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Stem cell therapy, epigenetics

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https://www.readbyqxmd.com/read/28339768/the-transcription-factor-olig2-is-important-for-the-biology-of-diffuse-intrinsic-pontine-gliomas
#1
Jane L Anderson, Ranjithmenon Muraleedharan, Nicole Oatman, Amanda Klotter, Satarupa Sengupta, Ronald R Waclaw, Jianqiang Wu, Rachid Drissi, Lili Miles, Eric H Raabe, Matthew L Weirauch, Maryam Fouladi, Lionel M Chow, Lindsey Hoffman, Mariko DeWire, Biplab Dasgupta
Background.: Diffuse intrinsic pontine glioma (DIPG) is a high-grade brainstem glioma of children with dismal prognosis. There is no single unifying model about the cell of origin of DIPGs. Proliferating cells in the developing human and mouse pons, the site of DIPGs, express neural stem/progenitor cell (NPC) markers, including Sox2, nestin, vimentin, Olig2, and glial fibrillary acidic protein, in an overlapping and non-overlapping manner, suggesting progenitor cell heterogeneity in the pons...
February 23, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28334277/in-bone-metastasis-mir-34a-5p-absence-inversely-correlates-with-met-expression-while-met-oncogene-is-unaffected-by-mir-34a-5p-in-non-metastatic-and-metastatic-breast-carcinomas
#2
Paola Maroni, Rossella Puglisi, Gianfranco Mattia, Alessandra Carè, Emanuela Matteucci, Paola Bendinelli, Maria Alfonsina Desiderio
The highlight of the molecular basis and therapeutic targets of the bone-metastatic process requires the identification of biomarkers of metastasis colonization. Here, we studied miR-34a-5p expression, and Met-receptor expression and localization in bone metastases from ductal breast carcinomas, and in ductal carcinomas without history of metastasis (20 cases). miR-34a-5p was elevated in non-metastatic breast carcinoma, intermediate in the adjacent tissue and practically absent in bone metastases, opposite to pair-matched carcinoma...
March 16, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28330383/progress-in-nonviral-gene-therapy-for-breast-cancer-and-what-comes-next
#3
Giulia Bottai, Marta Truffi, Fabio Corsi, Libero Santarpia
The possibility of correcting defective genes and modulating gene expression through gene therapy has emerged as a promising treatment strategy for breast cancer. Furthermore, the relevance of tumor immune microenvironment in supporting the oncogenic process has paved the way for novel immunomodulatory applications of gene therapy. Areas covered: In this review, the authors describe the most relevant delivery systems, focusing on nonviral vectors, along with the description of the major approaches used to modify target cells, including gene transfer, RNA interference (RNAi), and epigenetic regulation...
March 22, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28278128/cancer-metastasis-tricks-of-the-trade
#4
REVIEW
Rabia Zeeshan, Zeeshan Mutahir
Decades of cancer research have unraveled genetic, epigenetic and molecular pathways leading to plausible therapeutic targets; many of which hold great promise in improving clinical outcomes. Metastatic tumors become evident early on and are one of the major causes of cancer-related fatalities worldwide. This review depicts the sequential events of cancer metastasis. Genetic and epigenetic heterogeneity influences local tumor cell invasion, intravasation, survival in circulation, extravasation and colonization to distant sites...
