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Stem cell therapy, epigenetics

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https://www.readbyqxmd.com/read/28903069/cell-reprogramming-therapeutic-potential-and-the-promise-of-rejuvenation-for-the-aging-brain
#1
REVIEW
Micaela López-León, Tiago F Outeiro, Rodolfo G Goya
Aging is associated with a progressive increase in the incidence of neurodegenerative diseases, with Alzheimer's (AD) and Parkinson's (PD) disease being the most conspicuous examples. Within this context, the absence of efficacious therapies for most age-related brain pathologies has increased the interest in regenerative medicine. In particular, cell reprogramming technologies have ushered in the era of personalized therapies that not only show a significant potential for the treatment of neurodegenerative diseases but also promise to make biological rejuvenation feasible...
September 10, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28895566/wnt-signalling-in-prostate-cancer
#2
REVIEW
Virginia Murillo-Garzón, Robert Kypta
Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours - particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion...
September 12, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28895234/runx2-induction-during-differentiation-of-wharton-s-jelly-mesenchymal-stem-cells-to-osteoblasts-is-regulated-by-jarid1b-histone-demethylase
#3
Francisco Bustos, Hugo Sepúlveda, Catalina P Prieto, Margarita Carrasco, Lorena Díaz, José Palma, José Lattus, Martín Montecino, Verónica Palma
Novel bone regeneration approaches aim to obtain immature osteoblasts from somatic stem cells. Umbilical cord Wharton's jelly mesenchymal stem cells (WJ-MSC) are an ideal source for cell therapy. Hence, the study of mechanisms involved in WJ-MSC osteoblastic differentiation is crucial to exploit their developmental capacity. Here, we have assessed epigenetic control of the RUNX2 osteogenic master regulator gene in WJ-MSC. We present evidence indicating that modulation of RUNX2 expression through preventing JARID1B histone demethylase activity is relevant to enhance WJ-MSC osteoblastic potential...
September 12, 2017: Stem Cells
https://www.readbyqxmd.com/read/28883001/kdm4-inhibition-targets-breast-cancer-stem-like-cells
#4
Eric Metzger, Stella S Stepputtis, Juliane Strietz, Bogdan-Tiberius Preca, Sylvia Urban, Dominica Willmann, Anita Allen, Fides Zenk, Nicola Iovino, Peter Bronsert, Amelie Proske, Marie Follo, Melanie Boerries, Elmar Stickeler, Jiangchun Xu, Michael B Wallace, Jeffrey A Stafford, Toufike Kanouni, Jochen Maurer, Roland Schüle
Traditional treatments for breast cancer fail to address therapy-resistant cancer stem-like cells that have been characterized by changes in epigenetic regulators such as the lysine demethylase KDM4. Here we describe an orally available, selective and potent KDM4 inhibitor (QC6352) with unique preclinical characteristics. To assess the anti-tumor properties of QC6352, we established a method to isolate and propagate breast cancer stem-like cells (BCSC) from individual triple-negative tumors resected from patients after neoadjuvant chemotherapy...
September 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28864354/methods-of-reactivation-and-reprogramming-of-neural-stem-cells-for-neural-repair
#5
REVIEW
Zuojun Tian, Qiuge Zhao, Sangita Biswas, Wenbin Deng
Research on the biology of adult neural stem cells (NSCs) and induced NSCs (iNSCs), as well as NSC-based therapies for diseases in central nervous system (CNS) has started to generate the expectation that these cells may be used for treatments in CNS injuries or disorders. Recent technological progresses in both NSCs themselves and their derivatives have brought us closer to therapeutic applications. Adult neurogenesis presents in particular regions in mammal brain, known as neurogenic niches such as the dental gyrus (DG) in hippocampus and the subventricular zone (SVZ), within which adult NSCs usually stay for long periods out of the cell cycle, in G0...
