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ES cells

Pietro Parcesepe, Guido Giordano, Caterina Zanella, Jacopo Giuliani, Filippo Greco, Andrea Bonetti, Massimo Pancione, Erminia Manfrin, Enrico Molinari, Tiziana Pia Latiano, Mario Rosario D'Andrea, Matteo Fassan, Nunzio Olivieri, Andrea Remo
Ewing Sarcoma is a highly lethal undifferentiated tumor of bone. ES is a small round cell tumor with etiological and characteristic chromosomal translocations between TET/FET (TLS/FUS, EWSR1, and TAF15) and ETS (E26 transformation-specific) family genes. Generally, therapeutic approach for metastatic Ewing Sarcoma includes both local (surgery and radiotherapy) and systemic (chemotherapy) disease control with an overall cure rate of 20%. For extra-osseous tumors, the most common primary sites of disease are trunk, extremities, head and neck, retroperitoneum...
November 29, 2018: Pathology, Research and Practice
Fatemeh Sharifpanah, Enas Hussein Ali, Maria Wartenberg, Heinrich Sauer
The milk thistle compound Silibinin (i.e., a 1:1 mixture of Silybin A and Silybin B) stimulates vasculogenesis of mouse embryonic stem (ES) cells. Because vasculogenesis and leukopoiesis are interrelated, the effect of Silibinin on leukopoiesis of ES cells was investigated. Treatment of differentiating ES cells with hydrosoluble Silibinin-C-2',3-dihydrogen succinate dose-dependent increased the number of CD18+ , CD45+ , and CD68+ cells, indicating leukocyte/macrophage differentiation. Silibinin treatment activated phosphoinositide 3-kinase (PI3K), AKT (protein kinase B), signal transducer and activator of transcription 3 (STAT3), stimulated hypoxia-induced factor-1α (HIF-1α), and vascular endothelial growth factor receptor 2 (VEGFR2) expression and raised intracellular nitric oxide (NO)...
December 11, 2018: Phytotherapy Research: PTR
Yu Yang Soon, Huili Zheng, Shaun Zhirui Ho, Wee Yao Koh, Cheng Nang Leong, Jeremy Chee Seong Tey, Balamurugan Vellayappan, Swee Peng Yap, Ivan Weng Keong Tham, Kam Weng Fong
BACKGROUND: The survival benefit of PCI in ES-SCLC reported by a European randomized trial (RCT) in 2007 was not replicated by a Japanese RCT published in 2017. This study aimed to evaluate the uptake of PCI before and after publication of the European RCT and its association with survival in ES-SCLC. METHODS: We identified eligible patients in the only two Singapore national cancer centres from 2003 to 2010. We linked their electronic medical records to the national death registry...
December 14, 2018: Radiation Oncology
Juan P Gurria, Roshni Dasgupta
Rhabdomyosarcoma (RMS) is a malignant tumor that represents the most common form of pediatric soft tissue sarcoma. It arises from mesenchymal origin and forms part of the group of small round blue cell tumors of childhood. It has a constant annual incidence of 4.5 cases per 1,000,000 children. The known histological diagnosis of the two major subtypes (embryonal and alveolar) has been recently enhanced by tumor biological markers and molecular differentiation diagnostic tools that have improved not only the updated classification based on risk stratification, but also the treatment approach based on the clinical group...
December 10, 2018: Children
Ning Sheng, Yanyan Wang, Ying Xie, Sihan Chen, Jun Lu, Zifeng Zhang, Mengqiu Li, Qun Shan, Dongmei Wu, Guihong Zheng, Yuanlin Zheng, Shaohua Fan
Homo sapiens longevity assurance homolog 2 of yeast LAG1 (LASS2), is a gene isolated from a human liver complementary DNA library. In this study, we found that LASS2 protein level was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage and LASS2-negative tumors showed significant association with longer disease-free survival (DFS) and overall survival (OS) in ovarian cancer patients. The heterogeneous expression of LASS2 had been exhibited in diverse ovarian cancer cells...
