keyword
MENU ▼
Read by QxMD icon Read
search

JQ1

keyword
https://www.readbyqxmd.com/read/29767555/protective-effect-of-the-bet-protein-inhibitor-jq1-in-cisplatin-induced-nephrotoxicity
#1
Liping Sun, Jing Liu, Yanggang Yuan, Xinzhou Zhang, Zheng Dong
As a potent chemotherapy drug, cisplatin is also notorious for its side effects including nephrotoxicity in kidneys, presenting a pressing need to identify renoprotective agents. Cisplatin nephrotoxicity involves epigenetic regulations, including changes in histone acetylation. Bromodomain and extra-terminal (BET) proteins are "readers" of the epigenetic code of histone acetylation. Here, we investigated the potential renoprotective effects of JQ1, a small molecule inhibitor of BET proteins. We show that JQ1 significantly ameliorated cisplatin-induced nephrotoxicity in mice as indicated by the measurements of kidney function, histopathology, and renal tubular apoptosis...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29760044/nk-cells-mediate-synergistic-antitumor-effects-of-combined-inhibition-of-hdac6-and-bet-in-a-sclc-preclinical-model
#2
Yan Liu, Yuyang Li, Shengwu Liu, Dennis O Adeegbe, Camilla L Christensen, Max M Quinn, Ruben Dries, Shiwei Han, Kevin Buczkowski, Xiaoen Wang, Ting Chen, Peng Gao, Hua Zhang, Fei Li, Peter S Hammerman, James E Bradner, Steven N Quayle, Kwok-Kin Wong
Small cell lung cancer (SCLC) has the highest malignancy among all lung cancers, exhibiting aggressive growth and early metastasis to distant sites. For 30 years, treatment options for SCLC have been limited to chemotherapy, warranting the need for more effective treatments. Frequent inactivation of TP53 and RB1 as well as histone dysmodifications in SCLC suggest that transcriptional and epigenetic regulations play a major role in SCLC disease evolution. Here we performed a synthetic lethal screen using the BET inhibitor JQ1 and an shRNA library targeting 550 epigenetic genes in treatment-refractory SCLC xenograft models and identified HDAC6 as a synthetic lethal target in combination with JQ1...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29751762/hiv-latency-reversing-agents-act-through-tat-post-translational-modifications
#3
Georges Khoury, Talia M Mota, Shuang Li, Carolin Tumpach, Michelle Y Lee, Jonathan Jacobson, Leigh Harty, Jenny L Anderson, Sharon R Lewin, Damian F J Purcell
BACKGROUND: Different classes of latency reversing agents (LRAs) are being evaluated to measure their effects in reactivating HIV replication from latently infected cells. A limited number of studies have demonstrated additive effects of LRAs with the viral protein Tat in initiating transcription, but less is known about how LRAs interact with Tat, particularly through basic residues that may be post-translationally modified to alter the behaviour of Tat for processive transcription and co-transcriptional RNA processing...
May 11, 2018: Retrovirology
https://www.readbyqxmd.com/read/29748248/bromodomain-protein-brd4-is-increased-in-human-placentas-from-women-with-early-onset-preeclampsia
#4
Stella Liong, Gillian Barker, Martha Lappas
Preeclampsia affects 5% of all pregnancies and is a serious disorder of pregnancy, characterised by high maternal blood pressure, placental hypoxia, fluid retention (oedema) and proteinuria. Women with preeclampsia are associated with exaggerated levels of pro-inflammatory cytokines, chemokines and anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFLT1). Studies in non-gestational tissues have described the bromodomain (BRD) and extraterminal family of proteins, in particular BRD4 to play a critical role in propagating inflammation and is currently a therapeutic target for treating cancer, lung inflammation and asthma...
