Search results for "script"
showing 10 items of 5143 documents
Biological indicators of prognosis in Ewing's sarcoma: An emerging role for lectin galactoside-binding soluble 3 binding protein (LGALS3BP)
2009
Starting from an experimental model that accounts for the 2 most important adverse processes to successful therapy of Ewing's sarcoma (EWS), chemoresistance and the presence of metastasis at the time of diagnosis, we defined a molecular signature of potential prognostic value. Functional annotation of differentially regulated genes revealed 3 major networks related to cell cycle, cell-to-cell interactions and cellular development. The prognostic impact of 8 genes, representative of these 3 networks, was validated in 56 EWS patients. High mRNA expression levels of HINT1, IFITM2, LGALS3BP, STOML2 and c-MYC were associated with reduced risk to death and lower risk to develop metastasis. At mul…
Prognostic significance of interferon regulating factor 4 (IRF4) in node-negative breast cancer.
2014
620 Background: The transcription factor IRF4 (interferon regulating factor 4) regulates immunoglobulin class switch recombination as well as plasma cell differentiation. We examined the prognostic significance of IRF4 mRNA expression in node-negative breast cancer. Methods: Microarray based gene-expression data for IRF4 (204562_at) were analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n=824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of IRF4 on metastasis-free survival (MFS) was examined in the whole cohort and in…
Algorithmically deduced FREM2 molecular pathway is a potent grade and survival biomarker of human gliomas
2021
Gliomas are the most common malignant brain tumors with high mortality rates. Recently we showed that the FREM2 gene has a role in glioblastoma progression. Here we reconstructed the FREM2 molecular pathway using the human interactome model. We assessed the biomarker capacity of FREM2 expression and its pathway as the overall survival (OS) and progression-free survival (PFS) biomarkers. To this end, we used three literature and one experimental RNA sequencing datasets collectively covering 566 glioblastomas (GBM) and 1097 low-grade gliomas (LGG). The activation level of deduced FREM2 pathway showed strong biomarker characteristics and significantly outperformed the FREM2 expression level it…
STAT5 is crucial to maintain leukemic stem cells in acute myelogenous leukemias induced by MOZ-TIF2.
2012
Abstract MOZ-TIF2 is a leukemogenic fusion oncoprotein that confers self-renewal capability to hematopoietic progenitor cells and induces acute myelogenous leukemia (AML) with long latency in bone marrow transplantation assays. Here, we report that FLT3-ITD transforms hematopoietic cells in cooperation with MOZ-TIF2 in vitro and in vivo. Coexpression of FLT3-ITD confers growth factor independent survival/proliferation, shortens disease latency, and results in an increase in the number of leukemic stem cells (LSC). We show that STAT5, a major effector of aberrant FLT3-ITD signal transduction, is both necessary and sufficient for this cooperative effect. In addition, STAT5 signaling is essent…
SOCS2 controls proliferation and stemness of hematopoietic cells under stress conditions and its deregulation marks unfavorable acute leukemias
2015
Abstract Hematopoietic stem cells (HSC) promptly adapt hematopoiesis to stress conditions, such as infection and cancer, replenishing bone marrow–derived circulating populations, while preserving the stem cell reservoir. SOCS2, a feedback inhibitor of JAK–STAT pathways, is expressed in most primitive HSC and is upregulated in response to STAT5-inducing cytokines. We demonstrate that Socs2 deficiency unleashes HSC proliferation in vitro, sustaining STAT5 phosphorylation in response to IL3, thrombopoietin, and GM-CSF. In vivo, SOCS2 deficiency leads to unrestricted myelopoietic response to 5-fluorouracil (5-FU) and, in turn, induces exhaustion of long-term HSC function along serial bone marro…
Notch inhibition restores TRAIL-mediated apoptosis via AP1-dependent upregulation of DR4 and DR5 TRAIL receptors in MDA-MB-231 breast cancer cells.
2013
Notch is a family of transmembrane receptors whose activation through proteolytic cleavage by γ-secretase targets genes which participate in cell development, differentiation and tumorigenesis. Notch signaling is constitutively activated in various cancers, including breast cancer and its upregulation is usually related with poor clinical outcomes. Therefore, targeting Notch signaling with γ-secretase inhibitors (GSIs) is considered a promising strategy for cancer treatment. We report that the γ-secretase inhibitor-I (GSI-I) sensitizes human breast cancer cells to apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The antiproliferative GSI-I/TRAIL synergi…
Oligodendroglioma cells synthesize the differentiation-specific linker histone H1˚ and release it into the extracellular environment through shed ves…
2013
Chromatin remodelling can be involved in some of the epigenetic modifications found in tumor cells. One of the mechanisms at the basis of chromatin dynamics is likely to be synthesis and incorporation of replacement histone variants, such as the H1° linker histone. Regulation of the expression of this protein can thus be critical in tumorigenesis. In developing brain, H1° expression is mainly regulated at the post-transcriptional level and RNA-binding proteins (RBPs) are involved. In the past, attention mainly focused on the whole brain or isolated neurons and little information is available on H1° expression in other brain cells. Even less is known relating to tumor glial cells. In this st…
PO-298 MYC favours the onset of tumour initiating cells by inducing epigenetic reprogramming of mammary epithelial cells towards a stem cell-like sta…
2018
ABSTRACT Introduction Breast cancer consists of highly heterogenous tumours whose cell of origin resulted difficult to be defined. Recent findings highlighted the possibility that tumor-initiating cells (TICs) may arise from dedifferentiation of lineage-committed cells, by reactivation of multipotency in response to oncogenic insults. MYC is the most frequently amplified oncogene in breast cancer and the activation of MYC pathway has been associated with the basal-like subtype, which is characterised by poor survival and lack of a specific therapeutic strategy. Although MYC has been considered a driver oncogene in breast cancer, its mechanism of action in tumour initiation has been poorly a…
Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature.
2009
Abstract Tumors may be initiated and maintained by a cellular subcomponent that displays stem cell properties. We have used the expression of aldehyde dehydrogenase as assessed by the ALDEFLUOR assay to isolate and characterize cancer stem cell (CSC) populations in 33 cell lines derived from normal and malignant mammary tissue. Twenty-three of the 33 cell lines contained an ALDEFLUOR-positive population that displayed stem cell properties in vitro and in NOD/SCID xenografts. Gene expression profiling identified a 413-gene CSC profile that included genes known to play a role in stem cell function, as well as genes such as CXCR1/IL-8RA not previously known to play such a role. Recombinant int…
Expression of cytokeratin 17 mRNA in oral squamous cell carcinoma cells obtained by brush biopsy: preliminary results.
2009
Background: The aim of this study was to determine the detection of cytokeratin (CK) mRNA in oral squamous cell carcinoma (OSCC) cells and to evaluate the CK relevance for OSCC diagnosis in a brush biopsy test. Methods: Fifty-two pairs of OSCC cells and normal oral mucosal cells were obtained by brush biopsy from OSCC patients. mRNA was extracted from cell pellets for real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). The over-expression levels of CK 17, CK 19 and CK 20 mRNA in OSCC cells were examined by SYBR green real-time RT-qPCR. Results: Compared to normal mucosal cells, the over-expression of CK 17 mRNA was detectable in 40 OSCC cells (76.9%), that o…