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https://www.readbyqxmd.com/read/28214198/tumor-derived-cd4-cd25-regulatory-t-cells-inhibit-dendritic-cells-function-by-ctla-4
#1
Xin Chen, Yong Du, Qingqing Hu, ZhiMing Huang
PURPOSE: CD4+CD25+regulatoryT cells (Tregs) play an important role in anti-tumor immune responses. Poor prognosis and declining survival rates have intimate connection with high Treg expression in cancer patients. Cytotoxic T Lymphocyte-associated protein (CTLA-4) is one of the most prominent molecules on Treg. In our previous research, we have demonstrated that HCC-derived Tregs can interfere with Dendritic cells (DCs) function and down-modulate CD80/CD86 on DCs in vitro in a cell-contact dependent way...
December 21, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28213834/molecular-simulation-of-receptor-occupancy-and-tumor-penetration-of-an-antibody-and-smaller-scaffolds-application-to-molecular-imaging
#2
Kelly D Orcutt, Gregory P Adams, Anna M Wu, Matthew D Silva, Catey Harwell, Jack Hoppin, Manabu Matsumura, Masakatsu Kotsuma, Jonathan Greenberg, Andrew M Scott, Robert A Beckman
PURPOSE: Competitive radiolabeled antibody imaging can determine the unlabeled intact antibody dose that fully blocks target binding but may be confounded by heterogeneous tumor penetration. We evaluated the hypothesis that smaller radiolabeled constructs can be used to more accurately evaluate tumor expressed receptors. PROCEDURES: The Krogh cylinder distributed model, including bivalent binding and variable intervessel distances, simulated distribution of smaller constructs in the presence of increasing doses of labeled antibody forms...
February 17, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28213726/pd-1-and-pd-l1-antibodies-in-cancer-current-status-and-future-directions
#3
REVIEW
Arjun Vasant Balar, Jeffrey S Weber
Immunotherapy has moved to the center stage of cancer treatment with the recent success of trials in solid tumors with PD-1/PD-L1 axis blockade. Programmed death-1 or PD-1 is a checkpoint molecule on T cells that plays a vital role in limiting adaptive immune responses and preventing autoimmune and auto-inflammatory reactivity in the normal host. In cancer patients, PD-1 expression is very high on T cells in the tumor microenvironment, and PD-L1, its primary ligand, is variably expressed on tumor cells and antigen-presenting cells within tumors, providing a potent inhibitory influence within the tumor microenvironment...
February 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28213446/acetylcholine-release-in-prefrontal-cortex-promotes-gamma-oscillations-and-theta-gamma-coupling-during-cue-detection
#4
W M Howe, H J Gritton, N Lusk, Erik A Roberts, Vaughn L Hetrick, Joshua D Berke, Martin Sarter
The capacity for using external cues to guide behavior ("cue detection") constitutes an essential aspect of attention and goal-directed behavior. The cortical cholinergic input system, via phasic increases in prefrontal acetylcholine release, plays an essential role in attention by mediating such cue detection. However, the relationship between cholinergic signaling during cue detection and neural activity dynamics in prefrontal networks remains unclear. Here we combined sub-second measures of cholinergic signaling, neurophysiological recordings, and cholinergic receptor blockade to delineate the cholinergic contributions to prefrontal oscillations during cue detection in rats...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#5
Nicolas A Giraldo, Etienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez-Salas, Alexandre Ingels, Stephane Marie Oudard, Audrey Moatti, Bénédicte Buttard, Sarah Bourras, Claire Germain, Xavier Cathelineau, Wolf-Herman Fridman, Catherine Sautes-Fridman
PURPOSE: The efficacy of PD-1 Checkpoint Blockade (ChB) as adjuvant therapy in localized clear cell Renal Cell Carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help to define which patients could benefit from ChB and to uncover new therapeutic targets. EXPERIMENTAL DESIGN: We performed multiparametric flow cytometry immunophenotypic analysis of T cells isolated from tumor tissue (TIL), adjacent non-malignant renal tissue (RIL) and peripheral blood (PBL), in a cohort of patients (n=40) with localized ccRCC...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28213203/ghrelin-s-control-of-food-reward-and-body-weight-in-the-lateral-hypothalamic-area-is-sexually-dimorphic
#6
Lorena López-Ferreras, Jennifer E Richard, Rozita H Anderberg, Fredrik H Nilsson, Kajsa Olandersson, Scott E Kanoski, Karolina P Skibicka
Ghrelin is a stomach-produced hormone that stimulates ingestive behavior and increases motivated behavior to obtain palatable foods. Ghrelin receptors (growth hormone secretagogue receptors; Ghsr) are expressed in the lateral hypothalamic area (LHA), and LHA-targeted ghrelin application increases ingestive behavior in male rodents. However, the effects of LHA ghrelin signaling in females are unexplored. Here we investigated whether LHA ghrelin signaling is necessary and sufficient for control of ingestive and motivated behavior for food in male and female rats...
