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Cancer Detection Rates of Systematic and Targeted Prostate Biopsies after Biparametric MRI.

Prostate Cancer 2020 3;2020:4626781. Epub 2020 Apr 3.

Department of Electrical Engineering, Eindhoven University of Technology, De Rondom 70, 5612 AP, Eindhoven, Netherlands.

Objective: To compare prostate cancer detection rates (CDRs) and pathology results with targeted prostate biopsy (TB) and systematic prostate biopsy (SB) in biopsy-naive men.

Methods: An in-patient control study of 82 men undergoing SB and subsequent TB in case of positive prostate MRI between 2015 and 2017 in the Jeroen Bosch Hospital, the Netherlands.

Results: Prostate cancer (PCa) was detected in 54. Read More

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Filgotinib, a JAK1 Inhibitor, Modulates Disease-Related Biomarkers in Rheumatoid Arthritis: Results from Two Randomized, Controlled Phase 2b Trials.

Rheumatol Ther 2020 Mar 7;7(1):173-190. Epub 2020 Jan 7.

Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Introduction: The Janus kinase (JAK) inhibitor therapeutic class has shown significant clinical benefit in the treatment of rheumatoid arthritis (RA). We sought to gain insight into the mode of action and immunological effects of filgotinib, a JAK1 selective inhibitor, in active RA by analyzing secreted and cell-based biomarkers key to RA pathophysiology in two phase 2b trials of filgotinib in active RA.

Methods: Immune cell subsets and 34 serum biomarkers were analyzed longitudinally over 12 weeks using blood samples collected from patients with active RA receiving filgotinib (100 or 200 mg once daily) or placebo (PBO) in the two phase 2b trials (DARWIN 1, on a background of methotrexate, and DARWIN 2, as monotherapy). Read More

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Three-dimensional greyscale transrectal ultrasound-guidance and biopsy core preembedding for detection of prostate cancer: Dutch clinical cohort study.

BMC Urol 2019 Apr 16;19(1):23. Epub 2019 Apr 16.

Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.

Background: To overcome the limitations regarding two dimensional (2D) greyscale (GS) transrectal ultrasound (TRUS)-guided biopsy in prostate cancer (PCa) detection and tissue packaging in biopsy processing, there is an ongoing focus on new imaging and pathology techniques. A three-dimensional (3D) model of the prostate with biopsy needle guidance can be generate by the Navigo™ workstation (UC-care, Israel). The SmartBX™ system (UC-care, Israel) provides a prostate biopsy core preembedding method. Read More

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Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial.

Lancet 2018 12 22;392(10162):2367-2377. Epub 2018 Oct 22.

University of Toronto and Krembil Research Institute, Toronto Western Hospital, Toronto, Canada.

Background: The Janus kinase 1 (JAK1) pathway has been implicated in the pathogenesis of psoriatic arthritis. We aimed to investigate the efficacy and safety of filgotinib, a selective JAK1 inhibitor, for the treatment of psoriatic arthritis.

Methods: The EQUATOR trial was a randomised, double-blind, placebo-controlled phase 2 trial that enrolled adults from 25 sites in seven countries (Belgium, Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine). Read More

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December 2018

Influence of age and renal impairment on the steady state pharmacokinetics of filgotinib, a selective JAK1 inhibitor.

Br J Clin Pharmacol 2018 12 4;84(12):2779-2789. Epub 2018 Oct 4.

Galapagos NV, Generaal de Wittelaan L11 A3, 2800, Mechelen, Belgium.

Aims: Filgotinib (GS-6034, formerly GLPG0634) is an oral, selective Janus kinase 1 (JAK1) inhibitor that showed early response and sustained efficacy in patients with rheumatoid arthritis and with Crohn's disease. The aim of the present study was to investigate the impact of age and renal impairment (RI) on the pharmacokinetics (PK) of filgotinib and its main metabolite.

Methods: The effect of age was assessed in two groups of 10 elderly healthy subjects (65-74 and ≥75 years of age) and a control group of 10 younger healthy subjects (40-50 years of age). Read More

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December 2018

Effect of filgotinib, a selective JAK 1 inhibitor, with and without methotrexate in patients with rheumatoid arthritis: patient-reported outcomes.

Arthritis Res Ther 2018 03 23;20(1):57. Epub 2018 Mar 23.

University of California San Diego, La Jolla, CA, USA.

Background: The aim was to assess patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) treated with filgotinib during two phase 2b, 24-week, randomized, placebo-controlled studies.

