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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
#1
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/28427193/targeting-high-aurora-kinases-expression-as-an-innovative-therapy-for-hepatocellular-carcinoma
#2
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/28420331/arsenic-treatment-increase-aurora-a-overexpression-through-e2f1-activation-in-bladder-cells
#3
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/28410270/the-aurora-kinase-inhibitor-amg-900-increases-apoptosis-and-induces-chemosensitivity-to-anticancer-drugs-in-the-nci-h295-adrenocortical-carcinoma-cell-line
#4
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
#5
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/28402276/cell-cycle-protein-bora-serves-as-a-novel-poor-prognostic-factor-in-multiple-adenocarcinomas
#6
Qiong-Xia Zhang, Rui Gao, Jin Xiang, Zhong-Yu Yuan, Yuan-Min Qian, Min Yan, Zi-Feng Wang, Quentin Liu, Hai-Dong Zhao, Chang-Hong Liu
Cell cycle protein Bora has been identified to integrate the functions of three major mitotic kinases: Cyclin-dependent kinase-1, Polo-like kinase-1, and Aurora A kinase. Overexpression of Bora disrupts spindle assembly and causes genomic instability. However, the clinical relevance of Bora in cancer remains unclear. In this study, we examined the expression of Bora and its association with clinical characteristics in breast (n = 538), lung (n = 144) and gastric (n = 77) adenocarcinomas. We found that Bora was overexpressed in primary breast cancer tissues compared to paired non-cancerous tissues...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389630/identification-of-small-molecule-inhibitors-of-the-aurora-a-tpx2-complex
#7
Italia Anna Asteriti, Frederick Daidone, Gianni Colotti, Serena Rinaldo, Patrizia Lavia, Giulia Guarguaglini, Alessandro Paiardini
Aurora kinases are a family of cell division regulators that govern the correct assembly of a bipolar mitotic spindle and the fidelity of chromosome segregation. Their overexpression is associated with genomic instability and aneuploidy, and is frequently observed in cancer. Accordingly, competitive inhibitors targeting Aurora kinase activity at the ATP-binding site are being investigated for therapeutic purposes. Despite promising pre-clinical data, these molecules display moderate effects in clinical trials and incomplete selectivity, either against distinct family members, or other kinases...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28358124/domain-specific-interactions-between-mln8237-and-human-serum-albumin-estimated-by-std-and-waterlogsy-nmr-itc-spectroscopic-and-docking-techniques
#8
Hongqin Yang, Jiuyang Liu, Yanmei Huang, Rui Gao, Bin Tang, Shanshan Li, Jiawei He, Hui Li
Alisertib (MLN8237) is an orally administered inhibitor of Aurora A kinase. This small-molecule inhibitor is under clinical or pre-clinical phase for the treatment of advanced malignancies. The present study provides a detailed characterization of the interaction of MLN8237 with a drug transport protein called human serum albumin (HSA). STD and WaterLOGSY nuclear magnetic resonance (NMR)-binding studies were conducted first to confirm the binding of MLN8237 to HSA. In the ligand orientation assay, the binding sites of MLN8237 were validated through two site-specific spy molecules (warfarin sodium and ibuprofen, which are two known site-selective probes) by using STD and WaterLOGSY NMR competition techniques...
March 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28342286/switching-aurora-a-kinase-on-and-off-at-an-allosteric-site
#9
REVIEW
Richard Bayliss, Selena G Burgess, Patrick J McIntyre
Protein kinases are central players in the regulation of cell cycle and signalling pathways. Their catalytic activities are strictly regulated through post-translational modifications and protein-protein interactions that control switching between inactive and active states. These states have been studied extensively using protein crystallography, although the dynamic nature of protein kinases makes it difficult to capture all relevant states. Here, we describe two recent structures of Aurora-A kinase that trap its active and inactive states...
