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https://www.readbyqxmd.com/read/27911707/the-plk4-stil-sas-6-module-at-the-core-of-centriole-duplication
#1
REVIEW
Christian Arquint, Erich A Nigg
Centrioles are microtubule-based core components of centrosomes and cilia. They are duplicated exactly once during S-phase progression. Central to formation of each new (daughter) centriole is the formation of a nine-fold symmetrical cartwheel structure onto which microtubule triplets are deposited. In recent years, a module comprising the protein kinase polo-like kinase 4 (PLK4) and the two proteins STIL and SAS-6 have been shown to stay at the core of centriole duplication. Depletion of any one of these three proteins blocks centriole duplication and, conversely, overexpression causes centriole amplification...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27909341/intracellular-mechanisms-of-solar-water-disinfection
#2
María Castro-Alférez, María Inmaculada Polo-López, Pilar Fernández-Ibáñez
Solar water disinfection (SODIS) is a zero-cost intervention measure to disinfect drinking water in areas of poor access to improved water sources, used by more than 6 million people in the world. The bactericidal action of solar radiation in water has been widely proven, nevertheless the causes for this remain still unclear. Scientific literature points out that generation of reactive oxygen species (ROS) inside microorganisms promoted by solar light absorption is the main reason. For the first time, this work reports on the experimental measurement of accumulated intracellular ROS in E...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27908889/microrna-146a-induces-lineage-negative-bone-marrow-cell-apoptosis-and-senescence-by-targeting-polo-like-kinase-2-expression
#3
Shanming Deng, Huilan Wang, Chunling Jia, Shoukang Zhu, Xianming Chu, Qi Ma, Jianqin Wei, Emily Chen, Wei Zhu, Conrad J Macon, Dushyantha T Jayaweera, Derek M Dykxhoorn, Chunming Dong
OBJECTIVE: Lineage-negative bone marrow cells (lin- BMCs) are enriched in endothelial progenitor cells and mediate vascular repair. Aging-associated senescence and apoptosis result in reduced number and functionality of lin- BMCs, impairing their prorepair capacity. The molecular mechanisms underlying lin- BMC senescence and apoptosis are poorly understood. MicroRNAs (miRNAs) regulate many important biological processes. The identification of miRNA-mRNA networks that modulate the health and functionality of lin- BMCs is a critical step in understanding the process of vascular repair...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27906199/microduplication-of-the-arid1a-gene-causes-intellectual-disability-with-recognizable-syndromic-features
#4
Marie Bidart, Michèle El Atifi, Sarra Miladi, John Rendu, Véronique Satre, Pierre F Ray, Caroline Bosson, Françoise Devillard, Daphné Lehalle, Valérie Malan, Jeanne Amiel, Maria Antonietta Mencarelli, Margherita Baldassarri, Alessandra Renieri, Jill Clayton-Smith, Gaëlle Vieville, Julien Thevenon, Florence Amblard, François Berger, Pierre-Simon Jouk, Charles Coutton
PURPOSE: To determine whether duplication of the ARID1A gene is responsible for a new recognizable syndrome. METHODS: We describe four patients with a 1p36.11 microduplication involving ARID1A as identified by array-comparative genomic hybridization . We performed comparative transcriptomic analysis of patient-derived fibroblasts using RNA sequencing and evaluated the impact of ARID1A duplication on the cell cycle using fluorescence-activated cell sorting. Functional relationships between differentially expressed genes were investigated with ingenuity pathway analysis (IPA)...
December 1, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27905068/inhibition-of-mevalonate-pathway-and-synthesis-of-the-storage-lipids-in-human-liver-derived-and-non-liver-cell-lines-by-lippia-alba-essential-oils
#5
Sandra Montero-Villegas, Mónica Polo, Marianela Galle, Boris Rodenak-Kladniew, María Castro, Ana Ves-Losada, Rosana Crespo, Margarita García de Bravo
The essential oils (EOs) of Lippia alba, an herb extensively used as a folk medicine in Latin America, are today promoted as an effective means of eliminating problems caused by hyperlipemia. We hypothesized that L.alba EOs inhibited cholesterol and triacylglycerols synthesis and decreased the intracellular depots of those lipids (lipid droplets), mechanisms involving the induction of a hypolipidemic response. Our aim was, therefore, to evaluate the hypolipogenic capability of the EOs of four L. alba chemotypes on liver-derived (HepG2) and non-liver (A549) human cell lines and to identify the potential biochemical targets of those chemotypes, particularly within the mevalonate pathway (MP)...