August 31, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28854171/fate-mapping-of-human-glioblastoma-reveals-an-invariant-stem-cell-hierarchy
#6
Xiaoyang Lan, David J Jörg, Florence M G Cavalli, Laura M Richards, Long V Nguyen, Robert J Vanner, Paul Guilhamon, Lilian Lee, Michelle M Kushida, Davide Pellacani, Nicole I Park, Fiona J Coutinho, Heather Whetstone, Hayden J Selvadurai, Clare Che, Betty Luu, Annaick Carles, Michelle Moksa, Naghmeh Rastegar, Renee Head, Sonam Dolma, Panagiotis Prinos, Michael D Cusimano, Sunit Das, Mark Bernstein, Cheryl H Arrowsmith, Andrew J Mungall, Richard A Moore, Yussanne Ma, Marco Gallo, Mathieu Lupien, Trevor J Pugh, Michael D Taylor, Martin Hirst, Connie J Eaves, Benjamin D Simons, Peter B Dirks
Human glioblastomas harbour a subpopulation of glioblastoma stem cells that drive tumorigenesis. However, the origin of intratumoural functional heterogeneity between glioblastoma cells remains poorly understood. Here we study the clonal evolution of barcoded glioblastoma cells in an unbiased way following serial xenotransplantation to define their individual fate behaviours. Independent of an evolving mutational signature, we show that the growth of glioblastoma clones in vivo is consistent with a remarkably neutral process involving a conserved proliferative hierarchy rooted in glioblastoma stem cells...
August 30, 2017: Nature
https://www.readbyqxmd.com/read/28844656/methylome-analysis-of-human-bone-marrow-mscs-reveals-extensive-age-and-culture-induced-changes-at-distal-regulatory-elements
#7
Kalyan K Pasumarthy, Naresh Doni Jayavelu, Lotta Kilpinen, Colin Andrus, Stephanie L Battle, Matti Korhonen, Petri Lehenkari, Riikka Lund, Saara Laitinen, R David Hawkins
Human bone marrow stromal cells, or mesenchymal stem cells (BM-MSCs), need expansion prior to use as cell-based therapies in immunological and tissue repair applications. Aging and expansion of BM-MSCs induce epigenetic changes that can impact therapeutic outcomes. By applying sequencing-based methods, we reveal that the breadth of DNA methylation dynamics associated with aging and expansion is greater than previously reported. Methylation changes are enriched at known distal transcription factor binding sites such as enhancer elements, instead of CpG-rich regions, and are associated with changes in gene expression...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28828971/molecular-biomarkers-of-anaplastic-thyroid-carcinoma
#8
F Bozorg-Ghalati, M Hedayati
Anaplastic thyroid carcinoma is the rarest but extremely aggressive thyroid cancer subtype. This neoplasia is composed of undifferentiated tumor cells with poor prognosis and resistant to common thyroid cancer therapy. Early stage identification of this cancer for prompt treatment is very vital. Presently, cytological evaluation of fine needle aspiration biopsy (FNAB) which is known as invasive recognition assay, is the standard diagnostic method for the diagnosis of malignant thyroid tumors. Frequent studies have suggested that using the molecular biomarkers of thyroid cancer tissue alongside cytological examination, increase the accuracy of diagnostic tests...
August 21, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28818454/the-anti-tumor-effect-of-intravesical-administration-of-normal-urothelial-cells-on-bladder-cancer
#9
Chi-Ping Huang, Chi-Cheng Chen, Chih-Rong Shyr
BACKGROUND AIMS: Urothelial bladder cancer (UBC) is the second most common cancer of the genitourinary tract and for advanced forms of the disease it has a high mortality rate. There are no approved new molecularly targeted agents or chemotherapeutics for advanced UBC beyond cisplatin-based chemotherapy except the recently approved anti-programmed death ligand 1 (anti-PD-1/PD-L1) antibody. With complex genetic and epigenetic alterations in tumors, despite several druggable targets identified, to cure UBC is still a challenging unmet medical need...
August 14, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28807232/ovarian-cancer-novel-molecular-aspects-for-clinical-assessment
#10
REVIEW
Raffaele Palmirotta, Erica Silvestris, Stella D'Oronzo, Angela Cardascia, Franco Silvestris
Ovarian cancer is a very heterogeneous tumor which has been traditionally characterized according to the different histological subtypes and differentiation degree. In recent years, innovative molecular screening biotechnologies have allowed to identify further subtypes of this cancer based on gene expression profiles, mutational features, and epigenetic factors. These novel classification systems emphasizing the molecular signatures within the broad spectrum of ovarian cancer have not only allowed a more precise prognostic prediction, but also proper therapeutic strategies for specific subgroups of patients...
