Publications
152 results found
Mateos M, Gavriatopoulou M, Facon T, et al., 2020, Effect of Prior Treatment with Proteasome Inhibitors on the Efficacy and Safety of Once-Weekly Selinexor, Bortezomib, and Dexamethasone in Comparison with Twice-Weekly Bortezomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Subgroup Analysis from the Boston Study, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Richard S, Chari A, Delimpasi S, et al., 2020, Once Weekly Selinexor, Bortezomib, and Dexamethasone (SVd) Versus Twice Weekly Bortezomib and Dexamethasone (Vd) in Relapsed or Refractory Multiple Myeloma: High-Risk Cytogenetic Risk Planned Subgroup Analyses from the Phase 3 Boston Study, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
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- Citations: 1
Sanchez L, Leleu X, Beaumont J, et al., 2020, Peripheral Neuropathy Symptoms, Pain and Functioning in Relapsed or Refractory Multiple Myeloma Patients Treated with Selinexor, Bortezomib, and Dexamethasone, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Mateos M, Jagannath S, Delimpasi S, et al., 2020, Impact of Prior Therapies on the Safety and Efficacy of Once Weekly Selinexor, Bortezomib, and Dexamethasone Compared with Twice Weekly Bortezomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Results from the Boston Study, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Hinsley S, Walker K, Sherratt D, et al., 2020, The MUK eight protocol: A randomised phase II trial of Cyclophosphamide and Dexamethasone in combination with Ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a proteasome inhibitor, Trials, Vol: 21, ISSN: 1745-6215
BackgroundMultiple myeloma is a plasma cell tumour with approximately 5500 new cases in the UK each year. Ixazomib is a next generation inhibitor of the 20S proteasome and is thought to be an effective treatment for those who have relapsed from bortezomib. The combination of cyclophosphamide and dexamethasone (CD) is a recognised treatment option for patients with relapsed refractory multiple myeloma (RRMM) who have relapsed after treatment with bortezomib and lenalidomide, whilst also often being combined with newer proteasome inhibitors. The most apparent combination for ixazomib is therefore with CD.MethodsMUK eight is a randomised, controlled, open, parallel group, multi-centre phase II trial that will recruit patients with RRMM who have relapsed after treatment with thalidomide, lenalidomide, and a proteasome inhibitor. The primary objective of the trial is to evaluate whether ixazomib in combination with cyclophosphamide and dexamethasone (ICD) has improved clinical activity compared to CD in terms of progression-free survival (PFS). Secondary objectives include comparing toxicity profiles and the activity and cost-effectiveness of both treatments. Since opening, the trial has been amended to allow all participants who experience disease progression (as per the IMWG criteria) on the CD arm to subsequently switch to receive ICD treatment, once progression has been confirmed with two clinical members of the Trial Management Group (TMG). This ‘switch’ phase of the study is exploratory and will assess second progression-free survival measured from randomisation to second disease progression (PFS2) and progression-free survival from the point of switching to second disease progression (PFS Switch) in participants who switch from CD to ICD treatment.DiscussionDevelopment of ixazomib offers the opportunity to further investigate the value of proteasome inhibition through oral administration in the treatment of RRMM. Previous studies investigating the safe
Dimopoulos MA, Delimpasi S, Simonova M, et al., 2020, Weekly selinexor, bortezomib, and dexamethasone (SVd) versus twice weekly bortezomib and dexamethasone (Vd) in patients with multiple myeloma (MM) after one to three prior therapies: Initial results of the phase III BOSTON study., Annual Scientific Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
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- Citations: 21
Saavedra-Garcia P, Martini F, Auner HW, 2020, Proteasome inhibition in multiple myeloma: lessons for other cancers, AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, Vol: 318, Pages: C451-C462, ISSN: 0363-6143
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- Citations: 15
