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Aurora kinase

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https://www.readbyqxmd.com/read/28454467/investigation-of-differentially-expressed-micrornas-and-genes-in-cervical-cancer-using-an-integrated-bioinformatics-analysis
#1
Zhanzhan Xu, Yu Zhou, Fang Shi, Yexuan Cao, Thi Lan Anh Dinh, Jing Wan, Min Zhao
Cervical cancer is one of the most common types of cancer among women worldwide. In order to identify the microRNAs (miRNAs/miRs) and mRNAs associated with the carcinogenesis of cervical cancer, and to investigate the molecular mechanisms of cervical cancer, an miRNA microarray, GSE30656, and 3 mRNA microarrays, GSE63514, GSE39001 and GSE9750, for cervical cancer were retrieved from Gene Expression Omnibus. These datasets were analyzed in order to obtain differentially-expressed genes (DEGs) and miRNAs using the GEO2R tool...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453729/ablation-of-periostin-inhibits-post-infarction-myocardial-regeneration-in-neonatal-mice-mediated-by-the-phosphatidylinositol-3-kinase-glycogen-synthase-kinase-3%C3%AE-cyclin-d1-signalling-pathway
#2
Zhenhuan Chen, Jiahe Xie, Huixin Hao, Hairuo Lin, Long Wang, Yingxue Zhang, Lin Chen, Shiping Cao, Xiaobo Huang, Wangjun Liao, Jianping Bin, Yulin Liao
Aims: To resolve the controversy as to whether periostin plays a role in myocardial regeneration after myocardial infarction (MI), we created a neonatal mouse model of MI to investigate the influence of periostin ablation on myocardial regeneration and clarify the underlying mechanisms. Methods and results: Neonatal periostin-knockout mice and their wildtype littermates were subjected to MI or sham surgery. In the wildtype mice after MI, fibrosis was detectable at 3 days and fibrotic tissue was completely replaced by regenerated myocardium at 21 days...
May 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28447036/recent-translational-research-into-targeted-therapy-for-liposarcoma
#3
REVIEW
Rashi Bharat Patel, Ting Li, Zhichao Liao, Jivani Aakash Jaldeepbhai, H A Pavanika N V Perera, Sujani Kaushalya Muthukuda, Dholiya Hardeep Dhirubhai, Vaibhav Singh, Xiaoling Du, Jilong Yang
Liposarcomas (LPS) are among the most common soft tissue sarcomas, originating from adipocytes. Treatment for LPS typically involves surgical resection and radiation therapy, while the use of conventional cytotoxic chemotherapy for unresectable or metastatic LPS remains controversial. This review summarizes the results of recent translational research and trials of novel therapies targeting various genetic and molecular aberrations in different subtypes of LPS. Genetic aberrations such as the 12q13-15 amplicon, genetic amplification of MDM2, CDK4, TOP2A, PTK7, and CHEK1, point mutations in CTNNB1, CDH1, FBXW7, and EPHA1, as the fusion of FUS-DDIT3/EWSR1-DDIT3 are involved in the pathogenesis LPS and represent potential therapeutic candidates...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28444399/development-of-a-multipurpose-scaffold-for-the-display-of-peptide-loops
#4
Maxim Rossmann, Sandra J Greive, Tommaso Moschetti, Michael Dinan, Marko Hyvönen
Protein-protein interactions (PPIs) determine a wide range of biological processes and analysis of these dynamic networks is increasingly becoming a mandatory tool for studying protein function. Using the globular ATPase domain of recombinase RadA as a scaffold, we have developed a peptide display system (RAD display), which allows for the presentation of target peptides, protein domains or full-length proteins and their rapid recombinant production in bacteria. The design of the RAD display system includes differently tagged versions of the scaffold, which allows for flexibility in the protein purification method, and chemical coupling for small molecule labeling or surface immobilization...
April 24, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28442587/combined-aurka-and-h3k9-methyltransferase-targeting-inhibits-cell-growth-by-inducing-mitotic-catastrophe
#5
Angela Mathison, Ann Salmonson, Mckenna Missfeldt, Jennifer Bintz, Monique Williams, Sarah Kossak, Asha Nair, Thiago M de Assuncao, Trace A Christensen, Navtej S Buttar, Juan L Iovanna, Robert Huebert, Gwen Lomberk
The current integrative pathobiological hypothesis states that pancreatic cancer (PDAC) develops and progresses in response to an interaction between known oncogenes and downstream epigenomic regulators. Congruently, this study tests a new combinatorial therapy based on the inhibition of the Aurora kinase A (AURKA) oncogene and one of its targets, the H3K9 methylation-based epigenetic pathway. This therapeutic combination is effective at inhibiting the in vitro growth of PDAC cells both, in monolayer culture systems, and in 3D spheroids and organoids...
