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https://www.readbyqxmd.com/read/29913166/characterization-of-canonical-wnt-signalling-changes-after-induced-disruption-of-m%C3%A3-ller-cell-in-murine-retina
#1
Ling Zhu, Weiyong Shen, Ting Zhang, Ying Wang, Bobak Bahrami, Fanfan Zhou, Mark C Gillies
Müller cells are the primary glia in the retina, playing a critical role in retinal homeostasis and retinal pathology. This study evaluated the canonical Wnt signalling pathway and its downstream effects on retinal degeneration in a transgenic mouse model of inducible Müller cell disruption. Increased expression of the LacZ reporter gene in the retina suggested Wnt signalling had been activated after induced Müller cell disruption. Activation was validated by observing nuclear translocation of β-Catenin...
June 15, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29912936/low-dose-ionizing-radiation-exposure-represses-the-cell-cycle-and-protein-synthesis-pathways-in-in-vitro-human-primary-keratinocytes-and-u937-cell-lines
#2
Kazumasa Sekihara, Kaori Saitoh, Haeun Yang, Haruki Kawashima, Saiko Kazuno, Mika Kikkawa, Hajime Arai, Takashi Miida, Nobuhiro Hayashi, Keisuke Sasai, Yoko Tabe
The effects of the high-dose ionizing radiation used in radiotherapy have been thoroughly demonstrated in vitro and in vivo. However, the effects of low-dose ionizing radiation (LDIR) such as computed tomography-guided biopsies and X-ray fluoroscopy on skin cells remain controversial. This study investigated the molecular effects of LDIR on the human primary keratinocytes (HPKs) and U937 cells, monocytes-like cell lines. These cells were exposed to 0.1 Gray (Gy) X-ray as LDIR. The modulation of transcription was assessed using a cDNA array, and the protein expression after LDIR exposure was investigated using isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis at 24 hours...
2018: PloS One
https://www.readbyqxmd.com/read/29912438/an-oncolytic-measles-virus-sensitive-group-3-medulloblastoma-model-in-immune-competent-mice
#3
Sangeet Lal, Diego Carrera, Joanna J Phillips, William A Weiss, Corey Raffel
Background: Oncolytic measles virus (MV) is effective in xenograft models of many tumor types in immune-compromised mice. However, no murine cell line exists that is tumorigenic, grows in immune-competent mice, and is killed by MV. The lack of such a model prevents an examination of the effect of the immune system on MV oncotherapy. Methods: Cerebellar stem cells from human CD46-transgenic immunocompetent mice were transduced to express Sendai virus C-protein, murine C-Myc, and Gfi1b proteins...
June 14, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29910852/biochemical-pathway-analysis-of-gastric-atrophy
#4
Mostafa Rezaei Tavirani, Sina Rezaei Tavirani, Fatemeh Tajik Rostami
Aim: Pathway analysis of gastric atrophy to find new molecular prospective of disease. Background: Gastric atrophy as a process which is accompanied with "loss of glans" in stomach can be considered as a risk factor of gastric cancer. Here, the correlated biochemical pathways to the disorder have been analyzed via protein-protein interaction (PPI) network analysis. Methods: The genes related to gastric atrophy were retrieved by STRING database and organized in a network by Cytoscape...
