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https://www.readbyqxmd.com/read/29783958/sanguinarine-triggers-intrinsic-apoptosis-to-suppress-colorectal-cancer-growth-through-disassociation-between-strap-and-melk
#1
Xianling Gong, Zhihong Chen, Qinrui Han, Chunhui Chen, Linlin Jing, Yawei Liu, Liang Zhao, Xueqing Yao, Xuegang Sun
BACKGROUND: Previous studies showed sanguinarine induced apoptosis in CRC cells but did not define the underlying mechanisms. The purpose of this work was to determine the in vivo and in vitro effects of sanguinarine on CRC tumors and to elucidate the mechanism in regulating the intrinsic apoptosis. METHODS: Cell viability of CRC cell lines treated with sanguinarine was measured by MTT assay. Apoptotic cells stained with Annexin V and 7-AAD were detected by flow cytometry...
May 21, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29776755/neutral-ph-and-low-glucose-degradation-product-dialysis-fluids-induce-major-early-alterations-of-the-peritoneal-membrane-in-children-on-peritoneal-dialysis
#2
Betti Schaefer, Maria Bartosova, Stephan Macher-Goeppinger, Peter Sallay, Peter Vörös, Bruno Ranchin, Karel Vondrak, Gema Ariceta, Ariane Zaloszyc, Aysun K Bayazit, Uwe Querfeld, Rimante Cerkauskiene, Sara Testa, Christina Taylan, Johan VandeWalle, YokChin Yap, Rafael T Krmar, Rainer Büscher, Anne K Mühlig, Dorota Drozdz, Salim Caliskan, Felix Lasitschka, Sahar Fathallah-Shaykh, Enrico Verrina, Günter Klaus, Klaus Arbeiter, Raj Bhayadia, Anette Melk, Philipp Romero, Bradley A Warady, Franz Schaefer, Akos Ujszaszi, Claus Peter Schmitt
The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products...
May 15, 2018: Kidney International
https://www.readbyqxmd.com/read/29748441/maternal-embryonic-leucine-zipper-kinase-inhibitor-otssp167-has-preclinical-activity-on-multiple-myeloma-bone-disease
#3
Joséphine Muller, Arnold Bolomsky, Sophie Dubois, Elodie Duray, Kathrin Stangelberger, Erwan Plougonven, Margaux Lejeune, Angélique Léonard, Caroline Marty, Ute Hempel, Frédéric Baron, Yves Beguin, Martine Cohen-Solal, Heinz Ludwig, Roy Heusschen, Jo Caers
Multiple myeloma bone disease is characterized by an uncoupling of bone remodeling in the multiple myeloma microenvironment, resulting in the development of lytic bone lesions. Most myeloma patients suffer from these bone lesions, which not only causes morbidity but also negatively impacts survival. The development of novel therapies, ideally with a combined anti-resorptive and bone-anabolic effect, is of great interest because lesions persist with the current standard of care, even in patients in complete remission...
May 10, 2018: Haematologica
https://www.readbyqxmd.com/read/29700281/smad-proteins-differentially-regulate-obesity-induced-glucose-and-lipid-abnormalities-and-inflammation-via-class-specific-control-of-ampk-related-kinase-mpk38-melk-activity
#4
Hyun-A Seong, Ravi Manoharan, Hyunjung Ha
Smad proteins have been implicated in metabolic processes, but little is known about how they regulate metabolism. Because Smad 2, 3, 4, and 7 have previously been shown to interact with murine protein serine-threonine kinase 38 (MPK38), an AMP-activated protein kinase (AMPK)-related kinase that has been implicated in obesity-associated metabolic defects, we investigated whether Smad proteins regulate metabolic processes via MPK38. Smads2/3/4 increased, but Smad7 decreased, MPK38-mediated apoptosis signal-regulating kinase-1 (ASK1)/transforming growth factor-β (TGF-β)/p53 signaling...
April 27, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29670361/identification-of-molecular-target-genes-and-key-pathways-in-hepatocellular-carcinoma-by-bioinformatics-analysis
#5
Lei Zhou, Yanyan Du, Lingqun Kong, Xingyuan Zhang, Qiangpu Chen
Background and aim: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality and is increasing incidence worldwide. The aim of this study was to identify the key genes and microRNAs in HCC and explore their potential mechanisms. Methods: The gene expression profiles of GSE76427, GSE64041, GSE57957, and the microRNA dataset GSE67882 were downloaded from the Gene Expression Omnibus database. The online tool GEO2R was used to obtain differentially expressed genes (DEGs) and miRNAs (DEMs)...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29652412/correction-to-microrna-214-3p-inhibits-proliferation-and-cell-cycle-progression-by-targeting-melk-in-hepatocellular-carcinoma-and-correlates-cancer-prognosis
#6
Yue Li, You Li, Yao Chen, Qian Xie, Ningning Dong, Yanjun Gao, Huan Deng, Chunhua Lu, Suihai Wang
[This corrects the article DOI: 10.1186/s12935-017-0471-1.].
