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https://www.readbyqxmd.com/read/28647652/kinase-activity-in-recurring-primary-skull-base-chordomas-and-chondrosarcomas-identification-of-novel-pathways-of-oncogenesis-and-potential-drug-targets
#1
Philip Tatman, Joshua Osbun, Youssef Yakkioui, Sumanpret Kaur, Carolina Parada, Tina Busald, Donald Born, Owais Ahmad, Jing Zhang, Manuel Ferreira
OBJECTIVE: Chordomas and chondrosarcomas are tumors that can occur in the skull base. Currently, 45% of chordomas and 56% of chondrosarcomas recur within five years of surgery. The role of adjuvant therapy is highly debated. No pharmacotherapies have been approved by the FDA for chordomas or chondrosarcomas. The high propensity for recurrence and lack of definitive adjuvant therapy necessitates additional basic science research to identify molecular anomalies associated with recurrent disease...
June 21, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28646493/src-family-kinase-phosphorylation-of-the-motor-domain-of-the-human-kinesin-5-eg5
#2
Kathleen G Bickel, Barbara J Mann, Joshua S Waitzman, Taylor A Poor, Sarah E Rice, Patricia Wadsworth
Spindle formation in mammalian cells requires precise spatial and temporal regulation of the kinesin-5, Eg5, which generates outward force to establish spindle bipolarity. Our results demonstrate that Eg5 is phosphorylated in cultured cells by Src family kinases (SFKs) at three sites in the motor head: Y125, Y211, and Y231. Mutation of these sites diminishes motor activity in vitro, and replacement of endogenous Eg5 with phosphomimetic Y211 in LLC-Pk1 cells results in monopolar spindles, consistent with loss of Eg5 activity...
June 23, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28646122/nintedanib-a-triple-tyrosine-kinase-inhibitor-attenuates-renal-fibrosis-in-chronic-kidney-disease
#3
Feng Liu, Li Wang, Hualin Qi, Jun Wang, Wei Jiang, Yi Wang, Liuqing Xu, Na Liu, Shougang Zhuang
<span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">Nintedanib (BIBF1120) is a triple kinase inhibitor</span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;"> of </span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">platelet derived growth factor receptor (PDGFR), fibroblast growth factor receptors (FGFR)</span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">, </span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">vascular endothelial growth factor receptor (VEGFR)</span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;"> and Src family kinase, </span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">that has recently been approved by FDA to treat idiopathic pulmonary fibrosis...
June 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28645697/clinical-high-resolution-mapping-of-the-proteoglycan-bound-water-fraction-in-articular-cartilage-of-the-human-knee-joint
#4
Mustapha Bouhrara, David A Reiter, Kyle W Sexton, Christopher M Bergeron, Linda M Zukley, Richard G Spencer
PURPOSE: We applied a recently introduced method to achieve clinically-feasible in-vivo mapping of the proteoglycan water fraction (PgWF) of human knee cartilage with improved spatial resolution and stability as compared to existing methods. MATERIAL AND METHODS: Multicomponent driven equilibrium single-pulse observation of T1 and T2 (mcDESPOT) datasets were acquired from the knees of two healthy young subjects and one older subject with previous knee injury. Each dataset was processed using Bayesian Monte Carlo (BMC) analysis incorporating a two-component tissue model...
June 20, 2017: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/28645579/anti-androgenic-mechanisms-of-bisphenol-a-involve-androgen-receptor-signaling-pathway
#5
Hui Wang, Zhen Ding, Qiao-Mei Shi, Xing Ge, Heng-Xue Wang, Meng-Xue Li, Gang Chen, Qi Wang, Qiang Ju, Jin-Peng Zhang, Mei-Rong Zhang, Li-Chun Xu
We have shown Bisphenol A (BPA) acts as an androgen receptor (AR) antagonist in the previous study. However, the mechanisms underlying anti-androgenic effects of BPA remain unclear. The objective of this study was to explore whether the AR signaling was involved in AR antagonism of BPA. The Cell Counting Kit-8 (CCK-8) assay and Real-Time Cell Analysis (RTCA) iCELLigence system were applied to analyze the mouse Sertoli cell TM4 proliferation. The mammalian two-hybrid assays were performed to investigate the effects of BPA on the AR amino- and carboxyl-terminal regions (N/C) interaction and the interactions of the AR with steroid receptor coactivator-1 (SRC-1), co-repressors including silencing mediator for thyroid hormone receptors (SMRT) and nuclear receptor co-repressor (NCoR)...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28643869/mechanotransduction-properties-of-the-cytoplasmic-tail-of-pecam-1
#6
Jessica L Snyder, Elena McBeath, Tamlyn N Thomas, Yi Jen Chiu, Robert L Clark, Keigi Fujiwara
BACKGROUND: Vascular endothelial cells (ECs) are a well-known cell system used in the study of mechanobiology. Using cultured ECs, we found that platelet endothelial cell adhesion molecule 1 (PECAM-1, CD31), a cell adhesion protein localized to regions of EC-EC contact, was rapidly tyrosine phosphorylated in ECs exposed to shear or cyclic stretch. Src-homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) binds phosphorylated PECAM-1 and activates the extracellular signal-regulated kinase1/2 (ERK1/2) signaling cascade, a known flow-activated signaling pathway...
