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https://www.readbyqxmd.com/read/28424220/gababr-induced-egfr-transactivation-promotes-migration-of-human-prostate-cancer-cells
#1
Shuai Xia, Cong He, Yini Zhu, Suyun Wang, Huiping Li, Zhongling Zhang, Xinnong Jiang, Jianfeng Liu
G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) act in concert to regulate cell growth, proliferation, survival, and migration. Metabotropic GABAB receptor (GABABR) is the GPCR for the main inhibitory neurotransmitter GABA in the central nervous system. Increased expression of GABABR has been detected in human cancer tissues and cancer cell lines, but the role of GABABR in these cells is controversial and the underlying mechanism remains poorly understood. Here, we investigated whether GABABR hijacks RTK signaling to modulate the fates of human prostate cancer cells...
April 19, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28423521/therapeutic-sensitivity-to-rac-gtpase-inhibition-requires-consequential-suppression-of-mtorc1-akt-and-mek-signaling-in-breast-cancer
#2
Riley A Hampsch, Kevin Shee, Darcy Bates, Lionel D Lewis, Laurent Désiré, Bertrand Leblond, Eugene Demidenko, Kurtis Stefan, Yina H Huang, Todd W Miller
Rac GTPases have oncogenic roles in cell growth, survival, and migration. We tested response to the Rac inhibitor EHT1864 in a panel of breast cancer cell lines. EHT1864-induced growth inhibition was associated with dual inhibition of the PI3K/AKT/mTORC1 and MEK/ERK pathways. Breast cancer cells harboring PIK3CA mutations or HER2 overexpression were most sensitive to Rac inhibition, suggesting that such oncogenic alterations link Rac activation with PI3K/AKT/mTORC1 and MEK/ERK signaling. Interestingly, EHT1864 decreased activation of the mTORC1 substrate p70S6K earlier than AKT inhibition, suggesting that Rac may activate mTORC1/p70S6K independently of AKT...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423360/tiam1-variants-improve-clinical-outcome-in-neuroblastoma
#3
Elena Sanmartín, Yania Yáñez, Victoria Fornés-Ferrer, José L Zugaza, Adela Cañete, Victoria Castel, Jaime Font de Mora
Identification of tumor driver mutations is crucial for improving clinical outcome using a personalized approach to the treatment of cancer. Neuroblastoma is a tumor of the peripheral sympathetic nervous system for which only a few driver alterations have been described including MYCN amplification and ALK mutations. We assessed 106 primary neuroblastoma tumors by next generation sequencing using a customized amplicon-based gene panel. Our results reveal that genetic variants in TIAM1 gene associate with better clinical outcome, suggesting a role for these TIAM1 variants in preventing progression of this disease...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418053/a-new-route-for-the-preparation-of-enriched-iso-polylactide-from-rac-lactide-via-a-lewis-acid-catalyzed-ring-opening-of-an-epoxide
#4
Mathew Anker, Choumini Balasanthiran, Vagulejan Balasanthiran, Malcolm H Chisholm, Savithra Jayaraj, Kaleb Mathieu, Parichat Piromjitpong, Siriwan Praban, Balaram Raya, William J Simonsick
Tetraphenylporphyrin aluminum(iii) salts, TPPAlX, where X = Me, OEt, OiPr, OCHMeCH2Cl, and Cl, and bis(triphenylphosphine)imminium chloride, PPN(+)Cl(-) (1 : 1) react with rac-lactide, rac-LA, in neat propylene oxide, PO, to yield chains of enriched isotactic polylactide, PLA, with end groups of PO-Cl and with time these yield cyclic polymers (PO)n(PLA) where n = 2 or 3 and even higher. There is no reaction between TPPAlOR (R = Et or (i)Pr), PPN(+)Cl(-), and rac-LA in neat THF at 25 °C even though TPPAlOR (R = Et or (i)Pr) and PPN(+)Cl(-) in neat PO yields polypropylene oxide with a terminal OR group, H(PO)nOR...
April 18, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28416593/two-components-of-aversive-memory-in-drosophila-anesthesia-sensitive-and-anesthesia-resistant-memory-require-distinct-domains-within-the-rgk1-small-gtpase
#5
Satoshi Murakami, Maki Minami-Ohtsubo, Ryuichiro Nakato, Katsuhiko Shirahige, Tetsuya Tabata
For aversive olfactory memory in Drosophila, multiple components have been identified that exhibit different stabilities. These components have been defined by behavioral and genetic studies, and genes specifically required for a specific component have also been identified. Intermediate-term memory generated after single cycle conditioning is divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We determined that the ASM and ARM pathways converged on the Rgk1 small GTPase and that the N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation...
