References of "Beguin, Yves"
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See detailPrimary immune thrombocytopenia in adults
Janssens, A.; Lambert, C.; Bries, G. et al

in Belgian Journal of Hematology (2013), 4(1), 2-11

The Belgian Hematological Society (BHS) guideline panel on adult primary immune thrombocytopenia (ITP) reviewed the recent literature on diagnosis and treatment to make recommendations on the best ... [more ▼]

The Belgian Hematological Society (BHS) guideline panel on adult primary immune thrombocytopenia (ITP) reviewed the recent literature on diagnosis and treatment to make recommendations on the best strategies for frontline and subsequent-line treatment. No treatment is necessary for patients with platelet counts higher than 30000/ l in the absence of bleeding symptoms. Patients newly diagnosed or relapsing after a long-term treatment-free period can be managed with corticosteroids with or without intravenous immunoglobulins. A second line therapy is indicated for those patients who are intolerant or unresponsive to or relapse after initial corticosteroid treatment and have a risk of bleeding. The guideline panel recommends splenectomy as it is the treatment with the highest curative potential and an acceptable safety pro le. If possible, splenectomy should be delayed to at least twelve months after diagnosis as spontaneous remission can occur in this time period. Thrombopoietin receptor (TPO-R) agonists are recommended for patients who are refractory to or relapse after splenectomy or who have a contra-indication to splenectomy irrespective of the duration of ITP. The guideline panel agrees that rituximab, azathioprine, cyclophosphamide, cyclosporine A, danazol, dapsone, mycophenolate mofetil and vincristine/vinblastine are potential treatment options, especially for patients refractory to TPO-R agonists. [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 detailComparison of Immune Reconstitution after Hematopoietic Stem Cell Transplantation with Flu-TBI versus TLI-ATG Conditioning
Hannon, Muriel ULg; Humblet-Baron, S.; Graux, C. et al

in Belgian Journal of Hematology (2013), Abstracts book(Supplement of 28th General Meeting of the Belgian Hematological Society), 38

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See detailInfusion of CliniMACS (Myltenyi Biotec) Enriched Regulatory T Cells Delays Experimental Xenogeneic Graft-versus-Host Disease
Hannon, Muriel ULg; Lechanteur, C.; Somja, Joan ULg et al

in Belgian Journal of Hematology (2013), Abstracts book(Supplement of 28th General Meeting of the Belgian Hematological Society), 15

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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 detailKinetics of IL-7 and IL-15 Levels after Allogeneic Peripheral Blood Stem Cell Transplantation following Nonmyeloablative Conditioning
De Bock, Muriel; Fillet, Marianne ULg; Hannon, Muriel ULg et al

in PLoS ONE (2013), 8(2), 55876

Background: We analysed kinetics of IL-7 and IL-15 levels in 70 patients given peripheral blood stem cells after nonmyeloablative conditioning. Methods: EDTA-anticoagulated plasma and serum samples were ... [more ▼]

Background: We analysed kinetics of IL-7 and IL-15 levels in 70 patients given peripheral blood stem cells after nonmyeloablative conditioning. Methods: EDTA-anticoagulated plasma and serum samples were obtained before conditioning and about once per week after transplantation until day 100. Samples were aliquoted and stored at 280uC within 3 hours after collection until measurement of cytokines. IL-7 and IL-15 levels were measured by ELISAs. Results: Median IL-7 plasma levels remained below 6 pg/L throughout the first 100 days, although IL-7 plasma levels were significantly higher on days 7 (5.1 pg/mL, P = 0.002), 14 (5.2 pg/mL, P,0.001), and 28 (5.1 pg/mL, P = 0.03) (but not thereafter) than before transplantation (median value of 3.8 pg/mL). Median IL-15 serum levels were significantly higher on days 7 (12.5 pg/mL, P,0.001), 14 (10.5 pg/mL, P,0.001), and 28 (6.2 pg/mL, P,0.001) than before transplantation (median value of 2.4 pg/mL). Importantly, IL-7 and IL-15 levels on days 7 or 14 after transplantation did not predict grade II–IV acute GVHD. Conclusions: These data suggest that IL-7 and IL-15 levels remain relatively low after nonmyeloablative transplantation, and that IL-7 and IL-15 levels early after nonmyeloablative transplantation do not predict for acute GVHD. [less ▲]

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See detail(111)Indium-oxine labelling for evaluating the homing process of autologous osteoblasts implanted percutaneously in atrophic nonunion fractures.
Hauzeur, Jean-Philippe; Bernard, Claire ULg; Egrise, Dominique et al

in International Orthopaedics (2013), 37(1), 131-6

PURPOSE: The aim of the study was to control the in vivo localisation of implanted cells in cell-based therapies. Labelling cells with (111)indium-oxine is one of the most interesting methods proposed. We ... [more ▼]

