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Aurora kinase

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https://www.readbyqxmd.com/read/28938400/il-1%C3%AE-inhibits-connexin-43-and-disrupts-decidualization-of-human-endometrial-stromal-cells-through-erk1-2-and-p38-map-kinase
#1
Jie Yu, Sarah L Berga, Wei Zou, D Grace Yook, Joshua C Pan, Aurora Arroyo Andrade, Lijuan Zhao, Neil Sidell, Indrani C Bagchi, Milan K Bagchi, Robert N Taylor
Inflammation can interfere with endometrial receptivity. We examined how IL-1β affects expression of the uterine gap junction protein, Cx43, which is known to be critical for embryonic implantation. We used an in vitro model of human endometrial stromal cells (ESC), Western blotting and a combination of validated, selective kinase inhibitors to evaluate five canonical IL-1β signaling pathways. Cx43 and two other markers of ESC differentiation (prolactin and VEGF) were inhibited predominantly via IL-1β-activated ERK1/2 and p38 MAP kinase cascades...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28928489/the-phosphorylation-of-a-kinetochore-protein-dam1-by-aurora-b-ipl1-kinase-promotes-chromosome-bipolar-attachment-in-yeast
#2
Fengzhi Jin, Michael Bokros, Yanchang Wang
The interaction between chromosomes and spindle microtubules is essential for chromosome segregation. The kinetochore complex mediates this interaction. Previous studies indicate that the stability of kinetochore attachment is regulated by Aurora B/Ipl1 kinase and this regulation is conserved from yeast to mammalian cells. In budding yeast Saccharomyces cerevisiae, the ten-subunit Dam1/DASH complex bridges the interaction between kinetochores and microtubules, and some in vitro evidence indicates that the phosphorylation of Dam1 protein by Ipl1 kinase destabilizes this interaction...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28918096/a-comprehensive-review-on-aurora-kinase-small-molecule-inhibitors-and-clinical-trial-studies
#3
REVIEW
Ankit C Borisa, Hardik G Bhatt
Aurora kinase belongs to serine/threonine kinase family which controls cell division. Therapeutic inhibition of Aurora kinase showed great promise as probable anticancer regime because of its important role during cell division. Here, in this review, we have carried out exhaustive study of various synthetic molecules reported as Aurora kinase inhibitors and developed as lead molecule at various stages of clinical trials from its discovery in 1995 to till date. We reported details of small molecules, specifically inhibiting all 3 types of Aurora kinases, which includes extensive literature search in various database like various scientific journals, patents, scifinder and PubMed database, internet resources, books, etc...
August 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28916158/pyrrolizines-design-synthesis-anticancer-evaluation-and-investigation-of-the-potential-mechanism-of-action
#4
Ahmed M Gouda, Ahmed H Abdelazeem, Hany A Omar, Ashraf N Abdalla, Mohammed A S Abourehab, Hamed I Ali
A novel set of pyrrolizine-5-carboxamides has been synthesized and evaluated for their anticancer potential against human breast MCF-7, lung carcinoma A549 and hepatoma Hep3B cancer cell lines. Compound 10c was the most active against MCF-7 with IC50 value of 4.72µM, while compound 12b was the most active against A549 and Hep3B cell lines. Moreover, kinases/COXs inhibition and apoptosis induction were suggested as potential molecular mechanisms for the anticancer activity of the novel pyrrolizines based on their structural features...
