keyword
MENU ▼
Read by QxMD icon Read
search

Myc AND BRD4

keyword
https://www.readbyqxmd.com/read/28391274/inhibition-of-brd4-suppresses-cell-proliferation-and-induces-apoptosis-in-renal-cell-carcinoma
#1
Xinchao Wu, Dong Liu, Xuemei Gao, Fei Xie, Dan Tao, Xingyuan Xiao, Liang Wang, Guosong Jiang, Fuqing Zeng
BACKGROUND/AIMS: Renal cell carcinoma (RCC) remains an intractable genitourinary malignancy. Resistance to chemotherapy or targeted therapies in RCC is presumably due to the complicated underlying molecular mechanisms and insufficient understanding. The aim of this research was to assess the expression and role of bromodomain-4 protein (BRD4) in RCC and evaluate the effects of BRD4 inhibitor JQ1 for RCC treatment. METHODS: BRD4 expressionlevels were assessed by qRT-PCR and western blot in RCC tissues and cells...
April 7, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28369619/histone-deacetylase-class-i-inhibition-promotes-epithelial-gene-expression-in-pancreatic-cancer-cells-in-a-brd4-and-myc-dependent-manner
#2
Vivek Kumar Mishra, Florian Wegwitz, Robyn Laura Kosinsky, Madhobi Sen, Roland Baumgartner, Tanja Wulff, Jens T Siveke, Hans-Ulrich Schildhaus, Zeynab Najafova, Vijayalakshmi Kari, Hella Kohlhof, Elisabeth Hessmann, Steven A Johnsen
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a particularly dismal prognosis. Histone deacetylases (HDAC) are epigenetic modulators whose activity is frequently deregulated in various cancers including PDAC. In particular, class-I HDACs (HDAC 1, 2, 3 and 8) have been shown to play an important role in PDAC. In this study, we investigated the effects of the class I-specific HDAC inhibitor (HDACi) 4SC-202 in multiple PDAC cell lines in promoting tumor cell differentiation. We show that 4SC-202 negatively affects TGFβ signaling and inhibits TGFβ-induced epithelial-to-mesenchymal transition (EMT)...
March 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28281917/brd4-inhibitor-ibet-upregulates-p27kip-cip-protein-stability-in-neuroendocrine-tumor-cells
#3
Lei Wang, Smita Matkar, Gengchen Xie, Chiying An, Xin He, Xiangchen Kong, Xiuheng Liu, Xianxin Hua
The prevalence of neuroendocrine tumors (NETs) has recently been increasing. Although various drugs such as Octreotide and its analogs show certain efficacy, NETs in many patients progress and metastasize. It is desirable to develop new interventions to improve the therapy. Here we show that human neuroendocrine tumor BON cells are resistant to several drugs commonly used for NET therapy, including Octreotide that activates somatostatin receptor-induced anti-proliferation, and Capecitabine and Temozolimide that damage DNA...
March 10, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28249162/bet-bromodomain-inhibitors-engage-the-host-immune-system-and-regulate-expression-of-the-immune-checkpoint-ligand-pd-l1
#4
Simon J Hogg, Stephin J Vervoort, Sumit Deswal, Christopher J Ott, Jason Li, Leonie A Cluse, Paul A Beavis, Phillip K Darcy, Benjamin P Martin, Andrew Spencer, Anna K Traunbauer, Irina Sadovnik, Karin Bauer, Peter Valent, James E Bradner, Johannes Zuber, Jake Shortt, Ricky W Johnstone
BET inhibitors (BETi) target bromodomain-containing proteins and are currently being evaluated as anti-cancer agents. We find that maximal therapeutic effects of BETi in a Myc-driven B cell lymphoma model required an intact host immune system. Genome-wide analysis of the BETi-induced transcriptional response identified the immune checkpoint ligand Cd274 (Pd-l1) as a Myc-independent, BETi target-gene. BETi directly repressed constitutively expressed and interferon-gamma (IFN-γ) induced CD274 expression across different human and mouse tumor cell lines and primary patient samples...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28205554/the-oncoppi-network-of-cancer-focused-protein-protein-interactions-to-inform-biological-insights-and-therapeutic-strategies
#5
Zenggang Li, Andrei A Ivanov, Rina Su, Valentina Gonzalez-Pecchi, Qi Qi, Songlin Liu, Philip Webber, Elizabeth McMillan, Lauren Rusnak, Cau Pham, Xiaoqian Chen, Xiulei Mo, Brian Revennaugh, Wei Zhou, Adam Marcus, Sahar Harati, Xiang Chen, Margaret A Johns, Michael A White, Carlos Moreno, Lee A D Cooper, Yuhong Du, Fadlo R Khuri, Haian Fu