June 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29716963/plk1-inhibition-enhances-the-efficacy-of-bet-epigenetic-reader-blockade-in-castration-resistant-prostate-cancer
#5
Fengyi Mao, Jie Li, Qian Luo, Ruixin Wang, Yifan Kong, Colin Carlock, Zian Liu, Bennett D Elzey, Xiaoqi Liu
Polo-like kinase 1 (Plk1), a crucial regulator of cell cycle progression, is overexpressed in multiple types of cancers, and has been proven to be a potent and promising target for cancer treatment. In case of prostate cancer, we once showed that anti-neoplastic activity of Plk1 inhibitor is largely due to inhibition of androgen receptor (AR) signaling. However, we also discovered that Plk1 inhibition causes activation of the β-catenin pathway and increased ex-pression of c-Myc, eventually resulting in resistance to Plk1 inhibition...
May 1, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29709701/co-targeting-of-bet-proteins-and-hdacs-as-a-novel-approach-to-trigger-apoptosis-in-rhabdomyosarcoma-cells
#6
Julius C Enßle, Cathinka Boedicker, Marek Wanior, Meike Vogler, Stefan Knapp, Simone Fulda
Histone acetylation marks exert essential functions in regulating gene expression. These marks are written by histone acetyltransferases (HATs), removed by histone deacetylases (HDACs) and read by e.g. BET proteins. While BET inhibitors are promising new anticancer drugs, little is yet known on their antitumor activity in rhabdomyosarcoma (RMS). We therefore investigated the efficacy of the prototypic BET inhibitor JQ1 alone or in combination with other epigenetic modifiers, namely HDAC inhibitors (HDACIs)...
April 27, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29703820/insulin-like-growth-factor-2-mrna-binding-protein-3-is-a-novel-post-transcriptional-regulator-of-ewing-sarcoma-malignancy
#7
Caterina Mancarella, Michela Pasello, Selena Ventura, Andrea Grilli, Linda Calzolari, Lisa Toracchio, Pier Luigi Lollini, Davide Maria Donati, Piero Picci, Stefano Ferrari, Katia Scotlandi
PURPOSE: Large-scale sequencing studies have indicated that besides genomic alterations, the post-transcriptional regulation of gene expression or epigenetic mechanisms largely influences the clinical behavior of Ewing sarcoma (ES). We investigated the significance of the RNA-binding protein IGF2BP3 in the regulation of ES aggressiveness. EXPERIMENTAL DESIGN:  Explorative study was performed in 15 patients with localized ES using RNAseq. Next, 128 patients with localized ES were divided into two cohorts...
April 27, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29699387/the-bromodomain-inhibitor-jq1-enhances-the-responses-to-all-trans-retinoic-acid-in-hl-60-and-mv4-11-leukemia-cells
#8
Changhee Kang, C-Yoon Kim, Hyuk Soon Kim, Se-Pill Park, Hyung-Min Chung
All- trans retinoic acid (ATRA) is a highly effective treatment for acute promyelocytic leukemia (APL), a cytogenetically distinct subtype of acute myeloid leukemia (AML). However, ATRA-based treatment is not effective in other subtypes of AML. In non-APL AML, ATRA signaling pathway is impaired or downmodulated, and consequently fails to respond to pharmacological doses of ATRA. Therefore, complementary treatment strategies are needed to improve ATRA responsiveness in non-APL AML. In this study, we investigated the combined effect of ATRA and bromodomain inhibitor JQ1, proven to have potent anti-cancer activity mainly through inhibition of c-Myc...
April 30, 2018: International Journal of Stem Cells
https://www.readbyqxmd.com/read/29670088/a-cancer-vaccine-mediated-postoperative-immunotherapy-for-recurrent-and-metastatic-tumors
#9
Tingting Wang, Dangge Wang, Haijun Yu, Bing Feng, Fangyuan Zhou, Hanwu Zhang, Lei Zhou, Shi Jiao, Yaping Li
Vaccines to induce effective and sustained antitumor immunity have great potential for postoperative cancer therapy. However, a robust cancer vaccine simultaneously eliciting tumor-specific immunity and abolishing immune resistance continues to be a challenge. Here we present a personalized cancer vaccine (PVAX) for postsurgical immunotherapy. PVAX is developed by encapsulating JQ1 (a BRD4 inhibitor) and indocyanine green (ICG) co-loaded tumor cells with a hydrogel matrix. Activation of PVAX by 808 nm NIR laser irradiation significantly inhibits the tumor relapse by promoting the maturation of dendritic cells and eliciting tumor infiltration of cytotoxic T lymphocytes...