2018: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/29910604/ampk-as160-mediates-tiliroside-derivatives-stimulated-glut4-translocation-in-muscle-cells
#5
Chang Zhang, Yue Jiang, Jia Liu, Meina Jin, Nan Qin, Ying Chen, Wenyan Niu, Hongquan Duan
Introduction: The Chinese herb Potentilla chinensis can reduce blood glucose level of diabetic mice. Tiliroside is the main effective component, but the detailed mechanism is not clear. Skeletal muscles play an important role in whole body glucose homeostasis. Insulin and exercise/contraction stimulate glucose uptake by muscle cells via redistribution of glucose transporter GLUT4 to the cell surface. Materials and methods: We explored the effects of tiliroside derivatives on cell surface GLUT4 level (GLUT4 translocation) and the underlying mechanism in L6-GLUT4 myc muscle cells...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29909985/structural-alterations-driving-castration-resistant-prostate-cancer-revealed-by-linked-read-genome-sequencing
#6
Srinivas R Viswanathan, Gavin Ha, Andreas M Hoff, Jeremiah A Wala, Jian Carrot-Zhang, Christopher W Whelan, Nicholas J Haradhvala, Samuel S Freeman, Sarah C Reed, Justin Rhoades, Paz Polak, Michelle Cipicchio, Stephanie A Wankowicz, Alicia Wong, Tushar Kamath, Zhenwei Zhang, Gregory J Gydush, Denisse Rotem, J Christopher Love, Gad Getz, Stacey Gabriel, Cheng-Zhong Zhang, Scott M Dehm, Peter S Nelson, Eliezer M Van Allen, Atish D Choudhury, Viktor A Adalsteinsson, Rameen Beroukhim, Mary-Ellen Taplin, Matthew Meyerson
Nearly all prostate cancer deaths are from metastatic castration-resistant prostate cancer (mCRPC), but there have been few whole-genome sequencing (WGS) studies of this disease state. We performed linked-read WGS on 23 mCRPC biopsy specimens and analyzed cell-free DNA sequencing data from 86 patients with mCRPC. In addition to frequent rearrangements affecting known prostate cancer genes, we observed complex rearrangements of the AR locus in most cases. Unexpectedly, these rearrangements include highly recurrent tandem duplications involving an upstream enhancer of AR in 70%-87% of cases compared with <2% of primary prostate cancers...
June 11, 2018: Cell
https://www.readbyqxmd.com/read/29907862/publisher-correction-ncor-smrt-co-repressors-cooperate-with-c-myc-to-create-an-epigenetic-barrier-to-somatic-cell-reprogramming
#7
Qiang Zhuang, Wenjuan Li, Christina Benda, Zhijian Huang, Tanveer Ahmed, Ping Liu, Xiangpeng Guo, David P Ibañez, Zhiwei Luo, Meng Zhang, Mazid Md Abdul, Zhongzhou Yang, Jiayin Yang, Yinghua Huang, Hui Zhang, Dehao Huang, Jianguo Zhou, Xiaofen Zhong, Xihua Zhu, Xiuling Fu, Wenxia Fan, Yulin Liu, Yan Xu, Carl Ward, Muhammad Jadoon Khan, Shahzina Kanwal, Bushra Mirza, Micky D Tortorella, Hung-Fat Tse, Jiayu Chen, Baoming Qin, Xichen Bao, Shaorong Gao, Andrew P Hutchins, Miguel A Esteban
In the version of this Article originally published, in Fig. 2c, the '+' sign and 'OSKM' were superimposed in the label '+OSKM'. In Fig. 4e, in the labels, all instances of 'Ant' should have been 'Anti-'. And, in Fig. 7a, the label '0.0' was misplaced; it should have been on the colour scale bar. These figures have now been corrected in the online versions.
June 15, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29907650/jak2-is-dispensable-for-maintenance-of-jak2-mutant-b-cell-acute-lymphoblastic-leukemias
#8
Sang-Kyu Kim, Deborah A Knight, Lisa R Jones, Stephin Vervoort, Ashley P Ng, John F Seymour, James E Bradner, Michaela Waibel, Lev Kats, Ricky W Johnstone
Activating JAK2 point mutations are implicated in the pathogenesis of myeloid and lymphoid malignancies, including high-risk B-cell acute lymphoblastic leukemia (B-ALL). In preclinical studies, treatment of JAK2 mutant leukemias with type I JAK2 inhibitors (e.g., Food and Drug Administration [FDA]-approved ruxolitinib) provided limited single-agent responses, possibly due to paradoxical JAK2Y1007/1008 hyperphosphorylation induced by these agents. To determine the importance of mutant JAK2 in B-ALL initiation and maintenance, we developed unique genetically engineered mouse models of B-ALL driven by overexpressed Crlf2 and mutant Jak2, recapitulating the genetic aberrations found in human B-ALL...
