A5014350243- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Lymphoma Diagnosis and Treatment
- Antifungal resistance and susceptibility
- Chemokine receptors and signaling
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Connective tissue disorders research
- Chronic Lymphocytic Leukemia Research
- Cancer therapeutics and mechanisms
- Biosimilars and Bioanalytical Methods
- Cell Adhesion Molecules Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Hormonal Regulation and Hypertension
- Immunodeficiency and Autoimmune Disorders
- Epigenetics and DNA Methylation
- Insect Resistance and Genetics
- Chronic Myeloid Leukemia Treatments
- Dermatological and Skeletal Disorders
- Sphingolipid Metabolism and Signaling
Ghent University Hospital
2015-2024
Janssen (Belgium)
2023-2024
Universitair Ziekenhuis Brussel
2019-2023
Vrije Universiteit Brussel
2018-2023
Ghent University
2016-2020
Bio-Medical Science (South Korea)
2018
Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces accumulation activation tumor suppressor proteins, inhibits factor κB, reduces oncoprotein messenger RNA translation, is potential novel treatment for myeloma refractory to current therapeutic options.We administered oral selinexor (80 mg) plus dexamethasone (20 twice weekly patients with who had previous exposure bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, an alkylating...
We present clinical and molecular findings of three patients with an EDS VIB phenotype from two consanguineous families. The kyphoscoliotic type (EDS VIA B) comprise kyphoscoliosis, muscular hypotonia, hyperextensible, thin bruisable skin, atrophic scarring, joint hypermobility variable ocular involvement. Distinct craniofacial abnormalities, contractures, wrinkled palms, normal urinary pyridinoline ratios distinguish VIA. A genome-wide SNP scan sequence analyses identified a homozygous...
Autosomal recessive cutis laxa type I (ARCL I) is characterized by generalized with pulmonary emphysema and/or vascular complications. Rarely, mutations can be identified in FBLN4 or FBLN5. Recently, LTBP4 have been implicated a similar phenotype. Studying FBLN4, FBLN5, and 12 families ARCL I, we found bi-allelic FBLN5 two probands, whereas nine probands harbored biallelic LTBP4. cause very phenotype associated severe emphysema, the absence of tortuosity aneurysms. Gastrointestinal...
Multiple myeloma (MM) is well-known for the development of drug resistance, leading to relapse. Therefore, finding novel treatment strategies remains necessary. By performing a lipidomics assay on MM patient plasma, we aimed identify new targets. We observed dysregulation in sphingolipid metabolism, with upregulation several ceramides and downregulation sphingomyelin. This imbalance suggests an increase sphingomyelinase, enzyme responsible hydrolyzing sphingomyelin into ceramide. confirmed...
Summary Treatment benefit in multiple myeloma (MM) patients with high‐risk cytogenetics remains suboptimal. The phase 3 ICARIA‐MM trial (NCT02990338) showed that isatuximab plus pomalidomide–dexamethasone prolongs median progression‐free survival (mPFS) relapsed/refractory MM (RRMM). This subgroup analysis of compared the [defined by presence del(17p), t(4;14) or t(14;16)] versus standard‐risk patients. efficacy gain(1q21) abnormality was also assessed a retrospective analysis. In ICARIA‐MM,...
Multiple myeloma (MM) remains an incurable cancer despite advances in therapy. Therefore, the search for new targets is still essential to uncover potential treatment strategies. Metabolic changes, induced by hypoxic bone marrow, contribute both MM cell survival and drug resistance. Pyrroline-5-carboxylate reductase 1 2 (PYCR1 PYCR2) are two mitochondrial enzymes that facilitate last step glutamine-to-proline conversion. Overexpression of PYCR1 involved progression several cancers, however,...
Abstract Multiple myeloma (MM) remains an incurable haematological malignancy despite substantial advances in therapy. Hypoxic bone marrow induces metabolic rewiring MM cells contributing to survival and drug resistance. Therefore, targeting pathways may offer alternative treatment option. In this study, we repurpose two FDA‐approved drugs, syrosingopine metformin. Syrosingopine was used as a dual inhibitor of monocarboxylate transporter 1 4 (MCT1/4) metformin for oxidative phosphorylation...
Abstract The glucocorticoid receptor (GR) is a crucial drug target in multiple myeloma as its activation with glucocorticoids effectively triggers cell death. However, high-dose are also associated deleterious side effects, novel approaches urgently needed to improve GR action myeloma. Here, we reveal functional crosstalk between and the mineralocorticoid (MR) that plays role improved killing. We show agonist dexamethasone (Dex) downregulates MR levels GR-dependent way cells. Co-treatment of...