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29620242/corosolic-acid-induces-cell-cycle-arrest-and-cell-apoptosis-in-human-retinoblastoma-y-79-cells-via-disruption-of-melk-foxm1-signaling
#7
Ke Wang, Xue Zhu, Yong Yao, Min Yang, Fanfan Zhou, Ling Zhu
Retinoblastoma (Rb) is the most frequent primary intraocular tumor usually diagnosed in infants and children, and current therapy for such disease is still limited. Corosolic acid (CA), an ursane-type pentacyclic triterpene, has been assessed as a promising anticancer agent with little impact on untransformed cells. In the present study, we investigated the cytotoxic effect and underlying mechanism of CA on human retinoblastoma Y-79 cells. The viability of cells was verified by MTT assay. Cell cycle and apoptosis were evaluated by flow cytometric analysis...
March 28, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29548317/probing-depth-is-an-independent-risk-factor-for-hba1c-levels-in-diabetic-patients-under-physical-training-a-cross-sectional-pilot-study
#8
Katharina Wernicke, Sven Zeissler, Frank C Mooren, Torsten Frech, Stephanie Hellmann, Meike Stiesch, Jasmin Grischke, Silvia Linnenweber, Bernhard Schmidt, Jan Menne, Anette Melk, Pascal Bauer, Andree Hillebrecht, Jörg Eberhard
BACKGROUND: This cross-sectional study investigates the potential association between active periodontal disease and high HbA1c levels in type-2-diabetes mellitus subjects under physical training. METHODS: Women and men with a diagnosis of non-insulin-dependent diabetes mellitus and ongoing physical and an ongoing exercise program were included. Periodontal conditions were assessed according to the CDC-AAP case definitions. Venous blood samples were collected for the quantitative analysis of HbA1c...
March 16, 2018: BMC Oral Health
https://www.readbyqxmd.com/read/29542856/delay-in-maternal-transcript-degradation-in-ovine-embryos-derived-from-low-competence-oocytes
#9
Laura Masala, Federica Ariu, Luisa Bogliolo, Emanuela Bellu, Sergio Ledda, Daniela Bebbere
Oocytes from prepubertal animals have a reduced ability to undergo embryo development and produce viable offspring. The present work used an ovine model consisting of oocytes derived from adult and prepubertal donors to assess the molecular status of oocytes and preimplantation embryos with different developmental competence. The lower potential of oocytes of young donors was confirmed in terms of in vitro developmental capabilities and kinetics. A panel of genes including maternal effect (DPPA3, GDF9, NMP2, ZAR1) and housekeeping genes (ACTB, RPL19, SDHA, YWHAZ, ATP1A1), genes involved in DNA methylation (DNMT1, DNMT3A, DNMT3B), genomic imprinting (IGF2R), pluripotency (NANOG, POU5F1) and cell cycle regulation (CCNB1, CDK1, MELK) was relatively quantified...
March 15, 2018: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/29528283/correction-melk-is-an-oncogenic-kinase-essential-for-mitotic-progression-in-basal-like-breast-cancer-cells
#10
Yubao Wang, Young-Mi Li, Lukas Baitsch, Alan Huang, Yi Xiang, Haoxuan Tong, Ana Lako, Thanh Von, Christine Choi, Elgene Lim, Junxia Min, Li Li, Frank Stegmeier, Robert Schlegel, Michael J Eck, Nathanael S Gray, Timothy J Mitchison, Jean J Zhao
No abstract text is available yet for this article.
March 12, 2018: ELife
https://www.readbyqxmd.com/read/29481636/effects-of-nutritional-vitamin-d-supplementation-on-markers-of-bone-and-mineral-metabolism-in-children-with-chronic-kidney-disease
#11
Christian Lerch, Rukshana Shroff, Mandy Wan, Lesley Rees, Helen Aitkenhead, Ipek Kaplan Bulut, Daniela Thurn, Aysun Karabay Bayazit, Anna Niemirska, Nur Canpolat, Ali Duzova, Karolis Azukaitis, Ebru Yilmaz, Fatos Yalcinkaya, Jerome Harambat, Aysel Kiyak, Harika Alpay, Sandra Habbig, Ariane Zaloszyc, Oguz Soylemezoglu, Cengiz Candan, Alejandra Rosales, Anette Melk, Uwe Querfeld, Maren Leifheit-Nestler, Anja Sander, Franz Schaefer, Dieter Haffner
Background: We investigated the effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism, i.e. serum levels of fibroblast growth factor 23 (FGF23), Klotho, bone alkaline phosphatase (BAP) and sclerostin, in two cohorts with chronic kidney disease (CKD). Methods: In all, 80 vitamin D-deficient children were selected: 40 with mild to moderate CKD from the ERGO study, a randomized trial of ergocalciferol supplementation [estimated glomerular filtration rate (eGFR) 55 mL/min/1...
