keyword
MENU ▼
Read by QxMD icon Read
search

Cancer AND JQ1

keyword
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
#1
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/27872098/systematic-drug-screening-identifies-tractable-targeted-combination-therapies-in-triple-negative-breast-cancer
#2
Vikram B Wali, Casey G Langdon, Matthew A Held, James T Platt, Gauri A Patwardhan, Anton Safonov, Bilge Aktas, Lajos Pusztai, David F Stern, Christos Hatzis
Triple-negative breast cancer (TNBC) remains an aggressive disease without effective targeted therapies. In this study, we addressed this challenge by testing 128 FDA-approved or investigational drugs as either single agents or in 768 pairwise drug combinations in TNBC cell lines to identify synergistic combinations tractable to clinical translation. Medium-throughput results were scrutinized and extensively analyzed for sensitivity patterns, synergy, anticancer activity and validation in low-throughput experiments...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27864418/ampk-ulk1-mediated-autophagy-confers-resistance-to-bet-inhibitor-jq1-in-acute-myeloid-leukemia-stem-cells
#3
Ji Eun Jang, Ju In Eom, Hoi Kyung Jeung, June-Won Cheong, Jung Yeon Lee, Jin Seok Kim, Yoo Hong Min
PURPOSE: Bromodomain and extraterminal domain (BET) inhibitors are promising epigenetic agents for the treatment of various subsets of acute myeloid leukemia (AML). However, the resistance of leukemia stem cells (LSCs) to BET inhibitors remains a major challenge. In this study, we evaluated the mechanisms underlying LSC resistance to the BET inhibitor JQ1. EXPERIMENTAL DESIGN: We evaluated the levels of apoptosis and autophagy induced by JQ1 in LSC-like leukemia cell lines and primary CD34(+)CD38(-) leukemic blasts obtained from AML cases with normal karyotype without recurrent mutations...
November 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27821592/bromodomain-and-extra-terminal-proteins-bet-inhibitors-suppress-chondrocyte-differentiation-and-restrain-bone-growth
#4
Ningning Niu, Rui Shao, Guang Yan, Weiguo Zou
Small-molecule inhibitors for bromodomain and extra-terminal proteins (BET) have recently emerged as potential therapeutic agents in clinical trials for various cancers. However, to date, it is unknown whether these inhibitors have side effects on bone structures. Here, we report that inhibition of BET bromodomain proteins may suppress chondrocyte differentiation and restrain bone growth. We generated a luciferase reporter system using the chondrogenic cell line, ATDC5, in which the luciferase gene was driven by the promoter of Col2a1, an elementary collagen of chondrocyte...
November 7, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27803105/bet-inhibitors-suppress-aldh-activity-by-targeting-aldh1a1-super-enhancer-in-ovarian-cancer
#5
Yuhki Yokoyama, Hengrui Zhu, Jeong Heon Lee, Andrew V Kossenkov, Sherry Y Wu, Jayamanna M Wickramasinghe, Xiangfan Yin, Katherine C Palozola, Alessandro Gardini, Louise C Showe, Kenneth S Zaret, Qin Liu, David Speicher, Jose R Conejo-Garcia, James E Bradner, Zhiguo Zhang, Anil K Sood, Tamas Ordog, Benjamin G Bitler, Rugang Zhang
The emergence of tumor cells with certain stem-like characteristics, such as high aldehyde dehydrogenase (ALDH) activity due to ALDH1A1 expression, contributes to chemotherapy resistance and tumor relapse. However, clinically applicable inhibitors of ALDH activity have not been reported. There is evidence to suggest that epigenetic regulation of stem-related genes contributes to chemotherapy efficacy. Here, we show that bromodomain and extraterminal (BET) inhibitors suppress ALDH activity by abrogating BRD4-mediated ALDH1A1 expression through a super-enhancer element and its associated enhancer RNA...
November 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27769352/phospho-brd4-transcription-plasticity-and-drug-targeting
#6
REVIEW
Cheng-Ming Chiang
BRD4 is an epigenetic regulator and transcription cofactor whose phosphorylation by CK2 and dephosphorylation by PP2A modulates its function in chromatin targeting, factor recruitment, and cancer progression. While the bromodomains of BET family proteins, including BRD4, BRD2, BRD3 and BRDT, have been the primary targets of small compounds such as JQ1, I-BET and MS417 that show promising anticancer effects against some hematopoietic cancer and solid tumors, drug resistance upon prolonged treatment necessitates a better understanding of alternative pathways underlying not only the resistance but also persistent BET protein dependence for identifying new targets and effective combination therapy strategies...