June 15, 2018: Genes & Development
https://www.readbyqxmd.com/read/29907599/aggressive-b-cell-lymphomas-in-patients-with-myelofibrosis-receiving-jak1-2-inhibitor-therapy
#9
Edit Porpaczy, Sabrina Tripolt, Andrea Hoelbl-Kovacic, Bettina Gisslinger, Zsuzsanna Bago-Horvath, Emilio Casanova-Hevia, Emmanuelle Clappier, Thomas Decker, Sabine Fajmann, Daniela A Fux, Georg Greiner, Sinan Gueltekin, Gerwin Heller, Harald Herkner, Gregor Hoermann, Jean-Jacques Kiladjian, Thomas Kolbe, Christoph Kornauth, Maria-Theresa Krauth, Robert Kralovics, Leonhard Muellauer, Mathias Mueller, Michaela Prchal-Murphy, Eva Maria Putz, Emmanuel Raffoux, Ana-Iris Schiefer, Klaus Schmetterer, Christine Schneckenleithner, Ingrid Simonitsch-Klupp, Cathrin Skrabs, Wolfgang R Sperr, Philipp Bernhard Staber, Birgit Strobl, Peter Valent, Ulrich Jaeger, Heinz Gisslinger, Veronika Sexl
Inhibition of Janus-kinase 1/2 (JAK1/2) is a mainstay to treat myeloproliferative neoplasms (MPN). Sporadic observations reported the co-incidence of B-cell non-Hodgkin lymphomas during treatment of MPN with JAK1/2 inhibitors. We assessed 626 MPN patients including 69 with myelofibrosis receiving JAK1/2 inhibitors for lymphoma development. B-cell lymphomas evolved in 4/69 patients (5.8%) upon JAK1/2 inhibition compared to 2/557 (0.36%) with conventional treatment (16-fold increased risk). A similar 15-fold increase was observed in an independent cohort of 929 MPN patients...
June 14, 2018: Blood
https://www.readbyqxmd.com/read/29907594/repositioning-dopamine-d2-receptor-agonist-bromocriptine-to-enhance-docetaxel-chemotherapy-and-treat-bone-metastatic-prostate-cancer
#10
Yang Yang, Kenza Mamouni, Xin Li, Yanhua Chen, Sravan Kavuri, Yuhong Du, Haian Fu, Omer Kucuk, Daqing Wu
Docetaxel resistance remains a major obstacle in the treatment of prostate cancer (PCa) bone metastasis. In this study, we demonstrate that the dopamine D2 receptor (DRD2) agonist bromocriptine effectively enhances docetaxel efficacy and suppresses skeletal growth of PCa in preclinical models. DRD2 is ubiquitously expressed in PCa cell lines, and DRD2 is significantly reduced in PCa tissues with high Gleason score. Bromocriptine has weak to moderate cytotoxicity in PCa cells, but effectively induces cell cycle arrest...
June 15, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29906487/deferoxamine-suppresses-esophageal-squamous-cell-carcinoma-cell-growth-via-erk1-2-mediated-mitochondrial-dysfunction
#11
Linhua Lan, Wei Wei, Ying Zheng, Lili Niu, Xiaoling Chen, Dawei Huang, Yang Gao, Shouyong Mo, Jin Lu, Miaomiao Guo, Yongzhang Liu, Bin Lu
Deferoxamine (DFO) was found to modulate multiple cellular pathways involved in the growth of breast cancer, hepatocellular carcinoma, lung cancer and bladder cancer. However, the effect of DFO on esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we report that DFO-treated ESCC cells show strong anti-tumorigenic properties, such as inhibition of cell proliferation, induction of cell cycle arrest, and promotion of apoptosis. Mechanistically, DFO significantly activated ERK1/2 signaling, which is reactive oxygen species (ROS)-dependent...
June 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29906246/o-glycosylation-mediated-signaling-circuit-drives-metastatic-castration-resistant-prostate-cancer
#12
Sheue-Fen Tzeng, Chin-Hsien Tsai, Tai-Kuang Chao, Yu-Ching Chou, Yu-Chih Yang, Mong-Hsun Tsai, Tai-Lung Cha, Pei-Wen Hsiao
Disseminated castration-resistant prostate cancer (CRPC) is a common disease in men that is characterized by limited survival and resistance to androgen-deprivation therapy. The increase in human epidermal growth factor receptor 2 (HER2) signaling contributes to androgen receptor activity in a subset of patients with CRPC; however, enigmatically, HER2-targeted therapies have demonstrated a lack of efficacy in patients with CRPC. Aberrant glycosylation is a hallmark of cancer and involves key processes that support cancer progression...
