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https://www.readbyqxmd.com/read/29281720/reversible-dual-inhibitor-against-g9a-and-dnmt1-improves-human-ipsc-derivation-enhancing-met-and-facilitating-transcription-factor-engagement-to-the-genome
#1
Juan Roberto Rodriguez-Madoz, Edurne San Jose-Eneriz, Obdulia Rabal, Natalia Zapata-Linares, Estibaliz Miranda, Saray Rodriguez, Angelo Porciuncula, Amaia Vilas-Zornoza, Leire Garate, Victor Segura, Elizabeth Guruceaga, Xabier Agirre, Julen Oyarzabal, Felipe Prosper
The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of iPSCs and could be used for disease modelling, high throughput screenings and/or regenerative medicine applications. In this study, we showed that a new first-in-class reversible dual G9a/DNMT1 inhibitor compound (CM272) improves the efficiency of human cell reprogramming and iPSC generation from primary cells of healthy donors and patient samples, using both integrative and non-integrative methods...
2017: PloS One
https://www.readbyqxmd.com/read/29249668/gcn5-regulates-fgf-signaling-and-activates-selective-myc-target-genes-during-early-embryoid-body-differentiation
#2
Li Wang, Evangelia Koutelou, Calley Hirsch, Ryan McCarthy, Andria Schibler, Kevin Lin, Yue Lu, Collene Jeter, Jianjun Shen, Michelle C Barton, Sharon Y R Dent
Precise control of gene expression during development is orchestrated by transcription factors and co-regulators including chromatin modifiers. How particular chromatin-modifying enzymes affect specific developmental processes is not well defined. Here, we report that GCN5, a histone acetyltransferase essential for embryonic development, is required for proper expression of multiple genes encoding components of the fibroblast growth factor (FGF) signaling pathway in early embryoid bodies (EBs). Gcn5-/- EBs display deficient activation of ERK and p38, mislocalization of cytoskeletal components, and compromised capacity to differentiate toward mesodermal lineage...
December 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29229300/c-myc-g-quadruplex-binding-by-the-rna-polymerase-i-inhibitor-bmh-21-and-analogues-revealed-by-a-combined-nmr-and-biochemical-approach
#3
Loana Musso, Stefania Mazzini, Anna Rossini, Lorenzo Castagnoli, Leonardo Scaglioni, Roberto Artali, Massimo Di Nicola, Franco Zunino, Sabrina Dallavalle
BACKGROUND: Pyridoquinazolinecarboxamides have been reported as RNA polymerase I inhibitors and represent a novel class of potential antitumor agents. BMH-21, was reported to intercalate with GC-rich rDNA, resulting in nucleolar stress as a primary mechanism of cytotoxicity. METHODS: The interaction of BMH-21 and analogues with DNA G-quadruplex structures was studied by NMR and molecular modelling. The cellular response was investigated in a panel of human tumor cell lines and protein expression was examined by Western Blot analysis...
December 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29203894/combining-intratumoral-treg-depletion-with-androgen-deprivation-therapy-adt-preclinical-activity-in-the-myc-cap-model
#4
Ying-Chun Shen, Ali Ghasemzadeh, Christina M Kochel, Thomas R Nirschl, Brian J Francica, Zoila A Lopez-Bujanda, Maria A Carrera Haro, Ada Tam, Robert A Anders, Mark J Selby, Alan J Korman, Charles G Drake
BACKGROUND: Immune checkpoint blockade has shown promising antitumor activity against a variety of tumor types. However, responses in castration-resistant prostate cancer remain relatively rare-potentially due to low baseline levels of infiltration. Using an immunocompetent cMyc-driven model (Myc-CaP), we sought to understand the immune infiltrate induced by androgen deprivation therapy (ADT) and to leverage that infiltration toward therapeutic benefit. METHODS: Using flow cytometry, qPCR and IHC, we quantified ADT-induced immune infiltration in terms of cell type and function...
