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Stem cell therapy, epigenetics

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https://www.readbyqxmd.com/read/29343412/implementing-genome-driven-personalized-cardiology-in-clinical-practice
#1
REVIEW
Ares Pasipoularides
Genomics designates the coordinated investigation of a large number of genes in the context of a biological process or disease. It may be long before we attain comprehensive understanding of the genomics of common complex cardiovascular diseases (CVDs) such as inherited cardiomyopathies, valvular diseases, primary arrhythmogenic conditions, congenital heart syndromes, hypercholesterolemia and atherosclerotic heart disease, hypertensive syndromes, and heart failure with preserved/reduced ejection fraction. Nonetheless, as genomics is evolving rapidly, it is constructive to survey now pertinent concepts and breakthroughs...
January 14, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29335068/imprinted-gene-zinc-finger-protein-127-is-a-novel-regulator-of-master-pluripotency-transcription-factor-oct4
#2
Yoo-Wook Kwon, Hyo-Suk Ahn, Joo-Young Park, Han-Mo Yang, Hyun-Jai Cho, Hyo-Soo Kim
Induced pluripotent stem cells (iPSCs) show great promise for replacing current stem cell therapies in the field of regenerative medicine. However, the original method for cellular reprogramming, involving four exogenous transcription factors, is characterized by low efficiency. Here, we focused on using epigenetic modifications to enhance the reprogramming efficiency. We hypothesized that there would be a new reprogramming factor involved in DNA demethylation, acting on the promoters of pluripotency-related genes...
January 16, 2018: BMB Reports
https://www.readbyqxmd.com/read/29311580/lsd1-activation-promotes-inducible-emt-programs-and-modulates-the-tumour-microenvironment-in-breast-cancer
#3
T Boulding, R D McCuaig, A Tan, K Hardy, F Wu, J Dunn, M Kalimutho, C R Sutton, J K Forwood, A G Bert, G J Goodall, L Malik, D Yip, J E Dahlstrom, A Zafar, K K Khanna, S Rao
Complex regulatory networks control epithelial-to-mesenchymal transition (EMT) but the underlying epigenetic control is poorly understood. Lysine-specific demethylase 1 (LSD1) is a key histone demethylase that alters the epigenetic landscape. Here we explored the role of LSD1 in global epigenetic regulation of EMT, cancer stem cells (CSCs), the tumour microenvironment, and therapeutic resistance in breast cancer. LSD1 induced pan-genomic gene expression in networks implicated in EMT and selectively elicits gene expression programs in CSCs whilst repressing non-CSC programs...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29284798/high-expression-of-mkp1-dusp1-counteracts-glioma-stem-cell-activity-and-mediates-hdac-inhibitor-response
#4
Olatz Arrizabalaga, Leire Moreno-Cugnon, Jaione Auzmendi-Iriarte, Paula Aldaz, Inmaculada Ibañez de Cáceres, Laura Garros-Regulez, Veronica Moncho-Amor, Sergio Torres-Bayona, Olga Pernía, Laura Pintado-Berninches, Patricia Carrasco-Ramirez, María Cortes-Sempere, Rocío Rosas, Pilar Sanchez-Gomez, Irune Ruiz, Helena Caren, Steven Pollard, Idoia Garcia, Angel-Ayuso Sacido, Robin Lovell-Badge, Cristobal Belda-Iniesta, Nicolas Sampron, Rosario Perona, Ander Matheu
The elucidation of mechanisms involved in resistance to therapies is essential to improve the survival of patients with malignant gliomas. A major feature possessed by glioma cells that may aid their ability to survive therapy and reconstitute tumors is the capacity for self-renewal. We show here that glioma stem cells (GSCs) express low levels of MKP1, a dual-specificity phosphatase, which acts as a negative inhibitor of JNK, ERK1/2, and p38 MAPK, while induction of high levels of MKP1 expression are associated with differentiation of GSC...