June 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29904909/inactivation-of-tp53-and-pten-drives-rapid-development-of-pleural-and-peritoneal-malignant-mesotheliomas
#13
Eleonora Sementino, Craig W Menges, Yuwaraj Kadariya, Suraj Peri, Jinfei Xu, Zemin Liu, Richard G Wilkes, Kathy Q Cai, Frank J Rauscher, Andres J Klein-Szanto, Joseph R Testa
Malignant mesothelioma (MM) is a therapy-resistant cancer arising primarily from the lining of the pleural and peritoneal cavities. The most frequently altered genes in human MM are cyclin-dependent kinase inhibitor 2A (CDKN2A), which encodes components of the p53 (p14ARF) and RB (p16INK4A) pathways, BRCA1-associated protein 1 (BAP1), and neurofibromatosis 2 (NF2). Furthermore, the p53 gene (TP53) itself is mutated in ~15% of MMs. In many MMs, the PI3K-PTEN-AKT-mTOR signaling node is hyperactivated, which contributes to tumor cell survival and therapeutic resistance...
June 15, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29903764/inferior-survival-in-high-grade-b-cell-lymphoma-with-myc-and-bcl2-and-or-bcl6-rearrangements-is-not-associated-with-myc-ig-gene-rearrangements
#14
Ellen D McPhail, Matthew J Maurer, William R Macon, Andrew L Feldman, Paul J Kurtin, Rhett P Ketterling, Rakhee Vaidya, James R Cerhan, Stephen M Ansell, Luis F Porrata, Grzegorz S Nowakowski, Thomas E Witzig, Thomas M Habermann
High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-/triple-hit lymphoma) has an aggressive clinical course. We investigated prognostic value of transformation from low-grade lymphoma, cytologic features (high grade versus large cell), MYC gene rearrangement partners (immunoglobulin versus nonimmunoglobulin gene), and treatment. We evaluated 100 adults with double-/triple-hit lymphoma, reviewing cytologic features; cell of origin; and rearrangements of MYC, BCL2, and BCL6 using MYC, BCL2, and BCL6 break-apart and IGH/MYC, IGL/MYC, IGK/MYC, and IGH/BCL2 dual-fusion interphase fluorescence in situ hybridization probes...
June 14, 2018: Haematologica
https://www.readbyqxmd.com/read/29902866/disulfiram-copper-causes-ros-levels-alteration-cell-cycle-inhibition-and-apoptosis-in-acute-myeloid-leukaemia-cell-lines-with-modulation-in-the-expression-of-related-genes
#15
Saeed Hassani, Parisa Ghaffari, Bahram Chahardouli, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Shaban Alizadeh, Seyed H Ghaffari
The majority of acute myeloid leukaemia (AML) patients will die from their disease or therapy-related complications. There is an inevitable need to improve the survival of AML patients. Previous studies show that disulfiram (DSF), an anti-alcoholism drug with a low toxicity profile, demonstrates anticancer behaviors. Here, we evaluated the cytotoxicity and mechanistic action of DSF on the AML cell lines KG-1, NB4, and U937. The microculture tetrazolium test revealed that DSF alone or in combination with copper (Cu) is highly toxic to the AML cells at concentrations lower than those achievable in the clinical setting, with Cu increasing the DSF-induced inhibition of metabolic activity...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29902745/lymphoblast-derived-integration-free-ipsc-line-ad-trem2-3-from-a-74-year-old-alzheimer-s-disease-patient-expressing-the-trem2-p-r47h-variant
#16
Soraia Martins, Hatice Yigit, Martina Bohndorf, Nina Graffmann, Aurelian Robert Fiszl, Wasco Wruck, Kristel Sleegers, Christine Van Broeckhoven, James Adjaye
Human lymphoblast cells from a male diagnosed with Alzheimer's disease (AD) expressing the TREM2 p.R47H variant were used to generate integration-free induced pluripotent stem cells (iPSCs) by over-expressing episomal-based plasmids harbouring OCT4, SOX2, KLF4, LIN28, L-MYC and p53 shRNA. The derived iPSC line - AD-TREM2-3 was defined as pluripotent based on (i) expression of pluripotency-associated markers (ii) embryoid body-based differentiation into cell types representative of the three germ layers and (iii) the similarity between the transcriptome of the iPSC line and the human embryonic stem cell line H1 with a Pearson correlation of 0...
