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Stem cell therapy, epigenetics

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https://www.readbyqxmd.com/read/29776381/wnt-signaling-in-multiple-myeloma-a-central-player-in-disease-with-therapeutic-potential
#1
REVIEW
Ingrid Spaan, Reinier A Raymakers, Anja van de Stolpe, Victor Peperzak
Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow...
May 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29771197/emerging-insights-into-wnt-%C3%AE-catenin-signaling-in-head-and-neck-cancer
#2
K A Alamoud, M A Kukuruzinska
Head and neck cancer presents primarily as head and neck squamous cell carcinoma (HNSCC), a debilitating malignancy fraught with high morbidity, poor survival rates, and limited treatment options. Mounting evidence indicates that the Wnt/β-catenin signaling pathway plays important roles in the pathobiology of HNSCC. Wnt/β-catenin signaling affects multiple cellular processes that endow cancer cells with the ability to maintain and expand immature stem-like phenotypes, proliferate, extend survival, and acquire aggressive characteristics by adopting mesenchymal traits...
June 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29759441/nuclear-organization-mediates-cancer-compromised-genetic-and-epigenetic-control
#3
REVIEW
Sayyed K Zaidi, Andrew Fritz, Kirsten Tracy, Jonathan Gordon, Coralee Tye, Joseph Boyd, Andre Van Wijnen, Jeffrey Nickerson, Anthony Imbalzano, Jane Lian, Janet Stein, Gary Stein
Nuclear organization is functionally linked to genetic and epigenetic regulation of gene expression for biological control and is modified in cancer. Nuclear organization supports cell growth and phenotypic properties of normal and cancer cells by facilitating physiologically responsive interactions of chromosomes, genes and regulatory complexes at dynamic three-dimensional microenvironments. We will review nuclear structure/function relationships that include: 1. Epigenetic bookmarking of genes by phenotypic transcription factors to control fidelity and plasticity of gene expression as cells enter and exit mitosis; 2...
May 9, 2018: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29752436/foxm1-contributes-to-taxane-resistance-by-regulating-uhrf1-controlled-cancer-cell-stemness
#4
Bowen Yuan, Youhong Liu, Xiaohui Yu, Linglong Yin, Yuchong Peng, Yingxue Gao, Qianling Zhu, Tuoyu Cao, Yinke Yang, Xuegong Fan, Xiong Li
Therapy-induced expansion of cancer stem cells (CSCs) has been identified as one of the most critical factors contributing to therapeutic resistance, but the mechanisms of this adaptation are not fully understood. UHRF1 is a key epigenetic regulator responsible for therapeutic resistance, and controls the self-renewal of stem cells. In the present study, taxane-resistant cancer cells were established and stem-like cancer cells were expanded. UHRF1 was overexpressed in the taxane-resistant cancer cells, which maintained CSC characteristics...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29751067/clonal-expansion-and-myeloid-leukemia-progression-modeled-by-multiplex-gene-editing-of-murine-hematopoietic-progenitor-cells
#5
Xiangguo Shi, Ayumi Kitano, Yajian Jiang, Victor Luu, Kevin A Hoegenauer, Daisuke Nakada
Recent advances in next-generation sequencing have identified novel mutations and revealed complex genetic architectures in human hematological malignancies. Moving forward, new methods to quickly generate animal models that recapitulate the complex genetics of human hematological disorders are needed to transform the genetic information to new therapies. Here, we used a ribonucleoprotein-based CRISPR/Cas9 system to model human clonal hematopoiesis of indeterminate potential and acute myeloid leukemia (AML)...
May 8, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29742888/atypical-teratoid-rhabdoid-tumour-from-tumours-to-therapies
#6
REVIEW
Elizabeth Anne Richardson, Ben Ho, Annie Huang
Atypical teratoid rhabdoid tumours (ATRTs) are the most common malignant central nervous system tumours in children ≤1 year of age and represent approximately 1-2% of all pediatric brain tumours. ATRT is a primarily monogenic disease characterized by the bi-allelic loss of the SMARCB1 gene, which encodes the hSNF5 subunit of the SWI/SNF chromatin remodeling complex. Though conventional dose chemotherapy is not effective in most ATRT patients, high dose chemotherapy with autologous stem cell transplant, radiotherapy and/or intrathecal chemotherapy all show significant potential to improve patient survival...