April 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29644114/super-enhancer-inhibitors-suppress-myc-driven-transcriptional-amplification-and-tumor-progression-in-osteosarcoma
#10
Demeng Chen, Zhiqiang Zhao, Zixin Huang, Du-Chu Chen, Xin-Xing Zhu, Yi-Ze Wang, Ya-Wei Yan, Shaojun Tang, Subha Madhavan, Weiyi Ni, Zhan-Peng Huang, Wen Li, Weidong Ji, Huangxuan Shen, Shuibin Lin, Yi-Zhou Jiang
Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factors in osteosarcoma and development of better, effective therapeutic approaches are in urgent need for better treatment of osteosarcoma patients. In this study, we uncovered that the oncogene MYC is significantly upregulated in metastastic osteosarcoma samples. In addition, high MYC expression is associated with poor survival of osteosarcoma patients...
2018: Bone Research
https://www.readbyqxmd.com/read/29642934/correlation-of-gene-expression-and-associated-mutation-profiles-of-apobec3a-apobec3b-rev1-ung-and-fhit-with-chemosensitivity-of-cancer-cell-lines-to-drug-treatment
#11
Suleyman Vural, Richard Simon, Julia Krushkal
BACKGROUND: The APOBEC gene family of cytidine deaminases plays important roles in DNA repair and mRNA editing. In many cancers, APOBEC3B increases the mutation load, generating clusters of closely spaced, single-strand-specific DNA substitutions with a characteristic hypermutation signature. Some studies also suggested a possible involvement of APOBEC3A, REV1, UNG, and FHIT in molecular processes affecting APOBEC mutagenesis. It is important to understand how mutagenic processes linked to the activity of these genes may affect sensitivity of cancer cells to treatment...
April 11, 2018: Human Genomics
https://www.readbyqxmd.com/read/29567778/bet-inhibition-by-jq1-promotes-proliferation-and-self-renewal-capacity-of-hematopoietic-stem-cells
#12
Mark Wroblewski, Marina Scheller-Wendorff, Florian Udonta, Raimund Bauer, Jara Schlichting, Lin Zhao, Isabel Ben Batalla, Victoria Gensch, Sarina Päsler, Lei Wu, Marek Wanior, Hanna Taipaleenmäki, Simona Bolamperti, Zeynab Najafova, Klaus Pantel, Carsten Bokemeyer, Jun Qi, Eric Hesse, Stefan Knapp, Steven Johnsen, Sonja Loges
Although inhibitors of bromodomain and extra terminal domain (BET) proteins show promising clinical activity in different hematologic malignancies, a systematic analysis of the consequences of pharmacological BET inhibition on healthy hematopoietic (stem) cells is outstanding. We found that JQ1 treatment decreases the numbers of pre-, immature and mature B cells while numbers of early pro-B cells remain constant. In addition, it increases apoptosis in T cells, all together leading to reduced cellularity in thymus, bone marrow and spleen...
March 22, 2018: Haematologica
https://www.readbyqxmd.com/read/29567272/the-bet-inhibitor-incb054329-reduces-homologous-recombination-efficiency-and-augments-parp-inhibitor-activity-in-ovarian-cancer
#13
Andrew J Wilson, Matthew Stubbs, Phillip Liu, Bruce Ruggeri, Dineo Khabele
OBJECTIVE: Homologous recombination (HR)-proficient ovarian tumors have poorer clinical outcomes and show resistance to poly ADP ribose polymerase inhibitors (PARPi). A subset of HR-proficient ovarian tumors show amplification in bromodomain and extra-terminal (BET) genes such as BRD4. We aimed to test the hypothesis that BRD4 inhibition sensitizes ovarian cancer cells to PARPi by reducing HR efficiency and increasing DNA damage. METHODS: HR-proficient ovarian cancer cell lines (OVCAR-3, OVCAR-4, SKOV-3, UWB1...
