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https://www.readbyqxmd.com/read/28813671/oct4-and-sox2-work-as-transcriptional-activators-in-reprogramming-human-fibroblasts
#1
Santosh Narayan, Gene Bryant, Shivangi Shah, Georgina Berrozpe, Mark Ptashne
SOX2 and OCT4, in conjunction with KLF4 and cMYC, are sufficient to reprogram human fibroblasts to induced pluripotent stem cells (iPSCs), but it is unclear if they function as transcriptional activators or as repressors. We now show that, like OCT4, SOX2 functions as a transcriptional activator. We substituted SOX2-VP16 (a strong activator) for wild-type (WT) SOX2, and we saw an increase in the efficiency and rate of reprogramming, whereas the SOX2-HP1 fusion (a strong repressor) eliminated reprogramming...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28792659/molecular-alterations-in-pediatric-brainstem-gliomas
#2
Mikaela Porkholm, Anna Raunio, Reetta Vainionpää, Tarja Salonen, Juha Hernesniemi, Leena Valanne, Jarno Satopää, Atte Karppinen, Minna Oinas, Olli Tynninen, Virve Pentikäinen, Sanna-Maria Kivivuori
BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis. Previously, diagnosis was based on a typical clinical presentation and magnetic resonance imaging findings. After the start of the era of biopsies, DIPGs bearing H3 K27 mutations have been reclassified into a novel entity, diffuse midline glioma, based on the presence of this molecular alteration. However, it is not well established how clinically diagnosed DIPG overlap with H3 K27-mutated diffuse midline gliomas, and whether rare long-term survivors also belong to this group...
August 9, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28777741/critical-roles-of-smyd2-mediated-%C3%AE-catenin-methylation-for-nuclear-translocation-and-activation-of-wnt-signaling
#3
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...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28766538/-prognostic-value-of-1q21-amplification-in-multiple-myeloma
#4
T V Abramova, T N Obukhova, L P Mendeleeva, O S Pokrovskaya, E O Gribanova, V V Ryzhko, L A Grebenyuk, M V Nareyko, M V Solovyev, O M Votyakova, S M Kulikov, M A Rusinov, V G Savchenko
AIM: To determine the prevalence of amp1q21 and its relationship to the clinical manifestations of multiple myeloma (MM). SUBJECTS AND METHODS: In December 2009 to March 2016, a total 134 patients aged 30 to 81 years (median 57 years) underwent a pretreatment FISH-study of bone marrow (BM) with centromeric and locus-specific DNA probes to identify amp1q21, t(11;14), t(4;14), t(14;16), t(14;20), t(6;14), trisomies of chromosomes 5, 9, 15, del13q14, del17p13/TP53, and t(8q24)/cMYC...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28757909/metabolic-reprogramming-autophagy-and-reactive-oxygen-species-are-necessary-for-primordial-germ-cell-reprogramming-into-pluripotency
#5
D Sainz de la Maza, A Moratilla, V Aparicio, C Lorca, Y Alcaina, D Martín, M P De Miguel
Cellular reprogramming is accompanied by a metabolic shift from oxidative phosphorylation (OXPHOS) toward glycolysis. Previous results from our laboratory showed that hypoxia alone is able to reprogram primordial germ cells (PGCs) into pluripotency and that this action is mediated by hypoxia-inducible factor 1 (HIF1). As HIF1 exerts a myriad of actions by upregulating several hundred genes, to ascertain whether the metabolic switch toward glycolysis is solely responsible for reprogramming, PGCs were cultured in the presence of a pyruvate kinase M2 isoform (PKM2) activator, or glycolysis was promoted by manipulating PPARγ...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28756008/efficacy-of-the-cdk-inhibitor-dinaciclib-in%C3%A2-vitro-and-in%C3%A2-vivo-in-t-cell-acute-lymphoblastic-leukemia
#6
Sausan A Moharram, Kinjal Shah, Fatima Khanum, Alissa Marhäll, Mohiuddin Gazi, Julhash U Kazi
T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease of the blood affecting children, adolescents and adults. Although current treatment protocols for T-ALL have improved overall survival, a portion of T-ALL patients still experiences treatment failure. Thus, the development of novel therapies is needed. In this study, we used several patient-derived T-ALL cell lines to screen for an effective drug for T-ALL. Using a panel of 378 inhibitors against different kinases, we identified the CDK inhibitor dinaciclib as a potential drug for T-ALL...