May 2018: Journal of Korean Neurosurgical Society
https://www.readbyqxmd.com/read/29739872/chemical-compound-based-direct-reprogramming-for-future-clinical-applications
#7
REVIEW
Yukimasa Takeda, Yoshinori Harada, Toshikazu Yoshikawa, Ping Dai
Recent studies have revealed that a combination of chemical compounds enables direct reprogramming from one somatic cell type into another without the use of transgenes by regulating cellular signaling pathways and epigenetic modifications. The generation of induced pluripotent stem (iPS) cells generally requires virus vector-mediated expression of multiple transcription factors, which might disrupt genomic integrity and proper cell functions. The direct reprogramming is a promising alternative to rapidly prepare different cell types by bypassing the pluripotent state...
June 29, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29735111/management-of-pediatric-movement-disorders-present-and-future
#8
Jeffrey B Russ, Akila M Nallappan, Amy Robichaux-Viehoever
Management of movement disorders in children is an evolving field. This article outlines the major categories of treatment options for pediatric movement disorders and general guidelines for their use. We review the evidence for existing therapies, which continue to lack large-scale controlled trials to guide treatment decisions. The field continues to rely on extrapolations from adult studies and lower quality evidence such as case reports and case series to guide treatment guidelines and consensus statements...
April 2018: Seminars in Pediatric Neurology
https://www.readbyqxmd.com/read/29719832/microenvironment-induced-non-sporadic-expression-of-the-axl-and-ckit-receptors-are-related-to-epithelial-plasticity-and-drug-resistance
#9
Tiina A Jokela, Agnete S T Engelsen, Agata Rybicka, Fanny A Pelissier Vatter, James C Garbe, Masaru Miyano, Crina Tiron, Dan Ferariu, Lars A Akslen, Martha R Stampfer, James B Lorens, Mark A LaBarge
The existence of rare cancer cells that sporadically acquire drug-tolerance through epigenetic mechanisms is proposed as one mechanism that drives cancer therapy failure. Here we provide evidence that specific microenvironments impose non-sporadic expression of proteins related to epithelial plasticity and drug resistance. Microarrays of robotically printed combinatorial microenvironments of known composition were used to make cell-based functional associations between microenvironments, which were design-inspired by normal and tumor-burdened breast tissues, and cell phenotypes...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29717132/potential-role-of-cbx7-in-regulating-pluripotency-of-adult-human-pluripotent-like-olfactory-stem-cells-in-stroke-model
#10
Jia-Rong Fan, Hsu-Tung Lee, Wei Lee, Chen-Huan Lin, Chun Y Hsu, Chia-Hung Hsieh, Woei-Cherng Shyu
The adult olfactory mucosa, a highly regenerative tissue with unique life-long neurogenesis ability, is thought to harbor a naïve yet tightly controlled stem cell population. It will provide unique benefits in various stem cell-based therapies, such as stroke treatment. Here, we identified a subpopulation of adult pluripotent-like olfactory stem cells (APOSCs), which were modulated by an epigenetic repressor of CBX7. APOSCs form a floating sphere, express pluripotency markers Nanog, Oct-4, Sox-2, and SSEA-4 and show alkaline phosphatase activity...
May 2, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29714146/prdm14-a-potential-target-for-cancer-therapy
#11
Mengting Ou, Shun Li, Liling Tang
PRDM14 belongs to PR domain-containing (PRDM) family. Although a precise understanding is focused on the function of PRDM14 maintains stemness and pluripotency in embryonic stem cells via epigenetic mechanisms, there are growing experimental evidences have been linked PRDM14 to human cancers. In adults, PRDM14 is low expression in human tissues. Aberrant PRDM14 expression is connected with various malignant histological types and solid cancers, where PRDM14 can act as a driver of oncogenic processes. Overexpression of RPDM14 enhanced cancer cells growth and reduced cancer cells sensitive to chemotherapeutic agents...
