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https://www.readbyqxmd.com/read/27926868/cmyc-regulates-the-size-of-the-premigratory-neural-crest-stem-cell-pool
#1
Laura Kerosuo, Marianne E Bronner
The neural crest is a transient embryonic population that originates within the central nervous system (CNS) and then migrates into the periphery and differentiates into multiple cell types. The mechanisms that govern neural crest stem-like characteristics and self-renewal ability are poorly understood. Here, we show that the proto-oncogene cMyc is a critical factor in the chick dorsal neural tube, where it regulates the size of the premigratory neural crest stem cell pool. Loss of cMyc dramatically decreases the number of emigrating neural crest cells due to reduced self-renewal capacity, increased cell death, and shorter duration of the emigration process...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#2
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27884981/tissue-damage-and-senescence-provide-critical-signals-for-cellular-reprogramming-in-vivo
#3
Lluc Mosteiro, Cristina Pantoja, Noelia Alcazar, Rosa M Marión, Dafni Chondronasiou, Miguel Rovira, Pablo J Fernandez-Marcos, Maribel Muñoz-Martin, Carmen Blanco-Aparicio, Joaquin Pastor, Gonzalo Gómez-López, Alba De Martino, Maria A Blasco, María Abad, Manuel Serrano
Reprogramming of differentiated cells into pluripotent cells can occur in vivo, but the mechanisms involved remain to be elucidated. Senescence is a cellular response to damage, characterized by abundant production of cytokines and other secreted factors that, together with the recruitment of inflammatory cells, result in tissue remodeling. Here, we show that in vivo expression of the reprogramming factors OCT4, SOX2, KLF4, and cMYC (OSKM) in mice leads to senescence and reprogramming, both coexisting in close proximity...
November 25, 2016: Science
https://www.readbyqxmd.com/read/27875298/benzylisothiocyanate-bitc-induces-ros-dependent-repression-of-stat3-by-downregulation-of-specificity-proteins-in-pancreatic-cancer
#4
Ravi Kasiappan, Indira Jutooru, Keshav Karki, Erik Hedrick, Stephen H Safe
The antineoplastic agent benzylisothiocyanate (BITC) acts by targeting multiple pro-oncogenic pathways/genes, including signal transducer and activator of transcription 3 (STAT3); however, the mechanism of action is not well known. As previously reported, BITC induced ROS in Panc1, MiaPaCa2 and L3.6pL pancreatic cancer cells and this was accompanied by induction of apoptosis and inhibition of cell growth and migration, and these responses were attenuated in cells cotreated with BITC plus glutathione (GSH). BITC also decreased expression of Sp1, Sp3 and Sp4 transcription factors (TFs) and several pro-oncogenic Sp-regulated genes including STAT3 and phospho-STAT3 (pSTAT3), and GSH attenuated these responses...
November 15, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27875275/histone-chaperone-aplf-regulates-induction-of-pluripotency-in-murine-fibroblasts
#5
Khaja Mohieddin Syed, Sunu Joseph, Ananda Mukherjee, Aditi Majumder, Jose M Teixeira, Debasree Dutta, Madhavan Radhakrishna Pillai
Induction of pluripotency in differentiated cells by the exogenous expression of transcription factors, Oct4, Sox2, Klf4 and cMyc, involves reprogramming at the epigenetic level. Histones and their metabolism governed by histone chaperones constitute a significant aspect of epigenetics. We hypothesized that histone chaperones might facilitate or inhibit the course of reprogramming. For the first time, we report here that the downregulation of histone chaperone Aprataxin PNK-like factor (APLF) promotes reprogramming by augmenting the expression of E-cadherin (Cdh1), implicated in mesenchymal-to-epithelial transition (MET) involved in the generation of induced pluripotent stem cells (iPSCs) from mouse embryonic fibroblasts (MEFs)...
