References of "Caers, Jo"
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See detailAspects biologiques de l'angiogenèse dans le myélome multiple
Otjacques, Eléonore ULg; Binsfeld, Marilène ULg; Beguin, Yves ULg et al

in Oncohématologie (2013), 7(2), 6-12

Le myélome multiple (MM) est une maladie hématologique caractérisée par la prolifération excessive de plasmocytes cancéreux au sein de la moelle osseuse. Une des caractéristiques principales de cette ... [more ▼]

Le myélome multiple (MM) est une maladie hématologique caractérisée par la prolifération excessive de plasmocytes cancéreux au sein de la moelle osseuse. Une des caractéristiques principales de cette maladie est l’interaction entre les cellules myélomateuses et les cellules voisines situées dans la moelle. De par l’activation des cellules endothéliales, l’angiogenèse joue un rôle essentiel dans le développement du MM. Dans cet article, les processus permettant la progression du phénomène d’angiogenèse dans le MM seront abordés. Entre autres, nous identifierons les cellules interagissant avec les plasmocytes cancéreux, les cytokines influençant l’angiogenèse ou encore les protéases responsables de la dégradation de la matrice extracellulaire impliquées dans la pathologie. Finalement, l’influence du phénomène d’hypoxie (via l’expression de la protéine hypoxia-inducible factor-1) et le rôle de l’activation constitutive du Nuclear Factor-kB dans la néovascularisation seront mis en avant. [less ▲]

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See detailMithramycin Exerts an Anti-Myeloma Effect and Displays Anti-Angiogenic Effects through Up-Regulation of Anti-Angiogenic Factors.
Otjacques, Eléonore ULg; Binsfeld, Marilène ULg; Rocks, Natacha ULg et al

in PLoS ONE (2013), 8(5), 62818

Mithramycin (MTM), a cytotoxic compound, is currently being investigated for its anti-angiogenic activity that seems to be mediated through an inhibition of the transcription factor SP1. In this study we ... [more ▼]

Mithramycin (MTM), a cytotoxic compound, is currently being investigated for its anti-angiogenic activity that seems to be mediated through an inhibition of the transcription factor SP1. In this study we evaluated its anti-myeloma effects in the syngenic 5TGM1 model in vitro as well as in vivo. In vitro, MTM inhibited DNA synthesis of 5TGM1 cells with an IC50 of 400 nM and induced an arrest in cell cycle progression at the G1/S transition point. Western-blot revealed an up-regulation of p53, p21 and p27 and an inhibition of c-Myc, while SP1 remained unaffected. In rat aortic ring assays, a strong anti-angiogenic effect was seen, which could be explained by a decrease of VEGF production and an up-regulation of anti-angiogenic proteins such as IP10 after MTM treatment. The administration of MTM to mice injected with 5TGM1 decreased 5TGM1 cell invasion into bone marrow and myeloma neovascularisation. These data suggest that MTM displays anti-myeloma and anti-angiogenic effects that are not mediated by an inhibition of SP1 but rather through c-Myc inhibition and p53 activation. [less ▲]

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See detailThe Immunomodulating Peptide Thymosin Alpha 1 Has no Effect on Multiple Myeloma Evolution and on Immune Reconstitution
Binsfeld, Marilène ULg; Otjacques, Eléonore ULg; Hannon, Muriel ULg et al

in Belgian Journal of Hematology (2013), Abstracts book(Supplement of 28th General Meeting of the Belgian Hematological Society), 41

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See detailRapamycin Prevents Experimental Sclerodermatous Chronic Graft-versus-Host Disease in mice
Belle, Ludovic ULg; Binsfeld, Marilène ULg; DUBOIS, Sophie ULg et al

in Belgian Journal of Hematology (2012), Abstracts book(Supplement of 27th General Meeting of the Belgian Hematological Society), 14

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See detailRapamycin prevents experimental sclerodermatous chronic graft-versus-host disease in mice
Belle, Ludovic ULg; Binsfeld, Marilène ULg; DUBOIS, Sophie ULg et al

Conference (2012)

Background: The most widely used mice model of chronic graft-versus-host disease (cGvHD) is an MHC-matched bone marrow transplantation model of sclerodermatous cGvHD. A limitation of that model is that ... [more ▼]

