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Aurora

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https://www.readbyqxmd.com/read/28102366/aurora-kinase-a-is-a-biomarker-for-bladder-cancer-detection-and-contributes-to-its-aggressive-behavior
#1
Aaron Mobley, Shizhen Zhang, Jolanta Bondaruk, Yan Wang, Tadeusz Majewski, Nancy P Caraway, Li Huang, Einav Shoshan, Guermarie Velazquez-Torres, Giovanni Nitti, Sangkyou Lee, June Goo Lee, Enrique Fuentes-Mattei, Daniel Willis, Li Zhang, Charles C Guo, Hui Yao, Keith Baggerly, Yair Lotan, Seth P Lerner, Colin Dinney, David McConkey, Menashe Bar-Eli, Bogdan Czerniak
The effects of AURKA overexpression associated with poor clinical outcomes have been attributed to increased cell cycle progression and the development of genomic instability with aneuploidy. We used RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells. Knockdown had minimal effects on cell proliferation but blocked tumor cell invasion. Whole genome mRNA expression profiling identified nicotinamide N-methyltransferase (NNMT) as a downstream target that was repressed by AURKA...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102363/smarca4-inactivating-mutations-increase-sensitivity-to-aurora-kinase-a-inhibitor-vx-680-in-non-small-cell-lung-cancers
#2
Vural Tagal, Shuguang Wei, Wei Zhang, Rolf A Brekken, Bruce A Posner, Michael Peyton, Luc Girard, TaeHyun Hwang, David A Wheeler, John D Minna, Michael A White, Adi F Gazdar, Michael G Roth
Mutations in the SMARCA4/BRG1 gene resulting in complete loss of its protein (BRG1) occur frequently in non-small cell lung cancer (NSCLC) cells. Currently, no single therapeutic agent has been identified as synthetically lethal with SMARCA4/BRG1 loss. We identify AURKA activity as essential in NSCLC cells lacking SMARCA4/BRG1. In these cells, RNAi-mediated depletion or chemical inhibition of AURKA induces apoptosis and cell death in vitro and in xenograft mouse models. Disc large homologue-associated protein 5 (HURP/DLGAP5), required for AURKA-dependent, centrosome-independent mitotic spindle assembly is essential for the survival and proliferation of SMARCA4/BRG1 mutant but not of SMARCA4/BRG1 wild-type cells...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28101670/recombination-correlates-with-synaptonemal-complex-length-and-chromatin-loop-size-in-bovids-insights-into-mammalian-meiotic-chromosomal-organization
#3
Aurora Ruiz-Herrera, Miluse Vozdova, Jonathan Fernández, Hana Sebestova, Laia Capilla, Jan Frohlich, Covadonga Vara, Adrià Hernández-Marsal, Jaroslav Sipek, Terence J Robinson, Jiri Rubes
Homologous chromosomes exchange genetic information through recombination during meiosis, a process that increases genetic diversity, and is fundamental to sexual reproduction. In an attempt to shed light on the dynamics of mammalian recombination and its implications for genome organization, we have studied the recombination characteristics of 112 individuals belonging to 28 different species in the family Bovidae. In particular, we analyzed the distribution of RAD51 and MLH1 foci during the meiotic prophase I that serve, respectively, as proxies for double-strand breaks (DSBs) which form in early stages of meiosis and for crossovers...