February 14, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28213070/selective-a2a-receptors-blockade-reduces-degeneration-of-substantia-nigra-dopamine-neurons-in-a-rotenone-induced-rat-model-of-parkinson-s-disease-a-histological-study
#7
Ahmed M Fathalla, Amira M Soliman, Ahmed A Moustafa
Parkinson's disease (PD) is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Adenosine is a neuromodulator that inhibit the release of dopamine via a disinhibitory mechanism. In this study, we investigated the neuroprotective effect of 8-cyclopentyl-1,3-dipropylxanthine and ZM241385 (respectively, A1 and A2A receptors antagonists), on nigrostriatal dopamine neurons degradation reduction in a rotenone-induced PD model using histopathological and immunohistochemical methods...
February 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28212941/injections-of-the-of-the-%C3%AE-1-adrenoceptor-antagonist-prazosin-into-the-median-raphe-nucleus-increase-food-intake-and-fos-expression-in-orexin-neurons-of-free-feeding-rats
#8
Eduardo Simão da Silva, Rafael Appel Flores, Anderson Savaris Ribas, Ana Paula Taschetto, Moacir Serralvo Faria, Leandro Bueno Lima, Martin Metzger, José Donato, Marta Aparecida Paschoalini
Previously, we showed that the blockade of α1-adrenoreceptors in the median raphe nucleus (MnR) increased food intake in free-feeding rats, indicating that adrenergic mechanisms in the MnR participate in the regulation of food intake. However, the impact of such a pharmacological manipulation on other neural circuits related to food intake remains unknown. In the current study, we sought to identify forebrain regions which are responsive to α1-adrenergic receptor blockade and presumably involved in the modulation of the feeding response...
February 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28212885/epinephrine-promotes-cox-2-dependent-immune-suppression-in-myeloid-cells-and-cancer-tissues
#9
Ravikumar Muthuswamy, Nana J Okada, Frank J Jenkins, Kandace McGuire, Priscilla F McAuliffe, Herbert J Zeh, David L Bartlett, Callen Wallace, Simon Watkins, Jill D Henning, Dana H Bovbjerg, Pawel Kalinski
Activation of the sympathetic nervous system (e.g., due to stress) has been implicated in cancer progression and recurrence, but its cancer-promoting effects have been variable between different studies. Here, we report that although catecholamines, mediators of systemic sympathetic activity, display only weak immunosuppressive impact on their own, their combination with inflammatory signals leads to the induction of COX-2 and multiple COX-2-dependent suppressive factors in human myeloid cells and cancer tissues...
February 14, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28212842/pathophysiological-consequences-of-receptor-mistraffic-tales-from-the-platelet-p2y12-receptor
#10
Margaret R Cunningham, Riyaad Aungraheeta, Stuart J Mundell
Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function...