Background: The most widely used mice model of chronic graft-versus-host disease (cGvHD) is an MHC-matched bone marrow transplantation model of sclerodermatous cGvHD. A limitation of that model is that mortality is relatively low, making difficult to study the impact of potentially therapeutic compounds. Aims: To develop a more severe model of cGVHD and to assess the impact of Rapamycin administration in that model. Results: Lethally irradiated Balb/C mice were injected with 10x106 bone marrow cells and 70x106 splenocytes from B10.D2 donor mice. Twenty-one days later, all mice developed cGvHD. For the severe model, donor B10.D2 mice were injected with 0.5x106 splenocytes from Balb/C twenty-one days before transplantation. All mice from the severe model (n=8) died a median of 32 days while 3 of 7 mice in the classical model survived beyond day 52. Mean survival was decreased in the severe model compared to the classical model (32 days versus 37 days; p=0.0185). Recipient mice in the severe group experienced higher weight loss, hair loss and skin fi brosis. Numbers of T lymphocytes (231.9 ± 151.4 versus 951 ± 532.8; p=0.0032) and CD4+ T cells (63.25 ± 41.93 versus 135.0 ± 14.39; p=0.0018) per microliter of blood at day 21 were lower in the severe group than in the classical model. Moreover, number of regulatory T cells (Tregs) was decreased in the severe model (1.250 ± 0.8864 versus 8.000 ± 6.753; p=0.0151). We then investigated whether rapamycin administration could prevent GVHD in the severe model. All (n=8) mice treated with PBS (placebo) died a median of 32 days after transplantation, while 6 of 8 mice given 1 mg/kg/day i.p. rapamycin survived beyond day 52 (p=0.0012). Number of Tregs/μl was higher at day 21 in rapamycin-treated mice than in mice given PBS (2.000±1.195 versus 1.250±0.8864; p=0.0796). Moreover, number of naïve CD4+T (10.00±4.192 versus 30.25±5.185; p= 0.0089) and effector memory T cells (EMT) (30.67±3.180 versus 67.33±7.881; p= 0.0125) were higher in rapamycin mice. Finally, proliferation of EMT (assessed by fl ow cytometry using Ki-67) was higher in PBS than in rapamycin mice (45.28%±4.084 versus 31.90%± 2.003; p=0.0474). Conclusion: We have developed a mice model of severe cGVHD. Interestingly, rapamycin prevented death from cGVHD in that model, perhaps through in vivo expansion of Treg. [less ▲]

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See detailA novel mouse model for multiple myeloma (MOPC315.BM) that allows noninvasive spatiotemporal detection of osteolytic disease.
Hofgaard, PO; Jodal, HC; Bommert, K et al

in PLoS ONE (2012), 7(12), 51892

Multiple myeloma (MM) is a lethal human cancer characterized by a clonal expansion of malignant plasma cells in bone marrow. Mouse models of human MM are technically challenging and do not always ... [more ▼]

Multiple myeloma (MM) is a lethal human cancer characterized by a clonal expansion of malignant plasma cells in bone marrow. Mouse models of human MM are technically challenging and do not always recapitulate human disease. Therefore, new mouse models for MM are needed. Mineral-oil induced plasmacytomas (MOPC) develop in the peritoneal cavity of oil-injected BALB/c mice. However, MOPC typically grow extramedullary and are considered poor models of human MM. Here we describe an in vivo-selected MOPC315 variant, called MOPC315.BM, which can be maintained in vitro. When injected i.v. into BALB/c mice, MOPC315.BM cells exhibit tropism for bone marrow. As few as 10(4) MOPC315.BM cells injected i.v. induced paraplegia, a sign of spinal cord compression, in all mice within 3-4 weeks. MOPC315.BM cells were stably transfected with either firefly luciferase (MOPC315.BM.Luc) or DsRed (MOPC315.BM.DsRed) for studies using noninvasive imaging. MOPC315.BM.Luc cells were detected in the tibiofemoral region already 1 hour after i.v. injection. Bone foci developed progressively, and as of day 5, MM cells were detected in multiple sites in the axial skeleton. Additionally, the spleen (a hematopoietic organ in the mouse) was invariably affected. Luminescent signals correlated with serum myeloma protein concentration, allowing for easy tracking of tumor load with noninvasive imaging. Affected mice developed osteolytic lesions. The MOPC315.BM model employs a common strain of immunocompetent mice (BALB/c) and replicates many characteristics of human MM. The model should be suitable for studies of bone marrow tropism, development of osteolytic lesions, drug testing, and immunotherapy in MM. [less ▲]

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See detailAdaptation of a Murine Chronic GVH Model to Study Graft versus Myeloma Effect after Allogeneic Transplantation
Binsfeld, Marilène ULg; Belle, Ludovic ULg; Hannon, Muriel ULg et al

in Belgian Journal of Hematology (2012), Abstracts book(Supplement of 27th General Meeting of the Belgian Hematological Society), 16

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See detailLymphome du manteau : prise en charge 2011
Bonnet, Christophe ULg; CAERS, Jo ULg; DE PRIJCK, Bernard ULg et al

in Revue Médicale Suisse (2011), 7

Le lymphome du manteau (LM) représente 6% des lymphomes non hodgkiniens (LNH). Le diagnostic repose sur l'immunophénotypage et la démonstration de la présence de la location entre les chromosomes 11 et 14 ... [more ▼]

