- Abstract
Innovative therapeutic strategies have emerged over the past decade to improve outcomes for most lymphoma patients. Nevertheless, the aggressive presentation seen in high-risk mantle cell lymphoma (MCL) patients remains an unmet medical need. The highly proliferative cells that characterize these tumors depend on nucleotide synthesis to ensure high DNA replication and RNA synthesis. To take advantage of this vulnerability, STP-B, a clinically available small molecule selectively targeting CTP synthase 1 (CTPS1) has been recently developed. CTPS1 is a key enzyme of the pyrimidine synthesis pathway mediated through its unique ability to provide enough CTP in highly proliferating cells. Herein, we demonstrated that CTPS1 was expressed in all MCL cells, and that its high expression was associated with unfavorable outcomes for patients treated with chemotherapy. Using aggressive MCL models characterized by blastoid morphology, TP53 mutation or polyresistance to targeted therapies, we showed that STP-B was highly effective at nanomolar concentrations in vitro and in vivo, irrespective of these high-risk features. Inhibition of CTPS1 rapidly leads to cell cycle arrest in early S-phase accompanied by inhibition of translation, including of the anti-apoptotic protein MCL1. Consequently, CTPS1 inhibition induced synergistic cell death in combination with the selective BCL2 inhibitor venetoclax, both in vitro and in vivo. Overall, our study identified CTPS1 as a promising target for MCL patients and provided a mechanism-based combination with the BCL2 inhibitor venetoclax for the design of future chemotherapy-free treatment regimens to overcome resistance.
- Published
- 2024
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- View/download PDF
23. Sensori-motor neurofeedback improves inhibitory control and induces neural changes: a placebo-controlled, double-blind, event-related potentials study.
- Author
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Dousset C, Wyckmans F, Monseigne T, Fourdin L, Boulanger R, Sistiaga S, Ingels A, Kajosch H, Noël X, Kornreich C, and Campanella S
- Abstract
Background/objective: Inhibition is crucial for controlling behavior and is impaired in various psychopathologies. Neurofeedback holds promise in addressing cognitive deficits, and experimental research is essential for identifying its functional benefits. This study aimed to investigate whether boosting sensorimotor activity (SMR) improves inhibitory control in a final sample of healthy individuals ( N = 53), while exploring the underlying neurophysiological mechanism., Method: Participants were randomly divided into two groups: one receiving SMR neurofeedback training to enhance sensorimotor activity within the 12-15 Hz frequency range, and the other receiving sham feedback. Inhibition performance and neural correlates were evaluated with a Go-NoGo task before (T0) and after (T1) 10 neurofeedback sessions using event-related potentials. Data were analyzed via ANOVAs and regression analyses., Results: Compared to placebo, the active group demonstrated higher absolute SMR power ( p = 0.040) and improvements in inhibitory control, including faster response times and fewer inhibition errors ( p < 0.001, d = 6.06), associated with a larger NoGoP3d amplitude ( p < 0.001, d = 3.35). A positive correlation between the increase in SMR power and the rise in NoGoP3d amplitude (β=0.46, p = 0.015) explains 21 % of the observed variance., Conclusions: Uptraining SMR power is linked to heightened utilization of neural resources for executing optimal inhibition responses. These results uphold its effectiveness in cognitive rehabilitation., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare that they do not practice clinically with neurofeedback but have received blueprint certification training and supervision in preparation for the neurofeedback entry-level certification from the Biofeedback Certification International Alliance (BCIA)., (© 2024 The Authors. Published by Elsevier B.V.)
- Published
- 2024
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24. A p53 score derived from TP53 CRISPR/Cas9 HMCLs predicts survival and reveals a major role of BAX in the response to BH3 mimetics.
- Author
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Durand R, Descamps G, Bellanger C, Dousset C, Maïga S, Alberge JB, Derrien J, Cruard J, Minvielle S, Lilli NL, Godon C, Le Bris Y, Tessoulin B, Amiot M, Gomez-Bougie P, Touzeau C, Moreau P, Chiron D, Moreau-Aubry A, and Pellat-Deceunynck C
- Subjects
- Humans, bcl-2-Associated X Protein genetics, bcl-2-Associated X Protein metabolism, Myeloid Cell Leukemia Sequence 1 Protein genetics, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, CRISPR-Cas Systems, Cell Line, Proto-Oncogene Proteins c-bcl-2 metabolism, Cell Line, Tumor, Apoptosis, Multiple Myeloma drug therapy, Multiple Myeloma genetics, Multiple Myeloma metabolism, Antineoplastic Agents therapeutic use, Pyrimidines, Thiophenes
- Abstract
Abstract: To establish a strict p53-dependent gene-expression profile, TP53-/- clones were derived from TP53+/+ and TP53-/mut t(4;14) human myeloma cell lines (HMCLs) using CRISPR/Cas9 technology. From the 17 dysregulated genes shared between the TP53-/- clones from TP53+/+ HMCLs, we established a functional p53 score, involving 13 genes specifically downregulated upon p53 silencing. This functional score segregated clones and myeloma cell lines as well as other cancer cell lines according to their TP53 status. The score efficiently identified samples from patients with myeloma with biallelic TP53 inactivation and was predictive of overall survival in Multiple Myeloma Research Foundation-coMMpass and CASSIOPEA cohorts. At the functional level, we showed that among the 13 genes, p53-regulated BAX expression correlated with and directly affected the MCL1 BH3 mimetic S63845 sensitivity of myeloma cells by decreasing MCL1-BAX complexes. However, resistance to S63845 was overcome by combining MCL1 and BCL2 BH3 mimetics, which displayed synergistic efficacy. The combination of BH3 mimetics was effective in 97% of patient samples with or without del17p. Nevertheless, single-cell RNA sequencing analysis showed that myeloma cells surviving the combination had lower p53 score, showing that myeloma cells with higher p53 score were more sensitive to BH3 mimetics. Taken together, we established a functional p53 score that identifies myeloma cells with biallelic TP53 invalidation, demonstrated that p53-regulated BAX is critical for optimal cell response to BH3 mimetics, and showed that MCL1 and BCL2 BH3 mimetics in combination may be of greater effectiveness for patients with biallelic TP53 invalidation, for whom there is still an unmet medical need., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
- Published
- 2024
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- View/download PDF
25. CARD11 gain of function upregulates BCL2A1 expression and promotes resistance to targeted therapies combination in B-cell lymphoma.
