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Stem cell therapy, epigenetics

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https://www.readbyqxmd.com/read/27905327/potential-therapeutic-effect-of-epigenetic-therapy-on-treatment-induced-neuroendocrine-prostate-cancer
#1
Xiang Xu, Yu-Hua Huang, Yan-Jing Li, Alexa Cohen, Zhen Li, Jill Squires, Wei Zhang, Xu-Feng Chen, Min Zhang, Jiao-Ti Huang
Although adenocarcinomas of the prostate are relatively indolent, some patients with advanced adenocarcinomas show recurrence of treatment-induced neuroendocrine prostate cancer, which is highly aggressive and lethal. Detailed biological features of treatment-induced neuroendocrine prostate cancer have not been characterized owing to limited biopsies/resections and the lack of a cellular model. In this study, we used a unique cellular model (LNCaP/NE1.8) to investigate the potential role of cancer stem cells in treatment-induced neuroendocrine prostate cancer with acquired resistance to hormonal therapy and chemotherapy...
November 29, 2016: Asian Journal of Andrology
https://www.readbyqxmd.com/read/27900567/clinical-potential-of-human-induced-pluripotent-stem-cells-perspectives-of-induced-pluripotent-stem-cells
#2
REVIEW
Dharmendra Kumar, Taruna Anand, Wilfried A Kues
The recent establishment of induced pluripotent stem (iPS) cells promises the development of autologous cell therapies for degenerative diseases, without the ethical concerns associated with human embryonic stem (ES) cells. Initially, iPS cells were generated by retroviral transduction of somatic cells with core reprogramming genes. To avoid potential genotoxic effects associated with retroviral transfection, more recently, alternative non-viral gene transfer approaches were developed. Before a potential clinical application of iPS cell-derived therapies can be planned, it must be ensured that the reprogramming to pluripotency is not associated with genome mutagenesis or epigenetic aberrations...
November 29, 2016: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27889084/linking-telomere-regulation-to-stem-cell-pluripotency
#3
REVIEW
Lin Liu
Embryonic stem cells (ESCs), somatic cell nuclear transfer ESCs, and induced pluripotent stem cells (iPSCs) represent the most studied group of PSCs. Unlimited self-renewal without incurring chromosomal instability and pluripotency are essential for the potential use of PSCs in regenerative therapy. Telomere length maintenance is critical for the unlimited self-renewal, pluripotency, and chromosomal stability of PSCs. While telomerase has a primary role in telomere maintenance, alternative lengthening of telomere pathways involving recombination and epigenetic modifications are also required for telomere length regulation, notably in mouse PSCs...
November 23, 2016: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/27865365/implications-of-cancer-stem-cells-in-developing-therapeutic-resistance-in-oral-cancer
#4
REVIEW
Prajna Paramita Naik, Durgesh Nandini Das, Prashanta Kumar Panda, Subhadip Mukhopadhyay, Niharika Sinha, Prakash Priyadarshi Praharaj, Rajesh Agarwal, Sujit Kumar Bhutia
Conventional therapeutics are often frequented with recurrences, refraction and regimen resistance in oral cavity cancers which are predominantly manifested by cancer stem cells (CSCs). During oncoevolution, cancer cells may undergo structural and functional reprogramming wherein they evolve as highly tolerant CSC phenotypes with greater survival advantages. The CSCs possess inherent and exclusive properties including self-renewal, hierarchical differentiation, and tumorigenicity that serve as the basis of chemo-radio-resistance in oral cancer...
November 2016: Oral Oncology
https://www.readbyqxmd.com/read/27802135/transient-ectopic-expression-of-the-histone-demethylase-jmjd3-accelerates-the-differentiation-of-human-pluripotent-stem-cells
#5
Tomohiko Akiyama, Shunichi Wakabayashi, Atsumi Soma, Saeko Sato, Yuhki Nakatake, Mayumi Oda, Miyako Murakami, Miki Sakota, Nana Chikazawa-Nohtomi, Shigeru B H Ko, Minoru S H Ko
Harnessing epigenetic regulation is crucial for the efficient and proper differentiation of pluripotent stem cells (PSCs) into desired cell types. Histone H3 lysine 27 trimethylation (H3K27me3) functions as a barrier against cell differentiation through the suppression of developmental gene expression in PSCs. Here, we have generated human PSC (hPSC) lines in which genome-wide reduction of H3K27me3 can be induced by ectopic expression of the catalytic domain of the histone demethylase JMJD3 (called JMJD3c)...