January 18, 2017: Chromosoma
https://www.readbyqxmd.com/read/28101582/aurka-dlgap5-tpx2-kif11-and-ckap5-five-specific-mitosis-associated-genes-correlate-with-poor-prognosis-for-non-small-cell-lung-cancer-patients
#4
Marc A Schneider, Petros Christopoulos, Thomas Muley, Arne Warth, Ursula Klingmueller, Michael Thomas, Felix J F Herth, Hendrik Dienemann, Nikola S Mueller, Fabian Theis, Michael Meister
The growth of a tumor depends to a certain extent on an increase in mitotic events. Key steps during mitosis are the regulated assembly of the spindle apparatus and the separation of the sister chromatids. The microtubule-associated protein Aurora kinase A phosphorylates DLGAP5 in order to correctly segregate the chromatids. Its activity and recruitment to the spindle apparatus is regulated by TPX2. KIF11 and CKAP5 control the correct arrangement of the microtubules and prevent their degradation. In the present study, we investigated the role of these five molecules in non-small cell lung cancer (NSCLC)...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28101375/aurora-a-promotes-the-establishment-of-spindle-assembly-checkpoint-by-priming-the-haspin-aurora-b-feedback-loop-in-late-g2-phase
#5
Fazhi Yu, Ya Jiang, Lucy Lu, Mimi Cao, Yulong Qiao, Xing Liu, Dan Liu, Terry Van Dyke, Fangwei Wang, Xuebiao Yao, Jing Guo, Zhenye Yang
Aurora-A kinase functions mainly in centrosome maturation, separation and spindle formation. It has also been found to be amplified or overexpressed in a range of solid tumors, which is linked with tumor progression and poor prognosis. Importantly, Aurora-A inhibitors are being studied in a number of ongoing clinical trials. However, whether and how Aurora-A has a role in the regulation of the mitotic checkpoint is controversial. Additionally, the function of nuclear-accumulated Aurora-A in late G2 phase is not clear...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28100163/a-vector-based-short-hairpin-rna-targeting-aurora-b-suppresses-human-prostatic-carcinoma-growth
#6
Mei Cao, Panpan Qi, Chong Chen, Liju Song, Xuege Wang, Ningzhe Li, Daoyan Wu, Guoku Hu, Jian Zhao
Aurora kinase B, playing a vital, important role in mitosis, is frequently detected to be overexpressed in many cancer cell lines and various tumor tissues, including prostatic carcinoma. Given the essential function of Aurora kinase B in mitosis and its association with tumorigenesis, it might be a drug target for prostatic carcinoma treatment. In our study, short hairpin RNA targeting Aurora kinase B was cloned into a pGPU6 plasmid vector and then transfected into human prostatic carcinoma cells. The expression level of Aurora kinase B was verified by reverse transcription-polymerase chain reaction and Western blot...
February 2017: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/28099149/clinically-relevant-hif-1%C3%AE-dependent-metabolic-reprogramming-in-oropharyngeal-squamous-cell-carcinomas-includes-coordinated-activation-of-caix-and-the-mir-210-iscu-signaling-axis-but-not-mct1-and-mct4-upregulation
#7
Inés Sáenz-de-Santa-María, Cristóbal Bernardo-Castiñeira, Pablo Secades, Sandra Bernaldo-de-Quirós, Juan Pablo Rodrigo, Aurora Astudillo, María-Dolores Chiara
Metabolic reprogramming is a very heterogeneous phenomenon in cancer. It mostly consists on increased glycolysis, lactic acid formation and extracellular acidification. These events have been associated to increased activity of the hypoxia inducible factor, HIF-1α. This study aimed at defining the metabolic program activated by HIF-1α in oropharyngeal squamous cell carcinomas (SCC) and assessing its clinical impact. Global gene/miRNA expression was analyzed in SCC-derived cells exposed to hypoxia. Expression of HIF-1α, the carbonic anhydrase CAIX, and the lactate/H+ transporters MCT1 and MCT4 were analyzed by immunohistochemistry in 246 SCCs...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28095398/aurora-b-expression-modulates-paclitaxel-response-in-non-small-cell-lung-cancer
#8
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...
January 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28089889/myc-drives-progression-of-small-cell-lung-cancer-to-a-variant-neuroendocrine-subtype-with-vulnerability-to-aurora-kinase-inhibition
#9
Gurkan Mollaoglu, Matthew R Guthrie, Stefanie Böhm, Johannes Brägelmann, Ismail Can, Paul M Ballieu, Annika Marx, Julie George, Christine Heinen, Milind D Chalishazar, Haixia Cheng, Abbie S Ireland, Kendall E Denning, Anandaroop Mukhopadhyay, Jeffery M Vahrenkamp, Kristofer C Berrett, Timothy L Mosbruger, Jun Wang, Jessica L Kohan, Mohamed E Salama, Benjamin L Witt, Martin Peifer, Roman K Thomas, Jason Gertz, Jane E Johnson, Adi F Gazdar, Robert J Wechsler-Reya, Martin L Sos, Trudy G Oliver
Loss of the tumor suppressors RB1 and TP53 and MYC amplification are frequent oncogenic events in small cell lung cancer (SCLC). We show that Myc expression cooperates with Rb1 and Trp53 loss in the mouse lung to promote aggressive, highly metastatic tumors, that are initially sensitive to chemotherapy followed by relapse, similar to human SCLC. Importantly, MYC drives a neuroendocrine-low "variant" subset of SCLC with high NEUROD1 expression corresponding to transcriptional profiles of human SCLC. Targeted drug screening reveals that SCLC with high MYC expression is vulnerable to Aurora kinase inhibition, which, combined with chemotherapy, strongly suppresses tumor progression and increases survival...
