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https://www.readbyqxmd.com/read/28843004/single-nucleotide-polymorphisms-rs911160-in-aurka-and-rs2289590-in-aurkb-mitotic-checkpoint-genes-contribute-to-gastric-cancer-susceptibility
#1
Aner Mesic, Ela Markocic, Marija Rogar, Robert Juvan, Petra Hudler, Radovan Komel
BACKGROUND: Single nucleotide polymorphisms (SNPs) in mitotic checkpoint genes could confer increased susceptibility to gastric cancer (GC). We investigated the association of Aurora kinase A (AURKA), Aurora kinase B (AURKB), Aurora kinase C (AURKC), Polo-like kinase 1 (PLK1) and Budding uninhibited by benzimidazol 3, yeast (BUB3) gene polymorphisms with GC risk. MATERIALS AND METHODS: Genotyping of 6 SNPs in AURKA (rs911160 and rs8173), AURKB (rs2289590), AURKC (rs11084490), PLK1 (rs42873), and BUB3 (rs7897156) was performed using TaqMan genotyping assays...
August 26, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28733545/a-small-molecule-inhibitor-targeting-the-aurkc-i%C3%AE%C2%BAb%C3%AE-interaction-decreases-transformed-growth-of-mda-mb-231-breast-cancer-cells
#2
Eun Hee Han, Jin-Young Min, Shin-Ae Yoo, Sung-Joon Park, Yun-Jeong Choe, Hee Sub Yun, Zee-Won Lee, Sun Woo Jin, Hyung Gyun Kim, Hye Gwang Jeong, Hyun Kyoung Kim, Nam Doo Kim, Young-Ho Chung
The Aurora kinases, Aurora A (AURKA), Aurora B (AURKB), and Aurora C (AURKC), are serine/threonine kinases required for the control of mitosis (AURKA and AURKB) or meiosis (AURKC). Several Aurora kinase inhibitors are being investigated as novel anticancer therapeutics. Recent studies demonstrated that AURKC activation contributes to breast cancer cell transformation. Therefore, AURKC is both a promising marker and therapeutic target for breast cancer; however, its signaling network has not been fully characterized...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700337/polymorphisms-in-mitotic-checkpoint-related-genes-can-influence-survival-outcomes-of-early-stage-non-small-cell-lung-cancer
#3
Hyo-Gyoung Kang, Seung Soo Yoo, Jin Eun Choi, Mi Jeong Hong, Sook Kyung Do, Cheng Cheng Jin, Soyoun Kim, Won Kee Lee, Sun Ha Choi, So Yeon Lee, Hyun Jung Kim, Shin Yup Lee, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, Yangki Seok, Eungbae Lee, Sukki Cho, Sanghoon Jheon, Jae Yong Park
This study was conducted to investigate the association between variants in mitotic checkpoint-related genes and clinical outcomes of non-small cell lung cancer (NSCLC). A total of 766 patients with NSCLC who underwent curative surgery were enrolled. Among the 73 variants evaluated, 4 variants were related with survival outcomes. BUB3 rs7897156C>T was associated with worse overall survival under a recessive model (adjusted hazard ratio = 1.58, 95% confidence interval = 1.07-2.33, P = 0.02). AURKB rs1059476G>A was associated with better overall survival under a recessive model (adjusted hazard ratio = 0...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28659416/haspin-inhibition-reveals-functional-differences-of-interchromatid-axis-localized-aurkb-and-aurkc
#4
Suzanne M Quartuccio, Shweta S Dipali, Karen Schindler
Aneuploidy is the leading genetic abnormality contributing to infertility, and chromosome segregation errors are common during female mammalian meiosis I (MI). Previous results indicate that haspin kinase regulates resumption of meiosis from prophase arrest, chromosome condensation, and kinetochore-microtubule attachments during early prometaphase of MI. Here we report that haspin inhibition in late prometaphase I causes acceleration of MI, bypass of the spindle assembly checkpoint (SAC), and loss of interchromatid axis-localized Aurora kinase C...