April 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28412885/antenatal-taurine-supplementation-in-fetal-rats-with-growth-restriction-improves-neural-stem-cell-proliferation-by-inhibiting-the-activities-of-rho-family-factors
#6
Yan Wang, Xiang-Wen Li, Jing Liu, Wei Fu
OBJECTIVE: To investigate whether antenatal taurine supplementation improves neural stem cell proliferation in rats with fetal growth restriction (FGR) through regulating the activity of Rho family factors. METHODS: FGR models were established via food restriction throughout pregnancy. Pregnant rats were randomly divided into the control group, the FGR group (given 40% of the normal daily feeding in the control group), and the Taurine group (FGR model treated with 300 mg/kg·d taurine from gestational day seven)...
April 16, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28411215/the-effect-of-rho-drugs-on-mast-cell-activation-and-degranulation
#7
Avinash Sheshachalam, Alicia Baier, Gary Eitzen
Mast cells are tissue-resident immune cells that produce potent proinflammatory mediators, which are stored in cytoplasmic granules. Stimulation triggers degranulation, a process that mobilizes granules to dock and fuse to the plasma membrane, releasing mediators. Mast cell degranulation has an important role in immunity but can also intensify inflammation and contribute to allergic disorders. Hence, it is important to understand signaling pathways that regulate mast cell degranulation. Here, we examined the role of Rho proteins in regulating mast cell activation leading to degranulation...
April 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28409422/influence-of-long-term-equine-herpesvirus-type-1-ehv-1-infection-on-primary-murine-neurons-the-possible-effects-of-the-multiple-passages-of-ehv-1-on-its-neurovirulence
#8
Joanna Cymerys, A Słońska, A Tucholska, A Golke, A Chmielewska, M W Bańbura
Equine herpesvirus 1 (EHV-1), like other members of the Alphaherpesvirinae subfamily, is a neurotropic virus causing latent infections in the nervous system of the natural host. In the present study, we have investigated EHV-1 replication (wild-type Jan-E strain and Rac-H laboratory strain) during long-term infection and during the passages of the virus in cultured neurons. The studies were performed on primary murine neurons, which are an excellent in vitro model for studying neurotropism and neurovirulence of EHV-1...
April 13, 2017: Folia Microbiologica
https://www.readbyqxmd.com/read/28407307/adenosine-a1-receptors-measured-with-11-c-mpdx-pet-in-early-parkinson-s-disease
#9
Masahiro Mishina, Kenji Ishii, Yuichi Kimura, Masahiko Suzuki, Shin Kitamura, Kenji Ishibashi, Muneyuki Sakata, Keiichi Oda, Shiro Kobayashi, Kazumi Kimura, Kiichi Ishiwata
Adenosine A1 receptors (A1 Rs) interact negatively with dopamine D1 receptors (D1 Rs) in neurons of the basal ganglia's direct pathway, while adenosine A2A receptors (A2A Rs) negatively interact with dopamine D2 receptors (D2 Rs) in indirect-pathway neurons. The aim of this study was to investigate the cerebral density of A1 Rs in Parkinson's disease (PD) in its early stages, using PET scans with the radioligand 8-dicyclopropylmethyl-1-(11) C-methyl-3-propylxanthine ((11) C-MPDX). We studied 10 drug-naïve patients with early PD...
April 13, 2017: Synapse
https://www.readbyqxmd.com/read/28405665/expanding-the-substrate-scope-of-phenylalanine-ammonia-lyase-from-petroselinum-crispum-towards-styrylalanines
#10
László Csaba Bencze, Alina Filip, Gergely Bánóczi, Monica Ioana Toşa, Florin Dan Irimie, Ákos Gellért, László Poppe, Csaba Paizs
This study focuses on the expansion of the substrate scope of phenylalanine ammonia-lyase from Petroselinum crispum (PcPAL) towards the l-enantiomers of racemic styrylalanines rac-1a-d - which are less studied and synthetically challenging unnatural amino acids - by reshaping the aromatic binding pocket of the active site of PcPAL by point mutations. Ammonia elimination from l-styrylalanine (l-1a) catalyzed by non-mutated PcPAL (wt-PcPAL) took place with a 777-fold lower kcat/KM value than the deamination of the natural substrate, l-Phe...
