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https://www.readbyqxmd.com/read/27914241/engot-ov-6-trinova-2-randomised-double-blind-phase-3-study-of-pegylated-liposomal-doxorubicin-plus-trebananib-or-placebo-in-women-with-recurrent-partially-platinum-sensitive-or-resistant-ovarian-cancer
#1
Christian Marth, Ignace Vergote, Giovanni Scambia, Willi Oberaigner, Andrew Clamp, Regina Berger, Christian Kurzeder, Nicoletta Colombo, Peter Vuylsteke, Domenica Lorusso, Marcia Hall, Vincent Renard, Sandro Pignata, Rebecca Kristeleit, Sevilay Altintas, Gordon Rustin, Robert M Wenham, Mansoor Raza Mirza, Peter C Fong, Amit Oza, Bradley J Monk, Haijun Ma, Florian D Vogl, Bruce A Bach
AIMS: Trebananib, a peptide-Fc fusion protein, inhibits angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. This randomised, double-blind, placebo-controlled phase 3 study evaluated whether trebananib plus pegylated liposomal doxorubicin (PLD) improved progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer. METHODS: Women with recurrent ovarian cancer (platinum-free interval ≤12 months) were randomised to intravenous PLD 50 mg/m(2) once every 4 weeks plus weekly intravenous trebananib 15 mg/kg or placebo...
November 30, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27914215/lysine-specific-demethylase-1-lsd1-inhibitor-s2101-induces-autophagy-via-the-akt-mtor-pathway-in-skov3-ovarian-cancer-cells
#2
Shujun Feng, Ye Jin, Mengjiao Cui, Jianhua Zheng
BACKGROUND S2101 is one of the most potent LSD1 inhibitors, which can inhibit ovarian cancer cells viability. This study aimed to detect the mechanism behind the anticancer properties of S2101 in SKOV3 ovarian cells. MATERIAL AND METHODS Cell viability was tested by Cell Counting Kit-8 (CCK-8) assay. Cellular apoptosis and autophagy were evaluated by flow cytometric analysis using Annexin-V/PI staining methods and Green fluorescent protein (GFP)-fused-LC3 (GFP-LC3), respectively. Western blotting was performed for analyzing the Bax, Bcl-2, mTOR, p- mTOR, p62, LC3-I, LC3-II, AKT, and p-AKT protein expression...
December 3, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27914071/differential-radial-capillary-action-of-ligand-assay-dracala-for-high-throughput-detection-of-protein-metabolite-interactions-in-bacteria
#3
Mona W Orr, Vincent T Lee
Bacteria rely on numerous nucleotide second messengers for signal transduction such as cyclic AMP, cyclic-di-GMP, and cyclic-di-AMP. Although a number of receptors responsible for known regulated phenotypes have been established, the completeness of protein receptors in any given organism remains elusive. We have developed a method called differential radial capillary action of ligand assay (DRaCALA) that allows for an unbiased, systematic high-throughput screen for the detection of ligand binding proteins encoded by a genome...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27914008/igf1r-dental-pulp-stem-cells-enhanced-neuroplasticity-in-hypoxia-ischemia-model
#4
Hsiao-Yu Chiu, Chen-Huan Lin, Chung Y Hsu, John Yu, Chia-Hung Hsieh, Woei-Cherng Shyu
Until now, the surface markers of multipotent mesenchymal stem cells (MSCs) had not been fully identified. Here, we found that the IGF1 receptor (IGF1R), regarded as a pluripotent marker of embryonic stem cells (ESCs), was also expressed in human dental pulp derived-mesenchymal stem cells (hDSCs), which displayed a potential for both self-renewal and multipotency. hDSC-secreted IGF1 interacted with IGF1R through an autocrine signaling pathway to maintain this self-renewal and proliferation potential. Stereotaxic implantation of immunosorted IGF1R(+) hDSCs in rats with neonatal hypoxia-ischemia (NHI) promoted neuroplasticity, improving the neurological outcome by increasing expression of the anti-apoptotic protein Bcl-2, which enhanced both neurogenesis and angiogenesis...