Morris C, Chabannon C, Masszi T, et al., 2020, Results from a multi-center, non-interventional registry study for multiple myeloma patients who received stem cell mobilization regimens with and without plerixafor, Bone Marrow Transplantation, Vol: 55, Pages: 356-366, ISSN: 1476-5365
Plerixafor plus granulocyte-colony stimulating factor (G-CSF) enhances the mobilization of haematopoietic stem cells (HSCs) for collection and subsequent autologous haematopoietic stem cell transplantation (HSCT) in patients with multiple myeloma (MM).This international, multicenter, non-interventional registry study (NCT01362972), evaluated long-term outcomes for MM patients who received plerixafor versus other mobilization regimens. The comparisons were: G-CSF+plerixafor (G-CSF+P) versus G-CSF-; G-CSF+P versus G-CSF+chemotherapy (G-CSF+C); and G-CSF+P+C versus G-CSF+C. Propensity score matching was used to balance groups. Primary outcome measures were progression free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR) after transplantation. After propensity matching, 77 versus 41 patients in the G-CSF+P versus G-CSF cohorts, 129 versus 129 in the G-CSF+P versus G-CSF+C cohort and 117 versus 117 in the G-CSF+P+C versus G-CSF+C cohort, were matched, respectively. Propensity score matching resulted in a smaller sample size and imbalances were not completely overcome. For both PFS and OS, the upper limits of the hazard ratio 95% confidence intervals exceeded pre-specified boundaries; non-inferiority was not demonstrated. CIR rates were higher in the plerixafor cohorts. G-CSF+P remains an option for the mobilization of HSCs in poor-mobilizers with MM with no substantial differences in PFS, OS and CIR in comparison with other regimens.
Graziani G, Herget G, Ihorst G, et al., 2020, Time from first symptom onset to the final diagnosis of Multiple Myeloma (MM) - possible risks and future solutions: retrospective and prospective ‘Deutsche Studiengruppe MM’ (DSMM) and ‘European Myeloma Network’ (EMN) analysis, Leukemia and Lymphoma, Vol: 61, Pages: 875-886, ISSN: 1026-8022
Multiple Myeloma (MM) often presents with unspecific symptoms and is challenging to diagnose. We performed this DSMM/EMN-analysis via test-(retro-) and validation (prospective) study to determine the time interval from the onset of first symptoms to the diagnosis of MM. The retrospective and prospective analyses were performed in 101 and 176 patients, respectively. The median time from first symptoms to the MM diagnosis in both cohorts was 4 and 6 months, respectively. Frequencies of MM-related pathologic bone fractures, renal and infectious complications at diagnosis occurred in 41%, 35% and 16% of patients, respectively. Our MM-questionnaire determined that 39% of patients were dissatisfied with the diagnostic process. PFS and OS proved insignificantly different with shorter (≤6) and longer (>6 months) latency periods. In conclusion, our in depth studies demonstrate that delays in diagnosis do not decrease PFS or OS, but induce MM-related complications and influence patients' satisfaction with their medical care.
Ponnusamy K, Tzioni M-M, Begum M, et al., 2019, Novel ZBP1-IRF3 Dependency in Multiple Myeloma Mediated By IRF3-Driven Regulation of Cell Cycle Genes, BLOOD, Vol: 134, ISSN: 0006-4971
Saavedra-Garcia P, Al-Sadah HA, Penfold L, et al., 2019, Integrated Systems Level Examination of Proteasome Inhibitor Stress Recovery in Myeloma Cells Reveals Druggable Vulnerabilities Linked to Multiple Metabolic Processes, 61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Trasanidis N, Alvarez-Benayas J, Katsarou A, et al., 2019, Distinct Chromatin Accessibility Changes, Aberrant Transcription Factor Networks Combined with Novel Oncogenic Enhancers Characterise Myeloma-Initiating Genetic Events, 61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Caputo VS, Trasanidis N, Xiao X, et al., 2019, Myc and Bet Proteins Orchestrate the Early Regulatory Genome Changes Required for Osteoclast Lineage Commitment, 61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Brown SR, Hall A, Kendall J, et al., 2019, Muktwelve: A Randomized Phase II Trial of Selinexor, Cyclophosphamide and Prednisolone Vs Cyclophosphamide and Prednisolone in Relapsed or Refractory Multiple Myeloma (RRMM) Patients, 61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
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- Citations: 1