July 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28720304/characterization-of-the-single-cell-derived-bovine-induced-pluripotent-stem-cells
#7
Lixia Zhao, Zixin Wang, Jindun Zhang, Jian Yang, Xuefei Gao, Baojiang Wu, Gaoping Zhao, Siqin Bao, Shuxiang Hu, Pentao Liu, Xihe Li
Single-cell derived bovine induced pluripotent stem cells (iPSCs) were generated by the introduction of piggyBac transposons with CAG promoting transcription factors (Oct3/4, Sox2, Klf4 and cMyc). In the study, the bovine iPSCs colony from single cell could passage more than 50 passages after enzymatic dissociation into single cells. These bovine iPSCs cells kept the normal karyotype and displayed dome shaped clones similar to mouse embryonic stem cells. They showed pluripotency in many ways, including their expression of pluripotency markers, such as OCT3/4, NANOG, SOX2, SSEA1, SSEA4, and AP in immunofluorescence assay, Oct4, Nanog, Sox2, Klf4 and cMyc in RT-PCR...
May 22, 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28716817/pi3k-gamma-delta-and-notch1-cross-regulate-pathways-that-define-the-t-cell-acute-lymphoblastic-leukemia-disease-signature
#8
Evgeni Efimenko, Utpal P Davé, Irina V Lebedeva, Yao Shen, Maria J Sanchez-Quintero, Daniel Diolaiti, Andrew Kung, Brian J Lannutti, Jianchung Chen, Ronald Realubit, Zoya Niatsetskiya, Vadim Ten, Charles Karan, Xi Chen, Andrea Califano, Thomas G Diacovo
PI3K/AKT and NOTCH1 signaling pathways are frequently dysregulated in T-cell acute lymphoblastic leukemias (T-ALL). Although we have shown that the combined activities of the class I PI3K isoforms p110γ and p110δ play a major role in the development and progression of PTEN null T-ALL, it has yet to be determined whether their contribution to leukemogenic programing is unique from that associated with NOTCH1 activation. Using a Lmo2-driven mouse model of T-ALL in which both the PI3K/AKT and NOTCH1 pathways are aberrantly upregulated, we now demonstrate that the combined activities of PI3Kγ/δ have both overlapping and distinct roles from NOTCH1 in generating T-ALL disease signature and in promoting tumor cell growth...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28714365/conjugation-of-gold-nanoparticles-and-recombinant-human-endostatin-modulates-vascular-normalization-via-interruption-of-anterior-gradient-2-mediated-angiogenesis
#9
Fan Pan, Wende Yang, Wei Li, Xiao-Yan Yang, Shuhao Liu, Xin Li, Xiaoxu Zhao, Hui Ding, Li Qin, Yunlong Pan
Several studies have revealed the potential of normalizing tumor vessels in anti-angiogenic treatment. Recombinant human endostatin is an anti-angiogenic agent which has been applied in clinical tumor treatment. Our previous research indicated that gold nanoparticles could be a nanoparticle carrier for recombinant human endostatin delivery. The recombinant human endostatin-gold nanoparticle conjugates normalized vessels, which improved chemotherapy. However, the mechanism of recombinant human endostatin-gold nanoparticle-induced vascular normalization has not been explored...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28714063/microrna-206-prevents-the-pathogenesis-of-hepatocellular-carcinoma-via-modulating-expression-of-cmet-and-cdk6
#10
Heng Wu, Junyan Tao, Xiaolei Li, Tianpeng Zhang, Lei Zhao, Yao Wang, Lei Zhang, Jun Xiong, Zhi Zeng, Na Zhan, Clifford J Steer, Li Che, Mingjie Dong, Xiaomei Wang, Junqi Niu, Zhuoyu Li, Guiqing Yan, Xin Chen, Guisheng Song
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide and therapeutic agents for this malignancy are lacking. MicroRNAs play critical roles in carcinogenesis and present tremendous therapeutic potential. Here we report that microRNA-206 is a robust tumor suppressor that plays important roles in the development of HCC by regulating cell cycle progression and cMet signaling pathway. MicroRNA-206 was under-expressed in livers of two HCC mouse models, human individuals bearing HCC, and human HCC cell lines...