June 1, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29902576/lymphomas-with-pseudo-double-hit-bcl6-myc-translocations-due-to-t-3-8-q27-q24-are-associated-with-a-germinal-center-immunophenotype-extranodal-involvement-and-frequent-bcl2-translocations
#17
Steven M Johnson, Jayadev Manikkam Umakanthan, Ji Yuan, Yuri Fedoriw, R Gregory Bociek, Kathleen Kaiser-Rogers, Jennifer N Sanmann, Nathan D Montgomery
High-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements, "double hit" or "triple hit" lymphomas (DTHL), are aggressive neoplasms associated with a poor prognosis. A t(3;8)(q27;q24) rarely occurs in B-cell lymphomas that results in a unique "pseudo-double hit" BCL6-MYC fusion, indistinguishable by interphase fluorescence in situ hybridization (FISH) from more conventional DTHL with independent MYC and BCL6 translocations. Reports of t(3;8)(q27;q24) lymphomas are sparse, and to better characterize their pathologic, cytogenetic, and clinical features, 6 new cases from 2 institutions and 19 previously published cases were reviewed...
June 11, 2018: Human Pathology
https://www.readbyqxmd.com/read/29901569/clinicopathologic-features-of-a-series-of-primary-renal-cic-rearranged-sarcomas-with-comprehensive-molecular-analysis
#18
Shamlal Mangray, David R Kelly, Sophie LeGuellec, Eddie Fridman, Sangeeta Aggarwal, Mary Shago, Andres Matoso, Russell Madison, Sharmila Pramanik, Shan Zhong, Rong Li, Kara A Lombardo, Stuart Cramer, Joseph Pressey, Jeffrey S Ross, Robert J Corona, Gennady Bratslavsky, Pedram Argani, Jean-Michel Coindre, Gino R Somers, Siraj M Ali, Evgeny Yakirevich
CIC-rearranged sarcomas rarely occur in visceral organs including the kidney. The most common fusion partner with CIC is the DUX4 gene, but variant fusion partners have also been reported. Herein, we describe the clinicopathologic features and comprehensive molecular profiling of 4 cases of primary renal CIC-rearranged sarcomas. All cases occurred in females, age range 13 to 82 years and included 3 resections and 1 needle biopsy specimen. There was a tendency for development of metastatic disease predominantly to the lungs and poor disease outcome despite different treatment strategies...
June 12, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29901199/fibroblast-growth-factor-18-promotes-the-growth-migration-and-invasion-of-mda%C3%A2-mb%C3%A2-231-cells
#19
Ziyi Yu, Longquan Lou, Yi Zhao
Fibroblast growth factor 18 (FGF18) increases cell motility and invasion in colon tumors, and is linked with ovarian and lung tumors. Furthermore, the increased expression of FGF18 mRNA and protein has been associated with poor overall survival in cancer patients. However, its function has not been investigated in breast cancer. In the present study, we demonstrated that FGF18 promoted cell growth and metastasis in vitro and stimulated tumor growth in xenograft models in vivo. FGF18 mediated the proliferation of MDA‑MB‑231 cells via the ERK/c‑Myc signaling pathway and induced epithelial‑to‑mesenchymal transition (EMT) factors to promote cancer migration and invasion...
June 7, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29900911/canonical-wnt-pathway-gene-expression-and-their-clinical-correlation-in-oral-squamous-cell-carcinoma
#20
Madhulaxmi Marimuthu, Manoharan Andiappan, Abdul Wahab, M R Muthusekhar, Anandan Balakrishnan, Sambandham Shanmugam
Aim: The aim of this study is to explore the prognostic significance and clinicopathological correlations of the Wnt pathway genes in a cohort of surgically treated patients with oral squamous cell carcinoma (OSCC) patients. Settings and Design: A prospective genetic study on patients with OSCC was carried out during the period from July 2014 to January 2016. Informed consent from patients and institutional ethical approval for the study was obtained and the guidelines were strictly followed for collection of samples...
May 2018: Indian Journal of Dental Research: Official Publication of Indian Society for Dental Research
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