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54. The IL32/BAFF Axis Supports Prosurvival Dialog in the Lymphoma Ecosystem and Is Disrupted By NIK Inhibition

Author

Decombis, Salome, primary, Papin, Antonin, additional, Bellanger, Celine, additional, Sortais, Clara, additional, Dousset, Christelle, additional, Le Bris, Yannick, additional, Blandin, Stephanie, additional, Hulin, Philippe, additional, Tessoulin, Benoit, additional, Rouel, Mathieu, additional, Le Gouill, Steven, additional, Moreau-Aubry, Agnes, additional, Pellat-Deceunynck, Catherine, additional, and Chiron, David, additional

Published
2021
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55. Coercivity for travelling waves in the Gross-Pitaevskii equation in R 2 for small speed

Author

Chiron, David, Pacherie, Eliot, Laboratoire Jean Alexandre Dieudonné (JAD), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
35Q55, MSC classification (2010): 35C07, Local uniqueness, 35B35 Travelling waves, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Coercivity, 35A02
Abstract

International audience; In a previous paper, we constructed a smooth branch of travelling waves for the 2 dimensional Gross-Pitaevskii equation. Here, we continue the study of this branch. We show some coercivity results, and we deduce from them the kernel of the linearized operator, a spectral stability result, as well as a uniqueness result in the energy space. In particular, our result proves the non degeneracy of these travelling waves, which is a key step in the classification of these waves and for the construction of multi-travelling waves.

Published
2021

56. Commentary on Rodrigues et al : Towards ecosystem integration for a better understanding of B-cell lymphomas aggressiveness

Author

Chiron, David, Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, immune system diseases, hemic and lymphatic diseases, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

International audience; Commentary on Rodrigues et al Towards ecosystem integration for a better understanding of B-cell lymphomas aggressiveness In this issue of BJH, Rodrigues et al. investigate how tumor-infiltrating immune cells correlated with the clinical outcome of Mantle Cell Lymphoma (MCL), a rare but often aggressive subtype of Non-Hodgkin lymphoma. Based on a large cohort of patients (n=282), Rodrigues and colleagues suggest that the nature of MCL ecosystem could influence tumor progression. They identify several markers, i.e. CD163, FOXP3 and PDL1, which correlate with worse outcome, independent of established risk factors. Their work gives new insights into the nature of MCL ecosystem, especially T-cells and macrophages, and into its role in tumor expansion and resistance.

Published
2021

57. Oxaliplatin before autologous transplantation in combination with high-dose cytarabine and rituximab provides longer disease control than cisplatin or carboplatin in patients with mantle-cell lymphoma: results from the LyMA prospective trial.

Author

UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Service de gastro-entérologie, Tessoulin, Benoit, Chiron, David, Thieblemont, Catherine, Oberic, Lucie, Bouadballah, Kamal, Gyan, Emmanuel, Damaj, Gandhi, Ribrag, Vincent, Gressin, Rémy, Feugier, Pierre, Casasnovas, Olivier, Zerazhi, Hacène, Lemonnier, François, Maisonneuve, Hervé, Joubert, Clementine, Van Den Neste, Eric, Lamy, Thierry, Tilly, Hervé, Moreau, Anne, Hermine, Olivier, Le Gouill, Steven, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Service de gastro-entérologie, Tessoulin, Benoit, Chiron, David, Thieblemont, Catherine, Oberic, Lucie, Bouadballah, Kamal, Gyan, Emmanuel, Damaj, Gandhi, Ribrag, Vincent, Gressin, Rémy, Feugier, Pierre, Casasnovas, Olivier, Zerazhi, Hacène, Lemonnier, François, Maisonneuve, Hervé, Joubert, Clementine, Van Den Neste, Eric, Lamy, Thierry, Tilly, Hervé, Moreau, Anne, Hermine, Olivier, and Le Gouill, Steven