November 30, 2016: Lipids
https://www.readbyqxmd.com/read/27905053/seom-clinical-guideline-of-localized-rectal-cancer-2016
#6
E González-Flores, F Losa, C Pericay, E Polo, S Roselló, M J Safont, R Vera, J Aparicio, M T Cano, C Fernández-Martos
Localized rectal adenocarcinoma is a heterogeneous disease and current treatment recommendations are based on a preoperative multidisciplinary evaluation. High-resolution magnetic resonance imaging and endoscopic ultrasound are complementary to do a locoregional accurate staging. Surgery remains the mainstay of treatment and preoperative therapies with chemoradiation (CRT) or short-course radiation (SCRT) must be considered in more locally advanced cases. Novel strategies with induction chemotherapy alone or preceding or after CRT (SCRT) and surgery are in development...
November 30, 2016: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/27904765/volasertib-suppresses-the-growth-of-human-hepatocellular-carcinoma-in-vitro-and-in-vivo
#7
Di-Wei Zheng, You-Qiu Xue, Yong Li, Jin-Ming Di, Jian-Ge Qiu, Wen-Ji Zhang, Qi-Wei Jiang, Yang Yang, Yao Chen, Meng-Ning Wei, Jia-Rong Huang, Kun Wang, Xing Wei, Zhi Shi
Hepatocellular carcinoma (HCC) is the sixth most frequent malignant tumor with poor prognosis, and its clinical therapeutic outcome is poor. Volasertib, a potent small molecular inhibitor of polo-like kinase 1 (PLK1), is currently tested for treatment of multiple cancers in the clinical trials. However, the antitumor effect of volasertib on HCC is still unknown. In this study, our data show that volasertib is able to induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the spindle abnormalities in human HCC cells...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27902970/activity-of-the-novel-polo-like-kinase-4-inhibitor-cfi-400945-in-pancreatic-cancer-patient-derived-xenografts
#8
I Lohse, J M Mason, P J Cao, Melania Pintilie, M R Bray, D W Hedley
BACKGROUND: Polo-like kinase 4 (PKL4) plays a key role in centriole replication. Hence PLK4 inhibition disrupts mitosis, and offers a novel approach to treating chromosomally unstable cancers, including pancreatic cancer. CFI-400945 is a first in class small molecule PLK4 inhibitor, currently undergoing early phase clinical trials. RESULTS: Treatment with CFI-400945 significantly reduced tumor growth and increased survival in four out of the six models tested. Consistent with PLK4 inhibition, we observed reduced expression of the proliferation marker Ki-67 associated with an increase in nuclear diameter during treatment with CFI-400945...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902479/identification-of-a-novel-polo-like-kinase-1-inhibitor-that-specifically-blocks-the-functions-of-polo-box-domain
#9
Yunyu Chen, Jing Zhang, Dongsheng Li, Jiandong Jiang, Yanchang Wang, Shuyi Si
Polo-like kinase 1 (Plk1) is a promising target for cancer therapy due to its essential role in cell division. In addition to a highly conserved kinase domain, Plk1 also contains a Polo-Box domain (PBD), which is essential for Plk1's subcellular localization and mitotic functions. We adopted a fluorescence polarization assay and identified a new Plk1 PBD inhibitor T521 from a small-molecule compound library. T521 specifically inhibits the PBD of Plk1, but not those of Plk2-3. T521 exhibits covalent binding to some lysine residues of Plk1 PBD, which causes significant changes in the secondary structure of Plk1 PBD...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899378/cervical-cancer-growth-is-regulated-by-a-c-abl-plk1-signaling-axis
#10
Xu Yang, Gang Chen, Wei Li, Changmin Peng, Yue Zhu, Xiaoming Yang, Teng Li, Cheng Cao, Huadong Pei
The non-receptor tyrosine kinase c-ABL controls cell growth but its contributions in solid tumors are not fully understood. Here we report that the Polo-like kinase PLK1, an essential mitotic kinase regulator, is an important downstream effector of c-ABL in regulating the growth of cervical cancer. c-ABL interacted with and phosphorylated PLK1. Phosphorylation of PLK1 by c-ABL inhibited PLK1 ubiquitination and degradation and enhanced its activity, leading to cell cycle progression and tumor growth. Both c-ABL and PLK1 were overexpressed in cervical carcinoma...