Methods: Patients with moderate-to-severe active RA and an inadequate response to methotrexate (MTX) were randomized to daily placebo or filgotinib 50 mg, 100 mg, or 200 mg as add-on therapy to MTX (NCT01888874) or as monotherapy (NCT01894516). At week 12, nonresponders receiving filgotinib 50 mg in both studies or placebo in the add-on study, and all patients receiving placebo as monotherapy, were re-assigned to filgotinib 100 mg. Read More

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Concordance of Gleason grading with three-dimensional ultrasound systematic biopsy and biopsy core pre-embedding.

World J Urol 2018 Jun 1;36(6):863-869. Epub 2018 Feb 1.

Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.

Purpose: To determine the value of a three-dimensional (3D) greyscale transrectal ultrasound (TRUS)-guided prostate biopsy system and biopsy core pre-embedding method on concordance between Gleason scores of needle biopsies and radical prostatectomy (RP) specimens.

Methods: Retrospective analysis of prostate biopsies and subsequent RP for PCa in the Jeroen Bosch Hospital, the Netherlands, from 2007 to 2016. Two cohorts were analysed: conventional 2D TRUS-guided biopsies and RP (2007-2013, n = 266) versus 3D TRUS-guided biopsies with pre-embedding (2013-2016, n = 129). Read More

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Preliminary phytochemical screening, antioxidant and antihyperglycaemic activity of Moringa oleifera leaf extracts.

Pak J Pharm Sci 2017 Nov;30(6):2217-2222

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos, Idiaraba Campus, Lagos, Nigeria.

Moringa oleifera plant has been widely used for a vast number of folkloric medicinal purposes. The research aimed to investigate the antioxidant and antihyperglycaemic activity of Moringa oleifera leaf extracts obtained using different solvent systems for extraction. The solvent extracts of Moringa oleifera were: water extract (100% MoWE), 50% Methanolic extract (50% MoME), 100% Methanolic extract (100% MoME), 50% Ethanolic extract (50% MoEE), and 100% Ethanolic extract (100% MoEE). Read More

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November 2017

Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Filgotinib, a Selective JAK-1 Inhibitor, After Short-Term Treatment of Rheumatoid Arthritis: Results of Two Randomized Phase IIa Trials.

Arthritis Rheumatol 2017 10 31;69(10):1949-1959. Epub 2017 Aug 31.

Galápagos NV, Mechelen, Belgium.

Objective: JAK inhibitors have shown efficacy in rheumatoid arthritis (RA). We undertook this study to test our hypothesis that selective inhibition of JAK-1 would combine good efficacy with a better safety profile compared with less selective JAK inhibitors.

Methods: In two 4-week exploratory, double-blind, placebo-controlled phase IIa trials, 127 RA patients with an insufficient response to methotrexate (MTX) received filgotinib (GLPG0634, GS-6034) oral capsules (100 mg twice daily or 30, 75, 150, 200, or 300 mg once daily) or placebo, added onto a stable regimen of MTX, to evaluate safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of filgotinib. Read More

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October 2017

Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1).

Ann Rheum Dis 2017 Jun 19;76(6):998-1008. Epub 2016 Dec 19.

Galapagos NV, Mechelen, Belgium.

Objectives: To evaluate the efficacy and safety of different doses and regimens of filgotinib, an oral Janus kinase 1 inhibitor, as add-on treatment to methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and inadequate response to MTX.

Methods: In this 24-week phase IIb study, patients with moderate-to-severe active RA receiving a stable dose of MTX were randomised (1:1:1:1:1:1:1) to receive placebo or 50, 100 or 200 mg filgotinib, administered once daily or twice daily. Primary end point was the percentage of patients achieving a week 12 American College of Rheumatology (ACR)20 response. Read More

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Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2).

Ann Rheum Dis 2017 Jun 19;76(6):1009-1019. Epub 2016 Dec 19.

Galapagos NV, Mechelen, Belgium.

Objectives: To evaluate the efficacy and safety of different doses of filgotinib, an oral Janus kinase 1 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA) and previous inadequate response to methotrexate (MTX).

Methods: In this 24-week phase IIb study, patients with moderately to severely active RA were randomised (1:1:1:1) to receive 50, 100 or 200 mg filgotinib once daily, or placebo, after a ≥4-week washout from MTX. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR)20 response at week 12. Read More

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Clinical remission in patients with moderate-to-severe Crohn's disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial.