October 15, 2016: Development
https://www.readbyqxmd.com/read/27780147/stem-cell-therapies-for-congenital-heart-disease
#6
REVIEW
Masoumeh Ghafarzadeh, Mehrdad Namdari, Ali Eatemadi
Congenital heart disease (CHD) is the most prevalent congenital anomaly in newborn babies. Cardiac malformations have been induced in different animal model experiments, by perturbing some molecules that take part in the developmental pathways associated with myocyte differentiation, specification, or cardiac morphogenesis. The exact epigenetic, environmental, or genetic, basis for these molecules perturbations is yet to be understood. But, scientist have bridged this gap by introducing autologous stem cell into the defective hearts to treat CHD...
October 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27774908/epigenetically-active-drugs-inhibiting-dna-methylation-and-histone-deacetylation
#7
Dimitry A Chistiakov, Veronika A Myasoedova, Alexander N Orekhov, Yuri V Bobryshev
Epigenetic mechanisms, which are involved in the regulation of gene expression, are tightly controlled. Loss of a proper epigenetic control can lead to global epigenetic alterations frequently observed in various diseases including cancer. Aberrant epigenetic changes induced in malignant cells lead to emergence of neoplastic properties, which inhibit cell differentiation and strict cell cycle control but greatly enhance stemness-related features. However, abnormal epigenetic patterns can be reversed by action of epigenetically active agents...
October 21, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27774820/myelofibrosis-an-update-on-drug-therapy-in-2016
#8
Prithviraj Bose, Srdan Verstovsek
Primary myelofibrosis (PMF) is the least common but the most aggressive of the classic Philadelphia chromosome-negative myeloproliferative neoplasms. Survival is much shorter in PMF than in polycythemia vera (PV) or essential thrombocythemia (ET). Post-PV/ET myelofibrosis (MF) is clinically indistinguishable from PMF and approached similarly. Areas covered: Current pharmacologic therapy of MF revolves around the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib, which dramatically improves constitutional symptoms and splenomegaly in the majority of patients, and improves overall survival (OS)...
November 7, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27762153/olive-polyphenols-new-promising-agents-to-combat-aging-associated-neurodegeneration
#9
Fiorella Casamenti, Massimo Stefani
Clinical trials and population studies indicate the healthy virtues of the Mediterranean diet and its main lipid component, extra-virgin olive oil (EVOO). Olive leaves and EVOO contain many phenolics effective against several aging and lifestyle-related diseases, including neurodegeneration, both in animal models and in humans. Recent research has shown that such protection stems from several effects, including (i.) the interference with the aggregation of peptides/proteins found in amyloid diseases, particularly in Alzheimer's and Parkinson's diseases; (ii...
October 20, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27755245/novel-insights-in-pathophysiology-of-antiblastic-drugs-induced-cardiotoxicity-and-cardioprotection
#10
Martino Deidda, Rosalinda Madonna, Ruggiero Mango, Pasquale Pagliaro, Pier P Bassareo, Lucia Cugusi, Silvio Romano, Maria Penco, Francesco Romeo, Giuseppe Mercuro
Despite advances in supportive and protective therapy for myocardial function, heart failure caused by various clinical conditions, including cardiomyopathy due to antineoplastic therapy, remains a major cause of morbidity and mortality. Because of the limitations associated with current therapies, investigators have been searching for alternative treatments that can effectively repair the damaged heart and permanently restore its function. Damage to the heart can result from both traditional chemotherapeutic agents, such as anthracyclines, and new targeted therapies, such as trastuzumab...