November 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27895542/effect-of-tart-cherry-juice-on-recovery-and-next-day-performance-in-well-trained-water-polo-players
#11
Rachel McCormick, Peter Peeling, Martyn Binnie, Brian Dawson, Marc Sim
BACKGROUND: Tart Montmorency cherries contain high concentrations of phytochemicals and anthocyanins, which have recently been linked to improved athletic recovery and subsequent performance. To date however, previous work reporting promising results has focused on land-based endurance sports, with any potential benefits to team sports remaining unknown. As such, this investigation set-out to examine the effect of supplemental tart cherry juice (CJ) on recovery and next day athletic performance in highly-trained water-based team sport athletes over seven days...
2016: Journal of the International Society of Sports Nutrition
https://www.readbyqxmd.com/read/27888710/plk1-a-potential-target-for-cancer-therapy
#12
REVIEW
Zhixian Liu, Qingrong Sun, Xiaosheng Wang
Polo-like kinase 1 (PLK1) plays an important role in the initiation, maintenance, and completion of mitosis. Dysfunction of PLK1 may promote cancerous transformation and drive its progression. PLK1 overexpression has been found in a variety of human cancers and was associated with poor prognoses in cancers. Many studies have showed that inhibition of PLK1 could lead to death of cancer cells by interfering with multiple stages of mitosis. Thus, PLK1 is expected to be a potential target for cancer therapy. In this article, we examined PLK1's structural characteristics, its regulatory roles in cell mitosis, PLK1 expression, and its association with survival prognoses of cancer patients in a wide variety of cancer types, PLK1 interaction networks, and PLK1 inhibitors under investigation...
November 23, 2016: Translational Oncology
https://www.readbyqxmd.com/read/27882722/designed-inhibitor-for-nuclear-localization-signal-of-polo-like-kinase-1-induces-mitotic-arrest
#13
Fangjin Chen, Xiaolong Zhuo, Tan Qin, Xiao Guo, Chuanmao Zhang, Luhua Lai
Polo-like kinase 1 (Plk1), a member of polo-like kinase family, regulates multiple essential steps of the cell cycle progression. Plk1 is overexpressed in multiple cancer cell lines and considered to be a prime anticancer target. Plk1 accumulates in the nucleus during S and G2 phases by its bipartite nuclear localization signal (NLS) sequence, which is crucial for Plk1 regulation during normal cell cycle progression. Here, through combined computational and experimental studies, we identified compound D110, which inhibits Plk1 kinase activity with an IC50 of 85 nm and blocks the nuclear localization of Plk1 during S and G2 phases...
November 24, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27878946/targeted-inhibition-of-polo-like-kinase-1-by-a-novel-small-molecule-inhibitor-induces-mitotic-catastrophe-and-apoptosis-in-human-bladder-cancer-cells
#14
Zhe Zhang, Guojun Zhang, Chuize Kong
Bladder cancer is a common cancer with particularly high recurrence after transurethral resection. Despite improvements in neoadjuvant chemotherapy, the outcome of patients with advanced bladder cancer has changed very little. In this study, the anti-tumour activities of a novel Polo-like kinase 1 (PLK1) inhibitor (RO3280) was evaluated in vitro and in vivo in the bladder carcinoma cell lines 5637 and T24. MTT assays, colony-formation assays, flow cytometry, cell morphological analysis and trypan blue exclusion assays were used to examine the proliferation, cell cycle distribution and apoptosis of bladder carcinoma cells with or without RO3280 treatment...
November 23, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27875595/phosphorylation-of-serine-235-of-the-hepatitis-c-virus-non-structural-protein-ns5a-by-multiple-kinases
#15
Kuan-Ying Lee, Yi-Hung Chen, Shih-Chin Hsu, Ming-Jiun Yu
Phosphorylation at serine 235 (S235) of the hepatitis C virus (HCV) non-structural protein 5A (NS5A) plays a critical role in the viral life cycle. For medical and virological interests, we exploited the HEK293T kidney cells to test 3 candidate protein kinases on NS5A S235 phosphorylation. Inhibitors that inhibit casein kinase I α (CKIα), polo-like kinase I (PlKI) or calmodulin-dependent kinase II (CaMKII) all reduced NS5A S235 phosphorylation. CKIα was studied previously and PlKI had severe cytotoxicity, thus CaMKII was selected for validation in the Huh7...
