A5003041443- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Cell death mechanisms and regulation
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cancer-related Molecular Pathways
- Lymphoma Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- Cancer therapeutics and mechanisms
- Cell Adhesion Molecules Research
- Cytokine Signaling Pathways and Interactions
- RNA Interference and Gene Delivery
- Chronic Lymphocytic Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- HIV/AIDS drug development and treatment
- Cancer, Hypoxia, and Metabolism
- Growth Hormone and Insulin-like Growth Factors
- Cancer Treatment and Pharmacology
- interferon and immune responses
- Protease and Inhibitor Mechanisms
Université Paris Cité
1990-2024
Assistance Publique – Hôpitaux de Paris
2024
Hôpital Saint-Louis
1984-2024
Inserm
2012-2023
Nantes Université
2012-2023
Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers
2010-2023
Université d'Angers
2016-2020
Centre National de la Recherche Scientifique
2012-2020
Centre Hospitalier Universitaire de Nantes
2004-2019
Centre d'Investigation Clinique de Nantes
2015-2018
BCL-2 family proteins dictate survival of human multiple myeloma cells, making them attractive drug targets. Indeed, cells are sensitive to antagonists that selectively target prosurvival such as BCL-2/BCL-XL (ABT-737 and ABT-263/navitoclax) or only (ABT-199/GDC-0199/venetoclax). Resistance these three drugs is mediated by expression MCL-1. However, given the selectivity profile venetoclax it unclear whether coexpression BCL-XL also affects antitumor responses in myeloma. In cell lines (n =...
Mcl-1 is an anti-apoptotic member of the Bcl-2 family which tightly regulated during myeloid and B cell differentiation. We have recently reported that expressed in human myeloma cells Bcl-xL expression are correlated. In current study, we demonstrate IL-6, a survival factor for line MDN, rapidly up-regulates whereas it has no effect on protein level. MDN cells, IL-6 induces both extracellular signal-regulated kinase (ERK)1,2 STAT3 activation STAT1 STAT5 remains undetectable. Furthermore,...
Abstract Targeting the ubiquitin-proteasome pathway has emerged as a potent anticancer strategy. Bortezomib, specific proteasome inhibitor, been approved for treatment of relapsed or refractory multiple myeloma. Multiple myeloma cell survival is highly dependent on Mcl-1 antiapoptotic molecules. In recent study, inhibitors induced accumulation that slowed down their proapoptotic effects. Consequently, we investigated role Bcl-2 family members in bortezomib-induced apoptosis. We found...
Bisphosphonates have recently been introduced in the therapeutic armamentarium for long-term treatment of patients with multiple myeloma (MM). These pyrophosphate analogs not only reduce occurrence skeletal-related events but also provide a clinical benefit and improve survival some them. We investigated effects two bisphosphonates, pamidronate zoledronate, on both cells bone marrow stromal (BMSCs). show here that bisphosphonates induce cell BMSC apoptosis. Furthermore, at lower...
Background Multiple myeloma is a plasma-cell tumor with heterogeneity in molecular abnormalities and treatment response.Design Methods We have assessed whether human cell lines kept patients' using Affymetrix gene expression profiling of 40 obtained or without IL6 addition could provide signature for stratification patient risk.Results Human lines, especially those derived the presence IL6, displayed that overlaps patients multiple myeloma. segregated into 6 groups marked by overexpression...
Escape from apoptosis is one of the major hallmarks cancer cells. The B-cell Lymphoma 2 (BCL-2) gene family encodes pro-apoptotic and anti-apoptotic proteins that are key regulators apoptotic process. Overexpression pro-survival member BCL-2 a well-established mechanism contributing to oncogenesis chemoresistance in several cancers, including lymphoma leukemia. Thus, has become an attractive target for therapeutic strategy cancer, as demonstrated by recent approval ABT-199 (Venclexta™)...
Multiple myeloma (MM) arises from malignant immunoglobulin (Ig)-secreting plasma cells and remains an incurable, often lethal disease despite therapeutic advances. The unfolded-protein response sensor IRE1α supports protein secretion by deploying a kinase-endoribonuclease module to activate the transcription factor XBP1s. MM may co-opt IRE1α-XBP1s pathway; however, validity of as potential target is controversial. Genetic disruption or XBP1s, pharmacologic kinase inhibition, attenuated...
Multiple myeloma (MM) is a slowly proliferative malignancy in which malignant plasma cells accumulate within the bone marrow. The expression of several anti-apoptotic proteins was evaluated by immunoblotting human cell lines and highly purified native cells. Expression Bcl-xL, Mcl-1 Bcl-2 found most samples; Bcl-xL seemed to be related on In system apoptosis growth factor deprivation cells, we showed that effect minimal whereas were tightly regulated interleukin (IL)-6. These findings...