March 2016: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/27764802/mycl-is-a-target-of-a-bet-bromodomain-inhibitor-jq1-on-growth-suppression-efficacy-in-small-cell-lung-cancer-cells
#7
Fuyumi Kato, Francesco Paolo Fiorentino, Andreu Alibés, Manuel Perucho, Montse Sánchez-Céspedes, Takashi Kohno, Jun Yokota
We aimed to elucidate the effect of JQ1, a BET inhibitor, on small cell lung cancers (SCLCs) with MYCL amplification and/or expression. Fourteen SCLC cell lines, including four with MYCL amplification, were examined for the effects of JQ1 on protein and gene expression by Western blot and mRNA microarray analyses. The sensitivity of SCLC cells to JQ1 was assessed by cell growth and apoptosis assays. MYCL was expressed in all the 14 cell lines, whereas MYC/MYCN expression was restricted mostly to cell lines with gene amplification...
October 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27717711/bet-bromodomain-is-a-novel-regulator-of-taz-and-its-activity
#8
Qiong Duan, Yi Xiao, Lingyan Zhu, Zhenzhen Liu, Xiaoxiao Mao, Zhengxiang Zhou, Chaonan Liao, Jinxing Cai, Fulian Huang, Zehao Liu, Jian Zeng, Ke Xia, Cheng Chang, Jun Qi, Zihua Chen, He Huang, Tianlun Yang
Transcriptional coactivator with PDZ-binding motif (TAZ) is a key transcriptional mediator of Hippo signaling that has been recently reported to mediate Wnt-activated transcription and serve as a component to suppress canonical Wnt/β-catenin activity. The Bromodomain and Extra-terminal domain (BET) family of proteins can recognize the acetylated lysine chain on histones and plays a critical role in transcriptional regulation. However, the mechanisms underlying transcriptional repression by the BET bromodomain are poorly understood...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27678457/the-mapk-pathway-regulates-intrinsic-resistance-to-bet-inhibitors-in-colorectal-cancer
#9
Yufang Ma, Lihong Wang, Leif R Neitzel, Sudan Loganathan, Nan Tang, Lili Qin, Crispi E Emily, Yan Guo, Stefan Knapp, Robert D Beauchamp, Ethan Lee, Jialiang Wang
PURPOSE: The bromodomain and extra-terminal domain (BET) family proteins are epigenetic readers for acetylated histone marks. Emerging BET bromodomain inhibitors have exhibited antineoplastic activities in a wide range of human cancers through suppression of oncogenic transcription factors, including MYC. However, the preclinical activities of BET inhibitors in advanced solid cancers are moderate at best. To improve BET-targeted therapy, we interrogated mechanisms mediating resistance to BET inhibitors in colorectal cancer (CRC)...
September 27, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27651315/brd4-regulates-breast-cancer-dissemination-through-jagged1-notch1-signaling
#10
Guillaume Andrieu, Anna H Tran, Katherine J Strissel, Gerald V Denis
The bromodomain and extraterminal (BET) proteins are epigenetic "readers" of acetylated histones in chromatin and have been identified as promising therapeutic targets in diverse cancers. However, it remains unclear how individual family members participate in cancer progression and small molecule inhibitors such as JQ1 can target functionally independent BET proteins. Here, we report a signaling pathway involving BRD4 and the ligand/receptor pair Jagged1/Notch1 that sustains triple-negative breast cancer migration and invasion...
September 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27626654/bet-bromodomain-inhibition-promotes-anti-tumor-immunity-by-suppressing-pd-l1-expression
#11
Hengrui Zhu, Fee Bengsch, Nikolaos Svoronos, Melanie R Rutkowski, Benjamin G Bitler, Michael J Allegrezza, Yuhki Yokoyama, Andrew V Kossenkov, James E Bradner, Jose R Conejo-Garcia, Rugang Zhang
Restoration of anti-tumor immunity by blocking PD-L1 signaling through the use of antibodies has proven to be beneficial in cancer therapy. Here, we show that BET bromodomain inhibition suppresses PD-L1 expression and limits tumor progression in ovarian cancer. CD274 (encoding PD-L1) is a direct target of BRD4-mediated gene transcription. In mouse models, treatment with the BET inhibitor JQ1 significantly reduced PD-L1 expression on tumor cells and tumor-associated dendritic cells and macrophages, which correlated with an increase in the activity of anti-tumor cytotoxic T cells...