December 31, 2016: Cancer Cell
https://www.readbyqxmd.com/read/28086816/rationale-description-and-baseline-findings-of-a-community-based-prospective-cohort-study-of-kidney-function-amongst-the-young-rural-population-of-northwest-nicaragua
#10
Marvin González-Quiroz, Armando Camacho, Dorien Faber, Aurora Aragón, Catharina Wesseling, Jason Glaser, Jennifer Le Blond, Liam Smeeth, Dorothea Nitsch, Neil Pearce, Ben Caplin
BACKGROUND: An epidemic of Mesoamerican Nephropathy (MeN) is killing thousands of agricultural workers along the Pacific coast of Central America, but the natural history and aetiology of the disease remain poorly understood. We have recently commenced a community-based longitudinal study to investigate Chronic Kidney Disease (CKD) in Nicaragua. Although logistically challenging, study designs of this type have the potential to provide important insights that other study designs cannot...
January 13, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28079881/translational-upregulation-of-aurora-a-by-hnrnp-q1-contributes-to-cell-proliferation-and-tumorigenesis-in-colorectal-cancer
#11
Chien-Hsien Lai, Yu-Chuan Huang, Jenq-Chang Lee, Joseph Ta-Chien Tseng, Kung-Chao Chang, Yen-Ju Chen, Nai-Jhu Ding, Pao-Hsuan Huang, Wen-Chang Chang, Bo-Wen Lin, Ruo-Yu Chen, Yu-Chu Wang, Yi-Chien Lai, Liang-Yi Hung
By using RNA-immunoprecipitation assay following next-generation sequencing, a group of cell cycle-related genes targeted by hnRNP Q1 were identified, including Aurora-A kinase. Overexpressed hnRNP Q1 can upregulate Aurora-A protein, but not alter the mRNA level, through enhancing the translational efficiency of Aurora-A mRNA, either in a cap-dependent or -independent manner, by interacting with the 5'-UTR of Aurora-A mRNA through its RNA-binding domains (RBDs) 2 and 3. By ribosomal profiling assay further confirmed the translational regulation of Aurora-A mRNA by hnRNP Q1...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28078813/host-defense-peptide-derived-privileged-scaffolds-for-anti-infective-drug-discovery
#12
Ersilia Nigro, Irene Colavita, Daniela Sarnataro, Olga Scudiero, Aurora Daniele, Francesco Salvatore, Antonello Pessi
'Privileged scaffolds' are molecular frameworks which have been successfully exploited for small molecule drug discovery. Peptide privileged scaffolds, featuring a strictly conserved multiple-disulfide framework and high variability in the rest of the sequence, display a broad range of biological effects, including antimicrobial and antiviral activity. Unlike small molecules, however, the cost of manufacturing these peptides is high, and their synthesis challenging. We previously described a simplified privileged scaffold corresponding to the γ-core of human β-defensin-3 (HBD3)...
January 12, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28077821/ascending-aortic-constriction-promotes-cardiomyocyte-proliferation-in-neonatal-rats
#13
Zhenhua Wang, Sebastian Schmull, Hui Zheng, Jianggui Shan, Rongjiang Zou, Song Xue
Adult heart suffering from increased workload will undergo myocardial hypertrophy, subsequent cardiomyocyte (CM) death, and eventually heart failure. However, the effect of increasing afterload on the neonatal heart remains unknown. We performed ascending aortic constriction (AAC) in neonatal rats 8-12 hours after birth (P0, P indicates postpartum). Seven days after surgery, in vivo heart function was evaluated using cardiac ultrasonography. Haematoxylineosin and Masson staining were used to assess CM diameter and collagen deposition...