February 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28212543/metabotropic-glutamate-receptors-as-a-new-therapeutic-target-for-malignant-gliomas
#11
REVIEW
Mery Stefani Leivas Pereira, Fábio Klamt, Chairini Cássia Thomé, Paulo Valdeci Worm, Diogo Losch de Oliveira
Metabotropic glutamate receptors (mGluR) are predominantly involved in maintenance of cellular homeostasis of central nervous system. However, evidences have suggested other roles of mGluR in human tumors. Aberrant mGluR signaling has been shown to participate in transformation and maintenance of various cancer types, including malignant brain tumors. This review intends to summarize recent findings regarding the involvement of mGluR-mediated intracellular signaling pathways in progression, aggressiveness, and recurrence of malignant gliomas, mainly glioblastomas (GBM), highlighting the potential therapeutic applications of mGluR ligands...
February 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212375/epilepsy-associated-gene-nedd4-2-mediates-neuronal-activity-and-seizure-susceptibility-through-ampa-receptors
#12
Jiuhe Zhu, Kwan Young Lee, Kathryn A Jewett, Heng-Ye Man, Hee Jung Chung, Nien-Pei Tsai
The neural precursor cell expressed developmentally down-regulated gene 4-2, Nedd4-2, is an epilepsy-associated gene with at least three missense mutations identified in epileptic patients. Nedd4-2 encodes a ubiquitin E3 ligase that has high affinity toward binding and ubiquitinating membrane proteins. It is currently unknown how Nedd4-2 mediates neuronal circuit activity and how its dysfunction leads to seizures or epilepsies. In this study, we provide evidence to show that Nedd4-2 mediates neuronal activity and seizure susceptibility through ubiquitination of GluA1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, (AMPAR)...
February 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28212191/endothelial-cell-metabolism-an-update-anno-2017
#13
Laure-Anne Teuwen, Nihed Draoui, Charlotte Dubois, Peter Carmeliet
PURPOSE OF REVIEW: Endothelial cell metabolism has recently emerged as an important coregulator of angiogenesis and is therefore a promising new target in various angiogenesis-associated illnesses, like cancer. In this review, we discuss recent insights in endothelial cell metabolism in both physiological and pathological conditions and discuss possible translational implications. RECENT FINDINGS: Two metabolic pathways that determine the performance of endothelial cells are glycolysis and fatty acid oxidation (FAO)...
February 15, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28212163/multiple-organ-dysfunction-in-children-mechanically-ventilated-for-acute-respiratory-failure
#14
Scott L Weiss, Lisa A Asaro, Heidi R Flori, Geoffrey L Allen, David Wypij, Martha A Q Curley
OBJECTIVES: The impact of extrapulmonary organ dysfunction, independent from sepsis and lung injury severity, on outcomes in pediatric acute respiratory failure is unclear. We sought to determine the frequency, timing, and risk factors for extrapulmonary organ dysfunction and the independent association of multiple organ dysfunction syndrome with outcomes in pediatric acute respiratory failure. DESIGN: Secondary observational analysis of the Randomized Evaluation of Sedation Titration for Respiratory Failure cluster-randomized prospective clinical trial conducted between 2009 and 2013...
February 16, 2017: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/28211714/6%C3%AF-josephson-effect-in-majorana-box-devices
#15
A Zazunov, F Buccheri, P Sodano, R Egger
We study Majorana devices featuring a competition between superconductivity and multichannel Kondo physics. Our proposal extends previous work on single-channel Kondo systems to a topologically nontrivial setting of a non-Fermi liquid type, where topological superconductor wires (with gap Δ) represent leads tunnel coupled to a Coulomb-blockaded Majorana box. On the box, a spin degree of freedom with Kondo temperature T_{K} is nonlocally defined in terms of Majorana states. For Δ≫T_{K}, the destruction of Kondo screening by superconductivity implies a 4π-periodic Josephson current-phase relation...
