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https://www.readbyqxmd.com/read/29305979/target-gene-screening-and-evaluation-of-prognostic-values-in-non-small-cell-lung-cancers-by-bioinformatics-analysis
#1
Junjie Piao, Jie Sun, Yang Yang, Tiefeng Jin, Liyan Chen, Zhenhua Lin
BACKGROUND: Non-small cell lung cancer (NSCLC) is the major leading cause of cancer-related deaths worldwide. This study aims to explore molecular mechanism of NSCLC. METHODS: Microarray dataset was obtained from the Gene Expression Omnibus (GEO) database, and analyzed by using GEO2R. Functional and pathway enrichment analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Then, STRING, Cytoscape and MCODE were applied to construct the Protein-protein interaction (PPI) network and screen hub genes...
January 3, 2018: Gene
https://www.readbyqxmd.com/read/29216888/telomere-heterogeneity-linked-to-metabolism-and-pluripotency-state-revealed-by-simultaneous-analysis-of-telomere-length-and-rna-seq-in-the-same-human-embryonic-stem-cell
#2
Hua Wang, Kunshan Zhang, Yifei Liu, Yudong Fu, Shan Gao, Peng Gong, Haiying Wang, Zhongcheng Zhou, Ming Zeng, Zhenfeng Wu, Yu Sun, Tong Chen, Siguang Li, Lin Liu
BACKGROUND: Telomere length heterogeneity has been detected in various cell types, including stem cells and cancer cells. Cell heterogeneity in pluripotent stem cells, such as embryonic stem cells (ESCs), is of particular interest; however, the implication and mechanisms underlying the heterogeneity remain to be understood. Single-cell analysis technology has recently been developed and effectively employed to investigate cell heterogeneity. Yet, methods that can simultaneously measure telomere length and analyze the global transcriptome in the same cell have not been available until now...
December 8, 2017: BMC Biology
https://www.readbyqxmd.com/read/29212506/chromosome-9p-copy-number-gains-involving-pd-l1-are-associated-with-a-specific-proliferation-and-immune-modulating-gene-expression-program-active-across-major-cancer-types
#3
Jan Budczies, Carsten Denkert, Balázs Győrffy, Peter Schirmacher, Albrecht Stenzinger
BACKGROUND: Inhibition of the PD-L1/PD-1 immune checkpoint axis represents one of the most promising approaches of immunotherapy for various cancer types. However, immune checkpoint inhibition is successful only in subpopulations of patients emphasizing the need for powerful biomarkers that adequately reflect the complex interaction between the tumor and the immune system. Recently, recurrent copy number gains (CNG) in chromosome 9p involving PD-L1 were detected in many cancer types including lung cancer, melanoma, bladder cancer, head and neck cancer, cervical cancer, soft tissue sarcoma, prostate cancer, gastric cancer, ovarian cancer, and triple-negative breast cancer...
December 6, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/29212029/melk-promotes-melanoma-growth-by-stimulating-the-nf-%C3%AE%C2%BAb-pathway
#4
Radoslav Janostiak, Navin Rauniyar, TuKiet T Lam, Jianhong Ou, Lihua J Zhu, Michael R Green, Narendra Wajapeyee
Melanoma accounts for more than 80% of skin cancer-related deaths, and current therapies provide only short-term benefit to patients. Here, we show in melanoma cells that maternal embryonic leucine zipper kinase (MELK) is transcriptionally upregulated by the MAPK pathway via transcription factor E2F1. MELK knockdown or pharmacological inhibition blocked melanoma growth and enhanced the effectiveness of BRAFV600E inhibitor against melanoma cells. To identify mediators of MELK function, we performed stable isotope labeling with amino acids in cell culture (SILAC) and identified 469 proteins that had downregulated phosphorylation after MELK inhibition...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29194499/emotion-recognition-associated-with-polymorphism-in-oxytocinergic-pathway-gene-arnt2
#5
Daniel Hovey, Susanne Henningsson, Diana S Cortes, Tanja Bänziger, Anna Zettergren, Jonas Melke, Håkan Fischer, Petri Laukka, Lars Westberg
The ability to correctly understand the emotional expression of another person is essential for social relationships and appears to be a partly inherited trait. The neuropeptides oxytocin and vasopressin have been shown to influence this ability as well as face processing in humans. Here, recognition of the emotional content of faces and voices, separately and combined, was investigated in 492 subjects, genotyped for 25 single nucleotide polymorphisms (SNPs) in eight genes encoding proteins important for oxytocin and vasopressin neurotransmission...