June 23, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/28638122/synergistic-effects-of-various-her-inhibitors-in-combination-with-igf-1r-c-met-and-src-targeting-agents-in-breast-cancer-cell-lines
#7
Aryan Stanley, G Hossein Ashrafi, Alan M Seddon, Helmout Modjtahedi
Overexpression of HER2 has been reported in around 25% of human breast cancers. Despite recent advances in HER2 targeted therapy, many patients still experience primary and secondary resistance to such treatments, the mechanisms for which are poorly understood. Here, we investigated the sensitivity of a panel of breast cancer cell lines to treatment with various types of HER-family inhibitors alone or in combination with other tyrosine kinase inhibitors or chemotherapeutic agents. We found that treatment with the second-generation irreversible HER-family inhibitors, particularly afatinib and neratinib, were more effective than treatment with the first-generation reversible inhibitors in inhibiting growth, migration and downstream cell signalling in breast cancer cells...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637841/protein-tyrosine-phosphatase-%C3%AE-mediates-the-sema3a-induced-cortical-basal-dendritic-arborization-through-the-activation-of-fyn-tyrosine-kinase
#8
Fumio Nakamura, Takako Okada, Maria Shishikura, Noriko Uetani, Masahiko Taniguchi, Takeshi Yagi, Yoichiro Iwakura, Toshio Ohshima, Yoshio Goshima, Stephen M Strittmatter
Leukocyte common antigen related (LAR) class protein tyrosine phosphatases (PTPs) are critical for axonal guidance; however, their relation to specific guidance cues is poorly defined. We here show that PTP-3, LAR homologue in C. elegans, is involved in axon guidance regulated by Sema2A-signaling. PTPδ, one of vertebrate LAR class PTPs, participates in Sema3A-induced growth cone collapse response of primary cultured dorsal root ganglion neurons from M. musculus embryos. In vivo, however, the contribution of PTPδ in Sema3A-regualted axon guidance was minimal...
June 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28637715/tyrosine-kinase-inhibitors-protect-the-salivary-gland-from-radiation-damage-by-inhibiting-activation-of-protein-kinase-c-%C3%AE
#9
Sten M Wie, Elizabeth Wellberg, Sana D Karam, Mary E Reyland
In patients undergoing irradiation therapy, injury to non-tumor tissues can result in debilitating, and sometimes permanent, side effects. We have defined Protein Kinase C-delta (PKCδ) as a regulator of DNA damage induced apoptosis and have shown that phosphorylation of PKCδ by c-Abl and c-Src activates its pro-apoptotic function.  Here we have explored the use of tyrosine kinase inhibitors (TKIs) of c-Src and c-Abl to block activation of PKCδ for radioprotection of the salivary gland.  Dasatinib, imatinib, and bosutinib all suppressed tyrosine phosphorylation of PKCδ and inhibited IR-induced apoptosis in vitro  To determine if TKIs can provide radioprotection of salivary gland function in vivo, mice were treated with TKIs and a single or fractionated doses of irradiation...
June 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28637676/editorial-focus-on-balance-between-s-nitrosylation-and-denitrosylation-modulates-myoblast-proliferation-independently-of-soluble-guanylyl-cyclase-activation
#10
Hugo P Monteiro, Fernando T Ogata
Myogenesis involves a complex series of signaling events that will result in the formation of muscle fibers. The participation of nitric oxide (NO) in myogenesis is well established. NO generation in skeletal muscle comes from the neuronal isoform of the NO synthase (nNOS). NO signals through cGMP production and s-nitrosylation of proteins in skeletal muscle. In skeletal muscle, nNOS interacts with two domains of caveolin-3 which is part of caveolae, and forms a signaling complex through additional interactions with Src kinase and p21Ras...
