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1.  Aberrant expression and biological significance of Sox2, an embryonic stem cell transcriptional factor, in ALK-positive anaplastic large cell lymphoma 
Blood Cancer Journal  2012;2(8):e82-.
Sox2 (sex-determining region Y-Box) is one of the master transcriptional factors that are important in maintaining the pluripotency of embryonic stem cells (ESCs). In line with this function, Sox2 expression is largely restricted to ESCs and somatic stem cells. We report that Sox2 is expressed in cell lines and tumor samples derived from ALK-positive anaplastic large cell lymphoma (ALK+ALCL), for which the normal cellular counterpart is believed to be mature T-cells. The expression of Sox2 in ALK+ALCL can be attributed to nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), the oncogenic fusion protein carrying a central pathogenetic role in these tumors. By confocal microscopy, Sox2 protein was detectable in virtually all cells in ALK+ALCL cell lines. However, the transcriptional activity of Sox2, as assessed using a Sox2-responsive reporter construct, was detectable only in a small proportion of cells. Importantly, downregulation of Sox2 using short interfering RNA in isolated Sox2active cells, but not Sox2inactive cells, resulted in a significant decrease in cell growth, invasiveness and tumorigenicity. To conclude, ALK+ALCL represents the first example of a hematologic malignancy that aberrantly expresses Sox2, which represents a novel mechanism by which NPM-ALK mediates tumorigenesis. We also found that the transcriptional activity and oncogenic effects of Sox2 can be heterogeneous in cancer cells.
PMCID: PMC3432482  PMID: 22885405
Sox2; transcriptional activity; NPM-ALK; STAT3; tumorigenicity
2.  Anti‐β2GPI‐antibody‐induced endothelial cell gene expression profiling reveals induction of novel pro‐inflammatory genes potentially involved in primary antiphospholipid syndrome 
Annals of the Rheumatic Diseases  2007;66(8):1000-1007.
To determine the effects of primary antiphospholipid syndrome (PAPS)‐derived anti‐β2GPI antibodies on gene expression in human umbilical vein endothelial cells (HUVEC) by gene profiling using microarrays.
Anti‐β2GPI antibodies purified from sera of patients with PAPS or control IgG isolated from normal subjects were incubated with HUVEC for 4 h before isolation of RNA and processing for hybridisation to Affymetrix Human Genome U133A‐2.0 arrays. Data were analysed using a combination of the MAS 5.0 (Affymetrix) and GeneSpring (Agilent) software programmes. For selected genes microarray data were confirmed by real‐time PCR analysis or at the protein level by ELISA.
A total of 101 genes were found to be upregulated and 14 genes were downregulated twofold or more in response to anti‐β2GPI antibodies. A number of novel genes not previously associated with APS were induced, including chemokines CCL20, CXCL3, CX3CL1, CXCL5, CXCL2 and CXCL1, the receptors Tenascin C, OLR1, IL‐18 receptor 1, and growth factors CSF2, CSF3 IL‐6, IL1β and FGF18. The majority of downregulated genes were transcription factors/signalling molecules including ID2. Quantitative real‐time RT‐PCR analysis confirmed the microarray results for selected genes (CSF3, CX3CL1, FGF18, ID2, SOD2, Tenascin C).
This study reveals a complex gene expression response in HUVEC to anti‐β2GPI antibodies with multiple chemokines, pro‐inflammatory cytokines, pro‐thrombotic and pro‐adhesive genes regulated by these antibodies in vitro. Some of these newly identified anti‐β2GPI antibody‐regulated genes could contribute to the vasculopathy associated with this disease.
PMCID: PMC1954708  PMID: 17223652
3.  Axillary vein thrombosis in adolescent onset systemic sclerosis. 
Annals of the Rheumatic Diseases  1990;49(7):557-559.
A 16 year old girl with a two year history of systemic sclerosis developed left axillary vein thrombosis. Prolonged euglobulin clot lysis time, anti-endothelial cell antibodies, and raised von Willebrand factor antigen were shown.
PMCID: PMC1004151  PMID: 2383084
4.  Progressive multifocal leukoencephalopathy, myelodysplastic syndrome type II and prostatic carcinoma. 
Postgraduate Medical Journal  1984;60(700):157-158.
A case is described of progressive multifocal leukoencephalopathy (PML) occurring in a man with myelodysplastic syndrome type II (MDS II) and prostatic carcinoma. This is the first case, to our knowledge, of the association of PML with MDS II.
PMCID: PMC2417702  PMID: 6709552
5.  Regional lung function in ankylosing spondylitis. 
Thorax  1976;31(4):433-437.
Xenon-133 was used to study regional pulmonary function in nine patients with chest cage rigidity due to ankylosing spondylitis. In comparison with normal subjects, the patients showed an overall diminution in lung volume and the proportion of inhaled xenon reaching the lung apices was reduced but the distribution of injected xenon was normal. The possible relationship between these findings and apical lung disease in ankylosing spondylitis is mentioned.
PMCID: PMC470455  PMID: 968800
7.  IgG antiendothelial cell autoantibodies from scleroderma patients induce leukocyte adhesion to human vascular endothelial cells in vitro. Induction of adhesion molecule expression and involvement of endothelium-derived cytokines. 
Journal of Clinical Investigation  1996;97(1):111-119.
IgG autoantibodies that bind human endothelial cells (AECA) were detected by ELISA in 30 of 42 samples of sera from patients with scleroderma. Pretreatment of human umbilical vein endothelial cells with AECA-positive scleroderma sera, or IgG purified from these sera, led to a dose- and time-dependent increase in the ability of the cells to bind human U937 monocytic cells. Threshold-active IgG concentrations were 1-10 micrograms/ml; effects were significant after 3 h and maximal after 6-12 h. IgG from AECA-negative sera or normal sera were without effect. Increased adhesion of U937 cells was accompanied by increased expression of endothelial intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. Transfer of endothelial cell-conditioned media after pretreatment with AECA and immunodepletion of IgG demonstrated the presence of transferable activity that mimicked the effects of AECA. Treatment with neutralizing anticytokine antibodies indicated that IL-1, generated by the endothelial cells in response to AECA, was involved in the upregulation of adhesion molecules and U937 cell adhesion. We conclude that AECA can play a pathogenic role in scleroderma by activating endothelial cells, in part due to autocrine or paracrine actions of IL-1.
PMCID: PMC507068  PMID: 8550821
9.  The endothelium: its role in scleroderma. 
Annals of the Rheumatic Diseases  1991;50(Suppl 4):866-871.
PMCID: PMC1033322  PMID: 1750799

Results 1-9 (9)