Abstract

LyMA trial has demonstrated the benefit of rituximab maintenance after autologous stem cell transplantation (ASCT) in previously untreated mantle-cell lymphoma patients (MCL). Induction consisted of four courses of R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and platinum derivative). The platinum derivative (PD) choice was free: R-DHA-cisplatin, R-DHA-carboplatin, or R-DHA-oxaliplatin. We investigated the prognostic impact of each PD. PFS and OS calculated from inclusion and investigated in an intention-to-treat (ITT) (= 298) and per-protocol analyses (PP) (n = 227). R-DHACis, R-DHACa, or R-DHAOx were used at first cycle in 184, 76, and 38 patients, respectively. Overall, 71 patients (59 in the R-DHACis) required a change in PD, mainly because of PD toxicity. In ITT-analysis, PFS in the R-DHACis and R-DHACa groups were similar (4-year PFS of 65%), while R-DHAOx had a better PFS (4-year PFS of 65% versus 86.5%, respectively, HR = 0.44, p = 0.02). The 4-year OS was 92% for R-DHAOx versus 75.9% for R-DHACis/DHACa (HR = 0.37, p = 0.03). Similar results were yielded in the PP analysis. Low MIPI and R-DHAOx were independent favorable prognostic markers for both PFS (HR = 0.44, p = 0.035) and OS (HR = 0.36, p = 0.045). In vitro and in silico analyses confirmed that oxaliplatin has an anti-MCL cytotoxic effect that differs from that of other PD. R-DHAOx before ASCT provides better outcome in transplantation eligible young MCL patients.

Published
2021

60. Ibrutinib, Obinutuzumab And Venetoclax In Relapsed and Untreated Patients with Mantle-Cell Lymphoma, a phase I/II trial

Author

Le Gouill, Steven, Morschhauser, Franck, Chiron, David, Bouabdallah, Krimo, Cartron, Guillaume, Casasnovas, Olivier, Bodet-Milin, Caroline, Ragot, Sylviane, Bossard, Céline, Nadal, Nathalie, Herbaux, Charles, Tessoulin, Benoit, Tchernonog, Emmanuelle, Rossi, Cédric, Mc Culloch, Rory, Gastinne, Thomas, Callanan, Mary, Rule, Simon, Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pessac, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université de Bourgogne (UB), Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Saint Eloi (CHRU Montpellier), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Plymouth University, Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and CHU Saint-Eloi

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

International audience; Ibrutinib, obinutuzumab plus venetoclax demonstrate synergy in pre-clinical models of mantle-cell lymphoma (MCL). OAsIs (NCT02558816), a single-arm multi-center prospective phase I/II trial, aimed to determine the maximum tolerated dose (MTD) of venetoclax in combination with fixed doses of ibrutinib and obinutuzumab, in relapsed MCL patients. At the venetoclax MTD, extension cohorts were opened for relapsed and untreated patients. Safety and efficacy were secondary objectives. Minimal residual disease (MRD) was assessed by allele-specific oligonucleotide-quantitative polymerase chain reaction (ASO-qPCR). Between Oct 14, 2015 to May 29, 2018, forty-eight patients were enrolled. No dose limiting toxicity (DLT) was reported, and venetoclax at 400mg per day was chosen for extension. Eighteen (75%) relapsed and 8 (53%) untreated patients experienced grade 3/4 adverse events (AEs). The complete response rate assessed by positron-emission tomography at the end of cycle 6 was 67% in relapsed and 86.6% in untreated patients. MRD clearance for evaluable patients was seen in 71.5% of relapsed (10 out of 14) and 100% of untreated MRD-evaluable patients (n=12), at the end of three cycles. The median follow-up (mFU) for relapsed patients was 17 months (range, 10 to 35). The 2-years PFS was 69.5% (95% CI, 52.9-91.4%) and 68.6% (95% CI, 49.5-95.1%) for OS. The mFU was 14 months (range, 5 to 19) for untreated patients, the 1-year PFS was 93.3% (95% CI, 81.5-100%). Obinutuzimab, ibrutinib and venetoclax combination is well tolerated and provides high response rates including at the molecular level in relapsed and untreated MCL patients.