PURPOSE: The aim of the study was to control the in vivo localisation of implanted cells in cell-based therapies. Labelling cells with (111)indium-oxine is one of the most interesting methods proposed. We evaluated this method in the setting of autologous osteoblast implantation in nonunion fractures. METHODS: An in vitro study of osteoblasts was conducted after (111)indium-oxine labelling. Radioactivity retention and viability, proliferation and the ability to produce alkaline phosphatase were evaluated in a seven-day culture. In vivo labelling of implanted osteoblastic cells was conducted during a therapeutic trial of atrophic nonunion fractures, with the leakage outside the nonunion site and local uptake evolution at four, 24 and 48 hour being studied. RESULTS: The mean labelling efficiency for osteoprogenitors was 78.8 +/- 4.6 %. The intracellular retention was 89.4 +/- 2.1 % at three hours and 67.3 +/- 4.7 % at 18 hours. The viability assessed at three hours was 93.7 +/- 0.6 %. After seven days of culture, morphology and alkaline phosphatase staining were similar for both labelled and unlabelled control cells, although the proliferation rate was decreased in the labelled cells. Some local intraosseous leakage was observed in four of 17 cases. All patients showed uptake at the injection site, with four having no other uptake. Four patients showed additional uptake in the bladder, liver and spleen, while 11 patients had additional uptake in the lungs in addition to the bladder, liver and spleen. The activity ratios (injection site/body) were 48 +/- 28 % at four hours, 40 +/- 25 % at 24 hours and 35 +/- 25 % at 48 hours. After correcting for decay, the activity within the injection site was 82 +/- 15 % at 24 hours and 69 +/- 11 % at 48 hours compared with the activity measured at four hours. No relationship was found between uptake and radiological bone repair. CONCLUSIONS: The (111)indium-oxine labelling appears to be a good method for monitoring the behaviour of the osteoblastic cells after their implantation in atrophic nonunion fractures. [less ▲]

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See detailAllogreffe de cellules souches hématopoïétiques chez le patient âgé : jusqu'à quel âge ?
SERVAIS, Sophie ULg; WILLEMS, Evelyne ULg; Beguin, Yves ULg et al

in Revue Médicale de Liège (2013), 68(1), 38-43

In the last decades, the upper age limit for allogeneic hematopoietic cell transplantation has increased from 50-60 years to 70-75 years of age, in part due to the development of allogeneic ... [more ▼]

In the last decades, the upper age limit for allogeneic hematopoietic cell transplantation has increased from 50-60 years to 70-75 years of age, in part due to the development of allogeneic transplantation following reducedintensity or truly nonmyeloablative conditioning. This review describes challenges and opportunities of allogeneic hematopoietic cell transplantation in the elderly. [less ▲]

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See detailInfusion of third party mesenchymal stem cells (MSC) after kidney and liver transplantation: a phase I-II, open-label, clinical study
DETRY, Olivier ULg; DELBOUILLE, Marie-Hélène ULg; LECHANTEUR, Chantal ULg et al

Conference (2012, October 19)

MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC ... [more ▼]

MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC infusion after cadaveric kidney and liver transplantation in a prospective phase I-II study, taking advantage of our centre expertise and experience in MSC use in graft-versus-host disease (GVHD) after bone marrow transplantation and using an already functioning GMP-compliant laboratory producing clinical-grade MSC. Secondary end-points will help to evaluate the immunosuppressive potential of MSC after organ transplantation, and the opportunity to develop larger randomised, controlled, phase III trials. After successful transplantation, 10 liver and 10 kidney transplant recipients under standard immunosuppression (tacrolimus, MMF, steroids) will receive an intravenous infusion of 1.5-3x106/kg of third-party MSC on post-operative day 3±2. These patients will be prospectively compared to 10 liver and 10 kidney recipients who meet the inclusion criteria but deny MSC infusion. Safety will be assessed by recording side effects, including opportunistic infections and cancers. Immunosuppressive potential will be evaluated by rejection episode rates, by graft/patient survivals, by immunohistology of 3-months kidney and 6-month liver graft biopsies and by in vitro evaluation of the immunity profile of the recipients. In a second step, reduction (kidney) and progressive weaning (liver) of immunosuppression will be attempted in recipients who received MSC. This ongoing study is supported by research grants from the CHU of Liège, University of Liège, and by the Senior Clinical Research Grant from ESOT. The first patients were included and treated in early 2012, and final results expected in late 2013. [less ▲]

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See detailCord blood for allogeneic use: Clinical and scientific aspects?
BAUDOUX, Etienne ULg; BEGUIN, Yves ULg; Benoit, Yves et al

Report (2012)

In this science-policy advisory report, the Superior Health Council issues advice on cord blood as an allogeneic source of stem cells for human clinical use

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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 detailWhat is the Contribution of Host-Derived CMV Immunity after Allogeneic Transplantation following Non-Myeloablative Conditioning?
MENTEN, Catherine ULg; Castermans, E.; Hannon, Muriel ULg et al

in Haematologica (2012), 97(Supplement 1), 720

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See detailEvidence for Expansion of Host-derived CMV-specific CD8+ T cells after Allogeneic Transplantation with Non-Myeloablative Conditioning
MENTEN, Catherine ULg; Castermans, E.; 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 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 detailSpontaneous pneumomediastinum caused by bleomycin-induced pneumonitis
FRUSCH, Nicolas ULg; SERVAIS, Sophie ULg; DE PRIJCK, Bernard ULg et al

in Acta Clinica Belgica (2012)