April 25, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28441529/mps1-regulates-kinetochore-microtubule-attachment-stability-via-the-ska-complex-to-ensure-error-free-chromosome-segregation
#6
John Maciejowski, Hauke Drechsler, Kathrin Grundner-Culemann, Edward R Ballister, Jose-Antonio Rodriguez-Rodriguez, Veronica Rodriguez-Bravo, Mathew J K Jones, Emily Foley, Michael A Lampson, Henrik Daub, Andrew D McAinsh, Prasad V Jallepalli
The spindle assembly checkpoint kinase Mps1 not only inhibits anaphase but also corrects erroneous attachments that could lead to missegregation and aneuploidy. However, Mps1's error correction-relevant substrates are unknown. Using a chemically tuned kinetochore-targeting assay, we show that Mps1 destabilizes microtubule attachments (K fibers) epistatically to Aurora B, the other major error-correcting kinase. Through quantitative proteomics, we identify multiple sites of Mps1-regulated phosphorylation at the outer kinetochore...
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28436952/playing-polo-during-mitosis-plk1-takes-the-lead
#7
REVIEW
G Combes, I Alharbi, L G Braga, S Elowe
Polo-like kinase 1 (PLK1), the prototypical member of the polo-like family of serine/threonine kinases, is a pivotal regulator of mitosis and cytokinesis in eukaryotes. Many layers of regulation have evolved to target PLK1 to different subcellular structures and to its various mitotic substrates in line with its numerous functions during mitosis. Collective work is starting to illuminate an important set of substrates for PLK1: the mitotic kinases that together ensure the fidelity of the cell division process...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28435066/cross-talk-between-sumoylation-and-phosphorylation-in-mouse-spermatocytes
#8
Yuxuan Xiao, Benjamin Lucas, Elana Molcho, Margarita Vigodner
The meiotic G2/M1 transition is mostly regulated by posttranslational modifications, however, the cross-talk between different posttranslational modifications is not well-understood, especially in spermatocytes. Sumoylation has emerged as a critical regulatory event in several developmental processes, including reproduction. In mouse oocytes, inhibition of sumoylation caused various meiotic defects and led to aneuploidy. However, the role of sumoylation in male reproduction has only begun to be elucidated. Given the important role of several SUMO targets (including kinases) in meiosis, in this study, the role of sumoylation was addressed by monitoring the G2/M1 transition in pachytene spermatocytes in vitro upon inhibition of sumoylation...
April 20, 2017: Biochemical and Biophysical Research Communications
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/28431392/characterization-of-aurora-a-and-its-impact-on-the-effect-of-cisplatin-based-chemotherapy-in-patients-with-non-small-cell-lung-cancer
#10
Peng Kuang, Zuhua Chen, JiaYuan Wang, Zhentao Liu, Jingyuan Wang, Jing Gao, Lin Shen
BACKGROUND AND OBJECTIVE: Aurora A, as a member of serine/threonine kinase family and a common characteristic of epithelial cancers, plays a critical role in cell mitosis. However, the clinical significance of Aurora A in non-small cell lung cancer (NSCLC) remains undetermined. METHODS: The expression of Aurora A in NSCLC and paired normal adjacent lung tissues was determined by immunohistochemistry, Western blot, and reverse transcriptase polymerase chain reaction...