Published
2020
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63. Whole genome copy number analysis in search of new prognostic biomarkers in first line treatment of mantle cell lymphoma. A study by the LYSA group

Author

Le Bris, Yannick, primary, Magrangeas, Florence, additional, Moreau, Anne, additional, Chiron, David, additional, Guérin‐Charbonnel, Catherine, additional, Theisen, Olivier, additional, Pichon, Olivier, additional, Canioni, Danielle, additional, Burroni, Barbara, additional, Maisonneuve, Hervé, additional, Thieblemont, Catherine, additional, Oberic, Lucie, additional, Gyan, Emmanuel, additional, Pellat‐Deceunynck, Catherine, additional, Hermine, Olivier, additional, Delfau‐Larue, Marie‐Hélène, additional, Tessoulin, Benoît, additional, Béné, Marie‐Christine, additional, Minvielle, Stéphane, additional, and Le Gouill, Steven, additional

Published
2020
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66. Bridging Refract-Lyma and CHUN Clinical Data Warehouse: from a research cohort to a regional electronic medical record system and back

Author

Dabin, Aimeric, Goronflot, Thomas, Tessoulin, Benoît, Chiron, David, Monlien, Anne, Le Gouill, Steven, Gourraud, Pierre-Antoine, Karakachoff, Matilde, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), L'Héma-NexT and Sysmics from i-Site NexT Nantes, France., Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Le Bihan, Sylvie

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience

Published
2019

67. BCL2-Family Dysregulation in B-Cell Malignancies: From Gene Expression Regulation to a Targeted Therapy Biomarker

Author

Tessoulin, Benoit, Papin, Antonin, Gomez-Bougie, Patricia, Bellanger, Céline, Amiot, Martine, Pellat-Deceunynck, Catherine, Chiron, David, Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), Regulation of Bcl2 and p53 networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA - Département NOHMAD - Equipe 10), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Laboratoire Jean Alexandre Dieudonné (JAD), Université Nice Sophia Antipolis (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), This work was supported by grant from FFRMG, Action Cancer 44, LHéMA-NEXT (i-site NexT) and the SIRIC ILIAD (INCaDGOS-Inserm_12558). BT was supported by INSERM (poste d’accueil) and Foundation ARC., Bernardo, Elizabeth, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
BCL2, B-cell malignancy, cell death, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, predictive markers, lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, data mining, microenvironment, Original Research
Abstract

International audience; BCL2-family proteins have a central role in the mitochondrial apoptosis machinery and their expression is known to be deregulated in many cancer types. Effort in the development of small molecules that selectively target anti-apoptotic members of this family i.e., Bcl-2, Bcl-xL, Mcl-1 recently opened novel therapeutic opportunities. Among these apoptosis-inducing agents, BH3-mimetics (i.e., venetoclax) led to promising preclinical and clinical activity in B cell malignancies. However, several mechanisms of intrinsic or acquired resistance have been described ex vivo therefore predictive markers of response as well as mechanism-based combinations have to be designed. In the present study, we analyzed the expression of the BCL2-family genes across 10 mature B cell malignancies through computational normalization of 21 publicly available Affimetrix datasets gathering 1,219 patient samples. To better understand the deregulation of anti-and pro-apoptotic members of the BCL2-family in hematological disorders, we first compared gene expression profiles of malignant B cells to their relative normal control (naïve B cell to plasma cells, n = 37). We further assessed BCL2-family expression according to tissue localization i.e., peripheral blood, bone marrow, and lymph node, molecular subgroups or disease status i.e., indolent to aggressive. Across all cancer types, we showed that anti-apoptotic genes are upregulated while pro-apoptotic genes are downregulated when compared to normal counterpart cells. Of interest, our analysis highlighted that, independently of the nature of malignant B cells, the pro-apoptotic BH3-only BCL2L11 and PMAIP1 are deeply repressed in tumor niches, suggesting a central role of the microenvironment in their regulation. In addition, we showed selective modulations across molecular subgroups and showed that the BCL2-family expression profile was related to tumor aggressiveness. Finally, by integrating recent data on venetoclax-monotherapy clinical activity with the expression of BCL2-family members involved in the venetoclax response, we determined that the ratio (BCL2+BCL2L11+BAX)/BCL2L1 was the strongest predictor of venetoclax response for mature B cell malignancies in vivo. Q10