September 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27607580/inhibition-of-bet-bromodomain-dependent-xiap-and-flip-expression-sensitizes-kras-mutated-nsclc-to-pro-apoptotic-agents
#12
Olaf Klingbeil, Ralf Lesche, Kathy A Gelato, Bernard Haendler, Pascale Lejeune
Non-small cell lung cancer (NSCLC) has the highest incidence of cancer-related death worldwide and a high medical need for more effective therapies. Small-molecule inhibitors of the bromodomain and extra terminal domain (BET) family such as JQ1, I-BET762 and OTX-015 are active in a wide range of different cancer types, including lung cancer. Although their activity on oncogene expression such as c-Myc has been addressed in many studies, the effects of BET inhibition on the apoptotic pathway remain largely unknown...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27581642/structure-activity-relationship-study-of-n-6-benzoyladenine-type-brd4-inhibitors-and-their-effects-on-cell-differentiation-and-tnf-%C3%AE-production
#13
Seika Amemiya, Takao Yamaguchi, Taki Sakai, Yuichi Hashimoto, Tomomi Noguchi-Yachide
Bromodomains are epigenetic 'readers' of histone acetylation. The first potent bromodomain and extra-terminal domain (BET) inhibitors, (+)-JQ1 and I-BET762 (also known as GSK525762), were reported in 2010. Some BET inhibitors are already under clinical trial for the treatment of cancers, but so far, only a few chemical scaffolds are available. We have reported potent N(6)-benzoyladenine-based inhibitors of BRD4, a BET family member that serves as a key mediator of transcriptional elongation. Here we present an analysis of the structure-activity relationships of these inhibitors...
2016: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27572308/jq1-suppresses-tumor-growth-via-pten-pi3k-akt-pathway-in-endometrial-cancer
#14
Haifeng Qiu, Jing Li, Leslie H Clark, Amanda L Jackson, Lu Zhang, Hui Guo, Joshua E Kilgore, Paola A Gehrig, Chunxiao Zhou, Victoria L Bae-Jump
Overexpression of c-Myc is associated with worse outcomes in endometrial cancer, indicating that c-Myc may be a promising target for endometrial cancer therapy. A novel small molecule, JQ1, has been shown to block BRD4 resulting in inhibition of c-Myc expression and tumor growth. Thus, we investigated whether JQ1 can inhibit endometrial cancer growth in cell culture and xenograft models. In PTEN-positive endometrial cancer cells, JQ1 significantly suppressed cell proliferation via induction of G1 phase arrest and apoptosis in a dose-dependent manner, accompanied by a sharp decline in cyclin D1 and CDK4 protein expression...
August 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27550065/expression-and-role-of-paics-a-de-novo-purine-biosynthetic-gene-in-prostate-cancer
#15
Balabhadrapatruni V S K Chakravarthi, Moloy T Goswami, Satya S Pathi, Matthew Dodson, Darshan S Chandrashekar, Sumit Agarwal, Saroj Nepal, Sai Akshaya Hodigere Balasubramanya, Javed Siddiqui, Robert J Lonigro, Arul M Chinnaiyan, Lakshmi P Kunju, Nallasivam Palanisamy, Sooryanarayana Varambally
BACKGROUND: Our goal was to investigate de novo purine biosynthetic gene PAICS expression and evaluate its role in prostate cancer progression. METHODS: Next-generation sequencing, qRTPCR and immunoblot analysis revealed an elevated expression of a de novo purine biosynthetic gene, Phosphoribosylaminoimidazole Carboxylase, Phosphoribosylaminoimidazole Succinocarboxamide Synthetase (PAICS) in a progressive manner in prostate cancer. Functional analyses were performed using prostate cancer cell lines- DU145, PC3, LnCaP, and VCaP...
August 22, 2016: Prostate
https://www.readbyqxmd.com/read/27548527/bet-bromodomain-inhibition-enhances-t-cell-persistence-and-function-in-adoptive-immunotherapy-models
#16
Yuki Kagoya, Munehide Nakatsugawa, Yuki Yamashita, Toshiki Ochi, Tingxi Guo, Mark Anczurowski, Kayoko Saso, Marcus O Butler, Cheryl H Arrowsmith, Naoto Hirano
Adoptive immunotherapy is a potentially curative therapeutic approach for patients with advanced cancer. However, the in vitro expansion of antitumor T cells prior to infusion inevitably incurs differentiation towards effector T cells and impairs persistence following adoptive transfer. Epigenetic profiles regulate gene expression of key transcription factors over the course of immune cell differentiation, proliferation, and function. Using comprehensive screening of chemical probes with defined epigenetic targets, we found that JQ1, an inhibitor of bromodomain and extra-terminal motif (BET) proteins, maintained CD8+ T cells with functional properties of stem cell-like and central memory T cells...