April 18, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28430635/unsuccessful-mitosis-in-multicellular-tumour-spheroids
#11
Annie Molla, Morgane Couvet, Jean-Luc Coll
Multicellular spheroids are very attractive models in oncology because they mimic the 3D organization of the tumour cells with their microenvironment. We show here using 3 different cell types (mammary TSA/pc, embryonic kidney Hek293 and cervical cancer HeLa), that when the cells are growing as spheroids the frequency of binucleated cells is augmented as occurs in some human tumours.We therefore describe mitosis in multicellular spheroids by following mitotic markers and by time-lapse experiments. Chromosomes alignment appears to be correct on the metaphasic plate and the passenger complex is well localized on centromere...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429794/bone-in-culture-array-as-a-platform-to-model-early-stage-bone-metastases-and-discover-anti-metastasis-therapies
#12
Hai Wang, Lin Tian, Amit Goldstein, Jun Liu, Hin-Ching Lo, Kuanwei Sheng, Thomas Welte, Stephen T C Wong, Zbigniew Gugala, Fabio Stossi, Chenghang Zong, Zonghai Li, Michael A Mancini, Xiang H-F Zhang
The majority of breast cancer models for drug discovery are based on orthotopic or subcutaneous tumours. Therapeutic responses of metastases, especially microscopic metastases, are likely to differ from these tumours due to distinct cancer-microenvironment crosstalk in distant organs. Here, to recapitulate such differences, we established an ex vivo bone metastasis model, termed bone-in-culture array or BICA, by fragmenting mouse bones preloaded with breast cancer cells via intra-iliac artery injection. Cancer cells in BICA maintain features of in vivo bone micrometastases regarding the microenvironmental niche, gene expression profile, metastatic growth kinetics and therapeutic responses...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28427193/targeting-high-aurora-kinases-expression-as-an-innovative-therapy-for-hepatocellular-carcinoma
#13
Fuchen Liu, Guangyong Wang, Xiaoqiang Wang, Zhihui Che, Wei Dong, Xinggang Guo, Zhenguang Wang, Ping Chen, Daisen Hou, Qi Zhang, Wenli Zhang, Yida Pan, Dongqin Yang, Hui Liu
The Aurora kinases A and B control tumorigenesis by inhibiting apoptosis and promoting proliferation and metastasis, however, it remains unknown whether Aurora A and B overexpressed concomitantly and its clinical significance in hepatocellular carcinoma (HCC). Here, we obsearved Aurora A and B tended to overexpress parallelly on protein level (r = 0.8679, P < 0.0001) and their co-overexpression (Aurora AHBH), associated with the worst prognosis, was an independent predictor for the survival. Importantly, with the lower IC50 and stronger anti-tumor effect than selective inhibitors, SNS-314, the pan-inhibitor of Aurora kinases, which induced YAP (Yes-associated protein) reduction and resulted in P21 accumulation, significantly promoted the polyploidy (> 4N) formation and apoptosis in HCC...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423593/anti-cancer-effect-of-novel-pak1-inhibitor-via-induction-of-puma-mediated-cell-death-and-p21-mediated-cell-cycle-arrest
#14
Tae-Gyun Woo, Min-Ho Yoon, Shin-Deok Hong, Jiyun Choi, Nam-Chul Ha, Hokeun Sun, Bum-Joon Park
Hyper-activation of PAK1 (p21-activated kinase 1) is frequently observed in human cancer and speculated as a target of novel anti-tumor drug. In previous, we also showed that PAK1 is highly activated in the Smad4-deficient condition and suppresses PUMA (p53 upregulated modulator of apoptosis) through direct binding and phosphorylation. On the basis of this result, we have tried to find novel PAK1-PUMA binding inhibitors. Through ELISA-based blind chemical library screening, we isolated single compound, IPP-14 (IPP; Inhibitor of PAK1-PUMA), which selectively blocks the PAK1-PUMA binding and also suppresses cell proliferation via PUMA-dependent manner...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420331/arsenic-treatment-increase-aurora-a-overexpression-through-e2f1-activation-in-bladder-cells
#15
Yu-Ting Kao, Chin-Han Wu, Shan-Ying Wu, Sheng-Hui Lan, Hsiao-Sheng Liu, Ya-Shih Tseng
BACKGROUND: Arsenic is a widely distributed metalloid compound that has biphasic effects on cultured cells. In large doses, arsenic can be toxic enough to trigger cell death. In smaller amounts, non-toxic doses may promote cell proliferation and induces carcinogenesis. Aberration of chromosome is frequently detected in epithelial cells and lymphocytes of individuals from arsenic contaminated areas. Overexpression of Aurora-A, a mitotic kinase, results in chromosomal instability and cell transformation...
April 18, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28417568/cisplatin-resistant-cancer-cells-are-sensitive-to-aurora-kinase-a-inhibition-by-alisertib
#16
Lihong Wang, Janet Arras, Ahmed Katsha, Saif Hamdan, Abbes Belkhiri, Jeffrey Ecsedy, Wael El-Rifai
De novo and acquired resistance to platinum therapy such as cisplatin (CDDP) is a clinical challenge in gastric cancer treatment. Aberrant expression and activation of Aurora kinase A (AURKA) and eukaryotic translation initiation factor 4E (eIF4E) are detected in several cancer types. Herein, we investigated the role of AURKA in CDDP resistance in gastric cancer. Western blot analysis demonstrated overexpression of AURKA and phosphorylation of eIF4E in acquired and de novo CDDP-resistant gastric cancer models...