Lancet 2017 01 15;389(10066):266-275. Epub 2016 Dec 15.

Galapagos NV, Generaal De Wittelaan L11A3, Mechelen, Belgium.

Background: Filgotinib (GLPG0634, GS-6034) is a once-daily, orally administered, Janus kinase 1 (JAK1)-selective inhibitor. The FITZROY study examined the efficacy and safety of filgotinib for the treatment of moderate-to-severe Crohn's disease.

Methods: We did a randomised, double-blind, placebo-controlled phase 2 study, which recruited patients from 52 centres in nine European countries. Read More

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January 2017

Circulating interleukin-18: Association with IL-8, IL-10 and VEGF serum levels in patients with and without heart rhythm disorders.

Int J Cardiol 2016 Jul 13;215:105-9. Epub 2016 Apr 13.

Department of Fundamental and Applied Physiology, Russian National Research Medical University, Ostrovitjanova 1, Moscow 117997, Russia.

Background: An altered IL-18 pathway in patients with coronary artery disease has recently been described and this cytokine was shown to be of clinical and prognostic utility. Cardiomyocytes are a target of this cytokine which exerts inflammatory, hypertrophic and profibrotic activities.

Objectives: The aim of the study was to verify the ability of IL-18 to induce expression of other pro/anti-inflammatory cytokines and to analyse the relationship between these molecules in serum from patients with heart rhythm disorders and coronary artery disease. Read More

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Safety, pharmacokinetics and pharmacodynamics of GLPG0974, a potent and selective FFA2 antagonist, in healthy male subjects.

Br J Clin Pharmacol 2016 07 1;82(1):139-48. Epub 2016 May 1.

Galapagos NV, 2800, Mechelen, Belgium.

Aims: Free fatty acids (FFA) can act as direct signalling molecules through activation of several membrane-bound G-protein coupled receptors. The FFA2 receptor (known as GPR43) is activated by short chain fatty acids (SCFA) such as acetate and has been shown to play a major role in SCFA-induced neutrophil activation and migration and to contribute in the development and control of inflammation. GLPG0974 is a potent and selective antagonist of the human FFA2. Read More

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3D Navigo™ versus TRUS-guided prostate biopsy in prostate cancer detection.

World J Urol 2016 Sep 4;34(9):1255-60. Epub 2016 Feb 4.

Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.

Introduction: To overcome the limitations regarding transrectal ultrasound (TRUS)-guided biopsies in prostate cancer (PCa) detection, there is a focus on new imaging technologies. The Navigo™ system (UC-care, Israel) uses regular TRUS images and electrospatial monitoring to generate a 3D model of the prostate. The aim of this study was to compare cancer detection rates between the Navigo™ system and conventional TRUS, in patients without a history of PCa. Read More

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September 2016

A dose escalating phase I study of GLPG0187, a broad spectrum integrin receptor antagonist, in adult patients with progressive high-grade glioma and other advanced solid malignancies.

Invest New Drugs 2016 Apr 20;34(2):184-92. Epub 2016 Jan 20.

Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX Utrecht, The Netherlands.

Background: Integrin signaling is an attractive target for anti-cancer treatment. GLPG0187 is a broad spectrum integrin receptor antagonist (IRA). GLPG0187 inhibited tumor growth and metastasis in mouse models. Read More

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Clinical Confirmation that the Selective JAK1 Inhibitor Filgotinib (GLPG0634) has a Low Liability for Drug-drug Interactions.

Drug Metab Lett 2016 ;10(1):38-48

Galapagos SASU, 102 avenue Gaston Roussel, 93230 Romainville, France.

Objective: The selective Janus kinase 1 inhibitor filgotinib (GLPG0634), which is currently in clinical development for the treatment of rheumatoid arthritis (RA) and Crohn's disease, demonstrated encouraging safety and efficacy profiles in RA patients after 4 weeks of daily dosing. As RA patients might be treated with multiple medications simultaneously, possible drug-drug interactions of filgotinib with cytochrome P450 enzymes and with key drug transporters were evaluated in vitro and in clinical studies.

Methods: The enzymes involved in filgotinib's metabolism and the potential interactions of the parent and its active major metabolite with drug-metabolizing enzymes and drug transporters, were identified using recombinant enzymes, human microsomes, and cell systems. Read More

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December 2016

The value of magnetic resonance imaging and ultrasonography (MRI/US)-fusion biopsy platforms in prostate cancer detection: a systematic review.

