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Ewing sarcoma mesenchymal stem cell

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https://www.readbyqxmd.com/read/27923328/modeling-stroma-induced-drug-resistance-in-a-tissue-engineered-tumor-model-of-ewing-sarcoma
#1
Marco Santoro, Brian A Menegaz, Salah-Eddine Lamhamedi-Cherradi, Eric R Molina, Danielle Wu, Waldemar Priebe, Joseph A Ludwig, Antonios G Mikos
Three-dimensional (3D) tumor models are gaining traction in the research community given their capacity to mimic aspects of the tumor microenvironment absent in monolayer systems. In particular, the ability to spatiotemporally control cell placement within ex vivo 3D systems has enabled the study of tumor-stroma interactions. Furthermore, by regulating biomechanical stimuli, one can reveal how biophysical cues affect stromal cell phenotype and how their phenotype impacts tumor drug sensitivity. Both tumor architecture and shear force have profound effects on Ewing sarcoma (ES) cell behavior and are known to elicit ligand-mediated activation of the insulin-like growth factor-1 receptor (IGF-1R), thereby mediating resistance of ES cells to IGF-1R inhibitors...
December 6, 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/27894957/dna-methylation-profiling-identifies-ptrf-cavin-1-as-a-novel-tumor-suppressor-in-ewing-sarcoma-when-co-expressed-with-caveolin-1
#2
Juan Huertas-Martínez, Franck Court, Santiago Rello-Varona, David Herrero-Martín, Olga Almacellas-Rabaiget, Miguel Sáinz-Jaspeado, Silvia Garcia-Monclús, Laura Lagares-Tena, Raquel Buj, Lourdes Hontecillas-Prieto, Ana Sastre, Daniel Azorin, Xavier Sanjuan, Roser López-Alemany, Sebastian Moran, Josep Roma, Soledad Gallego, Jaume Mora, Xavier García Del Muro, Paloma H Giangrande, Miquel A Peinado, Javier Alonso, Enrique de Alava, Dave Monk, Manel Esteller, Oscar M Tirado
Epigenetic modifications have been shown to be important in developmental tumors as Ewing sarcoma. We profiled the DNA methylation status of 15 primary tumors, 7 cell lines, 10 healthy tissues and 4 human mesenchymal stem cells lines samples using the Infinium Human Methylation 450k. Differential methylation analysis between Ewing sarcoma and reference samples revealed 1,166 hypermethylated and 864 hypomethylated CpG sites (Bonferroni p<0.05, δ-β-value with absolute difference of >0.20) corresponding to 392 and 470 genes respectively...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27806299/widespread-chromatin-accessibility-at-repetitive-elements-links-stem-cells-with-human-cancer
#3
Nicholas C Gomez, Austin J Hepperla, Raluca Dumitru, Jeremy M Simon, Fang Fang, Ian J Davis
Chromatin regulation is critical for differentiation and disease. However, features linking the chromatin environment of stem cells with disease remain largely unknown. We explored chromatin accessibility in embryonic and multipotent stem cells and unexpectedly identified widespread chromatin accessibility at repetitive elements. Integrating genomic and biochemical approaches, we demonstrate that these sites of increased accessibility are associated with well-positioned nucleosomes marked by distinct histone modifications...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27735950/increased-survival-and-cell-cycle-progression-pathways-are-required-for-ews-fli1-induced-malignant-transformation
#4
Tahereh Javaheri, Zahra Kazemi, Jan Pencik, Ha Tt Pham, Maximilian Kauer, Rahil Noorizadeh, Barbara Sax, Harini Nivarthi, Michaela Schlederer, Barbara Maurer, Maximillian Hofbauer, Dave Nt Aryee, Marc Wiedner, Eleni M Tomazou, Malcolm Logan, Christine Hartmann, Jan P Tuckermann, Lukas Kenner, Mario Mikula, Helmut Dolznig, Aykut Üren, Günther H Richter, Florian Grebien, Heinrich Kovar, Richard Moriggl
Ewing sarcoma (ES) is the second most frequent childhood bone cancer driven by the EWS/FLI1 (EF) fusion protein. Genetically defined ES models are needed to understand how EF expression changes bone precursor cell differentiation, how ES arises and through which mechanisms of inhibition it can be targeted. We used mesenchymal Prx1-directed conditional EF expression in mice to study bone development and to establish a reliable sarcoma model. EF expression arrested early chondrocyte and osteoblast differentiation due to changed signaling pathways such as hedgehog, WNT or growth factor signaling...
