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Wu F.,University of Alberta | Ye X.,University of Alberta | Wang P.,University of Alberta | Jung K.,University of Alberta | And 7 more authors.
BMC Cancer | Year: 2013

Background: Sox2, an embryonic stem cell marker, is aberrantly expressed in a subset of breast cancer (BC). While the aberrant expression of Sox2 has been shown to significantly correlate with a number of clinicopathologic parameters in BC, its biological significance in BC is incompletely understood. Methods: In-vitro invasion assay was used to evaluate whether the expression of Sox2 is linked to the invasiveness of MCF7 and ZR751 cells. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and/or Western blots were used to assess if Sox2 modulates the expression of factors known to regulate epithelial mesenchymal transition (EMT), such as Twist1. Chromatin immunoprecipitation (ChIP) was used to assess the binding of Sox2 to the promoter region of Twist1. Results: We found that siRNA knockdown of Sox2 expression significantly increased the invasiveness of MCF7 and ZR751 cells. However, when MCF7 cells were separated into two distinct subsets based on their differential responsiveness to the Sox2 reporter, the Sox2-mediated effects on invasiveness was observed only in 'reporter un-responsive' cells (RU cells) but not 'reporter responsive' cells (RR cells). Correlating with these findings, siRNA knockdown of Sox2 in RU cells, but not RR cells, dramatically increased the expression of Twist1. Accordingly, using ChIP, we found evidence that Sox2 binds to the promoter region of Twist1 in RU cells only. Lastly, siRNA knockdown of Twist1 largely abrogated the regulatory effect of Sox2 on the invasiveness in RU cells, suggesting that the observed Sox2-mediated effects are Twist1-dependent. Conclusion: Sox2 regulates the invasiveness of BC cells via a mechanism that is dependent on Twist1 and the transcriptional status of Sox2. Our results have further highlighted a new level of biological complexity and heterogeneity of BC cells that may carry significant clinical implications. © 2013 Wu et al.; licensee BioMed Central Ltd. Source

Wang P.,University of Alberta | Zhang J.D.,University of Alberta | Zhang J.D.,First Hospital of China Medical University | Wu F.,University of Alberta | And 10 more authors.
Cellular Signalling | Year: 2012

SALL4 is one of the master transcriptional factors that are crucial in maintaining the pluripotency of embryonic stem cells (ESCs). While the expression of SALL4 is normally restricted to ESCs and somatic stem cells, we found that it is aberrantly expressed in ALK-positive anaplastic large cell lymphoma (ALK+ ALCL), a type of lymphoid malignancy carrying a mature T-cell immunophenotype. shRNA knockdown of SALL4 in ALK+ ALCL cell lines resulted in apoptosis and cell-cycle arrest, and significantly decreased colony formation on soft agar. These changes correlated with the downregulation of several anti-apoptotic proteins and facilitators of cell-cycle progression. Based on the differential response to a SALL4 reporter construct, we were able to separate two distinct cell subsets in Karpas 299 (an ALK+ ALCL cell line), namely SALL4high and SALL4low. Importantly, the biological effects induced by SALL4 knock-down in Karpas 299 were restricted to the purified SALL4high cells, and this finding further supports the concept that SALL4 is biologically important in ALK+ ALCL. Lastly, the expression of SALL4 was not dependent on the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK)/STAT3 signaling axis, the key oncogenic driver in ALK+ ALCL. To conclude, for the first time, our study has revealed the oncogenic contributions of an ESC protein in the pathogenesis of ALK+ ALCL. © 2012 Elsevier Inc. Source

Levine J.,Stonybrook University
Brain Research | Year: 2015

Oligodendrocyte precursor cells (OPCs) react rapidly to brain and spinal cord injuries. This reaction is characterized by the retraction of cell processes, cell body swelling and increased expression of the NG2 chondroitin sulfate proteoglycan. Reactive OPCs rapidly divide and accumulate surrounding the injury site where they become major cellular components of the glial scar. The glial reaction to injury is an attempt to restore normal homeostasis and re-establish the glia limitans but the exact role of reactive OPCs in these processes is not well understood. Traumatic injury results in extensive oligodendrocyte cell death and the proliferating OPCs generate the large number of precursor cells necessary for remyelination. Reactive OPCs, however, also are a source of axon-growth inhibitory proteoglycans and may interact with invading inflammatory cells in complex ways. Here, I discuss these and other properties of OPCs after spinal cord injury. Understanding the regulation of these disparate properties may lead to new therapeutic approaches to devastating injuries of the spinal cord. This article is part of a Special Issue entitled SI:NG2-glia(Invited only). © 2015 Elsevier B.V. Source

Hui-Yuen J.S.,Stonybrook University | Imundo L.F.,Morgan Stanley | Avitabile C.,Childrens Hospital of Philadelphia | Kahn P.J.,New York University | And 2 more authors.
Lupus | Year: 2011

The objective of the study was to compare clinical features, treatment and disease outcome in patients with early versus later onset of childhood-onset systemic lupus erythematosus (cSLE). A retrospective matched cohort study of cSLE patients diagnosed between 1988 and 2008 and followed for a minimum of one year was conducted. Thirty-four pre-pubertal cSLE patients with disease onset prior to their 12th birthday were matched by ethnicity and year of diagnosis to 34 pubertal cSLE patients. The most common criteria at diagnosis in both groups were malar rash, arthritis, hematologic manifestations, and renal disease. After a mean follow-up of more than six years, a similar proportion of patients in the two groups were still prescribed corticosteroids (47% and 41%); patients in the early onset group required a significantly higher daily dose (0.6 mg/kg prednisone-equivalent versus 0.2 mg/kg, p < 0.05). There were no significant differences in organ involvement, disease activity and disease damage between the two groups, and severe complications occurred at similar rates. There were a greater number of admissions to the pediatric intensive care unit (PICU) in the early onset group (18 versus 5, p = 0.01), with time-to-event analysis demonstrating a significantly shorter disease duration from diagnosis to first PICU admission in the early onset group (p < 0.001). While a similar proportion of patients in the early and later onset groups required treatment with cyclophosphamide, patients in the early onset group received treatment earlier in their disease course (mean 13.7 versus 19.9 months, p < 0.001). Early onset cSLE leads to earlier and more frequent PICU admission, earlier use of cyclophosphamide, and higher corticosteroid dose at long-term follow-up. © The Author(s), 2011. Source

Cardinaud M.,University of Western Brittany | Dheilly N.M.,Stonybrook University | Huchette S.,France Haliotis | Moraga D.,University of Western Brittany | Paillard C.,University of Western Brittany
Developmental and Comparative Immunology | Year: 2015

Vibrio harveyi is a marine bacterial pathogen responsible for episodic abalone mortalities in France, Japan and Australia. In the European abalone, V. harveyi invades the circulatory system in a few hours after exposure and is lethal after 2 days of infection. In this study, we investigated the responses of European abalone immune cells over the first 24 h of infection. Results revealed an initial induction of immune gene expression including Rel/NF-kB, Mpeg and Clathrin. It is rapidly followed by a significant immuno-suppression characterized by reduced cellular hemocyte parameters, immune response gene expressions and enzymatic activities. Interestingly, Ferritin was overexpressed after 24 h of infection suggesting that abalone attempt to counter V. harveyi infection using soluble effectors. Immune function alteration was positively correlated with V. harveyi concentration. This study provides the evidence that V. harveyi has a hemolytic activity and an immuno-suppressive effect in the European abalone. © 2015 Elsevier Ltd. Source

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