June 21, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28636830/attenuation-of-hepatic-steatosis-by-purple-sweet-potato-color-is-associated-with-blocking-src-erk-c-ebp%C3%AE-signalling-in-high-fat-diet-treated-mice
#11
Xin Wang, Zi-Feng Zhang, Gui-Hong Zheng, Ai-Min Wang, Chun-Hui Sun, Su-Ping Qin, Juan Zhuang, Jun Lu, Dai-Fu Ma, Yuan-Lin Zheng
Our previous work showed that purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, effectively improved hepatic glucose metabolic dysfunction in high-fat diet (HFD)-treated mice. This study investigated the effects of PSPC on HFD-induced hepatic steatosis and the signalling events associated with these effects. Mice were divided into four groups: Control group, HFD group, HFD+PSPC group and PSPC group. PSPC was administered daily for 20 weeks at oral doses of 700 mg/kg/day. Our results showed that PSPC significantly improved obesity and related metabolic parameters, as well as liver injury in HFD-treated mice...
June 21, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28634209/genetic-evidence-that-%C3%AE-arrestins-are-dispensable-for-the-initiation-of-%C3%AE-2-adrenergic-receptor-signaling-to-erk
#12
Morgan O'Hayre, Kelsie Eichel, Silvia Avino, Xuefeng Zhao, Dana J Steffen, Xiaodong Feng, Kouki Kawakami, Junken Aoki, Karen Messer, Roger Sunahara, Asuka Inoue, Mark von Zastrow, J Silvio Gutkind
The β2-adrenergic receptor (β2AR) has provided a paradigm to elucidate how G protein-coupled receptors (GPCRs) control intracellular signaling, including the discovery that β-arrestins, which bind to ligand-activated GPCRs, are central for GPCR function. We used genome editing, conditional gene deletion, and small interfering RNAs (siRNAs) to determine the roles of β-arrestin 1 (β-arr1) and β-arr2 in β2AR internalization, trafficking, and signaling to ERK. We found that only β-arr2 was essential for β2AR internalization...
June 20, 2017: Science Signaling
https://www.readbyqxmd.com/read/28634059/a-pumpkin-polysaccharide-induces-apoptosis-by-inhibiting-the-jak2-stat3-pathway-in-human-hepatoma-hepg2-cells
#13
Weixi Shen, Chunhong Chen, Yuanyuan Guan, Xiaowei Song, Yinghua Jin, Jingfang Wang, Yu Hu, Tao Xin, Qiuying Jiang, Li Zhong
The purpose of this study is to investigate the effect of a purified polysaccharide (PPPF) from pumpkin fruit on the Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling during apoptotic process. The results showed that PPPF or STAT3 siRNA inhibits the cell growth of HepG2 cells via induction of apoptosis. Moreover, PPPF is able to suppress both constitutive and IL-6-induced phosphorylation of STAT3 (on Tyr705) and subsequent nuclear translocation in cancer cells. Such inhibition is found to be achieved through down-regulation of constitutive phosphorylation of JAK2, but not JAk1, c-Src, ERK1/2, and Akt, which means STAT3 tyrosine phosphorylation in HepG2 cells following PPPF treatment is associated with a reduction in JAK2 activity...
June 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28633996/effects-of-monoaminergic-drugs-on-training-induced-motor-cortex-plasticity-in-older-adults
#14
Trisha M Kesar, Samir R Belagaje, Paola Pergami, Marc W Haut, Gerald Hobbs, Cathrin M Buetefisch
Primary motor cortex (M1) plasticity is involved in motor learning and stroke motor recovery, and enhanced by increasing monoaminergic transmission. Age impacts these processes but there is a paucity of systematic studies on the effects of monoaminergic drugs in older adults. Here, in ten older adults (age 61+ 4 years, 4 males), we determine the effects of a single oral dose of carbidopa/levodopa (DOPA), d-amphetamine (AMPH), methylphenidate (MEPH) and placebo (PLAC) on M1 excitability and motor training-induced M1 plasticity...