October 13, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27665785/arsenic-trioxide-potentiates-the-effectiveness-of-etoposide-in-ewing-sarcomas
#5
Karen A Boehme, Juliane Nitsch, Rosa Riester, Rupert Handgretinger, Sabine B Schleicher, Torsten Kluba, Frank Traub
Ewing sarcomas (ES) are rare mesenchymal tumours, most commonly diagnosed in children and adolescents. Arsenic trioxide (ATO) has been shown to efficiently and selectively target leukaemic blasts as well as solid tumour cells. Since multidrug resistance often occurs in recurrent and metastatic ES, we tested potential additive effects of ATO in combination with the cytostatic drugs etoposide and doxorubicin. The Ewing sarcoma cell lines A673, RD-ES and SK-N-MC as well as mesenchymal stem cells (MSC) for control were treated with ATO, etoposide and doxorubicin in single and combined application...
September 21, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27558972/trail-delivered-by-mesenchymal-stromal-stem-cells-counteracts-tumor-development-in-orthotopic-ewing-sarcoma-models
#6
Romain Guiho, Kevin Biteau, Giulia Grisendi, Julien Taurelle, Mathias Chatelais, Malika Gantier, Dominique Heymann, Massimo Dominici, Françoise Redini
Ewing sarcoma (EWS) is the second most frequent pediatric malignant bone tumor. EWS patients have not seen any major therapeutic progress in the last 30 years, in particular in the case of metastatic disease, which requires new therapeutic strategies. The pro-apoptotic cytokine TNF-Related Apoptosis Inducing Ligand (TRAIL) can selectively kill tumor cells while sparing normal cells, making it a promising therapeutic tool in several types of cancer. However, certain EWS cell lines appear resistant to recombinant human (rh) TRAIL-induced apoptosis...
December 15, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27446218/gene-expression-music-algorithm-based-characterization-of-the-ewing-sarcoma-stem-cell-signature
#7
Martin Sebastian Staege
Gene Expression Music Algorithm (GEMusicA) is a method for the transformation of DNA microarray data into melodies that can be used for the characterization of differentially expressed genes. Using this method we compared gene expression profiles from endothelial cells (EC), hematopoietic stem cells, neuronal stem cells, embryonic stem cells (ESC), and mesenchymal stem cells (MSC) and defined a set of genes that can discriminate between the different stem cell types. We analyzed the behavior of public microarray data sets from Ewing sarcoma ("Ewing family tumors," EFT) cell lines and biopsies in GEMusicA after prefiltering DNA microarray data for the probe sets from the stem cell signature...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27279906/recapitulating-the-size-and-cargo-of-tumor-exosomes-in-a-tissue-engineered-model
#8
Aranzazu Villasante, Alessandro Marturano-Kruik, Srikanth R Ambati, Zen Liu, Amandine Godier-Furnemont, Hesam Parsa, Benjamin W Lee, Malcolm A S Moore, Gordana Vunjak-Novakovic
There is a growing interest in the pivotal role of exosomes in cancer and in their use as biomarkers. However, despite the importance of the microenvironment for cancer initiation and progression, monolayer cultures of tumor cells still represent the main in vitro source of exosomes. As a result, their environmental regulation remains largely unknown. Here, we report a three-dimensional tumor model for studying exosomes, using Ewing's sarcoma type 1 as a clinically relevant example. The bioengineered model was designed based on the hypothesis that the 3-dimensionality, composition and stiffness of the tumor matrix are the critical determinants of the size and cargo of exosomes released by the cancer cells...