- Author
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Decombis S, Bellanger C, Le Bris Y, Madiot C, Jardine J, Santos JC, Boulet D, Dousset C, Menard A, Kervoelen C, Douillard E, Moreau P, Minvielle S, Moreau-Aubry A, Tessoulin B, Roue G, Bidère N, Le Gouill S, Pellat-Deceunynck C, and Chiron D
- Subjects
- Adult, Humans, CARD Signaling Adaptor Proteins genetics, CARD Signaling Adaptor Proteins metabolism, Cell Line, Tumor, Gain of Function Mutation, Guanylate Cyclase genetics, Guanylate Cyclase metabolism, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-2 metabolism, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse metabolism, Lymphoma, Mantle-Cell pathology
- Abstract
A strategy combining targeted therapies is effective in B-cell lymphomas (BCL), such as mantle cell lymphoma (MCL), but acquired resistances remain a recurrent issue. In this study, we performed integrative longitudinal genomic and single-cell RNA-sequencing analyses of patients with MCL who were treated with targeted therapies against CD20, BCL2, and Bruton tyrosine kinase (OAsIs trial). We revealed the emergence of subclones with a selective advantage against OAsIs combination in vivo and showed that resistant cells were characterized by B-cell receptor (BCR)-independent overexpression of NF-κB1 target genes, especially owing to CARD11 mutations. Functional studies demonstrated that CARD11 gain of function not only resulted in BCR independence but also directly increased the transcription of the antiapoptotic BCL2A1, leading to resistance against venetoclax and OAsIs combination. Based on the transcriptional profile of OAsIs-resistant subclones, we designed a 16-gene resistance signature that was also predictive for patients with MCL who were treated with conventional chemotherapy, underlying a common escape mechanism. Among druggable strategies to inhibit CARD11-dependent NF-κB1 transduction, we evaluated the selective inhibition of its essential partner MALT1. We demonstrated that MALT1 protease inhibition led to a reduction in the expression of genes involved in OAsIs resistance, including BCL2A1. Consequently, MALT1 inhibition induced synergistic cell death in combination with BCL2 inhibition, irrespective of CARD11 mutational status, both in vitro and in vivo. Taken together, our study identified mechanisms of resistance to targeted therapies and provided a novel strategy to overcome resistance in aggressive BCL. The OAsIs trial was registered at www.clinicaltrials.gov #NCT02558816., (© 2023 by The American Society of Hematology.)
- Published
- 2023
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26. The IL32/BAFF axis supports prosurvival dialogs in the lymphoma ecosystem and is disrupted by NIK inhibition.
- Author
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Decombis S, Papin A, Bellanger C, Sortais C, Dousset C, Le Bris Y, Riveron T, Blandin S, Hulin P, Tessoulin B, Rouel M, Le Gouill S, Moreau-Aubry A, Pellat-Deceunynck C, and Chiron D
- Subjects
- Adult, Humans, Cell Line, Tumor, Macrophages metabolism, NF-kappa B metabolism, Tumor Microenvironment, NF-kappaB-Inducing Kinase, Interleukins metabolism, Lymphoma, Mantle-Cell pathology, B-Cell Activating Factor metabolism, Protein Serine-Threonine Kinases metabolism
- Abstract
Aggressive B-cell malignancies, such as mantle cell lymphoma (MCL), are microenvironment-dependent tumors and a better understanding of the dialogs occurring in lymphoma-protective ecosystems will provide new perspectives to increase treatment efficiency. To identify novel molecular regulations, we performed a transcriptomic analysis based on the comparison of circulating MCL cells (n=77) versus MCL lymph nodes (n=107) together with RNA sequencing of malignant (n=8) versus normal B-cell (n=6) samples. This integrated analysis led to the discovery of microenvironment-dependent and tumor-specific secretion of interleukin-32 beta (IL32β), whose expression was confirmed in situ within MCL lymph nodes by multiplex immunohistochemistry. Using ex vivo models of primary MCL cells (n=23), we demonstrated that, through the secretion of IL32β, the tumor was able to polarize monocytes into specific MCL-associated macrophages, which in turn favor tumor survival. We highlighted that while IL32β-stimulated macrophages secreted several protumoral factors, they supported tumor survival through a soluble dialog, mostly driven by BAFF. Finally, we demonstrated the efficacy of selective NIK/alternative-NFkB inhibition to counteract microenvironment-dependent induction of IL32β and BAFF-dependent survival of MCL cells. These data uncovered the IL32β/BAFF axis as a previously undescribed pathway involved in lymphoma-associated macrophage polarization and tumor survival, which could be counteracted through selective NIK inhibition.
- Published
- 2022
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27. Comparison of Neural Correlates of Reactive Inhibition in Cocaine, Heroin, and Polydrug Users through a Contextual Go/No-Go Task Using Event-Related Potentials.
- Author
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Dousset C, Chenut C, Kajosch H, Kornreich C, and Campanella S
- Abstract
Recent global data indicates a worldwide increase in polydrug use associated with a shift from recreational to productive habits of consumption. Such non-responsible abuse of substances (alcohol, cocaine, heroin, etc.) is likely to lead to addictive disorders that are characterized by various neuropsychopharmacological effects. A main cognitive function involved in the onset and long-term maintenance of addiction is reactive inhibition, i.e., the ability to withhold a prepotent motor dominant response. In the present study, 63 (poly)drug user patients who were undergoing a detoxification program, in addition to 19 healthy controls matched for gender, age, and education, were subjected to a "contextual Go/No-Go task" with concomitant electroencephalography. Stimuli were superimposed on three contextual backgrounds: control (black screen), drug-unrelated (neutral pictures), or drug-related (pictures related to drug consumption). Of these patients, 23 were cocaine users (CU), 21 were heroin users (HU), and 19 were polydrug users (PDU). The main results showed that (1) at the behavioral level, more commission errors occurred with the PDU patients compared to the healthy controls; (2) at the neurophysiological level, specific alterations were found on classical event-related potentials that index reactive inhibition. Indeed, the higher rate of errors in the PDU group was subtended by both reduced amplitude and latency on the ∆N2 component and increased ∆P3 latency compared to controls. These data clearly suggest a more deleterious impact of polydrug use on inhibitory functions. In addition, our results provide evidence of reduced ERN amplitude in cocaine users, suggesting that impaired performance monitoring and error-processing may support impaired awareness, thereby preventing these patients from changing their behaviors.
- Published
- 2022
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28. Intact Error-Related Negativity at the Start of a Three-Week Detoxification Program Reflects a Short-Term Protective Factor Against Relapse in Alcoholic Patients: Some Preliminary Evidence from a Follow-up Event-Related Potentials Study.
- Author
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Dousset C, Schroder E, Ingels A, Kajosch H, Hanak C, Veeser J, Amiot M, Kornreich C, and Campanella S
- Subjects
- Electroencephalography, Evoked Potentials, Follow-Up Studies, Humans, Protective Factors, Recurrence, Alcoholism
- Published
- 2022
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29. Transcranial direct current stimulation combined with alcohol cue inhibitory control training reduces the risk of early alcohol relapse: A randomized placebo-controlled clinical trial.
