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https://www.readbyqxmd.com/read/28283778/plk1-associated-micrornas-are-correlated-with-pediatric-medulloblastoma-prognosis
#1
Julia Alejandra Pezuk, María Sol Brassesco, Ricardo Santos de Oliveira, Hélio Rubens Machado, Luciano Neder, Carlos Alberto Scrideli, Luiz Gonzaga Tone
PURPOSE: Medulloblastoma (MB) is the most common malignant tumor of the central nervous system (CNS) in children. Despite its relative good survival rates, treatment can cause long time sequels and may impair patients' lifespan and quality, making the search for new treatment options still necessary. Polo like kinases (PLKs) constitute a five-member serine/threonine kinases family (PLK 1-5) that regulates different stages during cell cycle. Abnormal PLKs expression has been observed in several cancer types, including MB...
March 10, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28239299/synthetic-curcumin-derivative-dk1-possessed-g2-m-arrest-and-induced-apoptosis-through-accumulation-of-intracellular-ros-in-mcf-7-breast-cancer-cells
#2
Norlaily Mohd Ali, Swee Keong Yeap, Nadiah Abu, Kian Lam Lim, Huynh Ky, Ahmad Zaim Mat Pauzi, Wan Yong Ho, Sheau Wei Tan, Han Kiat Alan-Ong, Seema Zareen, Noorjahan Banu Alitheen, M Nadeem Akhtar
AIMS: Curcumin is a lead compound of the rhizomes of Curcuma longa and possess a broad range of pharmacological activities. Chemically, curcumin is 1,3-dicarbonyl class of compound, which exhibits keto-enol tautomerism. Despite of its strong biological properties, curcumin has yet been recommended as a therapeutic agent because of its poor bioavailability. MAIN METHODS: A curcumin derivative (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1) was synthesized and its cytotoxicity was tested on breast cancer cell MCF-7 and normal cell MCF-10A using MTT assay...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28212994/an-open-label-phase-ii-study-of-the-polo-like-kinase-1-plk-1-inhibitor-bi-2536-in-patients-with-relapsed-small-cell-lung-cancer-sclc
#3
Mark M Awad, Quincy S-C Chu, Leena Gandhi, Joe J Stephenson, Ramaswamy Govindan, Daniel S Bradford, Philip D Bonomi, David M Ellison, Keith D Eaton, Holger Fritsch, Gerd Munzert, Bruce E Johnson, Mark A Socinski
OBJECTIVES: This phase II, open-label study was designed to evaluate the response rate to the polo-like kinase 1 (Plk-1) inhibitor BI 2536 in patients with sensitive-relapsed small cell lung cancer (SCLC). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response, and safety. MATERIALS AND METHODS: Patients were treated with the recommended phase II dose of 200mg of BI 2536 intravenously every 21days. This was a two-stage design with an early stopping rule in place if responses were not seen in at least 2 of the first 18 enrolled patients...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28187036/a-brief-report-of-immunohistochemical-markers-to-identify-aggressive-hepatoblastoma
#4
Vivekanand Singh, Michelle Manalang, Meenal Singh, Udayan Apte
Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although survival of patients has improved significantly over the last 2 decades, a significant number of patients do not respond to standard chemotherapy. We conducted a pilot study to understand if there was immunophenotypic difference between tumors that respond well to chemotherapy versus that do not. We selected 10 cases of HB from children presenting at our hospital. All patients had initial tissue diagnosis, underwent chemotherapy followed by surgical resection...
February 9, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28154193/dissecting-the-molecular-pathway-involved-in-plk2-mediated-%C3%AE-synuclein-selective-autophagic-degradation
#5
Manel Dahmene, Morgan Bérard, Abid Oueslati
Increasing lines of evidence support the causal link between α-synuclein (α-syn) accumulation in the brain and Parkinson disease (PD) pathogenesis. Therefore, lowering α-syn protein levels may represent a viable therapeutic strategy for the treatment of PD and related disorders. We recently described a novel selective α-syn degradation pathway, catalyzed by the activity of the Polo-like kinase 2 (PLK2), capable of reducing α-syn protein expression and suppressing its toxicity in vivo. However, the exact molecular mechanisms underlying this degradation route remain elusive...
