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https://www.readbyqxmd.com/read/28915556/critical-roles-of-smyd2-mediated-%C3%AE-catenin-methylation-for-nuclear-translocation-and-activation-of-wnt-signaling
#1
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
https://www.readbyqxmd.com/read/28881081/a-genetically-inducible-porcine-model-of-intestinal-cancer
#2
Morten Møbjerg Callesen, Sigrid Salling Árnadóttir, Iben Lyskjaer, Mai-Britt Worm Ørntoft, Søren Høyer, Frederik Dagnaes-Hansen, Ying Liu, Rong Li, Henrik Callesen, Mads Heilskov Rasmussen, Martin Fogtmann Berthelsen, Martin Kristian Thomsen, Pawel Jan Schweiger, Kim Bak Jensen, Søren Laurberg, Torben Falck Ørntoft, Jannik Ejnar Elverløv-Jakobsen, Claus Lindbjerg Andersen
Transgenic porcine cancer models bring novel possibilities for research. Their physical similarities with humans enable the use of surgical procedures and treatment approaches used for patients, which facilitates clinical translation. Here, we aimed to develop an inducible oncopig model of intestinal cancer. Transgenic (TG) minipigs were generated using somatic cell nuclear transfer by hand-made cloning. The pigs encode two TG cassettes: 1) An Flp-recombinase inducible oncogene cassette containing KRAS-G12D, cMYC, SV40LT - which inhibits p53 - and pRB...
September 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28875331/implication-of-connexin30-on-the-stemness-of-glioma-connexin30-reverses-the-malignant-phenotype-of-glioma-by-modulating-igf-1r-cd133-and-cmyc
#3
Sankaradoss Arun, Shantha Ravisankar, Arambakkam Janardhanam Vanisree
Gap-junctional intercellular communication (GJIC) plays a major role in the malignant growth of glioma. Although the mechanistic aspects of GJIC have been extensively studied, the role of connexins in the regulation of the malignant behavior of glioma stem cells (GSCs) remains unclear. In our previous studies, we have shown that connexin30 can interfere with the insulin-like growth factor 1 receptor (IGF-1R), which is known for self-renewal and pluripotency. Following our earlier in vitro observation, in this work, we aimed to study the consequence of this influence of Cx30 on IGF-1R by evaluating the marker of GSCs, CD133 and oncoprotein, cMyc...
September 5, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28859475/identification-of-slirp-as-a-g-quadruplex-binding-protein
#4
Preston Williams, Lin Li, Xiaoli Dong, Yinsheng Wang
The guanine quadruplex (G4) structure in DNA is a secondary structure motif that plays important roles in DNA replication, transcriptional regulation, and maintenance of genomic stability. Here, we employed a quantitative mass spectrometry-based approach to profile the interaction proteomes of three well-defined G4 structures derived from the human telomere and the promoters of cMYC and cKIT genes. We identified SLIRP as a novel G4-interacting protein. We also demonstrated that the protein could bind directly with G4 DNA with Kd values in the low nanomolar range and revealed that the robust binding of the protein toward G4 DNA requires its RRM domain...
September 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28830912/mapping-genetic-vulnerabilities-reveals-btk-as-a-novel-therapeutic-target-in-oesophageal-cancer
#5
Irene Yushing Chong, Lauren Aronson, Hanna Bryant, Aditi Gulati, James Campbell, Richard Elliott, Stephen Pettitt, Paul Wilkerson, Maryou B Lambros, Jorge S Reis-Filho, Anisha Ramessur, Michael Davidson, Ian Chau, David Cunningham, Alan Ashworth, Christopher J Lord
OBJECTIVE: Oesophageal cancer is the seventh most common cause of cancer-related death worldwide. Disease relapse is frequent and treatment options are limited. DESIGN: To identify new biomarker-defined therapeutic approaches for patients with oesophageal cancer, we integrated the genomic profiles of 17 oesophageal tumour-derived cell lines with drug sensitivity data from small molecule inhibitor profiling, identifying drug sensitivity effects associated with cancer driver gene alterations...
August 22, 2017: Gut
https://www.readbyqxmd.com/read/28819416/expression-of-cd133-in-endometrial-cancer-cells-and-its-implications
#6
Dah-Ching Ding, Hwan-Wun Liu, Yu-Hsun Chang, Tang-Yuan Chu
Cancer stem cells are an attractive therapeutic target for cancer. The present study examined stem cell characteristics of CD133+ cells isolated from endometrial cancer. Phenotypic characteristics, proliferation, migration, anchorage-independent growth, chemoresistance, gene expression profile and tumorigenicity of CD133+ tumor cells were assessed. Primary tumor exhibited immunoreactivity for CD133. Endometrial CD133+ tumor cells enhanced proliferation rate, colony formation, chemotaxis migration ability, and chemoresistance to cisplatin, paclitaxel, and doxorubicin than CD133- cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28815764/aligning-digital-cd8-scoring-and-targeted-next-generation-sequencing-with-pd-l1-expression-a-pragmatic-approach-in-early-stage-squamous-cell-lung-carcinoma
#7
Esther Conde, Alejandra Caminoa, Carolina Dominguez, Antonio Calles, Stefan Walter, Barbara Angulo, Elena Sánchez, Marta Alonso, Luis Jimenez, Luis Madrigal, Florentino Hernando, Julian Sanz-Ortega, Beatriz Jimenez, Pilar Garrido, Luis Paz-Ares, Javier de Castro, Susana Hernandez, Fernando Lopez-Rios
AIMS: To study PD-L1 expression, tumour-infiltrating T lymphocytes (TILs) and the molecular context in patients with early-stage squamous cell lung carcinomas (SCCs). METHODS AND RESULTS: The study included samples from 40 patients (discovery cohort) and 29 patients (validation cohort) diagnosed with early-stage SCC. PD-L1 immunohistochemistry (IHC) was performed with three commercially available clones (E1L3N, SP263 and SP142). CD8(+) TILs were scored with a digital algorithm...
August 16, 2017: Histopathology
https://www.readbyqxmd.com/read/28813671/oct4-and-sox2-work-as-transcriptional-activators-in-reprogramming-human-fibroblasts
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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...
October 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28720304/characterization-of-the-single-cell-derived-bovine-induced-pluripotent-stem-cells
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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