Trasanidis N, Katsarou A, Bergonia B, et al., 2019, PBX1 Co-Operates with FOXM1 to Regulate Myeloma Cell Proliferation and to Define an Ultra High-Risk chr1q Gain Myeloma Patient Subgroup, BLOOD, Vol: 134, ISSN: 0006-4971
Bringhen S, Milan A, D'Agostino M, et al., 2019, Prevention, monitoring and treatment of cardiovascular adverse events in myeloma patients receiving carfilzomib - A Consensus Paper by the European Myeloma Network and the Italian Society of Arterial Hypertension, Journal of Internal Medicine, Vol: 286, Pages: 63-74, ISSN: 0954-6820
The novel proteasome inhibitor carfilzomib alone or in combination with other agents is already one of the standard therapies in relapsed and/or refractory multiple myeloma (MM) patients and produces impressive response rates in newly diagnosed MM as well. However, carfilzomib-related cardiovascular adverse events (CVAEs) - including hypertension (all grades: 12.2%; grade ≥3: 4.3%), heart failure (all grades: 4.1%; grade ≥3: 2.5%) and ischemic heart disease (all grades: 1.8%; grade ≥3: 0.8%) - may lead to treatment suspensions. At present, there are neither prospective studies nor expert consensus on the prevention, monitoring and treatment of CVAEs in myeloma patients treated with carfilzomib. An expert panel of the European Myeloma Network in collaboration with the Italian Society of Arterial Hypertension and with the endorsement of the European Hematology Association aimed to provide recommendations to support health professionals in selecting the best management strategies for patients, considering the impact on outcome, the risk-benefit ratio of diagnostic and therapeutic tools and thereby to achieve myeloma response with novel combination approaches, while preventing CVAEs. Patients scheduled to receive carfilzomib need a careful cardiovascular evaluation before treatment and an accurate follow-up during treatment. A detailed clinical assessment before starting carfilzomib treatment is essential to identify patients at risk for CVAEs, and accurate monitoring of blood pressure and of early signs and symptoms suggestive of cardiac dysfunction remains pivotal to safely administer carfilzomib without treatment interruptions or dose reductions. This article is protected by copyright. All rights reserved.
Tornatore L, Capece D, D'Andrea D, et al., 2019, Clinical proof of concept for a safe and effective NF-κB-targeting strategy in multiple myeloma, British Journal of Haematology, Vol: 185, Pages: 588-592, ISSN: 1365-2141
Tornatore L, Capece D, D'Andrea D, et al., 2019, Preclinical toxicology and safety pharmacology of the first-in-class GADD45β/MKK7 inhibitor and clinical candidate, DTP3, Toxicology Reports, Vol: 6, Pages: 369-379, ISSN: 2214-7500
Aberrant NF-κB activity drives oncogenesis and cell survival in multiple myeloma (MM) and many other cancers. However, despite an aggressive effort by the pharmaceutical industry over the past 30 years, no specific IκBα kinase (IKK)β/NF-κB inhibitor has been clinically approved, due to the multiple dose-limiting toxicities of conventional NF-κB-targeting drugs. To overcome this barrier to therapeutic NF-κB inhibition, we developed the first-in-class growth arrest and DNA-damage-inducible (GADD45)β/mitogen-activated protein kinase kinase (MKK)7 inhibitor, DTP3, which targets an essential, cancer-selective cell-survival module downstream of the NF-κB pathway. As a result, DTP3 specifically kills MM cells, ex vivo and in vivo, ablating MM xenografts in mice, with no apparent adverse effects, nor evident toxicity to healthy cells. Here, we report the results from the preclinical regulatory pharmacodynamic (PD), safety pharmacology, pharmacokinetic (PK), and toxicology programmes of DTP3, leading to the approval for clinical trials in oncology. These results demonstrate that DTP3 combines on-target-selective pharmacology, therapeutic anticancer efficacy, favourable drug-like properties, long plasma half-life and good bioavailability, with no target-organs of toxicity and no adverse effects preclusive of its clinical development in oncology, upon daily repeat-dose administration in both rodent and non-rodent species. Our study underscores the clinical potential of DTP3 as a conceptually novel candidate therapeutic selectively blocking NF-κB survival signalling in MM and potentially other NF-κB-driven cancers.