August 24, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28915666/ard1-mediated-aurora-kinase-a-acetylation-promotes-cell-proliferation-and-migration
#5
Tam Thuy Lu Vo, Ji-Hyeon Park, Ji Hae Seo, Eun Ji Lee, Hoon Choi, Sung-Jin Bae, Hoang Le, Sunho An, Hye Shin Lee, Hee-Jun Wee, Kyu-Won Kim
Aurora kinase A (AuA) is a prerequisite for centrosome maturation, separation, and mitotic spindle assembly, thus, it is essential for cell cycle regulation. Overexpression of AuA is implicated in poor prognosis of many types of cancer. However, the regulatory mechanisms underlying the functions of AuA are still not fully understood. Here, we report that AuA colocalizes with arrest defective protein 1 (ARD1) acetyltransferase during cell division and cell migration. Additionally, AuA is acetylated by ARD1 at lysine residues at positions 75 and 125...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903407/mir-331-3p-and-aurora-kinase-inhibitor-ii-co-treatment-suppresses-prostate-cancer-tumorigenesis-and-progression
#6
Michael R Epis, Keith M Giles, Dianne J Beveridge, Kirsty L Richardson, Patrick A Candy, Lisa M Stuart, Jacqueline Bentel, Ronald J Cohen, Peter J Leedman
RNA-based therapeutics could represent a new avenue of cancer treatment. miRNA 331-3p (miR-331-3p) is implicated in prostate cancer (PCa) as a putative tumor suppressor, but its functional activity and synergy with other anti-tumor agents is largely unknown. We found miR-331-3p expression in PCa tumors was significantly decreased compared to non-malignant matched tissue. Analysis of publicly available PCa gene expression data sets showed miR-331-3p expression negatively correlated with Gleason Score, tumor stage, lymph node involvement and PSA value, and was significantly down regulated in tumor tissue relative to normal prostate tissue...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903390/association-between-the-functional-polymorphism-ile31phe-in-the-aurka-gene-and-susceptibility-of-hepatocellular-carcinoma-in-chronic-hepatitis-b-virus-carriers
#7
Zhiyu Bao, Lei Lu, Xinyi Liu, Bingqian Guo, Yun Zhai, Yuanfeng Li, Yahui Wang, Bobo Xie, Qian Ren, Pengbo Cao, Yuqing Han, Weihua Jia, Minshan Chen, Xinqiang Liang, Xuan Wang, Yi-Xin Zeng, Fuchu He, Hongxing Zhang, Ying Cui, Gangqiao Zhou
Aurora kinase A (AURKA) is a serine threonine kinase which affects chromosomal separation and mitotic spindle stability through interaction with the centrosome during mitosis. Two functional nonsynonymous polymorphisms of the AURKA gene (Ile31Phe and Val57Ile) have been reported recently. We analyzed the association between the two polymorphisms and risk of the occurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Guangxi population consisting of 348 patients with HCC and 359 control subjects, and then validated the significant association in the Guangdong population consisting of 440 cases and 456 controls...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28891222/global-population-pharmacokinetics-of-the-investigational-aurora-a-kinase-inhibitor-alisertib-in-cancer-patients-rationale-for-lower-dosage-in-asia
#8
X Zhou, D R Mould, T Takubo, E Sheldon-Waniga, D Huebner, A Milton, K Venkatakrishnan
AIMS: This population pharmacokinetic analysis was conducted to quantitatively describe the regional differences and sources of inter-patient variability on the apparent oral clearance of alisertib. METHODS: A population pharmacokinetic analysis was performed on data from 671 cancer patients in Western countries and in Japan/ East Asia administered alisertib 5-150 mg once or twice daily in multiple dosing schedules. The final model was used to simulate alisertib pharmacokinetics in patients in the West and East Asian regions in the single agent schedule of 7 days of dosing in a 21 day cycle...
September 11, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28885544/chemical-genomics-approach-leads-to-the-identification-of-hesperadin-an-aurora-b-kinase-inhibitor-as-a-broad-spectrum-influenza-antiviral
#9
Yanmei Hu, Jiantao Zhang, Rami Musharrafieh, Raymond Hau, Chunlong Ma, Jun Wang
Influenza viruses are respiratory pathogens that are responsible for annual influenza epidemics and sporadic influenza pandemics. Oseltamivir (Tamiflu(®)) is currently the only FDA-approved oral drug that is available for the prevention and treatment of influenza virus infection. However, its narrow therapeutic window, coupled with the increasing incidence of drug resistance, calls for the next generation of influenza antivirals. In this study, we discovered hesperadin, an aurora B kinase inhibitor, as a broad-spectrum influenza antiviral through forward chemical genomics screening...
