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https://www.readbyqxmd.com/read/28881998/systematic-identification-of-feature-combinations-for-predicting-drug-response-with-bayesian-multi-view-multi-task-linear-regression
#1
Muhammad Ammad-Ud-Din, Suleiman A Khan, Krister Wennerberg, Tero Aittokallio
Motivation: A prime challenge in precision cancer medicine is to identify genomic and molecular features that are predictive of drug treatment responses in cancer cells. Although there are several computational models for accurate drug response prediction, these often lack the ability to infer which feature combinations are the most predictive, particularly for high-dimensional molecular datasets. As increasing amounts of diverse genome-wide data sources are becoming available, there is a need to build new computational models that can effectively combine these data sources and identify maximally predictive feature combinations...
July 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28858266/kinases-involved-in-both-autophagy-and-mitosis
#2
REVIEW
Zhiyuan Li, Xin Zhang
Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis...
August 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28819179/identification-of-polo-like-kinases-as-potential-novel-drug-targets-for-influenza-a-virus
#3
Marie O Pohl, Jessica von Recum-Knepper, Ariel Rodriguez-Frandsen, Caroline Lanz, Emilio Yángüez, Stephen Soonthornvacharin, Thorsten Wolff, Sumit K Chanda, Silke Stertz
In recent years genome-wide RNAi screens have revealed hundreds of cellular factors required for influenza virus infections in human cells. The long-term goal is to establish some of them as drug targets for the development of the next generation of antivirals against influenza. We found that several members of the polo-like kinases (PLK), a family of serine/threonine kinases with well-known roles in cell cycle regulation, were identified as hits in four different RNAi screens and we therefore studied their potential as drug target for influenza...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28778089/identification-of-volasertib-resistant-mechanism-and-evaluation-of-combination-effects-with-volasertib-and-other-agents-on-acute-myeloid-leukemia
#4
Yoshiya Adachi, Yuichi Ishikawa, Hitoshi Kiyoi
Volasertib, a selective PLK1 inhibitor, was effective for acute myeloid leukemia (AML) patients in clinical trials. However, its efficacy was limited in mono-therapy, and a higher incidence of fatal events was revealed in the combination with low-dose cytarabine. Thus, optimization of combination therapy with volasertib and other agents is necessary for its clinical development, and the predictive factors for response or resistance to volasertib remain largely unknown. In this study, we investigated the resistance mechanism in volasertib-resistant cell lines and the combination effects with other agents, such as azacitidine (AZA), on AML cells...
July 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28652654/bcl-2-degradation-is-an-additional-pro-apoptotic-effect-of-polo-like-kinase-inhibition-in-cholangiocarcinoma-cells
#5
Svenja Sydor, Sami Jafoui, Lena Wingerter, Sandra Swoboda, Joachim C Mertens, Guido Gerken, Ali Canbay, Andreas Paul, Christian D Fingas
AIM: To examine the influence on apoptotic mechanisms following inhibition of polo-like kinases as therapeutically approach for cholangiocellular cancer treatment. METHODS: As most cholangiocarcinomas are chemotherapy-resistant due to mechanisms preventing tumor cell death, we investigated the effect of Cisplatin on cholangiocellular carcinoma (CCA) cell lines KMCH-1 and Mz-Ch-1. Polo-like kinases (PLK) are important regulators of the cell cycle and their inhibition is discussed as a potential therapy while PLK inhibition can regulate apoptotic mediators...