March 20, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29563491/rna-cytosine-methylation-and-methyltransferases-mediate-chromatin-organization-and-5-azacytidine-response-and-resistance-in-leukaemia
#14
Jason X Cheng, Li Chen, Yuan Li, Adam Cloe, Ming Yue, Jiangbo Wei, Kenneth A Watanabe, Jamile M Shammo, John Anastasi, Qingxi J Shen, Richard A Larson, Chuan He, Michelle M Le Beau, James W Vardiman
The roles of RNA 5-methylcytosine (RNA:m5 C) and RNA:m5 C methyltransferases (RCMTs) in lineage-associated chromatin organization and drug response/resistance are unclear. Here we demonstrate that the RCMTs, namely NSUN3 and DNMT2, directly bind hnRNPK, a conserved RNA-binding protein. hnRNPK interacts with the lineage-determining transcription factors (TFs), GATA1 and SPI1/PU.1, and with CDK9/P-TEFb to recruit RNA-polymerase-II at nascent RNA, leading to formation of 5-Azacitidine (5-AZA)-sensitive chromatin structure...
March 21, 2018: Nature Communications
https://www.readbyqxmd.com/read/29555663/targeting-bromodomain-and-extra-terminal-bet-family-proteins-in-castration-resistant-prostate-cancer-crpc
#15
Jonathan Welti, Adam Sharp, Wei Yuan, David Dolling, Daniel Nava Rodrigues, Ines Figueiredo, Veronica Gil, Antje Neeb, Matthew Clarke, George Seed, Mateus Crespo, Semini Sumanasuriya, Jian Ning, Eleanor Knight, Jeffrey C Francis, Ashley Hughes, Wendy S Halsey, Alec Paschalis, Ram S Mani, Ganesh V Raj, Stephen R Plymate, Suzanne Carreira, Gunther Boysen, Arul M Chinnaiyan, Amanda Swain, Johann S de Bono
Purpose: Persistent androgen receptor (AR) signaling drives castration-resistant prostate cancer (CRPC) and confers resistance to AR-targeting therapies. Novel therapeutic strategies to overcome this are urgently required. We evaluated how bromodomain and extra-terminal (BET) protein inhibitors (BETi) abrogate aberrant AR signaling in CRPC. Experimental Design: We determined associations between BET expression, AR-driven transcription, and patient outcome; and the effect and mechanism by which chemical BETi (JQ1 and GSK1210151A; I-BET151) and BET family protein knockdown regulates AR-V7 expression and AR signaling in prostate cancer models...
March 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29551266/multiplexed-proteome-dynamics-profiling-reveals-mechanisms-controlling-protein-homeostasis
#16
Mikhail M Savitski, Nico Zinn, Maria Faelth-Savitski, Daniel Poeckel, Stephan Gade, Isabelle Becher, Marcel Muelbaier, Anne J Wagner, Katrin Strohmer, Thilo Werner, Stephanie Melchert, Massimo Petretich, Anna Rutkowska, Johanna Vappiani, Holger Franken, Michael Steidel, Gavain M Sweetman, Omer Gilan, Enid Y N Lam, Mark A Dawson, Rab K Prinjha, Paola Grandi, Giovanna Bergamini, Marcus Bantscheff
Protein degradation plays important roles in biological processes and is tightly regulated. Further, targeted proteolysis is an emerging research tool and therapeutic strategy. However, proteome-wide technologies to investigate the causes and consequences of protein degradation in biological systems are lacking. We developed "multiplexed proteome dynamics profiling" (mPDP), a mass-spectrometry-based approach combining dynamic-SILAC labeling with isobaric mass tagging for multiplexed analysis of protein degradation and synthesis...