2016: PloS One
https://www.readbyqxmd.com/read/27874094/identification-of-polo-like-kinase-1-interaction-inhibitors-using-a-novel-cell-based-assay
#16
Karine Normandin, Jean-François Lavallée, Marie Futter, Alexandre Beautrait, Jean Duchaine, Sébastien Guiral, Anne Marinier, Vincent Archambault
Polo-like kinase 1 (Plk1) plays several roles in cell division and it is a recognized cancer drug target. Plk1 levels are elevated in cancer and several types of cancer cells are hypersensitive to Plk1 inhibition. Small molecule inhibitors of the kinase domain (KD) of Plk1 have been developed. Their selectivity is limited, which likely contributes to their toxicity. Polo-like kinases are characterized by a Polo-Box Domain (PBD), which mediates interactions with phosphorylation substrates or regulators. Inhibition of the PBD could allow better selectivity or result in different effects than inhibition of the KD...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872754/evaluation-of-contrast-sensitivity-chromatic-vision-and-reading-ability-in-patients-with-primary-open-angle-glaucoma
#17
Maria P Bambo, Blanca Ferrandez, Noemi Güerri, Isabel Fuertes, Beatriz Cameo, Vicente Polo, Jose M Larrosa, Elena Garcia-Martin
Purpose. To compare contrast sensitivity, acquired color vision deficiency, and reading ability in patients with glaucoma at different stages of the disease and to establish correlations between visual field parameters and visual function scores. Methods. This prospective cross-sectional study included 121 glaucoma patients. Subjects with a diagnosis of chronic open angle glaucoma were recruited and classified according to Hodapp-Parrish-Anderson criteria. Patients with severe visual field defects were excluded because they were older, which could bias the interpretation of visual function tests...
2016: Journal of Ophthalmology
https://www.readbyqxmd.com/read/27872092/plk4-promotes-cancer-invasion-and-metastasis-through-arp2-3-complex-regulation-of-the-actin-cytoskeleton
#18
Karineh Kazazian, Christopher D Go, Hannah Wu, Olga Brashavitskaya, Roland S Z Xu, James W Dennis, Anne-Claude Gingras, Carol Swallow
The polo family serine threonine kinase Plk4 has been proposed as a therapeutic target in advanced cancers based on increased expression in primary human cancers, facilitation of tumor growth in murine xenograft models, and centrosomal amplification induced by its overexpression. However, both the causal link between these phenomena and the feasibility of selective Plk4 inhibition remain unclear. Here we characterize Plk4-dependent cancer cell migration and invasion as well as local invasion and metastasis of cancer xenografts...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27869877/-computerized-decision-support-systems-ebm-at-the-bedside
#19
Matteo Capobussi, Rita Banzi, Lorenzo Moja, Stefanos Bonovas, Marien González-Lorenzo, Elisa Giulia Liberati, Hernan Polo Friz, Oriana Nanni, Massimo Mangia, Francesca Ruggiero
INTRODUCTION: One of the aims of Evidence-Based Medicine is to improve quality and appropriateness of care by the expedition of the knowledge transfer process. Computerized Decision Support Systems (CDSSs) are computer programs that provide alerts to the prescribing doctor directly at the moment of medical examination. In fact, alerts are integrated within the single patient electronic health record. CDSS based on the best available and updated evidence and guidelines may be an efficient tool to facilitate the transfer of the latest results from clinical research directly at the bedside, thus supporting decision-making...
November 2016: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/27869597/digital-pcr-for-quantifying-norovirus-in-oysters-implicated-in-outbreaks-france
#20
David Polo, Julien Schaeffer, Nelly Fournet, Jean-Claude Le Saux, Sylvain Parnaudeau, Catherine McLeod, Françoise S Le Guyader
Using samples from oysters clearly implicated in human disease, we quantified norovirus levels by using digital PCR. Concentrations varied from 43 to 1,170 RNA copies/oyster. The analysis of frozen samples from the production area showed the presence of norovirus 2 weeks before consumption.
December 2016: Emerging Infectious Diseases
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