BJU Int 2016 Mar 28;117(3):392-400. Epub 2015 Aug 28.

Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.

Despite limitations considering the presence, staging and aggressiveness of prostate cancer, ultrasonography (US)-guided systematic biopsies (SBs) are still the 'gold standard' for the diagnosis of prostate cancer. Recently, promising results have been published for targeted prostate biopsies (TBs) using magnetic resonance imaging (MRI) and ultrasonography (MRI/US)-fusion platforms. Different platforms are USA Food and Drug Administration registered and have, mostly subjective, strengths and weaknesses. Read More

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Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection.

Clin Pharmacokinet 2015 Aug;54(8):859-74

Galapagos SASU, 102 Avenue Gaston Roussel, 93230, Romainville, France,

Background And Objectives: Filgotinib (GLPG0634) is a selective inhibitor of Janus kinase 1 (JAK1) currently in development for the treatment of rheumatoid arthritis and Crohn's disease. While less selective JAK inhibitors have shown long-term efficacy in treating inflammatory conditions, this was accompanied by dose-limiting side effects. Here, we describe the pharmacokinetics of filgotinib and its active metabolite in healthy volunteers and the use of pharmacokinetic-pharmacodynamic modeling and simulation to support dose selection for phase IIB in patients with rheumatoid arthritis. Read More

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Prevalence of pernicious anemia in patients with macrocytic anemia and low serum B12.

Pak J Med Sci 2014 Nov-Dec;30(6):1218-22

Al-Gahtani FH, MD, College of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia.

Objective: The current research evaluated the prevalence of pernicious anemia (PA) in patients with macrocytic anemia (high MCV) and low serum B12 in Riyadh.

Methods: Blood testing was done in 77 patients (males: 45.5%, females: 54. Read More

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February 2015

Comparing responses to different selenium sources and dosages in laying hens.

Poult Sci 2014 Dec 28;93(12):3083-90. Epub 2014 Oct 28.

Orffa Additives BV, Vierlinghstraat 51, 4251 LC Werkendam, the Netherlands.

Developing new sources of organic Se has potential benefit for animal production and human nutrition via animal-based foods enriched in Se. The objectives of this trial were to compare L-selenomethionine with another organic Se source, Se-enriched yeast (SelPlex 2300), and sodium selenite, an inorganic Se source, against a commercial control diet. The effect of source and the dosage of Se supplementation on Se in eggs and blood variables was investigated. Read More

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December 2014

Oral administration of GLPG0259, an inhibitor of MAPKAPK5, a new target for the treatment of rheumatoid arthritis: a phase II, randomised, double-blind, placebo-controlled, multicentre trial.

Ann Rheum Dis 2013 May 17;72(5):741-4. Epub 2012 Nov 17.

Department of Rheumatology, University Hospital KU Leuven, Leuven, Belgium.

Background: Mitogen-activated protein (MAP) kinases are key regulators of cytokine production, and are therefore potential targets for treatment of rheumatoid arthritis (RA).

Objective: This two-part phase II study investigated the efficacy and safety of a once-daily 50 mg GLPG0259 (an inhibitor of MAP kinase-activated protein kinase 5) dose vs placebo (part A). An interim analysis after part A would determine whether the dose-finding part (part B) would be performed. Read More

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Surface area assessment of the murine intestinal tract as a prerequisite for oral dose translation from mouse to man.

Lab Anim 2010 Jul 10;44(3):176-83. Epub 2009 Dec 10.

Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, Belgium.

In many pharmacological and toxicological studies knowledge about the intestinal absorption, which is dependent upon the surface area of absorptive epithelia, is indispensible. Although mice are often used in such preclinical studies, very few quantitative data about their intestinal surface area are available. Especially for locally acting candidate drugs in development, this information is crucial for dose translation towards humans. Read More

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Rational design of a multiepitope vaccine encoding T-lymphocyte epitopes for treatment of chronic hepatitis B virus infections.

J Virol 2008 Jan 17;82(1):435-50. Epub 2007 Oct 17.

GENimmune NV (Innogenetics NV), Ghent, Belgium.