December 4, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29196542/cardiac-myosin-binding-protein-c-is-a-novel-marker-of-myocardial-injury-and-fibrosis-in-aortic-stenosis
#5
Atul Anand, Calvin Chin, Anoop S V Shah, Jacek Kwieciński, Alex Vesey, Joanna Cowell, Ekkehard Weber, Thomas Kaier, David E Newby, Marc Dweck, Michael S Marber, Nicholas L Mills
OBJECTIVE: Cardiac myosin-binding protein C (cMyC) is an abundant sarcomeric protein and novel highly specific marker of myocardial injury. Myocyte death characterises the transition from hypertrophy to replacement myocardial fibrosis in advanced aortic stenosis. We hypothesised that serum cMyC concentrations would be associated with cardiac structure and outcomes in patients with aortic stenosis. METHODS: cMyC was measured in two cohorts in which serum had previously been prospectively collected: a mechanism cohort of patients with aortic stenosis (n=161) and healthy controls (n=46) who underwent cardiac MRI, and an outcome cohort with aortic stenosis (n=104) followed for a median of 11...
December 1, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/29196266/tipe2-attenuates-liver-fibrosis-by-reversing-the-activated-hepatic-stellate-cells
#6
Dan-Dan Xu, Xiao-Feng Li, Yu-Huan Li, Yan-Hui Liu, Cheng Huang, Xiao-Ming Meng, Jun Li
TIPE2, the tumor necrosis factor (TNF)-α-induced protein 8-like 2 (TNFAIP8L2), plays an important role in regulating inflammation and immune homeostasis. Recent studies discovered that TIPE-2 involved in the development of several tumors and other proliferative diseases. The purpose of this study was to explore the function of TIPE-2 in the activation and proliferation in HSC-T6 cells. Our study showed low expression of TIPE-2 in primary HSCs from CCl4-treated mice and activated HSC-T6 cells. Functionally, over-expression of TIPE-2 by GV141-TIPE-2 hindered the HSC-T6 cells activation and proliferation and expressions of β-Catenin, Cmyc, Cyclin D1...
November 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29189162/tunneling-nanotubes-a-versatile-target-for-cancer-therapy
#7
Pragyaparamita Sahoo, Soumya Ranjan Jena, Luna Samanta
Acute Myeloid Leukemia (AML) and Acute Lymphocytic Leukemia (ALL) are common acute leukemia in adults and children respectively. In therapy process of these malignancies, chemotherapy is the main strategy that fails in many of cases. Moreover, chemotherapy is usually associated with adverse effects it also damages the healthy cells. In this regard, development of new therapies is essential. Monoclonal antibodies directed to the cell surface markers of leukemic blasts may have promising consequences. These tools can provide a specific cell targeting with minimal toxic effects on other normal cells...