March 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28337805/defining-the-anti-cancer-activity-of-tricarbonyl-rhenium-complexes-induction-of-g2-m-cell-cycle-arrest-and-blockade-of-aurora-a-kinase-phosphorylation
#10
Peter V Simpson, Ilaria Casari, Silvano Paternoster, Brian W Skelton, Marco Falasca, Massimiliano Massi
Rhenium and ruthenium complexes containing N-heterocylic carbene (NHC) ligands and conjugated to indomethacin were prepared. The anticancer properties were probed against pancreatic cell lines, revealing a remarkable activity of the rhenium fragment as anticancer agent. The ruthenium complexes were found to be inactive against the same pancreatic cancer cell lines, either alone or in conjugation with indomethacin. An in depth biological study revealed the origin of the anticancer properties of the rhenium tricarbonyl fragment, of which a complete elucidation had yet to be achieved...
March 23, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28298485/mcak-mediated-regulation-of-endothelial-cell-microtubule-dynamics-is-mechano-sensitive-to-myosin-ii-contractility
#11
Lauren D'Angelo, Nicole M Myer, Kenneth A Myers
Compliance and dimensionality mechanosensing, the processes by which cells sense the physical attributes of the extracellular environment (ECM), are known to drive cell branching and shape change largely through a myosin-II-mediated reorganization of the actin and microtubule (MT) cytoskeletons. Subcellular regulation of MT dynamics is spatially controlled through a Rac1-Aurora-A kinase pathway that locally inhibits the MT depolymerizing activity of MCAK, thereby promoting leading-edge MT growth and cell polarization...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28284839/depletion-of-tumor-suppressor-kank1-induces-centrosomal-amplification-via-hyperactivation-of-rhoa
#12
Jun-Ichiro Suzuki, Badal Chandra Roy, Takunori Ogaeri, Naoto Kakinuma, Ryoiti Kiyama
Chromosome instability, frequently found in cancer cells, is caused by a deficiency in cell division, including centrosomal amplification and cytokinesis failure, and can result in abnormal chromosome content or aneuploidy. The small GTPase pathways have been implicated as important processes in cell division. We found that knockdown of a tumor suppressor protein Kank1 increases the number of cells with a micronucleus or bi-/multi-nuclei, which was likely caused by centrosomal amplification. Kank1 interacts with Daam1, known to bind to and activate a small GTPase, RhoA, in actin assembly...
March 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28269755/microrna-124-3p-affects-proliferation-migration-and-apoptosis-of-bladder-cancer-cells-through-targeting-aurka
#13
Qiuyue Yuan, Tingge Sun, Feng Ye, Weisheng Kong, Haofan Jin
OBJECTIVE: The aim of this study was to establish the relationship between miR-124-3p and Aurora A kinase (AURKA) in bladder cancer (BC). METHODS: The expressions of miR-124-3p and AURKA in BC tissues and cell lines were detected using RT-PCR and western blot. BC cells were transfected with miR-124-3p mimics and AURKA siRNA. After this cell proliferation, migration, cell cycle and apoptosis were measured using CCK-8, colony formation assay, wound healing assay and cytometry tests...
February 27, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28269749/aurora-a-regulates-autophagy-through-the-akt-pathway-in-human-prostate-cancer
#14
Shiying Zhang, Jianye Li, Gaobiao Zhou, Dawei Mu, Jingmin Yan, Jizhang Xing, Zhiyong Yao, Haibo Sheng, Di Li, Chao Lv, Bin Sun, Quan Hong, Heqing Guo
BACKGROUND: Aurora A kinase is frequently overexpressed in a variety of tumor types, including the prostate. However, the function of Aurora A in autophagy in prostate cancer has not been investigated. Here, we aimed to study the functioning mechanism and autophagy associated signaling pathways of Aurora A in prostate cancer. METHODS: To investigate the biological function of Aurora A, down-regulation of Aurora A was performed followed by functional testing assays...
February 27, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28260026/ube2c-induces-emt-through-wnt-%C3%AE-%C3%A2-catenin-and-pi3k-akt-signaling-pathways-by-regulating-phosphorylation-levels-of-aurora-a
#15
Rui Wang, Yue Song, Xi Liu, Qixue Wang, Yunfei Wang, Liwei Li, Chunsheng Kang, Qingyu Zhang
The ubiquitin-conjugating enzyme 2C (UBE2C) is the key component in the ubiquitin proteasome system (UPS) by partnering with the anaphase‑promoting complex (APC/C). A high UBE2C protein expression level has been reported in various types of human tumors. However, little is known about the precise mechanism by which UBE2C expression is downregulated in gastric cancer. We found in MGC‑803 and SGC‑7901 gastric cancer cells UBE2C‑deficient G2/M phase arrest in the cell cycle and subsequently decreased gastric adenocarcinoma tumorigenesis...