- Author
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Dubuson M, Kornreich C, Vanderhasselt MA, Baeken C, Wyckmans F, Dousset C, Hanak C, Veeser J, Campanella S, Chatard A, Jaafari N, and Noël X
- Subjects
- Cues, Double-Blind Method, Humans, Prefrontal Cortex physiology, Recurrence, Transcranial Direct Current Stimulation methods
- Abstract
Background: Approximately half of all people with alcohol use disorder (AUD) relapse into alcohol reuse in the next few weeks after a withdrawal treatment. Brain stimulation and cognitive training represent recent forms of complementary interventions in the context of AUD., Objective: To evaluate the clinical efficacy of five sessions of 2 mA bilateral transcranial direct current stimulation (tDCS) for 20 min over the dorsolateral prefrontal cortex (DLPFC) (left cathodal/right anodal) combined with alcohol cue inhibitory control training (ICT) as part of rehabilitation. The secondary outcomes were executive functioning (e.g. response inhibition) and craving intensity, two mechanisms strongly related to abstinence., Methods: A randomized clinical trial with patients (n = 125) with severe AUD at a withdrawal treatment unit. Each patient was randomly assigned to one of four conditions, in a 2 [verum vs. sham tDCS] x 2 [alcohol cue vs. neutral ICT] factorial design. The main outcome of treatment was the abstinence rate after two weeks or more (up to one year)., Results: Verum tDCS improved the abstinence rate at the 2-week follow-up compared to the sham condition, independently of the training condition (79.7% [95% CI = 69.8-89.6] vs. 60.7% [95% CI = 48.3-73.1]; p = .02). A priori contrasts analyses revealed higher abstinence rates for the verum tDCS associated with alcohol cue ICT (86.1% [31/36; 95% CI = 74.6-97.6]) than for the other three conditions (64% [57/89; 95% CI = 54-74]). These positive clinical effects on abstinence did not persist beyond two weeks after the intervention. Neither the reduction of craving nor the improvement in executive control resulted specifically from prefrontal-tDCS and ICT., Conclusions: AUD patients who received tDCS applied to DLPFC showed a significantly higher abstinence rate during the weeks following rehabilitation. When combined with alcohol specific ICT, brain stimulation may provide better clinical outcomes., Trial Registration: ClinicalTrials.gov number NCT03447054 https://clinicaltrials.gov/ct2/show/NCT03447054., Competing Interests: Declaration of competing interest This study is part of Macha Dubuson Ph.D thesis. Dr Kornreich reported receiving grants from the King Baudouin Foundation and the CHU Brugmann Foundation during the study. Dubuson reported receiving salary support through grants of the King Baudouin Foundation and the Brugmann Foundation during the study. There are no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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30. Transcranial Direct Current Stimulation Combined With Cognitive Training Induces Response Inhibition Facilitation Through Distinct Neural Responses According to the Stimulation Site: A Follow-up Event-Related Potentials Study.
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Dousset C, Ingels A, Schröder E, Angioletti L, Balconi M, Kornreich C, and Campanella S
- Subjects
- Cognition, Electroencephalography, Evoked Potentials, Follow-Up Studies, Humans, Prefrontal Cortex, Transcranial Direct Current Stimulation
- Abstract
Objective: We investigated whether the mid-term impact (1 week posttraining) of a "combined cognitive rehabilitation (CRP)/transcranial direct current stimulation (tDCS) program" on the performance of a Go/No-go task was enhanced compared with isolated CRP and whether it varied according to the stimulation site (right inferior frontal gyrus [rIFG] vs right dorsolateral prefrontal cortex [rDLPFC])., Methods: A total of 150 healthy participants were assigned to (1) an Inhibition Training (IT) group, (2) a group receiving active tDCS over the rIFG in combination with IT (IT + IF), (3) a group receiving active tDCS over the rDLPFC in combination with IT (IT + DL), (4) a group receiving IT with sham tDCS (ITsham), and (5) a No-Training (NT) group to control for test-retest effects. Each group undertook 3 sessions of a Go/No-go task concomitant with the recording of event-related potentials (T0, before training; T1, at the end of a 4-day training session [20 minutes each day]; T2, 1 week after T1)., Results: With the exception of the NT participants, all the groups exhibited improved performances at T2. The IT + DL group exhibited the best improvement profile, indexed by faster response times (RTs) (T0 > T1 = T2), with a reduced rate of errors at the posttraining sessions compared with both T0 and T1. This "inhibitory learning effect" was neurophysiologically indexed by shorter No-go N2d latencies and enhanced No-go P3d amplitudes., Conclusion: CRP combined with active tDCS over the rDLPFC appears to be optimal for boosting long-term (one week) inhibitory skills as it induced specific and robust neural changes.
- Published
- 2021
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31. Training Inhibitory Control Induced Robust Neural Changes When Behavior Is Affected: A Follow-up Study Using Cognitive Event-Related Potentials.
- Author
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Schroder E, Dubuson M, Dousset C, Mortier E, Kornreich C, and Campanella S
- Subjects
- Follow-Up Studies, Humans, Reaction Time, Cognition, Electroencephalography, Evoked Potentials
- Abstract
Cognitive training results in significant, albeit modest, improvements in specific cognitive functions across a range of mental illnesses. Inhibitory control, defined as the ability to stop the execution of an automatic reaction or a planned motor behavior, is known to be particularly important for the regulation of health behaviors, including addictive behaviors. For example, several studies have indicated that inhibitory training can lead to reduced alcohol consumption or a loss of weight/reduced energy intake. However, the exact neurocognitive mechanisms that underlie such behavioral changes induced by training are still matter of debate. In the present study, we investigated the long-term impact (ie, at 1 week posttraining) of an inhibitory training program (composed of 4 consecutive daily training sessions of 20 minutes each) on the performance of a Go/No-go task. Healthy participants were randomly assigned to 1 of 3 designated groups: (1) an Inhibition Training (IT) group that received training based on a hybrid flanker Go/No-go task; (2) a group that received a noninhibition-based (ie, episodic memory; EM) training; and (3) a No-Training (NT) group to control for test-retest effects. Each group underwent 3 sessions of a Go/No-go task concomitant with the recording of event-related potentials. Our results revealed a specific impact of the Inhibitory Training on the Go/No-go task, indexed by a faster process compared with the other 2 groups. This effect was neurophysiologically indexed by a faster N2 component on the difference NoGo-Go waveform. Importantly, effects at both the behavioral and at the neural level were still readily discernible 1 week posttraining. Thus, our data clearly corroborate the notion that cognitive training is effective, while also indicating that it may persist over time.
- Published
- 2020
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32. Preventing relapse in alcohol disorder with EEG-neurofeedback as a neuromodulation technique: A review and new insights regarding its application.
- Author
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Dousset C, Kajosch H, Ingels A, Schröder E, Kornreich C, and Campanella S
- Subjects
- Attention, Brain, Electroencephalography, Humans, Recurrence, Neurofeedback
- Abstract
Alcohol Use Disorder (AUD) has a disconcertingly high relapse rate (70-80% within a year following withdrawal). Preventing relapse or minimizing its extent is hence a challenging goal for long-term successful management of AUD. New perspectives that rely on diverse neuromodulation tools have been developed in this regard as care supports. This paper focuses on electroencephalogram-neurofeedback (EEG-NF), which is a tool that has experienced renewed interest in both clinical and research areas. We review the literature on EEG-based neurofeedback studies investigating the efficacy in AUD and including at least 10 neurofeedback training sessions. As neurofeedback is a form of biofeedback in which a measure of brain activity is provided as feedback in real-time to a subject, the high degree of temporal resolution of the EEG interface supports optimal learning. By offering a wide range of brain oscillation targets (alpha, beta, theta, delta, gamma, and SMR) the EEG-NF procedure increases the scope of possible investigations through a multitude of experimental protocols that can be considered to reinforce or inhibit specific forms of EEG activity associated with AUD-related cognitive impairments. The present review provides an overview of the EEG-NF protocols that have been used in AUD and it highlights the current paucity of robust evidence. Within this framework, this review presents the arguments in favor of the application of EEG-NF as an add-on tool in the management of alcohol disorders to enhance the cognitive abilities required to maintain abstinence more specifically, with a focus on inhibition and attentional skills., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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33. Increased Neural Activity in Hazardous Drinkers During High Workload in a Visual Working Memory Task: A Preliminary Assessment Through Event-Related Potentials.
