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17 results on '"Eymard, N"'

7. Normal erythropoiesis and development of multiple myeloma

Author

Bouchnita A., Eymard N., Koury M., Moyo T., and Volpert V.

Subjects
Information technology, T58.5-58.64
Abstract

We develop a hybrid multi-scale model of normal and pathological erythropoiesis, the process of red blood cell production in the bone marrow. Cells are described by a soft sphere model. They can move, divide and die by apoptosis. Their fate is determined by intracellular proteins, by extracellular substances and surrounding cells. We apply this model to describe normal function of erythropoiesis and the development of multiple myeloma in the bone marrow. It is a malignant disease characterized by proliferation of mutated plasma cells which form multiple tumors in the bone marrow. They disrupt erythroblastic islands by direct mechanical contact and due to apoptotic cytokines produced by myeloma cells. The development of the disease leads to decrease of red blood cell production and to anemia.

Published
2015
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9. Physiologically based pharmacokinetic modelling of methotrexate and 6-mercaptopurine in adults and children. Part 2: 6-mercaptopurine and its interaction with methotrexate

Author

Ogungbenro, Kayode, Aarons, Leon, Bajard, A, Ballot, C, Bertrand, Y, Bretz, F, Caudri, D, Castellan, C, Chabaud, S, Dufour, F, Eymard, N, Fisch, R, Guerrini, R, Jullien, V, Kassai, Behrouz, Nony, Patrice, Pérol, D, Pons, G, Tiddens, H, Rosati, A, Alberti, C, Chiron, C, Cornu, C, Kurbatova, P, Nabbout, R., University of Manchester [Manchester], Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

10. Mathematical model of T-cell lymphoblastic lymphoma: disease, treatment, cure or relapse of a virtual cohort of patients.

Author

EYMARD, N., KURBATOVA, P., VOLPERT, V., BESSONOV, N., OGUNGBENRO, K., AARONS, L., JANIAUD, P., BAJARD, A., CHABAUD, S., BERTRAND, Y., KASSAÏ, B., CORNU, C., and NONY, P.

Subjects
*MATHEMATICAL models, *T-cell lymphoma, *CANCER relapse, *CLINICAL trials, *PROGNOSIS, *THERAPEUTICS, *CANCER risk factors
Abstract

T lymphoblastic lymphoma (T-LBL) is a rare type of lymphoma with a good prognosis with a remission rate of 85%. Patients can be completely cured or can relapse during or after a 2-year treatment. Relapses usually occur early after the remission of the acute phase. The median time of relapse is equal to 1 year, after the occurrence of complete remission (range 0.2-5.9 years) (Uyttebroeck et al., 2008). It can be assumed that patients may be treated longer than necessary with undue toxicity. The aim of our model was to investigate whether the duration of the maintenance therapy could be reduced without increasing the risk of relapses and to determine the minimum treatment duration that could be tested in a future clinical trial We developed a mathematical model of virtual patients with T-LBL in order to obtain a proportion of virtual relapses close to the one observed in the real population of patients from the EuroLB database. Our simulations reproduced a 2-year follow-up required to study the onset of the disease, the treatment of the acute phase and the maintenance treatment phase. [ABSTRACT FROM AUTHOR]

Published
2018
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13. 6 months versus 12 months of adjuvant trastuzumab in early breast cancer (PHARE): final analysis of a multicentre, open-label, phase 3 randomised trial