April 13, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28398052/mechanistic-aspects-of-the-polymerization-of-lactide-using-a-highly-efficient-aluminum-iii-catalytic-system
#11
Carine Robert, Thibault E Schmid, Vincent Richard, Pierre Haquette, Sumesh K Raman, Marie-Noelle Rager, Régis M Gauvin, Yohann Morin, Xavier Trivelli, Vincent Guérineau, Iker Del Rosal, Laurent Maron, Christophe M Thomas
We report here a unique example of an in situ generated aluminum initiator stabilized by a C2-symmetric salen ligand which shows a hitherto unknown high activity for the ROP of rac-lactide at room temperature. Using a simple and robust catalyst system, which is prepared from a salen complexe and an onium salt, this convenient route employs readily available reagents that afford polylactide in good yields with narrow polydispersity indices, without the need for time consuming and expensive processes that are typically required for catalyst preparation and purification...
April 11, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28390160/the-role-of-small-gtpases-of-the-rho-rac-family-in-tgf-%C3%AE-induced-emt-and-cell-motility-in-cancer
#12
REVIEW
Hendrik Ungefroren, David Witte, Hendrik Lehnert
BACKGROUND: This article focusses on the role of Rho family GTPases and particularly Rac1 and Rac1b in TGF-β-induced epithelial-mesenchymal transition (EMT) and EMT-associated responses such as cell migration, invasion, and metastasis in cancer. RESULTS: EMT is considered a prerequisite for cells to adopt a motile and invasive phenotype and eventually become metastatic. A major regulator of EMT and metastasis in cancer is TGF-β and its specific functions on tumor cells are mediated besides Smad proteins and mitogen-activated protein kinases (MAPKs) by small GTPases of the Rho/Rac1 family...
April 8, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28388666/picroside-ii-protects-the-blood-brain-barrier-by-inhibiting-the-oxidative-signaling-pathway-in-cerebral-ischemia-reperfusion-injury
#13
Li Zhai, Min Liu, Tingting Wang, Hongyan Zhang, Shan Li, Yunliang Guo
BACKGROUND AND PURPOSE: Thrombolysis is used to improve cerebral circulation; at the same time, neuroprotective drugs such as antioxidants should also be used. The aim of these experiments was to explore the protective mechanism of an antioxidant, picroside II, on the blood-brain barrier (BBB) after cerebral ischemia-reperfusion (CI/R) injury. METHODS: To observe the antagonistic effect of picroside II on CI/R damage, the neurological deficit score and the infarct volume were measured...
2017: PloS One
https://www.readbyqxmd.com/read/28384534/improving-treatment-results-with-reference-centres-for%C3%A2-rare-cancers-where-do-we-stand
#14
REVIEW
Isabelle Ray-Coquard, Eric Pujade Lauraine, Axel Le Cesne, Patricia Pautier, Marie Cecile Vacher Lavenue, Annalisa Trama, Paolo Casali, Jean Michel Coindre, Jean Yves Blay
Rare adult cancer (RAC) is characterised by an incidence of less than six cases per 100,000 people per annum; Four-million three-hundred thousand patients in the European Union are living with some or other rare cancer (22% of all new human cancers). These cancers are linked with worse survival rates than 'frequent' tumours (5-year survival: 47% for RAC against 65% for 'common' cancers), mainly because of: (1) delays in obtaining an accurate diagnosis, (2) inadequate treatments given in curative phases and (3) restricted opportunities for patients to participate in clinical trials because of the lack of support for dedicated trials for this disease group from both academic and industrial sponsors...
April 3, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28382498/assessing-the-relative-potency-of-s-and-r-warfarin-with-a-new-pk-pd-model-in-relation-to-vkorc1-genotypes
#15
Myriam Ferrari, Vittorio Pengo, Massimiliano Barolo, Fabrizio Bezzo, Roberto Padrini
PURPOSE: The purpose of this study is to develop a new pharmacokinetic-pharmacodynamic (PK-PD) model to characterise the contribution of (S)- and (R)-warfarin to the anticoagulant effect on patients in treatment with rac-warfarin. METHODS: Fifty-seven patients starting warfarin (W) therapy were studied, from the first dose and during chronic treatment at INR stabilization. Plasma concentrations of (S)- and (R)-W and INRs were measured 12, 36 and 60 h after the first dose and at steady state 12-14 h after dosing...