September 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28884479/transcriptional-repression-of-aurora-a-gene-by-wild-type-p53-through-directly-binding-to-its-promoter-with-histone-deacetylase-1-and-msin3a
#10
Tsung-Ying Yang, Chieh-Lin Teng, Tsung-Chieh Chester Lin, Kun-Chieh Chen, Shih-Lan Hsu, Chun-Chi Wu
In this study, we firstly showed that p53 transcriptionally represses Aurora-A gene expression through directly binding to its promoter. DNA affinity precipitation assay and chromatin immunoprecipitation assay indicated that p53 physically bound to the Aurora-A promoter. Moreover, the in vitro and in vivo assays showed that p53 directly bound to the Aurora-A promoter together with histone deacetylase 1 (HDAC1) and mSin3a as corepressors. Furthermore, we identified that the nucleotides -360 to -354 (CCTGCCC), upstream of the Aurora-A transcriptional start site, was responsible for the p53-mediated repression...
September 7, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28881819/apio-ee-9-is-a-novel-aurora-a-and-b-antagonist-that-suppresses-esophageal-cancer-growth-in-a-pdx-mouse-model
#11
Guoguo Jin, Ke Yao, Zhiping Guo, Zhenjiang Zhao, Kangdong Liu, Fangfang Liu, Hanyong Chen, Dhilli Rao Gorja, Kanamata Reddy, Ann M Bode, Ziming Dong, Zigang Dong
Esophageal cancer (EC) is one of the most aggressive malignancies of the upper aerodigestive tract. Over the past three decades, with advances in surgical techniques and treatment, the prognosis of esophageal cancer has only slowly improved. Thus identifying novel molecular targets and developing therapeutic agents are critical. Aurora kinases play a crucial role in mitosis and selective inhibitors might provide an effective therapeutic treatment for cancer. However, the role of Aurora kinases in EC is still inadequately studied...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881569/aurora-a-kinase-regulates-non-homologous-end-joining-and-poly-adp-ribose-polymerase-function-in-ovarian-carcinoma-cells
#12
Thuy-Vy Do, Jeff Hirst, Stephen Hyter, Katherine F Roby, Andrew K Godwin
Ovarian cancer is usually diagnosed at late stages when cancer has spread beyond the ovary and patients ultimately succumb to the development of drug-resistant disease. There is an urgent and unmet need to develop therapeutic strategies that effectively treat ovarian cancer and this requires a better understanding of signaling pathways important for ovarian cancer progression. Aurora A kinase (AURKA) plays an important role in ovarian cancer progression by mediating mitosis and chromosomal instability. In the current study, we investigated the role of AURKA in regulating the DNA damage response and DNA repair in ovarian carcinoma cells...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28875467/erratum-to-breast-cancer-risk-associated-with-genotype-polymorphisms-of-the-aurora-kinase-a-gene-aurka-a-case-control-study-in-a-high-altitude-ecuadorian-mestizo-population
#13
Andrés López-Cortés, Alejandro Cabrera-Andrade, Fabián Oña-Cisneros, Carolina Echeverría, Felipe Rosales, Malena Ortiz, Eduardo Tejera, César Paz-Y-Miño
No abstract text is available yet for this article.
September 5, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28869606/kctd12-promotes-tumorigenesis-by-facilitating-cdc25b-cdk1-aurora-a-dependent-g2-m-transition
#14
Y Zhong, J Yang, W W Xu, Y Wang, C-C Zheng, B Li, Q-Y He
Cell cycle dysregulation leads to uncontrolled cell proliferation and tumorigenesis. Understanding the molecular mechanisms underlying cell cycle progression can provide clues leading to the identification of key proteins involved in cancer development. In this study, we performed proteomics analysis to identify novel regulators of the cell cycle. We found that potassium channel tetramerization domain containing 12 (KCTD12) was significantly upregulated in M phase compared with S phase. We also found that KCTD12 overexpression not only facilitated the G2/M transition and induced cancer cell proliferation, but also promoted the growth of subcutaneous tumors and Ki-67 proliferation index in mice...
September 4, 2017: Oncogene
https://www.readbyqxmd.com/read/28869599/taxane-mediated-radiosensitization-derives-from-chromosomal-missegregation-on-tripolar-mitotic-spindles-orchestrated-by-aurka-and-tpx2
#15
M Orth, K Unger, U Schoetz, C Belka, K Lauber
Taxane-based radiochemotherapy is a central treatment option for various cancer entities in locally advanced stages. The therapeutic synergism of this combined modality approach due to taxane-mediated radiosensitization of cancer cells is well-known. However, the underlying molecular mechanisms remain largely elusive, and mechanism-derived predictive markers of taxane-based radiochemotherapy are currently not available. Here, we show that clinically relevant doses of Paclitaxel, the prototype taxane, stimulate a tripolar mode of mitosis leading to chromosomal missegregation and aneuploidization rather than interfering with cell cycle progression...