- Author
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Schroder E, Dousset C, Noel X, Kornreich C, and Campanella S
- Abstract
Despite equated behavioral performance levels, hazardous drinkers generally exhibited increased neural activity while performing simple cognitive tasks compared to light drinkers. Here, 49 participants (25 hazardous and 24 light drinkers) participated in an event-related potentials (ERPs) study while performing an n -back working memory task. In the control zero-back (N0) condition, the subjects were required to press a button when the number "2" or "6" was displayed. In the two-back and three-back (N2; N3) conditions, the subjects had to press a button when the displayed number was identical to the number shown two/three trials earlier. To assess for the impact of alcohol consumption on the updating of working memory processes under various cognitive loads, difference waveforms of "N2 minus N0" and "N3 minus N0" were computed by subtracting waveforms in the N0 condition from waveforms in the N2 and N3 conditions, for the light and the hazardous drinkers. Three main ERP components were noted for both groups: a P200/N200 complex, a P300 component, and an N400/P600 activity. The results show that, to perform the task at the same level as the light drinkers, the hazardous drinkers exhibited larger amplitude differences, mainly around the P300 and P600 components. These data may be considered, at the preventive level, as vulnerability factors for developing adult substance use disorders, and they stress the importance, at a clinical level, to consider such working memory processes in the management of alcohol dependence.
- Published
- 2019
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34. Targeting Oxidative Stress With Auranofin or Prima-1 Met to Circumvent p53 or Bax/Bak Deficiency in Myeloma Cells.
- Author
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Tessoulin B, Descamps G, Dousset C, Amiot M, and Pellat-Deceunynck C
- Abstract
Prima-1
Met (APR-246) was previously shown to be dependent on glutathione inhibition and on ROS induction in cancer cells with mutated or deleted TP53 . Because this ROS induction was, at least in part, due to a direct interference with the thioredoxin reductase enzyme, we investigated whether activity of Prima-1Met could be mimicked by auranofin, an inhibitor of the thioredoxin reductase. We thus compared the activity of auranofin and Prima-1Met in 18 myeloma cell lines and in 10 samples from patients with multiple myeloma or plasma cell leukemia. We showed that, similar to Prima-1Met , the activity of auranofin was not dependent on either TP53 status or p53 expression; was inhibited by N-acetyl-L-cysteine, a ROS scavenger; displayed a dramatic synergy with L-buthionine sulfoximine, an irreversible inhibitor of glutathione synthesis; and induced cell death that was not dependent on Bax/Bak expression. These data showed that auranofin and Prima-1Met similarly overcome cell death resistance in myeloma cells due to either p53 deficiency or to mitochondrial dysfunction.- Published
- 2019
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35. The selectivity of Marinopyrrole A to induce apoptosis in MCL1 high BCL2 low expressing myeloma cells is related to its ability to impair protein translation.
- Author
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Gomez-Bougie P, Dousset C, Descamps G, Schnitzler A, Audiger L, Tessier A, Dubreuil D, Lebreton J, Pellat-Deceunynck C, and Amiot M
- Subjects
- Apoptosis genetics, Cell Line, Tumor, Cell Survival drug effects, Cell Survival genetics, Gene Expression, Humans, Multiple Myeloma genetics, Myeloid Cell Leukemia Sequence 1 Protein genetics, Proto-Oncogene Proteins c-bcl-2 genetics, Apoptosis drug effects, Multiple Myeloma metabolism, Myeloid Cell Leukemia Sequence 1 Protein metabolism, Protein Biosynthesis drug effects, Proto-Oncogene Proteins c-bcl-2 metabolism, Pyrroles pharmacology
- Published
- 2018
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36. BH3 profiling as a tool to identify acquired resistance to venetoclax in multiple myeloma.
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Dousset C, Maïga S, Gomez-Bougie P, Le Coq J, Touzeau C, Moreau P, Le Gouill S, Chiron D, Pellat-Deceunynck C, Moreau-Aubry A, and Amiot M
- Subjects
- Antineoplastic Agents therapeutic use, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Humans, Melanoma diagnosis, Melanoma drug therapy, Sulfonamides therapeutic use, Antineoplastic Agents pharmacology, Biomarkers, Tumor, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Drug Resistance, Neoplasm genetics, Gene Expression Profiling, Melanoma genetics, Molecular Mimicry, Protein Interaction Domains and Motifs, Sulfonamides pharmacology
- Published
- 2017
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37. Deep and sustained response after venetoclax therapy in a patient with very advanced refractory myeloma with translocation t(11;14).
- Author
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Touzeau C, Le Gouill S, Mahé B, Boudreault JS, Gastinne T, Blin N, Caillon H, Dousset C, Amiot M, and Moreau P
- Subjects
- Adult, Cell Death drug effects, Chromosome Deletion, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 17, Disease Progression, Drug Resistance, Neoplasm, Female, Humans, Leukocytes, Mononuclear drug effects, Multiple Myeloma genetics, Multiple Myeloma pathology, Treatment Outcome, Antineoplastic Agents therapeutic use, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Compassionate Use Trials, Multiple Myeloma drug therapy, Sulfonamides therapeutic use, Translocation, Genetic
- Published
- 2017
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38. Rational targeted therapies to overcome microenvironment-dependent expansion of mantle cell lymphoma.