January 11, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28077684/targeting-aurora-kinase-a-and-jak2-prevents-gvhd-while-maintaining-treg-and-antitumor-ctl-function
#14
Brian C Betts, Anandharaman Veerapathran, Joseph Pidala, Hua Yang, Pedro Horna, Kelly Walton, Christopher L Cubitt, Steven Gunawan, Harshani R Lawrence, Nicholas J Lawrence, Said M Sebti, Claudio Anasetti
Graft-versus-host disease (GVHD) is a leading cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation. T cell costimulation by CD28 contributes to GVHD, but prevention is incomplete when targeting CD28, downstream mammalian target of rapamycin (mTOR), or Aurora A. Likewise, interleukin-6 (IL-6)-mediated Janus kinase 2 (JAK2) signaling promotes alloreactivity, yet JAK2 inhibition does not eliminate GVHD. We provide evidence that blocking Aurora A and JAK2 in human T cells is synergistic in vitro, prevents xenogeneic GVHD, and maintains antitumor responses by cytotoxic T lymphocytes (CTLs)...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28073841/activation-of-eif4e-by-aurora-kinase-a-depicts-a-novel-druggable-axis-in-everolimus-resistant-cancer-cells
#15
Ahmed Katsha, Lihong Wang, Janet Arras, Omar M Omar, Jeffrey A Ecsedy, Abbes Belkhiri, Wael El-Rifai
PURPOSE: In this study, we investigated the role of Aurora kinase A (AURKA) in regulating EIF4E, cap-dependent translation, and resistance to mTOR inhibitor, RAD001 (everolimus). EXPERIMENTAL DESIGN: Tumor xenografts and in vitro cell models of upper gastrointestinal adenocarcinomas (UGCs) were used to determine the role of AURKA in activation of EIF4E and cap-dependent translation. Overexpression, knockdown, and pharmacologic inhibition of AURKA were used in vitro and in vivo...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28072537/a-qm-mm-study-of-substituent-and-solvent-effects-on-the-excited-state-dynamics-of-the-photoactive-yellow-protein-chromophore
#16
Francisco Fernández García-Prieto, Aurora Muñoz-Losa, Ignacio Fdez Galván, M Luz Sánchez, Manuel Ángel Aguilar, M Elena Martín
Substituent and solvent effects on the excited state dynamics of the Photoactive Yellow Protein chromophore are studied using the average solvent electrostatic potential from molecular dynamics (ASEP/MD) method. Four molecular models were considered: the ester and thioester derivatives of the p-coumaric acid anion and their methyla ted derivatives. We found that the solvent produces dramatic modifications on the free energy profile of the S1 state: 1) Two twisted structures that are minima in gas phase could not be located in aqueous solution...
January 10, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28071729/rules-of-tissue-packing-involving-different-cell-types-human-muscle-organization
#17
Daniel Sánchez-Gutiérrez, Aurora Sáez, Pedro Gómez-Gálvez, Carmen Paradas, Luis M Escudero
Natural packed tissues are assembled as tessellations of polygonal cells. These include skeletal muscles and epithelial sheets. Skeletal muscles appear as a mosaic composed of two different types of cells: the "slow" and "fast" fibres. Their relative distribution is important for the muscle function but little is known about how the fibre arrangement is established and maintained. In this work we capture the organizational pattern in two different healthy muscles: biceps brachii and quadriceps. Here we show that the biceps brachii muscle presents a particular arrangement, based on the different sizes of slow and fast fibres...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28071063/acute-psychotic-episode-secondary-to-helicobacter-pylori-eradication-treatment
#18
Rubén Fernández Martos, Aurora Burgos García, Consuelo Froilán Torres
The side effects of Helicobacter pylori (H. pylori) eradication treatment are few, usually in the form of gastrointestinal or allergic complaints. However, occasionally, some antibiotics including clarithromycin, included in the classic eradication regimen, may result in reversible psychosis, a condition called "antibiomania" or "Hoigne syndrome".
January 10, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28070204/evaluation-of-lactobacillus-coryniformis-cect5711-strain-as-a-coadjuvant-in-a-vaccination-process-a-randomised-clinical-trial-in-healthy-adults
#19
Noemí Redondo, Esther Nova, Alina Gheorghe, Ligia Esperanza Díaz, Aurora Hernández, Ascensión Marcos
BACKGROUND: Although the effects of probiotics on the immune system have been extensively evaluated under disease states, their role in healthy situations remains unclear, since changes are hardly expected under immunological homeostasis. EFSA indicates that vaccination protocols could be used to evaluate the potential role of probiotics to improve the immune response against antigen challenges. The aim of the study was to evaluate the effect of Lactobacillus coryniformis CECT5711 (Lc) on the specific immunity of healthy volunteers undergoing vaccination with Hepatitis A virus (HAV)...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28069801/aurora-a-and-nf-%C3%AE%C2%BAb-survival-pathway-drive-chemoresistance-in-acute-myeloid-leukemia-via-the-traf-interacting-protein-tifa
#20
Tong-You Wade Wei, Pei-Yu Wu, Ting-Jung Wu, Hsin-An Hou, Wen-Chien Chou, Chieh-Lin Jerry Teng, Chih-Ru Lin, Jo-Mei Maureen Chen, Ting-Yang Lin, Hsiang-Chun Su, Chia-Chi Flora Huang, Chang-Tze Ricky Yu, Shih-Lan Hsu, Hwei-Fang Tien, Ming-Daw Tsai
Aurora A-dependent NF-κB signaling portends poor prognosis in acute myeloid leukemia (AML) and other cancers, but the functional basis underlying this association is unclear. Here, we report that Aurora A is essential for Thr9 phosphorylation of the TRAF-interacting protein TIFA, triggering activation of the NF-κB survival pathway in AML. TIFA protein was overexpressed concurrently with Aurora A and NF-κB signaling factors in patients with de novo AML relative to healthy individuals and also correlated with poor prognosis...
January 15, 2017: Cancer Research
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