As genomics advances reveal the cancer gene landscape, a daunting task is to understand how these genes contribute to dysregulated oncogenic pathways. Integration of cancer genes into networks offers opportunities to reveal protein-protein interactions (PPIs) with functional and therapeutic significance. Here, we report the generation of a cancer-focused PPI network, termed OncoPPi, and identification of >260 cancer-associated PPIs not in other large-scale interactomes. PPI hubs reveal new regulatory mechanisms for cancer genes like MYC, STK11, RASSF1 and CDK4...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28137841/dual-activity-pi3k-brd4-inhibitor-for-the-orthogonal-inhibition-of-myc-to-block-tumor-growth-and-metastasis
#6
Forest H Andrews, Alok R Singh, Shweta Joshi, Cassandra A Smith, Guillermo A Morales, Joseph R Garlich, Donald L Durden, Tatiana G Kutateladze
MYC is a major cancer driver but is documented to be a difficult therapeutic target itself. Here, we report on the biological activity, the structural basis, and therapeutic effects of the family of multitargeted compounds that simultaneously disrupt functions of two critical MYC-mediating factors through inhibiting the acetyllysine binding of BRD4 and the kinase activity of PI3K. We show that the dual-action inhibitor impairs PI3K/BRD4 signaling in vitro and in vivo and affords maximal MYC down-regulation...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28115161/cg13250-a-novel-bromodomain-inhibitor-suppresses-proliferation-of-multiple-myeloma-cells-in-an-orthotopic-mouse-model
#7
Natsuki Imayoshi, Makoto Yoshioka, Jay Chauhan, Susumu Nakata, Yuki Toda, Steven Fletcher, Jeffrey W Strovel, Kazuyuki Takata, Eishi Ashihara
Multiple myeloma (MM) is characterized by the clonal proliferation of neoplastic plasma cells. Despite a stream of new molecular targets based on better understanding of the disease, MM remains incurable. Epigenomic abnormalities contribute to the pathogenesis of MM. bromodomain 4 (BRD4), a member of the bromodomain and extraterminal (BET) family, binds to acetylated histones during M/G1 transition in the cell cycle promoting progression to S phase. In this study, we investigated the effects of a novel BET inhibitor CG13250 on MM cells...
January 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28073847/identification-of-ccr2-and-cd180-as-robust-pharmacodynamic-tumor-and-blood-biomarkers-for-clinical-use-with-brd4-bet-inhibitors
#8
Tammie C Yeh, Greg O'Connor, Philip Petteruti, Austin Dulak, Maureen Hattersley, J Carl Barrett, Huawei Chen
PURPOSE: AZD5153 is a novel BRD4/BET inhibitor with a distinctive bivalent bromodomain binding mode. To support its clinical development, we identified pharmacodynamic (PD) biomarkers for use in clinical trials to establish target engagement. EXPERIMENTAL DESIGN: CCR2 and CD180 mRNAs, initially identified from whole transcriptome profiling, were further evaluated by quantitative PCR in hematologic cell lines, xenografts, and whole blood from rat, healthy volunteers, and patients with cancer...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28062533/bet-bromodomain-proteins-as-cancer-therapeutic-targets
#9
Shaokun Shu, Kornelia Polyak
Epigenetic regulators are emerging therapeutic targets in a wide variety of human cancers. BET bromodomain proteins have been identified as key regulators of oncogenic transcription factors including MYC; therefore, their inhibition might provide a way to block these "undruggable" targets. Several BET bromodomain inhibitors are in clinical development with promising preliminary findings. However, tumors acquire resistance to these agents in several different ways. In this review, we summarize the role that BET bromodomain proteins play in tumorigenesis as well as the molecular mechanisms underlying therapeutic responses and resistance to their inhibition with emphasis on BRD4 and breast cancer...
January 6, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28042144/novel-bet-protein-proteolysis-targeting-chimera-exerts-superior-lethal-activity-than-bromodomain-inhibitor-beti-against-post-myeloproliferative-neoplasm-secondary-s-aml-cells
#10
D T Saenz, W Fiskus, Y Qian, T Manshouri, K Rajapakshe, K Raina, K G Coleman, A P Crew, A Shen, C P Mill, B Sun, P Qiu, T M Kadia, N Pemmaraju, C DiNardo, M-S Kim, A J Nowak, C Coarfa, C M Crews, S Verstovsek, K N Bhalla
The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. Although the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells...