Author

Pivot, Xavier, Romieu, Gilles, Debled, Marc, Pierga, Jean-Yves, Kerbrat, Pierre, Bachelot, Thomas, Lortholary, Alain, Espié, Marc, Fumoleau, Pierre, Serin, Daniel, Jacquin, Jean-Philippe, Jouannaud, Christelle, Rios, Maria, Abadie-Lacourtoisie, Sophie, Venat-Bouvet, Laurence, Cany, Laurent, Catala, Stéphanie, Khayat, David, Gambotti, Laetitia, Pauporté, Iris, Faure-Mercier, Céline, Paget-Bailly, Sophie, Henriques, Julie, Grouin, Jean Marie, Centre Paul Strauss, CRLCC Paul Strauss, CRLCC Val d'Aurelle - Paul Lamarque, Institut Bergonié [Bordeaux], UNICANCER, Institut Curie [Paris], Université Paris Descartes - Paris 5 (UPD5), CRLCC Eugène Marquis (CRLCC), Centre Léon Bérard [Lyon], Centre Catherine-de-Sienne [Nantes] (CCS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Sainte Catherine [Avignon], Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, CRLCC Jean Godinot, Institut Jean Godinot [Reims], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), CHU Limoges, Clinique Francheville [Périgueux], CHU Saint-Pierre, Clinique Bizet [Pais], Institut national du cancer [Boulogne] (INCA), Ligue Nationale Contre le Cancer - Paris, Ligue Nationale Contre le Cancer (LNCC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Unité de biostatistiques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), The French National Cancer Institute, PHARE trial investigators: C Piprot, L Cals, L Chaigneau, F Demarchi, T N'Guyen, U Stein, C Villanueva, J L Bréau, A K Chouahnia, P Saintigny, F Boué, P deSaint-Hilaire, I Guimont, N Grossat, B Valenza, E Lévy, J Médioni, C Delbaldo, J Grenier, D Pouessel, S Lavau-Denès, C Falandry, C Fournel-Fédérico, G Freyer, S Tartas, V Trillet-Lenoir, F Bons, G Auclerc, S Chièze, N Raban, C Tournigand, S Trager-Maury, G Bousquet, C Cuvier, S Giacchetti, A Hocini, C LeMaignan, J L Misset, D Avenin, C Beerblock, J Gligorov, P Rivera, H Roché, P Bougnoux, N Hajjaji, O Capitain, R Delva, P Maillart, P Soulié, H Bonnefoi, M Durand, N Madranges, L Mauriac, P Chollet, A F Dillies, X Durando, J P Ferrière, C Mouret-Reynier, J M Nabholtz, I Van Praagh, P Cottu, V Diéras, A Durieux, M Galotte, V Girre, S Henry, I Iurisci, M Jouve, V Laurence, L Mignot, S Piperno-Neumann, P Tresca, B Coudert, E Ferrant, F Mayer, A C Vanneuville, J Bonneterre, V Servent, L Vanlemmens, P Vennin, J P Guastalla, P Biron, L Dupuy-Brousseau, L Lancry, I Ray-Coquard, P Rebattu, O Trédan, J M Extra, F Rousseau, C Tarpin, M Fabbro, E Luporsi, L Uwer, B Weber, D Berton-Rigaud, E Bourbouloux, M Campone, J M Ferrero, P Follana, R Largillier, V Mari, B Costa, H Curé, J C Eymard, N Jovenin, D Lebrun, J Meunier, G Yazbek, D Gedoin, B Laguerre, C Lefeuvre, E Vauléon, A Chevrier, C Guillemet, M Leheurteur, O Rigal, I Tennevet, C Veyret, E Brain, M Guiterrez, F Mefti-Lacheraf, T Petit, F Dalenc, L Gladieff, H Roché, F André, S Delaloge, J Domont, J Ezenfis, M Spielmann, P Guillet, V Boulanger, J Provençal, L Stefani, C Alliot, D Ré, C Bellaiche-Miccio, G Boutan-Laroze, R Vanica, P Dion, A Hocini, G Sadki-Benaoudia, A Marti, A L Villing, B Slama, J L Dutel, S Nguyen, R Saad, O Arsène, Z Merad-Boudia, H Orfeuvre, J Egreteau, M J Goudier, R Lamy, B Leduc, C Sarda, B Salles, C Agostini, I Cauvin, A Dufresne, M Mangold, S Lebouvier-Sadot, B Audhuy, J C Barats, S Cluet-Dennetière, D Zylberait, G Netter, L Gautier-Felizot, I Cojean-Zelek, A Plantade, S Vignot, E Guardiola, P Marti, I deHartingh, R Diab, A Dietmann, S Ruck, C Portois, E Guardiola, S Oddou-Lagranière, F Campos-Gazeau, A Bourcier, F Priou, J F Geay, D Mayeur, P Gabez, R ElAmarti, M Combe, J Ezenfis, P Raichon-Patru, P Amsalhem, J Dauba, D Paraiso, F Guinet, B Duvert, M Litor, F Kara-Slimane, A Bichoffe, N Denizon, J Meunier, P Soyer, F Morvan, S Van-Hulst, L Vincent, C Alleaume, P Ibanez-Martin, A Youssef, Z Tadrist, E Carola, C Pourny, J F Toccanier, N Al-Aukla, K Mahour-Bacha, J Salvat, L Cals, P Nouyrigat, S Clippe, M C Gouttebel, L Vedrine, G Clavreul, O Collard, D Mille, Y Goubely, J Grenier, R Hervé, S Kirscher, F Plat, V Delecroix, V Ligeza-Poisson, D Coeffic, L Dupuy-Brousseau, D Fric, C Garnier, C Leyronnas, T Kreitman, R Largillier, E Teissier, P Martin, S Rohart deCordoue, C ElKouri, J F Ramée, C Laporte, O Bernard, T Altwegg, A Darut-Jouve, J P Dujols, F Darloy, C Giraud, V Pottier-Kyndt, N Achour, S Drony, M Moriceau, C Sarrazin, J C Legueul, J Mandet, D Besson, A C Hardy-Bessard, J Cretin, P Houyau, E Achille, D Genêt, H Thévenot, A Moran-Ribon, J M Pavlovitch, P Ardisson, I Moullet, B Couderc, V Fichet, F Burki, A Auliard, C B Levaché, G Auclerc, P Cailleux, F Schaeffer, N Albin, D Sévin-Robiche, J Domas, S Ellis, P Montcuquet, G A Baumont, M Bégue, S Gréget, J L Ratoanina, A Vanoli, C Bielsa, M Bonichon-Lamichhane, D Jaubert, H Laharie-Mineur, L Alcaraz, J Cretin, E Legouffe, H Bourgeois, G Cartron, F Denis, O Dupuis, G Ganem, S Roche-Forestier, L Delzenne, E Chirat, J L Baticle, E Béguier, S Jacquot, E Janssen, H Lauché, A LeRol, J P Chantelard, G A L'Helgoualc'h, E C Antoine, A Kanoui, J F Llory, J M Vannetzel, J Vignoud, C Bruna, T Facchini, K Moutel-Corviole, A Voloch, A Ghoul, D Loiseau, K Mahour-Bacha, N Barbet, N Dohollou, K Yakendji, CCSD, Accord Elsevier, and Ligue Nationnale Contre le Cancer