May 2016: Journal of Cardiovascular Medicine
https://www.readbyqxmd.com/read/27725592/myeloproliferative-neoplasms-updates-on-molecular-pathophysiology-diagnosis-and-treatment-strategies
#11
Katsuto Takenaka
Myeloproliferative neoplasms (MPNs) are chronic hematopoietic stem cell disorders, including polycythemia vera, essential thrombocytosis, and primary myelofibrosis. The JAK2V617F mutation was identified in 2005, followed by the discovery of the JAK2 exon12, MPNW515 mutation, and CALR mutation. About 90% of patients with BCR/ABL negative MPNs have been shown to have one of these driver mutations. In addition, mutations in epigenetic regulators and RNA splicing genes were found to co-exist with driver mutations and to play critical roles in the disease progression of MPNs...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27719639/hedgehog-signaling-pathway-as-genetic-and-epigenetic-target-in-ovarian-tumors
#12
Sonja Levanat, Maja Sabol, Vesna Musani, Petar Ozretić, Diana Trnski
BACKGROUND: Hedgehog signaling pathway is a developmental pathway mostly inactive in adult tissues, with the exception of stem cells. It is often found upregulated in various tumors, and associated with cancer stem cell maintenance. METHOD: This review focuses on different aspects of Hedgehog activation in tumors, with special emphasis on ovarian tumors and their treatment. RESULTS: Mutations in pathway components lead to a series of developmental malformations and syndromes...
October 6, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27719637/targeting-notch-as-a-therapeutic-approach-for-human-malignancies
#13
Platonova Natalia, Lesma Elena, Basile Andrea, Bignotto Monica, Garavelli Silvia, Palano Maria Teresa, Moschini Adriana, Neri Antonino, Colombo Michela, Chiaramonte Raffaella
BACKGROUND: Notch is a multifaceted protein that plays a fundamental role in fetal development and tissue homeostasis by directing many cellular functions, including cell growth and differentiation, cell fate determination and regulation of stem cells maintenance. The Notch family consists of four receptors (Notch 1-4) and five ligands (Jagged1-2 and Delta-like 1-3-4) widely expressed in human tissues. Given the crucial contribution of Notch signaling in many physiological processes, it is not surprising that a variety of human malignancies is characterized by a dysregulation of one or more components of this pathway Methods: In this review, we are going to provide a broad overview on the role of Notch pathway in solid and hematological malignancies and a survey on possible Notch-directed therapeutic strategies...
October 6, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27698904/an-integrated-analysis-of-the-genome-wide-profiles-of-dna-methylation-and-mrna-expression-defining-the-side-population-of-a-human-malignant-mesothelioma-cell-line
#14
Myung-Chul Kim, Na-Yon Kim, Yu-Ri Seo, Yongbaek Kim
Intratumoral heterogeneity is a hallmark of all cancers and functions as the major barrier against effective cancer therapy. In contrast to genetic mutations, the role of epigenetic modifications in the generation and maintenance of heterogeneous cancer cells remains largely undetermined. This study was performed to evaluate the epigenetic mechanisms involved in the tumor cell heterogeneity using side population (SP) and non-SP cells isolated from a human malignant mesothelioma (HMM) cell line. The subpopulations of cancer cells were analyzed by methylated DNA immunoprecipitation combined with high-throughput sequencing (MeDIP-seq) and RNA-seq methodology...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27697023/genetic-and-epigenetic-drug-targets-in-myelodysplastic-syndromes
#15
Karmen Stankov, Sunčica Stankov, Jasmina Katanić
BACKGROUND: Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal disorders of hematopoietic system, characterized by genetic, epigenetic or microenvironmental alterations of aging hematopoietic stem cells. Pathophysiology of MDS comprises the suppression of normal hematopoiesis and reduced myeloid progenitor cells differentiation, with the main consequence of peripheral cytopenias and increased risk to evolution in acute myeloid leukemia (AML). METHOD: This review summarizes the evolving understanding of the role of genetic and epigenetic alterations involved in pathogenesis and current and future strategies for therapeutic targeting in myelodysplastic syndromes...