July 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28684894/mouse-ipsc-generated-with-porcine-reprogramming-factors-as-a-model-for-studying-the-effects-of-non-silenced-heterologous-transgenes-on-pluripotency
#11
Stoyan G Petkov, Silke Glage, Heiner Niemann
Mouse somatic cells can be reprogrammed to pluripotency by the ectopic expression of four pluripotency transcription factors, Oct4, Sox2, cmyc, and Klf4. Usually, silencing of the exogenous reprogramming factors is considered to be essential for complete reprogramming and differentiation. In the vast majority of studies, murine pluripotency transcription factor sequences have been used for the reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPSC). The effectiveness of xenogeneic transcription factors in miPSC generation has not yet been investigated in detail...
2017: Journal of Stem Cells & Regenerative Medicine
https://www.readbyqxmd.com/read/28677533/generation-of-a-human-ipsc-line-from-a-patient-with-retinitis-pigmentosa-caused-by-mutation-in-prpf8-gene
#12
Dunja Lukovic, Aranzazu Bolinches Amoros, Ana Artero Castro, Beatriz Pascual, Miguel Carballo, Imma Hernán, Slaven Erceg
The human iPSC cell line, RP2-FiPS4F1 (RCPFi001-A), derived from dermal fibroblasts from the patient with retinitis pigmentosa caused by the mutation of the gene PRPF8, was generated by non-integrative reprogramming technology using OCT3/4, SOX2, CMYC and KLF4 reprogramming factors.
May 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28676221/myc-expression-correlates-with-pd-l1-expression-in-non-small-cell-lung-cancer
#13
Eun Young Kim, Arum Kim, Se Kyu Kim, Yoon Soo Chang
Objectives Programmed death-ligand 1 (PD-L1) is a widely used biomarker for predicting immune checkpoint inhibitors, but is of limited usefulness in the prediction of drug response. MYC, a transcription factor that is overexpressed in cancers, is involved in preventing immune cells from attacking tumor cells through inducing PD-L1 expression. This study evaluated the relationship between MYC and PD-L1 expression in 84 non-small cell lung cancer (NSCLC) patients who underwent curative surgical resection. Materials and Methods The relationship between MYC and PD-L1 was investigated by introducing pcDNA3-cMYC into A549 and H1299 cells with low PD-L1 expression and siRNA against MYC into H60 and H2009 cells with high PD-L1 expression...
August 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28673967/piperlongumine-induces-reactive-oxygen-species-ros-dependent-downregulation-of-specificity-protein-transcription-factors
#14
Keshav Karki, Erik Hedrick, Ravi Kasiappan, Un-Ho Jin, Stephen Safe
Piperlongumine is a natural product found in the plant species Piper longum, and this compound exhibits potent anticancer activity in multiple tumor types and has been characterized as an inducer of reactive oxygen species (ROS). Treatment of Panc1 and L3.6pL pancreatic, A549 lung, 786-O kidney, and SKBR3 breast cancer cell lines with 5 to 15 μmol/L piperlongumine inhibited cell proliferation and induced apoptosis and ROS, and these responses were attenuated after cotreatment with the antioxidant glutathione...
August 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28610450/novel-tumor-markers-provide-improved-prediction-of-survival-after-diagnosis-of-human-immunodeficiency-virus-hiv-related-diffuse-large-b-cell-lymphoma
#15
Chun Chao, Michael J Silverberg, Lie-Hong Chen, Lanfang Xu, Otoniel Martínez-Maza, Donald I Abrams, Hongbin D Zha, Reina Haque, Jonathan Said
Existing prognostic tools for HIV + diffuse large B-cell lymphoma (DLBCL) fail to accurately predict patient outcomes. To develop a novel prognostic algorithm incorporating molecular tumor characteristics and HIV disease factors, we included 80 patients with HIV-related DLBCL diagnosed between 1996 and 2007. Immunohistochemistry staining was used to analyze the expression of 26 tumor markers. Clinical data were collected from medical records. Logistic regression and bootstrapping were used to select and assess stability of the prognostic model, respectively...