Parzych K, Saavedra Garcia P, Valbuena G, et al., 2019, The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation, Oncogene, Vol: 38, Pages: 3216-3231, ISSN: 0950-9232
VCP/p97 regulates numerous cellular functions by mediating protein degradation through its segregase activity. Its key role in governing protein homoeostasis has made VCP/p97 an appealing anticancer drug target. Here, we provide evidence that VCP/p97 acts as a regulator of cellular metabolism. We found that VCP/p97 was tied to multiple metabolic processes on the gene expression level in a diverse range of cancer cell lines and in patient-derived multiple myeloma cells. Cellular VCP/p97 dependency to maintain proteostasis was increased under conditions of glucose and glutamine limitation in a range of cancer cell lines from different tissues. Moreover, glutamine depletion led to increased VCP/p97 expression, whereas VCP/p97 inhibition perturbed metabolic processes and intracellular amino acid turnover. GCN2, an amino acid-sensing kinase, attenuated stress signalling and cell death triggered by VCP/p97 inhibition and nutrient shortages and modulated ERK activation, autophagy, and glycolytic metabolite turnover. Together, our data point to an interconnected role of VCP/p97 and GCN2 in maintaining cancer cell metabolic and protein homoeostasis.
Ferreira SA, Motwani MS, Faull PA, et al., 2018, Bi-directional cell-pericellular matrix interactions direct stem cell fate (vol 9, 5419, 2018), NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723
Yong K, Hinsley S, De Tute RM, et al., 2018, Maintenance with Carfilzomib Following Carfilzomib, Cyclophosphamide and Dexamethasone at First Relapse or Primary Refractory Multiple Myeloma (MM) on the Phase 2 Muk <i>Five</i> Study: Effect on Minimal Residual Disease, 60th Annual Meeting of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
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- Citations: 2
Yong K, Hinsley S, Sherratt D, et al., 2018, Carfilzomib Versus Bortezomib in Combination with Cyclophosphamide and Dexamethasone for Treatment of First Relapse or Primary Refractory Multiple Myeloma (MM): Outcomes Based on Genetic Risk and Long Term Follow up of the Phase 2 Muk <i>Five</i> Study, 60th Annual Meeting of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
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- Citations: 2
Ferreira SA, Motwani MS, Faull PA, et al., 2018, Bi-directional cell-pericellular matrix interactions direct stem cell fate (vol 9, 4049, 2018), NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723
Caers J, Garderet L, Kortüm KM, et al., 2018, European Myeloma Network recommendations on tools for the diagnosis and monitoring of multiple myeloma: what to use and when., Haematologica, Vol: 103, Pages: 1772-1784, ISSN: 0390-6078
The diagnosis of multiple myeloma can be challenging, even for experienced physicians, and requires close collaboration between numerous disciplines (orthopedics, radiology, nuclear medicine, radiation therapy, hematology and oncology) before the final diagnosis of myeloma is made. The definition of multiple myeloma is based on the presence of clinical, biochemical, histopathological, and radiological markers of disease. Specific tests are needed both at presentation and during follow-up in order to reach the correct diagnosis and characterize the disease precisely. These tests can also serve prognostic purposes and are useful for follow-up of myeloma patients. Molecular analyses remain pivotal for defining high-risk myeloma and are used in updated patient stratifications, while minimal residual disease assessment via flow cytometry, molecular techniques and radiological approaches provides additional prognostic information on patients' long-term outcome. This pivotal information will guide our future treatment decisions in forthcoming clinical trials. The European Myeloma Network group updated their guidelines on different diagnostic recommendations, which should be of value to enable appropriate use of the recommendations both at diagnosis and during follow-up.