December 7, 2018: Journal of Cellular Physiology
Lifang Guo, Xingchao Geng, Li Liu, Yufa Miao, Zhi Lin, Min Yu, Yan Fu, Lihong Liu, Bo Li, Yongzhang Luo
Endostar, a potent endogenous antiangiogenic factor, is wildly used in clinics. However, it was easily degraded by enzymes and rapidly cleared by the kidneys. To overcome these shortcomings, PEGylated recombinant human endostatin was developed. In this study, the purity of M2 ES was evaluated by silver stain and reversed-phase high-performance liquid chromatography. Ultraviolet spectrum was used to examine the structural of M2 ES and endostar. The bioactivity and antitumor efficacy of M2 ES were evaluated using an in vitro endothelial cell migration model and athymic nude mouse xenograft model of a heterogeneous lung adenocarcinoma, respectively...
December 10, 2018: Journal of Biochemical and Molecular Toxicology
Dan Zhou, Lei Tan, Jian Li, Tanbin Liu, Yi Hu, Yalan Li, Sachiyo Kawamoto, Chengyu Liu, Shiyin Guo, Aibing Wang
Relative to the issues of off-target effects and the difficulty of inserting a long DNA fragment in the application of designer nucleases for genome editing, embryonic stem (ES) cell-based gene-targeting technology does not have these shortcomings and is widely used to modify animal/mouse genome ranging from large deletions/insertions to single nucleotide substitutions. Notably, identifying the relatively few homologous recombination (HR) events necessary to obtain desired ES clones is a key step, which demands accurate and reliable methods...
November 20, 2018: Journal of Visualized Experiments: JoVE
Kai Kretzschmar, Yorick Post, Marie Bannier-Hélaouët, Andrea Mattiotti, Jarno Drost, Onur Basak, Vivian S W Li, Maaike van den Born, Quinn D Gunst, Danielle Versteeg, Lieneke Kooijman, Stefan van der Elst, Johan H van Es, Eva van Rooij, Maurice J B van den Hoff, Hans Clevers
The significance of cardiac stem cell (CSC) populations for cardiac regeneration remains disputed. Here, we apply the most direct definition of stem cell function (the ability to replace lost tissue through cell division) to interrogate the existence of CSCs. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, we map all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium represented various noncardiomyocyte cell types...
December 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
Yong Fan, Beatrice Xuan Ho, Jeremy Kah Sheng Pang, Nicole Min Qian Pek, Jin Hui Hor, Shi-Yan Ng, Boon-Seng Soh
BACKGROUND: The Wnt/β-catenin signaling pathway plays an important role in the development of second heart field (SHF Isl1+) that gives rise to the anterior heart field (AHF) cardiac progenitor cells (CPCs) for the formation of the right ventricle, outflow tract (OFT), and a portion of the inflow tract (IFT). During early cardiogenesis, these AHF CPCs reside within the pharyngeal mesoderm (PM) that provides a microenvironment for them to receive signals that direct their cell fates. Here, N-cadherin, which is weakly expressed by CPCs, plays a significant role by promoting the adhesion of CPCs within the AHF, regulating β-catenin levels in the cytoplasm to maintain high Wnt signaling and cardioproliferation while also preventing the premature differentiation of CPCs...
December 7, 2018: Stem Cell Research & Therapy
Taofeek K Owonikoko, Suzanne E Dahlberg, Gabriel L Sica, Lynne I Wagner, James L Wade, Gordan Srkalovic, Bradley W Lash, Joseph W Leach, Ticiana B Leal, Charu Aggarwal, Suresh S Ramalingam
PURPOSE: Veliparib, a poly (ADP ribose) polymerase inhibitor, potentiated standard chemotherapy against small-cell lung cancer (SCLC) in preclinical studies. We evaluated the combination of veliparib with cisplatin and etoposide (CE; CE+V) doublet in untreated, extensive-stage SCLC (ES-SCLC). MATERIALS AND METHODS: Patients with ES-SCLC, stratified by sex and serum lactate dehydrogenase levels, were randomly assigned to receive four 3-week cycles of CE (75 mg/m2 intravenously on day 1 and 100 mg/m2 on days 1 through 3) along with veliparib (100 mg orally twice per day on days 1 through 7) or placebo (CE+P)...