November 28, 2017: Social Cognitive and Affective Neuroscience
https://www.readbyqxmd.com/read/29192136/up-regulated-maternal-embryonic-leucine-zipper-kinase-predicts-poor-prognosis-of-hepatocellular-carcinoma-patients-in-a-chinese-han-population
#6
Shaohan Wu, Xujian Chen, Chundong Hu, Jing Wang, Yiyu Shen, Zhengxiang Zhong
BACKGROUND Maternal embryonic leucine zipper kinase (MELK) has been implicated in various types of tumors, but its expression profile and clinicopathologic significance in hepatocellular carcinoma (HCC) in Chinese Han people remains unknown. Therefore, this study attempted to investigate the expression pattern of MELK in HCC tissues obtained from a Chinese Han population. MATERIAL AND METHODS The expression of MELK, from RNA to protein levels, in HCC or disease-free human liver tissues was evaluated using quantitative real-time polymerase chain reaction assays and immunohistochemistry staining, and its prognostic significance was determined based on its impact on HCC patients' survival...
December 1, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29191878/the-target-landscape-of-clinical-kinase-drugs
#7
Susan Klaeger, Stephanie Heinzlmeir, Mathias Wilhelm, Harald Polzer, Binje Vick, Paul-Albert Koenig, Maria Reinecke, Benjamin Ruprecht, Svenja Petzoldt, Chen Meng, Jana Zecha, Katrin Reiter, Huichao Qiao, Dominic Helm, Heiner Koch, Melanie Schoof, Giulia Canevari, Elena Casale, Stefania Re Depaolini, Annette Feuchtinger, Zhixiang Wu, Tobias Schmidt, Lars Rueckert, Wilhelm Becker, Jan Huenges, Anne-Kathrin Garz, Bjoern-Oliver Gohlke, Daniel Paul Zolg, Gian Kayser, Tonu Vooder, Robert Preissner, Hannes Hahne, Neeme Tõnisson, Karl Kramer, Katharina Götze, Florian Bassermann, Judith Schlegl, Hans-Christian Ehrlich, Stephan Aiche, Axel Walch, Philipp A Greif, Sabine Schneider, Eduard Rudolf Felder, Juergen Ruland, Guillaume Médard, Irmela Jeremias, Karsten Spiekermann, Bernhard Kuster
Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments...
December 1, 2017: Science
https://www.readbyqxmd.com/read/29151817/microrna-214-3p-inhibits-proliferation-and-cell-cycle-progression-by-targeting-melk-in-hepatocellular-carcinoma-and-correlates-cancer-prognosis
#8
Yue Li, You Li, Yao Chen, Qian Xie, Ningning Dong, Yanjun Gao, Huan Deng, Chunhua Lu, Suihai Wang
Background: MicroRNAs are considered as potential regulators in various biological pathways and contribute to the diagnosis and prognosis of cancers. MicroRNA-214-3p (miR-214-3p) was proved to be correlated with various cancers in recent studies. However, the biological functions of miR-214-3p in hepatocellular carcinoma (HCC) and its association with the prognosis of HCC after liver transplantation are still unevaluated. Here we intended to elucidate the functional implication of miR-214-3p in regulation of cell proliferation and apoptosis and its potential prediction of clinical prognosis of HCC patients...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29140069/dual-functions-of-cyclometalated-iridium-iii-complexes-anti-metastasis-and-lysosome-damaged-photodynamic-therapy
#9
Fang-Xin Wang, Mu-He Chen, Yan-Nan Lin, Hang Zhang, Cai-Ping Tan, Liang-Nian Ji, Zongwan Mao
Four phosphorescent cyclometalated iridium(III) complexes containing benzimidazole moiety have been designed and synthesized. These Ir(III) complexes can inhibit several cancerous processes including cell migration, invasion, colony formation and angiogenesis effectively. Interestingly, they show much higher singlet oxygen quantum yield in acidic solution than in neutral solution. Upon irradiation at 425 nm with low energy (1.2 J·cm(-2)), they can induce apoptosis through lysosomal damage, evaluation of ROS level and activation of caspase-3/7...
November 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29137494/trh-receptor-mobility-in-the-plasma-membrane-is-strongly-affected-by-agonist-binding-and-by-interaction-with-some-cognate-signaling-proteins
#10
Radka Moravcova, Barbora Melkes, Jiri Novotny
OBJECTIVES: Extensive research has been dedicated to elucidating the mechanisms of signal transduction through different G protein-coupled receptors (GPCRs). However, relatively little is known about the regulation of receptor movement within the cell membrane upon ligand binding. In this study we focused our attention on the thyrotropin-releasing hormone (TRH) receptor that typically couples to Gq/11 proteins. METHODS: We monitored receptor diffusion in the plasma membrane of HEK293 cells stably expressing yellow fluorescent protein (YFP)-tagged TRH receptor (TRHR-YFP) by fluorescence recovery after photobleaching (FRAP)...