Loaiza S, Ferreira SA, Chinn TM, et al., 2018, An engineered, quantifiable in vitro model for analysing the effect of proteostasis-targeting drugs on tissue physical properties., Biomaterials, Vol: 183, Pages: 102-113
Cellular function depends on the maintenance of protein homeostasis (proteostasis) by regulated protein degradation. Chronic dysregulation of proteostasis is associated with neurodegenerative and age-related diseases, and drugs targeting components of the protein degradation apparatus are increasingly used in cancer therapies. However, as chronic imbalances rather than loss of function mediate their pathogenesis, research models that allow for the study of the complex effects of drugs on tissue properties in proteostasis-associated diseases are almost completely lacking. Here, to determine the functional effects of impaired proteostatic fine-tuning, we applied a combination of materials science characterisation techniques to a cell-derived, in vitro model of bone-like tissue formation in which we pharmacologically perturbed protein degradation. We show that low-level inhibition of VCP/p97 and the proteasome, two major components of the degradation machinery, have remarkably different effects on the bone-like material that human bone-marrow derived mesenchymal stromal cells (hMSC) form in vitro. Specifically, whilst proteasome inhibition mildly enhances tissue formation, Raman spectroscopic, atomic force microscopy-based indentation, and electron microscopy imaging reveal that VCP/p97 inhibition induces the formation of bone-like tissue that is softer, contains less protein, appears to have more crystalline mineral, and may involve aberrant micro- and ultra-structural tissue organisation. These observations contrast with findings from conventional osteogenic assays that failed to identify any effect on mineralisation. Taken together, these data suggest that mild proteostatic impairment in hMSC alters the bone-like material they form in ways that could explain some pathologies associated with VCP/p97-related diseases. They also demonstrate the utility of quantitative materials science approaches for tackling long-standing questions in biology and medicine, and could f
Kaliszczak M, Hechanova E, Alsadah H, et al., 2018, The HDAC6 inhibitor C1A modulates autophagy substrates in diverse cancer cells and induces cell death, British Journal of Cancer, Vol: 119, Pages: 1278-1287, ISSN: 0007-0920
BACKGROUND: Cytosolic Deacetylase HDAC6 is involved in the autophagy degradationpathway of malformed proteins, an important survival mechanism in cancer cells. Weevaluated modulation of autophagy-related proteins and cell death by the HDAC6-selectiveinhibitor C1A.METHODS: Autophagy substrates (LC3 and p62 proteins) and endoplasmic reticulum (ER)stress phenotype were determined. Caspase 3/7 activation and cellular proliferation assayswere used to assess consequences of autophagy modulation.RESULTS: C1A potently resolved autophagy substrates induced by 3-MA and chloroquine.The mechanism of autophagy inhibition by HDAC6 genetic knockout or C1A treatmentwas consistent with abrogation of autophagosome-lysosome fusion, and decrease of Mycprotein. C1A alone or combined with the proteasome inhibitor, bortezomib, enhanced celldeath in malignant cells demonstrating the complementary roles of the proteasome andautophagy pathways for clearing malformed proteins. Myc positive neuroblastoma, KRASpositive colorectal cancer and multiple myeloma cells showed marked cell growthinhibition in response to HDAC6 inhibitors. Finally, growth of neuroblastoma xenograftswas arrested in vivo by single agent C1A, while combination with bortezomib slowed thegrowth of colorectal cancer xenografts.CONCLUSIONS: C1A resolves autophagy substrates in malignant cells and induces celldeath, warranting its use for in vivo pre-clinical autophagy research.
Ferreira SA, Motwani MS, Faull PA, et al., 2018, Bi-directional cell-pericellular matrix interactions direct stem cell fate, Nature Communications, Vol: 9, ISSN: 2041-1723
Modifiable hydrogels have revealed tremendous insight into how physical characteristics of cells’ 3D environment drive stem cell lineage specification. However, in native tissues, cells do not passively receive signals from their niche. Instead they actively probe and modify their pericellular space to suit their needs, yet the dynamics of cells’ reciprocal interactions with their pericellular environment when encapsulated within hydrogels remains relatively unexplored. Here, we show that human bone marrow stromal cells (hMSC) encapsulated within hyaluronic acid-based hydrogels modify their surroundings by synthesizing, secreting and arranging proteins pericellularly or by degrading the hydrogel. hMSC’s interactions with this local environment have a role in regulating hMSC fate, with a secreted proteinaceous pericellular matrix associated with adipogenesis, and degradation with osteogenesis. Our observations suggest that hMSC participate in a bi-directional interplay between the properties of their 3D milieu and their own secreted pericellular matrix, and that this combination of interactions drives fate.