November 14, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27867103/lymphoblastic-lymphoma-with-a-triple-hit-profile-a-rare-but-distinct-and-relevant-entity
#6
Laura S Hiemcke-Jiwa, Roos J Leguit, Lars T van der Veken, Arjan Buijs, Jan Willem Leeuwis, Mirthe de Boer, N Mehdi Jiwa, Andries C Bloem, Eefke J Petersen, Roel A de Weger, Manon M H Huibers
Follicular lymphoma with progression to a high grade lymphoma bears a poor prognosis. We describe a case of a 60-year old man who presented in 2012 with an epidural mass, diagnosed as a diffuse large B-cell lymphoma (DLBCL) with concurrent low grade follicular lymphoma. Three years later, the patient presented with a cervical mass, diagnosed as a lymphoblastic lymphoma (LBL). Both the DLBCL and LBL contained a "triple hit" with BCL2, BCL6 and cMYC translocations demonstrated by fluorescence in situ hybridization analysis and a complex karyotype by SNP-array analysis...
November 17, 2016: Human Pathology
https://www.readbyqxmd.com/read/27823568/pharmacological-histone-deacetylation-segregates-distinct-regulators-of-transcription
#7
Haloom Rafehi, Tom C Karagiannis, Assam El-Osta
INTRODUCTION: Histone deacetylase (HDAC) enzymes control the acetylation status of transcription factors that regulate chromatin structure and gene function. The transcriptional regulatory factors that distinguish histone acetylation and deacetylation patterns by pharmacological HDAC inhibition (HDACi) have been studied. METHODS: We analysed sequencing datasets derived from human aortic endothelial cells (HAECs) stimulated with the HDAC inhibitors, Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA)...
November 4, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27811009/penfluridol-represses-integrin-expression-in-breast-cancer-through-induction-of-reactive-oxygen-species-and-downregulation-of-sp-transcription-factors
#8
Erik Hedrick, Xi Li, Stephen Safe
It was recently demonstrated the penfluridol inhibited breast tumor growth and metastasis and this was associated with downregulation of α6- and β4-integrins. In this study, we observed the penfluridol induced reactive oxygen species (ROS) and this was the primary mechanism of action. Penfluridol-mediated growth inhibition, induction of apoptosis, and inhibition breast cancer cell migration was attenuated after cotreatment with glutathione (GSH). Penfluridol also downregulated Sp transcription factors Sp1, Sp3 and Sp4 through epigenetic downregulation of cMyc and cMyc-regulated microRNAs (miR-27a and miR-20a/miR-17) and induction of the miR-regulated Sp transcriptional repressors ZBTB10 and ZBTB4...
November 3, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27795300/eya1-s-conformation-specificity-in-dephosphorylating-phosphothreonine-in-myc-and-its-activity-on-myc-stabilization-in-breast-cancer
#9
Jun Li, Yoel Rodriguez, Chunming Cheng, Lei Zeng, Elaine Y M Wong, Chelsea Y Xu, Ming-Ming Zhou, Pin-Xian Xu
EYA1 is known to be overexpressed in human breast cancer in which Myc protein is also accumulated in association with decreased phospho-T58 levels. We have recently reported that EYA1 functions as a unique protein phosphatase to dephosphorylate Myc at phosphor-T58 to regulate Myc levels. However, it remains unclear whether EYA1-mediated Myc dephosphorylation on T58 1 is a critical function in regulating Myc protein stability in breast cancer. Furthermore, EYA1's substrate specificity has remained elusive. In this study, we have investigated these questions and here we report that depletion of EYA1 using shRNA in breast cancer cells destabilizes Myc protein and increases pT58 levels, leading to an increase in doubling time and impairment of cell cycle progression...
October 17, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27789397/generation-of-human-ips-cell-line-ctl07-ii-from-human-fibroblasts-under-defined-and-xeno-free-conditions
#10
Malin Kele, Kelly Day, Harriet Rönnholm, Jens Schuster, Niklas Dahl, Anna Falk
CTL07-II is a healthy feeder-free and characterized human induced pluripotent stem (iPS) cell line. Cultured under xeno-free and defined conditions. The line is generated from healthy human fibroblasts with non-integrating Sendai virus vectors encoding the four Yamanaka factors, OCT4, SOX2, KLF4 and cMYC. The generated iPS cells are free from reprogramming vectors and their purity, karyotypic stability and pluripotent capacity is confirmed.