August 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28600475/dual-inhibition-of-hdac-and-tyrosine-kinase-signaling-pathways-with-cudc-907-inhibits-thyroid-cancer-growth-and-metastases
#5
Shweta Kotian, Lisa Zhang, Myriem Boufraqech, Kelli Gaskins, Sudheer Kumar Gara, Martha Quezado, Naris Nilubol, Electron Kebebew
Purpose: There is currently no standard therapy for anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC), which account for two-thirds of thyroid cancer-related deaths. Driver mutations in the PI3K/AKT and RAF/RAS/MEK/ERK pathways are common in ATC and PDTC. Histone deacetylases (HDAC) regulate cancer initiation and progression. Our aim was to determine the therapeutic efficacy of simultaneously targeting these pathways in thyroid cancer with a single agent and to evaluate biomarkers of treatment response...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28595628/six3-a-tumor-suppressor-inhibits-astrocytoma-tumorigenesis-by-transcriptional-repression-of-aurka-b
#6
Zhibin Yu, Yingnan Sun, Xiaoling She, Zeyou Wang, Shuai Chen, Zhiyong Deng, Yan Zhang, Qiang Liu, Qing Liu, Chunhua Zhao, Peiyao Li, Changhong Liu, Jianbo Feng, Haijuan Fu, Guiyuan Li, Minghua Wu
BACKGROUND: SIX homeobox 3 (SIX3) is a member of the sine oculis homeobox transcription factor family. It plays a vital role in the nervous system development. Our previous study showed that the SIX3 gene is hypermethylated, and its expression is decreased in astrocytoma, but the role of SIX3 remains unknown. METHODS: Chromatin-immunoprecipitation (ChIP) and luciferase reporter assay were used to confirm the binding of SIX3 to the promoter regions of aurora kinase A (AURKA) and aurora kinase B (AURKB)...
June 8, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28588715/aurka-mrna-expression-is-an-independent-predictor-of-poor-prognosis-in-patients-with-non-small-cell-lung-cancer
#7
Ahmed S K Al-Khafaji, Michael W Marcus, Michael P A Davies, Janet M Risk, Richard J Shaw, John K Field, Triantafillos Liloglou
Deregulation of mitotic spindle genes has been reported to contribute to the development and progression of malignant tumours. The aim of the present study was to explore the association between the expression profiles of Aurora kinases (AURKA, AURKB and AURKC), cytoskeleton-associated protein 5 (CKAP5), discs large-associated protein 5 (DLGAP5), kinesin-like protein 11 (KIF11), microtubule nucleation factor (TPX2), monopolar spindle 1 kinase (TTK), and β-tubulins (TUBB) and (TUBB3) genes and clinicopathological characteristics in human non-small cell lung carcinoma (NSCLC)...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28562334/gene-co-expression-network-reveals-shared-modules-predictive-of-stage-and-grade-in-serous-ovarian-cancers
#8
Qian Sun, Haiyue Zhao, Cong Zhang, Ting Hu, Jianli Wu, Xingguang Lin, Danfeng Luo, Changyu Wang, Li Meng, Ling Xi, Kezhen Li, Junbo Hu, Ding Ma, Tao Zhu
Serous ovarian cancer (SOC) is the most lethal gynecological cancer. Clinical studies have revealed an association between tumor stage and grade and clinical prognosis. Identification of meaningful clusters of co-expressed genes or representative biomarkers related to stage or grade may help to reveal mechanisms of tumorigenesis and cancer development, and aid in predicting SOC patient prognosis. We therefore performed a weighted gene co-expression network analysis (WGCNA) and calculated module-trait correlations based on three public microarray datasets (GSE26193, GSE9891, and TCGA), which included 788 samples and 10402 genes...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28434146/differential-regulation-of-h3s10-phosphorylation-mitosis-progression-and-cell-fate-by-aurora-kinase-b-and-c-in-mouse-preimplantation-embryos
#9
Wenzhi Li, Peizhe Wang, Bingjie Zhang, Jing Zhang, Jia Ming, Wei Xie, Jie Na
Coordination of cell division and cell fate is crucial for the successful development of mammalian early embryos. Aurora kinases are evolutionarily conserved serine/threonine kinases and key regulators of mitosis. Aurora kinase B (AurkB) is ubiquitously expressed while Aurora kinase C (AurkC) is specifically expressed in gametes and preimplantation embryos. We found that increasing AurkC level in one blastomere of the 2-cell embryo accelerated cell division and decreasing AurkC level slowed down mitosis. Changing AurkB level had the opposite effect...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28404751/chromosomal-passenger-complex-hydrodynamics-suggests-chaperoning-of-the-inactive-state-by-nucleoplasmin-nucleophosmin
#10
Mariah L Hanley, Tae Yeon Yoo, Matthew Sonnett, Daniel J Needleman, Timothy J Mitchison
The chromosomal passenger complex (CPC) is a conserved, essential regulator of cell division. As such, significant anti-cancer drug development efforts have been focused on targeting it, most notably by inhibiting its AURKB kinase subunit. The CPC is activated by AURKB-catalyzed autophosphorylation on multiple subunits, but how this regulates CPC interactions with other mitotic proteins remains unclear. We investigated the hydrodynamic behavior of the CPC in Xenopus laevis egg cytosol using sucrose gradient sedimentation and in HeLa cells using fluorescence correlation spectroscopy...