2016: Theranostics
https://www.readbyqxmd.com/read/27115504/bioengineered-models-of-solid-human-tumors-for-cancer-research
#9
Alessandro Marturano-Kruik, Aranzazu Villasante, Gordana Vunjak-Novakovic
The lack of controllable in vitro models that can recapitulate the features of solid tumors such as Ewing's sarcoma limits our understanding of the tumor initiation and progression and impedes the development of new therapies. Cancer research still relies of the use of simple cell culture, tumor spheroids, and small animals. Tissue-engineered tumor models are now being grown in vitro to mimic the actual tumors in patients. Recently, we have established a new protocol for bioengineering the Ewing's sarcoma, by infusing tumor cell aggregates into the human bone engineered from the patient's mesenchymal stem cells...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/26979953/exploring-the-surfaceome-of-ewing-sarcoma-identifies-a-new-and-unique-therapeutic-target
#10
Jennifer Town, Helio Pais, Sally Harrison, Lucy F Stead, Carole Bataille, Wilawan Bunjobpol, Jing Zhang, Terence H Rabbitts
The cell surface proteome of tumors mediates the interface between the transformed cells and the general microenvironment, including interactions with stromal cells in the tumor niche and immune cells such as T cells. In addition, the cell surface proteome of individual cancers defines biomarkers for that tumor type and potential proteins that can be the target of antibody-mediated therapy. We have used next-generation deep RNA sequencing (RNA-seq) coupled to an in-house database of genes encoding cell surface proteins (herein referred to as the surfaceome) as a tool to define a cell surface proteome of Ewing sarcoma compared with progenitor mesenchymal stem cells...
March 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26846737/microrna-301a-promotes-cell-proliferation-via-pten-targeting-in-ewing-s-sarcoma-cells
#11
Masanori Kawano, Kazuhiro Tanaka, Ichiro Itonaga, Tatsuya Iwasaki, Hiroshi Tsumura
MicroRNAs (miRNAs) regulate cell proliferation and differentiation by affecting gene expression at the post-transcriptional level by binding to complementary sequences within mRNAs in cancer cells, indicating that miRNAs can function as tumor suppressors or oncogenes. Recent studies showed that dysregulation of miRNA expression was associated with increased tumorigenicity and poor prognosis in several types of cancers, including Ewing's sarcoma (ES). To explore possible oncogenic factors in ES, we conducted microarray-based investigation and profiled the changes in miRNA expression and their effects on downstream mRNAs in five ES cell lines and human mesenchymal stem cells (hMSCs)...
April 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/26807198/the-role-of-fli-1-ews-a-fusion-gene-reciprocal-to-ews-fli-1-in-ewing-sarcoma
#12
David J Elzi, Meihua Song, Peter J Houghton, Yidong Chen, Yuzuru Shiio
Ewing sarcoma is a cancer of bone and soft tissue in children that is characterized by a chromosomal translocation involving EWS and an Ets family transcription factor, most commonly FLI-1. The EWS-FLI-1 fusion oncogene is widely believed to play a central role in Ewing sarcoma. The EWS-FLI-1 gene product regulates the expression of a number of genes important for cancer progression, can transform mouse cells such as NIH3T3 and C3H10T1/2, and is necessary for proliferation and tumorigenicity of Ewing sarcoma cells, suggesting that EWS-FLI-1 is the causative oncogene...
November 2015: Genes & Cancer
https://www.readbyqxmd.com/read/26364611/rna-helicase-ddx3-a-novel-therapeutic-target-in-ewing-sarcoma
#13
B A Wilky, C Kim, G McCarty, E A Montgomery, K Kammers, L R DeVine, R N Cole, V Raman, D M Loeb
RNA helicase DDX3 has oncogenic activity in breast and lung cancers and is required for translation of complex mRNA transcripts, including those encoding key cell-cycle regulatory proteins. We sought to determine the expression and function of DDX3 in sarcoma cells, and to investigate the antitumor activity of a novel small molecule DDX3 inhibitor, RK-33. Utilizing various sarcoma cell lines, xenografts and human tissue microarrays, we measured DDX3 expression at the mRNA and protein levels, and evaluated cytotoxicity of RK-33 in sarcoma cell lines...