Multiple myeloma (MM) is an (epi)genetic highly heterogeneous plasma cell malignancy that remains mostly incurable. Deregulated expression and/or genetic defects in epigenetic-modifying enzymes contribute to high-risk disease and MM progression. Overexpression of the histone methyltransferase G9a was reported several cancers, including MM, correlating with progression, metastasis, poor prognosis. However, exact role its interaction partner G9a-like protein (GLP) biology underlying mechanisms...
Background The Ehlers-Danlos Syndrome (EDS) is a heritable connective tissue disorder characterized by hyperextensible skin, joint hypermobility and soft fragility. classic subtype of EDS caused mutations in one the type V collagen genes (COL5A1 COL5A2). Most affect helical domain lead to diminished or structurally abnormal protein. Remarkably, only two were reported extended, highly conserved N-propeptide domain, which plays an important role regulation heterotypic fibril diameter. We...
This prospective, multicenter, phase II study investigated the use of four cycles bortezomib-dexamethasone induction treatment, followed by high-dose melphalan and autologous stem cell transplantation (SCT) in patients with newly diagnosed light chain amyloidosis. The aim was to improve hematologic complete remission (CR) rate 6 months after SCT from 30% 50%. Fifty were enrolled 72% had two or more organs involved. overall response treatment 80% including 20% CR 38% very good partial...
Immunotherapy emerged as a promising treatment option for multiple myeloma (MM) patients. However, therapeutic efficacy can be hampered by the presence of an immunosuppressive bone marrow microenvironment including myeloid cells. S100A9 was previously identified key regulator cell accumulation and suppressive activity. Tasquinimod, small molecule inhibitor S100A9, is currently in phase Ib/IIa clinical trial MM patients (NCT04405167). We aimed to gain more insights into its mechanisms action...
Multiple myeloma (MM) is a hematological malignancy characterized by the presence of clonal plasma cells in bone marrow niche. Despite significant therapeutic advances, MM remains incurable for majority patients. Targeted radionuclide therapy (TRNT) has emerged as promising treatment option to eradicate residual cancer cells. In this study, we developed and single-domain antibodies (sdAbs) against MM-antigen CS1 evaluated its potential using TRNT. We first validated target expressed normal...
Early-stage chronic lymphocytic leukemia (CLL) challenges specialized management and follow-up.We developed validated a prognostic index to identify newly diagnosed patients without need of treatment (CLL-WONT) by training/validation approach using data on 4708 patients. Composite scores derived from weighted hazards multivariable analysis defined CLL-WONT risk groups.Age (>65 years: 1 point), Binet stage (B: 2 points), lactate dehydrogenase (LDH) (>205 U/L: absolute lymphocyte count (15-30...
Multiple Myeloma (MM) is the second most prevalent hematological malignancy and incurable due to inevitable development of drug resistance. The methionine adenosyltransferase 2α (MAT2A) primary producer methyl donor S-adenosylmethionine (SAM) several studies reported MAT2A deregulation in different solid cancers. As role MM not studied yet, aim this study was clarify potential underlying molecular mechanisms MM, exploring new therapeutic options overcome By analyzing publicly available gene...
Murine models for multiple myeloma (MM) are often used to investigate pathobiology of and disease progression. Unlike transgenic mice models, where it is known which oncogene driving MM disease, the somatic aberrations spontaneous syngeneic 5T have not yet been reported. Here, we analyzed copy-number alterations (CNA) mutational landscape 5T2, 5T33vv 5TGM1 murine using whole-genome whole-exome sequencing. Forty four percent genome 5T2 cells affected by CNAs while this was only 11% 17% cells,...
Abstract While multi‐drug combinations and continuous treatment have become standard for multiple myeloma, the disease remains incurable. Repurposing drugs that are currently used other indications could provide a novel approach to improve therapeutic efficacy of myeloma treatments. Here, we assessed anti‐tumor effects cardiac called β‐blockers as single agent in combination with commonly anti‐myeloma therapies. Expression β 2 ‐adrenergic receptor correlated poor survival outcomes patients...
The aggressive B-cell non-Hodgkin lymphomas diffuse large lymphoma (DLBCL) and mantle cell (MCL) are characterised by a high proliferation rate. anaphase-promoting complex/cyclosome (APC/C) its co-activators Cdc20 Cdh1 represent an important checkpoint in mitosis. Here, the role of APC/C is examined DLBCL MCL. expression prognostic value was investigated using GEP data immunohistochemistry. Moreover, therapeutic potential targeting evaluated small-molecule inhibitor proTAME underlying...