September 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28807014/epigenetic-reprogramming-converts-human-wharton-s-jelly-mesenchymal-stem-cells-into-functional-cardiomyocytes-by-differential-regulation-of-wnt-mediators
#11
G Bhuvanalakshmi, Frank Arfuso, Alan Prem Kumar, Arun Dharmarajan, Sudha Warrier
BACKGROUND: Lineage commitment of mesenchymal stem cells (MSCs) to cardiac differentiation is controlled by transcription factors that are regulated by epigenetic events, mainly histone deacetylation and promoter DNA methylation. Here, we studied the differentiation of human Wharton's jelly MSCs (WJMSCs) into the cardiomyocyte lineage via epigenetic manipulations. METHODS: We introduced these changes using inhibitors of DNA methyl transferase and histone deacetylase, DC301, DC302, and DC303, in various combinations...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28801671/the-cpg-sites-of-the-cbx3-ubiquitous-chromatin-opening-element-are-critical-structural-determinants-for-the-anti-silencing-function
#12
Jessica Kunkiel, Natascha Gödecke, Mania Ackermann, Dirk Hoffmann, Axel Schambach, Nico Lachmann, Dagmar Wirth, Thomas Moritz
Suppression of therapeutic transgene expression from retroviral gene therapy vectors by epigenetic defence mechanisms represents a problem that is particularly encountered in pluripotent stem cells (PSCs) and their differentiated progeny. Transgene expression in these cells, however, can be stabilised by CpG-rich ubiquitous chromatin opening elements (UCOEs). In this context we recently demonstrated profound anti-silencing properties for the small (679 bp) CBX3-UCO element and we now confirmed this observation in the context of the defined murine chromosomal loci ROSA26 and TIGRE...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790919/potential-new-therapies-for-pediatric-diffuse-intrinsic-pontine-glioma
#13
REVIEW
Wenyong Long, Yang Yi, Shen Chen, Qi Cao, Wei Zhao, Qing Liu
Diffuse intrinsic pontine glioma (DIPG) is an extensively invasive malignancy with infiltration into other regions of the brainstem. Although large numbers of specific targeted therapies have been tested, no significant progress has been made in treating these high-grade gliomas. Therefore, the identification of new therapeutic approaches is of great importance for the development of more effective treatments. This article reviews the conventional therapies and new potential therapeutic approaches for DIPG, including epigenetic therapy, immunotherapy, and the combination of stem cells with nanoparticle delivery systems...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28771724/aberrant-mirna-promoter-methylation-and-emt-involving-mirnas-in-breast-cancer-metastasis-diagnosis-and-therapeutic-implications
#14
REVIEW
Maryam Zare, Milad Bastami, Saeed Solali, Mohammad Reza Alivand
Breast cancer (BC) is the most prevalent cancer in women worldwide. Although extensive studies are ongoing concerning its intricate molecular mechanisms, development of novel therapies and more accurate diagnostic and prognostic approaches is still a challenge. Epithelial-mesenchymal transition (EMT) enables the invasion of metastatic cancer cells and has recently been highlighted in a Cancer Stem Cell (CSC) model of BC. Epigenetic events as well as miRNA expression are the master regulators of tumorigenesis and add a further layer to the complexity of BC pathogenesis...
August 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28762752/oxidative-stress-in-mesenchymal-stem-cell-senescence-regulation-by-coding-and-non-coding-rnas
#15
Rosa Vono, Eva Jover Garcia, Gaia Spinetti, Paolo Madeddu
SIGNIFICANCE: Mesenchymal stem cells (MSCs), adult stem cells with the potential of differentiation into mesodermal lineages, play an important role in tissue homeostasis and regeneration. In different organs, a subpopulation of MSCs is located near to the vasculature and possibly represents the original source of lineage-committed mesenchymal progenitors. Recent Advances. The plasticity and immune characteristics of MSCs render them a preferential tool for regenerative cell therapy. CRITICAL ISSUES: The culture expansion needed before MSC transplantation is associated with cellular senescence...