November 29, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29157834/16-hydroxycleroda-3-13-dien-15-16-olide-inhibits-the-proliferation-and-induces-mitochondrial-dependent-apoptosis-through-akt-mtor-and-mek-erk-pathways-in-human-renal-carcinoma-cells
#8
Cheng Liu, Wei-Chang Lee, Bu-Miin Huang, Yi-Chen Chia, Yu-Chi Chen, Yung-Chia Chen
BACKGROUND: Renal cell carcinoma (RCC) is well known that it cannot be treated with traditional chemotherapy or radiotherapy. 16-Hydroxycleroda-3,13-dien-15,16-olide (CD), isolated from Polyalthia longifolia Benth. & Hook. f. var. pendula had been reported to display significant efficacy against cancer cell lines. PURPOSE: To determine the anti-tumour activities of CD in two clear cell type RCC (ccRCC) cell lines (A-498 and 786-O). In addition, the underlying mechanisms were also examined...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29138277/coupling-shrna-screens-with-single-cell-rna-seq-identifies-a-dual-role-for-mtor-in-reprogramming-induced-senescence
#9
Marieke Aarts, Athena Georgilis, Meryam Beniazza, Patrizia Beolchi, Ana Banito, Thomas Carroll, Marizela Kulisic, Daniel F Kaemena, Gopuraja Dharmalingam, Nadine Martin, Wolf Reik, Johannes Zuber, Keisuke Kaji, Tamir Chandra, Jesús Gil
Expression of the transcription factors OCT4, SOX2, KLF4, and cMYC (OSKM) reprograms somatic cells into induced pluripotent stem cells (iPSCs). Reprogramming is a slow and inefficient process, suggesting the presence of safeguarding mechanisms that counteract cell fate conversion. One such mechanism is senescence. To identify modulators of reprogramming-induced senescence, we performed a genome-wide shRNA screen in primary human fibroblasts expressing OSKM. In the screen, we identified novel mediators of OSKM-induced senescence and validated previously implicated genes such as CDKN1A We developed an innovative approach that integrates single-cell RNA sequencing (scRNA-seq) with the shRNA screen to investigate the mechanism of action of the identified candidates...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29125889/pterostilbene-down-regulates-htert-at-physiological-concentrations-in-breast-cancer-cells-potentially-through-the-inhibition-of-cmyc
#10
Michael Daniel, Trygve O Tollefsbol
Human telomerase reverse transcriptase (hTERT) encodes the catalytic subunit of telomerase, which has been shown to be upregulated in many cancers. Pterostilbene is a naturally occurring stilbenoid and phytoalexin found primarily in blueberries that exhibits antioxidant activity and inhibits the growth of various cancer cell types. Therefore, the aim of this study was to determine whether treatment with pterostilbene, at physiologically achievable concentrations, can inhibit the proliferation of breast cancer cells and down-regulate the expression of hTERT...
November 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29108569/a-genome-inspired-reverse-selection-approach-to-aptamer-discovery
#11
Christina M Albanese, Suttipong Suttapitugsakul, Shruthi Perati, Linda B McGown
Limitations of Systematic Evolution of Ligands by Exponential Enrichment (SELEX) and related methods that depend upon combinatorial oligonucleotide libraries have hindered progress in this area. Our laboratory has introduced a new approach to aptamer discovery that uses oligonucleotides with sequences drawn from the human genome to capture proteins from biological samples. Specifically, we have focused on capture of proteins in nuclear extracts from human cell lines using G-quadruplex (G4) forming genomic sequences...
January 15, 2018: Talanta
https://www.readbyqxmd.com/read/29107034/histone-deacetylase-atsrt1-links-metabolic-flux-and-stress-response-in-arabidopsis
#12
Xiaoyun Liu, Wei Wei, Wenjun Zhu, Lufang Su, Zeyang Xiong, Man Zhou, Yu Zheng, Dao-Xiu Zhou
How plant metabolic flux alters gene expression to optimize plant growth and response to stress remains largely unclear. Here, we report that Arabidopsis thaliana NAD+-dependent histone deacetylase AtSRT1 negatively regulates plant tolerance to stress and glycolysis but stimulates mitochondrial respiration. We found that AtSRT1 interacts with Arabidopsis cMyc-Binding Protein 1 (AtMBP-1), a transcriptional repressor produced by alternative translation of the cytosolic glycolytic enolase gene LOS2/ENO2. We demonstrated that AtSRT1 could associate with the chromatin of AtMBP-1 targets LOS2/ENO2 and STZ/ZAT10, both of which encode key stress regulators, and reduce the H3K9ac levels at these genes to repress their transcription...