September 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27528027/stromal-remodeling-by-the-bet-bromodomain-inhibitor-jq1-suppresses-the-progression-of-human-pancreatic-cancer
#17
Keisuke Yamamoto, Keisuke Tateishi, Yotaro Kudo, Mayumi Hoshikawa, Mariko Tanaka, Takuma Nakatsuka, Hiroaki Fujiwara, Koji Miyabayashi, Ryota Takahashi, Yasuo Tanaka, Hideaki Ijichi, Yousuke Nakai, Hiroyuki Isayama, Yasuyuki Morishita, Taku Aoki, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo, Masashi Fukayama, Kazuhiko Koike
Inhibitors of bromodomain and extraterminal domain (BET) proteins, a family of chromatin reader proteins, have therapeutic efficacy against various malignancies. However, the detailed mechanisms underlying the anti-tumor effects in distinct tumor types remain elusive. Here, we show a novel antitumor mechanism of BET inhibition in pancreatic ductal adenocarcinoma (PDAC). We found that JQ1, a BET inhibitor, decreased desmoplastic stroma, a hallmark of PDAC, and suppressed the growth of patient-derived tumor xenografts (PDX) of PDACs...
August 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27472462/effective-combination-therapies-in-preclinical-endocrine-resistant-breast-cancer-models-harboring-er-mutations
#18
Brendon Ladd, Anne Marie Mazzola, Teeru Bihani, Zhongwu Lai, James Bradford, Michael Collins, Evan Barry, Anne U Goeppert, Hazel M Weir, Kelly Hearne, Jonathan G Renshaw, Morvarid Mohseni, Elaine Hurt, Sanjoo Jalla, Haifeng Bao, Robert Hollingsworth, Corinne Reimer, Michael Zinda, Stephen Fawell, Celina M D'Cruz
Although endocrine therapy is successfully used to treat patients with estrogen receptor (ER) positive breast cancer, a substantial proportion of this population will relapse. Several mechanisms of acquired resistance have been described including activation of the mTOR pathway, increased activity of CDK4 and activating mutations in ER. Using a patient derived xenograft model harboring a common activating ER ligand binding domain mutation (D538G), we evaluated several combinatorial strategies using the selective estrogen receptor degrader (SERD) fulvestrant in combination with chromatin modifying agents, and CDK4/6 and mTOR inhibitors...
July 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27452461/resistance-to-bet-bromodomain-inhibitors-is-mediated-by-kinome-reprogramming-in-ovarian-cancer
#19
Alison M Kurimchak, Claude Shelton, Kelly E Duncan, Katherine J Johnson, Jennifer Brown, Shane O'Brien, Rashid Gabbasov, Lauren S Fink, Yuesheng Li, Nicole Lounsbury, Magid Abou-Gharbia, Wayne E Childers, Denise C Connolly, Jonathan Chernoff, Jeffrey R Peterson, James S Duncan
Small-molecule BET bromodomain inhibitors (BETis) are actively being pursued in clinical trials for the treatment of a variety of cancers, but the mechanisms of resistance to BETis remain poorly understood. Using a mass spectrometry approach that globally measures kinase signaling at the proteomic level, we evaluated the response of the kinome to targeted BETi treatment in a panel of BRD4-dependent ovarian carcinoma (OC) cell lines. Despite initial inhibitory effects of BETi, OC cells acquired resistance following sustained treatment with the BETi JQ1...
August 2, 2016: Cell Reports
https://www.readbyqxmd.com/read/27443262/compensatory-rna-polymerase-2-loading-determines-the-efficacy-and-transcriptional-selectivity-of-jq1-in-myc-driven-tumors
#20
E Donato, O Croci, A Sabò, H Muller, M J Morelli, M Pelizzola, S Campaner
Inhibition of bromodomain and extraterminal motif (BET) proteins such as BRD4 bears great promise for cancer treatment and its efficacy has been frequently attributed to Myc downregulation. Here, we use B-cell tumors as a model to address the mechanism of action of JQ1, a widely used BET inhibitor. Although JQ1 led to widespread eviction of BRD4 from chromatin, its effect on gene transcription was limited to a restricted set of genes. This was unlinked to Myc downregulation or its chromatin association. Yet, JQ1-sensitive genes were enriched for Myc and E2F targets, were expressed at high levels, and showed high promoter occupancy by RNAPol2, BRD4, Myc and E2F...
July 22, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
keyword
keyword
90155
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"