March 9, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28273465/a-knockin-reporter-allows-purification-and-characterization-of-mda-neurons-from-heterogeneous-populations
#5
Ninuo Xia, Fang Fang, Pengbo Zhang, Jun Cui, Chhavy Tep-Cullison, Tim Hamerley, Hyun Joo Lee, Theo Palmer, Brian Bothner, Jin Hyung Lee, Renee Reijo Pera
Generation of midbrain dopaminergic (mDA) neurons from human pluripotent stem cells provides a platform for inquiry into basic and translational studies of Parkinson's disease (PD). However, heterogeneity in differentiation in vitro makes it difficult to identify mDA neurons in culture or in vivo following transplantation. Here, we report the generation of a human embryonic stem cell (hESC) line with a tyrosine hydroxylase (TH)-RFP (red fluorescent protein) reporter. We validated that RFP faithfully mimicked TH expression during differentiation...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28255276/melatonin-inhibits-glioblastoma-stem-like-cells-through-suppression-of-ezh2-notch1-signaling-axis
#6
Xiangrong Zheng, Bo Pang, Guangyan Gu, Taihong Gao, Rui Zhang, Qi Pang, Qian Liu
Glioblastoma stem-like cells (GSCs) play essential roles in glioma growth, radio- and chemo-resistance, and recurrence. Elimination of GSCs has therefore become a key strategy and challenge in glioblastoma therapy. Here, we show that melatonin, an indolamine derived from I-tryptophan, significantly inhibited viability and self-renewal ability of GSCs accompanied by a decrease of stem cell markers. We have identified EZH2-NOTCH1 signaling as the key signal pathway that regulated the effects of melatonin in the GSCs...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28249646/chromosomal-abnormalities-and-molecular-landscape-of-metastasizing-mucinous-salivary-adenocarcinoma
#7
Alex Panaccione, Yi Zhang, Yanfang Mi, Yoshitsugu Mitani, Guo Yan, Manju L Prasad, W Hayes McDonald, Adel K El-Naggar, Wendell G Yarbrough, Sergey V Ivanov
BACKGROUND: Mucinous adenocarcinoma of the salivary gland (MAC) is a lethal cancer with unknown molecular etiology and a high propensity to lymph node metastasis. Mostly due to its orphan status, MAC remains one of the least explored cancers that lacks cell lines and mouse models that could help translational and pre-clinical studies. Surgery with or without radiation remains the only treatment modality but poor overall survival (10-year, 44%) underscores the urgent need for mechanism-based therapies...
March 2017: Oral Oncology
https://www.readbyqxmd.com/read/28246302/acquired-resistance-with-epigenetic-alterations-under-long-term-anti-angiogenic-therapy-for-hepatocellular-carcinoma
#8
Yoshiteru Ohata, Shu Shimada, Yoshimitsu Akiyama, Kaoru Mogushi, Keisuke Nakao, Satoshi Matsumura, Arihiro Aihara, Yusuke Mitsunori, Daisuke Ban, Takanori Ochiai, Atsushi Kudo, Shigeki Arii, Minoru Tanabe, Shinji Tanaka
Anti-angiogenic therapy is initially effective for several solid tumors including hepatocellular carcinoma (HCC); however, they finally relapse and progress, resulting in poor prognosis. We here established in vivo drug-tolerant subclones of human HCC cells by long-term treatment with vascular endothelial growth factor receptor (VEGFR) inhibitor and serial transplantation in immunocompromised mice (total 12 months), and then compared them with the parental cells in molecular and biological features. Gene expression profiles elucidated a G-actin monomer binding protein thymosin β 4 (Tβ4) as one of the genes enriched in the resistant cancer cells relative to the initially sensitive ones...
February 28, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28228863/medulloblastoma-and-ependymoma-cells-display-increased-levels-of-5-carboxylcytosine-and-elevated-tet1-expression
#9
Ashley Ramsawhook, Lara Lewis, Beth Coyle, Alexey Ruzov
BACKGROUND: Alteration of DNA methylation (5-methylcytosine, 5mC) patterns represents one of the causes of tumorigenesis and cancer progression. Tet proteins can oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine (5caC). Although the roles of these oxidised forms of 5mC (oxi-mCs) in cancer pathogenesis are still largely unknown, there are indications that they may be involved in the mechanisms of malignant transformation. Thus, reduction of 5hmC content represents an epigenetic hallmark of human tumours, and according to our recent report, 5caC is enriched in a proportion of breast cancers and gliomas...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28216148/epigenetic-modification-of-the-ccl5-ccr1-erk-axis-enhances-glioma-targeting-in-dedifferentiation-reprogrammed-bmscs
#10