December 2, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27913949/epigenetic-cpg-methylation-of-the-promoter-and-reactivation-of-the-expression-of-gstp1-by-astaxanthin-in-human-prostate-lncap-cells
#5
Yuqing Yang, Francisco Fuentes, Limin Shu, Chao Wang, Doug Pung, Wenji Li, Chengyue Zhang, Yue Guo, Ah-Ng Kong
Astaxanthin (AST), a red dietary carotenoid, has synergistic antioxidant effects with polyunsaturated fatty acids at low concentrations via Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or Nrf2)/antioxidant response element (ARE) signaling. In addition, chromatin remodeling and DNA methylation-based gene silencing represent a common mechanism in prostate carcinogenesis and tumor progression from normal cells to pre-initiated cells and ultimately to invasive carcinoma. Therefore, the control of epigenetic modification and the transcriptional/translational control of the activation of Nrf2 and Nrf2-target genes, including glutathione S-transferases (GSTs), appear to be an important mechanism that protects cells against injuries from oxidative stress and cancer development...
December 2, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27913948/branched-chain-amino-acids-administration-suppresses-endurance-exercise-related-activation-of-ubiquitin-proteasome-signaling-in-trained-human-skeletal-muscle
#6
Evgeny A Lysenko, Tatiana F Vepkhvadze, Egor M Lednev, Olga L Vinogradova, Daniil V Popov
We tested whether post exercise ingestion of branched-chain amino acids (BCAA < 10 g) is sufficient to activate signaling associated with muscle protein synthesis and suppress exercise-induced activation of mechanisms associated with proteolysis in endurance-trained human skeletal muscle. Nine endurance-trained athletes performed a cycling bout with and without BCAA ingestion (0.1 g/kg). Post exercise ACC(Ser79/222) phosphorylation (endogenous marker of AMPK activity) was increased (~3-fold, P < 0...
December 3, 2016: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/27913859/complex-genetics-architecture-contributes-to-salmonella-resistance-in-acb60-mice
#7
Sean Beatty, Leïla Rached-D'Astous, Danielle Malo
Human infection with Salmonella is of global public health concern. In low- and middle-income countries, Salmonella infection is a major source of disease in terms of both mortality and morbidity, while in high-income nations, the pathogen is an ongoing threat to food security. The outcome of infection with Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) in mouse models is dependent upon a coordinated and complex immune response. A panel of recombinant congenic strains (RCS) derived from the reciprocal double backcross of A/J and C57BL/6J mice has been screened for their susceptibility to Salmonella infection, and the RCS AcB60 was identified to be the most resistant strain to Salmonella infection, more resistant than the parental strain A/J...
December 2, 2016: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/27913852/differential-effect-of-early-antibiotic-intervention-on-bacterial-fermentation-patterns-and-mucosal-gene-expression-in-the-colon-of-pigs-under-diets-with-different-protein-levels
#8
Chuanjian Zhang, Miao Yu, Yuxiang Yang, Chunlong Mu, Yong Su, Weiyun Zhu
The study aimed to evaluate the effects of early antibiotic intervention (EAI) on bacterial fermentation patterns and mucosal immune markers in the colon of pigs with different protein level diets. Eighteen litters of piglets at day (d) 7 were fed creep feed without or with growth promoting antibiotics until d 42. At d 42, pigs within each group were further randomly assigned to a normal- or low-crude protein (CP) diet. At d 77 and d 120, five pigs per group were slaughtered for analyzing colonic bacteria, metabolites, and mucosal gene expressions...
December 3, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27913741/aik1-a-mitogen-activated-protein-kinase-modulates-abscisic-acid-responses-through-the-mkk5-mpk6-kinase-cascade
#9
Kun Li, Fengbo Yang, Guozeng Zhang, Shufei Song, Yuan Li, Yuchen Miao, Dongtao Ren, Chun-Peng Song
The mitogen-activated protein kinase (MAPK) cascade is an evolutionarily conserved signal transduction module involved in transducing extracellular signals to the nucleus for appropriate cellular adjustment. This cascade essentially consists of three components, a MAPK kinase kinase (MAPKKK), a MAPK kinase (MAPKK) and a MAPK, connected to each other by the event of phosphorylation. Here we report the characterization of a MAPKKK, AIK1, which regulates abscisic acid (ABA) responses in Arabidopsis. T-DNA insertion mutants of AIK1 showed insensitivity to ABA in terms of both root growth and stomatal response...