Published
2019
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68. Additional file 1: of Whole-exon sequencing of human myeloma cell lines shows mutations related to myeloma patients at relapse with major hits in the DNA regulation and repair pathways

Author

Tessoulin, Benoît, Moreau-Aubry, Agnès, Descamps, Géraldine, Gomez-Bougie, Patricia, Maïga, Sophie, Gaignard, Alban, Chiron, David, Ménoret, Emmanuelle, Gouill, Steven, Moreau, Philippe, Amiot, Martine, and Pellat-Deceunynck, Catherine

Abstract

Additionnal Analyses and Plots. (DOCX 17568 kb)

Published
2018
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69. Ibrutinib, Venetoclax Plus Obinutuzumab in Newly Diagnosed Mantle Cell Lymphoma Patients

Author

Le Gouill, Steven, primary, Morschhauser, Franck, additional, Bouabdallah, Kamal, additional, Cartron, Guillaume, additional, Casasnovas, Olivier, additional, Gastinne, Thomas, additional, Chevallier, Patrice, additional, Rossi, Cédric, additional, Tchernonog, Emmanuelle, additional, McCulloch, Rory, additional, Herbaux, Charles, additional, Chiron, David, additional, Callanan, Mary, additional, and Rule, Simon, additional

Published
2019
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71. Correlations between p16 Protein Expression and Genomic Profile in Mantle Cell Lymphoma and Impact on Survival, a Lyma-Genomic Project Conducted on Behalf of the Lysa Group

Author

LE Bris, Yannick, primary, Canioni, Danielle, additional, Burroni, Barbara, additional, Moreau, Anne, additional, Tessoulin, Benoit, additional, Magrangeas, Florence, additional, Delfau, Marie-Helene, additional, Thieblemont, Catherine, additional, Oberic, Lucie, additional, Bouabdallah, Krimo, additional, Gyan, Emmanuel, additional, Chiron, David, additional, Pellat-deceunynck, Catherine, additional, Callanan, Mary, additional, Minvielle, Stephane, additional, Bene, Marie C, additional, Hermine, Olivier, additional, and Le Gouill, Steven, additional

Published
2018
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72. Poor Prognosis Associated with Gains of CCND1 in Mantle Cell Lymphoma Treated By First Line Immuno-Chemotherapy — a Study By the Lysa Group

Author

LE Bris, Yannick, primary, Theisen, Olivier, additional, Moreau, Anne, additional, Magrangeas, Florence, additional, Canioni, Danielle, additional, Burroni, Barbara, additional, Thieblemont, Catherine, additional, Oberic, Lucie, additional, Bouabdallah, Krimo, additional, Gyan, Emmanuel, additional, Chiron, David, additional, Pellat-deceunynck, Catherine, additional, Tessoulin, Benoit, additional, Godon, Catherine, additional, Delfau, Marie-Helene, additional, Callanan, Mary, additional, Minvielle, Stephane, additional, Bene, Marie C, additional, Hermine, Olivier, additional, and LE Gouill, Steven, additional

Published
2018
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73. Ibrutinib Plus Obinutuzumab and Venetoclax in Relapsed/Refractory Mantle Cells Lymphoma Patients, Results of the OASIS Phase I Clinical Trial

Author

Le Gouill, Steven, primary, Morschhauser, Franck, additional, Bouabdallah, Krimo, additional, Cartron, Guillaume, additional, Casasnovas, Rene-Olivier, additional, Milpied, Noel-Jean, additional, Gastinne, Thomas, additional, Davies, Andrew John, additional, Herbaux, Charles, additional, Chiron, David, additional, Callanan, Mary, additional, and Rule, Simon, additional

Published
2018
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74. CSF1R and BTK Inhibitions As Novel Strategies to Disrupt the Dialogue between Mantle Cell Lymphoma and Macrophages

Author

Papin, Antonin, primary, Tessoulin, Benoit, additional, Bellanger, Céline, additional, Moreau, Anne, additional, LE Bris, Yannick, additional, Maisonneuve, Herve, additional, Moreau, Philippe, additional, Touzeau, Cyrille, additional, Amiot, Martine, additional, Pellat-Deceunynck, Catherine, additional, Le Gouill, Steven, additional, and Chiron, David, additional