December 5, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Peter Baillie-Johnson, Octavian Voiculescu, Penny Hayward, Benjamin Steventon
Neuromesodermal progenitors (NMps) are a population of bipotent progenitors that maintain competence to generate both spinal cord and paraxial mesoderm throughout the elongation of the posterior body axis. Recent studies have generated populations of NMp-like cells in culture, which have been shown to differentiate to both neural and mesodermal cell fates when transplanted into either mouse or chick embryos. Here, we aim to compare the potential of mouse embryonic stem (ES) cell-derived progenitor populations to generate NMp behaviour against both undifferentiated and differentiated populations...
December 5, 2018: Cells, Tissues, Organs
Florian Winkler, Katia Herz, Sarah Rieck, Kenichi Kimura, Tianyuan Hu, Wilhelm Röll, Michael Hesse, Bernd K Fleischmann, Daniela Wenzel
For the monitoring of vascular growth as well as adaptive or therapeutic (re)vascularization endothelial-specific reporter mouse models are valuable tools. However, currently available mouse models have limitations, because not all endothelial cells express the reporter in all developmental stages. We have generated PECAM/eGFP embryonic stem (ES) cell and mouse lines where the reporter gene labels PECAM+ endothelial cells and vessels with high specificity. Native eGFP expression and PECAM staining were highly co-localized in vessels of various organs at embryonic stages E9...
December 4, 2018: Scientific Reports
Keriayn N Smith, Joshua Starmer, Terry Magnuson
Long noncoding RNAs (lncRNAs) constitute a significant fraction of mammalian transcriptomes and they have emerged as intricate regulators of many biological processes. Their broad capacity to adopt diverse structures facilitates their involvement in the transcriptional, translational and signaling processes that are central to embryonic stem (ES) cell self-renewal and pluripotency. While lncRNAs have been implicated in ES cell maintenance, detailed analyses of those that show significant expression in ES cells is largely absent...
December 4, 2018: Scientific Reports
Christopher Tsao, Laura Pandolfi, Xin Wang, Silvia Minardi, Cristina Lupo, Michael Evangelopoulos, Troy Hendrickson, Aaron Shi, Gianluca Storci, Francesca Taraballi, Ennio Tasciotti
The use of nanomaterials as carriers for the delivery of growth factors has been applied to a multitude of applications in tissue engineering. However, issues of toxicity, stability and systemic effects of these platforms have yet to be fully understood, especially for cardiovascular applications. Here, we proposed a delivery system composed of poly(DL-lactide-co-glycolide) acid (PLGA) and porous silica nanoparticles (pSi) to deliver vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)...
December 4, 2018: ACS Applied Materials & Interfaces
Simona V Antonova, Matthias Haffke, Eleonora Corradini, Mykolas Mikuciunas, Teck Y Low, Luca Signor, Robert M van Es, Kapil Gupta, Elisabeth Scheer, Harmjan R Vos, László Tora, Albert J R Heck, H T Marc Timmers, Imre Berger
TFIID is a cornerstone of eukaryotic gene regulation. Distinct TFIID complexes with unique subunit compositions exist and several TFIID subunits are shared with other complexes, thereby conveying precise cellular control of subunit allocation and functional assembly of this essential transcription factor. However, the molecular mechanisms that underlie the regulation of TFIID remain poorly understood. Here we use quantitative proteomics to examine TFIID submodules and assembly mechanisms in human cells. Structural and mutational analysis of the cytoplasmic TAF5-TAF6-TAF9 submodule identified novel interactions that are crucial for TFIID integrity and for allocation of TAF9 to TFIID or the Spt-Ada-Gcn5 acetyltransferase (SAGA) co-activator complex...