Rui Chen, Wayne Yuk-Wai Lee, Xiao Hu Zhang, Jie Ting Zhang, Sien Lin, Liang Liang Xu, Biao Huang, Fu Yuan Yang, Hai Long Liu, Bin Wang, Lai Ling Tsang, Sandrine Willaime-Morawek, Gang Li, Hsiao Chang Chan, Xiaohua Jiang
The success of stem cell-mediated gene therapy in cancer treatment largely depends on the specific homing ability of stem cells. We have previously demonstrated that after in vitro induction of neuronal differentiation and dedifferentiation, bone marrow stromal cells (BMSCs) revert to a primitive stem cell population (De-neu-BMSCs) distinct from naive BMSCs. We report here that De-neu-BMSCs express significantly higher levels of chemokines, and display enhanced homing abilities to glioma, the effect of which is mediated by the activated CCL5/CCR1/ERK axis...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28203307/epigenetic-strategies-to-reverse-drug-resistance-in-heterogeneous-multiple-myeloma
#11
REVIEW
Mark E Issa, Farnaz Sedigheh Takhsha, Chandra Sekhar Chirumamilla, Claudina Perez-Novo, Wim Vanden Berghe, Muriel Cuendet
Multiple myeloma (MM) is a hematological malignancy, which remains incurable because most patients eventually relapse or become refractory to current treatments. Due to heterogeneity within the cancer cell microenvironment, cancer cell populations employ a dynamic survival strategy to chemotherapeutic treatments, which frequently results in a rapid acquisition of therapy resistance. Besides resistance-conferring genetic alterations within a tumor cell population selected during drug treatment, recent findings also reveal non-mutational mechanisms of drug resistance, involving a small population of "cancer stem cells" (CSCs) which are intrinsically more refractory to the effects of a variety of anticancer drugs...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28199003/applications-of-induced-pluripotent-stem-cell-technologies-in-spinal-cord-injury
#12
REVIEW
Narihito Nagoshi, Hideyuki Okano
Numerous basic research studies have suggested the potential efficacy of neural precursor cell (NPC) transplantation in spinal cord injury (SCI). However, in most such studies the origin of the cells used was mainly fetal tissue or embryonic stem cells, both of which carry potential ethical concerns with respect to clinical use. The development of induced pluripotent stem cells (iPSCs) opened a new path toward regenerative medicine for SCI. iPSCs can be generated from somatic cells by induction of transcription factors, and induced to differentiate into NPCs with characteristics of cells of the central nervous system...
February 15, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28197667/discovery-and-progress-of-direct-cardiac-reprogramming
#13
REVIEW
Hidenori Kojima, Masaki Ieda
Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), that could convert mouse fibroblasts into cardiomyocyte-like cells, which were designated as induced cardiomyocyte-like cells (iCMs)...
February 14, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28193779/combination-targeted-therapy-to-disrupt-aberrant-oncogenic-signaling-and-reverse-epigenetic-dysfunction-in-idh2-and-tet2-mutant-acute-myeloid-leukemia
#14
Alan H Shih, Cem Meydan, Kaitlyn Shank, Francine E Garrett-Bakelman, Patrick S Ward, Andrew Intlekofer, Abbas Nazir, Eytan Stein, Kristina Knapp, Jacob Glass, Jeremy Travins, Kim Straley, Camelia Gliser, Chris Mason, Katharine Yen, Craig B Thompson, Ari Melnick, Ross L Levine
Genomic studies in acute myeloid leukemias (AML) have identified mutations which drive altered DNA methylation, including TET2 and IDH2. Here we show that models of AMLs resulting from TET2 or IDH2 mutations combined with FLT3ITD mutations are sensitive to 5-Azacytidine or to the IDH2 inhibitor AG-221, respectively. 5-Azacytidine and AG-221 treatment induced an attenuation of aberrant DNA methylation and transcriptional output, and resulted in a reduction in leukemic blasts consistent with anti-leukemic activity...
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28187790/retinoic-acid-and-tgf-%C3%AE-signalling-cooperate-to-overcome-mycn-induced-retinoid-resistance
#15
David J Duffy, Aleksandar Krstic, Melinda Halasz, Thomas Schwarzl, Anja Konietzny, Kristiina Iljin, Desmond G Higgins, Walter Kolch
BACKGROUND: Retinoid therapy is widely employed in clinical oncology to differentiate malignant cells into their more benign counterparts. However, certain high-risk cohorts, such as patients with MYCN-amplified neuroblastoma, are innately resistant to retinoid therapy. Therefore, we employed a precision medicine approach to globally profile the retinoid signalling response and to determine how an excess of cellular MYCN antagonises these signalling events to prevent differentiation and confer resistance...