April 30, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29700375/jib-04-a-small-molecule-histone-demethylase-inhibitor-selectively-targets-colorectal-cancer-stem-cells-by-inhibiting-the-wnt-%C3%AE-catenin-signaling-pathway
#12
Min Seong Kim, Hye In Cho, Hee Jung Yoon, Ye-Hyeon Ahn, Eun Jung Park, Yan Hua Jin, Yeun Kyu Jang
Although several epigenetic modulating drugs are suggested to target cancer stem cells (CSCs), additional identification of anti-CSC drugs is still necessary. Here we showed that JIB-04, a pan-selective inhibitor of histone demethylase(s), was identified as a small molecule that selectively target colorectal CSCs. Our data showed that JIB-04 is capable of reducing self-renewal and stemness of colorectal CSCs in three different colorectal cancer cell lines. JIB-04 significantly attenuated CSC tumorsphere formation, growth/relapse, invasion, and migration in vitro...
April 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29682980/aging-and-senescence-associated-changes-of-mesenchymal-stromal-cells-in-myelodysplastic-syndromes
#13
Domenico Mattiucci, Giulia Maurizi, Pietro Leoni, Antonella Poloni
Hematopoietic stem and progenitor cells reside within the bone marrow (BM) microenvironment. By a well-balanced interplay between self-renewal and differentiation, they ensure a lifelong supply of mature blood cells. Physiologically, multiple different cell types contribute to the regulation of stem and progenitor cells in the BM microenvironment by cell-extrinsic and cell-intrinsic mechanisms. During the last decades, mesenchymal stromal cells (MSCs) have been identified as one of the main cellular components of the BM microenvironment holding an indispensable role for normal hematopoiesis...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29676638/identification-of-novel-targets-for-lung-cancer-therapy-using-an-induced-pluripotent-stem-cell-model
#14
Vivek Shukla, Mahadev Rao, Hongen Zhang, Jeanette Beers, Darawalee Wangsa, Danny Wangsa, Floryne O Buishand, Yonghong Wang, Zhiya Yu, Holly Stevenson, Emily Reardon, Kaitlin C McLoughlin, Andrew Kaufman, Eden Payabyab, Julie A Hong, Mary Zhang, Sean R Davis, Daniel C Edelman, Guokai Chen, Markku Miettinen, Nicholas Restifo, Thomas Ried, Paul S Meltzer, David S Schrump
RATIONALE: Despite extensive studies, the genetic and epigenetic mechanisms that mediate initiation and progression of lung cancers have not been fully elucidated. Previously, we have demonstrated that via complementary mechanisms, including DNA methylation, polycomb repressive complexes, and noncoding RNAs, cigarette smoke induces stem-like phenotypes that coincide with progression to malignancy in normal respiratory epithelia as well as enhanced growth and metastatic potential of lung cancer cells...
April 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29671264/high-throughput-screening-of-a-luciferase-reporter-of-gene-silencing-on-the-inactive-x-chromosome
#15
Alissa Keegan, Kathrin Plath, Robert Damoiseaux
Assays of luciferase gene activity are a sensitive and quantitative reporter system suited to high-throughput screening. We adapted a luciferase assay to a screening strategy for identifying factors that reactivate epigenetically silenced genes. This epigenetic luciferase reporter is subject to endogenous gene silencing mechanisms on the inactive X chromosome (Xi) in primary mouse cells and thus captures the multilayered nature of chromatin silencing in development. Here, we describe the optimization of an Xi-linked luciferase reactivation assay in 384-well format and adaptation of the assay for high-throughput siRNA and chemical screening...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29670281/identification-of-the-tumour-transition-states-occurring-during-emt
#16
Ievgenia Pastushenko, Audrey Brisebarre, Alejandro Sifrim, Marco Fioramonti, Tatiana Revenco, Soufiane Boumahdi, Alexandra Van Keymeulen, Daniel Brown, Virginie Moers, Sophie Lemaire, Sarah De Clercq, Esmeralda Minguijón, Cédric Balsat, Youri Sokolow, Christine Dubois, Florian De Cock, Samuel Scozzaro, Federico Sopena, Angel Lanas, Nicky D'Haene, Isabelle Salmon, Jean-Christophe Marine, Thierry Voet, Panagiota A Sotiropoulou, Cédric Blanpain
In cancer, the epithelial-to-mesenchymal transition (EMT) is associated with tumour stemness, metastasis and resistance to therapy. It has recently been proposed that, rather than being a binary process, EMT occurs through distinct intermediate states. However, there is no direct in vivo evidence for this idea. Here we screen a large panel of cell surface markers in skin and mammary primary tumours, and identify the existence of multiple tumour subpopulations associated with different EMT stages: from epithelial to completely mesenchymal states, passing through intermediate hybrid states...