December 4, 2017: Molecular Plant
https://www.readbyqxmd.com/read/29067216/genotyping-tumour-dna-in-cerebrospinal-fluid-and-plasma-of-a-her2-positive-breast-cancer-patient-with-brain-metastases
#13
Giulia Siravegna, Elena Geuna, Benedetta Mussolin, Giovanni Crisafulli, Alice Bartolini, Danilo Galizia, Laura Casorzo, Ivana Sarotto, Maurizio Scaltriti, Anna Sapino, Alberto Bardelli, Filippo Montemurro
BACKGROUND: Central nervous system (CNS) involvement contributes to significant morbidity and mortality in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) and represents a major challenge for clinicians. Liquid biopsy of cerebrospinal fluid (CSF)-derived circulating tumour DNA (ctDNA) harbours clinically relevant genomic alterations in patients with CNS metastases and could be effective in tracking tumour evolution. METHODS: In a HER2-positive mBC patient with brain metastases, we applied droplet digital PCR (ddPCR) and next-generation whole exome sequencing (WES) analysis to measure ctDNA dynamic changes in CSF and plasma collected during treatment...
2017: ESMO Open
https://www.readbyqxmd.com/read/29042999/pien-tze-huang-inhibits-the-proliferation-of-colorectal-cancer-cells-by-increasing-the-expression-of-mir-34c-5p
#14
Yun Wan, Aling Shen, Fei Qi, Jianfeng Chu, Qiaoyan Cai, Thomas Joseph Sferra, Jun Peng, Youqin Chen
MicroRNAs (miRNAs) are small, short endogenous non-coding RNA that act as oncogenes or tumor suppressors, and serve an important role in various human malignant cancers, including colorectal cancer (CRC). Evidence has indicated that miRNAs regulate the expression of various genes associated with human cancer, in particular the miR-34 family. A well-known traditional Chinese formula, Pien Tze Huang (PZH), has a significant clinical effect on CRC. Previous studies have demonstrated that PZH inhibits CRC growth in vitro and in vivo via multiple mechanisms, including the induction of apoptosis, inhibition of cell proliferation and tumor angiogenesis...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29034900/generation-of-ipsc-line-from-patient-with-arrhythmogenic-right-ventricular-cardiomyopathy-carrying-mutations-in-pkp2-gene
#15
Aleksandr Khudiakov, Daria Kostina, Anna Zlotina, Natalia Yany, Alexey Sergushichev, Tatiana Pervunina, Alexey Tomilin, Anna Kostareva, Anna Malashicheva
Human iPSC line was generated from patient-specific adipose tissue-derived mesenchymal multipotent stromal cells carrying two mutations in plakophilin-2 (PKP2) gene using non-integrative reprogramming method. Reprogramming factors OCT4, KLF4, SOX2, CMYC were delivered using Sendai viruses. Pluripotency was confirmed in vitro using immunofluorescence and RT-PCR analysis and in vivo by teratoma assay. The reported iPSC line could be useful tool for in vitro modeling of arrhythmogenic right ventricular cardiomyopathy...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29034897/generation-of-ipsc-line-from-desmin-related-cardiomyopathy-patient-carrying-splice-site-mutation-of-des-gene
#16
Aleksandr Khudiakov, Daria Kostina, Anna Zlotina, Tatiana Nikulina, Alexey Sergushichev, Alexandra Gudkova, Alexey Tomilin, Anna Malashicheva, Anna Kostareva
Human iPSC line was generated from patient-specific adipose tissue-derived mesenchymal multipotent stromal cells carrying desmin (DES) gene heterozygous splice site mutation using non-integrative reprogramming method. Reprogramming factors OCT4, KLF4, SOX2, CMYC were delivered using Sendai viruses. iPSCs were characterized by sequencing, karyotype analysis, STR analysis, immunocytochemistry, RT-PCR and teratoma formation.