August 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28754000/the-role-of-tumor-microenvironment-in-chemoresistance-to-survive-keep-your-enemies-closer
#16
REVIEW
Dimakatso Alice Senthebane, Arielle Rowe, Nicholas Ekow Thomford, Hendrina Shipanga, Daniella Munro, Mohammad A M Al Mazeedi, Hashim A M Almazyadi, Karlien Kallmeyer, Collet Dandara, Michael S Pepper, M Iqbal Parker, Kevin Dzobo
Chemoresistance is a leading cause of morbidity and mortality in cancer and it continues to be a challenge in cancer treatment. Chemoresistance is influenced by genetic and epigenetic alterations which affect drug uptake, metabolism and export of drugs at the cellular levels. While most research has focused on tumor cell autonomous mechanisms of chemoresistance, the tumor microenvironment has emerged as a key player in the development of chemoresistance and in malignant progression, thereby influencing the development of novel therapies in clinical oncology...
July 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28748730/therapeutic-targeting-of-leukemic-stem-cells-in-acute-myeloid-leukemia-the-biological-background-for-possible-strategies
#17
Øystein Bruserud, Elise Aasebø, Maria Hernandez-Valladares, Galina Tsykunova, Håkon Reikvam
Acute myeloid leukemia (AML) is an aggressive malignancy, caused by the accumulation of immature leukemic blasts in blood and bone marrow. There is a relatively high risk of chemoresistant relapse even for the younger patients who can receive the most intensive antileukemic treatment. Treatment directed against the remaining leukemic and preleukemic stem cells will most likely reduce the risk of later relapse. Areas covered: Relevant publications were identified through literature searches. The authors searched for original articles and recent reviews describing (i) the characteristics of leukemic/preleukemic stem cells; (ii) the importance of the bone marrow stem cell niches in leukemogenesis; and (iii) possible therapeutic strategies to target the preleukemic/leukemic stem cells...
July 27, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28716899/hdac1-upregulation-by-nanog-promotes-multidrug-resistance-and-a-stem-like-phenotype-in-immune-edited-tumor-cells
#18
Kwon-Ho Song, Chel Hun Choi, Hyo-Jung Lee, Se Jin Oh, Seon Rang Woo, Soon-Oh Hong, Kyung Hee Noh, Hanbyoul Cho, Eun Joo Chung, Jae-Hoon Kim, Joon-Yong Chung, Stephen M Hewitt, Seungki Baek, Kyung-Mi Lee, Cassian Yee, Minjoo Son, Chih-Ping Mao, T C Wu, Tae Woo Kim
Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Immunoediting driven by antigen (Ag)-specific T cells enriches NANOG expression in tumor cells, resulting in a stem-like phenotype and immune resistance. Here, we identify HDAC1 as a key mediator of the NANOG-associated phenotype. NANOG upregulated HDAC1 through promoter occupancy, thereby decreasing histone H3 acetylation on K14 and K27. NANOG-dependent, HDAC1-driven epigenetic silencing of cell-cycle inhibitors CDKN2D and CDKN1B induced stem-like features...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28704968/epigenetic-modifications-and-head-and-neck-cancer-implications-for-tumor-progression-and-resistance-to-therapy
#19
REVIEW
Rogerio M Castilho, Cristiane H Squarize, Luciana O Almeida
Head and neck squamous carcinoma (HNSCC) is the sixth most prevalent cancer and one of the most aggressive malignancies worldwide. Despite continuous efforts to identify molecular markers for early detection, and to develop efficient treatments, the overall survival and prognosis of HNSCC patients remain poor. Accumulated scientific evidences suggest that epigenetic alterations, including DNA methylation, histone covalent modifications, chromatin remodeling and non-coding RNAs, are frequently involved in oral carcinogenesis, tumor progression, and resistance to therapy...
July 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28695747/novel-strategies-for-anti-aging-drug-discovery
#20
REVIEW
Komal Saraswat, Syed Ibrahim Rizvi
Scientific achievements in the last few decades, leading to effective therapeutic interventions, have dramatically improved human life expectancy. Consequently, aging has become a significant problem and represents the major risk factor for most human pathologies including diabetes, cardiovascular diseases, neurological disorders, and cancer. Scientific discoveries over the past two decades have been instrumental in dissecting molecular mechanism(s) which play important roles in determining longevity. The same understanding has also led to the acknowledgement of the plurality of 'causes' which act either alone or in combination to create the condition which can be defined as 'aging'...
September 2017: Expert Opinion on Drug Discovery
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