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Chiron D, Bellanger C, Papin A, Tessoulin B, Dousset C, Maiga S, Moreau A, Esbelin J, Trichet V, Chen-Kiang S, Moreau P, Touzeau C, Le Gouill S, Amiot M, and Pellat-Deceunynck C
- Subjects
- Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized pharmacology, Antigens, CD20 immunology, CD40 Ligand metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Coculture Techniques, Down-Regulation drug effects, Drug Resistance, Neoplasm drug effects, Female, Humans, Intercellular Signaling Peptides and Proteins metabolism, Lymphoid Tissue pathology, Male, Mesoderm pathology, Middle Aged, Mitochondria drug effects, Mitochondria metabolism, NF-kappa B metabolism, Up-Regulation drug effects, bcl-X Protein metabolism, Lymphoma, Mantle-Cell pathology, Lymphoma, Mantle-Cell therapy, Molecular Targeted Therapy, Tumor Microenvironment drug effects
- Abstract
Mantle cell lymphoma (MCL) accumulates in lymphoid organs, but disseminates early on in extranodal tissues. Although proliferation remains located in lymphoid organs only, suggesting a major role of the tumor ecosystem, few studies have assessed MCL microenvironment. We therefore cocultured primary circulating MCL cells from 21 patients several weeks ex vivo with stromal or lymphoid-like (CD40L) cells to determine which interactions could support their proliferation. We showed that coculture with lymphoid-like cells, but not stromal cells, induced cell-cycle progression, which was amplified by MCL-specific cytokines (insulin-like growth factor-1, B-cell activating factor, interleukin-6, interleukin-10). Of interest, we showed that our model recapitulated the MCL in situ molecular signatures (ie, proliferation, NF-κB, and survival signatures). We further demonstrated that proliferating MCL harbored an imbalance in Bcl-2 family expression, leading to a consequent loss of mitochondrial priming. Of interest, this loss of priming was overcome by the type II anti-CD20 antibody obinutuzumab, which counteracted Bcl-x
L induction through NF-κB inhibition. Finally, we showed that the mitochondrial priming directly correlated with the sensitivity toward venetoclax and alkylating drugs. By identifying the microenvironment as the major support for proliferation and drug resistance in MCL, our results highlight a selective approach to target the lymphoma niche., (© 2016 by The American Society of Hematology.)- Published
- 2016
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39. Biological rational for sequential targeting of Bruton tyrosine kinase and Bcl-2 to overcome CD40-induced ABT-199 resistance in mantle cell lymphoma.
- Author
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Chiron D, Dousset C, Brosseau C, Touzeau C, Maïga S, Moreau P, Pellat-Deceunynck C, Le Gouill S, and Amiot M
- Subjects
- Adenine analogs & derivatives, Agammaglobulinaemia Tyrosine Kinase, Apoptosis drug effects, Apoptosis genetics, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Humans, Lymph Nodes pathology, Lymphoma, Mantle-Cell enzymology, Lymphoma, Mantle-Cell pathology, Myeloid Cell Leukemia Sequence 1 Protein biosynthesis, Myeloid Cell Leukemia Sequence 1 Protein genetics, NF-kappa B metabolism, Neoplasm Proteins physiology, Piperidines, Protein-Tyrosine Kinases physiology, Proto-Oncogene Proteins c-bcl-2 physiology, Pyrazoles pharmacology, Pyrazoles therapeutic use, Pyrimidines pharmacology, Pyrimidines therapeutic use, RNA, Messenger biosynthesis, RNA, Neoplasm biosynthesis, Tumor Microenvironment drug effects, bcl-X Protein biosynthesis, bcl-X Protein genetics, Antineoplastic Agents pharmacology, Bridged Bicyclo Compounds, Heterocyclic pharmacology, CD40 Antigens physiology, Drug Resistance, Neoplasm drug effects, Lymphoma, Mantle-Cell drug therapy, Molecular Targeted Therapy, Neoplasm Proteins antagonists & inhibitors, Protein-Tyrosine Kinases antagonists & inhibitors, Proto-Oncogene Proteins c-bcl-2 antagonists & inhibitors, Sulfonamides pharmacology
- Abstract
The aggressive biological behavior of mantle cell lymphoma (MCL) and its short response to current treatment highlight a great need for better rational therapy. Herein, we investigate the ability of ABT-199, the Bcl-2-selective BH3 mimetic, to kill MCL cells. Among MCL cell lines tested (n = 8), only three were sensitive (LD50 < 200 nM). In contrast, all primary MCL samples tested (n = 11) were highly sensitive to ABT-199 (LD50 < 10 nM). Mcl-1 and Bcl-xL both confer resistance to ABT-199-specific killing and BCL2/(BCLXL+MCL1) mRNA ratio is a strong predictor of sensitivity. By mimicking the microenvironment through CD40 stimulation, we show that ABT-199 sensitivity is impaired through activation of NF-kB pathway and Bcl-x(L) up-regulation. We further demonstrate that resistance is rapidly lost when MCL cells detach from CD40L-expressing fibroblasts. It has been reported that ibrutinib induces lymphocytosis in vivo holding off malignant cells from their protective microenvironment. We show here for two patients undergoing ibrutinib therapy that mobilized MCL cells are highly sensitive to ABT-199. These results provide evidence that in situ ABT-199 resistance can be overcome when MCL cells escape from the lymph nodes. Altogether, our data support the clinical application of ABT-199 therapy both as a single agent and in sequential combination with BTK inhibitors.
- Published
- 2015
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40. A simple flow cytometry-based barcode for routine authentication of multiple myeloma and mantle cell lymphoma cell lines.
- Author
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Maïga S, Brosseau C, Descamps G, Dousset C, Gomez-Bougie P, Chiron D, Ménoret E, Kervoelen C, Vié H, Cesbron A, Moreau-Aubry A, Amiot M, and Pellat-Deceunynck C
- Subjects
- Algorithms, Antibodies immunology, Cell Line, Tumor, Humans, Immunophenotyping, Flow Cytometry methods, HLA-A2 Antigen immunology, Lymphoma, Mantle-Cell immunology, Multiple Myeloma immunology, Staining and Labeling methods
- Published
- 2015
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41. Is ASCT with TBI superior to ASCT without TBI in mantle cell lymphoma patients?
- Author
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Peterlin P, Leux C, Gastinne T, Roland V, Mahé B, Dubruille V, Delaunay J, Chevallier P, Guillaume T, Blin N, Ayari S, Clavert A, Mohty M, Dousset C, Milpied N, Harousseau JL, Moreau P, Wuilleme S, Moreau A, and Le Gouill S
- Subjects
- Adult, Aged, Disease-Free Survival, Female, Hemoglobins metabolism, Humans, Male, Middle Aged, Multivariate Analysis, Prognosis, Transplantation Conditioning methods, Transplantation, Autologous methods, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Mantle-Cell therapy, Whole-Body Irradiation methods
- Abstract
Background: Impact of total-body irradiation (TBI) in conditioning regimen on outcome for patients with mantle cell lymphoma (MCL) remains unknown., Methods: Patients with MCL who underwent autologous stem-cell transplantation (ASCT) in our institution were eligible for the present study (n=73). We analyzed the impact of various biologic and clinical parameters, with and without TBI, on patient outcome., Results: All patients presented with chemosensitive disease at transplantation. Median follow-up from ASCT was 37.2 months. One- and three-year overall survival (OS) rates were 90.3% and 74.5%, progression-free survival (PFS) rates were 85% and 59%, respectively. Three-year OS and PFS rates in the non-TBI group versus TBI group were similar: 80% versus 72.5% and 60% versus 57%, respectively. In univariate analysis, the use of TBI did not modify OS or PFS (P=0.93 and P=0.48, respectively). This remains true for patients who underwent ASCT up front. According to multivariate analysis, OS tended to be shorter for patients presenting with high Mantle Cell Lymphoma International Prognostic Index or low hemoglobin level., Conclusions: Absence of TBI in conditioning regimen modifies neither PFS nor OS. The present retrospective and monocentric analysis shows that transplant patients with MCL remain highly exposed to relapse.
