54 research outputs found
Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis
© 2010 Cascão et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained
synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and
perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil
and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease
duration and before treatment (VERA).
Methods: Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and
established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF)
from RA and osteoarthritis (OA) patients was also analyzed.
Results: VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1b and IL-6), as
well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In
established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led
to clinical improvement but without an impact on the cytokine pattern.
Conclusions: VERA patients already display increased levels of cytokines related with Th17 polarization and
neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest
that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis.This work was supported by a grant from Sociedade Portuguesa de Reumatologia/Schering-Plough 2005. RAM and RC were funded by Fundação para a Ciência e a Tecnologia (FCT) SFRH/BD/30247/2006 and
SFRH/BD/40513/2007, respectively. MMS-C was funded by Marie Curie Intra-European Fellowship PERG-2008-239422 and a EULAR Young Investigator Award
Multi-Target Drugs: The Trend of Drug Research and Development
Summarizing the status of drugs in the market and examining the trend of drug research and development is important in drug discovery. In this study, we compared the drug targets and the market sales of the new molecular entities approved by the U.S. Food and Drug Administration from January 2000 to December 2009. Two networks, namely, the target–target and drug–drug networks, have been set up using the network analysis tools. The multi-target drugs have much more potential, as shown by the network visualization and the market trends. We discussed the possible reasons and proposed the rational strategies for drug research and development in the future
A pilot study to evaluate the levels of inter-alpha inhibitor proteins (IAIPs) in metastatic cancer patients on chemotherapy.
A pilot study to evaluate the levels of inter-alpha inhibitor proteins (IAIPs) in metastatic cancer patients.
Incidence of solid tumors or lymphoma in patients with polycythemia vera: Data from the REVEAL study.
Vortex tracking on visualized temperature fields in a rotating Rayleigh-Benard convection
We established a vortex detection method using instantaneous temperature fields that were visualized using thermochromic liquid crystals (TLCs) to investigate behaviors of vortical structures in a rotating Rayleigh-Benard convection. Experimental testing was performed at a fixed Rayleigh number in water containing encapsulated TLCs. Vortices were recognized as undulations that appear in the horizontal temperature fields, thus making vortex detection with high spatial resolution possible, and this enabled quantitative investigation of the dynamics of vortical structures. Standard template matching was used to detect individual vortices on visualized temperature fields, and two-dimensional curved surface fitting was adopted to remove erroneous detections and to evaluate shapes of local temperature fields corresponding to vortical structures. Additionally, vortex tracking clearly showed geometric advection pattern of vortical structures
Interleukin-10 (IL-10) secretion in systemic lupus erythematosus and rheumatoid arthritis: IL-10-dependent CD4+CD45RO+ T cell-B cell antibody synthesis
Small Molecule 20S Proteasome Enhancer Regulates MYC Protein Stability and Exhibits Antitumor Activity in Multiple Myeloma
Despite the addition of several new agents to the armamentarium for the treatment of multiple myeloma (MM) in the last decade and improvements in outcomes, the refractory and relapsing disease continues to take a great toll, limiting overall survival. Therefore, additional novel approaches are needed to improve outcomes for MM patients. The oncogenic transcription factor MYC drives cell growth, differentiation and tumor development in many cancers. MYC protein levels are tightly regulated by the proteasome and an increase in MYC protein expression is found in more than 70% of all human cancers, including MM. In addition to the ubiquitin-dependent degradation of MYC by the 26S proteasome, MYC levels are also regulated in a ubiquitin-independent manner through the REGγ activation of the 20S proteasome. Here, we demonstrate that a small molecule activator of the 20S proteasome, TCH-165, decreases MYC protein levels, in a manner that parallels REGγ protein-mediated MYC degradation. TCH-165 enhances MYC degradation and reduces cancer cell growth in vitro and in vivo models of multiple myeloma by enhancing apoptotic signaling, as assessed by targeted gene expression analysis of cancer pathways. Furthermore, 20S proteasome enhancement is well tolerated in mice and dogs. These data support the therapeutic potential of small molecule-driven 20S proteasome activation for the treatments of MYC-driven cancers, especially MM
Polymyositis/Dermatomyositis: the current position
Polymyositis/dermatomyositis are a heterogeneous group of diseases characterised by
skeletal muscle inflammation and necrosis.' 2
Since an excellent clinical description in 1903 by
Steiner of dermatomyositis, which is essentially
still valid,3 much progress has been made
towards our understanding of this group of
diseases. The most widely used clinical classification of idiopathic inflammatory myopathies is
the one proposed by Bohan and Peter in 1975.4
That was a landmark, providing guidelines in
clinical practice to accurate diagnosis of inflammatory myopathies and standardisation of
studies. Nonetheless, the classification was
based on clinical data. In view of recent
histological and immunological studies the classification proposed by Karpati et al in 1987
seems better to fit our current view of such
diseases5 (table 1). In this review we focus on
recent developments in polymyositis/dermatomyositis, analysing separately the currently
considered third major form of inflammatory
myopathy-inclusion body myositis
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