May 19, 2016: Oncogene
https://www.readbyqxmd.com/read/25501132/cd99-triggering-in-ewing-sarcoma-delivers-a-lethal-signal-through-p53-pathway-reactivation-and-cooperates-with-doxorubicin
#14
Clara Guerzoni, Valentina Fiori, Mario Terracciano, Maria Cristina Manara, Diego Moricoli, Michela Pasello, Marika Sciandra, Giordano Nicoletti, Mara Gellini, Sabrina Dominici, Claudia Chiodoni, Pier Maria Fornasari, Pier-Luigi Lollini, Mario P Colombo, Piero Picci, Maurizio Cianfriglia, Mauro Magnani, Katia Scotlandi
PURPOSE: The paucity of new drugs for the treatment of Ewing sarcoma (EWS) limits the cure of these patients. CD99 has a strong membranous expression in EWS cells and, being also necessary for tumor survival, is a suitable target to aim at. In this article, we described a novel human monospecific bivalent single-chain fragment variable diabody (dAbd C7) directed against CD99 of potential clinical application. EXPERIMENTAL DESIGN: In vitro and in vivo evaluation of cell death and of the molecular mechanisms triggered by anti-CD99 agents were performed alone or in combination with doxorubicin to demonstrate efficacy and selectivity of the new dAbd C7...
January 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/25420617/mesenchymal-progenitors-expressing-trail-induce-apoptosis-in-sarcomas
#15
Giulia Grisendi, Carlotta Spano, Naomi D'souza, Valeria Rasini, Elena Veronesi, Malvina Prapa, Tiziana Petrachi, Serena Piccinno, Filippo Rossignoli, Jorge S Burns, Stefania Fiorcari, Donatella Granchi, Nicola Baldini, Edwin M Horwitz, Valentina Guarneri, Pierfranco Conte, Paolo Paolucci, Massimo Dominici
Sarcomas are frequent tumors in children and young adults that, despite a relative chemo-sensitivity, show high relapse rates with up to 80% of metastatic patients dying in 5 years from diagnosis. The real ontogeny of sarcomas is still debated and evidences suggest they may derive from precursors identified within mesenchymal stromal/stem cells (MSC) fractions. Recent studies on sarcoma microenvironment additionally indicated that MSC could take active part in generation of a supportive stroma. Based on this knowledge, we conceived to use modified MSC to deliver tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) targeting different sarcoma histotypes...
March 2015: Stem Cells
https://www.readbyqxmd.com/read/25015333/prognostic-significance-of-mir-34a-in-ewing-sarcoma-is-associated-with-cyclin-d1-and-ki-67-expression
#16
M T Marino, A Grilli, C Baricordi, M C Manara, S Ventura, R S Pinca, M Bellenghi, M Calvaruso, G Mattia, D Donati, C Tripodo, P Picci, S Ferrari, K Scotlandi
BACKGROUND: At diagnosis, identification of reliable biological indicators of prognosis to allow stratification of patients according to different risks is an important but still unresolved aspect in the treatment of Ewing sarcoma (EWS) patients. This study aimed to explore the role of miR-34A expression on prognosis of EWS patients. PATIENTS AND METHODS: Specimens from 109 patients with non-metastatic EWS treated at the Rizzoli Institute with neoadjuvant chemotherapy (protocols ISG/SSGIII, EW-1, EW-2, EW-REN2, EW-REN3, EW-PILOT) and 17 metastases were studied...