- Published
- 2012
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42. ABT-737 is highly effective against molecular subgroups of multiple myeloma.
- Author
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Bodet L, Gomez-Bougie P, Touzeau C, Dousset C, Descamps G, Maïga S, Avet-Loiseau H, Bataille R, Moreau P, Le Gouill S, Pellat-Deceunynck C, and Amiot M
- Subjects
- Antineoplastic Agents pharmacology, Apoptosis drug effects, Apoptosis Regulatory Proteins metabolism, Biphenyl Compounds pharmacology, Cell Line, Tumor, Cyclin D1 metabolism, Humans, Multiple Myeloma genetics, Multiple Myeloma metabolism, Myeloid Cell Leukemia Sequence 1 Protein, Nitrophenols pharmacology, Piperazines pharmacology, Piperazines therapeutic use, Proto-Oncogene Proteins c-bcl-2 metabolism, Sulfonamides pharmacology, Tumor Cells, Cultured, Antineoplastic Agents therapeutic use, Biphenyl Compounds therapeutic use, Gene Expression Regulation, Neoplastic, Multiple Myeloma drug therapy, Nitrophenols therapeutic use, Proto-Oncogene Proteins c-bcl-2 genetics, Sulfonamides therapeutic use
- Abstract
Multiple myeloma is a plasma cell malignancy that is heterogeneous with respect to its causative molecular abnormalities and the treatment response of patients. The Bcl-2 protein family is critical for myeloma cell survival. ABT-737 is a cell-permeant compound that binds to Bcl-2 and Bcl-x(L) but not to Mcl-1. Using a myeloma cell line collection (n = 25) representative of different molecular translocations, we showed that ABT-737 effectively kills a subset of cell lines (n = 6), with a median lethal dose ranging from 7 ± 0.4 nM to 150 ± 7.5 nM. Of interest, all sensitive cell lines harbored a t(11;14). We demonstrated that ABT-737-sensitive and ABT-737-resistant cell lines could be differentiated by the BCL2/MCL1 expression ratio. A screen of a public expression database of myeloma patients indicates that the BCL2/MCL1 ratio of t(11;14) and hyperdiploid patients was significantly higher than in all other groups (P < .001). ABT-737 first induced the disruption of Bcl-2/Bax, Bcl-2/Bik, or Bcl-2/Puma complexes, followed by the disruption of Bcl-2 heterodimers with Bak and Bim. Altogether, the identification of a subset of cell lines and primary cells effectively killed by ABT-737 alone supported the evaluation of ABT-263, an orally active counterpart to ABT-737, for the treatment of t(11;14) and hyperdiploid groups of myeloma harboring a Bcl-2(high)/Mcl-1(low) profile.
- Published
- 2011
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43. Noxa controls Mule-dependent Mcl-1 ubiquitination through the regulation of the Mcl-1/USP9X interaction.
- Author
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Gomez-Bougie P, Ménoret E, Juin P, Dousset C, Pellat-Deceunynck C, and Amiot M
- Subjects
- HEK293 Cells, Humans, Mitochondria metabolism, Myeloid Cell Leukemia Sequence 1 Protein, Proto-Oncogene Proteins c-bcl-2 genetics, Tumor Suppressor Proteins, Proteasome Endopeptidase Complex metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Ubiquitin Thiolesterase metabolism, Ubiquitin-Protein Ligases metabolism, Ubiquitination
- Abstract
The level of the Mcl-1 pro-survival protein is highly regulated, and the down-regulation of Mcl-1 expression favors the apoptotic process. Mcl-1 physically interacts with different BH3-only proteins; particularly, Noxa is involved in the modulation of Mcl-1 expression. In this study, we demonstrated that Noxa triggers the degradation of Mcl-1 at the mitochondria according to the exclusive location of Noxa at this compartment. The Noxa-induced degradation of Mcl-1 required the E3 ligase Mule, which is responsible for the polyubiquitination of Mcl-1. Because the USP9X deubiquitinase was recently demonstrated to be involved in Mcl-1 protein turnover by preventing its degradation through the removal of conjugated ubiquitin, we investigated whether Noxa affected the deubiquitination process. Interestingly, Noxa over-expression caused a decrease in the USP9X/Mcl-1 interaction associated with an increase in the Mcl-1 polyubiquitinated forms. Additionally, Noxa over-expression triggered an increase in the Mule/Mcl-1 interaction in parallel with the decrease in Mule/USP9X complex formation. Taken together, these modifications result in the degradation of Mcl-1 by the proteasome machinery. The implication of Noxa in the regulation of Mcl-1 proteasomal degradation adds complexity to this process, which is governed by multiple interactions., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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44. ABT-737 induces apoptosis in mantle cell lymphoma cells with a Bcl-2high/Mcl-1low profile and synergizes with other antineoplastic agents.
- Author
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Touzeau C, Dousset C, Bodet L, Gomez-Bougie P, Bonnaud S, Moreau A, Moreau P, Pellat-Deceunynck C, Amiot M, and Le Gouill S
- Subjects
- Apoptosis Regulatory Proteins metabolism, Cell Line, Tumor, Drug Resistance, Neoplasm drug effects, Drug Synergism, Humans, Membrane Proteins metabolism, Mitochondrial Proteins, Multiprotein Complexes metabolism, Myeloid Cell Leukemia Sequence 1 Protein, Piperazines pharmacology, bcl-2-Associated X Protein metabolism, Antineoplastic Agents pharmacology, Apoptosis drug effects, Biphenyl Compounds pharmacology, Lymphoma, Mantle-Cell metabolism, Nitrophenols pharmacology, Proto-Oncogene Proteins c-bcl-2 metabolism, Sulfonamides pharmacology
- Abstract
Purpose: Mantle cell lymphoma (MCL) is considered to be incurable. ABT-737 is a BH3 mimetic that targets Bcl-2, which is overexpressed in MCL and implicated in drug resistance. The present work investigated the antitumor effect of ABT-737., Experimental Design: Six MCL cell lines and primary MCL cells (n = 13) were used. Sensitivity to ABT-737 was assessed, and expression levels of Bcl-2 and Mcl-1 were analyzed. Finally, ABT-737 was combined with other cytotoxic agents to promote tailored therapy., Results: MINO and GRANTA-519 cell lines were highly sensitive to ABT-737 [the median lethal dose (LD₅₀) = 20 and 80 nmol/L, respectively], whereas other cell lines were resistant. In primary MCL cells, 46% of patients' samples were sensitive to ABT-737. The analysis of protein expression levels revealed that both sensitive cell lines and primary MCL cells could be characterized by a Bcl-2(high)/Mcl-1(low) profile, whereas resistant MCL cells contained high levels of Mcl-1. ABT-737 induced a rapid disruption of both Bcl-2/Bax and Bcl-2/Bik complexes. In addition, silencing of Mcl-1 by siRNA sensitized MCL cell lines to ABT-737. Similarly, flavopiridol, which induces Mcl-1 downregulation, in combination with ABT-737 led to a synergistic anti-MCL effect in ABT-737-resistant cell lines. This synergy was also observed when ABT-737 was combined with either bortezomib or cytarabine., Conclusions: The present work shows that ABT-737 induces strong apoptosis in MCL cells expressing a Bcl-2(high)/Mcl-1(low) profile. In ABT-737-resistant MCL cells, downregulation of Mcl-1 overcomes Mcl-1-induced resistance and synergizes ABT-737 effects. Our results strongly support the use of ABT-737 according to the Bcl-2/Mcl-1 tumor cell profiles in the treatment of MCL., (©2011 AACR.)