December 14, 2017: Oncogenesis
https://www.readbyqxmd.com/read/29245896/metabolomic-mapping-of-cancer-stem-cells-for-reducing-and-exploiting-tumor-heterogeneity
#5
Elisabet Cuyàs, Sara Verdura, Salvador Fernández-Arroyo, Joaquim Bosch-Barrera, Begoña Martin-Castillo, Jorge Joven, Javier A Menendez
Personalized cancer medicine based on the analysis of tumors en masse is limited by tumor heterogeneity, which has become a major obstacle to effective cancer treatment. Cancer stem cells (CSC) are emerging as key drivers of inter- and intratumoral heterogeneity. CSC have unique metabolic dependencies that are required not only for specific bioenergetic/biosynthetic demands but also for sustaining their operational epigenetic traits, i.e. self-renewal, tumor-initiation, and plasticity. Given that the metabolome is the final downstream product of all the -omic layers and, therefore, most representative of the biological phenotype, we here propose that a novel approach to better understand the complexity of tumor heterogeneity is by mapping and cataloging small numbers of CSC metabolomic phenotypes...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29222267/new-therapeutic-targets-in-transfusion-dependent-and-independent-thalassemia
#6
REVIEW
M Domenica Cappellini, Irene Motta
β-Thalassemias are characterized by reduced production of β-globin chain, resulting in α/β-chain unbalance and precipitation of α-globin-heme complexes and determining ineffective erythropoiesis. Ineffective erythropoiesis, chronic hemolytic anemia, and compensatory hematopoietic expansion are the disease hallmarks, and they are related to the severity of the chain unbalance. Several clinical forms of β-thalassemia, including the coinheritance of β-thalassemia with hemoglobin E resulting in hemoglobin E/β-thalassemia, have been described...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29216265/oct4-expression-mediates-partial-cardiomyocyte-reprogramming-of-mesenchymal-stromal-cells
#7
Gustavo Yannarelli, Natalia Pacienza, Sonia Montanari, Diego Santa-Cruz, Sowmya Viswanathan, Armand Keating
Mesenchymal stem/stromal cells (MSCs) are in numerous cell therapy clinical trials, including for injured myocardium. Acquisition of cardiomyocyte characteristics by MSCs may improve cardiac regeneration but the mechanisms regulating this process are unclear. Here, we investigated whether the pluripotency transcription factor OCT4 is involved in the activation of cardiac lineage genetic programs in MSCs. We employed our established co-culture model of MSCs with rat embryonic cardiomyocytes showing co-expression of cardiac markers on MSCs independent of cell fusion...
2017: PloS One
https://www.readbyqxmd.com/read/29208029/tissue-source-determines-the-differentiation-potentials-of-mesenchymal-stem-cells-a-comparative-study-of-human-mesenchymal-stem-cells-from-bone-marrow-and-adipose-tissue
#8
Liangliang Xu, Yamei Liu, Yuxin Sun, Bin Wang, Yunpu Xiong, Weiping Lin, Qiushi Wei, Haibin Wang, Wei He, Bin Wang, Gang Li
BACKGROUND: Mesenchymal stem cells (MSCs) possess intrinsic regeneration capacity as part of the repair process in response to injury, such as fracture or other tissue injury. Bone marrow and adipose tissue are the major sources of MSCs. However, which cell type is more effective and suitable for cell therapy remains to be answered. The intrinsic molecular mechanism supporting the assertion has also been lacking. METHODS: Human bone marrow-derived MSCs (BMSCs) and adipose tissue-derived MSCs (ATSCs) were isolated from bone marrow and adipose tissue obtained after total hip arthroplasty...
December 6, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29203199/overexpression-of-oct4-induced-by-modulation-of-histone-marks-plays-crucial-role-in-breast-cancer-progression
#9
Swayamsiddha Kar, Samir Kumar Patra
OCT4 is known as the gatekeeper of pluripotent embryonic state as it is responsible for maintenance of pluripotency via self-renewal of embryonic stem cells and acquisition of induced pluripotency via somatic cell reprogramming. OCT4 is responsible for oncogenic transformation by disrupting pre-scheduled differentiation programs and in general, favoring evolution of cancer cells into a more aggressive cancer stem cell phenotype. In this study, we have investigated in details, the epigenetic regulatory mechanisms responsible for over-expression and subsequent aberrant function of OCT4 in breast cancer...