Le lymphome du manteau (LM) représente 6% des lymphomes non hodgkiniens (LNH). Le diagnostic repose sur l'immunophénotypage et la démonstration de la présence de la location entre les chromosomes 11 et 14, avec surexpression de la cycline D1. Le traitement de première ligne du sujet jeune associe trois cures de R-CHOP21 alternées avec trois cures de R-DHAP21, suivies d'une autogreffe conditionnée par irradiation corporelle totale, cyclophosphamide et aracytine. Le sujet de plus de 65 ans peut bénéficier de huit cures de R-CHOP21. L'intérêt du traitement de maintenance est en cours d'évaluation. L'allogreffe de cellules souches hématopoïétiques offre une chance de guérison aux patients en rechute en bon état général. Les traitements ciblés permettront une amélioration du pronostic de cette maladie. [less ▲]

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See detailBiological aspects of angiogenesis in multiple myeloma.
Otjacques, Eléonore ULg; Binsfeld, Marilène ULg; Noël, Agnès ULg et al

in International Journal of Hematology (2011), 94(6), 505-18

Multiple myeloma (MM) is a hematological malignancy characterized by the aberrant expansion of malignant plasma cells within the bone marrow (BM). One of the hallmarks of this disease is the close ... [more ▼]

Multiple myeloma (MM) is a hematological malignancy characterized by the aberrant expansion of malignant plasma cells within the bone marrow (BM). One of the hallmarks of this disease is the close interaction between myeloma cells and neighboring cells within the BM. Angiogenesis, through the activation of endothelial cells, plays an essential role in MM biology. In the current review, we describe the angiogenesis process in MM by identifying the interacting cells, the pro- and anti-angiogenic cytokines modulated, and the extracellular matrix degrading proteases liable to participate in the pathophysiology. Finally, we highlight the impact of hypoxia (through hypoxia-inducible factor-1) and constitutive activation of nuclear factor-κB in this tumor-induced neo-vascularization. [less ▲]

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See detailPrise en charge actuelle des syndromes myélodysplasiques
CAERS, Jo ULg; BONNET, Christophe ULg; GRAUX, Carlos et al

in Revue Médicale Suisse (2011), 7

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See detailThe Belgian 2010 consensus recommendations for the treatment of multiple myeloma
Schots, R.; Delforge, M.; André, M. et al

in Acta Clinica Belgica (2010), 65

Since the introduction of novel therapeutic agents including thalidomide, lenalidomide and bortezomib, the prognosis of multiple myeloma (MM) has significantly improved. These agents have been ... [more ▼]

Since the introduction of novel therapeutic agents including thalidomide, lenalidomide and bortezomib, the prognosis of multiple myeloma (MM) has significantly improved. These agents have been incorporated into numerous treatment schedules for newly diagnosed as well as more advanced MM patients. Hence, the therapeutic options for MM have become more complex and subject to rapid changes. The multiple myeloma study group (MMSG) of the Belgian Hematological Society has established recommendations for the treatment of MM as based on an extensive review of the literature which is also summarized in this paper. The recommendations are the result of a consensus opinion between hematologists with experience in the field and representing most hematology centers in Belgium. Where applicable, reimbursement criteria are also taken into account. The consensus recommendations should be a reference for use by clinical hematologists in daily practice. [less ▲]

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See detailDiffuse xanthomatosis as a presenting feature of multiple myeloma.
Segner, Sophie; Theate, Ivan; Poire, Xavier et al

in European Journal of Haematology (2010), 84

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See detailRetroperitoneal fibrosis and multiple myeloma: fortuitous association?
Sinapi, Isabelle; Caers, Jo ULg; Connerotte, Thierry et al

in Revue de Médecine Interne (2010), 31(5), 4-6

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See detailThe effects of forodesine in murine and human multiple myeloma cells
Bieghs, Liesbeth; Caers, Jo ULg; De Bruyne, Elke et al

in Advances in Hematology (2010)

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See detailEnteroviral meningoencephalitis as complication of Rituximab therapy in a patient treated for diffuse large B-cell lymphoma
Servais, Sophie ULg; Caers, Jo ULg; Warling, Odette et al

in British Journal of Haematology (2010), 150(3), 379-381

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See detailThymosin Beta 4 has tumor suppressive effects and its decreased expression results in poor prognosis and decreased survival in multiple myeloma
Caers, Jo ULg; Hose, Dirk; Kuijpers, Ine et al

in Haematologica (2010), 95(1), 163-167

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See detailThymosin beta4 in multiple myeloma: friend or foe
Caers, Jo ULg; Otjacques, Eléonore ULg; Hose, Dirk et al

in Annals of the New York Academy of Sciences (2010), 1194(1), 125-130

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