November 14, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/29122991/maternal-embryonic-leucine-zipper-kinase-is-a-novel-target-for-proliferation-associated-high-risk-myeloma
#11
Arnold Bolomsky, Roy Heusschen, Karin Schlangen, Kathrin Stangelberger, Joséphine Muller, Wolfgang Schreiner, Niklas Zojer, Jo Caers, Heinz Ludwig
Treatment of high-risk patients is a major challenge in multiple myeloma. This is especially true for patients assigned to the gene-expression-profiling defined proliferation subgroup. Although recent efforts have identified some key players of proliferative myeloma, genetic interactions and players that can be targeted with clinically effective drugs have to be identified to overcome the poor prognosis of these patients. We therefore examined maternal embryonic leucine zipper kinase (MELK) for its implications in hyper-proliferative myeloma and analysed the activity of the MELK inhibitor OTSSP167 in vitro and in vivo...
November 9, 2017: Haematologica
https://www.readbyqxmd.com/read/29100313/g2-m-checkpoint-plays-a-vital-role-at-the-early-stage-of-hcc-by-analysis-of-key-pathways-and-genes
#12
Li Yin, Cuifang Chang, Cunshuan Xu
The present study was designed to explore the molecular mechanism at the early stage of hepatocarcinoma (HCC) and identify the candidate genes and pathways changed significantly. We downloaded the gene expression file dataset GSE6764 from GEO, adopted the Robust Multi-array Average (RMA) algorithm to preprocess the raw file. 797 differentially expressed genes (DEGs) were screened out based on the SAM method using R language. Ingenuity Pathway Analysis (IPA) was used to perform canonical pathway analysis in order to calculate the most significantly changed pathways and predict the upstream regulators...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29025594/gene-expression-profiling-pathway-analysis-and-subtype-classification-reveal-molecular-heterogeneity-in-hepatocellular-carcinoma-and-suggest-subtype-specific-therapeutic-targets
#13
Rahul Agarwal, Jitendra Narayan, Amitava Bhattacharyya, Mayank Saraswat, Anil Kumar Tomar
A very low 5-year survival rate among hepatocellular carcinoma (HCC) patients is mainly due to lack of early stage diagnosis, distant metastasis and high risk of postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis and patient specific therapeutics is crucial and urgent. Here, we have performed a comprehensive analysis of the expression data of 423 HCC patients (373 tumors and 50 controls) downloaded from The Cancer Genome Atlas (TCGA) followed by pathway enrichment by gene ontology annotations, subtype classification and overall survival analysis...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28938528/p53-independent-p21-induction-by-melk-inhibition
#14
Tatsuo Matsuda, Taigo Kato, Kazuma Kiyotani, Yunus Emre Tarhan, Vassiliki Saloura, Suyoun Chung, Koji Ueda, Yusuke Nakamura, Jae-Hyun Park
MELK play critical roles in human carcinogenesis through activation of cell proliferation, inhibition of apoptosis and maintenance of stemness. Therefore, MELK is a promising therapeutic target for a wide range of cancers. Although p21 is a well-known p53-downstream gene, we found that treatment with a potent MELK inhibitor, OTS167, could induce p21 protein expression in cancer cell lines harboring loss-of-function TP53 mutations. We also confirmed that MELK knockdown by siRNA induced the p21 expression in p53-deficient cancer cell lines and caused the cell cycle arrest at G1 phase...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28926375/early-effects-of-renal-replacement-therapy-on-cardiovascular-comorbidity-in-children-with-end-stage-kidney-disease-findings-from-the-4c-t-study
#15
Bernhard M W Schmidt, Rizky I Sugianto, Daniela Thurn, Karolis Azukaitis, Aysun K Bayazit, Nur Canpolat, Ayse Guler Eroglu, Salim Caliskan, Anke Doyon, Ali Duzova, Tevfik Karagoz, Ali Anarat, Murat Deveci, Sevgi Mir, Bruno Ranchin, Rukshana Shroff, Esra Baskin, Mieczyslaw Litwin, Z Birsin Özcakar, Rainer Büscher, Oguz Soylemezoglu, Jiri Dusek, Markus Kemper, Maria C Matteucci, Sandra Habbig, Guido Laube, Elke Wühl, Uwe Querfeld, Anja Sander, Franz Schaefer, Anette Melk
BACKGROUND: The early impact of renal transplantation on subclinical cardiovascular measures in pediatric patients has not been widely investigated. This analysis is performed for pediatric patients participating in the prospective 4C study and focuses on the early effects of RRT modality on cardiovascular comorbidity in patients receiving a preemptive transplant or started on dialysis. METHODS: We compared measures indicating subclinical cardiovascular organ damage (aortal pulse wave velocity, carotid intima media thickness, left ventricular mass index) and evaluated cardiovascular risk factors in 166 pediatric patients before and 6 to 18 months after start of RRT (n=76 transplantation, n=90 dialysis)...