September 4, 2017: Oncogene
https://www.readbyqxmd.com/read/28861148/a-proteomics-based-investigation-on-the-anticancer-activity-of-alisertib-an-aurora-kinase-a-inhibitor-in-hepatocellular-carcinoma-hep3b-cells
#16
Qiaohua Zhu, Meihua Luo, Chengyu Zhou, Zhiwei Zhou, Zhixu He, Xinfa Yu, Shufeng Zhou
Targeted therapy may provide survival benefit for advanced hepatocellular carcinoma (HCC) and Aurora A kinase (AURKA) represents a feasible target in cancer treatment. The purpose of this study is to investigate the anticancer activity of alisertib (ALS) on Hep3B cells based on a proteomic study conducted with the stable-isotope labeling by amino acids in cell culture (SILAC). The proteomic response to ALS was obtained with SILAC-based proteomic study. Cell cycle distribution and apoptosis were assessed using flow cytometry and autophagy was determined using flow cytometry and confocal microscopy...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28860275/14-3-3-regulation-of-ncd-reveals-a-new-mechanism-for-targeting-proteins-to-the-spindle-in-oocytes
#17
Robin Beaven, Ricardo Nunes Bastos, Christos Spanos, Pierre Romé, C Fiona Cullen, Juri Rappsilber, Régis Giet, Gohta Goshima, Hiroyuki Ohkura
The meiotic spindle is formed without centrosomes in a large volume of oocytes. Local activation of crucial spindle proteins around chromosomes is important for formation and maintenance of a bipolar spindle in oocytes. We found that phosphodocking 14-3-3 proteins stabilize spindle bipolarity in Drosophila melanogaster oocytes. A critical 14-3-3 target is the minus end-directed motor Ncd (human HSET; kinesin-14), which has well-documented roles in stabilizing a bipolar spindle in oocytes. Phospho docking by 14-3-3 inhibits the microtubule binding activity of the nonmotor Ncd tail...
August 31, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28858266/kinases-involved-in-both-autophagy-and-mitosis
#18
REVIEW
Zhiyuan Li, Xin Zhang
Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis...
August 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28855673/aurora-a-phosphorylation-of-yy1-during-mitosis-inactivates-its-dna-binding-activity
#19
Karen E Alexander, Raed Rizkallah
Successful execution of mitotic cell division requires the tight synchronisation of numerous biochemical pathways. The underlying mechanisms that govern chromosome segregation have been thoroughly investigated. However, the mechanisms that regulate transcription factors in coordination with mitotic progression remain poorly understood. In this report, we identify the transcription factor YY1 as a novel mitotic substrate for the Aurora A kinase, a key regulator of critical mitotic events, like centrosome maturation and spindle formation...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28852909/effects-of-rifampin-itraconazole-and-esomeprazole-on-the-pharmacokinetics-of-alisertib-an-investigational-aurora-a-kinase-inhibitor-in-patients-with-advanced-malignancies
#20
Xiaofei Zhou, Shubham Pant, John Nemunaitis, A Craig Lockhart, Gerald Falchook, Todd M Bauer, Manish Patel, John Sarantopoulos, Michael Bargfrede, Andreas Muehler, Lakshmi Rangachari, Bin Zhang, Karthik Venkatakrishnan
Aim Two studies investigated the effect of gastric acid reducing agents and strong inducers/inhibitors of CYP3A4 on the pharmacokinetics of alisertib, an investigational Aurora A kinase inhibitor, in patients with advanced malignancies. Methods In Study 1, patients received single doses of alisertib (50 mg) in the presence and absence of either esomeprazole (40 mg once daily [QD]) or rifampin (600 mg QD). In Study 2, patients received single doses of alisertib (30 mg) in the presence and absence of itraconazole (200 mg QD)...
August 30, 2017: Investigational New Drugs
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