January 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28123064/guanylate-binding-protein-1-gbp1-contributes-to-the-immunity-of-human-mesenchymal-stromal-cells-against-toxoplasma-gondii
#6
Aiping Qin, De-Hua Lai, Qifa Liu, Weijun Huang, Ya-Ping Wu, Xiaoyong Chen, Sunxing Yan, Huimin Xia, Geoff Hide, Zhao-Rong Lun, Francisco J Ayala, Andy Peng Xiang
Mesenchymal stromal cells (MSCs) have recently been shown to play important roles in mammalian host defenses against intracellular pathogens, but the molecular mechanism still needs to be clarified. We confirmed that human MSCs (hMSCs) prestimulated with IFN-γ showed a significant and dose-dependent ability to inhibit the growth of two types of Toxoplasma gondii [type I RH strain with green fluorescent proteins (RH/GFP) or type II PLK strain with red fluorescent proteins (PLK/RED)]. However, in contrast to previous reports, the anti-T...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28063003/effect-of-poly-l-arginine-in-inhibiting-scrapie-prion-protein-of-cultured-cells
#7
Muhammad Waqas, Hye-Mi Lee, Jeeyoung Kim, Glenn Telling, Jin-Ki Kim, Dae-Hwan Kim, Chongsuk Ryou
Biological effect of poly-L-arginine (PLR), the linear homopolymer comprised of L-arginine, was investigated to determine the activity of suppressing prions. PLR decreased the level of scrapie prion protein (PrP(Sc)) in cultured cells permanently infected with prions in a concentration-dependent manner. The PrP(Sc) inhibition efficacy of PLR was greater than that of another prion-suppressant poly-L-lysine (PLK) in a molecular mass-dependent fashion. The effective concentration of PLR to inhibit prions was achieved safely below the cytotoxic concentrations, and overall cytotoxicity of PLR was similar to that of PLK...
April 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28061448/targeting-basal-like-breast-tumors-with-bromodomain-and-extraterminal-domain-bet-and-polo-like-kinase-inhibitors
#8
Cristina Nieto-Jiménez, Ana Alcaraz-Sanabria, Javier Pérez-Peña, Verónica Corrales-Sánchez, Gemma Serrano-Heras, Eva M Galán-Moya, Leticia Serrano-Oviedo, Juan Carlos Montero, Miguel Burgos, Juan Llopis, Atanasio Pandiella, Alberto Ocaña
Metastatic triple negative breast cancer (TNBC) is an incurable disease with limited therapeutic options, and no targeted therapies available. Triple negative tumors and the basal-like genomic subtype, are both characterized by a high proliferation rate and an increase in cell division. In this context, protein kinases involved in the mitotic formation have a relevant role in this tumor subtype. Recently, Bromodomain and extraterminal domain (BET) inhibitors have shown to be active in this disease by modulating the expression of several transcription factors...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27987384/salmonella-typhimurium-ptsj-is-a-novel-mocr-like-transcriptional-repressor-involved-in-regulating-the-vitamin-b6-salvage-pathway
#9
Angela Tramonti, Teresa Milano, Caterina Nardella, Martino L di Salvo, Stefano Pascarella, Roberto Contestabile
The vitamin B6 salvage pathway, involving pyridoxine 5'-phosphate oxidase (PNPOx) and pyridoxal kinase (PLK), recycles B6 vitamers from nutrients and protein turnover to produce pyridoxal 5'-phosphate (PLP), the catalytically active form of the vitamin. Regulation of this pathway, widespread in living organisms including humans and many bacteria, is very important to vitamin B6 homeostasis but poorly understood. Although some information is available on the enzymatic regulation of PNPOx and PLK, little is known on their regulation at the transcriptional level...