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, skin and connective tissue diseases
Abstract

International audience; Background: In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events.Methods: PHARE is an open-label, phase 3, non-inferiority randomised trial of patients with HER2-positive early breast cancer comparing 6 months versus 12 months of trastuzumab treatment concomitant with or following standard neoadjuvant or adjuvant chemotherapy. The study was undertaken in 156 centres in France. Eligible patients were women aged 18 years or older with non-metastatic, operable, histologically confirmed adenocarcinoma of the breast and either positive axillary nodes or negative axillary nodes but a tumour of at least 10 mm. Participants must have received at least four cycles of a chemotherapy for this breast cancer and have started receiving adjuvant trastuzumab-treatment. Eligible patients were randomly assigned to either 6 months or 12 months of trastuzumab therapy duration between the third and sixth months of adjuvant trastuzumab. The randomisation was stratified by concomitant or sequential treatment with chemotherapy, oestrogen receptor status, and centre. The primary objective was non-inferiority in the intention-to-treat population in the 6-month group in terms of disease-free survival with a prespecified hazard margin of 1·15. This trial is registered with ClinicalTrials.gov, number NCT00381901.Findings: 3384 patients were enrolled and randomly assigned to either 12 months (n=1691) or 6 months (n=1693) of adjuvant trastuzumab. One patient in the 12-month group and three patients in the 6-month group were excluded, so 1690 patients in each group were included in the intention-to-treat analysis. At a median follow-up of 7·5 years (IQR 5·3-8·8), 704 events relevant to disease-free survival were observed (345 [20·4%] in the 12-month group and 359 [21·2%] in the 6-month group). The adjusted hazard ratio for disease-free survival in the 12-month group versus the 6-month group was 1·08 (95% CI 0·93-1·25; p=0·39). The non-inferiority margin was included in the 95% CI. No differences in effects pertaining to trastuzumab duration were found in any of the subgroups. After the completion of trastuzumab treatment, rare adverse events occurred over time and the safety analysis remained similar to the previously published report. In particular, we found no change in the cardiac safety comparison, and only three additional cases in which the left ventricular ejection fraction decreased to less than 50% have been reported in the 12-month group.Interpretation: The PHARE study did not show the non-inferiority of 6 months versus 12 months of adjuvant trastuzumab. Hence, adjuvant trastuzumab standard duration should remain 12 months.

Published
2019

14. Bone marrow infiltration by multiple myeloma causes anemia by reversible disruption of erythropoiesis.

Author

Bouchnita A, Eymard N, Moyo TK, Koury MJ, and Volpert V

Subjects
Adult, Aged, Anemia diagnosis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Bone Marrow physiopathology, Bortezomib administration & dosage, Dexamethasone administration & dosage, Erythrocyte Indices, Erythroid Cells pathology, Female, Humans, Lenalidomide, Male, Middle Aged, Models, Theoretical, Multiple Myeloma drug therapy, Thalidomide administration & dosage, Thalidomide analogs & derivatives, Treatment Outcome, Anemia etiology, Anemia physiopathology, Bone Marrow pathology, Erythropoiesis drug effects, Multiple Myeloma complications, Multiple Myeloma pathology
Abstract