Protein sequences from multiple hepatitis B virus (HBV) isolates were analyzed for the presence of amino acid motifs characteristic of cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes with the goal of identifying conserved epitopes suitable for use in a therapeutic vaccine. Specifically, sequences bearing HLA-A1, -A2, -A3, -A24, -B7, and -DR supertype binding motifs were identified, synthesized as peptides, and tested for binding to soluble HLA. The immunogenicity of peptides that bound with moderate to high affinity subsequently was assessed using HLA transgenic mice (CTL) and HLA cross-reacting H-2(bxd) (BALB/c x C57BL/6J) mice (HTL). Read More

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January 2008

Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI).

Cancer Immunol Immunother 2008 Mar 25;57(3):303-15. Epub 2007 Aug 25.

ZellNet Consulting, Inc, Fort Lee, NJ, USA.

The Cancer Vaccine Consortium of the Sabin Vaccine Institute (CVC/SVI) is conducting an ongoing large-scale immune monitoring harmonization program through its members and affiliated associations. This effort was brought to life as an external validation program by conducting an international Elispot proficiency panel with 36 laboratories in 2005, and was followed by a second panel with 29 participating laboratories in 2006 allowing for application of learnings from the first panel. Critical protocol choices, as well as standardization and validation practices among laboratories were assessed through detailed surveys. Read More

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Design and evaluation of a computer reminder system to improve prescribing behaviour of GPs.

Stud Health Technol Inform 2006 ;124:617-23

Integrated Care Unit, University Hospital Maastricht, The Netherlands.

Objective: To evaluate the implementation of a decision support system with reactive computer reminders to improve drug prescribing behaviour.

Methods: A clustered RCT with an incomplete block design was carried out in the south of the Netherlands: 25 GPs received reminders on antibiotics and asthma/COPD prescriptions, 28 GPs received reminders on cholesterol prescriptions. Prescribing guidelines were integrated into the GP information system, which was installed in the GPs practices of the intervention group. Read More

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January 2007

The use of a locked plate in the treatment of ununited femoral shaft fractures.

J Trauma 2004 Oct;57(4):832-6

From the Department of Orthopaedics and Traumatology, Assiut University Hospital, Assiut, Egypt.

Background: Sixteen patients with ununited fractures of the femur were treated by locked plate. There were 14 men and 2 women. The youngest patient was 18 years old and the oldest was 48 years (average, 32. Read More

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October 2004

Functional properties of myelin oligodendrocyte glycoprotein-reactive T cells in multiple sclerosis patients and controls.

J Neuroimmunol 2003 Apr;137(1-2):164-76

Biomedical Research Institute, Limburgs Universitair Centrum, Diepenbeek, Belgium.

Autoimmune T-cell reactivity to myelin components may be implicated in the initiation or maintenance of the inflammation leading to myelin destruction in multiple sclerosis (MS). Myelin oligodendrocyte glycoprotein (MOG), a quantitatively minor myelin protein, is an important candidate autoantigen in MS. We studied T-cell responses to recombinant MOG (extracellular domain, rMOG) and a panel of four peptides within this domain (amino acids 1-22, 34-56, 64-86 and 74-96) in MS patients and healthy controls (NS). Read More

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T cell vaccination in multiple sclerosis patients with autologous CSF-derived activated T cells: results from a pilot study.

Clin Exp Immunol 2003 Jan;131(1):155-68

Biomedisch onderzoeksinstituut (BIOMED), Limburgs Universitair Centrum and School of Life Sciences, Transnational University Limburg (tUL), Diepenbeek, Belgium.

Myelin-reactive T cells are considered to play an essential role in the pathogenesis of multiple sclerosis (MS), an autoimmune disease of the central nervous system. We have previously studied the effects of T cell vaccination (TCV), a procedure by which MS patients are immunized with attenuated autologous myelin basic protein (MBP)-reactive T cell clones. Because several myelin antigens are described as potential autoantigens for MS, T cell vaccines incorporating a broad panel of antimyelin reactivities may have therapeutic effects. Read More

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January 2003

Antiproliferative effect of plant cytokinin analogues with an inhibitory activity on cyclin-dependent kinases.

Leukemia 2002 Mar;16(3):299-305

Laboratory of Experimental Hematology, University of Antwerp, Antwerp University Hospital, Edegem, Belgium.

In this study, analogues of olomoucine, a previously described plant cytokinin analogue with cyclin-dependent kinase (CDK) inhibitory activity, were investigated for effect on CDK1 and CDK2 and for effect on cell proliferation. Eight new compounds exhibit stronger inhibitory activity on CDK1 and CDK2 and on cell proliferation than olomoucine. Some active compounds showed low inhibition of proliferation of normal myeloid growth. Read More

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