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Stem cell therapy, epigenetics

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https://www.readbyqxmd.com/read/28640953/overview-of-transgenic-mouse-models-of-myeloproliferative-neoplasms-mpns
#1
Andrew Dunbar, Abbas Nazir, Ross Levine
Myeloproliferative neoplasms (MPNs) are a class of hematologic diseases characterized by aberrant proliferation of one or more myeloid lineages and progressive bone marrow fibrosis. In 2005, seminal work by multiple groups identified the JAK2V617F mutation in a significant fraction of MPN patients. Since that time, murine models of JAK2V617F have greatly enhanced the understanding of the role of aberrant JAK-STAT signaling in MPN pathogenesis and have provided an in vivo pre-clinical platform that can be used to develop novel therapies...
June 22, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/28640191/phenotypic-plasticity-and-cell-fate-decisions-in-cancer-insights-from-dynamical-systems-theory
#2
REVIEW
Dongya Jia, Mohit Kumar Jolly, Prakash Kulkarni, Herbert Levine
Waddington's epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of "landscape" in the context of dynamical systems theory represents a high-dimensional space, in which each cell phenotype is considered as an "attractor" that is determined by interactions between multiple molecular players, and is buffered against environmental fluctuations. In addition, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions between different phenotypes...
June 22, 2017: Cancers
https://www.readbyqxmd.com/read/28632820/the-nexus-of-stem-cell-derived-beta-cells-and-genome-engineering
#3
Sara D Sackett, Aida Rodriguez, Jon S Odorico
Diabetes, type 1 and type 2 (T1D and T2D), are diseases of epidemic proportions, which are complicated and defined by genetics, epigenetics, environment, and lifestyle choices. Current therapies consist of whole pancreas or islet transplantation. However, these approaches require life-time immunosuppression, and are compounded by the paucity of available donors. Pluripotent stem cells have advanced research in the fields of stem cell biology, drug development, disease modeling, and regenerative medicine, and importantly allows for the interrogation of therapeutic interventions...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28629288/p53-mutation-and-epigenetic-imprinted-igf2-h19-gene-analysis-in-mesenchymal-stem-cells-derived-from-amniotic-fluid-amnion-endometrium-and-wharton-s-jelly
#4
Tatsanee Phermthai, Puttachart Pokathikorn, Suparat Wichitwiengrat, Sasiprapa Thongbopit, Kittima Tungprasertpol, Suphakde Julavijitphong
Mesenchymal stem cells (MSC) are promising cells for medical therapy. In in vitro expansion, MSC can give rise to progeny with genomic and epigenomic alterations, resulting in senescence, loss terminal differentiation and transformation to cancer. However, MSC genome protects its genetic instability via a guardian function of the P53 tumor suppressor gene and epigenetic balance system during MSC culture. Mutations of P53 and epigenetic alterations have been reported to disrupt the quality and quantity of MSC and initiate tumorigenesis...
June 19, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28627410/current-and-upcoming-mitochondrial-targets-for-cancer-therapy
#5
REVIEW
Hyoung Kyu Kim, Yeon Hee Noh, Bernd Nilius, Kyung Soo Ko, Byoung Doo Rhee, Nari Kim, Jin Han
Mitochondria are essential intracellular organelles that regulate energy metabolism, cell death, and signaling pathways that are important for cell proliferation and differentiation. Therefore, mitochondria are fundamentally implicated in cancer biology, including initiation, growth, metastasis, relapse, and acquired drug resistance. Based on these implications, mitochondria have been proposed as a major therapeutic target for cancer treatment. In addition to classical view of mitochondria in cancer biology, recent studies found novel pathophysiological roles of mitochondria in cancer...