December 17, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27967123/head-on-collision-of-dust-acoustic-solitons-in-a-nonextensive-plasma-with-variable-size-dust-grains-of-arbitrary-charge
#10
E E Behery
The head-on collision of two dust acoustic solitons (DASs) in a nonextensive plasma with positive or negative dust grains fluid including the effect of dust size distribution (DSD) is studied. The phase shifts for the two solitons due to the collision are derived by applying the extended Poincaré-Lighthill-Kuo (PLK) method. The influences of the power law DSD and the nonextensivity of plasma particles on the characteristic properties of the head-on collision of DASs are analyzed. It is found that the phase shifts can vanish, only for the case of positive dust grains, for certain values and ranges of the dust grain radius and the entropic index of ions (q_{i})...
November 2016: Physical Review. E
https://www.readbyqxmd.com/read/27935233/kinetic-analysis-of-de-novo-centriole-assembly-in-heat-shocked-mammalian-cells
#11
In Keol Baek, Yeun Kyu Jang, Tae H Lee, JooHun Lee
Mammalian cells are capable of de novo centriole formation after the removal of existing centrioles. This suggests that de novo centriole assembly is repressed in normally duplicating cells to maintain a constant number of centrioles in the cells. However, neither the mechanism of de novo centriole assembly nor that of its hypothesized repression is understood due to the lack of an experimental system. We found that the heat shock (HS; 42°C, 2 h) of mouse embryonic fibroblasts caused the separation of centriole pairs, a transient increase in polo-like kinase (Plk) 4 expression, and the formation of a complex containing γ-tubulin, pericentrin, HS protein (Hsp) 90, and Plk4, in approximately half of the cells...
December 9, 2016: Cytoskeleton
https://www.readbyqxmd.com/read/27906199/microduplication-of-the-arid1a-gene-causes-intellectual-disability-with-recognizable-syndromic-features
#12
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/27872092/plk4-promotes-cancer-invasion-and-metastasis-through-arp2-3-complex-regulation-of-the-actin-cytoskeleton
#13
Karineh Kazazian, Christopher Go, Hannah Wu, Olga Brashavitskaya, Roland Xu, James W Dennis, Anne-Claude Gingras, Carol J 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...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/27733867/probing-unnatural-amino-acid-integration-into-enhanced-green-fluorescent-protein-by-genetic-code-expansion-with-a-high-throughput-screening-platform
#14
Georg Wandrey, Joel Wurzel, Kyra Hoffmann, Tobias Ladner, Jochen Büchs, Lorenz Meinel, Tessa Lühmann
BACKGROUND: Genetic code expansion has developed into an elegant tool to incorporate unnatural amino acids (uAA) at predefined sites in the protein backbone in response to an amber codon. However, recombinant production and yield of uAA comprising proteins are challenged due to the additional translation machinery required for uAA incorporation. RESULTS: We developed a microtiter plate-based high-throughput monitoring system (HTMS) to study and optimize uAA integration in the model protein enhanced green fluorescence protein (eGFP)...
2016: Journal of Biological Engineering
https://www.readbyqxmd.com/read/27720619/a-surveillance-system-ensures-crossover-formation-in-c-%C3%A2-elegans
#15
Tyler S Machovina, Rana Mainpal, Anahita Daryabeigi, Olivia McGovern, Dimitra Paouneskou, Sara Labella, Monique Zetka, Verena Jantsch, Judith L Yanowitz
Crossover (CO) recombination creates a physical connection between homologs that promotes their proper segregation at meiosis I (MI). Failure to realize an obligate CO causes homologs to attach independently to the MI spindle and separate randomly, leading to nondisjunction. However, mechanisms that determine whether homolog pairs have received crossovers remain mysterious. Here we describe a surveillance system in C. elegans that monitors recombination intermediates and couples their formation to meiotic progression...