June 13, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28599486/knockout-of-kr%C3%A3-ppel-like-factor-10-suppresses-hepatic-cell-proliferation-in-a-partially-hepatectomized-mouse-model
#16
Seung-Ho Heo, Eui-Suk Jeong, Kyoung-Sun Lee, Jin-Hee Seo, Woon-Kyu Lee, Yang-Kyu Choi
The liver has marked regenerative capabilities, and numerous signaling pathways are involved in liver regeneration. The transforming growth factor-β (TGF-β)/Smad pathway, which is also involved in liver regeneration, regulates numerous biological processes. Krüppel-like factor 10 (KLF10) has been reported to activate the TGF-β/Smad signaling pathway; however, the exact functions of KLF10 under various pathophysiological conditions remain unclear. In the present study, the role of KLF10 in liver regeneration following partial hepatectomy (PH) was investigated using KLF10-knockout (KO) mice...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28595007/impact-of-target-warhead-and-linkage-vector-on-inducing-protein-degradation-comparison-of-bromodomain-and-extra-terminal-bet-degraders-derived-from-triazolodiazepine-jq1-and-tetrahydroquinoline-i-bet726-bet-inhibitor-scaffolds
#17
Kwok-Ho Chan, Michael Zengerle, Andrea Testa, Alessio Ciulli
The design of proteolysis-targeting chimeras (PROTACs) is a powerful small-molecule approach for inducing protein degradation. PROTACs conjugate a target warhead to an E3 ubiquitin ligase ligand via a linker. Here we examined the impact of derivatizing two different BET bromodomain inhibitors, triazolodiazepine JQ1 and the more potent tetrahydroquinoline I-BET726, via distinct exit vectors, using different polyethylene glycol linkers to VHL ligand VH032. Triazolodiazepine PROTACs exhibited positive cooperativities of ternary complex formation and were more potent degraders than tetrahydroquinoline compounds, which showed negative cooperativities instead...
June 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28586009/fli-1-overexpression-in-erythroleukemic-cells-promotes-erythroid-de-differentiation-while-spi-1-pu-1-exerts-the-opposite-effect
#18
Laura M Vecchiarelli-Federico, Tangjingjun Liu, Yao Yao, Yuanyuan Gao, Yanmei Li, You-Jun Li, Yaacov Ben-David
The ETS transcription factors play a critical role during hematopoiesis. In F-MuLV-induced erythroleukemia, Fli‑1 insertional activation producing high expression of this transcription factor required to promote proliferation. How deregulated Fli‑1 expression alters the balance between erythroid differentiation and proliferation is unknown. To address this issue, we exogenously overexpressed Fli‑1 in an erythroleukemic cell harboring activation of spi‑1/PU.1, another ETS gene involved in erythroleukemogenesis...
June 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28550411/isolation-characterization-and-expression-of-proto-oncogene-cmyc-in-large-yellow-croaker-larimichthys-crocea
#19
Yonghua Jiang, Kunhuang Han, Shihai Chen, Yilei Wang, Ziping Zhang
cMyc is a vital transcription factor that involves in the regulation of cell proliferation, growth, differentiation, and apoptosis. In the present study, cMyc in Larimichthys crocea (Lc-cMyc) was cloned and analyzed for investigating its function. The full-length cDNA of Lc-cMyc was 2089 bp encoding a 440-amino-acid protein (Lc-cMyc). Lc-cMyc had the characteristic helix-loop-helix-leucine-zipper (HLH-LZ) DNA-binding domain and highly conservative in evolution. The expression of Lc-cMyc was detected by quantitative real-time PCR (qRT-PCR) and in situ hybridization, respectively...
May 27, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28545044/differentiation-of-spontaneously-contracting-cardiomyocytes-from-non-virally-reprogrammed-human-amniotic-fluid-stem-cells
#20
Aaron J Velasquez-Mao, Christopher J M Tsao, Madeline N Monroe, Xavier Legras, Beatrice Bissig-Choisat, Karl-Dimiter Bissig, Rodrigo Ruano, Jeffrey G Jacot
Congenital heart defects are the most common birth defect. The limiting factor in tissue engineering repair strategies is an autologous source of functional cardiomyocytes. Amniotic fluid contains an ideal cell source for prenatal harvest and use in correction of congenital heart defects. This study aims to investigate the potential of amniotic fluid-derived stem cells (AFSC) to undergo non-viral reprogramming into induced pluripotent stem cells (iPSC) followed by growth-factor-free differentiation into functional cardiomyocytes...
2017: PloS One
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