February 15, 2018: Gene
https://www.readbyqxmd.com/read/29193029/recent-progress-in-understanding-and-manipulating-haemoglobin-switching-for-the-haemoglobinopathies
#10
REVIEW
Divya S Vinjamur, Daniel E Bauer, Stuart H Orkin
The major β-haemoglobinopathies, sickle cell disease and β-thalassaemia, represent the most common monogenic disorders worldwide and a steadily increasing global disease burden. Allogeneic haematopoietic stem cell transplantation, the only curative therapy, is only applied to a small minority of patients. Common clinical management strategies act mainly downstream of the root causes of disease. The observation that elevated fetal haemoglobin expression ameliorates these disorders has motivated longstanding investigations into the mechanisms of haemoglobin switching...
November 28, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29179494/combinatorial-effects-of-an-epigenetic-inhibitor-and-ionizing-radiation-contribute-to-targeted-elimination-of-pancreatic-cancer-stem-cell
#11
Hyun-Mi Kwon, Eun-Jin Kang, Keunsoo Kang, Sung-Dae Kim, Kwangmo Yang, Joo Mi Yi
Pancreatic cancer is associated with a high mortality rate, owing to de novo and acquired drug resistance, thereby leading to highly invasive and metastatic pancreatic cancer cells. Therefore, targeting pancreatic cancer stem cells (CSCs) may be a novel therapeutic strategy for the treatment of pancreatic cancer. Here, we combined a DNA methylation inhibitor (5-aza-2'-deoxycytidine; 5-aza-dC) and ionizing radiation (IR) to improve anti-cancer effects by inhibiting growth and proliferation and promoting apoptosis of pancreatic cancer cells in vitro and in vivo...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29175473/mechanisms-underlying-the-heterogeneity-of-myelodysplastic-syndromes
#12
REVIEW
Charles Dussiau, Michaela Fontenay
Myelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) disorders in which recurrent chromosome abnormalities and gene mutations define a clonal hematopoiesis. The MDS-initiating cell is a rare HSC which transmits the genetic abnormalities to its myeloid and lymphoid progeny. The heterogeneity of MDS phenotypes could be linked to the diversity of genetic events involving epigenetic regulators, chromatin modifiers, splicing factors, transcription factors and signaling adaptors, the various combinations and order of mutations in cooperating genes, and the variegation of clonal hematopoietic hierarchy...
November 22, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29173899/distinct-gene-expression-and-epigenetic-signatures-in-hepatocyte-like-cells-produced-by-different-strategies-from-the-same-donor
#13
Yimeng Gao, Xiaoran Zhang, Ludi Zhang, Jin Cen, Xuan Ni, Xiaoying Liao, Chenxi Yang, Ying Li, Xiaotao Chen, Zhao Zhang, Yajing Shu, Xin Cheng, David C Hay, Dongmei Lai, Guoyu Pan, Gang Wei, Lijian Hui
Hepatocyte-like cells (HLCs) can be generated through directed differentiation or transdifferentiation. Employing two strategies, we generated induced pluripotent stem cell (iPSC)-HLCs and hiHeps from the same donor cell line. Both types of HLCs clustered distinctly from each other during gene expression profiling. In particular, differences existed in gene expression for phase II drug metabolism and lipid accumulation, underpinned by H3K27 acetylation status in iPSC-HLCs and hiHeps. While distinct phenotypes were achieved in vitro, both types of HLCs demonstrated similar phenotypes following transplantation into Fah-deficient mice...
November 17, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29156535/hdacis-class-i-cancer-stem-cell-and-phytochemicals-cancer-therapy-and-prevention-implications
#14
REVIEW
Sahar Bayat, Mahmoud Shekari Khaniani, Jalal Choupani, Mohammad Reza Alivand, Sima Mansoori Derakhshan
Epigenetics is independent of the sequence events that physically affect the condensing of chromatin and genes expression. The unique epigenetic memories of various cells trigger exclusive gene expression profiling. According to different studies, the aberrant epigenetic signatures and impaired gene expression profiles are master occurrences in cancer cells in which oncogene and tumor suppressor genes are affected. Owing to the facts that epigenetic modifications are performed earlier than expression and are reversible, the epigenetic reprogramming of cancer cells could be applied potentially for their prevention, control, and therapy...