June 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28386317/alisertib-induces-g2-m-arrest-apoptosis-and-autophagy-via-pi3k-akt-mtor-and-p38-mapk-mediated-pathways-in-human-glioblastoma-cells
#11
Zheng Liu, Feng Wang, Zhi-Wei Zhou, He-Chun Xia, Xin-Yu Wang, Yin-Xue Yang, Zhi-Xu He, Tao Sun, Shu-Feng Zhou
Glioblastoma (GBM) is the most common brain tumor with poor response to current therapeutics. Alisertib (ALS), a second-generation selective Aurora kinase A (AURKA) inhibitor, has shown potent anticancer effects on solid tumors in animal studies. This study aimed to investigate the killing effect of ALS on GBM cell line DAOY and the possible underlying mechanisms using both bioinformatic and cell-based approaches. Our molecular docking showed that ALS preferentially bound AURKA over AURKB via hydrogen bond formation, charge interaction, and π-π stacking...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28369513/identification-and-characterization-of-aurora-kinase-b-and-c-variants-associated-with-maternal-aneuploidy
#12
Alexandra L Nguyen, Diego Marin, Anbo Zhou, Amanda S Gentilello, Evan M Smoak, Zubing Cao, Anastasia Fedick, Yujue Wang, Deanne Taylor, Richard T Scott, Jinchuan Xing, Nathan Treff, Karen Schindler
STUDY QUESTION: Are single nucleotide variants (SNVs) in Aurora kinases B and C (AURKB, AURKC) associated with risk of aneuploid conception? SUMMARY ANSWER: Two SNVs were found in patients with extreme aneuploid concepti rates with respect to their age; one variant, AURKC p.I79V, is benign, while another, AURKB p.L39P, is a potential gain-of-function mutant with increased efficiency in promoting chromosome alignment. WHAT IS KNOWN ALREADY: Maternal age does not always predict aneuploidy risk, and rare gene variants can be drivers of disease...
June 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28359584/specialize-and-divide-twice-functions-of-three-aurora-kinase-homologs-in-mammalian-oocyte-meiotic-maturation
#13
REVIEW
Alexandra L Nguyen, Karen Schindler
The aurora kinases (AURKs) comprise an evolutionarily conserved family of serine/threonine kinases involved in mitosis and meiosis. While most mitotic cells express two AURK isoforms (AURKA and AURKB), mammalian germ cells also express a third, AURKC. Although much is known about the functions of the kinases in mitosis, less is known about how the three isoforms function to coordinate meiosis. This review is aimed at describing what is known about the three isoforms in female meiosis, the similarities and differences between kinase functions, and speculates as to why mammalian germ cells require expression of three AURKs instead of two...
May 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28330808/germline-genetic-biomarkers-of-sunitinib-efficacy-in-advanced-renal-cell-carcinoma-results-from-the-renal-effect-trial
#14
Robert J Motzer, Robert A Figlin, Jean-François Martini, Subramanian Hariharan, Neeraj Agarwal, Chun Xiao Li, J Andrew Williams, Thomas E Hutson
BACKGROUND: Sunitinib, the vascular endothelial growth factor pathway inhibitor, is an established standard-of-care for advanced renal cell carcinoma (RCC). This study aimed to assess correlations between candidate germline single nucleotide polymorphisms (SNPs) and sunitinib efficacy in patients from the RENAL EFFECT trial (NCT00267748), a randomized phase II study in patients with metastatic RCC comparing the 4-weeks-on/2-weeks-off schedule and a continuous daily dosing schedule. PATIENTS AND METHODS: Informed consent for pharmacogenetics research was obtained from 202 out of 289 treated patients in the trial...