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28981733/prognostic-factors-for-primary-central-nervous-system-lymphomas-treated-with-high-dose-methotrexate-based-chemo-radiotherapy
#17
Jeunghun Lee, Yukiko Shishido-Hara, Kaori Suzuki, Saki Shimizu, Keiichi Kobayashi, Hiroshi Kamma, Yoshiaki Shiokawa, Motoo Nagane
Background: Primary central nervous system lymphoma (PCNSL) remains an aggressive and refractory tumor despite high-dose methotrexate-based chemo-radiotherapy. Age and performance status have been shown to be important clinical prognostic factors, however others, especially molecular factors, affecting the prognosis are still uncertain. Methods: We investigate clinical, neuroimaging and immunohistochemical data in tissue from 41 PCNSL patients treated primarily with methotrexate-based chemo-radiotherapy and evaluate the influence of potential prognostic factors on clinical outcome as well as correlation among these factors...
October 1, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28974238/cmyc-expression-in-thyroid-follicular-cell-derived-carcinomas-a-role-in-thyroid-tumorigenesis
#18
Hany I Sakr, Deborah J Chute, Christian Nasr, Charles D Sturgis
BACKGROUND: cMYC regulates approximately 15% of human genes and is involved in up to 20% of all human cancers. Reports discussing cMYC protein expression in thyroid carcinomas are limited, with controversies pertaining to cMYC expression patterns noted in the literature. The aims of the current study were to clarify patterns and intensities of cMYC expression in follicular cell-derived thyroid carcinomas across a spectrum of cancer morphologies and disease aggressivities, to correlate cMYC with BRAF(V600E) expression, and to evaluate the potential role of cMYC in progression of well-differentiated thyroid carcinomas into less well-differentiated carcinomas...
October 3, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28972002/direct-comparison-of-cardiac-myosin-binding-protein-c-with-cardiac-troponins-for-the-early-diagnosis-of-acute-myocardial-infarction
#19
MULTICENTER STUDY
Thomas E Kaier, Raphael Twerenbold, Christian Puelacher, Jack Marjot, Nazia Imambaccus, Jasper Boeddinghaus, Thomas Nestelberger, Patrick Badertscher, Zaid Sabti, Maria Rubini Giménez, Karin Wildi, Petra Hillinger, Karin Grimm, Sarah Loeffel, Samyut Shrestha, Dayana Flores Widmer, Janosch Cupa, Nikola Kozhuharov, Òscar Miró, F Javier Martín-Sánchez, Beata Morawiec, Katharina Rentsch, Jens Lohrmann, Wanda Kloos, Stefan Osswald, Tobias Reichlin, Ekkehard Weber, Michael Marber, Christian Mueller
BACKGROUND: Cardiac myosin-binding protein C (cMyC) is a cardiac-restricted protein that is more abundant than cardiac troponins (cTn) and is released more rapidly after acute myocardial infarction (AMI). We evaluated cMyC as an adjunct or alternative to cTn in the early diagnosis of AMI. METHODS: Unselected patients (N=1954) presenting to the emergency department with symptoms suggestive of AMI, concentrations of cMyC, and high-sensitivity (hs) and standard-sensitivity cTn were measured at presentation...
October 17, 2017: Circulation
https://www.readbyqxmd.com/read/28915556/critical-roles-of-smyd2-mediated-%C3%AE-catenin-methylation-for-nuclear-translocation-and-activation-of-wnt-signaling
#20
Xiaolan Deng, Ryuji Hamamoto, Theodore Vougiouklakis, Rui Wang, Yuichiro Yoshioka, Takehiro Suzuki, Naoshi Dohmae, Yo Matsuo, Jae-Hyun Park, Yusuke Nakamura
Accumulation of β-catenin in the nucleus is a hallmark of activation of the Wnt/β-catenin signaling pathway, which drives development of a large proportion of human cancers. However, the mechanism of β-catenin nuclear translocation has not been well investigated. Here we report biological significance of SMYD2-mediated lysine 133 (K133) methylation of β-catenin on its nuclear translocation. Knockdown of SMYD2 attenuates the nuclear localization of β-catenin protein in human cancer cells. Consequently, transcriptional levels of well-known Wnt-signaling molecules, cMYC and CCND1, are significantly reduced...
August 22, 2017: Oncotarget
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