Published
2018
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77. Stationary solutions with vacuum for a one-dimensional chemotaxis model with non-linear pressure

Author

Berthelin, Florent, Chiron, David, Ribot, Magali, Laboratoire Jean Alexandre Dieudonné (LJAD), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), COmplex Flows For Energy and Environment (COFFEE), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Alexandre Dieudonné (LJAD), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), Laboratoire Jean Alexandre Dieudonné (JAD), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Alexandre Dieudonné (JAD), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), and Université Nice Sophia Antipolis (... - 2019) (UNS)

Subjects
[MATH.MATH-NA]Mathematics [math]/Numerical Analysis [math.NA]
Abstract

International audience; In this article, we study a one-dimensional hyperbolic quasi-linear model of chemotaxis with a non-linear pressure and we consider its stationary solutions, in particular with vacuum regions. We study both cases of the system set on the whole line $\Er$ and on a bounded interval with no-flux boundary conditions. In the case of the whole line $\Er$, we find only one stationary solution, up to a translation, formed by a positive density region (called bump) surrounded by two regions of vacuum. However, in the case of a bounded interval, an infinite of stationary solutions exists, where the number of bumps is limited by the length of the interval. We are able to compare the value of an energy of the system for these stationary solutions. Finally, we study the stability of these stationary solutions through numerical simulations.

Published
2016

78. Microenvironment-dependent proliferation and mitochondrial priming loss in mantle cell lymphoma is overcome by anti-CD20

Author

Chiron, David, Bellanger, Céline, Papin, Antonin, Tessoulin, Benoit, Dousset, Christelle, Maiga, Sophie, Moreau, Anne, Esbelin, Julie, Trichet, Valérie, Chen-Kiang, Selina, Moreau, Philippe, Touzeau, Cyrille, Le Gouill, Steven, Amiot, Martine, Pellat-Deceunynck, Catherine, Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Anatomie pathologique, Service de Gynécologie Obstétrique (NANTES - Gynéco Obstétrique), UMR957 (LPRO), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN), The Weill medical college, and Cornell University

Subjects
immune system diseases, hemic and lymphatic diseases, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

International audience; Key Points • CD40L plus cytokines induces cell-cycle progression and loss of mitochondrial priming, leading to drug resistance in MCL. • CD40L plus cytokines mimics in situ molecular profiles and allows the development of new approaches by integrating the role of the microenvironment. 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 Q : 5-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-kB, 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 interesting, this loss of priming was overcome by the type II anti-CD20 antibody obinutuzumab, which counteracted Bcl-x L induction through NF-kB 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. (Blood. 2016;00(00):1-11)

Published
2016
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79. Decitabine and Melphalan Fail to Reactivate p73 in p53 Deficient Myeloma Cells

Author

Gillardin, Pierre-Samuel, primary, Descamps, Géraldine, additional, Maiga, Sophie, additional, Tessoulin, Benoit, additional, Djamai, Hanane, additional, Lucani, Benedetta, additional, Chiron, David, additional, Moreau, Philippe, additional, Le Gouill, Steven, additional, Amiot, Martine, additional, Pellat-Deceunynck, Catherine, additional, and Moreau-Aubry, Agnès, additional

Published
2017
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81. A p53 score derived from TP53CRISPR/Cas9 HMCLs predicts survival and reveals a major role of BAX in the response to BH3 mimetics

Author

Durand, Romane, Descamps, Géraldine, Bellanger, Céline, Dousset, Christelle, Maïga, Sophie, Alberge, Jean-Baptiste, Derrien, Jennifer, Cruard, Jonathan, Minvielle, Stéphane, Lilli, Nicoletta Libera, Godon, Catherine, Le Bris, Yannick, Tessoulin, Benoit, Amiot, Martine, Gomez-Bougie, Patricia, Touzeau, Cyrille, Moreau, Philippe, Chiron, David, Moreau-Aubry, Agnès, and Pellat-Deceunynck, Catherine

Abstract

•A functional p53 score identifies cells with biallelic TP53invalidation and predicts survival in myeloma.•p53-regulated BAX, but not BAK, expression governs the death response to BH3 mimetics.