February 10, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28170201/concise-review-hematopoietic-stem-cell-origins-lessons-from-embryogenesis-for-improving-regenerative-medicine
#16
Adriana De La Garza, Arpan Sinha, Teresa V Bowman
Hematopoietic stem cells (HSCs) have extensive regenerative capacity to replace all blood cell types, an ability that is harnessed in the clinic for bone marrow transplantation. Finding appropriate donors remains a major limitation to more extensive usage of HSC-based therapies. Derivation of patient-specific HSCs from pluripotent stem cells offers great promise to remedy this problem if scientists could crack the code on how to make robust, transplantable HSCs in a dish. Studies delving into the native origins of HSC production during embryonic development should supply the necessary playbook...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28148257/epigenetics-in-cancer-stem-cells
#17
REVIEW
Tan Boon Toh, Jhin Jieh Lim, Edward Kai-Hua Chow
Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" that has been proposed to be a strong driving force of tumorigenesis and a key mechanism of therapeutic resistance. Recent advances in epigenomics have illuminated key mechanisms by which epigenetic regulation contribute to cancer progression. In this review, we present a discussion of how deregulation of various epigenetic pathways can contribute to cancer initiation and tumorigenesis, particularly with respect to maintenance and survival of cancer stem cells...
February 1, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28144824/cellular-reprogramming-for-clinical-cartilage-repair
#18
REVIEW
Britta J H Driessen, Colin Logie, Lucienne A Vonk
The repair of articular cartilage needs a sufficient number of chondrocytes to replace the defect tissue, and therefore, expansion of cells is generally required. Chondrocytes derived by cellular reprogramming may provide a solution to the limitations of current (stem) cell-based therapies. In this article, two distinct approaches-induced pluripotent stem cell (iPSC)-mediated reprogramming and direct lineage conversion-are analysed and compared according to criteria that encompass the qualification of the method and the derived chondrocytes for the purpose of clinical application...
January 31, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28142087/synergistic-activity-of-n-hydroxy-7-2-naphthylthio-heptanomide-and-sorafenib-against-cancer-stem-cells-anaplastic-thyroid-cancer
#19
Ki Cheong Park, Seok-Mo Kim, Jeong Yong Jeon, Bup-Woo Kim, Hyeung Kyoo Kim, Ho Jin Chang, Yong Sang Lee, Soo Young Kim, Seung Hoon Choi, Cheong Soo Park, Hang-Seok Chang
Anaplastic thyroid carcinoma (ATC) although rare is the most deadly form of thyroid cancer. The fatality rate for ATC is high-pitched, the survival rate at 1 year after diagnosis is <20%. Control of ATC is severely hard and widespread with unpredictability. We Previous proved that histone gene reviser and epigenetic changes role significant parts in papillary and anaplastic thyroid cancer tumorigenesis. Herein, the goal of this study was to investigate the anti-tumor activities of a HDAC inhibitor, HNHA alone and in combination with sorafenib in ATC cells in vitro and in vivo and to explore its effects on apoptotic cell death pathways...
January 27, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28108626/a-new-role-for-er%C3%AE-silencing-via-dna-methylation-of-basal-stem-cell-and-emt-genes
#20
Eric A Ariazi, John C Taylor, Michael A Black, Emmanuelle Nicolas, Michael J Slifker, Diana J Azzam, Jeff Boyd
Resistance to hormonal therapies is a major clinical problem in the treatment of estrogen receptor α-positive (ERα(+)) breast cancers. Epigenetic marks, namely DNA methylation of cytosine at specific CpG sites (5mCpG), are frequently associated with ERα(+) status in human breast cancers. Therefore, ERα may regulate gene expression in part via DNA methylation. This hypothesis was evaluated using a panel of breast cancer cell line models of antiestrogen resistance. Microarray gene expression profiling was used to identify genes normally silenced in ERα(+) cells but derepressed upon exposure to the demethylating agent decitabine, derepressed upon long-term loss of ERα expression, and resuppressed by gain of ERα activity/expression...
February 2017: Molecular Cancer Research: MCR
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