June 13, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28625518/histone-chaperone-asf1a-predicts-poor-outcomes-for-patients-with-gastrointestinal-cancer-and-drives-cancer-progression-by-stimulating-transcription-of-%C3%AE-catenin-target-genes
#6
Xiuming Liang, Xiaotian Yuan, Jingya Yu, Yujiao Wu, Kailin Li, Chao Sun, Shuyan Li, Li Shen, Feng Kong, Jihui Jia, Magnus Björkholm, Dawei Xu
Epigenetic mechanisms play a key role in gastrointestinal cancer (GIC) development and progression, and most studies have been focused on aberrant DNA methylation and histone modifying enzymes. However, the histone H3-H4 chaperone ASF1A is an important factor regulating chromatin assembling and gene transcription, while it is currently unclear whether ASF1A is involved in cancer pathogenesis. The present study is thus designed to address this issue. Here we showed that ASF1A expression was widespread in GIC-derived cell lines and up-regulated in primary GIC...
June 8, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28621420/the-retinal-pigmented-epithelium-from-basic-developmental-biology-research-to-translational-approaches
#7
Benjamin Amram, Yamit Cohen-Tayar, Ahuvit David, Ruth Ashery-Padan
The development of the eye has been a topic of extensive investigation, from the early studies on tissue induction to more recent breakthroughs in resolving the mechanism regulating progenitor patterning and their gradual and coordinated differentiation into diverse tissue types that function together throughout life. Among the ocular tissue types, the retinal pigmented epithelium (RPE) is at the forefront of developmental biology and stem cell research. The growing interest in this lineage stems from its importance for photoreceptor function as well as from its requirement during embryogenesis for the development of the photoreceptors and the choroid...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28620760/notch-an-interactive-player-in-neurogenesis-and-disease
#8
REVIEW
Runrui Zhang, Anna Engler, Verdon Taylor
Notch signaling is evolutionarily conserved from Drosophila to human. It plays critical roles in neural stem cell maintenance and neurogenesis in the embryonic brain as well as in the adult brain. Notch functions greatly depend on careful regulation and cross-talk with other regulatory mechanisms. Deregulation of Notch signaling is involved in many neurodegenerative diseases and brain disorders. Here, we summarize the fundamental role of Notch in neuronal development and specification and discuss how epigenetic regulation and pathway cross-talk contribute to Notch function...
June 15, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28613929/dna-methylation-and-hydroxymethylation-profile-of-cd34-enriched-cell-products-intended-for-autologous-cd34-cell-transplantation
#9
Jasmina-Ziva Rozman, Maja Pohar Perme, Mojca Jez, Elvira Malicev, Metka Krasna, Bojan Vrtovec, Primoz Rozman
Epigenetic dysregulation has been shown to limit functional capacity of aging hematopoietic stem cells, which may contribute to impaired outcome of hematopoietic stem cell-based therapies. The aim of our study was to gain better insight into the epigenetic profile of CD34(+)-enriched cell products intended for autologous CD34(+) cell transplantation in patients with cardiomyopathy. We found global DNA methylation content significantly higher in immunoselected CD34(+) cells compared to leukocytes in leukapheresis products (2...
June 14, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28607134/dysfunctional-diversity-of-p53-proteins-in-adult-acute-myeloid-leukemia-projections-on-diagnostic-work-up-and-therapy
#10
Miron Prokocimer, Alina Molchadsky, Varda Rotter
The heterogeneous nature of Acute Myeloid Leukemia (AML) and its poor prognosis necessitate therapeutic improvement. Current advances in AML research yield important insights regarding AML genetic, epigenetic, evolutional, and clinical diversity, all in which dysfunctional p53 plays a key role. As p53 is central to hematopoietic stem cell functions, its aberrations affect AML evolution, biology and therapy response, and usually predict poor prognosis. While in human solid tumors TP53 is mutated in more than half of cases, TP53 mutations occur in less than a tenth of de-novo AML cases...
June 12, 2017: Blood
https://www.readbyqxmd.com/read/28589491/synthesis-and-characterization-of-novel-bmi1-inhibitors-targeting-cellular-self-renewal-in-hepatocellular-carcinoma
#11
Monica Bartucci, Mohamed S Hussein, Eric Huselid, Kathleen Flaherty, Michele Patrizii, Saurabh V Laddha, Cindy Kui, Rachel A Bigos, John A Gilleran, Mervat M S El Ansary, Mona A M Awad, S David Kimball, David J Augeri, Hatem E Sabaawy
BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most lethal cancers worldwide due to therapy resistance and disease recurrence. Tumor relapse following treatment could be driven by the persistence of liver cancer stem-like cells (CSCs). The protein BMI1 is a member of the polycomb epigenetic factors governing cellular self-renewal, proliferation, and stemness maintenance. BMI1 expression also correlates with poor patient survival in various cancer types. OBJECTIVE: We aimed to elucidate the extent to which BMI1 can be used as a potential therapeutic target for CSC eradication in HCC...