February 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28228757/regulation-of-epigenetic-modifiers-including-kdm6b-by-interferon-%C3%AE-and-interleukin-4-in-human-macrophages
#15
Gökçe Yıldırım-Buharalıoğlu, Mark Bond, Graciela B Sala-Newby, Charles C T Hindmarch, Andrew C Newby
BACKGROUND: Interferon-γ (IFN-γ) or interleukin-4 (IL-4) drives widely different transcriptional programs in macrophages. However, how IFN-γ and IL-4 alter expression of histone-modifying enzymes involved in epigenetic regulation and how this affects the resulting phenotypic polarization is incompletely understood. METHODS AND RESULTS: We investigated steady-state messenger RNA levels of 84 histone-modifying enzymes and related regulators in colony-stimulating factor-1 differentiated primary human macrophages using quantitative polymerase chain reaction...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28147341/aurora-kinases-novel-therapy-targets-in-cancers
#16
REVIEW
Anqun Tang, Keyu Gao, Laili Chu, Rui Zhang, Jing Yang, Junnian Zheng
Aurora kinases, a family of serine/threonine kinases, consisting of Aurora A (AURKA), Aurora B (AURKB) and Aurora C (AURKC), are essential kinases for cell division via regulating mitosis especially the process of chromosomal segregation. Besides regulating mitosis, Aurora kinases have been implicated in regulating meiosis. The deletion of Aurora kinases could lead to failure of cell division and impair the embryonic development. Overexpression or gene amplification of Aurora kinases has been clarified in a number of cancers...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28095398/aurora-b-expression-modulates-paclitaxel-response-in-non-small-cell-lung-cancer
#17
Ahmed Sk Al-Khafaji, Michael Pa Davies, Janet M Risk, Michael W Marcus, Maria Koffa, John R Gosney, Richard J Shaw, John K Field, Triantafillos Liloglou
BACKGROUND: Taxanes are mitotic poisons widely used in the treatment of non-small cell lung cancer (NSCLC), however, little is known about potential molecular modulators of response to these compounds. Aurora B (AURKB) is a critical regulator of the mitotic spindle assembly, previously shown overexpressed in NSCLC. Here we investigated the hypothesis that AURKB expression modulates the efficacy of taxanes in NSCLC cells. METHODS: AURKB mRNA expression was determined by qPCR in 132 frozen NSCLC tissues and nine NSCLC cell lines...
February 28, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28028179/functional-effects-of-akt3-on-aurora-kinase-inhibitor-induced-aneuploidy
#18
Kohji Noguchi, Keita Hongama, Shiori Hariki, Yuma Nonomiya, Kazuhiro Katayama, Yoshikazu Sugimoto
The suppression of mitotic Aurora kinases (AURKs) by AURK inhibitors frequently causes cytokinetic failure, leading to polyploidy or aneuploidy, indicating the critical role of AURK-mediated phosphorylation during cytokinesis. We demonstrate the deregulated expression of AKT3 in Aurora kinase inhibitor (AURKi)-resistant cells, which we established from human colorectal cancer HCT 116 cells. The AKT family, which includes AKT1, -2, and -3, plays multiple roles in antiapoptotic functions and drug resistance and is involved in cell growth and survival pathways...
February 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28008150/prkar2b-plays-an-oncogenic-role-in-the-castration-resistant-prostate-cancer
#19
Jianjun Sha, Wei Xue, Baijun Dong, Jiahua Pan, Xiaorong Wu, Dong Li, Dongming Liu, Yiran Huang
Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer. Despite some progresses have been made, the mechanism of CRPC development is still largely unknown, including the genes involved in its development have not been well defined. Here, we identifiedPRKAR2B to be a gene over-expressingin castration-resistant prostate cancer by analyzing the different online databases. Followed functional validation experiments showed that PRKAR2B promoted CRPC cell proliferation and invasion, and inhibited CRPC cell apoptosis...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/27895801/in-vitro-evaluation-of-a-combination-treatment-involving-anticancer-agents-and-an-aurora-kinase-b-inhibitor
#20
Senna Sakai, Hiroto Izumi, Yukiko Yoshiura, Yoshifumi Nakayama, Takahiro Yamaguchi, Yoshikazu Harada, Chiho Koi, Hiroyuki Kurata, Yasuo Morimoto
Aurora kinase B (AURKB) inhibitors are regarded as potential molecular-targeting drugs for cancer therapy. The present study evaluated the cytotoxic effect of a combination of AZD1152-hQPA, an AURKB inhibitor, and various anticancer agents on the HeLa human cervical cancer cell line, as well as its cisplatin-resistant equivalent HCP4 cell line. It was demonstrated that AZD1152-hQPA had an antagonistic effect on the cytotoxicity of cisplatin, etoposide and doxorubicin, but had a synergistic effect on that of all-trans-retinoic acid (ATRA), Am80 and TAC-101, when tested on HeLa cells...
November 2016: Oncology Letters
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