April 18, 2018: Nature
https://www.readbyqxmd.com/read/29667069/the-versatile-role-of-exosomes-in-cancer-progression-diagnostic-and-therapeutic-implications
#17
REVIEW
Vignesh Sundararajan, Fazlul H Sarkar, Thamil Selvee Ramasamy
BACKGROUND: Recent advances in cancer biology have highlighted the relevance of exosomes and nanovesicles as carriers of genetic and biological messages between cancer cells and their immediate and/or distant environments. It has been found that these molecular cues may play significant roles in cancer progression and metastasis. Cancer cells secrete exosomes containing diverse molecules that can be transferred to recipient cells and/or vice versa to induce a plethora of biological processes, including angiogenesis, metastasis formation, therapeutic resistance, epithelial-mesenchymal transition and epigenetic/stemness (re)programming...
April 17, 2018: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29665657/recent-advances-in-the-diagnosis-and-management-of-primary-myelofibrosis
#18
Katsuto Takenaka, Kazuya Shimoda, Koichi Akashi
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) in which dysregulation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways is the major pathogenic mechanism. Most patients with PMF carry a driver mutation in the JAK2, MPL (myeloproliferative leukemia), or CALR (calreticulin) genes. Mutations in epigenetic regulators and RNA splicing genes may also occur, and play critical roles in PMF disease progression. Based on revised World Health Organization diagnostic criteria for MPNs, both screening for driver mutations and bone marrow biopsy are required for a specific diagnosis...
April 20, 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29643458/pro-inflammatory-cytokines-activate-hypoxia-inducible-factor-3%C3%AE-via-epigenetic-changes-in-mesenchymal-stromal-stem-cells
#19
Francesca Cuomo, Antonietta Coppola, Chiara Botti, Ciro Maione, Amalia Forte, Lucia Scisciola, Giuseppina Liguori, Ilaria Caiafa, Matilde Valeria Ursini, Umberto Galderisi, Marilena Cipollaro, Lucia Altucci, Gilda Cobellis
Human mesenchymal stromal/stem cells (hMSCs) emerged as a promising therapeutic tool for ischemic disorders, due to their ability to regenerate damaged tissues, promote angiogenesis and reduce inflammation, leading to encouraging, but still limited results. The outcomes in clinical trials exploring hMSC therapy are influenced by low cell retention and survival in affected tissues, partially influenced by lesion's microenvironment, where low oxygen conditions (i.e. hypoxia) and inflammation coexist. Hypoxia and inflammation are pathophysiological stresses, sharing common activators, such as hypoxia-inducible factors (HIFs) and NF-κB...
April 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29626983/hematopoietic-changes-in-the-offspring-induced-by-maternal-overweight-effect-on-placenta-and-fetal-liver-populations
#20
Luana Leirós, Juliana Barbosa Torreão Dáu, Daphne Pinheiro, Ana Carolina Stumbo Machado, Alessandra Alves Thole, Erika Afonso Costa Cortez, Laís de Carvalho, Simone Nunes de Carvalho
INTRODUCTION: Bone marrow cells (BMC) from obese adult mice display an increased apoptosis rate over proliferation. Hematopoietic stem cells (HSC) form all blood cells and are important BMC used in cell therapy. Because it is known that prenatal development can be affected by adverse metabolic epigenetic programming from the maternal organism, this work aimed to investigate the effects of maternal overweight on placenta and fetal liver hematopoietic niches. METHODS: Overweight was induced in female mice by overfeeding during lactation...
April 2018: Placenta
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