February 21, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29432282/phase-i-study-of-multiple-epitope-peptide-vaccination-in-patients-with-recurrent-or-persistent-cervical-cancer
#12
Kosei Hasegawa, Yuji Ikeda, Yuko Kunugi, Akira Kurosaki, Yuichi Imai, Shunsuke Kohyama, Shoji Nagao, Eito Kozawa, Koji Yoshida, Takuya Tsunoda, Yusuke Nakamura, Keiichi Fujiwara
Cancer immunotherapy has now been established as a leading standard therapeutic option in a subset of patients with cancer. In this study, we conducted a phase I dose-escalation trial using a mixture of 5 peptides to vaccinate cervical cancer patients with HLA-A*2402. The primary endpoints were safety and determination of a recommended vaccine dose, and the secondary endpoints were evaluations of immunologic responses and clinical efficacy. All patients had recurrent or persistent disease and had failed to respond to or were intolerant to prior standard chemotherapy...
May 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29426831/cardiovascular-risk-factors-and-subclinical-organ-damage-after-hematopoietic-stem-cell-transplantation-in-pediatric-age
#13
Bianca Borchert-Mörlins, Nima Memaran, Martin Sauer, Britta Maecker-Kolhoff, Karl-Walter Sykora, Ricarda Blöte, Elena Bauer, Bernhard M W Schmidt, Anette Melk, Rita Beier
Advances in allogeneic hematopoietic stem cell transplantation (HSCT) in malignant and non-malignant diseases result in more long-term survivors, in whom cardiovascular (CV) disease is one leading non-cancer cause of death. This study aimed to evaluate risk factors and subclinical CV organ damage in survivors after HSCT in pediatric age. We enrolled 64 children in a cross-sectional approach 3.3 ± 3.1 years after HSCT. Anthropometric data, laboratory values, office and 24-h ambulatory blood pressure monitoring (ABPM) were evaluated, showing a high prevalence of obesity, hypertension and dyslipidemia...
February 9, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29417930/melk-expression-correlates-with-tumor-mitotic-activity-but-is-not-required-for-cancer-growth
#14
Christopher J Giuliano, Ann Lin, Joan C Smith, Ann C Palladino, Jason M Sheltzer
The Maternal Embryonic Leucine Zipper Kinase (MELK) has been identified as a promising therapeutic target in multiple cancer types. MELK over-expression is associated with aggressive disease, and MELK has been implicated in numerous cancer-related processes, including chemotherapy resistance, stem cell renewal, and tumor growth. Previously, we established that triple-negative breast cancer cell lines harboring CRISPR/Cas9-induced null mutations in MELK proliferate at wild-type levels in vitro (<xref ref-type="bibr" rid="bib34">Lin et al...
February 8, 2018: ELife
https://www.readbyqxmd.com/read/29417929/challenges-in-validating-candidate-therapeutic-targets-in-cancer
#15
Jeffrey Settleman, Charles L Sawyers, Tony Hunter
More than 30 published articles have suggested that a protein kinase called MELK is an attractive therapeutic target in human cancer, but three recent reports describe compelling evidence that it is not. These reports highlight the caveats associated with some of the research tools that are commonly used to validate candidate therapeutic targets in cancer research.
February 8, 2018: ELife
https://www.readbyqxmd.com/read/29416794/melk-is-a-novel-therapeutic-target-in-high-risk-neuroblastoma
#16
Shan Guan, Jiaxiong Lu, Yanling Zhao, Yang Yu, Hui Li, Zhenghu Chen, Zhongcheng Shi, Haoqian Liang, Mopei Wang, Kevin Guo, Xiangmei Chen, Wenjing Sun, Shayahati Bieerkehazhi, Xin Xu, Surong Sun, Saurabh Agarwal, Jianhua Yang
Maternal embryonic leucine zipper kinase (MELK) is known to modulate intracellular signaling and control cellular processes. However, the role of MELK in oncogenesis is not well defined. In this study, using two microarray datasets of neuroblastoma (NB) patients, we identified that MELK expression is significantly correlated to poor overall survival, unfavorable prognosis, and high-risk status. We found that MELK is a direct transcription target of MYCN and MYC in NB, and MYCN increases MELK expression via direct promoter binding...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29411820/structure-based-discovery-of-new-maternal-embryonic-leucine-zipper-kinase-inhibitors
#17
Shu Zhou, Guo-Bo Li, Lin Luo, Lei Zhong, Kai Chen, Hui Li, Xiao-Juan Jiang, Qi Fu, Xin Long, Jin-Ku Bao
Maternal embryonic leucine zipper kinase (MELK), a serine/threonine protein kinase, has oncogenic properties and plays a key functional role in various cancer cells. Although MELK may not be a cancer addiction target, the development of specific MELK inhibitors would provide useful chemical tools for synthetic lethal investigation. Herein, we identified several hit compounds using a customized structure-based virtual screening, among which compounds 4 and 16 showed the most potent inhibition to MELK with IC50 values of 3...
February 28, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29305979/target-gene-screening-and-evaluation-of-prognostic-values-in-non-small-cell-lung-cancers-by-bioinformatics-analysis
#18
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...
March 20, 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
#19
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
#20
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
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