April 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28415769/aurora-kinase-b-dependent-phosphorylation-of-53bp1-is-required-for-resolving-merotelic-kinetochore-microtubule-attachment-errors-during-mitosis
#17
Haibo Wang, Bin Peng, Raj K Pandita, David A Engler, Risë K Matsunami, Xingzhi Xu, Pavana M Hegde, Brian E Butler, Tej K Pandita, Sankar Mitra, Bo Xu, Muralidhar L Hegde
Defects in resolving kinetochore-microtubule attachment mistakes during mitosis is linked to chromosome instability associated with carcinogenesis as well as resistance to cancer therapy. Here we report for the first time that tumor suppressor p53-binding protein 1 (53BP1) is phosphorylated at serine 1342 (S1342) by Aurora kinase B both in vitro and in human cells, which is required for optimal recruitment of 53BP1 at kinetochores. Furthermore, 53BP1 staining normally localized on the outer kinetochore, extended to the whole kinetochore when it is merotelically-attached, in concert with mitotic centromere-associated kinesin...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410270/the-aurora-kinase-inhibitor-amg-900-increases-apoptosis-and-induces-chemosensitivity-to-anticancer-drugs-in-the-nci-h295-adrenocortical-carcinoma-cell-line
#18
Kleiton S Borges, Augusto F Andrade, Vanessa S Silveira, David S Marco Antonio, Elton J R Vasconcelos, Sonir R R Antonini, Luiz G Tone, Carlos A Scrideli
Adrenocortical tumor (ACT) is a malignancy with a low incidence rate and the current therapy for advanced disease has a limited impact on overall patient survival. A previous study from our group suggested that elevated expression of aurora-A and aurora-B is associated with poor outcome in childhood ACT. Similar results were also reported for adult ACTs. The present in-vitro study shows that AMG 900 inhibits aurora kinases in adrenocortical carcinoma cells. AMG 900 inhibited cell proliferation in NCI-H295 cells as well as in the ACT primary cultures and caused apoptosis in the cell line NCI-H295...
April 13, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28404933/aurora-a-affects-radiosenstivity-in-cervical-squamous-cell-carcinoma-and-predicts-poor-prognosis
#19
Yuhua Ma, Jie Yang, Ruozheng Wang, Zegao Zhang, Xiaoli Qi, Chunhua Liu, Miaomiao Ma
BACKGROUND: Definitive radiation therapy (RT) (with or without cisplatin-based chemotherapy) is one of the most effective treatments for cervical squamous cell carcinoma (CSCC), but efficacy is limited due to resistance. In the present study, we investigated the relationship between the expression of Aurora kinase A (Aurora-A, AURKA)and response to RT in patients with CSCC. METHODS: The expression of Aurora-A in biopsy specimens of untreated primary tumors in 129 Uyghur patients with CSCC was investigated immunohistochemically...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404010/risk-stratification-of-barrett-s-oesophagus-using-a-non-endoscopic-sampling-method-coupled-with-a-biomarker-panel-a-cohort-study
#20
Caryn S Ross-Innes, Hamza Chettouh, Achilleas Achilleos, Nuria Galeano-Dalmau, Irene Debiram-Beecham, Shona MacRae, Petros Fessas, Elaine Walker, Sibu Varghese, Theodore Evan, Pierre S Lao-Sirieix, Maria O'Donovan, Shalini Malhotra, Marco Novelli, Babett Disep, Phillip V Kaye, Laurence B Lovat, Rehan Haidry, Michael Griffin, Krish Ragunath, Pradeep Bhandari, Adam Haycock, Danielle Morris, Stephen Attwood, Anjan Dhar, Colin Rees, Matt D Rutter, Richard Ostler, Benoit Aigret, Peter D Sasieni, Rebecca C Fitzgerald
BACKGROUND: Barrett's oesophagus predisposes to adenocarcinoma. However, most patients with Barrett's oesophagus will not progress and endoscopic surveillance is invasive, expensive, and fraught by issues of sampling bias and the subjective assessment of dysplasia. We investigated whether a non-endoscopic device, the Cytosponge, could be coupled with clinical and molecular biomarkers to identify a group of patients with low risk of progression suitable for non-endoscopic follow-up. METHODS: In this multicentre cohort study (BEST2), patients with Barrett's oesophagus underwent the Cytosponge test before their surveillance endoscopy...
January 2017: Lancet. Gastroenterology & Hepatology
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