January 31, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28024472/-effect-of-brd4-inhibitor-gsk525762a-on-proliferation-and-apoptosis-of-sup-b15-cells-in-vitro-and-its-possible-mechanism
#11
Xue Wang, Na Qi, Sha Ma, Zhi-Ling Yan, Qing-Yun Wu, Lin Wang, Chong Chen, Kai-Lin Xu
OBJECTIVE: To investigate the effect of BRD4 inhibitor GSK525762A on the proliferation and apoptosis of Philadelphia chromosome-positive acute lymphoblastic leukemia SUP-B15 cells and its mechanism. METHODS: SUP-B15 cells were treated with different concentration of GSK525762A, the proliferation-inhibition curve was assayed and plotted by CCK-8 method, the cell viability and apoptosis were detected by flow cytometry with Annexin V and 7-AAD staining. The transcripts of anti-apoptotic genes C-MYC, CDK6 and BCL-2 were detected by real-time PCR...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27864512/epstein-barr-virus-super-enhancer-ernas-are-essential-for-myc-oncogene-expression-and-lymphoblast-proliferation
#12
Jun Liang, Hufeng Zhou, Catherine Gerdt, Min Tan, Tyler Colson, Kenneth M Kaye, Elliott Kieff, Bo Zhao
Epstein-Barr virus (EBV) super-enhancers (ESEs) are essential for lymphoblastoid cell (LCL) growth and survival. Reanalyses of LCL global run-on sequencing (Gro-seq) data found abundant enhancer RNAs (eRNAs) being transcribed at ESEs. Inactivation of ESE components, EBV nuclear antigen 2 (EBNA2) and bromodomain-containing protein 4 (BRD4), significantly decreased eRNAs at ESEs -428 and -525 kb upstream of the MYC oncogene transcription start site (TSS). shRNA knockdown of the MYC -428 and -525 ESE eRNA caused LCL growth arrest and reduced cell growth...
December 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27827996/the-bromodomain-and-extra-terminal-domain-bet-family-functional-anatomy-of-bet-paralogous-proteins
#13
REVIEW
Yasushi Taniguchi
The Bromodomain and Extra-Terminal Domain (BET) family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. The mammalian BET family of proteins comprises BRD2, BRD3, BRD4, and BRDT, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code...
November 7, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27769357/clinical-trials-for-bet-inhibitors-run-ahead-of-the-science
#14
REVIEW
Guillaume Andrieu, Anna C Belkina, Gerald V Denis
Several cancer clinical trials for small molecule inhibitors of BET bromodomain proteins have been initiated. There is enthusiasm for the anti-proliferative effect of inhibiting BRD4, one of the targets of these inhibitors, which is thought to cooperate with MYC, a long-desired target for cancer therapeutics. However, no current inhibitor is selective for BRD4 among the three somatic BET proteins, which include BRD2 and BRD3; their respective functions are partially overlapping and none are functionally redundant with BRD4...
March 2016: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/27732564/pharmacological-targeting-of-bet-proteins-inhibits-renal-fibroblast-activation-and-alleviates-renal-fibrosis
#15
Chongxiang Xiong, Monica V Masucci, Xiaoxu Zhou, Na Liu, Xiujuan Zang, Evelyn Tolbert, Ting C Zhao, Shougang Zhuang
Bromodomain and extra-terminal (BET) protein inhibitors have been shown to effectively inhibit tumorgenesis and ameliorate pulmonary fibrosis by targeting bromodomain proteins that bind acetylated chromatin markers. However, their pharmacological effects in renal fibrosis remain unclear. In this study, we examined the effect of I-BET151, a selective and potent BET inhibitor, on renal fibroblast activation and renal fibrosis. In cultured renal interstitial fibroblasts, exposure of cells to I-BET151, or silencing of bromodoma in-containing protein 4 (Brd4), a key BET protein isoform, significantly reduced their activation as indicated by decreased expression of α-smooth muscle actin, collagen 1 and fibronectin...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27707886/exploitation-of-castration-resistant-prostate-cancer-transcription-factor-dependencies-by-the-novel-bet-inhibitor-abbv-075
#16
Emily J Faivre, Denise Wilcox, Xiaoyu Lin, Paul Hessler, Maricel Torrent, Wei He, Tamar Uziel, Daniel H Albert, Keith McDaniel, Warren Kati, Yu Shen
Competitive inhibitors of acetyl-lysine binding to the bromodomains of the BET (bromodomain and extra terminal) family are being developed for the treatment of solid and hematologic malignancies. The function of BET family member BRD4 at enhancers/super-enhancers has been shown to sustain signal-dependent or pathogenic gene expression programs. Here the hypothesis was tested that the transcription factor drivers of castration-resistant prostate cancer (CRPC) clinical progression, including the Androgen Receptor (AR), are critically dependent on BRD4 and thus represent a sensitive solid tumor indication for the BET inhibitor ABBV-075...