Published
2024
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82. Some questions related to the lifting problem in Sobolev spaces

Author

Bethuel, Fabrice, Chiron, David, Laboratoire Jacques-Louis Lions (LJLL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Chiron, David

Subjects
010101 applied mathematics, 010102 general mathematics, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], [MATH.MATH-AP] Mathematics [math]/Analysis of PDEs [math.AP], 0101 mathematics, 01 natural sciences, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2007

83. High-Resolution Whole-Genome Copy Number Profiling Identifies High-Risk and Low-Risk Patients with Mantle Cell Lymphoma, a Result of the Lyma-Genomic Project Conducted on Behalf the Lysa Group

Author

Le Bris, Yannick, primary, Magrangeas, Florence, additional, Hermine, Olivier, additional, Chiron, David, additional, Canioni, Danielle, additional, Moreau, Anne, additional, Bene, Marie C, additional, Campion, Loic, additional, Minvielle, Stephane, additional, and Le Gouill, Steven, additional

Published
2016
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84. Lymphoid-like Environment, Which Promotes Proliferation and Induces Resistance to BH3-Mimetics, Is Counteracted By Obinutuzumab in MCL: Biological Rationale for the Oasis Clinical Trial

Author

Chiron, David, primary, Bellanger, Celine, additional, Papin, Antonin, additional, Tessoulin, Benoit, additional, Dousset, Christelle, additional, Maiga, Sophie, additional, Moreau, Anne, additional, Esbelin, Julie, additional, Trichet, Valerie, additional, Chen-Kiang, Selina, additional, Moreau, Philippe, additional, Touzeau, Cyrille, additional, Le Gouill, Steven, additional, Amiot, Martine, additional, and Pellat-Deceunynck, Catherine, additional

Published
2016
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90. Rationale for targeting tumor cells in their microenvironment for mantle cell lymphoma treatment.

Author

Papin, Antonin, Chiron, David, and Le Gouill, Steven

Subjects
*MANTLE cell lymphoma, *LYMPHOMAS, *DRUG resistance, *CELL proliferation, *HODGKIN'S disease, *THERAPEUTICS, *PROGNOSIS
Abstract

Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma associated with poor prognosis, and despite recent improvements in the therapeutic strategies for treating MCL, its management remains challenging. While improvements in next generation sequencing technology have greatly increased our understanding of the intrinsic abnormalities of MCL, the role of extrinsic signaling remains largely unknown. Recent studies have highlighted the central role of the MCL microenvironment in tumor cell survival, drug resistance and proliferation. Characterization of the diverse MCL tumoral niches and comprehension of the crosstalk between tumor cells and surrounding cells within the MCL microenvironment are needed to increase treatment efficacy. Here, we reviewed the recent findings regarding the MCL microenvironment that could be rapidly translated into new therapeutic strategies to overcome drug resistance during MCL treatment. [ABSTRACT FROM AUTHOR]

Published
2018
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91. Decitabine and Melphalan Fail to Reactivate p73 in p53 Deficient Myeloma Cells.

Author

Gillardin, Pierre-Samuel, Descamps, Géraldine, Maiga, Sophie, Tessoulin, Benoit, Djamai, Hanane, Lucani, Benedetta, Chiron, David, Moreau, Philippe, Le Gouill, Steven, Amiot, Martine, Pellat-Deceunynck, Catherine, and Moreau-Aubry, Agnès

Subjects
MULTIPLE myeloma, P53 protein, CELL lines, PROTEIN expression, METHYLATION, DECITABINE
Abstract