November 7, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27699933/effect-of-akt3-expression-on-myc-and-caspase-8-dependent-apoptosis-caused-by-polo-like-kinase-inhibitors-in-hct-116-cells
#16
Yuma Nonomiya, Kohji Noguchi, Noritaka Tanaka, Takahiro Kasagaki, Kazuhiro Katayama, Yoshikazu Sugimoto
Polo-like kinase (PLK) is a cell-cycle regulator that is overexpressed in several cancer cell types. Polo-like kinase is considered a novel target for cancer therapies, and several PLK inhibitors (PLKis), including BI 2536, BI 6727, and GSK461364, have been developed. In this study, we established five BI 2536-resistant cell lines from human colorectal cancer HCT 116 cells, to explore the resistance mechanism and identify predictable biomarkers of PLKis. We showed that PLKi-induced caspase-8 activation was attenuated in the BI 2536-resistant cell lines...
December 2016: Cancer Science
https://www.readbyqxmd.com/read/27632389/deregulation-of-vital-mitotic-kinase-phosphatase-signaling-in-hematopoietic-stem-progenitor-compartment-leads-to-cellular-catastrophe-in-experimental-aplastic-anemia
#17
Ritam Chatterjee, Sukalpa Chattopadhyay, Sujata Law
Aplastic anemia, the paradigm of bone marrow failure, is characterized by pancytopenic peripheral blood and hypoplastic bone marrow. Among various etiologies, inappropriate use of DNA alkylating drugs like cyclophosphamide and busulfan often causes the manifestation of the dreadful disease. Cell cycle impairment in marrow hematopoietic stem/progenitor compartment together with cellular apoptosis has been recognized as culpable factors behind aplastic pathophysiologies. However, the intricate molecular mechanisms remain unrevealed till date...
November 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27608133/a-systems-biology-approach-for-elucidating-the-interaction-of-curcumin-with-fanconi-anemia-fanc-g-protein-and-the-key-disease-targets-of-leukemia
#18
David Mahato, Dipayan Samanta, Sudit S Mukhopadhyay, R Navanietha Krishnaraj
Fanconi anemia (FA) is an autosomal recessive disorder with a high risk of malignancies including acute myeloid leukemia and squamous cell carcinoma. There is a constant search out of new potential therapeutic molecule to combat this disorder. In most cases, patients with FA develop haematological malignancies with acute myeloid leukemia and acute lymphoblastic leukemia. Identifying drugs which can efficiently block the pathways of both these disorders can be an ideal and novel strategy to treat FA. The curcumin, a natural compound obtained from turmeric is an interesting therapeutic molecule as it has been reported in the literature to combat both FA as well as leukemia...
September 8, 2016: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/27592392/identification-of-acylthiourea-derivatives-as-potent-plk1-pbd-inhibitors
#19
Taikangxiang Yun, Tan Qin, Ying Liu, Luhua Lai
Thiourea derivatives have drawn much attention for their latent capacities of biological activities. In this study, we designed acylthiourea compounds as polo-like kinase 1 (Plk1) polo-box domain (PBD) inhibitors. A series of acylthiourea derivatives without pan assay interference structure (PAINS) were synthesized. Four compounds with halogen substituents exhibited binding affinities to Plk1 PBD in low micromole range. The most potent compound (3v) showed selectivity over other subtypes of Plk PBDs and inhibited the kinase activity of full-length Plk1...
November 29, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27591191/polo-like-kinase-phosphorylation-determines-caenorhabditis-elegans-centrosome-size-and-density-by-biasing-spd-5-toward-an-assembly-competent-conformation
#20
Oliver Wueseke, David Zwicker, Anne Schwager, Yao Liang Wong, Karen Oegema, Frank Jülicher, Anthony A Hyman, Jeffrey B Woodruff
Centrosomes are major microtubule-organizing centers composed of centrioles surrounded by an extensive proteinacious layer called the pericentriolar material (PCM). In Caenorhabditis elegans embryos, the mitotic PCM expands by Polo-like kinase 1 (PLK-1) phosphorylation-accelerated assembly of SPD-5 molecules into supramolecular scaffolds. However, how PLK-1 phosphorylation regulates SPD-5 assembly is not known. We found that a mutant version of SPD-5 that is insensitive to PLK-1 phosphorylation (SPD-5(4A)) could localize to PCM but was unable to rescue the reduction in PCM size and density when wild-type SPD-5 levels were decreased...
October 15, 2016: Biology Open
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