November 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29145503/zinc-sulfate-contributes-to-promote-telomere-length-extension-via-increasing-telomerase-gene-expression-telomerase-activity-and-change-in-the-tert-gene-promoter-cpg-island-methylation-status-of-human-adipose-derived-mesenchymal-stem-cells
#15
Raheleh Farahzadi, Ezzatollah Fathi, Seyed Alireza Mesbah-Namin, Nosratollah Zarghami
The use of mesenchymal stem cells (MSCs) for cell therapy and regenerative medicine has received widespread attention over the past few years, but their application can be complicated by factors such as reduction in proliferation potential, the senescent tendency of the MSCs upon expansion and their age-dependent decline in number and function. It was shown that all the mentioned features were accompanied by a reduction in telomerase activity and telomere shortening. Furthermore, the role of epigenetic changes in aging, especially changes in promoter methylation, was reported...
2017: PloS One
https://www.readbyqxmd.com/read/29143176/the-treatment-landscape-and-new-opportunities-of-molecular-targeted-therapies-in-gastroenteropancreatic-neuroendocrine-tumors
#16
REVIEW
Fabiola Amair-Pinedo, Ignacio Matos, Tamara Saurí, Jorge Hernando, Jaume Capdevila
Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms that originate from neuroendocrine stem cells and express both neural and endocrine markers. They are found in almost every organ, and while NENs are mostly associated with slow growth, complications due to the uncontrolled secretion of active peptides, and metastatic disease, may significantly impair the quality of life and can ultimately lead to the death of affected individuals. Expanding knowledge of the genetic, epigenetic, and proteomic landscapes of NENs has led to a better understanding of their molecular pathology and consequently increased treatment options for patients...
November 15, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29129488/dna-hypomethylating-agents-as-epigenetic-therapy-before-and-after-allogeneic-hematopoietic-stem-cell-transplantation-in-myelodysplastic-syndromes-and-juvenile-myelomonocytic-leukemia
#17
REVIEW
Christian Flotho, Sebastian Sommer, Michael Lübbert
Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents 5-azacytidine (azacitidine) or decitabine...
November 9, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29122288/bioprocessing-strategies-for-pluripotent-stem-cells-based-on-waddington-s-epigenetic-landscape
#18
REVIEW
Mee-Hae Kim, Masahiro Kino-Oka
As increasing numbers of cell-based therapies advance through clinical trials towards approval for use in humans, the need for robust and well-characterized cell culturing strategies is becoming increasingly apparent. We discuss here novel stem cell bioprocessing strategies based on the concept of using Waddington's epigenetic landscape to represent the process of cellular decision-making during development. Specifically, we focus on the manner in which cell behavior triggers cell signaling pathways related to the initial cell fate decision...
November 6, 2017: Trends in Biotechnology
https://www.readbyqxmd.com/read/29098608/novel-therapies-for-myelofibrosis
#19
REVIEW
Kristen Pettit, Olatoyosi Odenike
PURPOSE OF REVIEW: The purpose of the review was to provide a contemporary update of novel agents and targets under investigation in myelofibrosis in the Janus kinase (JAK) inhibitor era. RECENT FINDINGS: Myelofibrosis (MF) is a clonal stem cell disease characterized by marrow fibrosis and a heterogeneous disease phenotype with a variable degree of splenomegaly, cytopenias, and constitutional symptoms that significantly impact quality of life and survival. Overactive JAK/STAT signaling is a hallmark of MF...
December 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29082354/biophysical-regulation-of-cancer-stem-initiating-cells-implications-for-disease-mechanisms-and-translation
#20
Joseph Chen, Sanjay Kumar
Cancer stem/initiating cells (CSCs) are a subset of tumor cells proposed to play privileged roles in seeding tumors and driving metastasis. CSCs have emerged as an increasingly important target of interest in cancer biology and therapy. Recent work has suggested that CSC maintenance and metastatic potential may be modulated by physical inputs within the tissue microenvironment, including interstitial pressure and extracellular matrix stiffness. Here we review recent progress in our understanding of CSC regulation by biophysical signals within the tumor microenvironment...
March 2017: Curr Opin Biomed Eng
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