February 3, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28210917/adjuvant-agents-in-regional-anesthesia-in-the-ambulatory-setting
#16
REVIEW
Veerandra Koyyalamudi, Sudipta Sen, Shilpadevi Patil, Justin B Creel, Elyse M Cornett, Charles J Fox, Alan D Kaye
PURPOSE OF REVIEW: A majority of surgical practice has involved ambulatory centers with the number of outpatient operations in the USA doubling to 26.8 million per year. Local anesthesia delivery provides numerous benefits, including increased satisfaction, earlier discharge, and reduction in unplanned hospital admission. Further, with the epidemic of opioid mediated overdoses, local anesthesia can be a key tool in providing an opportunity to reduce the need for other analgesics postoperatively...
January 2017: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/28210905/hypermagnesemia-disturbances-in-rats-no-related-pentadecapeptide-bpc-157-abrogates-l-name-and-l-arginine-worsen
#17
Maria Medvidovic-Grubisic, Vasilije Stambolija, Danijela Kolenc, Jadranka Katancic, Tamara Murselovic, Ivna Plestina-Borjan, Sanja Strbe, Domagoj Drmic, Ivan Barisic, Aleksandra Sindic, Sven Seiwerth, Predrag Sikiric
AIM: Stable gastric pentadecapeptide BPC 157, administered before a high-dose magnesium injection in rats, might be a useful peptide therapy against magnesium toxicity and the magnesium-induced effect on cell depolarization. Moreover, this might be an NO-system-related effect. Previously, BPC 157 counteracts paralysis, arrhythmias and hyperkalaemia, extreme muscle weakness; parasympathetic and neuromuscular blockade; injured muscle healing and interacts with the NOS-blocker and NOS-substrate effects...
February 16, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28210865/the-impact-of-melanoma-genetics-on-treatment-response-and-resistance-in-clinical-and-experimental-studies
#18
M Kunz, M Hölzel
Recent attempts to characterize the melanoma mutational landscape using high-throughput sequencing technologies have identified new genes and pathways involved in the molecular pathogenesis of melanoma. Apart from mutated BRAF, NRAS, and KIT, a series of new recurrently mutated candidate genes with impact on signaling pathways have been identified such as NF1, PTEN, IDH1, RAC1, ARID2, and TP53. Under targeted treatment using BRAF and MEK1/2 inhibitors either alone or in combination, a majority of patients experience recurrences, which are due to different genetic mechanisms such as gene amplifications of BRAF or NRAS, MEK1/2 and PI3K mutations...
February 16, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28210021/opiate-analgesia-treatment-reduced-early-inflammatory-response-after-severe-chest-injuries
#19
Goran Krdzalic, Nermin Musanovic, Alisa Krdzalic, Indira Mehmedagic, Amar Kesetovic
BACKGROUND: The frequency of severe chest injuries are increased. Their high morbidity is followed by systemic inflammatory response. The efficacy of pharmacological blockade of the response could prevent complications after chest injures. AIM: The aim of the study was to show an inflammatory response level, its prognostic significant and length of hospital stay after chest injures opiate analgesia treatment. METHODS: Sixty patients from Department of Thoracic Surgery with severe chest injures were included in the prospective study...
December 2016: Medical Archives
https://www.readbyqxmd.com/read/28209997/antisense-mir-132-blockade-via-the-ache-r-splice-variant-mitigates-cortical-inflammation
#20
Nibha Mishra, Lyndon Friedson, Geula Hanin, Uriya Bekenstein, Meshi Volovich, Estelle R Bennett, David S Greenberg, Hermona Soreq
MicroRNA (miR)-132 brain-to-body messages suppress inflammation by targeting acetylcholinesterase (AChE), but the target specificity of 3'-AChE splice variants and the signaling pathways involved remain unknown. Using surface plasmon resonance (SPR), we identified preferential miR-132 targeting of soluble AChE-R over synaptic-bound AChE-S, potentiating miR-132-mediated brain and body cholinergic suppression of pro-inflammatory cytokines. Inversely, bacterial lipopolysaccharide (LPS) reduced multiple miR-132 targets, suppressed AChE-S more than AChE-R and elevated inflammatory hallmarks...
February 17, 2017: Scientific Reports
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