December 3, 2018: Nature Structural & Molecular Biology
Richard Behringer, Marina Gertsenstein, Kristina Vintersten Nagy, Andras Nagy
To obtain ubiquitous or simply widespread transgene expression from a single stable integrant transgene is quite challenging because the random genomic integration sites of transgenes may create expression variation or frequent silencing. The tetracycline (Tet)-inducible system requires two reliable working transgenes, one for the tetracycline transactivators (tTA or rtTA) and one for the responder transgene driven by the tet-O promoter. Therefore, the challenge of getting this system working properly is a serious prospect...
December 3, 2018: Cold Spring Harbor Protocols
Luis M Aguilera-Sáez, Francisco M Arrabal-Campos, Ángel J Callejón-Ferre, María D Suárez Medina, Ignacio Fernández
We have introduced the use of multivariate NMR analysis in the development of accurate and robust prediction models, potentially arising from a correlation between soluble metabolite profiles and cell wall composition, for the determination of hemicellulose, cellulose and lignin contents in 8 species of greenhouse crop residues. The present paper demonstrates that discriminant buckets coming from a PLS-DA model in combination with linear models provide a useful and rapid tool for the determination of cell wall composition of these plant wastes...
November 28, 2018: Phytochemistry
Huili Hu, Helmuth Gehart, Benedetta Artegiani, Carmen LÖpez-Iglesias, Florijn Dekkers, Onur Basak, Johan van Es, Susana M Chuva de Sousa Lopes, Harry Begthel, Jeroen Korving, Maaike van den Born, Chenhui Zou, Corrine Quirk, Luis Chiriboga, Charles M Rice, Stephanie Ma, Anne Rios, Peter J Peters, Ype P de Jong, Hans Clevers
The mammalian liver possesses a remarkable regenerative ability. Two modes of damage response have been described: (1) The "oval cell" response emanates from the biliary tree when all hepatocytes are affected by chronic liver disease. (2) A massive, proliferative response of mature hepatocytes occurs upon acute liver damage such as partial hepatectomy (PHx). While the oval cell response has been captured in vitro by growing organoids from cholangiocytes, the hepatocyte proliferative response has not been recapitulated in culture...
November 29, 2018: Cell
Cheryl Stork, Zhelin Li, Lin Lin, Sika Zheng
X-inactive-specific transcript (Xist) is a long noncoding RNA (lncRNA) essential for inactivating one of the two X chromosomes in mammalian females. Random X chromosome inactivation is mediated by Xist RNA expressed from the inactive X chromosome. We found that Xist RNA is unspliced in naïve embryonic stem (ES) cells. Upon differentiation, Xist splicing becomes efficient across all exons independent of transcription, suggesting interdependent or coordinated removal of Xist introns. In female cells with mutated polypyrimidine tract binding protein 1 (Ptbp1), differentiation fails to substantially upregulate mature Xist RNA because of a defect in Xist splicing...
November 29, 2018: Nucleic Acids Research
Elizabeth Lieschke, Zilu Wang, Gemma L Kelly, Andreas Strasser
Activation of the tumour suppressor p53 upon cellular stress can induce a number of different cellular processes. The diverse actions of these processes are critical for the protective function of p53 in preventing the development of cancer. However, it is still not fully understood which process(es) activated by p53 is/are critical for tumour suppression and how this might differ depending on the type of cells undergoing neoplastic transformation and the nature of the drivers of oncogenesis. Moreover, it is not clear why upon activation of p53 some cells undergo cell cycle arrest and senescence whereas others die by apoptosis...
November 29, 2018: Journal of Molecular Cell Biology
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