Ferreira SA, Faull PA, Seymore AJ, et al., 2018, Neighboring cells override 3D hydrogel matrix cues to drive human MSC quiescence, Biomaterials, Vol: 176, Pages: 13-23, ISSN: 0142-9612
Physical properties of modifiable hydrogels can be tuned to direct stem cell differentiation in a role akin to that played by the extracellular matrix in native stem cell niches. However, stem cells do not respond to matrix cues in isolation, but rather integrate soluble and non-soluble signals to balance quiescence, self-renewal and differentiation. Here, we encapsulated single cell suspensions of human mesenchymal stem cells (hMSC) in hyaluronic acid-based hydrogels at high and low densities to unravel the contributions of matrix- and non-matrix-mediated cues in directing stem cell response. We show that in high-density (HD) cultures, hMSC do not rely on hydrogel cues to guide their fate. Instead, they take on characteristics of quiescent cells and secrete a glycoprotein-rich pericellular matrix (PCM) in response to signaling from neighboring cells. Preventing quiescence precluded the formation of a glycoprotein-rich PCM and forced HD cultures to differentiate in response to hydrogel composition. Our observations may have important implications for tissue engineering as neighboring cells may act counter to matrix cues provided by scaffolds. Moreover, as stem cells are most regenerative if activated from a quiescent state, our results suggest that ex vivo native-like niches that incorporate signaling from neighboring cells may enable the production of clinically relevant, highly regenerative cells.
Taheem DK, Foyt DA, Loaiza S, et al., 2018, Differential regulation of human bone marrow mesenchymal stromal cell chondrogenesis by hypoxia inducible factor-1α hydroxylase inhibitors, Stem Cells, Vol: 36, Pages: 1380-1392, ISSN: 1066-5099
The transcriptional profile induced by hypoxia plays important roles in the chondrogenic differentiation of marrow stromal/stem cells (MSC) and is mediated by the Hypoxia Inducible Factor complex. However, various compounds can also stabilise HIF's oxygen-responsive element, HIF-1α, at normoxia and mimic many hypoxia-induced cellular responses. Such compounds may prove efficacious in cartilage tissue engineering, where microenvironmental cues may mediate functional tissue formation. Here, we investigated three HIF stabilising compounds, which each have distinct mechanisms of action, to understand how they differentially influenced the chondrogenesis of human bone marrow-derived MSC (hBM-MSC) in vitro. hBM-MSCs were chondrogenically-induced in TGF-β3 -containing media in the presence of HIF-stabilising compounds. HIF-1α stabilisation was assessed by HIF-1α immunofluorescence staining, expression of HIF target and articular chondrocyte specific genes by qPCR, and cartilage-like extracellular matrix (ECM) production by immunofluorescence and histochemical staining. We demonstrate that all three compounds induced similar levels of HIF-1α nuclear localisation. However, whilst the 2-oxoglutarate analogue Dimethyloxalylglycine (DMOG) promoted upregulation of a selection of HIF target genes, Desferrioxamine (DFX) and Cobalt Chloride (CoCl2 ), compounds that chelate or compete with Fe2+ , respectively, did not. Moreover, DMOG induced a more chondrogenic transcriptional profile, which was abolished by Acriflavine, an inhibitor of HIF-1α-HIF-β binding, whilst the chondrogenic effects of DFX and CoCl2 were more limited. Together, these data suggest that HIF-1α function during hBM-MSC chondrogenesis may be regulated by mechanisms with a greater dependence on 2-oxoglutarate than Fe2+ availability. These results may have important implications for understanding cartilage disease and developing targeted therapies for cartilage repair. T
Morris C, Chabannon C, Masszi T, et al., 2018, Analysis of Data Collected in the European Group for Blood and Marrow Transplantation (EBMT) Registry on a Cohort of Myeloma Patients Receiving Plerixafor, 44th Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: 761-762, ISSN: 0268-3369
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