Multiple myeloma (MM) infiltrates bone marrow and causes anemia by disrupting erythropoiesis, but the effects of marrow infiltration on anemia are difficult to quantify. Marrow biopsies of newly diagnosed MM patients were analyzed before and after four 28-day cycles of non-erythrotoxic remission induction chemotherapy. Complete blood cell counts and serum paraprotein concentrations were measured at diagnosis and before each chemotherapy cycle. At diagnosis, marrow area infiltrated by myeloma correlated negatively with hemoglobin, erythrocytes, and marrow erythroid cells. After successful chemotherapy, patients with less than 30% myeloma infiltration at diagnosis had no change in these parameters, whereas patients with more than 30% myeloma infiltration at diagnosis increased all three parameters. Clinical data were used to develop mathematical models of the effects of myeloma infiltration on the marrow niches of terminal erythropoiesis, the erythroblastic islands (EBIs). A hybrid discrete-continuous model of erythropoiesis based on EBI structure/function was extended to sections of marrow containing multiple EBIs. In the model, myeloma cells can kill erythroid cells by physically destroying EBIs and by producing proapoptotic cytokines. Following chemotherapy, changes in serum paraproteins as measures of myeloma cells and changes in erythrocyte numbers as measures of marrow erythroid cells allowed modeling of myeloma cell death and erythroid cell recovery, respectively. Simulations of marrow infiltration by myeloma and treatment with non-erythrotoxic chemotherapy demonstrate that myeloma-mediated destruction and subsequent reestablishment of EBIs and expansion of erythroid cell populations in EBIs following chemotherapy provide explanations for anemia development and its therapy-mediated recovery in MM patients., (© 2016 Wiley Periodicals, Inc.)

Published
2016
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15. An in silico approach helped to identify the best experimental design, population, and outcome for future randomized clinical trials.

Author

Bajard A, Chabaud S, Cornu C, Castellan AC, Malik S, Kurbatova P, Volpert V, Eymard N, Kassai B, and Nony P

Subjects
Cross-Over Studies, Forecasting, Humans, Migraine Disorders drug therapy, Sumatriptan therapeutic use, Computer Simulation, Randomized Controlled Trials as Topic standards, Research Design
Abstract

Objectives: The main objective of our work was to compare different randomized clinical trial (RCT) experimental designs in terms of power, accuracy of the estimation of treatment effect, and number of patients receiving active treatment using in silico simulations., Study Design and Setting: A virtual population of patients was simulated and randomized in potential clinical trials. Treatment effect was modeled using a dose-effect relation for quantitative or qualitative outcomes. Different experimental designs were considered, and performances between designs were compared. One thousand clinical trials were simulated for each design based on an example of modeled disease., Results: According to simulation results, the number of patients needed to reach 80% power was 50 for crossover, 60 for parallel or randomized withdrawal, 65 for drop the loser (DL), and 70 for early escape or play the winner (PW). For a given sample size, each design had its own advantage: low duration (parallel, early escape), high statistical power and precision (crossover), and higher number of patients receiving the active treatment (PW and DL)., Conclusion: Our approach can help to identify the best experimental design, population, and outcome for future RCTs. This may be particularly useful for drug development in rare diseases, theragnostic approaches, or personalized medicine., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Published
2016
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16. A methodological framework for drug development in rare diseases.

Author

Nony P, Kurbatova P, Bajard A, Malik S, Castellan C, Chabaud S, Volpert V, Eymard N, Kassai B, and Cornu C

Subjects
Humans, Clinical Trials as Topic, Orphan Drug Production, Rare Diseases drug therapy, Research Design
Abstract

Introduction: Developing orphan drugs is challenging because of their severity and the requisite for effective drugs. The small number of patients does not allow conducting adequately powered randomized controlled trials (RCTs). There is a need to develop high quality, ethically investigated, and appropriately authorized medicines, without subjecting patients to unnecessary trials., Aims and Objectives: The main aim is to develop generalizable framework for choosing the best-performing drug/endpoint/design combinations in orphan drug development using an in silico modeling and trial simulation approach. The two main objectives were (i) to provide a global strategy for each disease to identify the most relevant drugs to be evaluated in specific patients during phase III RCTs, (ii) and select the best design for each drug to be used in future RCTs., Methodological Approach: In silico phase III RCT simulation will be used to find the optimal trial design and was carried out in two steps: (i) statistical analysis of available clinical databases and (ii) integrative modeling that combines mathematical models for diseases with pharmacokinetic-pharmacodynamics models for the selected drug candidates., Conclusion: There is a need to speed up the process of orphan drug development, develop new methods for translational research and personalized medicine, and contribute to European Medicines Agency guidelines. The approach presented here offers many perspectives in clinical trial conception.

Published
2014
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17. [Rights and responsibilities in cases of blood exposure accidents].

Author

Cohen A and Eymard N

Subjects
France, Humans, Accidents, Occupational legislation & jurisprudence, Blood-Borne Pathogens, Health Personnel legislation & jurisprudence, Needlestick Injuries prevention & control, Occupational Health legislation & jurisprudence, Patient Rights legislation & jurisprudence
Published
2002

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