October 3, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27689934/epigenetic-signatures-at-the-runx2-p1-and-sp7-gene-promoters-control-osteogenic-lineage-commitment-of-umbilical-cord-derived-mesenchymal-stem-cells
#16
Hugo Sepulveda, Rodrigo Aguilar, Catalina P Prieto, Francisco Bustos, Sócrates Aedo, José Lattus, Brigitte van Zundert, Veronica Palma, Martin Montecino
Wharton's Jelly mesenchymal stem cells (WJ-MSCs) are an attractive potential source of multipotent stem cells for bone tissue replacement therapies. However, the molecular mechanisms involved in their osteogenic conversion are poorly understood. Particularly, epigenetic control operating at the promoter regions of the two master regulators of the osteogenic program, RUNX2/P57 and SP7 has not yet been described in WJ-MSCs. Via quantitative PCR profiling and chromatin immunoprecipitation (ChIP) studies here we analyze the ability of WJ-MSCs to engage osteoblast lineage...
September 30, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27670965/the-development-of-targeted-new-agents-to-improve-the-outcome-for-children-with-leukemia
#17
Francisco Bautista, Jasper Van der Lugt, Pamela R Kearns, Francis J Mussai, C Michel Zwaan, Lucas Moreno
Survival rates in pediatric leukemia have greatly improved in the last decades but still a substantial number of patients will relapse and die. New agents are necessary to overcome the limitations of conventional chemotherapy and hematopoietic stem cell transplantation and to reduce their undesirable long-term toxicities. The identification of driving molecular alterations of leukemogenesis in subsets of patients will allow the incorporation of new-targeted therapies. Areas covered: In this article the authors present a detailed review of the most recent advances in targeted therapies for pediatric leukemias...
November 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27641993/profiling-of-dna-and-histone-methylation-reveals-epigenetic-based-regulation-of-gene-expression-during-retinal-differentiation-of-stem-progenitor-cells-isolated-from-the-ciliary-pigment-epithelium-of-human-cadaveric-eyes
#18
Srilatha Jasty, Subramanian Krishnakumar
Millions of people around the world suffer from retinal degenerative diseases at varying degrees of vision loss including, complete blindness that are caused by the damage to cells of the retina. The cell replacement therapy could be a promising tool in treating these conditions, since the stem/progenitor cells could be isolated form adult ciliary pigment epithelial cells and could be differentiated into retinal phenotypes in vitro and could be of great importance. The present study aims to identify the role of epigenetic regulators during cellular differentiation, which involves loss of pluripotency and gain of lineage and cell type-specific characteristics...
September 15, 2016: Brain Research
https://www.readbyqxmd.com/read/27635042/molecular-or-metabolic-reprograming-what-triggers-tumor-subtypes
#19
REVIEW
Katherine Eason, Anguraj Sadanandam
Tumor heterogeneity is reflected and influenced by genetic, epigenetic, and metabolic differences in cancer cells and their interactions with a complex microenvironment. This heterogeneity has resulted in the stratification of tumors into subtypes, mainly based on cancer-specific genomic or transcriptomic profiles. Subtyping can lead to biomarker identification for personalized diagnosis and therapy, but stratification alone does not explain the origins of tumor heterogeneity. Heterogeneity has traditionally been thought to arise from distinct mutations/aberrations in "driver" oncogenes...
September 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27634890/epigenetic-therapy-potential-of-suberoylanilide-hydroxamic-acid-on-invasive-human-non-small-cell-lung-cancer-cells
#20
Shirong Zhang, Kan Wu, Jianguo Feng, Zhibing Wu, Qinghua Deng, Chao Guo, Bing Xia, Jing Zhang, Haixiu Huang, Lucheng Zhu, Ke Zhang, Binghui Shen, Xufeng Chen, Shenglin Ma
Metastasis is the reason for most cancer death, and a crucial primary step for cancer metastasis is invasion of the surrounding tissue, which may be initiated by some rare tumor cells that escape the heterogeneous primary tumor. In this study, we isolated invasive subpopulations of cancer cells from human non-small cell lung cancer (NSCLC) H460 and H1299 cell lines, and determined the gene expression profiles and the responses of these invasive cancer cells to treatments of ionizing radiation and chemotherapeutic agents...
September 12, 2016: Oncotarget
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