March 3, 2018: Cell
https://www.readbyqxmd.com/read/29545201/bromodomain-and-extraterminal-bet-proteins-regulate-hepatocyte-proliferation-in-hepatocyte-driven-liver-regeneration
#17
Jacquelyn O Russell, Sungjin Ko, Harvinder S Saggi, Sucha Singh, Minakshi Poddar, Donghun Shin, Satdarshan P Monga
Bromodomain and extraterminal (BET) proteins recruit key components of basic transcriptional machinery to promote gene expression. Aberrant expression and mutations in BET genes have been identified in many malignancies. Small molecule inhibitors of BET proteins such as JQ1 have shown efficacy in preclinical cancer models, including affecting growth of hepatocellular carcinoma. BET proteins also regulate cell proliferation in nontumor settings. We recently showed that BET proteins regulate cholangiocyte-driven liver regeneration...
March 12, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29490948/yap1-mediated-suppression-of-usp31-enhances-nf%C3%AE%C2%BAb-activity-to-promote-sarcomagenesis
#18
Shuai Ye, Matthew A Lawlor, Adrian Rivera-Reyes, Shaun Egolf, Susan Chor, Koreana Pak, Gabrielle E Ciotti, Avery C Lee, Gloria E Marino, Jennifer Shah, David Niedzwicki, Kristy Weber, Paul M C Park, Md Zahidul Alam, Alison Grazioli, Malay Haldar, Mousheng Xu, Jennifer A Perry, Jun Qi, T S Karin Eisinger-Mathason
To date, no consistent oncogenic driver mutations have been identified in most adult soft tissue sarcomas; these tumors are thus generally insensitive to existing targeted therapies. Here we investigated alternate mechanisms underlying sarcomagenesis to identify potential therapeutic interventions. Undifferentiated pleomorphic sarcoma (UPS) is an aggressive tumor frequently found in skeletal muscle where deregulation of the Hippo pathway and aberrant stabilization of its transcriptional effector yes-associated protein 1 (YAP1) increases proliferation and tumorigenesis...
February 28, 2018: Cancer Research
https://www.readbyqxmd.com/read/29475942/induction-of-autophagy-by-pi3k-mtor-and-pi3k-mtor-brd4-inhibitors-suppresses-hiv-1-replication
#19
Grant R Campbell, Rachel S Bruckman, Shayna D Herns, Shweta Joshi, Donald L Durden, Stephen A Spector
In this study, we investigated the effects of the dual phosphatidylinositol 3-kinase/mechanistic target of rapamycin (PI3K/MTOR) inhibitor dactolisib (NVP-BEZ235), the PI3K/MTOR/bromodomain-containing protein 4 (BRD4) inhibitor SF2523, and the bromodomain and extra terminal domain inhibitor JQ1 on the productive infection of primary macrophages with human immunodeficiency type-1 (HIV). These inhibitors did not alter the initial susceptibility of macrophages to HIV infection. However, dactolisib, JQ1, and SF2523 all decreased HIV replication in macrophages in a dose-dependent manner via degradation of intracellular HIV through autophagy...
April 20, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29472861/1-2-3-4-6-penta-o-galloyl-beta-d-glucopyranoside-inhibits-proliferation-of-multiple-myeloma-cells-accompanied-with-suppression-of-myc-expression
#20
Duurenjargal Tseeleesuren, Rajni Kant, Chia-Hung Yen, Hui-Hua Hsiao, Yi-Ming A Chen
Multiple myeloma (MM) still remains an incurable disease, therefore discovery of novel drugs boosts the therapeutics for MM. The natural compound 1,2,3,4,6-Penta- O -galloyl-beta-D-glucopyranoside (PGG) has been shown to exhibit antitumor activities against various cancer cells. Here, we aim to evaluate antitumor effects of PGG on MM cell lines. PGG inhibited the growth of three different MM cell lines in a dose- and time-dependent manner. Cell cycle analysis revealed that PGG treatment caused cell cycle arrest in G1 phase...
2018: Frontiers in Pharmacology
keyword
keyword
79464
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"