June 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28648742/polo-like-kinase-2-modulates-%C3%AE-synuclein-protein-levels-by-regulating-its-mrna-production
#6
Rikke H Kofoed, Jin Zheng, Nelson Ferreira, Søren Lykke-Andersen, Mauro Salvi, Cristine Betzer, Lasse Reimer, Torben Heick Jensen, Karina Fog, Poul H Jensen
Variations in the α-synuclein-encoding SNCA gene represent the greatest genetic risk factor for Parkinson's disease (PD), and duplications/triplications of SNCA cause autosomal dominant familial PD. These facts closely link brain levels of α-synuclein with the risk of PD, and make lowering α-synuclein levels a therapeutic strategy for the treatment of PD and related synucleinopathies. In this paper, we corroborate previous findings on the ability of overexpressed Polo-like kinase 2 (PLK-2) to decrease cellular α-synuclein, but demonstrate that the process is independent of PLK-2 phosphorylating S129 in α-synuclein because a similar reduction is achieved with the non-phosphorable S129A mutant α-synuclein...
June 23, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28626898/polo-like-kinase-1-immunoreactivity-is-associated-with-metastases-in-cutaneous-melanoma
#7
Maciej Kaczorowski, Tomasz Borowiec, Piotr Donizy, Konrad Pagacz, Wojciech Fendler, Artur Lipinski, Agnieszka Halon, Rafal Matkowski
BACKGROUND: Polo-like kinase-1 (PLK-1) is one of the key regulators of cell cycle progression. Increased expression of PLK-1 was observed in several tumor types. METHODS: We immunohistochemically assessed PLK-1 expression in neoplastic and stromal compartments of 96 cutaneous melanomas, and analyzed associations between PLK-1 expression and clinicopathological characteristics. RESULTS: PLK-1 expression in cancer cells was not associated with basic clinical (eg, age, gender and tumor location) or histopathological (eg, Breslow thickness, mitotic rate and ulceration) parameters...
June 19, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28591657/agc-kinases-mechanisms-of-regulation-%C3%A2-and-innovative-drug-development
#8
REVIEW
Alejandro E Leroux, Jörg O Schulze, Ricardo M Biondi
The group of AGC kinases consists of 63 evolutionarily related serine/threonine protein kinases comprising PDK1, PKB/Akt, SGK, PKC, PRK/PKN, MSK, RSK, S6K, PKA, PKG, DMPK, MRCK, ROCK, NDR, LATS, CRIK, MAST, GRK, Sgk494, and YANK, while two other families, Aurora and PLK, are the most closely related to the group. Eight of these families are physiologically activated downstream of growth factor signalling, while other AGC kinases are downstream effectors of a wide range of signals. The different AGC kinase families share aspects of their mechanisms of inhibition and activation...
June 4, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28581882/nutriproteomic-analysis-of-hwangmaemok-induced-antiangiogenic-effect-using-antibody-arrayed-protein-chip-assay
#9
Yu Mi Park, Min-A Kim, Hee Tae Jung, Hwa Jeong Kang, Hwa-Seung Yoo, In-Cheol Kang
We investigated the antiangiogenic effects of Lindera obtusiloba Blume (Hwangmaemok, HMM), which is a plant in the Lauraceae family that is commonly used to treat colds and gastritis. Moreover, given that a recent study reported the inhibitory effects of HMM extract on cancer metastasis, we hypothesized that HMM extract might possess and antiangiogenic function. Thus, this study was conducted to investigate the effects of HMM extract on endothelial cell proliferation, migration, and neovascularization in chick chorioallantoic membrane (CAM), and investigated the molecular mechanism of antiangiogenesis using a ProteoChip-based proteomics technology...
June 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28433941/self-assembled-dual-responsive-micelles-stabilized-with-protein-for-co-delivery-of-drug-and-sirna-in-cancer-therapy
#10
M R Aji Alex, Chetan Nehate, Srivani Veeranarayanan, D Sakthi Kumar, Ritu Kulshreshtha, Veena Koul
Design of safe and efficient vehicles for the combinatorial delivery of drugs and genetic agents is an emerging requisite for achieving enhanced therapeutic effect in cancer. Even though several nanoplatforms have been explored for the co-delivery of drugs and genetic materials the translation of these systems to clinical phase is still a challenge, mainly due to tedious synthesis procedures, lack of serum stability, inefficient scalability etc. Here in, we report development of reduction and pH sensitive polymeric graft of low molecular weight poly (styrene -alt -maleic anhydride) and evaluation of its efficacy in co-delivering drug and siRNA...