June 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28631712/-the-molecular-mechanisms-and-morphological-manifestations-of-leiomyoma-reduction-induced-by-selective-progesterone-receptor-modulators
#15
T A Demura, Z V Revazova, E A Kogan, L V Adamyan
AIM: to investigate the molecular mechanisms and morphological substrate of reduced uterine leiomyoma in patients receiving the selective progesterone receptor modulator (SPRM) ulipristal acetate for 3 months, by estimating the immunohistochemical expression of the markers steroid receptor coactivator 1 (SRC-1), nuclear receptor corepressor 1 (NCoR-1), ER, PgR, Ki-67, p16, TGF-β, and VEGF in tumor tissue. SUBJECTS AND METHODS: The investigation enrolled 75 women with uterine leiomyoma, menorrhagias, and anemia...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28630500/hyperuricemia-and-overexcretion-of-uric-acid-increase-the-risk-of-simple-renal-cysts-in-type-2-diabetes
#16
Ying Han, Mingliang Zhang, Junxi Lu, Lei Zhang, Junfeng Han, Fangya Zhao, Haibing Chen, Yuqian Bao, Weiping Jia
Previous studies have discussed the relationship between simple renal cysts (SRC) and serum uric acid level in healthy individuals. We performed a cross-sectional study to evaluate the association between serum uric acid level and fractional excretion of uric acid (FEUA) and simple renal cysts in males and postmenopausal females with type 2 diabetes. The overall prevalence of SRC was 18.1% in our population. SRC prevalence was significantly higher in hyperuricemic than normouricemic subjects (27.3% vs. 16.8%, P < 0...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28629162/promotion-of-tumor-invasion-by-tumor-associated-macrophages-the-role-of-csf-1-activated-phosphatidylinositol-3-kinase-and-src-family-kinase-motility-signaling
#17
REVIEW
Amy R Dwyer, Eloise L Greenland, Fiona J Pixley
Macrophages interact with cells in every organ to facilitate tissue development, function and repair. However, the close interaction between macrophages and parenchymal cells can be subverted in disease, particularly cancer. Motility is an essential capacity for macrophages to be able to carry out their various roles. In cancers, the macrophage's interstitial migratory ability is frequently co-opted by tumor cells to enable escape from the primary tumor and metastatic spread. Macrophage accumulation within and movement through a tumor is often stimulated by tumor cell production of the mononuclear phagocytic growth factor, colony-stimulating factor-1 (CSF-1)...
June 18, 2017: Cancers
https://www.readbyqxmd.com/read/28627476/deciphering-the-protein-protein-interaction-network-regulating-hepatocellular-carcinoma-metastasis
#18
Guoxuan Qin, Mengjiao Dang, Huajun Gao, Hao Wang, Fengting Luo, Ruibing Chen
Hepatocellular carcinoma (HCC) is one of the leading causes of mortality related to cancer all over the world. To better understand the molecular mechanisms of HCC metastasis, we analyzed the proteome of three HCC cell lines with different metastasis potentials by quantitative proteomics and bioinformatics analysis. As a result, we identified 378 cellular proteins potentially associated to HCC metastasis, and constructed a highly connected protein-protein interaction (PPI) network. Functional annotation of the network uncovered prominent pathways and key roles of these proteins, suggesting that the metabolism and cytoskeleton biological processes are greatly involved with HCC metastasis...
June 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28626446/gnrh-induces-erk-dependent-bleb-formation-in-gonadotrope-cells-involving-recruitment-of-members-of-a-gnrh-receptor-associated-signalosome-to-the-blebs
#19
Liat Rahamim-Ben Navi, Anna Tsukerman, Alona Feldman, Philippa Melamed, Melanija Tomić, Stanko S Stojilkovic, Ulrich Boehm, Rony Seger, Zvi Naor
We have previously described a signaling complex (signalosome) associated with the GnRH receptor (GnRHR). We now report that GnRH induces bleb formation in the gonadotrope-derived LβT2 cells. The blebs appear within ~2 min at a turnover rate of ~2-3 blebs/min and last for at least 90 min. Formation of the blebs requires active ERK1/2 and RhoA-ROCK but not active c-Src. Although the following ligands stimulate ERK1/2 in LβT2 cells: EGF > GnRH > PMA > cyclic adenosine monophosphate (cAMP), they produced little or no effect on bleb formation as compared to the robust effect of GnRH (GnRH > PMA > cAMP > EGF), indicating that ERK1/2 is required but not sufficient for bleb formation possibly due to compartmentalization...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28626342/effects-of-src-kinase-inhibition-on-expression-of-protein-tyrosine-phosphatase-1b-after-brain-hypoxia-in-a-piglet-animal-model
#20
Dimitrios Angelis, Maria Delivoria-Papadopoulos
BACKGROUND: Protein tyrosine phosphatases (PTPs) in conjunction with protein tyrosine kinases (PTKs) regulate cellular processes by posttranslational modifications of signal transduction proteins. PTP nonreceptor type 1B (PTP-1B) is an enzyme of the PTP family. We have previously shown that hypoxia induces an increase in activation of a class of nonreceptor PTK, the Src kinases. In the present study, we investigated the changes that occur in the expression of PTP-1B in the cytosolic component of the brain of newborn piglets acutely after hypoxia as well as long term for up to 2 weeks...
2017: Mediators of Inflammation
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