(1) Background: TP53 deficiency remains a major adverse event in Multiple Myeloma (MM) despite therapeutic progresses. As it is not possible to target TP53 deficiency with pharmacological agents, we explored the possibility of activating another p53 family member, p73, which has not been well studied in myeloma. (2) Methods: Using human myeloma cell lines (HMCLs) with normal or abnormal TP53 status, we assessed TP73 methylation and expression. (3) Results: Using microarray data, we reported that TP73 is weakly expressed in 47 HMCLs and mostly in TP53 wild type (TP53wt) HMCLs (p = 0.0029). Q-RT-PCR assays showed that TP73 was expressed in 57% of TP53wt HMCLs (4 out of 7) and 11% of TP53 abnormal (TP53abn) HMCLs (2 out of 18) (p = 0.0463). We showed that TP73 is silenced by methylation in TP53abn HMCLs and that decitabine increased its expression, which, however, remained insufficient for significant protein expression. Alkylating drugs increased expression of TP73 only in TP53wt HMCLs but failed to synergize with decitabine in TP53abn HMCLs. (4) Conclusions: Decitabine and melphalan does not appear as a promising combination for inducing p73 and bypassing p53 deficiency in myeloma cells. [ABSTRACT FROM AUTHOR]

Published
2018
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93. Abstract 3099: Longitudinal genomic and transcriptomic analysis of mantle cell lymphoma in a targeted combination trial of a selective CDK4/6 inhibitor

Author

Vijay, Priyanka, primary, Blecua, Pedro, additional, Di Liberto, Maurizio, additional, Chiron, David, additional, Huang, Xiangao, additional, Elemento, Olivier, additional, Martin, Peter, additional, Leonard, John P., additional, Mason, Christopher E., additional, and Chen-Kiang, Selina, additional

Published
2015
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94. Abstract 3095: Longitudinal integrative whole transcriptome and exome sequencing identifies genes that reprogram lymphoma cells for clinical response to CDK4/6 inhibition in combination therapy

Author

Di Liberto, Maurizio, primary, Martin, Peter, additional, Chiron, David, additional, Vijay, Priyanka, additional, Huang, Xiangao, additional, Blecua, Pedro, additional, Ely, Scott, additional, Elemento, Olivier, additional, Leonard, John P., additional, Mason, Christopher E., additional, and Chen-Kiang, Selina, additional

Published
2015
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96. A simple flow cytometry-based barcode for routine authentication of multiple myeloma and mantle cell lymphoma cell lines

Author

Maïga, Sophie, primary, Brosseau, Carole, additional, Descamps, Géraldine, additional, Dousset, Christelle, additional, Gomez-Bougie, Patricia, additional, Chiron, David, additional, Ménoret, Emmanuelle, additional, Kervoelen, Charlotte, additional, Vié, Henri, additional, Cesbron, Anne, additional, Moreau-Aubry, Agnès, additional, Amiot, Martine, additional, and Pellat-Deceunynck, Catherine, additional

Published
2015
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98. THREE LONG WAVE ASYMPTOTIC REGIMES FOR THE NONLINEAR SCHRODINGER EQUATION

Author

Chiron, David, Laboratoire Jean Alexandre Dieudonné (JAD), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), and Edizioni della normale

Subjects
[MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP]
Abstract

International audience; We survey some recent results related to three long wave asymptotic regimes for the Nonlinear-Schrödinger Equation: the Euler regime corresponding to the WKB method, the linear wave regime and finally the KdV/KP-I asymptotic dynamics.

Published
2008

99. On the definition of Sobolev and BV spaces into metric spaces and the trace problem

Author

Chiron, David, Laboratoire Jean Alexandre Dieudonné (JAD), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Mathematics::Analysis of PDEs, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP]
Abstract

International audience; The purpose of this paper is to relate two notions of Sobolev and BV spaces into metric spaces, due to Korevaar and Schoen on the one hand, and Jost on the other hand. We prove that these two notions coincide and define the same p-energies. We review also other definitions, due to Ambrosio (for BV maps into metric spaces), Reshetnyak and finally to the notion of Newtonian-Sobolev spaces. These last approaches define the same Sobolev (or BV) spaces, but with a different energy, which does not extend the standard Dirichlet energy. We also prove a characterization of Sobolev spaces in the spirit of Bourgain, Brezis and Mironescu in terms of "limit" of the space W^{s,p} as s → 1, 0 < s < 1, and finally following the approach proposed by Nguyen. We also establish the regularity of traces of maps in W^{s,p} (0 < s ≤ 1 < sp).

Published
2007
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