December 2, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27913731/disentangling-polydispersity-in-the-pcna-p15paf-complex-a-disordered-transient-and-multivalent-macromolecular-assembly
#10
Tiago N Cordeiro, Po-Chia Chen, Alfredo De Biasio, Nathalie Sibille, Francisco J Blanco, Jochen S Hub, Ramon Crehuet, Pau Bernadó
The intrinsically disordered p15(PAF) regulates DNA replication and repair when interacting with the Proliferating Cell Nuclear Antigen (PCNA) sliding clamp. As many interactions between disordered proteins and globular partners involved in signaling and regulation, the complex between p15(PAF) and trimeric PCNA is of low affinity, forming a transient complex that is difficult to characterize at a structural level due to its inherent polydispersity. We have determined the structure, conformational fluctuations, and relative population of the five species that coexist in solution by combining small-angle X-ray scattering (SAXS) with molecular modelling...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27913706/stat1-promotes-kras-colon-tumor-growth-and-susceptibility-to-pharmacological-inhibition-of-translation-initiation-factor-eif4a
#11
Shuo Wang, Cedric Darini, Laurent Désaubry, Antonis E Koromilas
The transcription factor STAT1 displays antitumor functions for certain forms of cancer via immunoregulatory and cell-autonomous pathways. Paradoxically, STAT1 can promote the survival of different tumor types treated with chemotherapeutic drugs through mechanisms that are not clearly defined. Herein, we demonstrate that STAT1 displays prosurvival effects in human KRAS colon tumor cells by regulating pathways that converge on the initiation of mRNA translation. Specifically, STAT1 increases PI3K class IB signaling and promotes the downregulation of the programmed cell death protein 4 (PDCD4), a protein with tumor-suppressive properties...
December 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27913682/translational-regulation-of-mitochondrial-biogenesis
#12
REVIEW
Yi Zhang, Hong Xu
Mitochondria are generated by the expression of genes on both nuclear and mitochondrial genome. Mitochondrial biogenesis is highly plastic in response to cellular energy demand, developmental signals and environmental stimuli. Mechanistic target of rapamycin (mTOR) pathway regulates mitochondrial biogenesis to co-ordinate energy homeostasis with cell growth. The local translation of mitochondrial proteins on the outer membrane facilitates their efficient import and thereby allows prodigious mitochondrial biogenesis during rapid cell growth and proliferation...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913681/the-borg-family-of-cdc42-effector-proteins-cdc42ep1-5
#13
REVIEW
Aaron J Farrugia, Fernando Calvo
Despite being discovered more than 15 years ago, the Borg (binder of Rho GTPases) family of Cdc42 effector proteins (Cdc42EP1-5) remains largely uncharacterised and relatively little is known about their structure, regulation and role in development and disease. Recent studies are starting to unravel some of the key functional and mechanistic aspects of the Borg proteins, including their role in cytoskeletal remodelling and signalling. In addition, the participation of Borg proteins in important cellular processes such as cell shape, directed migration and differentiation is slowly emerging, directly linking Borgs with important physiological and pathological processes such as angiogenesis, neurotransmission and cancer-associated desmoplasia...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913678/regulation-of-protein-phosphatase-2a-pp2a-tumor-suppressor-function-by-pme-1
#14
REVIEW
Amanpreet Kaur, Jukka Westermarck
Protein phosphatase 2A (PP2A) plays a major role in maintaining cellular signaling homeostasis by dephosphorylation of a variety of signaling proteins and acts as a tumor suppressor. Protein phosphatase methylesterase-1 (PME-1) negatively regulates PP2A activity by highly complex mechanisms that are reviewed here. Importantly, recent studies have shown that PME-1 promotes oncogenic MAPK/ERK and AKT pathway activities in various cancer types. In human glioma, high PME-1 expression correlates with tumor progression and kinase inhibitor resistance...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913677/phlpping-through-history-a-decade-in-the-life-of-phlpp-phosphatases
#15
REVIEW
Agnieszka T Grzechnik, Alexandra C Newton