June 6, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28576946/flt3-inhibitors-in-acute-myeloid-leukemia-current-status-and-future-directions
#12
REVIEW
Maria Larrosa-Garcia, Maria R Baer
The receptor tyrosine kinase fms-like tyrosine kinase 3 (FLT3), involved in regulating survival, proliferation, and differentiation of hematopoietic stem/progenitor cells, is expressed on acute myeloid leukemia (AML) cells in most patients. Mutations of FLT3 resulting in constitutive signaling are common in AML, including internal tandem duplication (ITD) in the juxtamembrane domain in 25% of patients and point mutations in the tyrosine kinase domain in 5%. Patients with AML with FLT3-ITD have a high relapse rate and short relapse-free and overall survival after chemotherapy and after transplant...
June 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28576744/jak-stat-signaling-and-cancer-opportunities-benefits-and-side-effects-of-targeted-inhibition
#13
REVIEW
Bernd Groner, Viktoria von Manstein
The effects of Jak Stat signaling and the persistent activation of Stat3 and Stat5 on tumor cell survival, proliferation and invasion have made the Jak Stat pathway a favorite target for drug development and cancer therapy. This notion was strengthened when additional biological functions of Stat signaling in cancer and their roles in the regulation of cytokine dependent inflammation and immunity in the tumor microenvironment were discovered. Stats act not only as transcriptional inducers, but affect gene expression via epigenetic modifications, induce epithelial mesenchymal transition, generate a pro-tumorigenic microenvironment, promote cancer stem cell self-renewal and differentiation, and help to establish the pre-metastatic niche formation...
May 30, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28562519/epigenetic-combination-therapy-for-children-with-secondary-myelodysplastic-syndrome-mds-acute-myeloid-leukemia-aml-and-concurrent-solid-tumor-relapse
#14
Chana L Glasser, Alice Lee, Don Eslin, Lianna Marks, Shakeel Modak, Julia L Glade Bender
Secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) is a rare but devastating complication of solid tumor treatment involving high-dose topoisomerase II inhibitor and alkylator chemotherapy. For relapsed or elderly MDS and AML patients ineligible for hematopoietic stem cell transplantation, epigenetic therapies, including DNA methyltransferase inhibitors and histone deacetylase inhibitors, have been utilized as palliative therapy, offering a well-tolerated approach to disease stabilization, prolonged survival, and quality of life...
May 29, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28561650/higher-level-pathway-objectives-of-epigenetic-therapy-a-solution-to-the-p53-problem-in-cancer
#15
Vamsidhar Velcheti, Tomas Radivoyevitch, Yogen Saunthararajah
Searches for effective yet nontoxic oncotherapies are searches for exploitable differences between cancer and normal cells. In its core of cell division, cancer resembles normal life, coordinated by the master transcription factor MYC. Outside of this core, apoptosis and differentiation programs, which dominantly antagonize MYC to terminate cell division, necessarily differ between cancer and normal cells, as apoptosis is suppressed by biallelic inactivation of the master regulator of apoptosis, p53, or its cofactor p16/CDKN2A in approximately 80% of cancers...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28560682/epithelial-to-mesenchymal-transition-in-tumor-progression
#16
REVIEW
Elena Prieto-García, C Vanesa Díaz-García, Inmaculada García-Ruiz, M Teresa Agulló-Ortuño
The epithelial-to-mesenchymal transition (EMT) is a biological process in which a non-motile epithelial cell changes to a mesenchymal state with invasive capacities. However, the EMT program is involved in both physiological and pathological processes. Cancer-associated EMT is known to contribute to increase invasiveness and metastasis, resistance to therapies, and generation of cell populations with stem cell-like characteristics and therefore is deeply involved in tumor progression. This process is finely orchestrated by multiple signaling pathways and regulatory transcriptional networks...