September 18, 2017: Transplantation
https://www.readbyqxmd.com/read/28926338/melk-is-not-necessary-for-the-proliferation-of-basal-like-breast-cancer-cells
#16
Hai-Tsang Huang, Hyuk-Soo Seo, Tinghu Zhang, Yubao Wang, Baishan Jiang, Qing Li, Dennis L Buckley, Behnam Nabet, Justin M Roberts, Joshiawa Paulk, Shiva Dastjerdi, Georg E Winter, Hilary McLauchlan, Jennifer Moran, James E Bradner, Michael J Eck, Sirano Dhe-Paganon, Jean J Zhao, Nathanael S Gray
Thorough preclinical target validation is essential for the success of drug discovery efforts. In this study, we combined chemical and genetic perturbants, including the development of a novel selective maternal embryonic leucine zipper kinase (MELK) inhibitor HTH-01-091, CRISPR/Cas9-mediated MELK knockout, a novel chemical-induced protein degradation strategy, RNA interference and CRISPR interference to validate MELK as a therapeutic target in basal-like breast cancers (BBC). In common culture conditions, we found that small molecule inhibition, genetic deletion, or acute depletion of MELK did not significantly affect cellular growth...
September 19, 2017: ELife
https://www.readbyqxmd.com/read/28804814/factors-associated-with-cardiovascular-target-organ-damage-in-children-after-renal-transplantation
#17
Bianca Borchert-Mörlins, Daniela Thurn, Bernhard M W Schmidt, Anja K Büscher, Jun Oh, Tanja Kier, Elena Bauer, Sabrina Baig, Nele Kanzelmeyer, Markus J Kemper, Rainer Büscher, Anette Melk
BACKGROUND: Cardiovascular disease is the second-most common cause of death in pediatric renal transplant recipients. The aim of this study was to evaluate subclinical cardiovascular target organ damage defined as the presence of arterio- and atherosclerotic lesions and cardiac remodeling and to analyze contributing risk factors in a large cohort of children after renal transplantation (RT). METHODS: A total of 109 children aged 13.1 ± 3.3 years who had undergone RT at one of three German transplant centers were enrolled in this study...
November 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28796785/low-renal-but-high-extrarenal-phenotype-variability-in-schimke-immuno-osseous-dysplasia
#18
Beata S Lipska-Ziętkiewicz, Jutta Gellermann, Olivia Boyer, Olivier Gribouval, Szymon Ziętkiewicz, Jameela A Kari, Mohamed A Shalaby, Fatih Ozaltin, Jiri Dusek, Anette Melk, Aysun K Bayazit, Laura Massella, Lidia Hyla-Klekot, Sandra Habbig, Astrid Godron, Maria Szczepańska, Beata Bieniaś, Dorota Drożdż, Rasha Odeh, Wioletta Jarmużek, Katarzyna Zachwieja, Agnes Trautmann, Corinne Antignac, Franz Schaefer
Schimke immuno-osseous dysplasia (SIOD) is a rare multisystem disorder with early mortality and steroid-resistant nephrotic syndrome (SRNS) progressing to end-stage kidney disease. We hypothesized that next-generation gene panel sequencing may unsurface oligosymptomatic cases of SIOD with potentially milder disease courses. We analyzed the renal and extrarenal phenotypic spectrum and genotype-phenotype associations in 34 patients from 28 families, the largest SMARCAL1-associated nephropathy cohort to date. In 11 patients the diagnosis was made unsuspectedly through SRNS gene panel testing...
2017: PloS One
https://www.readbyqxmd.com/read/28764577/melk-a-potential-novel-therapeutic-target-for-tnbc-and-other-aggressive-malignancies
#19
REVIEW
Mary Kathryn Pitner, Juliana M Taliaferro, Kevin N Dalby, Chandra Bartholomeusz
There is an unmet need in triple-negative breast cancer (TNBC) patients for targeted therapies. Maternal embryonic leucine zipper kinase (MELK) is a promising target for inhibition based on the abundance of correlative and functional data supporting its role in various cancer types. Areas covered: This review endeavors to outline the role of MELK in cancer. Studies covering a range of biological functions including proliferation, apoptosis, cancer stem cell phenotypes, epithelial-to-mesenchymal transition, metastasis, and therapy resistance are discussed here in order to understand the potential of MELK as a clinically significant target for TNBC patients...
September 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28729036/molecular-mechanisms-of-renal-aging
#20
REVIEW
Roland Schmitt, Anette Melk
Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of acute kidney injury and chronic kidney disease. The aging kidney undergoes complex changes that predispose to renal pathology. The underlying molecular mechanisms could be the target of therapeutic strategies in the future. Here, we summarize recent insight into cellular and molecular processes that have been shown to contribute to the renal aging phenotype.The main clinical finding of renal aging is the decrease in glomerular filtration rate, and its structural correlate is the loss of functioning nephrons...
September 2017: Kidney International
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