We report the case of a 24-yr-old woman treated for lymphoma who developed bleomycin-induced intersitial pneumonia. This interstitial pneumonia was complicated by spontaneous pneumomediastinum ... [more ▼]

We report the case of a 24-yr-old woman treated for lymphoma who developed bleomycin-induced intersitial pneumonia. This interstitial pneumonia was complicated by spontaneous pneumomediastinum. Pneumomediastinum is an unfrequent side effect of high dose bleomycin-induced pneumonitis (BIP) and we describe the first case occurring with low-dose of bleomycin. [less ▲]

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See detailDifferential signalling through ALK-1 and ALK-5 regulates leptin expression in Mesenchymal Stem Cells
Zeddou, M.; RELIC, Biserka ULg; MALAISE, Olivier ULg et al

in Stem Cells & Development (2012), 21(11), 1948-54

Leptin plays a central role in maintaining energy balance, with multiple other systemic effects. Despite leptin importance in peripheral regulation of mesenchymal stem cells (MSC) differentiation, little ... [more ▼]

Leptin plays a central role in maintaining energy balance, with multiple other systemic effects. Despite leptin importance in peripheral regulation of mesenchymal stem cells (MSC) differentiation, little is known on its expression mechanism. Leptin is often described as adipokine, while it is expressed by other cell types. We have recently shown an in vitro leptin expression, enhanced by glucocorticoids in synovial fibroblasts. Here, we investigated leptin expression in MSC from bone marrow (BM-MSC), cord matrix (UMSC), and primary and dedifferentiated chondrocytes (DCH). Results showed that BM-MSC, but not UMSC, expressed leptin that was strongly enhanced by glucocorticoids. Interestingly, chondrocytes gained leptin expression progressively with dedifferentiation. This dedifferentiation was correlated with downregulation of ALK-5 expression, Smad2 phosphorylation (p-Smad2), and gain of ALK-1 expression and Smad1/5 phosphorylation (p-Smad1/5). TGF-β1 was shown to signal via ALK-5-Smad2/3 and/or ALK-1-Smad1/5 pathways. In BM-MSC, TGF-β1 increased p-Smad2 expression and markedly inhibited endogenous- and glucocorticoidinduced leptin expression, while ALK-5 inhibitor (SB431542) induced and restored this expression. In addition, both prednisolone and <br />SB431542 increased p-Smad1/5 expression. These results suggested ALK-5-Smad2 pathway as inhibitor of leptin expression, while ALK-1-Smad1/5 as activator. Indeed, Smad1 expression silencing induced leptin expression inhibition. Furthermore, prednisolone enhanced the expression of TGF-βRII while decreasing p-Smad2 in BM-MSC and SVF but not in UMSC. In vitro differentiation revealed differential osteogenic potential in SVF, BM-MSC and UMSC that correlates to their leptin expression potential. Our results suggest that ALK-1/ALK-5 balance regulates leptin expression in MSC. It also underlines UMSC as leptin non-producer MSC for cell therapy protocols where leptin expression is not suitable. [less ▲]

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See detailMyocardial infarct size quantification in mice by SPECT using a novel algorithm independent of a normal perfusion database
Roelants, Véronique; DELGAUDINE, Marie ULg; Walrand, Stephan et al

in European Journal of Nuclear Medicine and Molecular Imaging Research (2012), 2

Background: There is a growing interest in developing non-invasive imaging techniques permitting infarct size (IS) measurements in mice. The aim of this study was to validate the high-resolution rodent ... [more ▼]

Background: There is a growing interest in developing non-invasive imaging techniques permitting infarct size (IS) measurements in mice. The aim of this study was to validate the high-resolution rodent Linoview single photon emission computed tomography (SPECT) system for non-invasive measurements of IS in mice by using a novel algorithm independent of a normal database, in comparison with histology. Methods: Eleven mice underwent a left coronary artery ligature. Seven days later, animals were imaged on the SPECT 2h30 after injection of 173 ± 27 MBq of Tc-99m-sestamibi. Mice were subsequently killed, and their hearts were excised for IS determination with triphenyltetrazolium chloride (TTC) staining. SPECT images were reconstructed using the expectation maximization maximum likelihood algorithm, and the IS was calculated using a novel algorithm applied on the 20-segment polar map provided by the commercially available QPS software (Cedars-Sinai Medical Center, CA, USA). This original method is attractive by the fact that it does not require the implementation of a normal perfusion database. Results: Reconstructed images allowed a clear delineation of the left ventricles borders in all mice. No significant difference was found between mean IS determined by SPECT and by TTC staining [37.9 ± 17.5% vs 35.6 ± 17.2%, respectively (P = 0.10)]. Linear regression analysis showed an excellent correlation between IS measured on the SPECT images and IS obtained with TTC staining (y = 0.95x + 0.03 (r = 0.97; P < 0.0001)), without bias, as demonstrated by the Bland-Altman plot. Conclusion: Our results demonstrate the accuracy of the method for the measurement of myocardial IS in mice with the Linoview SPECT system. [less ▲]

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