September 30, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27766528/wnt-signaling-inhibitor-fh535-selectively-inhibits-cell-proliferation-and-potentiates-imatinib-induced-apoptosis-in-myeloid-leukemia-cell-lines
#11
Kran Suknuntha, Thanyatip Thita, Padma Priya Togarrati, Piyanee Ratanachamnong, Patompon Wongtrakoongate, Sirada Srihirun, Igor Slukvin, Suradej Hongeng
Wnt signaling pathway plays a major role in leukemogenesis of myeloid leukemia. Aberrancy in its regulation results in hyperactivity of the pathway contributing to leukemia propagation and maintenance. To investigate effects of Wnt pathway inhibition in leukemia, we used human leukemia cell lines (i.e., K562, HL60, THP1, and Jurkat) and several Wnt inhibitors, including XAV939, IWP2 and FH535. Our results showed that leukemia cell lines (>95 % cells) had increased endogenous levels of β-catenin as compared to mononuclear cells from healthy donors (0 %)...
October 20, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27746612/silibinin-inhibits-proliferation-and-migration-of-human-hepatic-stellate-lx-2-cells
#12
Devaraj Ezhilarasan, Jonathan Evraerts, Sid Brice, Pedro Buc-Calderon, Sivanesan Karthikeyan, Etienne Sokal, Mustapha Najimi
BACKGROUND: Proliferation of hepatic stellate cells (HSCs) play pivotal role in the progression of hepatic fibrosis consequent to chronic liver injury. Silibinin (SBN), a flavonoid compound, has shown to possess cell cycle arresting potential against many actively proliferating cancers cell lines. The objective of this study was to evaluate the anti-proliferative and cell cycle arresting properties of SBN in rapidly proliferating human hepatic stellate LX-2 cell line. METHODS: LX-2 cells were fed with culture medium supplemented with different concentrations of SBN (10, 50 and 100 μM)...
September 2016: Journal of Clinical and Experimental Hepatology
https://www.readbyqxmd.com/read/27742621/tsp1-cd47-signaling-is-upregulated-in-clinical-pulmonary-hypertension-and-contributes-to-pulmonary-arterial-vasculopathy-and-dysfunction
#13
Natasha M Rogers, Maryam Sharifi-Sanjani, Mingyi Yao, Kedar Ghimire, Raquel Bienes-Martinez, Stephanie M Mutchler, Heather E Knupp, Jeffrey Baust, Enrico M Novelli, Mark Ross, Claudette St Croix, Johannes C Kutten, Caitlin A Czajka, John C Sembrat, Mauricio Rojas, David Labrousse-Arias, Timothy N Bachman, Rebecca R Vanderpool, Brian S Zuckerbraun, Hunter C Champion, Ana L Mora, Adam C Straub, Richard A Bilonick, Maria J Calzada, Jeffrey S Isenberg
AIMS: Thrombospondin-1 (TSP1) is a ligand for CD47 and TSP1(-/-) mice are protected from pulmonary hypertension (PH). We hypothesized the TSP1-CD47 axis is upregulated in human PH and promotes pulmonary arterial vasculopathy. METHODS AND RESULTS: We analyzed the molecular signature and functional response of lung tissue and distal pulmonary arteries (PAs) from individuals with (n=23) and without (n=16) PH. Compared to controls, lungs and distal PAs from PH patients showed induction of TSP1-CD47 and endothelin-1/endothelin A receptor (ET-1/ETA) protein and mRNA...
October 13, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27738323/synergistic-targeting-of-sp1-a-critical-transcription-factor-for-myeloma-cell-growth-and-survival-by-panobinostat-and-proteasome-inhibitors
#14
Ariunzaya Bat-Erdene, Hirokazu Miki, Asuko Oda, Shingen Nakamura, Jumpei Teramachi, Ryota Amachi, Hirofumi Tenshin, Masahiro Hiasa, Masami Iwasa, Takeshi Harada, Shiro Fujii, Kimiko Sogabe, Kumiko Kagawa, Sumiko Yoshida, Itsuro Endo, Kenichi Aihara, Masahiro Abe
Panobinostat, a pan-deacetylase inhibitor, synergistically elicits cytotoxic activity against myeloma (MM) cells in combination with the proteasome inhibitor bortezomib. Because precise mechanisms for panobinostat's anti-MM action still remain elusive, we aimed to clarify the mechanisms of anti-MM effects of panobinostat and its synergism with proteasome inhibitors. Although the transcription factor Sp1 was overexpressed in MM cells, the Sp1 inhibitor terameprocol induced MM cell death in parallel with reduction of IRF4 and cMyc...