October 2014: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/24934313/matrilin-3-as-a-putative-effector-of-c-type-natriuretic-peptide-signaling-during-tgf-%C3%AE-induced-chondrogenic-differentiation-of-mesenchymal-stem-cells
#17
Mustafa Ege Babadagli, Berna Tezcan, Seda Tasir Yilmaz, A Cevik Tufan
C-type natriuretic peptide (CNP) signaling has been implicated as an important regulator of chondrogenic differentiation during endochondral bone development. This preliminary study further investigated the putative effectors and/or targets of CNP signaling in transforming growth factor (TGF)-β induced in vitro chondrogenic differentiation of mesenchymal stem cells (MSCs). Previously characterized human trabecular bone derived MSCs were induced either with only TGF-β1 or with a combination of TGF-β1 and CNP in micromass culture for 10 or 20 days...
September 2014: Molecular Biology Reports
https://www.readbyqxmd.com/read/24716831/in-vitro-biosafety-profile-evaluation-of-multipotent-mesenchymal-stem-cells-derived-from-the-bone-marrow-of-sarcoma-patients
#18
Enrico Lucarelli, Chiara Bellotti, Melissa Mantelli, Maria Antonietta Avanzini, Rita Maccario, Francesca Novara, Giulia Arrigo, Orsetta Zuffardi, Monia Zuntini, Martina Pandolfi, Luca Sangiorgi, Daniela Lisini, Davide Donati, Serena Duchi
BACKGROUND: In osteosarcoma (OS) and most Ewing sarcoma (EWS) patients, the primary tumor originates in the bone. Although tumor resection surgery is commonly used to treat these diseases, it frequently leaves massive bone defects that are particularly difficult to be treated. Due to the therapeutic potential of mesenchymal stem cells (MSCs), OS and EWS patients could benefit from an autologous MSCs-based bone reconstruction. However, safety concerns regarding the in vitro expansion of bone marrow-derived MSCs have been raised...
2014: Journal of Translational Medicine
https://www.readbyqxmd.com/read/24667836/differentially-expressed-mirnas-in-ewing-sarcoma-compared-to-mesenchymal-stem-cells-low-mir-31-expression-with-effects-on-proliferation-and-invasion
#19
COMPARATIVE STUDY
Bianca Karnuth, Nicolas Dedy, Tilmann Spieker, Elizabeth R Lawlor, Stefan Gattenlöhner, Andreas Ranft, Uta Dirksen, Heribert Jürgens, Andreas Bräuninger
Ewing sarcoma, the second most common bone tumor in children and young adults, is an aggressive malignancy with a strong potential to metastasize. Ewing sarcoma is characterised by translocations encoding fusion transcription factors with an EWSR1 transactivation domain fused to an ETS family DNA binding domain. microRNAs are post-transcriptional regulators of gene expression and aberrantly expressed microRNAs have been identified as tumor suppressors or oncogenes in most cancer types. To identify potential oncogenic and tumor suppressor microRNAs in Ewing sarcoma, we determined and compared the expression of 377 microRNAs in 40 Ewing sarcoma biopsies, 6 Ewing sarcoma cell lines and mesenchymal stem cells, the putative cellular origin of Ewing sarcoma, from 6 healthy donors...
2014: PloS One
https://www.readbyqxmd.com/read/24498265/characterization-of-human-mesenchymal-stem-cells-from-ewing-sarcoma-patients-pathogenetic-implications
#20
Ana Teresa Amaral, Maria Cristina Manara, Dagmar Berghuis, José Luis Ordóñez, Michele Biscuola, Maria Angeles Lopez-García, Daniel Osuna, Enrico Lucarelli, Francesco Alviano, Arjan Lankester, Katia Scotlandi, Enrique de Álava
BACKGROUND: Ewing Sarcoma (EWS) is a mesenchymal-derived tumor that generally arises in bone and soft tissue. Intensive research regarding the pathogenesis of EWS has been insufficient to pinpoint the early events of Ewing sarcomagenesis. However, the Mesenchymal Stem Cell (MSC) is currently accepted as the most probable cell of origin. MATERIALS AND METHODS: In an initial study regarding a deep characterization of MSC obtained specifically from EWS patients (MSC-P), we compared them with MSC derived from healthy donors (MSC-HD) and EWS cell lines...
2014: PloS One
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