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Stem cell therapy, epigenetics

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https://www.readbyqxmd.com/read/28716899/hdac1-upregulation-by-nanog-promotes-multidrug-resistance-and-a-stem-like-phenotype-in-immune-edited-tumor-cells
#1
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 inhibitor 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
#2
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
#3
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'...
July 11, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28691093/wnt-antagonists-exhibit-unique-combinatorial-antitumor-activity-with-taxanes-by-potentiating-mitotic-cell-death
#4
Marcus M Fischer, Belinda Cancilla, V Pete Yeung, Fiore Cattaruzza, Cecile Chartier, Christopher L Murriel, Jennifer Cain, Raymond Tam, Chieh-Yang Cheng, James W Evans, Gilbert O'Young, Xiaomei Song, John Lewicki, Ann M Kapoun, Austin Gurney, Wan-Ching Yen, Timothy Hoey
The WNT pathway mediates intercellular signaling that regulates cell fate in both normal development and cancer. It is widely appreciated that the WNT pathway is frequently dysregulated in human cancers through a variety of genetic and epigenetic mechanisms. Targets in the WNT pathway are being extensively pursued for the development of new anticancer therapies, and we have advanced two WNT antagonists for clinical development: vantictumab (anti-FZD) and ipafricept (FZD8-Fc). We examined the antitumor efficacy of these WNT antagonists in combination with various chemotherapies in a large set of patient-derived xenograft models...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28679862/mysm1-2a-dub-is-an-epigenetic-regulator-in-human-melanoma-and-contributes-to-tumor-cell-growth
#5
Christina Wilms, Carsten M Kroeger, Adelheid V Hainzl, Ishani Banik, Clara Bruno, Ioanna Krikki, Vida Farsam, Meinhard Wlaschek, Martina V Gatzka
Histone modifying enzymes, such as histone deacetylases (HDACs) and polycomb repressive complex (PRC) components, have been implicated in regulating tumor growth, epithelial-mesenchymal transition, tumor stem cell maintenance, or repression of tumor suppressor genes - and may be promising targets for combination therapies of melanoma and other cancers. According to recent findings, the histone H2A deubiquitinase 2A-DUB/Mysm1 interacts with the p53-axis in hematopoiesis and tissue differentiation in mice, in part by modulating DNA-damage responses in stem cell and progenitor compartments...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28675638/azacitidine-successfully-maintained-the-second-remission-in-an-infant-with-kmt2a-rearranged-acute-lymphoblastic-leukemia-who-relapsed-after-unrelated-cord-blood-transplantation
#6
Ikue Chijimatsu, Yusuke Imanaka, Daisuke Tomizawa, Mariko Eguchi, Shiho Nishimura, Shuhei Karakawa, Mizuka Miki, Kazuko Hamamoto, Naoto Fujita
The outcome for infants with KMT2A (MLL)-rearranged acute lymphoblastic leukemia (MLL-r ALL) is dismal despite intensive therapy, including hematopoietic stem cell transplantation (HSCT). Epigenetic dysregulation is considered a key driver of MLL-r leukemogenesis, which theoretically supports the use of epigenetic modifiers as a treatment option. We report an infant MLL-r ALL case with post-HSCT relapse. After achieving a second remission, which was maintained for 10 months using only the DNA methyltransferase inhibitor, azacitidine, the patient successfully received the second HSCT...
July 4, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28664454/microrna-directed-neuronal-reprogramming-as-a-therapeutic-strategy-for-neurological-diseases
#7
REVIEW
Irene Faravelli, Stefania Corti
The loss of neurons due to injury and disease results in a wide spectrum of highly disabling neurological and neurodegenerative conditions, given the apparent limited capacity of endogenous repair of the adult central nervous system (CNS). Therefore, it is important to develop technologies that can promote de novo neural stem cell and neuron generation. Current insights in CNS development and cellular reprogramming have provided the knowledge to finely modulate lineage-restricted transcription factors and microRNAs (miRNA) to elicit correct neurogenesis...
June 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28664386/novel-therapies-for-acute-myeloid-leukemia-are-we-finally-breaking-the-deadlock
#8
REVIEW
Maximilian Stahl, Benjamin Y Lu, Tae Kon Kim, Amer M Zeidan
Acute myeloid leukemia (AML) is one of the best studied malignancies, and significant progress has been made in understanding the clinical implications of its disease biology. Unfortunately, drug development has not kept pace, as the '7+3' induction regimen remains the standard of care for patients fit for intensive therapy 40 years after its first use. Temporal improvements in overall survival were mostly confined to younger patients and driven by improvements in supportive care and use of hematopoietic stem cell transplantation...
June 29, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28659499/intersections-of-lung-progenitor-cells-lung-disease-and-lung-cancer
#9
Carla F Kim
The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer...
June 30, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28654205/driving-toward-precision-medicine-for-acute-leukemias-are-we-there-yet
#10
Clement Chung, Hilary Ma
Despite recent progress in the understanding of the molecular basis of acute leukemias, treatment options for these diseases have not shown significant changes over the last few decades. In this review, we present a nonexhaustive key summary of the current cytogenetic and molecular changes associated with acute leukemias in disease prognostication and potential targeted therapies. An emerging paradigm is that many genetic or molecular alterations target similar signal transduction, transcriptional, and epigenetic pathways...
June 27, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28649654/cell-state-plasticity-stem-cells-emt-and-the-generation-of-intra-tumoral-heterogeneity
#11
Geoffrey M Wahl, Benjamin T Spike
Cellular heterogeneity in cancer represents a significant challenge. In order to develop effective and lasting therapies, it is essential to understand the source of this heterogeneity, and its role in tumor progression and therapy resistance. Here, we consider not only genetic and epigenetic mechanisms, but also inflammation and cell state reprogramming in creating tumor heterogeneity. We discuss similarities between normal mammary epithelial developmental states and various breast cancer molecular sub-types, and the cells that are thought to propagate them...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28640953/overview-of-transgenic-mouse-models-of-myeloproliferative-neoplasms-mpns
#12
REVIEW
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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