July 2017: Medical Oncology
https://www.readbyqxmd.com/read/28553634/neural-stem-cell-plasticity-advantages-in-therapy-for-the-injured-central-nervous-system
#17
REVIEW
Linda Ottoboni, Arianna Merlini, Gianvito Martino
The physiological and pathological properties of the neural germinal stem cell niche have been well-studied in the past 30 years, mainly in animals and within given limits in humans, and knowledge is available for the cyto-architectonic structure, the cellular components, the timing of development and the energetic maintenance of the niche, as well as for the therapeutic potential and the cross talk between neural and immune cells. In recent years we have gained detailed understanding of the potentiality of neural stem cells (NSCs), although we are only beginning to understand their molecular, metabolic, and epigenetic profile in physiopathology and, further, more can be invested to measure quantitatively the activity of those cells, to model in vitro their therapeutic responses or to predict interactions in silico...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28537931/the-network-of-dab2ip-mir-138-in-regulating-drug-resistance-of-renal-cell-carcinoma-associated-with-stem-like-phenotypes
#18
Eun-Jin Yun, Jiancheng Zhou, Chun-Jung Lin, Shan Xu, John Santoyo, Elizabeth Hernandez, Chih-Ho Lai, Ho Lin, Dalin He, Jer-Tsong Hsieh
Targeted therapy is a standard of care for metastatic renal cell carcinoma (RCC) but the response rate is not overwhelmed, which only prolongs a short survival of patients due to the onset of therapeutic resistance. Although the mechanisms are not fully understood, the presence of cancer initiating cells (CIC) may underlie the drug resistance. Nevertheless, identifying CIC phenotypes with its biomarkers in RCC appear to be diverse and controversial from many reports. In this study, we took a different approach to focus on the regulatory mechanism in RCC-CIC and unveil DAB2IP-mediated miR-138 expression that plays a critical role in modulating stem-like phenotypes in RCC via targeting the ABC transporter (ABCA13) as well as oncogenic histone methyltransferase EZH2 while down regulation of miR-138 gene expression in RCC is due to epigenetic gene silencing by DNA methyltransferase 1 (DNMT1)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28529134/direct-reprogramming-epigenetics-and-cardiac-regeneration
#19
REVIEW
Shota Kurotsu, Takeshi Suzuki, Masaki Ieda
The discovery of induced pluripotent stem cells (iPSCs) has revolutionized regenerative medicine. Autologous iPSCs can be generated by introducing 4 stem cell-specific factors (Oct4, Sox2, Klf4, c-Myc) into fibroblasts. iPSCs can propagate indefinitely and differentiate into clinically important cell types, including cardiomyocytes, in vitro. The iPSC-derived cardiomyocytes represent a promising source of cells for cell-based therapeutic approaches for cardiac regeneration. However, there are several challenges in the clinical application of iPSCs: tumorigenicity of immature cells, poor survival of the transplanted myocardial cells, and cost and efficacy of this therapeutic approach...
May 18, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28518147/survivin-a-key-player-in-cancer-progression-increases-in-obesity-and-protects-adipose-tissue-stem-cells-from-apoptosis
#20
Miriam Ejarque, Victòria Ceperuelo-Mallafré, Carolina Serena, Gisela Pachón, Yaiza Núñez-Álvarez, Margarida Terrón-Puig, Enrique Calvo, Catalina Núñez-Roa, Wilfredo Oliva-Olivera, Francisco J Tinahones, Miguel Angel Peinado, Joan Vendrell, Sonia Fernández-Veledo
Adipose tissue (AT) has a central role in obesity-related metabolic imbalance through the dysregulated production of cytokines and adipokines. In addition to its known risk for cardiovascular disease and diabetes, obesity is also a major risk for cancer. We investigated the impact of obesity for the expression of survivin, an antiapoptotic protein upregulated by adipokines and a diagnostic biomarker of tumor onset and recurrence. In a cross-sectional study of 111 subjects classified by body mass index, circulating levels of survivin and gene expression in subcutaneous AT were significantly higher in obese patients and positively correlated with leptin...
May 18, 2017: Cell Death & Disease
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