- Published
- 2011
- Full Text
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45. Early triggering of exclusive IFN-gamma responses of human Vgamma9Vdelta2 T cells by TLR-activated myeloid and plasmacytoid dendritic cells.
- Author
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Devilder MC, Allain S, Dousset C, Bonneville M, and Scotet E
- Subjects
- Cells, Cultured, Dendritic Cells cytology, Humans, Immunity, T-Lymphocyte Subsets immunology, Yellow fever virus immunology, Dendritic Cells immunology, Interferon-gamma immunology, Receptors, Antigen, T-Cell, gamma-delta immunology, Toll-Like Receptors immunology
- Abstract
gammadelta T cells, a major innate-like T cell subset, are thought to play in vivo an important role in innate and adaptive immune responses to various infection agents like parasites, bacteria, or viruses but the mechanisms contributing to this immune process remain ill defined. Owing to their ability to recognize a broad set of microbial molecular patterns, TLRs represent a major innate pathway through which pathogens induce dendritic cells (DC) maturation and acquisition of immunostimulatory functions. In this study, we studied the effects of various TLR ligands on the activation of human Vgamma9Vdelta2 T cells, a main human gammadelta PBL subset, which has been recently involved in the licensing of mycobacteria-infected DC. Both TLR3 and TLR4, but not TLR2 ligands, induced a rapid, strong, and exclusive IFN-gamma production by Vgamma9Vdelta2 T cells. This gammadelta subset contributed to a large extent to the overall PBL IFN-gamma response induced after short-term TLR stimulation of human PBMC. Importantly, this phenomenon primarily depended on type I IFN, but not IL-12, produced by monocytic DC upon TLR engagement. Vgamma9Vdelta2 T cells were similarly activated by plasmacytoid DC upon TLR8/9 activation or Yellow Fever virus infection. Moreover TLR-induced Vgamma9Vdelta2 IFN-gamma noncytolytic response led to efficient DC polarization into IL-12p70-producing cells. Our results support an adjuvant role played by Vgamma9Vdelta2 T cells along microbial infections through a particular cross-talk with pathogen-associated molecular patterns-activated DC. Moreover they provide new insights into the mechanisms underlying functional activation of this unique peripheral innate-like T cell subset during viral infections.
- Published
- 2009
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46. Vaccination with recombinant NY-ESO-1 protein elicits immunodominant HLA-DR52b-restricted CD4+ T cell responses with a conserved T cell receptor repertoire.
- Author
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Bioley G, Dousset C, Yeh A, Dupont B, Bhardwaj N, Mears G, Old LJ, Ayyoub M, and Valmori D
- Subjects
- Amino Acid Sequence, Antigen Presentation physiology, Antigens, Neoplasm chemistry, Antigens, Neoplasm therapeutic use, CD4-Positive T-Lymphocytes metabolism, Cancer Vaccines therapeutic use, Cells, Cultured, Epitope Mapping, HLA-DR Antigens metabolism, Humans, Immunodominant Epitopes analysis, Immunodominant Epitopes immunology, Lymphocyte Activation immunology, Membrane Proteins chemistry, Membrane Proteins therapeutic use, Peptide Fragments immunology, Recombinant Proteins chemistry, Recombinant Proteins immunology, Recombinant Proteins therapeutic use, Substrate Specificity immunology, T-Cell Antigen Receptor Specificity immunology, Antigens, Neoplasm immunology, CD4-Positive T-Lymphocytes immunology, Cancer Vaccines immunology, HLA-DR Antigens immunology, Membrane Proteins immunology, Receptors, Antigen, T-Cell metabolism, Vaccination methods
- Abstract
Purpose: ESO is a tumor-specific antigen with wide expression in human tumors of different histologic types and remarkable spontaneous immunogenicity. We have previously shown that specific T(H)1 and antibody responses can be elicited in patients with no detectable preexisting immune responses by vaccination with rESO administered with Montanide ISA-51 and CpG ODN 7909. The purpose of the present study was to characterize vaccine-induced ESO-specific CD4(+) T cell responses., Experimental Design: We generated CD4(+) T cell clones from patient C2, who had the highest CD4(+) T cell response to the vaccine, and analyzed their fine specificity and HLA class II restriction to determine the recognized epitope. We then assessed the response to the identified epitope in all vaccinated patients expressing the corresponding HLA class II allele., Results: We found that ESO-specific CD4(+) T cell clones from patient C2 recognize peptide ESO(119-143) (core region 123-137) presented by HLA-DR52b (HLA-DRB3*0202), a MHC class II allele expressed by about half of Caucasians. Importantly, following vaccination, all patients expressing DR52b developed significant responses to the identified epitope, accounting for, on average, half of the total CD4(+) T cell responses to the 119-143 immunodominant region. In addition, analysis of ESO-specific DR52b-restricted CD4(+) T cells at the clonal level revealed significant conservation of T cell receptor usage among different individuals., Conclusions: The identification of a DR52b-restricted epitope from ESO that is immunodominant in the context of vaccine-elicited immune responses is instrumental for the immunologic monitoring of vaccination trials targeting this important tumor antigen.
- Published
- 2009
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47. Human memory FOXP3+ Tregs secrete IL-17 ex vivo and constitutively express the T(H)17 lineage-specific transcription factor RORgamma t.
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Ayyoub M, Deknuydt F, Raimbaud I, Dousset C, Leveque L, Bioley G, and Valmori D
- Subjects
- Humans, Interleukin-17 immunology, Nuclear Receptor Subfamily 1, Group F, Member 3, Phenotype, T-Lymphocytes, Regulatory metabolism, Cell Lineage immunology, Forkhead Transcription Factors immunology, Immunologic Memory immunology, Interleukin-17 metabolism, Receptors, Retinoic Acid immunology, Receptors, Thyroid Hormone immunology, T-Lymphocytes, Helper-Inducer immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Recent studies have suggested a close relationship between CD4(+)FOXP3(+) regulatory T cells (Tregs) and proinflammatory IL-17-producing T helper cells (T(H)17) expressing the lineage-specific transcription factor RORgamma t. We report here the unexpected finding that human memory Tregs secrete IL-17 ex vivo and constitutively express RORgamma t. IL-17-secreting Tregs share some phenotypic and functional features with conventional T(H)17 cells, expressing high levels of CCR4 and CCR6 and low levels of CXCR3. However, unlike conventional T(H)17 cells, they express low levels of CD161 and mostly fail to cosecrete IL-22 and TNF-alpha ex vivo. Ex vivo secretion of IL-17 and constitutive expression of RORgamma t by human memory Tregs suggest that, in addition to their well-known suppressive functions, these cells likely play additional, as yet undescribed, proinflammatory functions.