April 5, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28382316/connecting-markov-random-fields-and-active-contour-models-application-to-gland-segmentation-and-classification
#16
Jun Xu, James P Monaco, Rachel Sparks, Anant Madabhushi
We introduce a Markov random field (MRF)-driven region-based active contour model (MaRACel) for histological image segmentation. This Bayesian segmentation method combines a region-based active contour (RAC) with an MRF. State-of-the-art RAC models assume that every spatial location in the image is statistically independent, thereby ignoring valuable contextual information among spatial locations. To address this shortcoming, we incorporate an MRF prior into energy term of the RAC. This requires a formulation of the Markov prior consistent with the continuous variational framework characteristic of active contours; consequently, we introduce a continuous analog to the discrete Potts model...
April 2017: Journal of Medical Imaging
https://www.readbyqxmd.com/read/28378455/phosphasalen-indium-complexes-showing-high-rates-and-isoselectivities-in-rac-lactide-polymerizations
#17
Dominic Myers, Andrew J P White, Craig M Forsyth, Mark Bown, Charlotte K Williams
Polylactide (PLA) is the leading bioderived polymer produced commercially by the metal-catalyzed ring-opening polymerization of lactide. Control over tacticity to produce stereoblock PLA, from rac-lactide improves thermal properties but is an outstanding challenge. Here, phosphasalen indium catalysts feature high rates (30±3 m(-1)  min(-1) , THF, 298 K), high control, low loadings (0.2 mol %), and isoselectivity (Pi =0.92, THF, 258 K). Furthermore, the phosphasalen indium catalysts do not require any chiral additives...
April 5, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28375013/regio-and-stereocontrolled-synthesis-of-3-substituted-1-2-diazetidines-by-asymmetric-allylic-amination-of-vinyl-epoxide
#18
Sundaram Rajkumar, Guy J Clarkson, Michael Shipman
Pd-catalyzed asymmetric allylic amination of rac-vinyl epoxide with unsymmetrical 1,2-hydrazines proceeds with excellent regio- and stereocontrol, which after further ring closure provides differentially protected 3-vinyl-1,2-diazetidines in good yields. The chirality at C-3 exerts stereocontrol over the nitrogen centers in the 1,2-diazetidine with all substituents orientating themselves trans to their neighbors. Efficient functionalization without rupture of the strained ring is demonstrated (e.g., by cross-metathesis), establishing the first general route to C-3-substituted 1,2-diazetidines in enantioenriched form...
April 4, 2017: Organic Letters
https://www.readbyqxmd.com/read/28374021/a-structurally-characterised-redox-pair-involving-an-indigo-radical-indigo-based-redox-activity-in-complexes-with-one-or-two-ru-bpy-2-fragments
#19
Madhumita Chatterjee, Prasenjit Mondal, Katharina Beyer, Alexa Paretzki, Wolfgang Kaim, Goutam Kumar Lahiri
The reaction between indigo, H2Ind, and {Ru(bpy)2(EtOH)2}(2+) in EtOH/NaOH produced the compounds [Ru(bpy)2(HInd)]ClO4 [1]ClO4, rac-{[Ru(bpy)2]2(μ-Ind)}(ClO4)2 [2](ClO4)2, and meso-{[Ru(bpy)2]2(μ-Ind)}(ClO4)3 [2](ClO4)3, which were structurally characterised, the latter as the first stable, isolable radical complex of indigo. The redox pair 2(2+)/2(3+) showed little structural difference, as confirmed using DFT calculations. The redox series 1(n) and 2(n) were investigated using voltammetry and spectroelectrochemistry (EPR, UV-vis-NIR)...
April 11, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28370511/di-zinc-aryl-complexes-co2-insertions-and-applications-in-polymerization-catalysis
#20
Charles Romain, Jennifer A Garden, Gemma Trott, Antoine Buchard, Andrew J P White, Charlotte Katherine Williams
Two new di-zinc aryl complexes, [LZn2Ph2] and [LZn2(C6F5)2], coordinated by a diphenol tetraamine macrocyclic ligand are prepared and fully characterized, including by single crystal X-ray diffraction experiments. The complexes' reactivities with monomers including carbon dioxide, cyclohexene oxide, phthalic anhydride, iso-propanol and phenol are investigated using both experimental studies and density functional theory calculations. In particular, [LZn2Ph2] readily inserts carbon dioxide to form a carboxylate, at 1 bar pressure, whereas [LZn2(C6F5)2] does not react...
March 30, 2017: Chemistry: a European Journal
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