In the decade since their discovery, the PH domain leucine-rich repeat protein phosphatases (PHLPP) have emerged as critical regulators of cellular homeostasis, and their dysregulation is associated with various pathophysiologies, ranging from cancer to degenerative diseases, such as diabetes and heart disease. The two PHLPP isozymes, PHLPP1 and PHLPP2, were identified in a search for phosphatases that dephosphorylate Akt, and thus suppress growth factor signaling. However, given that there are over 200 000 phosphorylated residues in a single cell, and fewer than 50 Ser/Thr protein phosphatases, it is not surprising that PHLPP has many other cellular functions yet to be discovered, including a recently identified role in regulating the epigenome...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913667/molecular-basis-for-specificity-of-the-met1-linked-polyubiquitin-signal
#16
REVIEW
Paul R Elliott
The post-translational modification of proteins provides a rapid and versatile system for regulating all signalling pathways. Protein ubiquitination is one such type of post-translational modification involved in controlling numerous cellular processes. The unique ability of ubiquitin to form polyubiquitin chains creates a highly complex code responsible for different subsequent signalling outcomes. Specialised enzymes ('writers') generate the ubiquitin code, whereas other enzymes ('erasers') disassemble it...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913664/receptor-activity-modifying-protein-directed-g-protein-signaling-specificity-for-the-calcitonin-gene-related-peptide-family-of-receptors
#17
Cathryn Weston, Ian Winfield, Matthew Harris, Rose Hodgson, Archna Shah, Simon J Dowell, Juan Carlos Mobarec, David A Woodcock, Christopher A Reynolds, David R Poyner, Harriet A Watkins, Graham Ladds
No abstract text is available yet for this article.
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27913654/novel-small-molecule-jp-153-targets-the-src-fak-paxillin-signaling-complex-to-inhibit-vegf-induced-retinal-angiogenesis
#18
Jordan J Toutounchian, Jayaprakash Pagadala, Duane D Miller, Jerome Baudry, Frank Park, Edward Chaum, Charles R Yates
Targeting vascular endothelial growth factor (VEGF) is a common treatment strategy for neovascular eye disease, a major cause of vision loss in diabetic retinopathy and age-related macular degeneration. However, the decline in clinical efficacy over time in many patients suggests that monotherapy of anti-VEGF protein therapeutics may benefit from adjunctive treatments. Our previous work has shown that through decreased activation of the cytoskeletal protein paxillin, growth factor-induced ischemic retinopathy in the murine oxygen-induced retinopathy model could be inhibited...
January 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/27913625/absence-of-mir-146a-in-podocytes-increases-risk-of-diabetic-glomerulopathy-via-upregulation-of-erbb4-and-notch-1
#19
Ha Won Lee, Samia Q Khan, Shehryar Khaliqdina, Mehmet M Altintas, Florian Grahammer, Jimmy L Zhao, Kwihey Koh, Nicholas J Tardi, Mohd Hafeez Faridi, Terese Geraghty, David J Cimbaluk, Katalin Susztak, Luis F Moita, David Baltimore, Pierre-Louis Tharaux, Tobias B Huber, Matthias Kretzler, Markus Bitzer, Jochen Reiser, Vineet Gupta
Podocyte injury is an early event in diabetic kidney disease and is a hallmark of glomerulopathy. MicroRNA-146a (miR-146a) is highly expressed in many cell types under homeostatic conditions, and plays an important anti-inflammatory role in myeloid cells. However, its role in podocytes is unclear. Here, we show that miR-146a expression levels decrease in the glomeruli of patients with type 2 diabetes (T2D), which correlates with increased albuminuria and glomerular damage. MiR-146a levels are also significantly reduced in the glomeruli of albuminuric BTBR ob/ob mice, indicating its significant role in maintaining podocyte health...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27913589/integrin-linked-kinase-ilk-deletion-disrupts-oligodendrocyte-development-by-altering-cell-cycle
#20
Rashad Hussain, Wendy B Macklin
: During development, oligodendrocytes are initially specified, after which oligodendrocyte precursor cells (OPCs) migrate and proliferate before differentiating into myelinating cells. Lineage specific programming of oligodendrocytes results from sensing environmental cues through membrane-bound receptors and related intracellular signaling molecules. Integrin linked kinase (ILK) is an important protein expressed at the inner margins of the plasma membrane, which can mediate some of these signals...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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