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- 2009
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48. Complex interplay of activating and inhibitory signals received by Vgamma9Vdelta2 T cells revealed by target cell beta2-microglobulin knockdown.
- Author
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Trichet V, Benezech C, Dousset C, Gesnel MC, Bonneville M, and Breathnach R
- Subjects
- Antibodies pharmacology, Cell Line, Tumor, Coculture Techniques, Down-Regulation, Humans, Lymphocyte Activation, NK Cell Lectin-Like Receptor Subfamily D metabolism, NK Cell Lectin-Like Receptor Subfamily K, Receptors, Immunologic antagonists & inhibitors, Receptors, Immunologic metabolism, Receptors, KIR, Receptors, Natural Killer Cell, Tumor Escape, beta 2-Microglobulin genetics, Cytotoxicity, Immunologic genetics, Histocompatibility Antigens Class I metabolism, Neoplasms immunology, T-Lymphocyte Subsets immunology, beta 2-Microglobulin antagonists & inhibitors
- Abstract
Tumor cells often escape immunosurveillance by down-regulating MHC class I molecule expression. For human Vgamma9Vdelta2 T cells, a major peripheral blood T cell subset with broad antitumor reactivity, this down-regulation can affect signals transmitted by both the inhibitory and the activating MHC class I and Ib-specific NK receptors (NKRs) that these lymphocytes frequently express. To assess the overall impact of MHC down-regulation on Vgamma9Vdelta2 T cell activation, we used stable beta(2)-microglobulin knockdown to generate tumor cells with a approximately 10-fold down-modulation of all MHC class I molecules. This down-modulation had little effect on T cell proliferation or cytokine production, but modified tumor cell killing efficiency. Ab-blocking studies identified ILT2 as an important inhibitor of tumor cell killing by Vgamma9Vdelta2 T cells. Down-modulation of MHC class I and Ib molecules severely reduced ILT2 inhibitory signaling, but still allowed signaling by activating CD94-based receptors. It also unveiled a frequent enhancing effect of NKG2D on tumor killing by Vgamma9Vdelta2 T cells. Current models suggest that activating NKRs have less affinity for their MHC ligands than homologous inhibitory NKRs. Our results show that, despite this, activating NKRs recognizing MHC class I molecules play an important role in the increased killing by Vgamma9Vdelta2 T cells of tumor cells with down-regulated MHC class I molecule expression, and suggest that these T cells will best lyse tumor cells combining MHC class I molecule expression down-regulation with up-regulated NKG2D ligand expression.
- Published
- 2006
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49. AP2 clathrin adaptor complex, but not AP1, controls the access of the major histocompatibility complex (MHC) class II to endosomes.
- Author
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Dugast M, Toussaint H, Dousset C, and Benaroch P
- Subjects
- Adaptor Protein Complex 1 deficiency, Adaptor Protein Complex 1 genetics, Adaptor Protein Complex 2 deficiency, Adaptor Protein Complex 2 genetics, Base Sequence, Cell Compartmentation, Cell Line, DNA genetics, HeLa Cells, Humans, Kinetics, Lysosomes immunology, Lysosomes metabolism, RNA Interference, RNA, Small Interfering genetics, Transfection, Adaptor Protein Complex 1 metabolism, Adaptor Protein Complex 2 metabolism, Endosomes immunology, Endosomes metabolism, Histocompatibility Antigens Class II metabolism
- Abstract
Newly synthesized MHC II alpha- and beta-chains associated with the invariant chain chaperone (Ii) enter the endocytic pathway for Ii degradation and loading with peptides before transport to the cell surface. It is unclear how alphabetaIi complexes are sorted from the Golgi apparatus and directed to endosomes. However, indirect evidence tends to support direct transport involving the AP1 clathrin adaptor complex. Surprisingly, we show here that knocking down the production of AP1 by RNA interference did not affect the trafficking of alphabetaIi complexes. In contrast, AP2 depletion led to a large increase in surface levels of alphabetaIi complexes, inhibited their rapid internalization, and strongly delayed the appearance of mature MHC II in intracellular compartments. Thus, in the cell systems studied here, rapid internalization of alphabetaIi complexes via an AP2-dependent pathway represents a key step for MHC II delivery to endosomes and lysosomes.
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- 2005
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50. [Complications due to peripheral venous catheterization. Prospective study].
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Barbut F, Pistone T, Guiguet M, Gaspard R, Rocher M, Dousset C, Meynard JL, Carbonell N, Maury E, Offenstadt G, Poupon R, Frottier J, Valleron AJ, and Petit JC
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Candidiasis prevention & control, Catheters, Indwelling microbiology, Cross Infection prevention & control, Cross-Sectional Studies, Female, France, Health Surveys, Humans, Intensive Care Units statistics & numerical data, Male, Middle Aged, Phlebitis etiology, Phlebitis prevention & control, Risk Factors, Staphylococcal Infections prevention & control, Wound Infection prevention & control, Candidiasis etiology, Catheterization, Peripheral adverse effects, Catheters, Indwelling adverse effects, Cross Infection etiology, Staphylococcal Infections etiology, Wound Infection etiology
- Abstract
Objective: Peripheral venous catheter (PVC)-associated complications were prospectively evaluated in a 2 month-study performed in 3 different wards., Methods: For each inserted PVC, the following complications were observed daily by an external investigator: tenderness, erythema, swelling or induration, palpable cord and purulence. PVC that were removed were systematically sent to the Microbiology department and analysed according to the semi-quantitative method described by Brun-Buisson et al., Results: A total of 525 PVC (corresponding to 1,036 catheterisation-days) were included. Main clinical complications were erythema (22.1%), tenderness (21.9%), swelling or induration (20.9%), palpable cord (2.7%) and purulence (0.2%). Phlebitis, defined by 2 or more of the following signs: tenderness, erythema, swelling or induration and palpable cord, was observed in 22%. Catheter colonization (> or = 103 CFU/ml) occurred in 13%. Bacteria isolated from colonized catheters were coagulase-negative staphylococci (88.1%), Staphylococcus aureus (7.1%) and Candida sp. (4.8%). Multivariate risk factor analysis showed that age > or = 55 y. (OR = 3.16, p = 0.003), insertion on articulation site (OR = 2.94, p = 0.01) or in jugular vein (OR = 8.18, p = 0.01) and > 72 hour-catheterisation (OR = 4.74, p = 0.0003) were significantly associated with PVC colonization. Risk factors for phlebitis were skin lesions (OR = 1.88, p < 0.016), active infection unrelated to PVC (OR = 2.8, p = 0.001), "poor quality" peripheral vein (OR = 2.46, p < 0.02) and > 72 hour-catherisation (OR = 2.38, p = 0.009)., Conclusion: Complications associated with peripheral venous catheters are frequent but remain benign. They could probably be reduced by a systematic change every 72-96 hours as recommended by different guidelines.
- Published
- 2003
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