October 5, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27682507/discovery-of-a-potent-and-selective-in-vivo-probe-gne-272-for-the-bromodomains-of-cbp-ep300
#17
Terry D Crawford, F Anthony Romero, Kwong Wah Lai, Vickie Tsui, Alexander M Taylor, Gladys de Leon Boenig, Cameron L Noland, Jeremy Murray, Justin Ly, Edna F Choo, Thomas L Hunsaker, Emily W Chan, Mark Merchant, Samir Kharbanda, Karen E Gascoigne, Susan Kaufman, Maureen H Beresini, Jiangpeng Liao, Wenfeng Liu, Kevin X Chen, Zhongguo Chen, Andrew R Conery, Alexandre Côté, Hariharan Jayaram, Ying Jiang, James R Kiefer, Tracy Kleinheinz, Yingjie Li, Jonathan Maher, Eneida Pardo, Florence Poy, Kerry L Spillane, Fei Wang, Jian Wang, Xiaocang Wei, Zhaowu Xu, Zhongya Xu, Ivana Yen, Laura Zawadzke, Xiaoyu Zhu, Steven Bellon, Richard Cummings, Andrea G Cochran, Brian K Albrecht, Steven Magnuson
The single bromodomain of the closely related transcriptional regulators CBP/EP300 is a target of much recent interest in cancer and immune system regulation. A co-crystal structure of a ligand-efficient screening hit and the CBP bromodomain guided initial design targeting the LPF shelf, ZA loop, and acetylated lysine binding regions. Structure-activity relationship studies allowed us to identify a more potent analogue. Optimization of permeability and microsomal stability and subsequent improvement of mouse hepatocyte stability afforded 59 (GNE-272, TR-FRET IC50 = 0...
December 8, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27650498/bromodomain-and-extraterminal-protein-inhibition-blocks-growth-of-triple-negative-breast-cancers-through-the-suppression-of-aurora-kinases
#18
Jennifer M Sahni, Sylvia S Gayle, Kristen L Weber Bonk, Leslie Cuellar Vite, Jennifer L Yori, Bryan Webb, Erika K Ramos, Darcie D Seachrist, Melissa D Landis, Jenny C Chang, James E Bradner, Ruth A Keri
Bromodomain and extraterminal (BET) proteins are epigenetic "readers" that recognize acetylated histones and mark areas of the genome for transcription. BRD4, a BET family member protein, has been implicated in a number of types of cancer, and BET protein inhibitors (BETi) are efficacious in many preclinical cancer models. However, the drivers of response to BETi vary depending on tumor type, and little is known regarding the target genes conveying BETi activity in triple-negative breast cancer (TNBC). Here, we show that BETi repress growth of multiple in vitro and in vivo models of TNBC by inducing two terminal responses: apoptosis and senescence...
November 4, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27573714/jq1-a-small-molecule-inhibitor-of-brd4-suppresses-cell-growth-and-invasion-in-oral-squamous-cell-carcinoma
#19
Limei Wang, Xiuyin Wu, Ping Huang, Zhijun Lv, Yuping Qi, Xiujuan Wei, Pishan Yang, Fenghe Zhang
The present study aimed to evaluate whether bromodomain 4 (BRD4) is expressed in Cal27 cells and to assess the effect of JQ1 on cell proliferation, apoptosis, invasion and BRD4, C-Myc and Twist expression in Cal27 cells. Immunofluorescence staining was used to determine whether BRD4 was expressed in Cal27 cells. Cell viability and proliferation were evaluated using CCK-8 assay. Flow cytometry was used to determine the apoptosis and cell cycle distribution. The cell invasion was evaluated using Transwell plate...
October 2016: Oncology Reports
https://www.readbyqxmd.com/read/27573426/azd5153-a-novel-bivalent-bet-bromodomain-inhibitor-highly-active-against-hematologic-malignancies
#20
Garrett W Rhyasen, Maureen M Hattersley, Yi Yao, Austin Dulak, Wenxian Wang, Philip Petteruti, Ian L Dale, Scott Boiko, Tony Cheung, Jingwen Zhang, Shenghua Wen, Lillian Castriotta, Deborah Lawson, Michael Collins, Larry Bao, Miika J Ahdesmaki, Graeme Walker, Greg O'Connor, Tammie C Yeh, Alfred A Rabow, Jonathan R Dry, Corinne Reimer, Paul Lyne, Gordon B Mills, Stephen E Fawell, Michael J Waring, Michael Zinda, Edwin Clark, Huawei Chen
The bromodomain and extraterminal (BET) protein BRD4 regulates gene expression via recruitment of transcriptional regulatory complexes to acetylated chromatin. Pharmacological targeting of BRD4 bromodomains by small molecule inhibitors has proven to be an effective means to disrupt aberrant transcriptional programs critical for tumor growth and/or survival. Herein, we report AZD5153, a potent, selective, and orally available BET/BRD4 bromodomain inhibitor possessing a bivalent binding mode. Unlike previously described monovalent inhibitors, AZD5153 ligates two bromodomains in BRD4 simultaneously...
November 2016: Molecular Cancer Therapeutics
keyword
keyword
90153
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"