October 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27698814/effect-of-api-1-and-fr180204-on-cell-proliferation-and-apoptosis-in-human-dld-1-and-lovo-colorectal-cancer-cells
#15
Atiye Seda Yar Saglam, Ebru Alp, Zubeyir Elmazoglu, Emine Sevda Menevse
The activation of the phosphatidylinositol-3 kinase/v-akt murine thymoma viral oncogene homolog (Akt) and mitogen activated protein kinase kinase/extracellular signal-regulated kinase (ERK) pathways are implicated in the majority of cancers. Selective inhibition of Akt and ERK represents a potential approach for cancer therapy. Therefore, the present study aimed to investigate the apoptotic and anti-proliferative effects of the novel and selective Akt inhibitor 4-amino-5,8-dihydro-5-oxo-8-β-D-ribofuranosyl-pyrido[2,3-d]pyrimidine-6-carboxamide (API-1) and selective ERK1/2 inhibitor FR180204 (FR) alone and in combination on colorectal cancer (CRC) cells (DLD-1 and LoVo)...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27558600/integration-free-t-cell-derived-human-induced-pluripotent-stem-cells-ipscs-from-a-patient-with-recessive-dystrophic-epidermolysis-bullosa-rdeb-carrying-two-compound-heterozygous-mutations-in-the-col7a1-gene
#16
Munenari Itoh, Shiho Kawagoe, Katsuto Tamai, Hirotaka James Okano, Hidemi Nakagawa
Expanded human T cells from a Japanese female with recessive dystrophic epidermolysis bullosa (RDBE) were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, RDEB-iPSC26, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layer. RDEB-iPSC26 may be a useful cell resource for the establishment of in vitro RDEB modeling and the study for developing gene and cell therapy...
May 17, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27558599/integration-free-t-cell-derived-human-induced-pluripotent-stem-cells-ipscs-from-a-healthy-individual-wt-ipsc1
#17
Munenari Itoh, Shiho Kawagoe, Hirotaka James Okano, Hidemi Nakagawa
Expanded human T cells from a Japanese healthy male were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, WT-iPSC1, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layers. WT-iPSC1 may be a useful cell resource as a normal control for the comparative study using disease-specific iPSCs...
May 11, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27558598/integration-free-t-cell-derived-human-induced-pluripotent-stem-cells-ipscs-from-a-healthy-individual-wt-ipsc4
#18
Munenari Itoh, Shiho Kawagoe, Hirotaka James Okano, Hidemi Nakagawa
Expanded human T cells from a Japanese healthy male were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, WT-iPSC4, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layer. WT-iPSC4 may be a useful cell resource as a normal control for the comparative study using disease-specific iPSCs...
May 11, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27558597/integration-free-t-cell-derived-human-induced-pluripotent-stem-cells-ipscs-from-a-healthy-individual-wt-ipsc2
#19
Munenari Itoh, Shiho Kawagoe, Hirotaka James Okano, Hidemi Nakagawa
Expanded human T cells from a Japanese healthy male were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, WT-iPSC2, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layer. WT-iPSC2 may be a useful cell resource as a normal control for the comparative study using disease-specific iPSCs...
May 11, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27558426/an-essential-role-of-ini1-hsnf5-chromatin-remodeling-protein-in-hiv-1-posttranscriptional-events-and-gag-gag-pol-stability
#20
Annalena La Porte, Jennifer Cano, Xuhong Wu, Doyel Mitra, Ganjam V Kalpana
: INI1/hSNF5/SMARCB1/BAF47 is an HIV-specific integrase (IN)-binding protein that influences HIV-1 transcription and particle production. INI1 binds to SAP18 (Sin3a-associated protein, 18 kDa), and both INI1 and SAP18 are incorporated into HIV-1 virions. To determine the significance of INI1 and the INI1-SAP18 interaction during HIV-1 replication, we isolated a panel of SAP18-interaction-defective (SID)-INI1 mutants using a yeast reverse two-hybrid screen. The SID-INI1 mutants, which retained the ability to bind to IN, cMYC, and INI1 but were impaired for binding to SAP18, were tested for their effects on HIV-1 particle production...
November 1, 2016: Journal of Virology
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