July 2017: Biomaterials
https://www.readbyqxmd.com/read/28415805/regulatory-functional-territory-of-plk-1-and-their-substrates-beyond-mitosis
#11
REVIEW
Shiv Kumar, Garima Sharma, Chiranjib Chakraborty, Ashish Ranjan Sharma, Jaebong Kim
Polo-like kinase 1 (PLK-1) is a well-known (Ser/Thr) mitotic protein kinase and is considered as a proto-oncogene. As hyper-activation of PLK-1 is broadly associated with poor prognosis and cancer progression, it is one of the most extensively studied mitotic kinases. During mitosis, PLK-1 regulates various cell cycle events, such as spindle pole maturation, chromosome segregation and cytokinesis. However, studies have demonstrated that the role of PLK-1 is not only restricted to mitosis, but PLK-1 can also regulate other vital events beyond mitosis, including transcription, translation, ciliogenesis, checkpoint adaptation and recovery, apoptosis, chromosomes dynamics etc...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28346135/polo-like-kinase-dependent-phosphorylation-of-the-synaptonemal-complex-protein-syp-4-regulates-double-strand-break-formation-through-a-negative-feedback-loop
#12
Saravanapriah Nadarajan, Talley J Lambert, Elisabeth Altendorfer, Jinmin Gao, Michael D Blower, Jennifer C Waters, Monica P Colaiácovo
The synaptonemal complex (SC) is an ultrastructurally conserved proteinaceous structure that holds homologous chromosomes together and is required for the stabilization of pairing interactions and the completion of crossover (CO) formation between homologs during meiosis I. Here, we identify a novel role for a central region component of the SC, SYP-4, in negatively regulating formation of recombination-initiating double-strand breaks (DSBs) via a feedback loop triggered by crossover designation in C. elegans...
March 27, 2017: ELife
https://www.readbyqxmd.com/read/28339470/meiotic-recombination-modulates-the-structure-and-dynamics-of-the-synaptonemal-complex-during-c-elegans-meiosis
#13
Divya Pattabiraman, Baptiste Roelens, Alexander Woglar, Anne M Villeneuve
During meiotic prophase, a structure called the synaptonemal complex (SC) assembles at the interface between aligned pairs of homologous chromosomes, and crossover recombination events occur between their DNA molecules. Here we investigate the inter-relationships between these two hallmark features of the meiotic program in the nematode C. elegans, revealing dynamic properties of the SC that are modulated by recombination. We demonstrate that the SC incorporates new subunits and switches from a more highly dynamic/labile state to a more stable state as germ cells progress through the pachytene stage of meiotic prophase...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28330257/generation-of-an-inducible-system-to-express-polo-like-kinase-cdc5-as-tap-fusion-protein-during-meiosis-in-saccharomyces-cerevisiae
#14
Rajni Vaid, Kamal Dev, Michael Lichten, Anuradha Sourirajan
Tandem affinity purification (TAP) is a highly efficient method for isolation of protein complexes from endogenous biological macromolecules. TAP system consists of dual affinity tags that facilitates the sequential purification of the desired proteins expressed at their low levels in vivo. Polo-like kinases (PLK) are serine/threonine protein kinases that are the crucial regulators of cell cycle. Cdc5, the solitary PLK in budding yeast Saccharomyces cerevisiae, has diverse array of targets in cell cycle. The present study was undertaken to construct an estrogen-inducible system for expression of Cdc5-TAP to isolate the substrates of Cdc5 during meiosis, particularly, pachytene stage of meiosis I...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28283778/plk1-associated-micrornas-are-correlated-with-pediatric-medulloblastoma-prognosis
#15
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...
April 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
#16
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
#17
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
#18
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-kinase-mediated-%C3%AE-synuclein-selective-autophagic-degradation
#19
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's 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...
March 3, 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
#20
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
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