April 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28249963/cell-death-response-to-anti-mitotic-drug-treatment-in-cell-culture-mouse-tumor-model-and-the-clinic
#16
Jue Shi, Timothy J Mitchison
Anti-mitotic cancer drugs include classic microtubule-targeting drugs, such as taxanes and vinca alkaloids, and the newer spindle-targeting drugs, such as inhibitors of the motor protein, Kinesin-5 (aka KSP, Eg5, KIF11), and Aurora-A, Aurora-B and Polo-like kinases. Microtubule-targeting drugs are among the first line of chemotherapies for a wide spectrum of cancers, but patient responses vary greatly. We still lack understanding of how these drugs achieve a favorable therapeutic index, and why individual patient responses vary...
March 1, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28207834/a-cyclin-dependent-kinase-inhibitor-dinaciclib-in-preclinical-treatment-models-of-thyroid-cancer
#17
Shu-Fu Lin, Jen-Der Lin, Chuen Hsueh, Ting-Chao Chou, Richard J Wong
BACKGROUND: We explored the therapeutic effects of dinaciclib, a cyclin-dependent kinase (CDK) inhibitor, in the treatment of thyroid cancer. MATERIALS AND METHODS: Seven cell lines originating from three pathologic types of thyroid cancer (papillary, follicular and anaplastic) were studied. The cytotoxicity of dinaciclib was measured using a lactate dehydrogenase assay. The expression of proteins associated with cell cycle and apoptosis was assessed using Western blot analysis and immunofluorescence microscopy...
2017: PloS One
https://www.readbyqxmd.com/read/28205582/aurora-a-regulates-expression-of-ar-v7-in-models-of-castrate-resistant-prostate-cancer
#18
Dominic Jones, Martin Noble, Steve R Wedge, Craig N Robson, Luke Gaughan
Androgen receptor variants (AR-Vs) provide a mechanism of therapy evasion in castrate-resistant prostate cancer (CRPC), yet mechanisms of regulation remain largely unknown. Here we investigate the role of Aurora A kinase on AR-Vs in models of CRPC and show depletion of Aurora A reduces AR-V target gene expression. Importantly, knockdown of Aurora A reconfigures splicing of AR pre-mRNA to discriminately down-regulate synthesis of AR-V transcripts, including AR-V7, without effecting full-length AR mRNA; and as a consequence, AR-V-driven proliferation and survival of CRPC cells is markedly reduced...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202658/mechanisms-for-nonmitotic-activation-of-aurora-a-at-cilia
#19
REVIEW
Vladislav Korobeynikov, Alexander Y Deneka, Erica A Golemis
Overexpression of the Aurora kinase A (AURKA) is oncogenic in many tumors. Many studies of AURKA have focused on activities of this kinase in mitosis, and elucidated the mechanisms by which AURKA activity is induced at the G2/M boundary through interactions with proteins such as TPX2 and NEDD9. These studies have informed the development of small molecule inhibitors of AURKA, of which a number are currently under preclinical and clinical assessment. While the first activities defined for AURKA were its control of centrosomal maturation and organization of the mitotic spindle, an increasing number of studies over the past decade have recognized a separate biological function of AURKA, in controlling disassembly of the primary cilium, a small organelle protruding from the cell surface that serves as a signaling platform...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28188792/recruitment-of-pp1-to-the-centrosomal-scaffold-protein-cep192
#20
Isha Nasa, Laura Trinkle-Mulcahy, P Douglas, Sibapriya Chaudhuri, S P Lees-Miller, Kyung S Lee, Greg B Moorhead
Centrosomal protein of 192 kDa (CEP192) is a scaffolding protein that recruits the mitotic protein kinases Aurora A and PLK1 to the centrosome. Here we demonstrate that CEP192 also recruits the type one protein phosphatase (PP1) via a highly conserved KHVTF docking motif. The threonine of the KHVTF motif is phosphorylated during mitosis and protein kinase inhibition studies suggest this to be a PLK1-dependent process.
February 8, 2017: Biochemical and Biophysical Research Communications
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